COSMECEUTICALS

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Chapter 1

EXPLORING THE VERSATILITY OF FRENCH MARITIME PINE BARK

THE GROWTH of the natural personal care market has been dramatic. Demand continues to boom, as consumers become interested in green chemistry. According to Euromonitor, within the facial skin care market, the nourishing/anti-aging

category was the fastest growing section, with a 67% gain from 2002-2007 to $14.9 billion. The benefits of plant extracts continue to weave their way into our every day health routines as we each look to natural means to enhance our feeling of well being.

This column will briefly examine French maritime pine bark extract, a botanical antioxidant known for its health and nutritional benefits. The material is already formulated into several commercial skin care products and is available from Horphag Research and other companies. French maritime pine bark extract is a natural plant extract derived from the bark of the maritime pine that grows along the coast of southwest France. It contains a unique combination of phenolic compounds such as catechins, procyanidins, bio-flavonoids and organic acids, which offer extensive natural health benefits and are potent free radical scavengers. These compounds are also found in grape seeds, green tea, blueberry, red wine, blackberry, black cherry, grape skin and red cabbage.1

French Maritime Pine Bark is finding its way into more anti-aging skin care products.

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102 EXPLORING THE VERSATILITY OF FRENCH MARITIME PINE BARK

Antioxidant: French maritime pine bark extract does more than neutralize free radicals; it also has anti-inflammatory effects. Free radical reactions result in a loss of active cells. Since they are involved in the aging process, and French maritime pine bark extract destroys them, it has an aging-retarding effect. As an anti-inflammatory, the ingredient helps the skin fight stress and generally keeps it from “acting up” in the wrong ways. It increases defensive cell activity, helps maintain a healthier structure and look to the skin, and fights a host of challenges linked to inflammation such as under-eye puffiness, blemishes and rosacea.

De-pigmenting: French maritime pine bark extract inhibits melanogenesis and lowers skin pigmentation intensity so that skin is more evenly toned. Melasma (chloasma) is over-pigmentation of the skin that affects sun-exposed areas of the skin such as the face. This phenomenon often affects young mothers or women taking contraceptive hormones. Sometimes oxidative stress is involved in the excessive production of skin pigments. Dr. Ni Zhigang at the Chinese Academy of Traditional Chinese Medicine found 30 days of treatment with 75 milligrams of French maritime pine bark extract daily to be very effective and safe. In the study, 80% of patients responded very favorably, with the area and the intensity of hyper-pigmentation greatly reduced.

Anti-inflammatory: Inflammation in the body could be a result of allergies, asthma, arthritis, stress or wound infections. The anti-inflammatory potency of French maritime pine bark extract is due to its ability to inhibit the transcription factor NF-KB, which dictates the pro-inflammatory process in immune cells. The extract also improves microcirculation of the skin’s tiny capillaries. This activity helps supply more oxygen, nutrients and moisture to the skin resulting in a healthier look and vibrant glow.

Sun Protection: Sunburn is an inflammation caused by the free radicals that are produced by the effect of sunlight on skin. In clinical studies, Dr. Peter Rohdewald of the University of Munster, Germany marked different areas of the forearm and applied different strengths of French maritime pine bark extract to these areas and then exposed the forearm to sunlight. French maritime pine bark extract protected the skin in a dose-related manner, proving that it prevents inflammation of the UV-exposed skin. Dr. Lester Packer, University of California, Berkeley, and Dr. Ronald Watson, University of Arizona, Tucson, showed that after four weeks of supplementation, it took skin longer to redden in the sun.

Wrinkle Reduction: French maritime pine bark extract protects the cell membranes from sun damage, provides capillary support and helps preserve collagen. In this manner it acts as a collagen stabilizer because it binds to collagen and elastin, and protect these proteins from various enzymes that break them down, thus maintaining skin elasticity. This action reduces the thinning of skin that develops with aging. It also helps the skin rebuild its thickness and elasticity which are essential for skin smoothness and firmness hence preventing wrinkles. It is useful in supplementing antioxidant effects of vitamins C and E. Its skin care benefits may help protect the skin inside and out.

Health and Nutrition: Published research studies have demonstrated French maritime pine bark extract’s beneficial effects in cardiovascular and circulatory health, diabetes care, eye health, venous disorders, inflammatory skin care, healthy aging and menstrual disorders. Overall, it has been found to be very effective in the treatment of many degenerative diseases associated with aging.

French maritime pine bark extract can be taken orally too. It is utilized as a nutritional supplement and as a phytochemical remedy for various disorders, because it possesses potent antioxidant, anti-inflammatory and anti-carcinogenic properties.2,3

103 EXPLORING THE VERSATILITY OF FRENCH MARITIME PINE BARK

References:1. Packer L. et al. Antioxidant activity and biological properties of a procyanidin-rich

extract from pine bark, Pycnogenol. Free radic. Biol. Med. 1999 : 27,704.2. Rohdewald P. et al Encyclopedia of Dietary Supplements, M Dekker 2005, 545-553.3. Sime S, et al Protection from inflammation induced by UV radiation in mice by

topical Pycnogenol. Photochem Photobiol 2004 : 79 : 193.

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Chapter 2

A PRIMER ON EMERGING ANTI-AGING TECHNOLOGIES

ANTI-AGING creams and treatments are a big business these days because everyone wants to look good and ultimately, feel better. Whether we like it or not, looks do count!

Appearance has become an obsession for women and men, and this concern only intensifies as they age. Sales of anti-aging products are predicted to grow by 35% between 2004 and 2009, reaching $2.4 billion by 2009, according to Euromonitor. Total skin care product sales are forecast to grow 6% to $7.5 billion in 2009.

Consumers scan the internet, print and TV media to learn about all sorts of new anti-aging technologies, raw materials, botanicals and new delivery systems, all allegedly offering health and beauty enhancing benefits and compelling product performance claims. The FDA is primarily concerned with safety. So if the product is safe, the companies have a lot of liberty in terms of their exaggerations and their ability to promote and advertise their products, which has many of the companies making claims that are just not true.

What Consumers WantWe have all heard that consumers are well educated and very demanding, but is this really true? Let us also see how well informed they are. We get our answer in a survey sponsored a year ago by the Society of Dermatology Skincare Specialists (SDSS). It asked American women who use skin care products to answer a few simple questions about skin care, including identifying which types of ingredients they should use to treat common skin concerns such as dark spots, fine lines/wrinkles around the eyes or inflammation and bruising. Age, level of education and household income did not seem to matter; the results were poor all across the board.

According to Susanne Warfield, executive director of SDSS, the survey demonstrates that women who do not go to a skin care expert, such as a dermatologist or a licensed aesthetician, may be using wrong products, which may actually be making their condition worse. This survey also showed that U.S. women may be wasting money, as they spent an average of approximately $28 per month (or $336 per year) on skin care products that they rarely or never use because they are not right for them.

This column examines anti-aging science in three broad categories: technologies, new actives and botanicals. Let’s start with some of the newest ideas in anti-aging technology.

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Shock Chill the Skin: Talk about cold cream! Ice-Source is a new French cream featuring rapid refrigeration packaging that drops the product’s temperature from 22°C to 2°C in two minutes. The low temperature enables the cream to enter the skin better, creating a mini face-lift effect that lasts for eight hours. According to the manufacturer, the high-speed cooling causes the molecular retraction of a natural lipid inside the cream, which can penetrate deeply into the skin. Once the cream equilibrates to body temperature, the lipids regain their initial structure and fill the wrinkles by pushing them toward the skin surface.

The face, now smoothed and plumped, seems to have undergone an instant lifting. This product sells for $350 for 22 ml and is suitable for just a few topical applications. Ice-Source may produce temporary botox-like effects, but botox injections provide months of wrinkle relief and cost only a bit more.

But just how can refrigerating a cream make it fast absorbing? Actually, when frozen, the emulsion ingredients can barely be rubbed into the skin, making it unlikely that it would even get past the epidermis. The only temporary benefit of sudden cooling is constriction of blood vessels which result in transient skin tightening, and hydration which may have a short term beneficial effect. Neither is comparable to the effects produced by injected botox. Furthermore, it is possible that sudden change of temperature could induce redness which could be a real problem for those with rosacea.

Ozone Exposure: Chronic ozone exposure damages skin, but a brief exposure offers therapeutic benefits. G.Valacchi and colleagues published a study in British Journal of Dermatology (2005,153(6): 1096- 1100), in which they found that a progressive depletion of antioxidant content occurrs in the stratum corneum, which may lead to a cascade of effects resulting in an active cellular response in the deeper layers of the skin. Using an in-vivo model, they have shown an increase of proliferative, adaptive and pro-inflammatory cutaneous tissue responses.

In the same study, the authors investigated topical application of ozonated olive oil in several kinds of skin infection (including sores, diabetic ulcers, burns, traumatic and surgical wounds, abscesses and skin reactions after radiation). They observed an excellent cleansing effect with improved oxygenation and enhanced healing of these conditions.

Delivery Systems: B&P Company and Peter Passalacqua have developed a facial skin treatment known as Immune Perfect. When the product is applied to the skin, the caramel colored emulsion becomes clear and allegedly immediately penetrates the skin without residue, according to the manufacturer.

Cellulite: FDA has granted a 510(K) pre marketing clearance to Syneron’s VelaSmooth medical device. It offers an effective treatment for those seeking a medical solution to cellulite. It is powered by Electro-optical synergy (ELOS). According to Tina Alster, a clinical professor of dermatology at Georgetown University, VelaSmooth incorporates a combination of technologies enabling deeper heating and mechanical manipulation of cellulite in a non-invasive manner. It is only sold to physicians for use by trained professionals under their direction.

Oral/Topical: Keratec, a New Zealand biotechnology company, has developed two new natural raw materials: Cynergy TK, a topical active, and Cynergy NK, an oral supplement. Both are used simultaneously for synergistic effects. They contain keratin extracted from New Zealand sheep wool. Keratin, a structural protein, is a main constituent of hair and skin and has cell strengthening and softening properties.

UV Damage Control: Helioplex is a patented complex that stabilizes avobenzone, an important UVA protectant. Unfortunately, the longer avobenzone remains on the skin and is exposed to UV radiation, the more it degrades, reducing the sun protection it affords. By stabilizing the ingredient, Helioplex provides enhanced UV protection, which is a major anti-aging benefit.


Heliocare capsules, manufactured by Ivax Dermatologicals, contain fern plant extracts which help stabilize the DNA in the cells and provide some protection from UV damage. Heliocare should be taken as a vitamin supplement—although users must still apply sunscreen, wear protective clothing or minimize exposure altogether.

Similarly, Sun Pill reportedly protects the skin against sun damage. But dermatologists are less than enthusiastic about these daily sun protection pills that work in conjunction with sunscreen lotions.

Night Creams: These overnight creams are said to work their magic while you sleep, but do they really work? Yes, says Richard Glogau a clinical professor of dermatology at the University of California, San Francisco. Dr. Glogau maintains that without the environmental distractions and with cells’ natural ability to renew during the night, the right treatment can help make the complexion look fresher and brighter.

Another study found that the skin temperature increases during sleep and that warmer skin absorbs more of a skin care product’s active ingredients. Consumers are advised to choose a night cream that is packed with vitamins to maximize the benefits. These include Almay Antiaging Night Concentrate, Clinique Repairwear intensive night cream, Lancôme Renergie Night and Sally Hanson Nighttime Heal Repair ointment.

Facial Stimulators: These devices are based on the medically unproven hypothesis that electrical stimulation of facial muscles improves tone, and hence reduces the signs of aging.

But according to a research study conducted by Sam Most of University of Washington Medical Center’s Cosmetic Surgery Center, there was no detectable improvement in signs of facial aging from the use of facial stimulator devices.New Actives

Muscle relaxant: Gamma amino butyric acid (GABA) has entered a category dominated by peptides. According to the manufacturer, Freeze 24-7 contains GABA which produces visible reduction in the appearance of fine lines and wrinkles, without side effects. It is not however known how soon the beneficial effect is produced or how long it lasts.

No matter what their age, more consumers are purchasing anti-aging products.


Polypeptides: R3P Cream is formulated with three polypeptides, sugar derivative, green tea, white tea, grape seed, she a butter and olive oil as skin emollients and moisturizers. This peptide-based cream is said to boost collagen and elastin formation to improve skin texture, clarity and tone. But the manufacturer won’t say how long the consumer must wait to see results or how long they last.

Glucosamine: Best known for treating arthritis, it is recognized for stopping the formation of new age spots and also helps fade the existing ones. According to Alexa Kimball, assistant professor of dermatology at Harvard Medical School, these findings on glucosamine may impact the way dermatologists treat UV related skin damage in the future.

Amino acids: Many skin creams contain collagen, which supposedly nourishes the skin and reverses the signs of aging. But collagen is not absorbed through the skin and hence does not increase the production of collagen. Applying collagen cream may make skin look firm, but this may be due to hydration that could be achieved by any moisturizer.

The question is, how you deliver collagen to the skin? Saverio Dioguardi, a professor of internal medicine and gastroenterology, has researched the skin’s ability to absorb amino acids. He discovered that, with the right vehicle, amino acids form a functional cluster that gets absorbed deep into the dermis, sending a message to fibroblast cells to stimulate collagen production. Collagen is a large, fibrous protein that keeps skin supple and smooth. Clinical study results showed remarkable reduction in the depth of wrinkles and rejuvenated skin.

Chelator: Believe it or not, your skin could develop problems if you drink tap water. According to dermatologist Dennis Gross, heavy metals and other impurities found in water can build up on the skin’s surface. His Hydra-Pure chelating complex eliminates these heavy metals. In fact, Dr. Gross predicts that chelators could be as important as sunscreens for the complexion. Still, I wonder just how universal this problem really is? After all, don’t most households have water purifiers or filters which remove heavy metals anyway? Furthermore, many of the products available on the market today already contain chelators, which are added in the product to enhance the efficacy of the preservative system.

Elastatropin: This product, from DermaPlus, Inc., contains Tropoelastin, a precursor to human elastin and a complex chain of more than 600 amino acids. Clinical studies showed a significant reduction in the onset of wrinkles and facial sagging. According to the company, the active compound enters into the outer skin layers, crosslinks with other skin proteins and expands the flexible backbone of the skin. The cream reduces the need for botox or cosmetic surgery and extends the life of previous procedure.

As most well known brands such as Olay Regenerist and Strivectin have less then 10 amino acids containing peptides, it would be safe to assume the product efficacy is comparable or better.

BotanicalsRevive skin: Kosé Corp. recently reported that birch sap helps revive human skin and boosts its ability to retain moisture. However, Kosé did not specify which fraction of the sap has skin-friendly effects. Sap was applied to human epidermal cells. Compared with untreated cells, the sap-enhanced cells showed more than a 100-fold surge in production of involucrin, a protein for forming cell layers, and a 50% increase in filaggrin, another protein that boosts skin moisture.

Body odor: Offensive body odor may be due to a certain diet or medical condition, but whatever the cause, Kanebo has come to the rescue. The company has developed Otoko Kaoru, a gum that contains geraniol, a fragrant component found in roses,


that is also easily emitted from sweat glands. In theory, chewing this gum would leave consumer’s bodies smelling like a rose!

Skin is the first organ that reveals the effects of aging. Antioxidants, chemical peels, exfoliators and collagen stimulants all boost, rather than replace, skin’s natural activity. Additional research will provide plenty of new information. Of course, you cannot change your age, but biological aging can be delayed if the consumer follows a sensible diet, always protects the skin from sun and uses clinically proven anti-aging products.

Biological aging can be delayed with the right combination of diet, UV protection and skin care products.

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Chapter 3

LOOKING FOR BETTER SKIN? THEN JUST ADD WATER!

DEMAND FOR VITAMIN-ENRICHED products continues to heat up. Datamonitor estimates that sales of nutraceutical beverages will reach $7.4 billion by 2008. At the same time, sales of cosmeceuticals are expected to top

$12.4 billion according to Market Trends.Moreover, sports-related supplements accounted for $1.9 billion of the $19

billion Americans spent on dietary supplements in 2003, according to Nutrition Business Journal. What’s driving this growth? According Vincent Salvia, president of Millenium Natural Health, educated consumers are increasingly looking for a balanced line of results-oriented nutritional products. Our bodies are being ravaged every day by disease-carrying organisms and toxins that we absorb from food, water and air. The correct high quality supplements can combat these effects and help us maintain or even improve our health.

Furthermore, according to analyst Anil Naidu, of Frost and Sullivan, “in today’s fast-paced environment, a healthy lifestyle is absolutely essential. Enhanced awareness toward health and wellness is leading to a drastic change in the nutritional behavior of consumers.”

U.S. consumers already buy more bottled water than beer, milk or coffee according to Beverage Marketing Group, a New York-based consulting firm. Now, they’re starting to chug vitamin-enriched H2O. This column will review two bottled water products, their active ingredients and anti-aging skin claims.Skin Balance Water: This product makes an assortment of antiaging claims such as:

• For optimal results, two bottles/day is suggested to slow the visible signs of aging in just seven days.

• Specifically formulated to work with your unique body chemistry, and developed to help aging skin, fine lines and wrinkles.

• Water contains age-fighting skin-renewers to help soften fine lines and wrinkles, increase elasticity and renews skin’s natural glow.

• Increases the potential for bioavailable absorption of skin-caring ingredients into the dermis.

According to the manufacturer, this product combines the goodness of water with the benefits of topical skin-enhancing products. The label shows clearly all the active ingredients and associated anti-aging skin care benefits.

Airforce Radiant Nutrisoda: According to the nutrition specialist at Ardea Beverage, when it comes to radiant skin, you are what you drink. Radiant is said to

110 LOOKING FOR BETTER SKIN? THEN JUST ADD WATER!

help improve skin’s natural elasticity and firmness for beautiful, healthy, youthful-looking skin.

It contains skin-healthy nutrients such as amino acids, L-lysine, L-proline, L-arginine, plus gotu kola to help stimulate and maintain the body’s production of collagen and facilitate soft tissue repair. Another active, alpha lipoic acid, enhances the performance of antioxidants to help fight free radicals that contribute to the signs of premature aging. Vitamin D provides nourishment for the skin. Antioxidants vitamin A, selenium and green tea help defend against oxidative tissue damage and signs of premature aging. Rhodiola Rosea helps to relieve the tension and anxiety that can contribute to skin stress.

Regulatory IssuesNutraceuticals are not recognized by the U.S. Food and Drug Administration. But because Airforce Radiant Nutrisoda and Skin Balance Water are food, they are regulated by the generally recognized as safe (GRAS) nutritional guidelines. They also may be monitored by the FTC for their marketing language on the label and the promotional materials. The Dietary Supplement Health and Education Act (DSHEA), passed in 1994, gave supplement makers a legal clearance to make claims on their labels and also permitted advertising claims regarding their benefits to the structure or function of the body—among other claims. These products are not approved by the FDA prior to their market launch.

What Drives the Claims?There is a general agreement that peptide-based topical creams, lotions and serums have emerged as a lead alternative to Botox and other wrinkle-fighting products that have been launched in recent years.

Peptide-based products are often the ingredients of choice in helping rejuvenate skin, firm its texture and smooth its appearance. Several clinical studies produced

Skin care you can sip? Drinking Borba Skin Balance Water reportedly improves the appearance of skin in just seven days. The manufacturer insists it increases the potential for bioavailable absorption of skin-caring ingredients into the dermis.

111 LOOKING FOR BETTER SKIN? THEN JUST ADD WATER!

visible antiaging benefits after nearly 90 days of use. Yet, Skin Balance Water claims visible benefits in just seven days. How can it deliver benefits so fast when the formula does not contain a trace of peptide?

The benefits derived from these bottled waters may be explained by carefully examining product labels.

First, it is important to remember that skin is an excellent indicator of vitamin deficiencies. Vitamin A deficiency leads to abnormally dry skin and horny thickening of hair follicles. Vitamin B6 or riboflavin deficiencies result in seborrheic dermatitis (oily facial skin with associated itching). Deficiency of niacin causes skin to become red and inflamed with blister-like eruptions. Deficiency of vitamin C causes capillary walls to break and bleed. Excessive wrinkling of the skin may also result because of smoking, diet and environmental pollution.

Vitamin B5 provides moisturizing benefits. Magnesium activates many enzymes and helps nerve and muscle function. Zinc is also part of many enzymes involved in digestion, metabolism, reproduction and wound healing. Vitamin K is needed for normal blood clotting and bone health. Vitamin B12 is vital for blood formation and a healthy nervous system. Vitamin E helps protect cells from free radical injury, serves as an antioxidant, may help protect against heart disease, cataract and certain cancers and is necessary for normal growth and development.

How Do They Work?Peptides, vitamins and water all play a vital role in skin health. Here’s a closer look at all three components.Peptides: The lack of collagen is a major cause of aging skin. Peptides are chains of naturally-occurring amino acids that stimulate the production of collagen. They have a wide range of activities in all living systems such as binding of enzymes, cellular communication mediating differentiation and proliferation, antibacterial, activating and/or inhibiting specific biochemical pathways. Peptides, and the protein they make up, coax aging skin into producing collagen along with hyaluronic acid, another ingredient that provides moisture. Such a process results in a plumping effect and a smooth, soft and younger-looking skin texture.

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Chapter 4

REMARKABLE RETINOID

Global anti-aging product sales are forecast to grow 26% from 2011- 2016 to $28 billion. During this time, US anti-aging sales will climb 24% to $3.6 billion, according to Euromonitor International. Some of the most potent, collagen-

boosting raw materials are peptides and forms of vitamin A.Although they are completely synthetic, they are among the most potent anti-

aging ingredients and are used extensively by dermatologists and consumer health care companies. This column will briefly review retinol, which is rightly considered the gold standard of anti-aging raw materials.

According to Mintel, during the past three years, there have been 185 skin care product launches in North America, which cite retinol as an ingredient. These launches have occurred across all channels of distribution, from mass to class. Synthetic forms of vitamin A called retinoids have been used as drugs for a long time, and one of them, tretinoin (aka all-trans-retinoic acid) has proved effective for treatment of acne and wrinkles. Retinol became well known shortly after Retin-A made headlines as a prescription wrinkle cream back in 1987. Tretinoin is the active ingredient in Retin-A (Renova). Topical tretinoin is approved for the treatment and prevention of photo-aging.

Vitamin A, found primarily in red and green vegetables, is converted by the body from beta-carotene into retinol and then into retinoic acid. Retinol is a natural form of vitamin A that stimulates cell repair, regulates skin functions and is necessary for skin cell regeneration. It is incorporated into serums and moisturizers to stimulate collagen production. Its side effects include redness and irritation. Retinol is not active when applied to skin. Applying retinol to damp skin does not maximize its potency. Retinol potency is related to skin chemistry and retinol receptors.

Skin cells receive the retinol, and hold on to it until needed, converting only the needed amount into retinoic acid. This attribute can dramatically reduce the adverse effects of retinoic acid, which include peeling, flaking, sun-sensitivity and redness. Despite these temporary side effects, ultimately, retinol generates beneficial skin results. Retinol-induced skin flaking is not like the exfoliation you get from use of glycolic acid. Retinol is gentler than retinoic acid. Biochemically, it accomplishes the same objective as retinoic acid, but at a slower pace. Retinol is the most studied and most common ingredient found in cosmeceuticals. Retinoic acid is a very small

The structural formula of retinol.

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molecule that easily penetrates all layers of the skin, prompting rapid cell-turnover and exfoliation in the process. This mechanism helps explain its efficacy in repairing photoaging, treatment of brown spots, acne and roughness. Its regular application improves the signs of photo-aging and chronological skin aging. Retinoic acid is marketed in three concentrations: 0.025%, 0.05% and 0.1%. Avoid physical contact with eyes, mouth and during pregnancy.

EffectivenessRetinoids work at a much more profound level by affecting gene expression and causing enhanced production of collagen and hyaluronic acid, two of the main components of dermis, which give skin firmness, fullness, skin smoothing, even skin pigmentation while also slowing the age-related loss of these two components, resulting in proactively preventing lines and wrinkles that have not yet formed. Retinoids cannot alter the gene itself or its DNA, hence you must keep using them to retain anti-aging effects.

Furthermore, they prevent the production of collagenase, the enzyme that breaks down collagen after UV exposure. It takes an average of 12 weeks of use to produce noticeable changes in the skin. Several clinical research studies have shown that retinoids trigger changes in the skin to make it look clearer and youthful. On the subject of skin lightning, retinol and retinoic acid are well known for their ability to increase skin-cell turnover. They are added to many skin lightning formulations to speed the removal of pigment granules and accelerate the effects of other whitening agents.

Some CaveatsThey must be used continually for best results. It is important to remember that retinoids breakdown in sunlight, which is why they are packaged in opaque packaging and are best applied at night. It is better to use micro-encapsulated retinol in the formula because it remains protected from light, oxygen, moisture etc. When the finished product is applied on face, the polymeric encapsulation film is broken, releasing free retinol to show its benefits.

Retinoids make skin thinner, and thus more vulnerable and sensitive to sun exposure. Always use a sunscreen if you choose skin lightener that is formulated with retinoids. Dryness can also be a problem.

According to Kate Spetrino, a marketing manager with BASF, claims that are currently used in the marketplace include: anti-aging, collagen boosting, reduce fine lines, increase cell turn over, even out skin tone, repair, smooth, firm, illuminate and protect the skin, boost skin’s radiance, visibly lift skin, enhance skin texture for smoothness and softness, brighten skin tone, firming and illuminating.

Retinoic acid was originally intended for acne treatment. Clinical studies surprisingly proved that retinoic acid not only prevented skin aging but also improved pre-existing skin damage. Vitamin A and retinoic acid are both the mainstay of prescription medical treatment for acne. They affect the production and cohesiveness of cells that line and plug the follicle, thus preventing the progression of acne from becoming severe. Retin-A (tretenoin) works by decongesting follicular debris, helping to clear the follicles of comedones and opening up clogged pores. It is also an excellent agent for oily skin and pimples. Tretinoin, available in cream, gel and liquid form, requires a physician’s prescription.

The question arises: if retinol works as well as well as the label promises, then why would you ever need to use Retin-A or Renova? Tretenoin addresses only one aspect of aging skin, which is bound to generate skin irritation and inflammation.

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To avoid this, just remember to use a moisturizer that is formulated with sunscreens, antioxidants, and anti-inflammatory agents. It is safe to caution consumers that over-use of retinoids would thin the skin, causing chronic inflammation leading to premature aging.

Supporting this thought is the comment made by well-known dermatologist Tina Alster that too much skin inflammation breaks down collagen leading to more lines and sagging.

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Chapter 5

COTTON THISTLE SHOWS PROMISE AS SKIN REPAIR COSMECEUTICAL

IT IS NO LONGER enough for skin care products to make claims about their role in preventing the signs of aging—they are now under pressure to prove it. For ingredient suppliers, active skin ingredients with proven efficacy are already

among the stars of the personal care ingredients market.According to Euromonitor International, sales of active skin ingredients rose 5% a

year from 2004 to 2009 and are projected to grow 3% annually from 2009- 2014. That’s nearly double the growth rate forecast for all personal care ingredients, so it is no surprise to see ingredient suppliers dedicating hefty R&D budgets to exploring new active ingredients and their delivery.

Take, for example, cotton thistle, which has the unexpected property of epidermal repair and skin hydration.1

Who could possibly have thought that something as spiky and prickly as a thistle could repair burned skin damaged by overexposure to the sun? A new active ingredient for skin care extracted from Onopordum acanthium, better known as cotton thistle, has provided exactly this benefit. This botanical name comes from ancient Greek words meaning “donkey food.” Cotton thistle is a wild plant growing in central France. It is well known in folklore and within the medical world for its stimulating and cardio-toning effects and has been used to treat gastric ulcers.2 Furthermore, additional research has now demonstrated its repairing efficacy on the skin’s barrier function.

Barrier Function: This term relates to health and function of the stratum corneum. A healthy

Cotton thistle may improve skin’s barrier function.

116 COTTON THISTLE SHOWS PROMISE AS SKIN REPAIR COSMECEUTICAL

barrier function prevents water loss and protects against irritants, insults and bacterial infections. Promoting barrier repair refers to the repair of both surface and follicular stratum corneum, which tends to be different in acne and rosacea skin conditions. Factors that promote healthy barrier include intercellular lipids, natural moisturizing factor (NMF), and number of layers of stratum corneum. Promoting barrier repair improves dryness, roughness, redness, irritation, acne, rosacea, facial flushing, fine lines and uneven skin tone.

Sun-Damaged Skin: The natural aging process and excessive sun exposure have a negative effect on the skin’s barrier function. Cotton thistle extract was topically applied to both artificially damaged and normal human skin ex-plant. Results showed for both cases an increase of keratinocyte differentiation through increased expression of loricrine, involucrine and LEKT1. In addition, LEKT1 expression promoted cellular cohesion, improving the barrier protection properties of the skin.

Treated Skin: When skin has undergone certain cosmetic procedures such as chemical peels, dermabrasion and laser, it is vital that a new epidermis is rapidly regenerated. Topical application of cotton thistle was shown to stimulate cutaneous repair. A decrease in transepidermal water loss was demonstrated in-vivo using stripped skin. This observation clearly indicates its role in epidermal restoration.

ConclusionsEveryone wants to repair sun and environmental damage. However, this can be difficult for women with acne, skin allergies and rosacea, because they have different surface and follicular stratum corneum. Because many products use plant extracts as performance ingredients, based on their anecdotal benefits, their efficacy is questionable. On the other hand, as a new botanical active, cotton thistle may deliver efficacy for barrier-compromised skin care products since this active has successfully promoted keratinocyte differentiation, cellular cohesion, epidermal repair and skin hydration.

References1. Repair of sun-damaged skin by Cotton Thistle Active, Dr. Paula Lennon, Gattefossé

SAS 36 Chemin De Genas, BP 603, F-69804 Saint Priest Cedex France.2. Cysarz D. et al (2002). Effects of an Anthroposophical Remedy on Cardiorespiratory

Regulation. Alter. Ther. Health Med, 8(6), 78-83.

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Chapter 6

THE ROLE OF PHYTOSTEROLS IN COSMECEUTICAL PRODUCTS

THE ANTI-AGING trend is now a global phenomenon. The desire to maintain a youthful appearance is strongest in the affluent markets of North America, Europe and Australasia where consumers spent a combined $7.7 billion on

wrinkle-reducing facial creams in 2007 according to Euromonitor. New cosmeceuticals are driving this trend. It is a market projected to reach $15.8 billion by 2010 according to Tera Hawkins, founder of the Carol Cole Company, San Diego, CA, a facial esthetic technology company. This month’s column will briefly review emerging antiaging benefits of phytosterols, which are powerful chemical compounds found in many plants.

Phytosterols are extracted from different botanical sources such as olives, avocados, coconut, cocoa butter, sunflower seeds and soy. They are a type of sterol, a specific class of chemical compound, and are very similar to cholesterol, the type of sterol found in animals. In plants, phytosterols contribute to the structure of the cell membrane just like cholesterol does in animals. Foods rich in phytosterols include oils, nuts and wheat germ.

The fundamental biological effect of phytosterols is its anti-inflammatory properties for which it is used in anti-aging products. In clinical studies, phytosterols and polyphenols improved sun-damaged skin. Shea butter and avocado oil offer skin protection and rejuvenation benefits because of their high content of phytosterols. These compounds are used in skin care products with the objective of improving skin health. Hair care products use a mixture of phytosterols such as avocado or similar compounds primarily for their hair softening and conditioning properties. Still, the skin and hair benefits of phytosterols are not widely known, and in fact, are now evolving.

Clinical StudiesOne of the contributing factors in the aging of the skin is the breakdown and loss of collagen, primarily because of unprotected sun exposure. As the body ages, it cannot produce collagen as it once did. This was the subject of the clinical study by National Institute of Health of Germany. In this study, various topical preparations

118 THE ROLE OF PHYTOSTEROLS IN COSMECEUTICAL PRODUCTS

were tested on skin for 10 days. The topical treatment that showed the most anti-aging benefits to the skin was the one that contained phytosterols and other natural fats. The study further found that phytosterols not only stopped the sun-induced slow down of collagen production, it actually encouraged new collagen production.

A second clinical study evaluated cutaneous reconstruction by apple seed phytosterols (International Journal of Cosmetic Science, Vol. 27, Issue 2, Mar. 2005). The study authors analyzed the effects of apple seed phytosterols on age-related structural and functional parameters using cell biochemical, molecular, biological and bioengineering techniques. This study was initiated because plant secondary metabolites such as flavonoids, isoflavones and phytosterols have been proposed as cosmetic ingredients displaying antiaging effects. In the study, the expression of age-related genes was studied using skin equivalents and DNA microarrays. Incubation of skin equivalents with apple seed phytosterols had significant consequences, namely differential regulation of a set of genes associated with keratinocyte proliferation and differentiation, stimulation of hyaluronic acid synthesis and increase of epidermal thickness. Furthermore, in-vivo studies revealed that apple seed phytosterols improved skin elasticity while decreasing skin roughness. The study concluded that phytosterols displayed distinct biological effects and significantly improved the structure and function of mature skin.

A third clinical study examined in-vivo spectrophotometric evaluation of skin barrier recovery after topical application of soybean phytosterols. The study results showed clearly that phytosterols exerted positive results on skin repair. In fact, three days after tape stripping, the sites treated with a formulation containing phytosterols showed an appreciable recovery of barrier function compared to those treated with a vehicle control without soy phytosterols. Klaber coined the term, “phyto-photodermatitis” to address skin reactions that could be caused by external contact with plants or plant products and subsequent exposure to light (Brit. J. Dermatol., 64: 193, 1942).

Formulations and ClaimsAdding oils that are high in phytosterols to cosmetic emulsions would surely help damaged skin recover from environment-induced injuries such as pollution and sun damage. Formulators are advised to conduct adequate safety studies prior to the product launch. It is also important to know that phytosterols are not watersoluble and they have very poor solubility in oils and fats. This solubility issue is largely resolved by Extracts & Ingredients, Union, NJ, through the use of its patented Vortex micronizing technology. This technique creates an easily suspendable material, MicroPhyte, which is suitable for both food and skin care products.

As noted in the clinical studies cited here, phytosterol-based skin care products deliver moisture to the skin, as well as softening, skin barrier strengthening, elasticity boosting and anti-inflammatory benefits. Phytosterols also have applications in hair care and bath products.

Phytosterols aid the skin’s barrier mechanism recovery by penetrating into, rather than occluding onto, the skin. New uses will be explored for these botanical actives as consumers become more interested in using personal care products based on natural ingredients.

119

Chapter 7

BEAUTY AND THE BEACH: WONDERS FROM THE SEA

MARINE-DERIVED ingredients, including seaweed, algae and sea salts, often have excellent anti-irritant, antioxidant, moisturizing, and antiaging properties, which makes them integral components of products for the

fast-growing spa industry. Seaweeds are extremely hardy, adapting to changes in temperature and intense exposure to UV radiation. As a result, they thrive even as they are immersed in water and exposed to air. There are more than 3000 types of seaweed and each has unique properties. Seaweed extracts are loaded with amino acids, such as alanine, glycine and proline, to stimulate collagen synthesis and inhibit enzymes that destroy collagen and elastin. Seaweeds are broadly divided in three classes based on their color— brown, red and green. Many types of seaweeds are known by their Japanese names such as wakame, hijiki and kombu. Twelve seaweeds are widely used in spas: arame, bladderwrack, dulse, hijiki, irish moss, kelps, kombu, nori, sea lettuce, sea palm and wakame. The traditional Japanese bath includes strips of kombu or bladderwrack to dissipate excess fat deposits and soften the skin. With regular use, it reportedly improves the skin barrier and slows the aging process. Seaweeds have almost no calories, are extremely low in fat and are a great source of high quality protein and calcium.

Seaweeds are available in a variety of forms: whole, powder, extract, liquid and gel. They have a predominant amount of iodine, protein and minerals—all of them good for the skin. Laminaria or green algae is especially rich in iodine and reportedly stimulates cell oxygen content. Fucus or brown algae is rich in antioxidants and has a detoxifying benefit to the body. Spirulina is a single-cell algae that is loaded with protein and antioxidants. Rich in calcium and magnesium, white algae is an antiinflammatory and boosts blood circulation.

Seaweeds contain rare minerals, soluble salts and other skin beneficial ingredients, too. Concentrated seaweed extracts yield superior cosmetic properties thanks to key components such as amino acids, polysaccharide and oligo elements which must be carefully preserved during processing. Both seaweeds and seawater are said to firm the skin. Seawater and human blood plasma reportedly have identical composition. No wonder why the French have practiced La Thalasso Therapie or seawater therapy for a long time.

Other ingredients, such as sea salts, sea mud and coral powder are used in wraps, creams, lotions and scrubs. Their active constituents are said to oxygenate and promote healthy skin.

120 BEAUTY AND THE BEACH: WONDERS FROM THE SEA

The Dead Sea ThrivesSeawater, mud and salt are all rich sources of minerals and have healing and soothing benefits. The Dead Sea is a unique source for these ingredients due to its dense concentration of minerals, including potassium, magnesium, sodium, calcium and chloride. Muds have high absorption capacity due to its colloidal size particles. But Dead Sea mud is different from other muds as it is not created by decomposing seaweeds or clays. Nor does it have any known side effects. Due to its high aluminum silicate content, Dead Sea mud provides relief from eczema and is often incorporated into face masks, body masks and baths.

Mud masks help refresh and pamper skin as well as promote cell rejuvenation. They remove dead skin cells and excess oil, while their deep cleansing action refreshes and revives the skin. The mud is usually applied to the skin without causing sensitization or irritation. Sea water and algae contain magnesium, strontium and algal polysaccharides fucoidan laminara which have antibacterial and antiviral properties. These cumulatively provide relief to psoriatic skin.

A Range of UsesSeaweed body wraps are thick pastes made from fresh or dried seaweed, seawater and sea minerals. They are applied on the skin to create a coated surface which is then covered with a plastic sheet followed by a couple of warm blankets for 30-40 minutes. This occlusive skin treatment facilitates close contact of enzymes, mineral and other active ingredients with skin to provide remineralization and balance the whole body. Before they are washed off in a warm shower, wraps moisturize, firm and tone the skin giving it a healthy glow.

C-phycocyanin is a protein-bound pigment in blue-green algae, which occurs in four different structural forms. In vivo and in-vitro experimental models confirmed C-phycocyanin’s antioxidant and anti-inflammatory benefits.1

These studies also demonstrated that blue-green algae is a bio-modulator with immuno-enhancing properties that could be beneficial in the treatment of AIDS and cancer.2 Alginates and carrageenans are extracted from seaweeds. When carrageenans are hydrolyzed, the resulting oligosaccharides yield additional

The Dead Sea is alive with therapeutic minerals and salts.


skin benefits.3 Adequately purified algae maintains its pale beige color. Poorly purified material assumes a brown color. To maintain a superior cosmetic product appearance, a lighter pale grade material should always be used. Anticellulite preparations often contain seaweeds, as they are rich in vitamins, oligo elements, amino acids, iodine and mineral salts, which drain adipose accumulation, and stimulate and strengthen relaxed tissues. Clay, on the other hand, creates an isolating layer that increases body temperature to dialate pores and reduce water retention to reduce cellulite.

In cosmetic formulations, algae and its derivatives thicken products such as toothpastes, shaving creams and lotions. They also possess skin moisturizing and conditioning benefits. These ingredients can be difficult to preserve, hence suppliers sell them in different forms such as alcoholic extracts, infusions or suspensions.

Kelp from the South Atlantic Ocean is a renewable resource of minerals, amino acids and natural gels. Sea parsley is saturated with antiinflammatory and skin-soothing components. It is grown under controlled conditions to provide a consistent quality extract to the cosmetic industry.

An extract of the red seaweed Rhodophyta has a balance of minerals similar to those found in blood plasma, which reportedly gives it great affinity to skin. It contains more vitamin C than apples, more zinc than oysters, considerably more iron and potassium than spinach and more vitamin A than tomatoes, according to Collaborative Laboratories. Clinical studies have shown that this material provides 16% better protection from skin redness and 64% better skin barrier protection than Sea Whip extract against which it was measured. Bluegreen algae has potent amounts of anti-irritants and inhibitors of collagenase and elastase. Upon fermentation, it transforms into sea-derived antioxidants.

Anti-aging ActivesSeveral recent technological advances are providing unique opportunities for

formulators to select specific marine ingredients for their antiaging products. One of these, squalene, is sourced from shark liver oil. It smoothes and softens the skin texture. It makes skin look more radiant and supple while hydrating and soothing dry, irritated skin. It helps protect the skin from free radical damage.

Marine Plant Extract is developed by extracting fluid from the cellular mass of various marine organisms.4 It contains polysaccharides, vitamins and essential sea minerals. It is made from a combination of seaweeds specifically red algae and marine animals. It also contains small quantities of water soluble B, A and C vitamins, niacinamide and pantothenic acid in its co-factor form. It is suggested for use in spa products, moisturizers, serums and body washes.

Apt material is bio-engineered from a strain of the red marine algae.5 Its remarkable bio-activity is derived from its molecular weight peptide fraction of between 500 to 5,000 daltons. Its polypeptide fraction synergizes well with the polysaccharides to impart moisturization, soothing and aesthetic skin benefits. In cell culture studies, it stimulated fibroblast proliferation, triggering cellular synthesis. Both in-vitro and in-vivo studies confirmed its cosmetic benefits such as reducing wrinkles, improving short and long term moisturization, and improving and soothing irritated skin.

Homeostatine is an active complex of and Andean tree and a marine seaweed. It is designed to prevent and reduce wrinkles by increasing the production of dermal collagen and other extracellular matrix components in fibroblasts, by inhibiting the synthesis of pro-inflammatory mediators.5 This natural cosmetic ingredient combines the activity of both of its components to produce a remarkable anti-wrinkle effect.


An Effective Cellulite TreatmentPlankton Total Extract consists of organisms which float freely and involuntarily

in open water.5 In cosmetics, the glucides provided by the phytoplankton fraction make it useful in moisturizing products such as body milks, hand creams and bath gels. The large amount of oligo elements and iodine, due to their attributed lipolitic action, make it suitable in cellulite and slimmimg formulations. The oligo elements and free amino acids are also fundamental in tissue restructuring and may be incorporated into anti-aging products.

Aldavine is a highly-potent cosmetic active ingredient derived from two different algae leading to the association of two sulphated algal polysaccharides.6 It mainly targets the cytokine VEGF and also modulates PGE2 activity. Three biochemical mediators are upregulated in the skin upon aging, exposure to UV and environmental insults and are associated with microcapillary dilation and hyper-permeability. It is suggested for anti-aging, acne, sensitive skin and after-sun care products. It improves skin barrier function. The VEGF pathway is the most innovative feature of this new material.

Homeosta-sea, an anti-aging raw material, is created from four algae derivatives.6 Together, they complement each other and improve the appearance of skin. Homeo-Shield (INCI: Fucus serratus extract and glycerol) is derived from brown algae. It improves skin barrier function. Homeo-Age (INCI: Acsophyllum nodosum extract and sorbitol and water) is derived from brown algae which is rich in vitamins and minerals. It stimulates cellular growth. It rejuvenates cells at the molecular level. Homeoxy (INCI: Entermorpha compressa extract and Palmaria palmate extract, sorbitol and water) is made from two algae known for their high vitamin B content. It prevents UV-induced skin damage. Finally, Homeo-Soothe (INCI: Acsophyllum nodosum extract, sorbitol and water) is extracted from brown seaweed. It reduces inflammatory response and protects the skin from environmental pollutants.

According to the manufacturer, when these four algae extracts are merged together their biological profiles combine to form an ingredient that acts effectively as an anti-aging product. Marine Biopolymer6 enhances the viscosity of skin and

Brittany has always been an excellent source for marine extracts.


hair formulations. It is the only natural polymer that is positively charged, allowing interaction with biological surfaces such as skin and hair. Tensa-Lift6 is a compound based on marine biopolymer with a specific tensing activity. Within minutes after application, this tensorial activity softens skin and makes it appear younger. Since it uses a carefully selected grade of polymer, the poly-cationic feature of this raw material increases its bio-adhesion to the skin thereby intensifying its tensing effect according to the manufacturer. Lanablue6 is sourced from blue algae. This retinoid-like ingredient activates the proliferation of keratinocytes and inhibits the differentiation of corneocytes. It is an anti-aging active with soothing power which has been demonstrated by several clinical studies.

Most enzymes, be they of plant, animal or bacterial origin, are inactive or have low potency level at room temperature.7 Marine enzymes, on the other hand, are at their peak potency level at skin temperature. Cold-adapted marine enzymes are derived from cod fish. These enzymes exfoliate, reduce inflammation, heal wounds and scars, and improve acne and other skin conditions. The self-preserving nature of certain marine enzymes allow for preservative-free cosmetic compositions. These aqueous marine enzyme formulas are pure and safe, thereby appealing to the consumer searching for natural and effective skin care therapies.

A Powerful AntioxidantAstaxanthin comes from the microalgae Haematococcus pluvialis found in abundance in arctic marine environments. A natural carotenoid, it is a powerful antioxidant and is often referred to as “red gold from the sea.” It provides wrinkle reduction by internal supplementation and reduces hyper-pigmentation. The material also has very good anti-inflammatory properties Gorgonian Extract GC8 is a natural marine extract derived from Pseudo-pterogorgia elisabethae (Sea Whip). This anti-inflammatory ingredient is safe, effective and environmentally friendly. The anti-inflammatory properties of pseudopterosins are well documented. This ingredient (INCI: Caprylic/capric triglyceride and Sea Whip extract), is ideal for use in sun care products, aftershaves and skin care treatments.

Pseudopterosin, Sea Whip’s active component, is currently under review as a new drug for treating burns, contact dermatitis, psoriasis and arthritis.

Kimarine, derived from edible seaweed, has been clinically proven to lighten skin and provide protection from reactive oxygen species.

Helionori is a marine active ingredient providing protection against UVA irradiation, due to the presence of special compounds called mycosporine-like amino acid.

Actiseane, developed from brown seaweeds, counters several factors that contribute to skin aging including slower cellular turnover assisting in wound healing and inflammation soothing.9 Several well-known skin care companies use seaweed and seawater as their products “magic” ingredient. Crème de La Mer, a broth of bio-fermented Pacific Coast sea kelp, was developed by Dr. Max Huber to treat his scarred skin and the cream is sold for more than $100 an ounce. Phytomer’s skin care line contains marine actives, while Repechage’s skin care lines are based on different seaweeds to provide skin anti-aging benefits.

Natural and organic products are the fastest-growing sector of the cosmetic industry. Several studies have found that seawater in cosmetic products revitalizes and remineralizes skin cells. It boosts the immune system, prevents infection, stimulates basic enzymes and protects the skin from allergies by antihistaminic action. Seaweeds cleanse the toxins out of the body, beautify the complexion and slow the aging process.


References:1. C. Romay et al, Inflamm. Res. 47(1998) 36-41, 1023-3830/98/010036-062. Gitte Jensen et al, Holger N. I. S. Inc, Port Dover, Ontario, Canada.3. C. Bodeau-Bellion, M. Boue Grabot and C. Chesne, Carrageenan oligosaccharides.

Cosmet. Toil. 112(9) 93-96 (1997).4. Arch personal Care, Inc., S. Plainfield, NJ 07080.5. Centerchem, Inc., Norwalk, CT 068506. Atrium Biotechnologies, Quebec, Canada.7. J. Bjarnason, Les Nouvelles Esthetiques and Spa. Nov. 2007.8. Lipo Chemicals, Paterson, NJ 07504. 9. Biosil, Paterson, NJ.9. Biosil, Paterson, NJ.

125

Chapter 8

ANTI-AGING SUPPLEMENTS FINALLY COME OF AGE

On Jan. 1, no matter what the year, nearly everyone makes a resolution to adopt a healthier lifestyle. Healthier living and proactive health management are two megatrends impacting the supplement industry. The wealth of

knowledge available to the average consumer is greater today than it has ever been before. Consumers are paying attention to their outward appearance and resolving to do something to improving it. This focus creates opportunities for supplement manufacturers. According to Euromonitor International, despite some negative press reports regarding adverse health effects of consuming vitamins, sales of vitamins and dietary supplements are expected to grow 4% to reach $26.8 billion by 2016.

This column will briefly review antiaging supplements that are widely recognized for slowing down the aging process and also keep skin younger and healthierlooking. The theory that supplements don’t absorb well and are thus, a waste of money is not accurate. It appears that modern food processing methods, poor dietary choices, atmospheric pollution and stressful living may inhibit the body’s ability to assimilate all of the nutrients that are required for the maintenance of good health, which explains, consumers growing interest in this growing, vibrant category. Although none of the supplements have been proven to slow aging, they are recommended by medical authorities on the basis of suggestive scientific evidence that supplements significantly inhibit inflammatory reactions and block damaging free radicals that are linked to the aging process.

Açai: This antioxidant-rich, energyboosting fruit is known for its healing and immune-stimulating benefits. It improves heart health, aids in weight loss and helps with digestive problems. Açai is rich in antioxidants, catechins, procyanidins, sterols and phenolic acids. It protects against oxidative damage, lipid peroxidation, reduces ROS and pro-inflammatory cytokines.

Acetyl-L-Carnitine Arginate: The amino acid acetyl-L-carniti ne boosts mitochondrial energy production through its ability to facilitate fatty acid transport and oxidation in the cell. Acetyl-L-Carnitine Arginate is a patented form of carnitine that stimulates the growth of neurites in the brain.

Fish oil has a wide range of beauty benefits.

126 ANTI-AGING SUPPLEMENTS FINALLY COME OF AGE

Alpha Lipoic Acid: This ingredient is a powerful antioxidant that promotes healthy cell function, boosts skin’s radiance and minimizes enlarged pores and surface imperfections. It is taken orally and applied topically. Alpha lipoic acid is also effective in recycling other antioxidants such as vitamin E back into their original form after they detoxify free radicals. There also is evidence that alpha lipoic acid can reduce the damage caused by excess glucose in the blood.

L-Alpha-glycerylphosphorylcholine (GPC): GPC is a byproduct of phosphatidylcholine, which helps to boost acetylcholine. It aids in the synthesis of several brain phospholipids, which increases the availability of acetylcholine in various brain tissues. The GPC form of choline has been shown in studies to help protect against cognitive decline that normally occurs with aging.

Carnosine: Found both in food and in the human body, carnosine levels decline with age. Aging causes irreversible damage to the body’s proteins. The underlying mechanism behind this damage is glycation, which causes wrinkles. Carnosine is a unique dipeptide that interferes with the glycation process, conferring anti-aging skin benefits

Coenzyme Q10: This is an essential component of healthy mitochondrial function. Mitochondria are power centers within cells that generate energy throughout the body where it facilitates and regulates the oxidation of fats and sugars into energy. Most of the cellular energy is produced by mitochondria. With age, cellular mitochondria levels decrease, and cause other health maladies essentially due to mitochondrial disorders.

Fish Oil: This oil is a most popular dietary supplement. Studies on omega-3 fatty acids are so important that a National Institute of Health report noted that fish oil can help reduce death caused by heart disease. The FDA itself states supportive but not conclusive research shows that consumption of ecosopentanoic acid (EPA) and DHA omega-3-fatty acids may reduce the risk of coronary heart disease as they fight free radicals and inflammation. Fish oil helps skin retain moisture and protect it from sunburn. There are several mechanisms attributed to fish oil’s beneficial effects. The latest government report cites the triglyceride-lowering effects of fish oil on reducing heart and blood vessel disorders. Another beneficial mechanism of fish oil is to protect healthy blood flow in arteries.

Grape Seed Extract: This extract is the richest source of oligomeric proanthocyanidin (OPC), making it one of the most powerful antioxidants. It is rich

Açai is rich in antioxidants, catechins,procyanidins, sterols and phenolic acids.


in polyphenols. It helps protect cells from free radical damage and also promotes healthy blood circulation. It promotes brain, skin and eye health and it improves cardiac health and mental alertness.

Green Tea Extract: What makes green tea extract such an important nutrient is the large volume of published scientific findings that validate its multiple biological benefits. The most significant findings involve studies showing that green tea extract helps maintain cellular DNA and membrane structural integrity. Decades of research shows that green tea inhibits the development of undesirable cell colonies. The active constituents in green tea are powerful antioxidants called polyphenols (catechins) and flavonols. Several catechins are present in green tea and account for the bulk of favorable research reports. Epigallocatechin (EGCG) is the most powerful of these catechins. EGCG functions as an antioxidant that is about 25-100 times more potent than vitamins C and E. Green tea’s high antioxidant activity helps protect the body from oxidative damage caused by free radicals.

Lutein/Zeaxanthin: These are potent antioxidant carotenoids found in green leafy vegetables such as spinach, kale and collard greens. They offer eye and skin health benefits, such as improving skin elasticity and hydration. Daily intake of 6-10mg may be beneficial.

Lycopene: Lycopene is a type of carotenoid found naturally in foods that are red, such as tomatoes, watermelon, apricots, pink grapefruit and guava. It helps promote smoother, younger looking skin, and high levels of lycopene in the skin block UV rays to some degree. Lycopene also helps to improve cell metabolism and cell communication. The daily requirement is between 25-75mg a day.

Melatonin: Melatonin is a hormone produced by the pineal gland, which is located beneath the brain. Melatonin is a highly potent antioxidant, and has been described as the pacemaker of the aging clock in humans. It is released every night as part of our time-dependent biorhythms to help induce sleep and recuperate from fatigue. Published studies indicate the importance of maintaining youthful levels of melatonin to protect against age-related degenerative diseases.

Polypodium leucotomos: This is a phenolic antioxidant with photo-protective, anti-inflammatory and immunemodulating effects. In a study of 21 human subjects, polypodium leucotomos administered orally or topically provided photo-protection to skin.

Pycnogenol: This ingredient has a range of antimicrobial, antioxidant, antiinflammatory, photo-protective, anti-carcinogenic effects. Oral supplements taken for eight weeks reduced UV-induced cutaneous erythema.

Quercetin: A bioflavanoid, providing body with anti-inflammatory and antioxidant protection, quercetin is found in many plants such as black tea, broccoli, onions, red apples and red wine. Ideally, 100-250mg of this nutrient should be taken three times a day.

Resveratrol: Resveratrol packs a powerful antioxidant punch to soothe inflammation, protect skin against environmental damage and fight premature aging. It is said to offer a broad range of health benefits. It hydrates, firms and lifts the skin according to some research studies. It is found in red grape skin, raspberries and mulberries.

Vitamin C: This well-known vitamin improves the appearance of sun-damaged skin. It reduces inflammation, promotes collagen production and strengthens skin’s barrier response. This water-soluble antioxidant is not produced by the body. Vitamin C reduces melanin formation via tyrosinase inhibition.

The only way to flawless skin is to keep the inside of the body healthy. Skin’s endogenous supply of antioxidants is reinforced by orally or topically administered antioxidants, thus combating an overload of oxidative stress. Regular exercise also has an anti-aging effect and could delay premature aging.


As a general rule, it is preferable to eat healthy food and try taking supplements for maintenance of good health before considering drugs for any minor ailments. Because supplements are taken orally, their activity is systemic, providing skin benefits.

No one can rewind time, nor can anyone reverse the ravages that the aging process puts on our bodies. The only sensible thing we can do to manage the aging process is to make intelligent decisions about what we consume, how we protect ourselves from UV and how we live.•

129

Chapter 9

THE ANTI-AGING BENEFITS OF MATRIXYL SUBSTANTIATED

IT IS THE RESPONSIBILITY of manufacturers of anti-aging products to make sure that all product claims, either on the label or those made in advertising, are fully substantiated. Companies rely on different kinds of substantiation methods

to support their claims because there is no particular method of claim validation for different kinds of products. Consumers are drawn to purchase the product because of the claims. Companies must choose the claims they want to make, as there are so many types of claims to choose from, such as objective, comparative, superiority, parity or pre-emptive. Several clinical methods are available to substantiate product performance claims, such as skin barrier and trans-epidermal water loss, skin moisture measurement by conductivity, skin surface replicas and their measurements, skin firmness and elasticity, fine line and wrinkle reduction and skin extensibility measurements.There are clinical research laboratories that customize protocols to fit the specific need of each client and each product. Standard or custom protocols can provide clinical evaluations for skin care and cosmetic product claim validation. They offer safety and efficacy testing.

A Brief BackgroundPeptides are amino-based substances with different activities such as pain perception, antibacterial activity, cellular communication, mediating anabolic/catabolic activity, binding to enzymes and mediating differentiation/ proliferation. Research by Katayama and others2 suggests that small peptide fragments of collagen may be involved as messengers directing skin fibroblasts to generate extra cellular matrix production.

This research also reported that the KTTKS peptide sequence from type I pro-collagen stimulated production of collagen I, III and fibronectin in cell culture. Lintner and others4 have modified KTTKS by reacting it with palmitic acid for the purpose of enhancing skin penetration.

They also reported that pal-KTTKS amino peptide increases glycosaminoglycan synthesis in human fibroblast culture. This is comparable to TGFB in increasing collagen I synthesis as measured in ex-vivo studies of a product containing 3 ppm of pal-KTTKS vs. placebo and vs. a 0.07% retinol product has suggested that pal-KTTKS reduces the appearance of wrinkles much like retinol.

130 THE ANTI-AGING BENEFITS OF MATRIXYL SUBSTANTIATED

Scientists I have independently evaluated, in a large base clinical study, a fully developed moisturizer containing 3 ppm pal-KTTKS vs. moisturizer placebo (both containing 7% glycerin).

A 14-week, randomized, doubleblind, split-face clinical study was designed to compare both the technical and subjective efficacy of a facial moisturizer containing 3 ppm of pal-KTTKS vs. placebo moisturizer on the visual appearance of photo-aged human skin. It consisted of a two week pre-conditioning period and 12 week treatment period. Each product was tested on 92 female subjects aged 35 to 55 years old. Subjects were in general good health, with moderate to severe photo damaged facial skin and Fitzpatrick skin types I, II and III.

During the pre-conditioning period, subjects were required to use a mild facial cleanser and a UVA/UVB SPF 15 moisturizing lotion (containing zinc oxide), both provided for them, twice each day in place of their regular cleansing and moisturizing products. Subjects were instructed to refrain from using any other skin products until the study was completed. Subjects were permitted to use eye and lip makeup along with an oil-free foundation that did not contain AHA or salicylic acid. Subjects also had to refrain from exposing their face to tanning lights and excessive outdoor sunlight.

During the treatment period of the study, the panelists continued to use the cleanser daily and UV protectant as needed. During the 12-week treatment period,

Of course, there is no Fountain of Youth, but with a range of effective anti-aging ingredients to choose from, marketers can concoct a variety of skin care products to help keep skin looking younger and healthier.

Seeing is believing. During a 12-week treatment period, Sederma’s Matrixyl anti-aging ingredient has a dramatic effect on the appearance of fine lines and wrinkles around the eye area.

131 THE ANTI-AGING BENEFITS OF MATRIXYL SUBSTANTIATED

the subjects were given both test products and instructed to use the product twice a day, in the morning and night, on their right or left side of their face. On Day 1 of the treatment period, and at weeks 4, 8 and 12, digital images were acquired under controlled lighting conditions and using a panelist positioning system design to allow for exact re-positioning of subjects for images at all time intervals.

These digital images were analyzed via image analysis techniques to measure fine lines and wrinkles. and skin barrier function was assessed using Dermalab TEWL instrument. The 4-, 8- and 12-week images were visually graded vs. the baseline image of each individual by expert graders for assessment of fine lines and wrinkles. In addition, the panelists completed a self assessment questionnaire regarding their skin appearance at 4-, 8-, and 12-weeks.

SummaryMatrixyl, a palmitoyl pentapeptide pal-KTTKS, is a modified chain of five amino acids developed and patented as an antiaging active ingredient by the French company Sederma SA.3 A clinical study described in this presentation validated the following benefits:

• Reduction of fine lines/wrinkles vs. placebo as measured by analysis of digital images;

• Significant reduction of visual appearance of fine lines/wrinkles at week 4 and 8 relative to placebo;

• At week 12, improvements were noted for age spots, dark circles and skin firmness

• Skin barrier was not affected as measured by TEWL.

Anti-aging benefits of Matrixyl are as effective as retinol without the accompanying skin irritation, because it does not energize inflammatory pathways as aggressively as retinol. These research conclusions shoud be a welcome news to consumers and formulators of anti-aging products.Reflecting this sentiment is Linda Wells, editor of Allure, who states that skin care has progressed radically from the days of hope in a jar. Now women are looking for products that truly change and improve skin in ways that go beyond simple moisturization. They look for ingredients by name that have been proven in clinical studies to build collagen or protect the skin cells from environmental damage.

References1. L. Robinson, N. Fitzerald, D. Doughty, N. Dawes, C. Berge, D. Bissett, (P&G,

Cincinnati, OH.)2. K. Katayama, J. ArmendarizBorunda, R. Raghow, A. Kang, M. Seyer (1993) J.Biol.

Chem. 268, 9941-9944.3. Sederma Inc., A member of the Croda International Group, Edison, NJ 08837- 3907.4. K. Lintner, C. Mas-Chamberlin, P. Mondou, Penta peptide facilitates matrix

regeneration in photo-aged skin. World Congress of Dermatology, Paris, France, July 2002.

132

Chapter 10

PROMISING COSMECEUTIC

The anti-aging category certainly isn’t showing its age. Global sales of anti-aging products are expected to grow 26% from 2011-2016 to reach $28 billion, according to a study by Euromonitor International. During that time, US sales

of anti-aging products are expected to grow 46% to reach $12 billion.No wonder why supermarkets and department store shelves are crowded with

anti-aging products formulated with new cosmeceuticals, some of which make unsupported claims. Most consumers mistakenly believe that these products are regulated and tested as rigidly as drugs and that the claims made in advertisements are valid.

This column will briefly review promising cosmeceutical ingredients for which there is available clinical data that support skin appearance improvement effects. This information, hopefully, will help marketers to substantiate anti-aging claims for their new product launch in this growing category.

EfficacyEffective cosmeceutical ingredients, when added to a formula correctly, provide optimum anti-aging efficacy. Ingredients such as retinoids, antioxidants, ascorbic acid, peptides, broad-spectrum sunscreens and MMP inhibitors provide collagen-boosting and matrix protection benefits. A combination of retinoids and alpha hydroxy acids provide skin texture improvement benefits too.Skin pigmentation correction benefit is derived when retinoids are combined with l-ascorbic acid, anti-inflammatory agents, and melanogenesis inhibitors. These cosmeceuticals, alone or in combination, treat signs of aging which provide skin anti-aging benefits such as improving firmness, elasticity, tone, clarity, radiance, sensitivity and texture, while reducing redness, blotchiness, fine lines and wrinkles, dryness, dullness, spider veins, drooping neck, sagging cheeks, lip wrinkles, frown lines, crow’s feet, photo-aging, enlarged pores and age spots.

AntioxidantsThe most-widely studied antioxidants include resveratrol, ferulic acid, ergothioneine and idebenone. Resveratrol has chemo-preventative and cytostatic properties. When used topically, it provides UVB skin protection. It is effective antioxidant with strong anti-inflammatory properties.1

Ferulic acid prevents nitric oxide production and lipid peroxidation. It absorbs UV radiation. Its free-radical scavaging effects are not as potent as green tea polyphenols.2,3

133 Promising Cosmeceutic

Ergothioneine increases the protective activity of l-ascorbic acid and vitamin E. It accumulates within epidermal keratinocytes for long term protective benefits.4,5

Idebenone is an analog of coenzyme Q-10. It decreases lipid peroxidation. It inhibits UVB-induced DNA damage and erythema.6

Green tea’s antioxidant activity is due to epigalocatechin gallate (EGCG). It prevents the formation of nitric oxide, hydroxyl radicals and singlet oxygen. It induces degradation of carcinogenic cutaneous cells.7,8

Plant stem cells have antioxidant benefits. They provide protection and stimulation to epidermal stem cells.

Vitamin C reduces collagenase synthesis, as well as post-inflammatory and UVinduced erythema.

RetinoidsThis family of cosmeceuticals includes retinoic acid, retinol, retinaldehyde and vitamin A esters.Retinol and retinaldehyde provide topical benefits with reduced risk of irritation, while pure retinoic acid and retinol formulae may cause irritation.

Retinoids encourage proliferation of elastin and glycosaminoglycans. They decrease collagenase and elastase levels and reduce fine lines, roughness and dyspigmentation.9

PeptidesThese synthetic compounds contain two or more amino acids connected by peptide bonds. They perform targeted functions in the skin when applied topically. There are four main categories. Signal peptides are palmitoyl pentapeptide-4, palmitoyl oligopeptide, palmitoyl tetra peptide-7 and palmitoyl tripeptide-38. They help produce collagen.

Neurotransmitter affecting peptides help relax wrinkles; e.g., acetyl hexapeptide-8 inhibits soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex.10

Enzyme-inhibitor peptides help improve under-eye circles and hyper-pigmentation and carrier peptides. They enhance delivery of active ingredients within skin layers; e.g., copper peptide increases collagen and elastin production. The evidence to support their use is growing. Popular peptides are Matrixyl (pentapeptide-4) and Argiriline (acetylhexapeptide-8).

Skin LightenersThese botanical ingredients interfere with melanogenesis cascade, prevent the occurrence of future pigments and reduce the appearance of current skin pigmentations.

Hydroquinone is synthetically derived, but is also found in wheat, berries, coffee and tea. It increases the degradation of melanosomes, inhibits DNA and RNA synthesis and induces melanocyte-specific cytotoxicity.

Arbutin is found in blueberry leaves, wheat and pears. This potent antioxidant inhibits tyrosinase activity. It is less cytotoxic to cultured melanocytes than hydroquinone.

Kojic acid is derived from soy, rice and mushrooms. It inhibits nuclear factor-kappa B(NF-kB) activation in keratinocytes.11 Other effective skin lighteners include retinoids, lascorbic acid, lactic acid, licorice root extract, azelaic acid and phenylethyl resorcinol.

134 Promising Cosmeceutic

Hydroxy AcidsThis class of cosmeceuticals can turn dry, dull skin into smooth radiant skin more quickly than any other ingredient type. Hydroxy acids improve skin texture, skin barrier function and the appearance of photo-aged skin. However, they can cause redness, stinging, and burning in those with sensitive skin. Polyhydroxy acids or PHA are less irritating and are equally effective.Although acids work rapidly, remember that there is no quick fix when it comes to skin benefit. If you see an instant effect, most probably it is due to visual correctors in the formula that temporarily tighten, swell or irritate skin.

For real benefits to occur, skin needs a minimum of eight weeks to undergo any significant change. It is therefore important to track clinical results for at least four months. To be effective, they must first cross the epidermis, and penetrate through the dermis and the fatty layer.

References:1. J. Cos. Derm. 2008:2-72. J. of the Science of Food & Agriculture 1999:476-4803. Free Radical Research Communication 1993.241-2534. Biochemical Communications 2003:860-8645. Free Radical Medicine 2009: 46:1168-11766. J. Cos. Derm. 2005-10-177. Experimental Dermatol. 2006-678-684.8. Proceedings of NAS 2002:12455-124609. Cosm. Derm. 2005-3-510. Int. J. Cos. Sci 2002:24 :303-31011. Cosmetic Formulations of Skin Care Products.-2006:40

135

Chapter 11

UNDERSTANDING THE ANTI-AGING BENEFITS OF NUTRICOSMETIC

The latest trends in beauty, health and wellness sectors are giving rise to a new realm of possibilities by fusing anti-aging cosmeceuticals with nutraceuticals and resulting in nutricosmetics. In this sense, a cosmeceutical is an ingestible

ingredient for functional foods or nutritional supplements that has cosmetic benefits. This contrasts with the cosmetics definition, which is based on the topical nature of the ingredient. Hence nutricosmetics, beauty foods, beauty supplements and beauty from within are synonymous terms. This column will briefly examine anti-aging benefits of nutricosmetics.

CategoriesNutricosmetics: These ingestible products are developed and marketed specifically for beauty purposes. Nutricosmetics first gained popularity in Asia and Europe. Both traditional and Eastern medicines have used nutrition as a way to promote optimal health and beauty. According to Euromonitor, sales of nutricosmetics will reach $209 million by 2017. Trends that are fueling this growth are aging population, environmental factors, consumer awareness, aversion to invasive procedures and the rise of holistic spa-yoga centers.

Phytocompounds: Eating certain foods dramatically improves the appearance of your skin, hair and nails. These compounds undergo chemical changes in body to promote good health. They stimulate DNA repair, reduce inflammation and increase collagen production. They are classified into terpenes (carotenes, limonoids and saponin).

Organosulfur compounds: Organosulfur compounds are found in onions, garlic, cabbage, brussels sprouts and broccoli (which contain indoles, thiosulfonates, isothiocyanates) and phenols such as polyphenols and isoflavones.1 All have a strong odor due to the presence of sulfur.

Green foods have chlorophyll, isothiocynates, lutein and zeaxanthin antioxidants. They may reduce the risk of macular degeneration that causes blindness.

Yellow foods such as carrots, squash, tomatoes and oranges contain terpenes. They help heal wounds and are powerful antioxidants.

Orange foods have beta carotene, which improves immunity and oral health.

136 UNDERSTANDING THE ANTI-AGING BENEFITS OF NUTRICOSMETIC

Purple foods such as blueberries, cherries, beets, purple grapes, eggplants, plums, purple figs, black currant and purple cabbage are nature’s best weapon in the battle against aging and prevent collagen breakdown.

Red foods contain powerful antiaging active lycopene and ellagic acid, which help reduce DNA damage.

White foods contain allicin and quercetin. They improve immune function. Cauliflower contains cancer-fighting sulforphane.

Efficacy ClaimsBeauty foods, supplements and the science backing them are still evolving along with the nutricosmetic category. Regulators want to ensure that the products are backed by science and make claims that are not misleading. For this reason, uncertainty and ambiguity still clouds this category.

In the US, regulatory policy is shared between Food and Drug Administration (FDA) and the Federal Trade Commission (FTC). For example, recently the National Advertising Division (NAD) of the Council of Better Business Bureau, recommended Irwin Naturals’ dietary supplement, discontinue the claim: “Doctor Developed Clear Pure Complexion.”

According to NAD, the claim was not supported. Elsewhere, the European Food Safety Authority (EFSA) health claim panel recently rejected claims made by Inneov. The panel found that clinical studies were conducted on the individual ingredients, but not on the entire final product formula.

Japan remains the biggest nutraceutical market, and its FOSHU (Foods For Specified Health Issues) regulatory laws are very strict. Therefore it is very common to find product labels only list “active” ingredients such as collagen, lycopene and coenzyme Q-10 without making specific skin, nail, health and appearance claims.

Purple foods, such as plums, prevent collagen breakdown.


BenefitsNutritionists and doctors advocate that foods provide the best sources of antioxidants and vitamins. When malnourished, the skin becomes gray, scaly, uneven and patchy. We all know that some skin and hair problems are directly linked to vitamin deficiency. For example, vitamin A deficiency results in dry skin, dry hair and fragile fingernails.

Overall key beauty benefits are antioxidant and anti-inflammatory. Specific benefits occur for skin, hair and nails. Skin benefits include repair and prevention, photo-protection, firmness, pigmentation control, whitening and slimming. Hair benefits include retention and growth, restoration, nourishment and volumizing. For nails, the key benefit is strengthening. Overall nutraceutical ingredients are safe and ingestible when derived from food.

Nutricosmetics differ from dietary supplements, which are usually taken for medical/health benefi ts. Nutricosmetics are foods or supplements that are specifically consumed to produce an appearance benefi t, most notably for anti-aging effects and fi ghting the toxic effects of free radicals.

Tomatoes contain active lycopene and ellagic acid, which help reduce DNA damage.


DermatologistsNutricosmetics were fi rst introduced in skin care routines by innovative dermatologists such as Nicholas V. Perricone, MD and Fredric Brandt, MD. Improving your eating habits is not going to eliminate wrinkles or sagging, but research shows that proper nutrition will improve the tone and texture of your skin according to Mary Lupo MD, clinical professor of dermatology at Tulane University, School of Medicine. According to Perricone, numerous scientifi c studies from around the world show that carotene supplementation, especially lycopene and beta carotene, improve skin structure, have powerful woundhealing properties and offer great protection from damage caused by sunlight.

According to Zoe Diana Draelos, MD, anything edible that is “good for you” can be considered a nutraceutical (Dermatological Times). Nutricosmetics represent the newest category in the anti-aging market, combining cosmeceuticals and nutraceuticals.

Jessica Wu, MD, assistant clinical professor of dermatology at the University of Southern California, contends that certain supplements, such as fi sh oil, may improve the quality of your skin, but there is no FDA oversight of them, so it is hard to know how much of the nutrient is actually being absorbed by your body and is affecting your complexion.

ConclusionsOral and topical nutricosmetics obviously improve both body and skin health. An internal approach to beauty and wellness is the future of beauty, but the category is still in infancy in the US. Some of the reasons for this, according to Kline and Company are the fact that consumers are more skeptical of the “beauty-from-within” philosophy.

Moreover, Americans are less patient and generally less health conscious than their European and Japanese counterparts; they expect instant results and they demand scientifi c proof of benefi ts. In addition, this category lacks a clear distribution channel, many consumers prefer not to buy ingestible products from cosmetic brands, and lastly, the pharmacies do not have same infl uence in US as they do in Europe. Because of these drawbacks, many top brands entered the market and exited after disappointing sales.

Although the category is expected to remain a niche opportunity, it offers an opportunity for food, beverage and supplement manufacturers more so than cosmetic companies.

Reference1. Isabele Roces, P. Daily Inquire News 3/12/2010

139

Chapter 12

THE ANTI-AGING POWER OF TOPICAL VITAMIN

The arrival of a new year can be such a motivating event to make improvements in one’s life. If it’s February, most folks have already forgotten the resolution they made on January 1. But no matter what the calendar reads, it is always

a good time to take care of your skin. It is clinically proven that topically applied vitamins are well absorbed through the skin. This column will briefly describe the benefits of using daily skin care products formulated with anti-aging vitamins such as vitamins A, B, C, E and K, and co-enzyme Q-10.

These six vitamins are the most frequently used for healthy skin. Using them regularly is a sure way to prevent skin damage, before it even begins. Baby Boomers continue to seek new and effective ways to slow down the passage of time and this is reflected in the Euromonitor International market research study that predicts the skin care products market will reach $91 billion this year.

Vitamin A: The term “retinoids” refers to vitamin A and all of its natural and synthetic derivatives. Retinoids influence the function of a cell by altering the gene expression pattern. Some of their biologic effects include regulating growth and differentiation of epithelial cells; decreasing inflammation; enhancing the immune system; improving acne, photoaging, psoriasis and skin discoloration; reversing sun damage; and inhibiting collagen and elastin breakdown. A very low level, 0.05%, of retinol provides efficacy by its conversion to intermediate retinaldehyde to retinoic acid that actually is the endogenous active form.

Vitamin B (vitamin B3, niacinamide and nicotinamide): easily penetrates the stratum corneum, providing a variety of beneficial effects to skin such as improvement of dry skin, elasticity, texture and color, decrease in age spots, evening out of overall skin tone, skin-barrier enhancement, moisturization, improvement of lipid barrier component of the epidermis.

As a result, there is a reduction in transepidermal water loss (TEWL), sebaceous lipid excretion and pore size, leading to an overall improvement in skin appearance. Clinical research study results have shown a significant reduction in fine lines, wrinkles, hyper-pigmented spots, red blotchiness and skin sallowness.1,2 Usually 2-5% vitamin B has been used in topical formulations to achieve these effects. Vitamin B reduces the appearance of wrinkles.

140 THE ANTI-AGING POWER OF TOPICAL VITAMIN

Vitamin C (L- ascorbic acid): fights off free radicals, slows down the aging process and even reverses the signs of aging. Many anti-aging products containing vitamin C are not effective on the skin because of several reasons:

• The concentration of L-ascorbic acid could be too low;• Exposure of the product to air and light compromising the stability of the

product; or• The L-ascorbic acid is in the form of an ester or a mixture of isomers, which

cannot be absorbed or metabolized effectively by the skin.In high enough concentration (at least 10%) of the non-esterified, optimal isomer

vitamin C inhibits UV damage. It is important to know that stabilizing ascorbic acid presents challenges. However, a formulation that has an acid pH of approximately 3.5 may optimize vitamin C absorption. Clinical studies support the use of topical vitamin C to improve fine lines and reduce both pigmentation and inflammation.3

In another clinical research study, vitamin C is formulated with potent antioxidant ferulic acid and vitamin E. This stabilizes the formula and doubles the photoprotection from four- to eight-fold. This combination of actives is featured in Skinceuticals’ CE Ferulic, which contains 15% vitamin C, 1% vitamin E and 0.5% ferulic acid.4

Vitamin E (alpha-tocopherol): an excellent moisturizer and an emollient. It inhibits the acute UV damage of erythema, sunburn and tanning as well as chronic UV photo-aging and skin cancer.5 It protects cells from oxidative stress and is primarily used for the treatment of minor burns, surgical scars and wounds.

Vitamin C regenerates oxidized vitamin E when they are used together in the formulation. This combination in a formulation is synergistic, particularly with regard to UV protection. Usually topical preparations contain vitamin E in concentrations ranging from 0.1% to 20%. Because there is no dose-response relationship information available, there is no way of knowing how much vitamin E concentration is required to achieve clinical efficacy. Side effects of topical preparations in some consumers include irritant allergic contact dermatitis.

Vitamin K: There are several forms of vitamin K. There is no information available on its oxidative stability. Under-eye dark circles are visible because of leaking capillaries under the skin. This is visible because undereye skin is very thin. Vitamin K is believed to actually constrict capillaries under the skin. However, there is no information available on controlled studies to support this observation.

Coenzyme Q10 (Ubiquinone, or CoQ10): This lipid soluble antioxidant is present in the mitochondria of all living cells and is utilized in the synthesis of adenosine triphosphate. A prolonged oral supplementation of CoQ10 in humans has shown to reduce crow’s feet wrinkle formation. Ubiquinone significantly suppresses the expression of collagenase in human dermal fibroblasts following UVA irradiation.6

Another study showed that ubiquinone inhibits oxidative stress in the skin induced by UVB.7 An effective antioxidant, it protects skin from intrinsic and extrinsic aging.8

Cosmetic brands such as Nivea and Eucerin are formulated with coenzyme Q10. A decreased wrinkle depth was documented by optical profilometry using 0.3% ubiquinone cream for six months.9 A low molecular weight synthetic analog of coenzyme Q10 with superior skin penetrating properties is called idebenone. Skin care products containing idebenone are available as Prevage MD by Allergan. Prevage Eye Anti-aging Moisturizer is available from Elizabeth Arden and Allergan companies.

Clearly, there is significant data confirming the anti-aging benefits of topically applied vitamins. In a market dominated by older consumers with busy lifestyles and abundant leisure time, it is hard to accomplish all health goals. However, a strict

141 THE ANTI-AGING POWER OF TOPICAL VITAMIN

adherence to a disciplined use of anti-aging products could protect the skin from future damage.

References:1. Bissett et al., Int. J. Cosmet. Sci 26(5): 231-8 (2004 Oct.)2. Bissett et al., Dermatol. Surg. 31 (7 Pt 2): 860-5 (2005 July)3. Gasper LR et al. Int. J. Pharm. 343(1-2): 181-9 (2007 Oct.)4. Lin FH et al., J. Invest. Dermatol. 125, 826-325. Burke KE; Dermatol. Ther. 20 (5): 314-21 (2007 Sept-Oct.)6. Choi CM, Barson DS. Semin. Cutan Med surg 25(3): 163-8 (2006 Sept.)7. Burke KE, Cosmeceuticals, Elsevier Saunders pp 125-32 (2005)8. Bissett D, et al. 64th Annual Meeting AAD, San Francisco, CA. March 3-7, 2006,

poster p2359. Eucerin Q10 Product Compendium, Wilton, CT: Beiersdorf Inc. p11

142

Chapter 13

UNDERSTANDING THE ANTI-AGING POWER OF PEPTIDES

GROWTH IN THE skin care market is driven by innovative specialty actives and delivery systems. Choosing the right anti-aging ingredients is crucial for success. While many consumers are willing to pay a premium to stave off

the signs of aging, a proven track record of scientific efficacy remains the key selling point in this segment.

Astute ingredient suppliers understand that active skin ingredients with clinically demonstrated efficacy are the stars of the personal care ingredient market. According to Euromonitor, overall volume sales of active skin ingredients posted a compound annual growth rate of 5% during 2004-2009 and are projected to grow 3% annually from 2009-2014. This is almost double the growth rate forecast for all personal care ingredients. Therefore, it is no surprise to see ingredient suppliers dedicating hefty R&D budgets to the exploration of new actives.

Facial skin care is one of the fastest growing sectors in the US toiletries and cosmetics market. Some of the most promising anti-wrinkle, anti-aging products contain peptides. This column will briefly review the anti-aging power of peptides.

Repairing Peptides: Dipeptide-2 and tetrapeptide-7 peptides both have demonstrated anti-inflammatory properties and hence may offer beneficial applications for post-procedure treatments and may aid in repairing skin barrier dysfunction. While these peptides soothe inflammation, copper peptides such as GHK peptides made by ProCyte, for use in the company’s Neova line, work by repairing skin injury caused by either wound or photodamage.

Relaxing Peptides: These peptides have an effect on the neurotransmitters that control the communication between the nerves and the muscles that cause expression-related wrinkles. Peptides like acetyl hexapeptide-3, also known by the trade name Argireline, relax the muscles and produce a Botox-like effect. Hexapeptides are known as wrinkle-relaxing peptides.

Firming Peptides: Tetra and penta peptides are face-firming peptides. They stimulate the skin’s natural production of collagen to help restore the structure of the skin and smooth wrinkles. Their benefits are comparable to the benefits provided by retinoids minus their chemical instability and irritation.

143 UNDERSTANDING THE ANTI-AGING POWER OF PEPTIDES

Some Key PeptidesPeptides are bio-safe treatment ingredients with anti-wrinkle properties.The first peptide, Matrixyl (also known as pal-KTTKS), was developed and launched by Sederma, a division of Croda. In clinical studies it was shown to increase the synthesis of collagen I, collagen III and fibronectin. Copper peptide and the lipo-peptide (Matrixyl) are both used to stimulate collagen production and promote elasticity. Another category of peptides that modulate function at the neuromuscular junction is Myoxinol (Cognis) and Argireline (Centerchem). More recently, Merck launched the first of a new peptide generation, RonaCare Cyclopeptide-5. It reinforces the extracellular matrix resulting in firm, youthful skin.

EfficacyAdvancing age leads to decreased synthesis of matrix molecules such as collagen, elastin, fibronectin and glucosaminoglycans. Thinning skin leads to drying out and the disruption and weakening of the epidermal junction, which leads to wrinkle formation. Wrinkles truly are“skin deep;”i.e., they do not exist beyond the dermis and epidermal dermal junction. As we grow older, collagen production slows, resulting in a loss of skin elasticity and a decrease in the skin’s ability to hold moisture as the collagenelastin network weakens over time.

The primary function of most peptides is a signaling one. They bring a biochemical “message” and incite an action. Peptides trick older skin into producing collagen along with hyaluronic acid, a key factor in retaining moisture in the skin, which results in a plumping effect and a smoother, softer and younger looking complexion. Peptides’anti-aging benefits derive from its many forms such as tri, tetra, penta and hexa. Peptides act as messengers in the skin, providing signals to cells to regenerate. Some peptides stimulate new collagen formation while others prevent the breakdown of existing collagen.

Overall, peptides help improve the appearance of fine lines and wrinkles along with skin’s texture and tone. Different peptides have different functions. Since peptides are derived from protein building blocks, they are easily utilized and subsequently absorbed by the skin on many levels making them very effective skin care actives. Peptides in skin care mimic peptides produced by cells. This process slows down or reverses biological elements of aging and other skin conditions. The most important characteristic of a peptide, besides its size, is the precise order in which the various amino acids are linked together. Small peptide molecules easily penetrate the top layer of the skin to repair fine lines and wrinkles caused by sun damage. Topical collagen and elastin creams, on the other hand, have difficulty targeting collagen-producing cells to trigger regeneration in the bottom-up mode.

Many peptides, however, are incapable of penetrating through the stratum corneum, and thus are not able to exert their function. Gly-His-Lys peptide, being highly water soluble and also charged with ions, will stay at the skin surface and remain inactive. Chemical derivation such as palmitoylation (attachment of fatty acid) however, allows the peptide to reach the epidermis and even dermis.1

ClaimsTrue proof of the peptide efficacy comes from appropriate clinical studies. Antiaging finished products do not base their various claims on a specific ingredient. It is the entire composition as commercialized that produces the desired effect on skin or hair. In this way, peptides are not directly linked to the final claims. Advertised claims and their exact wording are critically important, so that peptide products are

144 UNDERSTANDING THE ANTI-AGING POWER OF PEPTIDES

not considered drugs, which would need regulatory approval—a filing process that involves costly and time-consuming new drug applications.

ConclusionPeptides are the leading technology for skin care being marketed today. All skin types tolerate them and they have better pH stability, broader application and biological activity. This is because peptides speak the language of the cells.There is some controversy over which peptides actually penetrate the skin. Pentapeptides such as Argireline and Matrixyl are by far the most effective in making skin look plump and youthful. New peptides with new activity are researched continuously, and are reported in the literature. The market is full of a variety of cosmetic products touting peptide’s antiaging benefits. There does seem to be science that shows that peptides have the potential to improve the appearance of aging skin. Most peptide products are reported to be safe with no side effects.

Reference:1. Lintner K et al. Int. J. Cosm. Sci. 22, 207- 218.

145

Chapter 14

THERE ARE NO NEGATIVES REGARDING ANTIOXIDANTS

ANTIOXIDANTS are widely used in cosmetics to prevent oxidation. When added to a formula, they ensure that all kinds of personal care products reach consumers in excellent condition and stay that way even after months

of use. Oxidation occurs when fats or oils react with oxygen. An oxidized product usually breaks down, develops a rancid odor and discolors. Common antioxidant preservatives include butylated hydroxyl toluene (BHT), butylated hydroxyanisole (BHA), tertiary butyl hydroquinone (TBHQ) and propyl gallate (PG). All are used at very low level, are very safe and effective. But today, in addition to their preservation benefits, antioxidants are recognized for protecting the skin. Accordingly, cosmetic products formulated with well-recognized antioxidants such as vitamin E, co-enzyme Q-10, ascorbic acid, alpha lipoic acid and soy isoflavones have appeared in the market.1 Consumers may not understand how antioxidants work, but they consume multivitamin supplements and apply antioxidant-based cosmetics every day.

Oxidation BasicsOxidation involves the donation of electrons by complete transfer from one molecule (donor) to another (receptor). The donor molecule is oxidized while the receptor is reduced. Oxygen radicals belong to a family of molecules known as the reactive oxygen species (ROS), which is widely thought to cause wrinkles, age spots, dryness, acne, cellulite and skin cancer. Electrons prefer to travel in pairs, but when there is one electron by itself, it immediately seeks a new electron to pair itself with by robbing one from another healthy molecule, thus creating singlet electrons and new free radicals. A chain reaction of oxidation is set in motion. Unless this chain stopped by the action of an antioxidant, basically an electron donor or receiver that gets electrons paired-up again, cell damage could occur. Damage is miniscule, but it is cumulative over time.

Antioxidants (Topical)Antioxidants neutralize the free radicals that occur naturally on the skin. They can reduce sun damage and skin aging. Antioxidants in other words, are those substances that interfere with oxidation either by blocking or reversing the action.

146 THERE ARE NO NEGATIVES REGARDING ANTIOXIDANTS

Antioxidants include vitamins A, C, D and E, alpha lipoic acid, co-enzymeQ10, genistein and green tea. Alpha lipoic acid is considered a universal antioxidant because it is soluble in both aqueous and lipid environments and can interact with both antioxidants and oxidants present in various cell compartments. It boosts levels of glutathione in all cells and improves antioxidant functionality of vitamin C, vitamin E and co-enzyme Q-10. It is known to strengthen the entire antioxidant network and rapidly penetrates human skin. It is a very potent antioxidant. Although it is produced by the body its production declines with age. It helps prevent cataracts, strokes, heart diseases and it is an antidote for mushroom poisoning. It is a powerful anti-inflammatory agent and is very helpful in the treatment of aging skin. Vitamin E: It is considered an antioxidant superstar. It is lipid soluble and has eight different forms. It is the anti-aging antioxidant, helpful via both oral and topical route. It has skin emollient and moisturizing properties. It helps control oxidative stress in the body. It helps heal arthritis and reduces inflammation. Vitamin C is called the hub of antioxidants. It is central to linking fat-soluble antioxidants to water-soluble ones. Its benefits are provided by both oral and topical route. It reduces the risk of heart diseases and cancer. It maintains a well- functioning immune system, may reduce the severity and length of a cold and minimizes the presence of viruses in the body. It boosts collagen production, making it essential for great skin and a healthy complexion. It protects against photodamage and is stimulant to wound healing.Co-enzyme Q-10 is present in virtually all living cells. It is both an energy generator and a fat-soluble antioxidant, and provides protection against both intrinsic and extrinsic aging. It regenerates vitamin E, a coenzyme that works with an enzyme to produce chemical changes in the body.

Genistein is an isoflavone from soy, with potent antioxidant properties, protecting against lipid peroxidation and UV damage.

Several studies support green tea’s potent antioxidant and anticarcinogenic properties. Other key antioxidants include beta carotene, plant extract of ginkgo biloba, centella asiatica, ginseng, rosemary, juniper, horse chestnut, phytic acid, and iron chelators.

Antioxidants (Botanical)Phytochemicals in chamomile, mustard, rosemary and turmeric may have a phase II boosting effect. EGCG (tea) neutralizes more than 70% of lipid peroxide, the free radical that destroys skin’s barrier properties. Cranberry oil protects skin’s barrier from free radical attack and oxidation. It also protects cell membranes, keeping them fluid and youthful by forming an antioxidant reservoir for long-lasting protection.

Thermus thermophilus, available from Sederma, is heat activated and stimulates the body’s natural enzymatic antioxidants during heat exposure. It repairs and protects against UVA damage. Dietary antioxidants such as vitamins and plant nutrients such as carotenoids are thought to significantly contribute to the antioxidant defense system; all are predominantly found in fruits and vegetables.2 Excellent botanical sources of antioxidants include berries, pomegranate, ginger, grapes, orange, plum, pineapple, lemon, dates, kiwi and grapefruit; legumes such as broad beans, pinto beans and soybeans. nuts, seeds and dry fruits such as walnuts, sunflower seeds, apricots and prunes; vegetables such as kale, chili pepper, red cabbage, peppers, parsley, artichoke, Brussel sprouts and spinach; and cereals such as barley, millet and oats; and finally, roots and tubers such as ginger and red beet. Grapeseed extract, pycnogenol and green tea extract all contain polyphenols, which are not only powerful antioxidants, but are complimentary in enhancing the effects of other antioxidants. Protection is accomplished via free radical scavengers and endogenous


enzymatic protection. Free radical scavengers directly bind to free radicals and thus inactivate them. For example, alpha tocopherol works by scavenging lipid peroxyl and hydroxyl radicals. Ascorbates or vitamin C work as a synergist to vitamin E and scavanges hydroxyl radicals. Ubiquinol-10 interrupts the chain at mitochondrial level of the cell. Beta carotene provides benefits by scavenging hydroxyl radicals.

Enzymatic protection enzymes support production of body’s own natural antioxidants by assisting cells in their production of antioxidant enzymes. This process is called endogenous antioxidants. These enzymes are made by the cells as and when they are needed during times of oxidative stress, and they optimize the body’s own natural antioxidant defense system. They primarily trigger activity of phase II enzymes (detoxifying enzymes), they recycle free radical scavenger antioxidants and contribute chemical reactants needed by the body to make cellular antioxidant enzymes.

Superoxide dismutase, catalase and glutathione peroxidase are the three antioxidant enzymes responsible for providing protection against free radical damage. Superoxide dismutase functions by trapping superoxide radicals. It exists in the body in two basic classes, copper/zinc superoxide dismutase is found in the cell cytoplasam, and manganese superoxide dismutase is found in the mitochondria.

Catalase exists throughout all body tissues and it provides benefits by detoxifying hydrogen peroxide. Glutathione peroxidase imparts its benefits by detoxifying lipid peroxidase and hydrogen peroxide. It uses selenium as its metal center and is found in the blood or the cell membranes. Antioxidant enzymes optimize the body’s natural cellular antioxidant defense system and deliver a long duration skin protection from reactive oxygen species (ROS). Skin derives antioxidant benefits both by free radical scavengers and antioxidant enzymes.

Free Radicals and AgingFree radicals are a by-product of the body’s natural function. If left unchecked they cause harmful oxidation that can lead to cancer and heart disease. Oxidation caused by free radicals in the body can best be compared to the rusting of metal which is known as oxidation. Researchers, who are studying age-related diseases, agree that excess free radicals are a major factor in the aging process. They are also responsible for the development of killer diseases such as heart, cancer and Alzheimer’s diseases. A free radical is any substance that contains an unpaired electron. They are highly unstable and react with other molecules. A free radical scavenger is any substance that terminates or blocks the free radical chain reaction. They either donate an electron to the free radical or absorb the extra electron to make the molecule stable.

Free radical scavengers are called antioxidants. If however the level of antioxidants is not enough or if the free radical damage is excessive, damage to the cells and tissue could result. When the body does not get enough antioxidant protection, either from the body’s production, from the dietary sources or from the topical products, the free radical damage continues, causing cell damage and resulting in their poor performance. This lack of antioxidant reserve leads to skin damage, which is manifested visually in the form of superficial lines, wrinkles, hyper-pigmentation and inflammation, correspondingly causing within skin, cross-linking of collagen and elastin, damage to the DNA resulting in cell deterioration.

There are many types of free radicals, the most common is reactive oxygen species that include hydroxyl anions, hydrogen peroxide, super oxides, and singlet oxygen. Studies have shown that reactive oxygen causes UV-induced damage to the skin. Oxygen free radicals cause lipid peroxidation, resulting in damage to cell membranes


that can cause premature aging and eventual cell death. Most researchers think ROS cause acne, wrinkles, skin age spots, sagging, dryness and cancer.

Environmental toxins and pollutants are all around us and their levels are increasing. Although the body is naturally equipped to fight off these free radicals, they can still contribute to inflammation and premature skin aging. Free radicals may be the result of diet, smoking, stress, aerobic exercise, inflammation, exposure to sunlight and air pollutants, and natural biological processes. It is medically recognized that degenerative skin conditions such as wrinkles and skin discolorations are caused primarily by free-radical damage.3 The primary causes of this damage are air and sunlight, but it can also be triggered by cigarette smoke, herbicides, pesticides, pollution and solvents. Antioxidants can reduce and potentially neutralize the rampage of free-radical damage.4

Topical BenefitsTopically-applied antioxidants help reduce damage caused by ultraviolet radiation, including erythema and cell damage. They induce the generation of glycosaminoglycans, reduce wrinkling and hyperplasia, and inhibit lipid peroxide formation. They also have anti-inflammatory properties and accelerate wound healing, stimulate collagen synthesis and enhance the immune system. Some antioxidants, such as vitamin C and E, reportedly deliver additional benefits of enhancing immune function, accelerating wound healing,5 boosting antiinflammatory action, reversing photodamage and stimulating collagen synthesis.6

Effective SkinCare Products Consumers get superior benefits from using products that are antioxidant dense and are used for protecting and repairing skin damage, because they work better when applied topically than when ingested. A study reported in Skin and Allergy News, confirm that antioxidants added to sunscreens provided greater protection from solar radiation, inhibited more lines and wrinkles and maintained greater skin elasticity and thickness than sunscreens without antioxidants.

It is FDA’s position that, while antioxidants may be beneficial, there is no guarantee that the use level is high enough to impact the skin. In fact, antioxidants may have been included merely to retard spoilage. In addition, vitamins C and E are large molecules that are difficult to getting through the epidermis. Even if they do penetrate, there is no hard proof that antioxidants have any effect.

Still, the science of skin-aging process is advancing at an accelerated pace. Some cosmetic ingredients do indeed get through the skin, and may deliver drug-like benefits. So even if antioxidant potions are changing the way cells function—there is no solid proof that they are—the FDA does not allow such claims.7

ConclusionAntioxidants provide a variety of benefits. They stop free-radical damage in our bodies. These molecules are linked to host of detrimental effects from illnesses to premature aging. Antioxidants help these toxins out of our bodies because as they accumulate, they produce an unwanted synergy of damage to the brain, lungs, livers and the entire body.

Antioxidants in the skin produce many benefits such as reduce or eliminate erythema or redness of skin, soothe skin irritation, reduce the signs of wrinkles, lighten age spots or uneven skin pigmentation, moisturize and soften dry, rough skin, also fight signs of acne and cellulite. Antioxidant enzymes optimize the body’s natural cellular antioxidant defense system and deliver skin protection from


reactive oxygen species (ROS). Skin derives antioxidant benefits both by free radical scavengers and antioxidant enzymes and protects skin from the damaging effects of ROS. Free radical damage is constant and extensive, but at this time no one is certain what level of antioxidants are needed in the skin care formulations and how long they do last.

References1. B. J. Salsbury, HAPPI, Jan., 2001, p. 752. S.J. Duthi et al. “Antioxidant supplementation human lymphocytes.” Cancer4. Journal of Clinical Pathology, March 2001, Vol.18, number 9, pages, 685-716.5. Darr, D., Combs et al. “Topical vitamin C protects porcine skin from UV radiation

induced damage,” J. Derm. 127:247- 253, 1992.6. Djerassi, D., Machlin and Noka, “Vitamin E biochemical function and its role in

cosmetics,” Drug & Cosmetic Industry, March, 1986.7. New York Times magazine, December 5, 1995.

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Chapter 15

DO STEM CELLS HOLD THE KEY TO YOUNGER-LOOKING SKIN?

STEM CELLS, though controversial, often play a key role in drug research. Now these materials are finding new applications in skin care, and stem cells are the latest buzzword in the anti-aging category. Yet scientific opinion remains

divided on their origin. One opinion is that stem cells arise when sperm fertilizes an egg, while the other is that they originate in the inner cell mass of the blastocyst. Stem cells have the ability to go through numerous cycles and cell divisions while maintaining their undifferentiated state. They also have the capacity to differentiate into other cell types such as muscle, blood and nerve tissue.

Adult stem cells reorganize, heal and repopulate the skin with new cells. They arise from the basal layer of the epidermis and at the hair follicle base. Adult stem cells, as opposed to embryonic stem cells, repair and regenerate damaged tissues. Theoretically they possess the ability to create new skin cells and regenerate the skin for a lifetime, but age and environmental factors cause them to function less efficiently, resulting in olderlooking, aged skin. Stem cell-based creams reportedly stave-off this process by either stimulating or protecting stem cells deep in the basal layer of the epidermis.

Stem cells divide relatively infrequently. With age, stem cells lose their proliferative capacity and perhaps their ability to respond to signals to produce more epithelial cells, according to R. Ghadially, a dermatologist and skin stem cell specialist at the University of California at San Franciscco’s Institute for Regenerative Medicine. Increasing proliferation is the ultimate complexion rejuvenator.

Stem Cells in SkinEpithelial skin stem cells are found in the basal layer of the epidermis, while hair bulge stem cells are found in hair follicles. Furthermore, hair follicular stem cells, tooth stem cells and skin stem cells all show therapeutic promise and may one day restore hair to bald men, teeth to those in need and skin to scarred patients, according to Dr. Denis English, editor of Journal of Stem Cells and director of cell biology at the University of South Florida.

151 DO STEM CELLS HOLD THE KEY TO YOUNGER-LOOKING SKIN?

Changes in the skin are caused by aging, disease or injuries. Although drugs can relieve consequences of the disease, they will not suppress the cause. Therefore, the most attractive strategy is to replace disabled cells, and to this end, to take advantage of stem cells.1 According to Gregory Brown, creator of ReVive, accessibility also makes skin stem cells appealing to cosmetic chemists. Stem cells are readily available in hair follicles and sweat glands. The ratio of stem cells to regular cells in skin is still hotly debated. It was once thought to be 1 in 10, but is now suspected to be more like 1 in 10,000.

Stem Cells and AgingStem cells have a limited life expectancy because UV, smoking and ozone all hasten skin cell depletion, resulting in DNA damage, telomere shortening and oxidative stress. Cell depletion does not activate stem cells to change into new cells. Aging stem cells lead to a decreased capacity for repair, an increased incidence of degenerative diseases and an increased incidence of cancer in tissues that contain stem cells. Skin rejuvenation comes to a halt when stem cells remain inactive. Under the right stimulus, stem cell activity could be jump-started to initiate skin rejuvenation.

Stem cells have unique secondary structures of DNA and RNA. Stem cells have special components in the cytosol-epigenetic factors. Stem cells are sensitive to environmental stress factors and hence protection and maintenance of stem cells is of great importance. Epigenetic profiles regulate the gene expression in stem cells, which enable cells to stabilize and maintain different characteristics despite containing the same genomic material. This is achieved by chromatin remodeling by DNA methylation (gene silencing), post-translational modification of histone proteins (e.g., acetylation for transcriptional competence) or mRNA inactivation through micro RNAs or small interfering RNA (siRNA).

High-Priced ProductsMarketers are presenting stem cell creams as the future of skin care. This article will review major stem cell-based anti-aging consumer products and the science surrounding stem cell technology.

Amatokin is available from Voss Laboratories in collaboration with Beilis Development Company. It has a hefty price tag of 190 euros or $258 per 30ml. Less

expensive is Christian Dior’s Capture R 60/80 XP cream, which still costs more than $100 for 30ml. StimulCell from N.V. Perricone retails for $155 for 1.7fl.oz. Another product based on cellular tune-up action that is similar to stem cell is Estée Lauder’s Re-Nutriv, which costs approximately $130. But the costliest product is ReVive’s Peau Magnifique Youth Recruit. It comes in a lucite cube that houses four small silver tubes. A one month supply of this super serum costs $1,500…can you believe it? The company insists that the high cost is because of a telomerase which is a bio-engineered enzyme costing about $4 million per gram.

Voss’ Amatokin

Estee Lauder’s Re-Nutriv creme does not contain stem cells, but its formula provides many of the same benefits.


Actives and ClaimsAlthough all of these products make similar claims, their backgrounds are quite different. For example, Amatokin got its start in 1988 when Russian scientist Taras Nikolaev from the Biotechnical Institute in Moscow and St. Petersburg studied peptide research to accelerate wound healing and skin repair. His team created a polypeptide with the ability to stimulate dormant stem cells in the skin, rejuvenate the skin and speed healing—truly a bold, astonishing claim. Amatokin is the first topical polypeptide that lights up stem cell markers (the means by which cell activity is measured). The polypeptide acts as a catalyst when it comes into contact with the upper keratinocyte cells of the epidermis, initiating a molecular signaling cascade that produces the increase in activity which was measured by the stem cell markers.2

In the case of StimulCell, young, undamaged cells were created by applying chemically reproducible oxidative stress to stem cells, which forces them to pump out 145 different proteins, carbohydrates and lipids. These materials are protect cells and relay regenerating messages, according to Dr. Perricone.

For Dior Capture R 60/80 XP crème, the active is a vitamin E derivative called alpha-tocopheryl phosphate, which creates a protective shield. ReVive Peau Magnifique Youth Recruit has an enzyme active called telomerase, which was first discovered in 1984, according to Bays Brown, the brand’s founder. Finally, Re-Nutriv contains a stabilized version of reservatrol, an antioxidant produced by some plants to ward-off fungi and bacteria.

Amatokin initiates the release of very powerful growth factors responsible for cell proliferation, according to Louie Rinaldi of Voss Laboratories.

According to R. Ghadially a dermatologist and skin stem cell specialist at the University of California at San Francisco’s Institute for Regeneration Medicine, this product increased the expression of certain stem cell markers. We only know what those markers indicate in embryonic cells. It has not been proven that they have the same correlation in adult cells. It is very promising, but more work needs to be done. His lab is conducting independent research on whether the markers in question do in fact indicate the presence of adult stem cells.3

How it WorksAmatokin highlights the expression of stem cell markers in the skin to reduce the appearance of serious wrinkles. It focuses on using polypeptides and enzymes to “awaken” the body’s own reservoir of stem cells. We only know what those markers indicate in embryonic cells. There is no proof that the same holds true in adult cells. While very promising, more work needs to be done.

StimulCell contains cell-protecting and regenerating messengers. When the product is applied topically, these messengers reportedly attach to skin cells, signaling them to begin the reparative process. In one study, Dr. Perricone’s product

reduced acne, skin damage and wrinkles using the cell’s own messengers. A cell is carefully guided toward rejuvenation.

In an in-vitro study by Dior, the alpha-tocopheryl phosphate in Capture R60/80 XP reduced the number of stem cells lost in the epidermis after sun exposure. The company recruited 30 women scheduled for facelifts and asked them to use the cream on one cheek

ReVive Peau Magnifique Youth Recruit’s efficacy is due to the telomerase enzyme.


for two months before surgery. The treated skin showed 19% more epidermal cells. Rather than purporting to stimulate stem cells, this product makes rather modest claims that it protects and prolongs the functioning of the stem cells. The company asserts that the product’s effectiveness is due to Stemsome, a sophisticated delivery system that transports ingredients into the skin. The system envelops each active ingredient in multi-stacked layers, which progressively melt as they are absorbed by the skin, releasing the active ingredient. According to Edouard Mauvais-Jarvis, director of scientific communications, each time a layer melts, the next one opens, enabling the ingredients to reach their target deep within the skin. This technology doesn’t enhance the cells in any way, it merely creates a more beneficial environment to allow the stem cells to play their optimum role in regulating the skin.

ReVive Peau Magnifique Youth Recruit’s efficacy is due to telomerase, an enzyme that aids DNA replication to prevent chromosomal strands from losing bits of information when they split, thus warding off genetic mutations. When applied topically, it can also send a signal to stem cells, rallying them to respond as they would to an injury. Epidermal Growth Factor (EGF), a protein found naturally in the human body that is released from the cells after injury to increase cell turnover, does accomplish regeneration of aging skin. The product does not alter the body’s natural functions nor changes skin in any abnormal way. It does not add or inject stem cells into the skin. It merely stimulates and accelerates a natural process. It purports to convert resting adult stem cells to newly minted skin cells.

The active in ReNutriv, reservatrol, extends the life of cells, actually slowing down turnover rather than speeding it up—possibly the best way to ward-off cell breakdown.

DiscussionSome observers complain that Amatokin, and any other ingredient that causes cells to multiply, could cause cancer due to cell division.

“You don’t want a signal that just says: ‘turn on’ to stem cell activity. That’s like a car that just has a gas pedal—it could be dangerous, resulting in overproduction, potentially even cancer,” agreed Dr. Perricone. “You want cells that turn on, cells that moderate, cells that suppress activity, cells that steer.”

However such fears are dismissed2 because you are stimulating adult stem cells which start as pristine, unformed cells. Given the proper environment, they undergo a maturation process to become a new cell and then migrate, through cellular communication, to the area of damage, telling the fibroblast cells, “it is time for you to die, I am here to take your place.”

So, you get a brand new cell replacing an old, aging cell that is removed naturally from the body.

Stem cells’ low rate of division is actually a protective measure, according to Dr. Geraldine Guasch, a researcher at Rockefeller University, New York, NY. The more cells divide, the greater their chance of DNA mutation. Cancer is basically the result of haywire cell production. Mutated stem cells may cause cancers to grow back even after chemotherapy, which could make skin stem cells’ inherent accessibility more of a bane than a benefit. Susceptibility to UV damage could mean they are prey to even more mutations than internal cells. In skin, it has not been demonstrated yet that a stem cell can be the start of cancer. If a company claims to increase stemcell activity, Dr. Guasch wants proof that the chromosomes of these new cells do not accumulate mutations. Besides, as Dennis Gross, a New York City dermatologist, points out, anything that alters cellular activity, constitutes a drug claim and require FDA approval. Dr. Perricone is considering equipping his Madison Avenue flagship


boutique with a machine that would enable him to harvest and store clients’ individual stem cells — other innovators are focusing on preserving the cells we already have.1

Some experts question whether the enzyme found in ReVive Peau Magnifique Youth Recruit truly ignites stem cell differentiation. Telomerase plays a role in some, but probably not all, stem cells, says Amy Wagers, a principal faculty member of the Harvard Stem Cell Institute in Cambridge, MA. Dr. Wagers is not familiar with any data suggesting it directs their differentiation or wakes them up. Regarding before and after photos that show a dramatic improvement in skin tone and texture with fewer fine lines, Dr. Gross noted that many active ingredients work on skin cells to stimulate them to make byproducts like collagen. This is very different from stem cell technology in which the cells themselves form tissue.

Meanwhile, with the debut of Capture R60/80 XP, Christian Dior became the first global luxury brand to tap into stem cell technology.

Storage BanksRecently two teams of researchers transformed ordinary skin cells into batches of cells that look and act like embryonic stem cells— those master cells that give rise to every cell and tissue in the body. Moreover, they accomplished that without cloning technology or embryos. Dr. Shinya Yamanaka of Kyoto University, Japan, recently said that creating a bank to store a new type of stem cell produced from donor’s ordinary skin cells could reduce time and money for treating patients. This research makes it possible to reset an aging cell to become an entirely new being, and may give rise to powerful anti-aging actives in the future. Several companies, including Bio Eden, C’elle, Neostem and Store A Tooth, provide stem cell extraction and storage services, though viable therapies may be years away

Apple Stem CellsMibelle Biochemistry launched an anti-aging active based on an extremely rare form of apple stem cells. It promises to protect skin stem cells and slow the senescence of hair follicles. In vivo and in vitro tests proved that the ingredient, PhytoCell TecMalus Domestica, boosted the production of human stem cells, protected them from stress and decreased facial wrinkle depth. It also delayed the aging of the hair follicles, suggesting a possible use in anti-aging hair preparations.

Not everyone is convinced that stem cell creams are the future of anti-aging. There are not enough published scientific data available to support its safety and efficacy in skin care products at this time. Stem cells are very popular, but many dermatologists remain skeptical. Alan Matarasso, a cosmetic plastic surgeon in New York City, noted that the theory of stem cells sounds good but the question is, whether or not a topically-applied cream can send signals to activate these stem cells. Until there are double-blind clinical studies, their efficacy is unproven. Ultimately it is up to the consumer to decide if the results live up to all the hype.

An apple a day...keeps wrinkles away?


According to David Colbert, a New York City dermatologist, it may be premature to choose a stem cell cream over one with, say, time-proven retinols or hydroxyl acids. Stem cell research is still very young. There is much more information to unravel.

Nanotechnology, DNA and now stem cell technology have all recently entered the skin care category. My concern is that these highly scientific technologies are marketed to consumers at ridiculously high price. No one is looking seriously at whether the drug-like claims that are being made for these technologies are truly accurate or if their long-term use would put the consumer’s health and safety at risk.

References:1. Stem cells, P. Jones, Nov. 2007, SPC.2. L. Rinaldi, Voss Laboratories, Salt Lake City, Utah.3. Investigation, micromanagement, M. Bullock, Elle, Dec. 2007.

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Chapter 16

ANTI-AGING BENEFITS OF ASCORBIC ACID

ASCORBIC ACID is a potent, naturally occurring, water-soluble vitamin with photo-protective and anti-inflammatory properties. This antioxidant is not produced by the human body. Free radicals, those rogue molecules

that irreparably harm cells, cause inflammation, tissue damage, age-related health problems and accelerate the aging process, are generated by pollutants, smoking, radiation and UV light. This column will briefly review the antioxidant and anti-aging properties of this important component to human health.

There are a variety of ways to boost your vitamin C intake.

157 ANTI-AGING BENEFITS OF ASCORBIC ACID

Ascorbic acid, also known as vitamin C, has become one of the most widely used ingredients in anti-wrinkle and anti-aging creams. Anti-aging products accounted for 23% of the total global skin care market in 2008 and grew faster than any other product type within skin care. The category was forecast to grow at a compound annual growth rate of 5% in real terms, to reach $22.5 billion by 2013.

Product DevelopmentL-ascorbic acid is closest to a natural form of vitamin C found in skin care products. It is unstable due to its low pH, which increases its irritation potential. It oxidizes when exposed to air. It can be formulated into water or lipid soluble forms. It must be stored in a dark, cool place. Light breaks down vitamin C, making it acidic and thereby rendering it ineffective.

Magnesium ascorbyl phosphate (MAP) is a gentle form of vitamin C ester. It is least irritating and is known for its ability to plump and brighten skin and remains active against free radicals. It is easy to formulate, absorbs well into the skin and is good for collagen production. MAP is made from a mix of l-ascorbic acid and palm oil. The combination creates a nonacidic, fat-soluble vitamin C that does not generate free radicals, so there is no inflammation. It does not oxidize like the acidic form and does not degrade easily. It absorbs well by penetrating skin better and more rapidly, stimulating fibroblasts which, in turn, generate new collagen and thus help inhibit wrinkle formation while protecting skin cells against damage.

Vitamin C is very sensitive to oxidation and gives finished formulas a yellowish color as they age. There are many cosmetic products available that contain different forms of vitamin C.1-4 In order to develop an effective vitamin C topical product, usually it is preferable to use l-ascorbic acid at 10% level with the formulation having pH 3.5 for superior efficacy. However, some consumers’ skin can be irritated by daily application of low pH product. Studies have suggested that l-ascorbic acid is absorbed by the skin when formulated in an anhydrous waterin-oil emulsion system. It is helpful to add metal-chelating agents such as EDTA to improve storage stability. Vitamins C and E contribute to mutual stability and increase overall efficacy.5 Vitamin C plays part in reactivating the vitamin E molecule after it has reacted with a free radical. Further studies have shown that this combination product when applied topically provides a four-fold skin protection.6 There are products that have combined 3% l-ascorbic acid with 0.04% retinol. Vitamin C, when combined with phloretin and ferrulic acid, showed a protective effect against photodamage.7

Efficacy & BenefitsTopical products have an advantage over ingestibles in that they can target vitamin C to the area of the skin needing the protection. Tissue levels are saturated after three daily applications; the half-life of tissue disappearance is about four days.8 There is evidence that vitamins C and E accumulate in the skin. Many different topical products with varying vitamin C concentration are available, but some studies show that skin absorption of lascorbic acid at pH 3.2 peaks at 20% and decreases at higher levels. Some studies have shown that skin requires more vitamin C as it ages.

There is considerable evidence to support vitamin C’s effectiveness on skin. Vitamin C neutralizes free radicals before they attack skin cells and prevent premature signs of aging including fine lines and wrinkles, protects against future damage and helps prevent the development of skin cancer caused by UVA and UVB exposure.9 The collagen synthesis stimulating properties of vitamin C accelerates An increase in collagen synthesis helps thicken skin. It also helps fight tumor formation

158 ANTI-AGING BENEFITS OF ASCORBIC ACID

and slows down skin cancer. It increases moisture content of skin by thickening it. Its skin-barrier improvement and anti-inflammatory properties make it an ideal component of post-laser skin resurfacing treatments. Vitamin C may even prove to be an effective treatment for melasma.

In conclusion, topically applied vitamin C has an important role in the treatment of aging skin. Due to confl icting research, there is no way to know which grade, concentration or pH of vitamin C has the best stability.12 Unfortunately, many of the current topical products cannot penetrate the stratum corneum and are consequently, useless. Furthermore, these products are not packaged in airtight and light-resistant containers and hence become inactive just hours after opening the package.

References:1. Humbert et al. Exp. Derm. 2003; 12:237-2442. Traikovich S. Arch. Otolary. Head, Neck surgery 1999, 125:1091-1098.3. Epinal-Perez et al. Int. J. derm 2004:43; 604-6074. Seite et al. Skin Pharmacol. Physio. 2005; 18(2);81-75. S. Pinnel et al, Derm. surgery 27, 137-142(2001)6. J. Lin et al J. Am. Acad. Derm. 48, 866-874(2003)7. C. Oresajo et al. J. Cosm. Derm. 7 , 290-297 (2008)8. Pinnell et al. Derm. Surgery 2001:27(2) 137-429. Pinnell, J. Am. Acad. Derm. 2003:48 1-19.10. Humbert. Eu. J. Derm 2002: 11:172-17311. W. Smith Int. J. Cos. J. 1999, 21:33-4012. Derm. Surg. Feb. 2001, pages 137-142.

159

Chapter 17

SKIN LIGHTENING PROPERTIES OF ASCORBIC ACID

Popularly known as vitamin C in its primary form, L-ascorbic acid has a proven track record for improving the appearance of aging skin; no wonder it is the most common antioxidant ingredient in OTC skin care products. Vitamin C

stimulates formation of collagen, which is the natural cement and scaffolding found throughout the body. It also plays a role as a water-soluble antioxidant that helps prevent free radical damage to cells.

This column will briefly review the skin lightning properties of vitamin C.

Skin LighteningVitamins C and E behave as antioxidants by protecting cells from oxidized compounds and free radicals by giving up their electrons to compounds that need them. This action keeps those compounds from going out and injuring other molecules. Humans lack the enzyme necessary for synthesizing vitamin C, so they must obtain it through oral ingestion or topical application.1

Topical application has shown to be superior for replenishing skin concentrations of vitamin C.2 Researchers have identified three vitamin C derivatives— magnesium ascorbyl phosphate, sodium ascorbyl phosphate and ascorbyl-glucoside—all with improved stability that efficiently convert to L-ascorbic acid in the skin to leave it firmer, healthier and more youthful.3,4 OTC creams that contain vitamins C and A, and/or soy, all have a mild pigmentlightening effect. This lightening process can be accelerated using home peels and home micro-dermabrasion as exfoliation enables actives to more effectively penetrate skin. Clinical studies have shown that ascorbyl glucoside safely modulates common forms of hyper-pigmentation such as: age spots and difficult-to-treat melisma.5,6 This stems from its ability to block the action of tyrosinase, a key enzyme involved in the formation of new melanin.7,8

In one clinical study, patients ages 30 to 50 with facial hyperpigmentation applied an ascorbyl glucoside topical formula to one side of their face daily for four weeks. At the end of the study, the treated side of the panelists’ faces showed a significant reduction in total area of hyper pigmented spots. Furthermore, 70% of subjects treated with ascorbyl glucoside reported lighter skin compared to 16.6% in the untreated group.9

Another popular ingredient is a stabilized derivative of vitamin C called magnesium ascorbyl phosphate or MAP. It inhibits tyrosinase, the main pigment

160 Skin Lightening Properties of Ascorbic Acid

forming enzyme. Research has shown that MAP enhances the skin’s ability to retain water, making it visibly softer and smoother.10,11 In a controlled clinical study, human volunteers applied topical MAP to their forearm skin daily for four weeks. Researchers used corneometry and cutometery to objectively measure skin hydration. By these measures, MAP significantly increases hydration in both the outer and deeper layers of the skin, thereby demonstrating sustained effects.10 This finding was later confirmed in yet another trial.11

FormulationsVitamin C inhibits tyrosinase, but not as effectively as other agents. MAP is a stable derivative of ascorbic acid and can suppress melanin formation at levels of 3-10%. It is converted to vitamin C in the skin by non-specific esterases. Barnet Products supplies BV-OSC (Tetrahexyl decyl ascorbate), a very stable oilsoluble vitamin C. It penetrates the cells more effectively which is confirmed by data on keratinocytes, and fibroblasts. It reduces melanin synthesis by 80%. It is approved as a quasi-drug skin lightener in Japan.

Vitamin C-based products should be formulated at a low pH to help skin absorb the vitamin. Product jars should be kept airtight to prevent oxidation. These products have been shown to penetrate the skin and protect against free radical formation. Although adverse effects are minimal, ascorbic acid is relatively ineffective when used alone. Therefore it is usually combined with other agents such as licorice extract, according to Zoe Diana Draelos, MD. It helps to formulate the product with ferulic acid, a powerful free radical scavenger slows down the breakdown of vitamin C and enhances its protective effects against ultraviolet damage. When added to a combination of vitamin C and E, ferulic acid doubled its photo-protection properties from 4- to 8-fold.12

To be effective, lightening products must be formulated in a high concentration of at least 5% or greater strength of active material. There are brightening formulations that combine retinol and vitamin C for brightening. Every clinical study has proved that stabilized forms of vitamin C in its active form as L-ascorbic acid has multiple skin benefits, but its susceptibility to oxidation limits its stability in topical preparations.

References:1 Naidu, K.A., et. al., Nutr. J. 2003: 2:72 Telang, P.S., Indian. Derm. Online J. 2013:4 (2):143-63 Austria, R., et. al., J. Pharm. Biomed. Anal. 1997:15(6) 795-8014 Knaggs, H. Cosmet. Derm. 2009:8(2) 77-825 Taylor, M.B., et. al., J. Drugs. Derm. 2013:12(1) 45-506 Kinetiktech.com/brochures/pdf/rahn leaflet7 Sarkar, R., et. al. J. Cutan. Aesth. Surg. 2013, 6(1): 4-118 E Banks, J.P., et. al, Int. J. Mol. Sci 2009: 10(9):4066-879 Hakozaki T., et al. Skin Res. Tech. 2006-12(2): 105-13.10 Campos P.M., et al. Skin Res. Tech. 2008:14(3): 376-8011 Campos P.M., et al. Photochem. Photobiol. 2012:88(3): 748- 5212. Lin F. et al. J. Invest. Derm. 2005:125(4) 826:32

161

Chapter 18

THE HEALTH & BEAUTY BENEFITS OF ASTAXANTHIN

THE CONCEPT of ingestible beauty is gradually gaining acceptance. According to Datamonitor, 2005 sales of oral beauty supplements were $767.6 million in Europe compared with $741.9 million in the U.S. and will reach $1.16 billion in 2010.

Growth drivers include consumer’s need to stop the aging process, their fondness for natural products and their belief that only limited benefits come from slathering creams and lotions on the body. As a result, botanical extracts, fats and oils and other natural products are expected to register sustained growth because they are ideal ingredients for formulated products and consumers see them as improving their health. With Baby Boomers starting to gray, there’s a real need for unique raw materials and make-me-feelbeautiful technologies focused on delivering anti-aging benefits.

One of them is a relatively unknown compound called Astaxanthin which belongs to the family of carotenoids and is more familiar than you think. The pink color of salmon is a result of astaxanthin. Salmon accumulate high level of astaxanthin from their diet which may help to protect them from free radical damage caused by the environment or the physical stress caused by upstream spawing

ChemistryAstaxanthin is extracted from the marine microalgae, Haematococcus pluvialis. It contains astaxanthin and other carotenoids such as carotene, canthaxanthin and lutein in its own natural oil that also contains Omega- 3 and Omega-6 essential fatty acids. These natural compounds are important nutrients and protectants for the skin and for the whole body health.1 Astaxanthin’s potency has to do with its chemical structure. A cell membrane is like an Oreo cookie. It has two lipid layers (the cookie wafer) separated by a center (the cream). Antioxidants reside either outside the first cookie layer or inside the cream.

Antioxidant BenefitsAstaxanthin is powerful and safe antioxidant. It is more potent than vitamin E and beta carotene. It exerts its action by physical quenching rather than by a chemical reaction. It occupies a superior position in cell membranes because it is both aqueous and lipid soluble. How does it work? We know that it is produced by micro-algae when they are exposed to intense sunlight. As an antioxidant, it protects the algae from UV radiation allowing them to survive even in the harshest of conditions. Similarly, it protects body tissue from oxidation.

162 THE HEALTH & BEAUTY BENEFITS OF ASTAXANTHIN

Product DevelopmentTypical white creams and lotions, when formulated with astaxanthin would develop a strong red, orange or yellow color. A topical cream would develop a salmon color when 0.03- 0.07% astaxanthin is incorporated. Adding micronized titanium dioxide helps reduce color intensity. Colorless carotenoids for topical application and oral consumption are available from IBR Ltd. Co., Ramat-Gan, Israel.

Health BenefitsPositioned at the bottom of the food chain, single cell micro-algae plants take energy from the sun and combine it with organic residues to produce nearly all living material and food on earth. They represent one of the most concentrated, healthiest and power-packed foods humans can consume. Mass cultured, micro-algae produces a number of nutritionally beneficial substances such as polyunsaturated fatty acids, carotenoids and polysaccharides. Health benefits include boosting the body’s overall antioxidant status and protecting it from a variety of oxidative stresslinked diseases. Astaxanthin has proven to be a multifunctional supplement. Research has shown that its oral consumption is helpful in the areas of muscle endurance, skin protection, eye strength, gastrointestinal health, immune function and fertility.

Wrinkle ReductionA preliminary human clinical study demonstrated anti-wrinkle benefits in females using topical cream containing astaxanthin (Table I). A dermatological assessment revealed a significant reduction of wrinkles and puffiness on the lower eye and cheeks after two weeks of use.2

Moisturization: In a separate study using female subjects, instrumental analysis recorded a significant moisture improvement in the skin (p<0.05) after three weeks of product use.

Anti-inflammatory: It is known that inflammation that normally follows sun exposure is modulated by powerful antioxidants. In a clinical study it was shown that topical astaxanthin significantly reduced burn level (erythema) by 60% at 98 hours after UVB exposure.3 Suppression of post UVB hyperpigmentation: Synthetic and natural form of astaxanthin reduces the reddening and recovery after UVB radiation.

Table I: How Astaxanthin Maintains Skin Health

Benefits MechanismTopical Route

Dietary Route

Increase skin’s ability to resist environmental stripping of skin nutrients.

Restores skin’s natural antioxidant balance (SOD, CAT, GSH) Protects cell membrane against lipid peroxidation

Reduce puffiness and erythema.

Suppresses the inflmmatory pathway

Prevent and reduce presence of UV-induced wrinkles. Firmer and elastic skin. Increased moisture

Protects the dermal layer against oxidative stress dysfunction.Allowing repair process to heal collagen network.

Reduce the risk of skin cancer.

Protects against accumulated DNA damage.


This is also the leading cause for a skin condition called hyper-pigmentation. Natural astaxanthin demonstrated faster recovery times of the erythma index suggesting anti-inflammatory properties that may also contribute to the reduction of hyper-pigmentation.4

Melanin synthesis inhibition (cell study): Skin pigmentation such as stains and freckles are caused by excessive, uneven melanin production. Melanin is known to reduce tyrosinase activity which will reduce pigmentation. This can be achieved by inhibiting the synthesis of tyrosinase or by using an antagonist substrate for tyrosinase. Pigmentation is also prevented by inhibiting auto-oxidation of dopa and suppressing inflammatory reactions such as erythema following UV irradiation. Whitening agents such as arbutin, kojic acid and ascorbic acid derivative inhibit tyrosinase synthesis. This study conducted by Kose investigated the potential whitening effect of astaxanthin relative to the other whitening agents. Astaxanthin dose-dependently reduced melanin deposition. Astaxanthin did not inactivate isolated tyrosinase and this suggests the mechanism of melanin reduction by inhibition of the auto-oxidation of dopa and dopaquinone. There are other astaxanthin containing preparations for prevention of skin aging that have been developed.5

Oral: True beauty starts from within. Unhealthy skin is dry, dull, discolored without its youthful glow. Astaxanthin is consumed as a supplement for skin benefits. Although this may not strike the consumer initially as a means of caring for the skin, it is the concept of beauty from within which Fuji Health Science was the first to promote in Japan. Several clinical studies have clearly shown benefit for the skin in elasticity and subsequent reduction of fine wrinkles. Best results were seen when the oral supplementation (Astavita skin defense complex) was accompanied by using a topical products branded as Astacure–a retail line marketed throughout Japan.

Wrinkles: The benefits of daily astaxanthin supplementation (4mg) were demonstrated in a single blind placebo controlled study. There were significant improvements in fine lines/wrinkles, elasticity and in moisture content.2

Anti-inflammatory: It provides cytokine regulation inhibiting the expression of inflammatory cytokines and chemokines. Thus it acts as an outstanding anti-inflammatory. In a clinical study, each capsule contained 2 mg. of astaxanthin. Skin dryness, moisture, roughness, elasticity and fine lines were reduced. Over 50% of subjects in the treated group had subjective improvement of all items. Elasticity in treated group was significantly improved at week 6. Moisture content and elasticity were improved when measured at week 3 and week 6 compared to the baseline initial values.3 Skin surface photographs of four subjects in the treated group at week 6 showed improvements of elasticity, wrinkles and fine lines.Astaxanthin is determined safe for topical use. It is listed in the J P Cosmetics, and the INCI name is: Haemotococcus pluvialis extract. There were no adverse topical reactions in animal sensitization models.5

ConclusionHealthy, beautiful skin requires a sensible diet, topicals and daily supplements. You can utilize the potent cosmetic properties of this new ingredient as part of the daily skin care program. The cosmetic effects on the skin observed from the oral use of astaxanthin and the cosmetic effects of topical use of astaxanthin in clinical study have established astaxanthin as both a potent anti-aging cosmeceutical as well as a nutricosmeceutical ingredient. It plays an important role in protection of cells because of its exceptional anti-inflammatory properties. New skin care products combine topical and oral ingredients.Last year, the Beauty-from-Within concept bloomed and today’s cosmeceuticals merge supplements with creams, lotions and other topically-applied skin care


products. Many of the newest cosmeceuticals are actually based on ingredients with a long history of use in other applications, making them familiar to manufacturers and consumers alike.6 Astavita holds a library of patents relating to these health and beauty benefits.7 There is a substantial body of published scientific and medical literature about astaxanthin including the results of pre-clinical studies and human clinical trials. All clinical studies conducted, used astaxanthin branded as AstaREAL, a high quality, purified raw material from Fuji Health Science, Mt. Laurel, NJ.

References1. Astaxanthin- Antioxidant from the sea. Dr. R.C. Honour, chairman , Elura (Seattle,

WA).2. The effects of dietary supplement containing astaxanthin on skin condition., Dr, E.

Yamashita, Fuji Health Science Co., Japan.3. Seki, T. et al(2001), Effects of astaxanthin on human skin. Fragrance Journal 12:98-

103.4. Yamashita E. (1995), Suppression of post-UVB hyperpigmentation by topical

astaxanthin from Krill. Fragrance Journal 14:180-185.5. Koura, S (2005), skin sensitization study of astaxanthin in guinea pigs. Study

number 05035. New drug Research Center Inc. Hokaido, japan.6. D. Schatzman, Nutritional Outlook, p.39-43, vol.10, issue 5.7. Suzuki. JP # 08073311 and JP 08073312.

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Chapter 19

A ‘STINGING’ ENDORSEMENT FOR HONEY AND BEE VENOM

The term “natural” has considerable market value in promoting skin care cosmetic products to consumers. We are familiar with natural ingredients such as jojoba, safflower oil, rose hip seed oil, shea butter, beeswax, aloe vera, witch

hazel, tea tree oil and chamomile, to name just a few.More recently, cosmetics manufacturers have latched on to two natural

ingredients: honey and bee venom. Neither material is new; in fact, honey’s and bee venom’s medicinal use can be traced back to ancient China and Greece. This column will briefly discuss their emerging anti-aging benefits that are creating a lot of buzz in the cosmetics industry. Let’s take a closer look at both of these natural ingredients.

Honey: You may not be aware that honey has been used to treat wounds for centuries. Honey soothes dryness, protects against sun damage and fights acne. In the US alone, there are nearly 300 varieties of honey ranging in color from translucent yellow to dark brown. Different colors signify varying nutrient content. A darker color suggests a higher antioxidant value, as it has less water and therefore is more concentrated.

Honey benefits the skin complexion with a trace amount cocktail of important vitamins and minerals such as vitamin B complex, vitamin C, minerals, amino acids, riboflavin, niacin, magnesium, potassium, zinc and enzymes. Honey’s flavonoids and phenolic acids are a mixture of potent antioxidants that scavenge and eliminate free radicals.

A Honey of an IngredientAs the skin ages, it progressively thins and its capacity to retain moisture is diminished. Topically applied honey-containing products come to the rescue because they attract moisture from the air and lock into the upper layer of the skin1 creating a moisturized skin. Honey is an excellent anti-inflammatory and antibacterial agent, providing help in healing acne wounds because it clears infection, stimulates immune system and reduces inflammation.

Laura Mercier recently launched Crème Brulee Honey Bubble Bath. A honey dipper is provided for swirling the skin-softening vanilla emulsion into the tub. New Zealand-based Bee Bio company has launched a complete honeybased anti-aging range. Product claims include reduction in fine lines, wrinkles, improvement in skin tone, dark spots, firmer, smoother, softer, more radiant skin.

166 A ‘STINGING’ ENDORSEMENT FOR HONEY AND BEE VENOM

Bee Venom: contains a peptide known as melittin, which is known to increase blood circulation. It is used cosmetically to “fool” the skin into thinking it has been lightly stung. This causes the body to direct blood toward the area, tightening the skin. This stimulates body’s own natural chemicals: collagen and elastin. Collagen strengthens the tissue while elastin helps the skin remain taut and elastic. This is often accompanied by slight tingling— a sign that the product is working.2

The process of extracting the venom from bees is an arduous process. Bees are shocked at a low level, which causes them to secrete their venom, which is then collected on glass plates. According to agricultural researchers, it takes 10,000 bee stings to generate just one gram of dry venom, which explains why high-end products containing bee venom are so costly.

Yet, the high cost hasn’t stifled a stampede for bee venom-based products in the UK. Demand for the stuff surged even higher, when it was revealed that Catherine, Duchess of Cambridge, tried a bee venom mask prior to the royal wedding in 2011.

The UK’s Beetox Co. has launched a skin care range employing anti-aging claims such as reduction in redness, lines, wrinkles and large pores; calming and soothing of the skin; and improving skin texture. Another UK-based company, Rodial, has launched a bee venom skin care range with prices ranging from $178 to $248.

The Doctors’ OpinionHoney is one of the most time-tested skin fixes around, according to Dr. Joshua Zeichner, a dermatologist at Mount Sinai Medical Center, New York. It has been used as an antibacterial remedy for centuries because it naturally contains hydrogen peroxide. Honey’s anti-aging benefits are confirmed by dermatologist Dr. Mervyn Patterson who suggests that the sugar in the honey draws water out of the skin, producing skin tightening, creating a smooth skin surface. Dr. Kristine Schmalenberg of Johnson & Johnson maintains that bee venom has really risen to the top of the list of new efficacious skin care ingredients.

According to Dr. Sang Mittan, a research biologist at the national academy of Agricultural Science in South Korea, bee venom is an effective alternative treatment to antibiotic acne therapy, and a must for anti-aging and collagen production. According to Mittan, bee venom works on both dermal and epidermal levels to reduce fine lines and wrinkles through accelerated cell regeneration, increasing production of epidermal growth factor (EGF) that, in turn, helps boost skin elasticity.

How sweet it is! Honey has many beauty benefits.But not everyone agrees with that assessment. According to Dr. David Leffell, a

professor of dermatology at Yale University, the advantageous effects of bee venom products are over blown. Similarly, New York dermatologist Francesca Fusco calls bee venom, the new flavor of the month, much like apple stem cells were a few years back. She admits that bee venom does decrease inflammation. Although some bee-venom creams claim to be safe for people with bee allergies, Dr. Fusco recommends consulting with an internist or allergist before use—as there are some kinds of hives you just don’t want!

Anecdotally, we have known for decades that Cleopatra maintained her beauty by soaking in baths laced with aromatic rose petals and honey. Research has now confirmed the beauty and anti-aging benefits of honey and bee venom. I hope this buildup of consumer expectations for beauty that comes straight from the hives is not misplaced and does not leave consumers stung by disillusionment and disappointment.•

167 A ‘STINGING’ ENDORSEMENT FOR HONEY AND BEE VENOM

References1. K. Erickson, Better Nutrition, 4/11/132. E. Holmes, W. Journal, Style & Fashion, April 27, 2013.

168

Chapter 20

UNDERSTANDING RESVERATROL AS TOPICAL SKIN BRIGHTENERS

The global skin lightening market is expected to reach $10 billion by 2015, driven by new markets in the West and sustained growth in Asia, according to a recent report by Global Industry Analysts (GIA). Japan dominates the market, while

India and China are the fastest growing markets in the segment. According to GIA, the Asian market for skin lighteners will cross the $2 billion mark this year.

Skin whitening is widely practiced in Asia, where white skin is considered to be beautiful. In North America and Europe, skin lightening is considered more of an anti-aging treatment to hide unwanted signs of aging. Although the pigmentation disorders affect all skin types, individuals with darker skin, including Asians, Blacks and Latinos are more susceptible. Older individuals throughout the world suffering from liver spots or age spots, and other age related skin darkening conditions, are increasingly turning to skin lightening formulations in an effort to maintain what is perceived to be clearer and more youthful looking skin. Women from China, Japan and India have used traditional plants and their extracts, commercially available precisely for this purpose.1 Some natural compounds partially inhibit melanin synthesis or modulate tyrosinase activity. Chemically, the botanical brightening compounds sourced are usually polyphenols, benzaldehyde and benzoate derivatives, long-chain lipids and steroids, other natural or synthetic inhibitors. These compounds may have weak to strong whitening effects on the skin.2 These plant extracts have a distinct disadvantage of nonuniformity from batch to batch, instability, pesticide residue, lack of standardized product consistency, uncertain efficacy and dependable availability. To overcome these obvious disadvantages associated with botanical actives, DSM Nutritional Products Company inaugurated a nature identical version of resveratrol, trademarked as Regu-Fade (active) which is composed of transresveratrol, an antioxidant found in red grapes, to the global cosmetic industry at the 2011 In-Cosmetics show in Milan, Italy. This column will briefly discuss its skin brightening properties.

169 Understanding Resveratrol as Topical Skin Brighteners

Composition and FormulationResveratrol, a phytochemical, is found in red grapes, grape juice and red wine, and has been shown to prolong life in yeast and animals because of its antioxidant anti-inflammatory properties. Natural resveratrol contains both cis and trans forms, with its pigment-controlling properties residing in its trans form, which is only found in the active. It is grayish to tan powder, practically odorless, preservative-free and is thermostable. It is sensitive to light, almost insoluble in water and in lipophilic components. Optimal pH range is from 3 to 6.5 in formulations. The final formulation should not be exposed to direct sunlight and it should contain UV filters for additional stability.

In-Vivo EfficacyDSM Nutritional Products Company conducted a double-blind, placebo-controlled study using 52 female volunteers in India. Three test ingredients were added to an SPF 10 cream, applied twice daily on the forearms, and colorimetric measurements were taken after 14, 28, 60 and 90 days.

The formula containing 1% active provided the brightest skin, followed by the 0.2% active formula, a 2% ascorbyl glucoside formula, and the cream base was last. Up to 1% active is recommended for skin brightening facial and body care products or anti-aging creams.

Melanin is a polyanionic pigment that is produced by the melanocytes. Melanocytes are the melaninproducing epidermal cells. Melanogenesis is the process of production and distribution of melanin by the melanocytes to epidermal keratinocytes. Melanin synthesis can be manipulated by changing the tyrosinase activity, which is usually accomplished in many different ways. Effective skin brightening requires attenuating the melanin production cascade at multiple points. Melanogenesis-associated genes in hyper-pigmented skin; e.g., TYRP1 (tyrosinase-related protein 1), DCT (dopachrome tautomerase), Pmel- 17 (SILV protein), and MITF (microphthalmia- associated transcription factor), are all increased in actinic lentigos. There is also a role for stem cell factor (SCF) in hyperpigmentation—especially solar lentigos. Several of these genes were down regulated, which targeted a broad spectrum of different functions in the pigmentation process from initial signaling, gene expression and final melanosome transfer.

In plants, resveratrol functions as a protective agent and is synthesized in response to stress, infections or strong UV radiation. Many raw material suppliers are actively researching botanical extracts that can work with other actives and synergistically provide tyrosinase enzyme inhibition.

In the mad rush to incorporate truly natural ingredients, it is important to ensure that the selected actives have met all the skin safety testing requirements. Not all treatments fi t all skin types. Harsh treatments sometimes trigger unwanted hyperpigmentation. Usually it takes anywhere from 8 to 16 weeks to see results, so it is important to use the product diligently and for a prolonged time. Patience is a necessity. In the case of this active, in-vivo studies showed skin brightening after two weeks of product use. Most commercial skin brightening products combine different actives in order to attack the pigment-generating process at many levels. Sometimes adverse effects, such as toxicity or environmental concerns, sidetrack an experimental active from entering the market. It is safe to conclude that one should focus more on taking good care of his skin.

References:1. Lee et al. Int. J. Cosmet. Sci 19, 291-298, 1997. 2. Shimizu et al. Planta Med, 66, 11-15, 2000. A growing dem

170

Chapter 21

AGE-OLD POMEGRANATE HAS ANTI-AGING BENEFITS

BOTANICALS have been used to treat illness and maintain health for years. Modern delivery systems utilize whole plants, seeds, fruits and flowers in their extracted form. In skin care formulas they have skin-firming, soothing

and moisturizing properties. They also act as diuretics or laxatives to rid the body of toxins, or by stimulating body’s own healing powers and help preserve health. At present there is a huge surge of interest in this type of holistic health care.

Pomegranate, a crimson colored seasonal fruit is juicy, full of flavor and extremely nutritious. There is a general agreement that it first appeared in Persia and migrated to India, Northern Africa, China, Europe and the U.S. It is one of the oldest cultivated fruit for its both edible and medicinal properties.

It has been held sacred in many religions. The ancient Egyptians called it the fruit of immortality because of its powerful antioxidant properties and it is prominent in ancient literature, mythology and spiritual writings.

CompositionPomegranate contains various nutrients and pharmacological substances such as vitamins (B1, B2 , C and niacin), minerals (potassium), amino acids (glutamic acids, aspartic acids) tannins (punicalagin, ellagic acid) and alkaloids (pelletierines), and is a rich source of antioxidants, polyphenols and hydrolyzed tannins.1

Tufts University researchers evaluated the antioxidant needs of the average person plus the antioxidant power of fruits and vegetables, which is referred to as ORAC(oxygen radical absorbancy capacity). They concluded that people need approximately 5000 ORAC units a day to counteract free radical damage. A minimum of three servings of fruits and vegetables per day provides only approximately 1,200 ORAC units. This is the first biological standardization method for antioxidants. Pomegranate provides 2,750 ORAC units. Here’s how that compares to other fruits and vegetables:

• blueberries, 2,400;• blackberries, 2,036;• kale, 1,770;• strawberries, 1,540;• spinach, 1,260;• raspberries, 1,220;

171 Age-Old Pomegranate has Anti-Aging Benefits

• brussel sprouts, 980;• plums, 949;• alfalfa sprouts, 930;• broccoli, 890;• oranges, 750;• red grapes, 739;• red bell peppers, 710;• cherries, 670;• onions, 450;• corn, 400 and• eggplant, 390.

BenefitsAs evidenced from the above chart pomegranate has the highest ORAC value and hence it is most powerful antioxidant to neutralize the skin damaging free radicals, thus providing superior anti-aging results. The fruit has many benefits when taken internally. Pomegranate has a higher concentration of natural ellagic acid and other polyphenols to neutralize free radicals. Studies in animal have shown a marked reduction of plaque build up in arteries by 44%. Ellagic acid and other components have been shown to lower LDL levels in blood serum, thereby potentially offering a reduction of blood pressure in humans. According to one study, a combination of pomegranate juice extract and cold pressed oil has been shown to selectively destroy estrogen dependant cancer cells. Pomegranate Health launched CardioGranate and EstraGranate, 100% pomegranate dietary supplements. The health benefits of this seasonal fruit now could be available all year round. Benefits include its use as an alternative to hormone replacement therapy, to maintain heart health and as an antioxidant.

Pomegranate provides many skin care benefits, too. Its high level of ellagic acid and punicic acid may have anti-inflammatory and anti-aging properties. In fact, University of Michigan researchers found that topical applications of pomegranate extract and its seed oil prevent fine wrinkles and firm the epidermis. At 1-3%, organic cold-pressed pomegranate seed oil in a topical preparation had superior emolliency and protection.2

Skin aging is caused, in large measure, by free radicals, which inflame collagen. Pomegranate extracts and especially the oil has been proven to inhibit the eicosanoid metabolism that eventually causes the inflammation.3 Many dermatologist-developed skin care brands have included pomegranate as an active ingredient.

References1. Brunswick Laboratories, Wareham, MA 02571.2. Asia Moore, Simple Health Secrets, 2/18/04.3. Extracts and IngredientsLtd., (Affiliate of Morre-Tec Ind.) One GaryRd., Union, NJ 07083-5527. E-mail:, [email protected]

172

Chapter 22

DO STEM CELLS HOLD THE KEY TO YOUNGER-LOOKING SKIN?

Stem cells though controversial, often play a key role in drug research. Now these materials are finding new applications in skin care, and stem cells are the latest buzzword in the anti-aging category. Yet scientific opinion remains

divided on their origin. One opinion is that stem cells arise when sperm fertilizes an egg, while the other is that they originate in the inner cell mass of the blastocyst. Stem cells have the ability to go through numerous cycles and cell divisions while maintaining their undifferentiated state. They also have the capacity to differentiate into other cell types such as muscle, blood and nerve tissue. Adult stem cells reorganize, heal and repopulate the skin with new cells. They arise from the basal layer of the epidermis and at the hair follicle base. Adult stem cells, as opposed to embryonic stem cells, repair and regenerate damaged tissues. Theoretically they possess the ability to create new skin cells and regenerate the skin for a lifetime, but age and environmental factors cause them to function less efficiently, resulting in olderlooking, aged skin. Stem cell-based creams reportedly stave-off this process by either stimulating or protecting stem cells deep in the basal layer of the epidermis. Stem cells divide relatively infrequently. With age, stem cells lose their proliferative capacity and perhaps their ability to respond to signals to produce more epithelial cells, according to R. Ghadially, a dermatologist and skin stem cell specialist at the University of California at San Franciscco’s Institute for Regenerative Medicine. Increasing proliferation is the ultimate complexion rejuvenator.

Stem Cells in SkinEpithelial skin stem cells are found in the basal layer of the epidermis, while hair bulge stem cells are found in hair follicles. Furthermore, hair follicular stem cells, tooth stem cells and skin stem cells all show therapeutic promise and may one day restore hair to bald men, teeth to those in need and skin to scarred patients, according to Dr. Denis English, editor of Journal of Stem Cells and director of cell biology at the University of South Florida. Changes in the skin are caused by aging, disease or injuries. Although drugs can relieve consequences of the disease, they will not suppress the cause. Therefore, the most attractive strategy is to replace disabled

173 Do Stem Cells Hold the Key To Younger-Looking Skin?

cells, and to this end, to take advantage of stem cells.1 According to Gregory Brown, creator of ReVive, accessibility also makes skin stem cells appealing to cosmetic chemists. Stem cells are readily available in hair follicles and sweat glands. The ratio of stem cells to regular cells in skin is still hotly debated. It was once thought to be 1 in 10, but is now suspected to be more like 1 in 10,000.

Stem Cells and AgingStem cells have a limited life expectancy because UV, smoking and ozone all hasten skin cell depletion, resulting in DNA damage, telomere shortening and oxidative stress. Cell depletion does not activate stem cells to change into new cells. Aging stem cells lead to a decreased capacity for repair, an increased incidence of degenerative diseases and an increased incidence of cancer in tissues that contain stem cells. Skin rejuvenation comes to a halt when stem cells remain inactive.

Under the right stimulus, stem cell activity could be jump-started to initiate skin rejuvenation. Stem cells have unique secondary structures of DNA and RNA. Stem cells have special components in the cytosol-epigenetic factors. Stem cells are sensitive to environmental stress factors and hence protection and maintenance of stem cells is of great importance. Epigenetic profiles regulate the gene expression in stem cells, which enable cells to stabilize and maintain different characteristics despite containing the same genomic material. This is achieved by chromatin remodeling by DNA methylation (gene silencing), post-translational modification of histone proteins (e.g., acetylation for transcriptional competence) or mRNA inactivation through micro RNAs or small interfering RNA (siRNA).

High-Priced ProductsMarketers are presenting stem cell creams as the future of skin care. This article will review major stem cell-based antiaging consumer products and the science surrounding stem cell technology. Amatokin is available from Voss Laboratories in collaboration with Beilis Development Company. It has a hefty price tag of 190 euros or $258 per 30ml. Less expensive is Christian Dior’s Capture R 60/80 XP cream, which still costs more than $100 for 30ml. StimulCell from N.V.Perricone retails for $155 for 1.7fl.oz. Another product based on cellular tune-up action that is similar to stem cell is Estée Lauder’s Re-Nutriv, which costs approximately $130. But the costliest product is ReVive’s Peau Magnifique Youth Recruit. It comes in a lucite cube that houses four small silver tubes. A onemonth supply of this super serum costs $1,500…can you believe it? The company insists that the high cost is because of a telomerase which is a bio-engineered enzyme costing about $4 million per gram.

Actives and ClaimsAlthough all of these products make similar claims, their backgrounds are quite different. For example, Amatokin got its start in 1988 when Russian scientist Taras Nikolaev from the Biotechnical Institute in Moscow and St. Petersburg studied peptide research to accelerate wound healing and skin repair. His team created a polypeptide with the ability to stimulate dormant stem cells in the skin, rejuvenate the skin and speed healing—truly a bold, astonishing claim. Amatokin is the first topical polypeptide that lights up stem cell markers (the means by which cell activity is measured). The polypeptide acts as a catalyst when it comes into contact with the upper keratinocyte cells of the epidermis, initiating a molecular signaling cascade that produces the increase in activity which was measured by the stem cell markers.2

In the case of StimulCell, young, undamaged cells were created by applying chemically reproducible oxidative stress to stem cells, which forces them to pump out


145 different proteins, carbohydrates and lipids. These materials are protect cells and relay regenerating messages, according to Dr. Perricone. For Dior Capture R 60/80 XP crème, the active is a vitamin E derivative called alpha-tocopheryl phosphate, which creates a protective shield. ReVive Peau Magnifique Youth Recruit has an enzyme active called telomerase, which was first discovered in 1984, according to Bays Brown, the brand’s founder. Finally, Re-Nutriv contains a stabilized version of reservatrol, an antioxidant produced by some plants to ward-off fungi and bacteria. Amatokin initiates the release of very powerful growth factors responsible for cell proliferation, according to Louie Rinaldi of Voss Laboratories.

According to R. Ghadially a dermatologist and skin stem cell specialist at the University of California at San Francisco’s Institute for Regeneration Medicine, this product increased the expression of certain stem cell markers. We only know what those markers indicate in embryonic cells. It has not been proven that they have the same correlation in adult cells. It is very promising, but more work needs to be done. His lab is conducting independent research on whether the markers in question do in fact indicate the presence of adult stem cells.3

How it WorksAmatokin highlights the expression of stem cell markers in the skin to reduce the appearance of serious wrinkles. It focuses on using polypeptides and enzymes to “awaken” the body’s own reservoir of stem cells. We only know what those markers indicate in embryonic cells. There is no proof that the same holds true in adult cells. While very promising, more work needs to be done.StimulCell contains cell-protecting and regenerating messengers. When the product is applied topically, these messengers reportedly attach to skin cells, signaling them to begin the reparative process. In one study, Dr. Perricone’s product reduced acne, skin damage and wrinkles using the cell’s own messengers. A cell is carefully guided toward rejuvenation.

In an in-vitro study by Dior, the alpha-tocopheryl phosphate in Capture R60/80 XP reduced the number of stem cells lost in the epidermis after sun exposure. The company recruited 30 women scheduled for facelifts and asked them to use the cream on one cheek for two months before surgery. The treated skin showed 19% more epidermal cells. Rather than purporting to stimulate stem cells, this product makes rather modest claims that it protects and prolongs the functioning of the stem cells. The company asserts that the product’s effectiveness is due to Stemsome, a sophisticated delivery system that transports ingredients into the skin. The system envelops each active ingredient in multi-stacked layers, which progressively melt as they are absorbed by the skin, releasing the active ingredient. According to Edouard Mauvais-Jarvis, director of scientific communications, each time a layer melts, the next one opens, enabling the ingredients to reach their target deep within the skin. This technology doesn’t enhance the cells in any way, it merely creates a more beneficial environment to allow the stem cells to play their optimum role in regulating the skin.

ReVive Peau Magnifique Youth Recruit’s efficacy is due to telomerase, an enzyme that aids DNA replication to prevent chromosomal strands from losing bits of information when they split, thus warding off genetic mutations. When applied topically, it can also send a signal to stem cells, rallying them to respond as they would to an injury. Epidermal Growth Factor (EGF), a protein found naturally in the human body that is released from the cells after injury to increase cell turnover, does accomplish regeneration of aging skin. The product does not alter the body’s natural functions nor changes skin in any abnormal way. It does not add or inject stem cells into the skin. It merely stimulates and accelerates a natural process. It purports to


convert resting adult stem cells to newly minted skin cells. The active in Re-Nutriv, reservatrol, extends the life of cells, actually slowing down turnover rather than speeding it up—possibly the best way to ward-off cell breakdown.

DiscussionSome observers complain that Amatokin, and any other ingredient that causes cells to multiply, could cause cancer due to cell division. “You don’t want a signal that just says: ‘turn on’ to stem cell activity. That’s like a car that just has a gas pedal—it could be dangerous, resulting in overproduction, potentially even cancer,” agreed Dr. Perricone. “You want cells that turn on, cells that moderate, cells that suppress activity, cells that steer.”

However such fears are dismissed because you are stimulating adult stem cells which start as pristine, unformed cells. Given the proper environment, they undergo a maturation process to become a new cell and then migrate, through cellular communication, to the area of damage, telling the fibroblast cells, “it is time for you to die, I am here to take your place.”

So, you get a brand new cell replacing an old, aging cell that is removed naturally from the body. Stem cells’ low rate of division is actually a protective measure, according to Dr. Geraldine Guasch, a researcher at Rockefeller University, New York, NY. The more cells divide, the greater their chance of DNA mutation. Cancer is basically the result of haywire cell production. Mutated stem cells may cause cancers to grow back even after chemotherapy, which could make skin stem cells’ inherent accessibility more of a bane than a benefit.

Susceptibility to UVdamage could mean they are prey to even more mutations than internal cells. In skin, it has not been demonstrated yet that a stem cell can be the start of cancer. If a company claimsto increase stemcell activity, Dr. Guasch wants proof that the chromosomes of these new cells do not accumulate mutations.

Besides, as Dennis Gross, a New York City dermatologist, points out, anything that alters cellular activity, constitutes a drug claim and require FDA approval. Dr. Perricone is considering equipping his Madison Avenue flagship boutique with a machine that would enable him to harvest and store clients’ individual stem cells— other innovators are focusing on preserving the cells we already have.1Some experts question whether the enzyme found in ReVive Peau Magnifique Youth Recruit truly ignites stem cell differentiation. Telomerase plays a role in some, but probably not all, stem cells, says Amy Wagers, a principal faculty member of the Harvard Stem Cell Institute in Cambridge, MA. Dr. Wagers is not familiar with any data suggesting it directs their differentiation or wakes them up. Regarding before and after photos that show a dramatic improvement in skin tone and texture with fewer fine lines, Dr. Gross noted that many active ingredients work on skin cells to stimulate them to make byproducts like collagen. This is very different from stem cell technology in which the cells themselves form tissue. Meanwhile, with the debut of Capture R60/80 XP, Christian Dior became the first global luxury brand to tap into stem cell technology.

Storage BanksRecently two teams of researchers transformed ordinary skin cells into batches of cells that look and act like embryonic stem cells— those master cells that give rise to every cell and tissue in the body. Moreover, they accomplished that without cloning technology or embryos. Dr. Shinya Yamanaka of Kyoto University, Japan, recently said that creating a bank to store a new type of stem cell produced from donor’s ordinary skin cells could reduce time and money for treating patients. This research


makes it possible to reset an aging cell to become an entirely new being, and may give rise to powerful anti-aging actives in the future. Several companies, including Bio Eden, C’elle, Neostem and Store A Tooth, provide stem cell extraction and storage services, though viable therapies may be years away.

Apple Stem CellsMibelle Biochemistry launched an anti-aging active based on an extremely rare form of apple stem cells. It promises to protect skin stem cells and slow the senescence of hair follicles. In vivo and in vitro tests proved that the ingredient, PhytoCell TecMalus Domestica, boosted the production of human stem cells, protected them from stress and decreased facial wrinkle depth. It also delayed the aging of the hair follicles, suggesting a possible use in anti-aging hair preparations.

Not everyone is convinced that stem cell creams are the future of anti-aging. There are not enough published scientific data available to support its safety and efficacy in skin care products at this time. Stem cells are very popular, but many dermatologists remain skeptical. Alan Matarasso, a cosmetic plastic surgeon in New York City, noted that the theory of stem cells sounds good but the question is, whether or not a topically- applied cream can send signals to activate these stem cells. Until there are double-blind clinical studies, their efficacy is unproven. Ultimately it is up to the consumer to decide if the results live up to all the hype. According to David Colbert, a New York City dermatologist, it may be premature to choose a stem cell cream over one with, say, time-proven retinols or hydroxyl acids. Stem cell research is still very young. There is much more information to unravel. Nanotechnology, DNA and now stem cell technology have all recently entered the skin care category. My concern is that these highly scientific technologies are marketed to consumers at ridiculously high price. No one is looking seriously at whether the drug-like claims that are being made for these technologies are truly accurate or if their long-term use would put the consumer’s health and safety at risk.

References:1. Stem cells, P. Jones, Nov. 2007, SPC.2. L. Rinaldi, Voss Laboratories, Salt Lake City, Utah.3. Investigation, micromanagement, M. Bullock, Elle, Dec. 2007.

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Chapter 23

NEW ANTI-AGING BENEFITS EMERGE FOR PROBIOTICS

How does smearing yogurt all over your face lead to a clearer complexion and softer, smoother skin that’s less prone to breakouts? This column examines the science surrounding the multibillion-dollar probiotics market.

According to the Health and Wellness Trends database, global probiotic product sales are expected to soar from $15.9 billion in 2008 to more than $32 billion in 2014.

Probiotic means “in favor of life.” They are defined by the World Health Organization as living microorganisms or good bacteria which, when administered in adequate amounts, confer a health benefit on the host.

Oral probiotic supplements are well recognized for protecting the gut’s microflora and supporting the body’s immune system. Healthy bacteria in the gut improve overall health and, consequently, help slow the aging process, enabling skin to retain its youthful glow much longer. Researchers may reason that topical use of probiotics will confer similar protective balance to the skin, and therefore help keep skin strong, healthy and age resistant.

We all know that skin hosts friendly bacteria. Probiotics work to protect this environment by replacing lost bacteria and preventing further loss with a fully functioning and thriving probiotic environment, making skin balanced, calmer and more resistant to aging. Given that the good-bad interaction of bacteria takes place on the skin’s surface, deep penetration of topical probiotics is not a huge concern. These topical probiotics need not be absorbed too deeply into the stratum corneum, but rather would be more effective if they stayed on the upper layer of the epidermis.

Products and ClaimsConsumer magazines, websites and blogs are rife with details about how applying yogurt on the face, billed as a “yogurt facial,” improves the complexion. This is due to the lactic acid found in yogurt, which gently soothes, smoothes and exfoliates skin. The good bacteria in yogurt help to combat pathogenic bacteria that may be at the root, or at least exacerbating areas of redness and swelling. Some spas combine yogurt with dried orange peel powder in their facial preparations, which is rinsed off the face after leaving on for 15 minutes.

Probiotics are also incorporated into cleansers or masks. All these anecdotal probiotic topical treatments have been around for years because they have consumer benefits, thus proving that yogurt is surely an effective beauty boost. In health food

178 New Anti-Aging Benefits Emerge for Probiotics

stores, we find probioticbased personal care products such as soaps and lotions. British skin care company Nude was the first to develop and launch a whole line of skin care around friendly bacteria. Clinique, Lancôme, Burt’s Bees, Bioelements Chatecaille, Amala and Revive are just a few of the brands injecting probiotics into anti-aging serums and moisturizers in the belief that they help soothe and plump skin and can even turn back the clock.

Clinique’s Probiotic Anti-Aging Serum contains lactobacillus bifidus cultures encased in soy and milk proteins to help ward off wrinkles and irritation by keeping the skin’s bacterial balance in check. Clinique holds a patent on lactobacillus in cosmetics. Its Redness Solutions Makeup SPF15 helps alleviate mild and moderate rosacea while concealing facial flush.

Burt’s Bees’ intense hydration cream cleanser is also formulated with probiotics, which are said to boost skin’s protective bacterial layer.

L’Oréal Paris Youth Code Serum Intense delivers Biolysat, a concentrated probiotic, with other ingredients that improves barrier function while prompting skin cells to behave like younger versions of themselves.

Amala Rejuvenating Face Cream encourages the growth of good bacteria with pH-normalizing lactic acid, while silver sulfite fights the bad bugs.

The Doctors’ OpinionsThere is no unanimous agreement among dermatologists regarding topical anti-aging benefits of probiotics. Richard Gallo, MD, chief of the division of dermatology at the University of California, San Diego, notes that beneficial bugs live in our bodies and help fight off myriad diseases, making them extremely important to us. So why is there difficulty accepting that perhaps the bacteria living on skin are also beneficial to us? We have good and bad bacteria on our skin, just as they are in our gut, according to Ellen Marmur, MD, an associate professor of dermatology and genetics at the Mount Sinai School of Medicine in New York City.

“If the balance is off-kilter, it can result in acne or rosacea,” explained Dr. Marmur. “The right bacteria may also keep skin young.”

Nick Lowe, a consultant and dermatologist, agrees that probiotics have applications in skin care, but more research is needed.

“There is a lot of hope and hype with probiotics. There is some evidence, probiotics help with eczema and acne, the research is not there yet to prove, it can be anti-aging,” said Lowe. “People should understand that normal healthy skin has its own very good system for managing bacteria. As far as turning back the clock, we will have to wait and see.”

Scientists at the 2007 World Congress of Dermatology produced data showing that probiotics help your body build a better barrier for the skin and gut. Leslie Baumann, MD, a dermatologist, recognizes the potential of helpful bacteria to treat skin disorders. However, the bacteria in your colon are not the same as those on your skin, so you can’t make the leap that if probiotics work internally they are going to work topically.

Research StudiesAccording to a study published in a recent issue of the Journal of the Society of Cosmetic Chemists (Nov-Dec 2012; 63(6):385-95), certain types of probiotics are good for the skin. Researchers drew the conclusion that probiotics can really work if you use enough of the right kind. The bad news is that yogurt won’t have the same effect because it contains lactobacillus casei a different kind of probiotic. If you want to get the right kind (lactobacillus plantarum) from natural food products, you would have to rub sauerkraut, pickles, brined olives, or sourdough on your face.


According to Natural Solutions (Jul. 2008, issue 109, p.89), probiotics can clear up one’s complexion. Authors concluded that when the good bacteria enter the body, they strengthen the skin’s acid mantle and protects the outermost layer of the skin from pathogens and free radicals.

Basic Food and Drug Administration (FDA) guidelines for probiotic use suggest less than 1000 CFU except for eye area products, where the suggested limit is less than 500 CFU. It is estimated that most cosmetic use for probiotics is around 10 CFU.

More Research Is NeededResearch is emerging to explain how probiotics interact with skin as well as which strains are most beneficial and whether topical or oral preparations work best. We do not know how many microorganisms that naturally reside on the skin are friendly and beneficial and combat the inflammation that causes premature aging and wrinkling, just as they reduce gut inflammation.

There will always be a market for anti-aging products with bioactive natural actives. Their popularity is due, in part, to consumer perception that natural ingredients are well suited for soothing problem skin. Consumers believe that harsh, chemically-derived products are strictly verboten for anyone with irritated skin. These consumers reason that these chemicals disrupt skin’s healthy eco-balance of the skin, strip and irritate it.

Health and Beauty Benefits of CurcuminEven though primary role of spices is to impart flavor to food, there is a lot of scientific evidence that they are indeed used as medicines. We all know, for example, spices such as garlic to have a reputation for being good for the heart and combating infections, while cinnamon has anti-diabetic effects. And who has not heard of the idea of consuming a cup of warm ginger tea to sooth a sore throat and treat colds and nausea?

In the market research study, “Specialty Actives in Personal Care 2011: U.S. Market Analysis and Opportunities,” Kline & Company found that sales of specialty actives in the US reached nearly $240 million in 2010. Botanical actives are the largest category of specialty actives, with a 38% share of the market.

This column will briefly discuss turmeric, a golden yellow spice from the East that is known to bring beauty, good health and good luck to those who use it and carry it, according to an old Indian folk song. Indian brides and grooms ritually shower with turmeric powder and milk before marriage to make skin look smooth and more beautiful. Turmeric has been considered “skin food” for thousands of years in India and Far East Asia. Curcumin, a yellow pigment found in the root of the tropical turmeric plant, Curcuma longa, has both a water soluble component turmerin and a lipid soluble component, curcumin.1Curcumin has been shown to have a wide range of pharmaceutical benefits that include antioxidant, anti-inflammatory, anti- carcinogenic, antibacterial, and wound healing properties and consequently it has broad range of clinical applications.2 Dermatologically, it is used for prevention and treatment of psoriasis, acne, wounds, burns, eczema, photo-damage and photo-aging.3

Antioxidant: Turmeric has very high antioxidant levels. It is a very potent scavenger of reactive oxygen species ROS, including superoxide anion radicals, hydroxyl radicals and nitrogen radicals.4 According to the US Department of Agriculture (USDA) ORAC (oxygen radical absorbance capacity) database, culinary spices have some of the highest ORAC values by weight. This makes them a valuable part of a high antioxidant diet which has been linked to a number of positive health


outcomes, including cardiovascular and brain health. Turmeric’s antioxidant activity resides with its phenolic fraction curcuminoids.

Anti-Inflammatory: Inflammation represents one of the hottest areas of medical research. Three herbal remedies with anti-inflammatory benefits are ginger, turmeric and Boswellia. Curcumin’s powerful anti-inflammatory property with few toxic side effects is validated in a numerous clinical studies that have been reported in various scientific journals.5 Curcumin has long been employed in Chinese and Ayurvedic medicine as an anti-inflammatory agent. Curcuminoids reportedly inhibit enzymes, which participate in the synthesis of inflammatory mediators leukotrienes and prostglandins derived from arachadonic acid. Topically used, turmeric can reduce localized inflammation associated with burns, eczema and psoriasis.

Wound Healing: According to the University of Maryland Medical Center, turmeric has both antiviral and antibacterial properties that speeds up woundhealing and prevent infection. In India, Johnson & Johnson sells BandAids infused with turmeric powder as it is reputed to help heal wounds. Turmeric, when mixed with aloe vera, soothes burns and helps heal red, irritated eczematous skin.

Skin cancer: Curcumin reduces healing delays caused by radiation and other injuries.7 It blocks tumor necrosis factor (TNF), a natural chemical, which contributes to cancer, arthritis and is resistant to chemotherapy drugs. Curcumin has been exhaustively studied for its potential chemo-preventive activity.8 It slows the progression of cancerous cells throughout the body, including breast, esophagus and skin. According to Razelle Kurzrock, an investigator at M.D. Anderson Cancer Center in Houston, curcumin could be very potent in terms of killing tumor cells. According to data, it diminishes the severity of radiation dermatitis, a common adverse event in cancer patients undergoing radiation therapy.

Products: There are many foodinspired cosmetic products currently available, but with only a token level of food ingredient in the formula which cannot provide any meaningful benefit. Maintaining stability and bioavailability through the manufacturing process represents a challenge. Furthermore, curcumin has classic distinct characteristic pungent odor and intense yellow color such that it could stain teeth, clothing and whatever it comes in contact with, making it impossible to develop cosmetically elegant products. However, the yellowish tint can be ameliorated by using tetrahydrocurcumin (colorless grade), which has been shown to slow the synthesis of melanin, making it a potential skin lightener. It is still unknown what is the optimum use concentration, stability, co-actives, vehicles and emulsifiers that would result in a most effective product.

Despite curcumin’s obvious negative sensory attributes, consumers find these products in the global marketplace, particularly in India.9

ConclusionAll published literature show that turmeric is one of the most aggressively studied herb for its antioxidant, anti-inflammatory, UV damage reducing, slowing down the accumulation of age related pigments in the skin, cancer protective and antiaging benefits. More clinical studies are still needed to study curcumin’s effect on human skin.

References:1. Cohly etal. Free Radic. Biol. Med. 1998; 24-492. M. Singh et al. Life Sci: 78, 2081-2087(2006)3. Br. J. dermatol. 2000;143:937-49; phytother. Res. 2003:17:987-10004. Conney AH et al. Adv. Enzyme regul. 1991;31:385


5. Indian J. Med. Res. 1982:75:574-86. Skin Therapy Lett.2000:5:1-2,57. J. Wound Care 2004:13:107-98. Mutat. Res.1999;428:305-279. Skin Pharmacol. Appl. Skin Phy.2001;14:373-85

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Chapter 24

UNDERSTANDING ANTI-AGING BENEFITS OF MUSHROOMS

There are nearly 150,000 different known species of mushrooms in the world. Some of the most popular are shiitake, reishi, maitaki, enoki, oyster, lion’s mane, hericium erinaceous, coriolus versicolor, cordyceps, cloud, chager,

cremini, astragalus, agarikon and agaricus.All of them contain polysaccharides, those long-chain molecules composed of

sugar units, which seem to be responsible for their action as immunopotentiators. Many ancient civilizations used mushrooms for more than just food. They believed mushrooms had significant healing powers.

Mushrooms are fungi, and they do not belong to the plant or animal kingdom. Whereas plants reproduce with seeds, mushrooms rely on spores. These fungi break down dead organic material and continue the cycle of nutrients through the ecosystem.

Anti-Aging PropertiesTopical applications of a variety of mushrooms, such as shiitake, maitake and tremella are used widely for their skin beautifying qualities. They contain antioxidants as well as compounds that have anti-inflammatory properties, which help treat many skin problems caused by inflammation and excessive free radical activity. Several mushroom varieties contain kojic acid, which is renowned as a skin lightener. Kojic acid is useful as a natural alternative to dangerous, and often toxic, chemical skin lighteners, such as hydroquinone which has recently been linked to skin cancer.

Shiitake mushrooms contain the antioxidant L-ergothioneine, which helps prevent cell breakdown and helps exfoliate the skin. Shiitake mushrooms, as a rich source of kojic acid, are used to brighten the skin, and fade sunspots and acne scars. Shiitake’s anti-inflammatory properties help improve vitality and also encourage faster skin renewal and increase skin elasticity. Hence, this variety is often found in skin care products particularly those with anti-aging benefits. Reishi mushrooms have superior antioxidant characteristics, making them applicable in a broad range of products to treat pathological aging.

183 Understanding Anti-Aging Benefits of Mushrooms

Health BenefitsMany health food stores carry capsules, liquid extracts and dried varieties of mushrooms, which are promoted for their overall immune-boosting benefits. They enhance the immune system, are anti-inflammatory, and have antioxidant, antiviral and antibacterial properties. Maitake variety contains beta-glucans, which has a wide range of immunestimulating and protective effects within the body. Mushrooms have numerous and diverse health benefits including: treating cancer, fighting infections, treating diabetes, lowering cholesterol and blood pressure and helping prevent dementia and Alzheimer’s.

Dermatological UseDietary substances known to be good for the complexion are sometimes better applied topically rather than ingesting them because, “you can get higher concentrations in the skin this way,” observed Dr. David McDaniel, director for the Institute of Antiaging Research and an assistant professor of clinical dermatology and plastic surgery at Eastern Virginia Medical School. Other experts specifically acknowledge the benefits of these fungi.

“Mushrooms are packed with compounds such as proteins, lipids and phenol and are rich in vitamins and amino acids,” noted Dr. Leslie Baumann, director of the University of Miami Cosmetic Medicine and Research Institute. “There is even greater evidence that some species have strong antioxidant, anti-inflammatory and tumorinhibiting activity when applied topically, but their effectiveness is not based on the ingredient alone. Extracts must be specially formulated so that they get into skin.”

Dr. Andrew Weil contends that mushrooms straddle the line between food and medicine and can combat the effects of aging, including specters such as cancer and Alzheimer’s. Think of penicillin, Weil says, which is derived from mold, which is a lower fungi. Mushrooms are higher fungi, with immune-enhancing and antiinflammatory effects.

In addition, at the recent Annual American Academy of Dermatology (AAD) meeting in March 2013, world renowned mycologist Dr. Paul Stamets said that mushrooms and fungi are the key to creating necessary biodiversity, by producing a lot of interesting compounds that are medically significant.

Commercial UseCosmetic chemists are taking note of the mushroom’s anti-aging benefits. Popular mushrooms are found in everything from anti-aging serums to daily moisturizers. The extracts are often cited as potent antioxidants.

The researchers at Aveeno, a Johnson & Johnson brand that is known for harnessing the powers of innovative, active natural technologies, created a natural shiitake complex that is featured in the Aveeno Positively Ageless range of products. According to J&J researchers, these formulations have been shown to enhance the youthful appearance of skin.

Weil has developed a mushroombased skin care regimen for Origins that claims to reduce skin’s inflammatory response and calm redness. According to Origins’ studies, there is a dramatic improvement to dull, ashy skin and facial redness including rosacea. More than 80% of those using mushroom-infused products felt soothed and calmed.

Long valued in the nutritional medicines of China, Korea and Japan, mushrooms are now attracting more interest from researchers and clinicians in the West. Mushroom-based products support the natural defenses of the skin and improve


its appearance by keeping it healthier. Many scientists believe the beta- glucan content of mushrooms offers anti-aging skin care-related benefits. There is a lot of enthusiasm for developing mushroom-based skin products, but more basic research is still needed.•

The Bizarre for the BeautifulThe growing obsession with anti-aging and wellness has led to significant growth of the cosmeceutical market, which is projected to exceed $4 billion by 2011. Moreover, the industry will sustain growth at almost double-digit rates for quite a while after 2011, according to IBISWorld Forecasts.

To satisfy this ever-growing demand for anti-aging formulas, some companies have launched products that contain strange ingredients such as turtle and shark oils, queen bee royal jelly, horse blood serum, chicken embryo and pigskin extract. These offbeat additives reportedly promote skin rejuvenation or tighten skin muscles.

The U.S. spa market is currently valued at $16 billion, but according to Diagonal Reports, the market will remain stagnant during the next couple of years, with no change expected until 2012. To survive these hard economic times, some spas are offering treatments based on questionable ingredients that promise perfect skin, but at first glance may make you gag. This column will review some bizarre current anti-aging products, spa treatments and their claims.

Infant skin fibroblasts are particularly regenerative, which means they can be used for wound healing and wrinkle reduction. Skin Medica uses stabilized human-growth factors derived from circumcised infant foreskin. Another option is bovine colostrum. It contains high levels of enzymes and vitamins, making it ideal for skin care applications. Meanwhile, creams made from bee mucus extract are said to remove and prevent wrinkles and balance skin’s natural oils.

Caviar is a delicacy that is associated with luxury and wealth. It is said that it has the same composition as human skin. It is composed of 70% amino acids and trace minerals. Just one application is said to soften fine lines and wrinkles. Cellex-C’s Bio-Tan Sunless Tanning Gel contains cuttlefish ink that is said to have excellent antioxidant and free radical scavenging abilities. Just like octopus or squid, the glands of cuttlefish contain ink which is rich in melanin pigment and provides the tanning benefits. EMK Placental Anti-aging Serum contains a placenta protein extract. Since placenta contains such high amounts of nutrients, collagen and amino acids, it is suggested that it may rejuvenate the skin, while also promoting increased cell renewal.

In Japan, some people are lining up to drink ground pig placenta. The Japanese believe that it gives them energy and revitalizes their youth. Some doctors have also used placental extract to treat burns. I wonder if consumers would think twice before applying placenta extract-containing topical products on their skin. The hormone content could potentially result in breast growth in children, breast cancer or other serious health problems. Skinscience Antiaging Normal Cream contains spermine extracted from seminal fluid. It is said to be 30 times stronger than vitamin E. This $100 cream may protect the skin from UV rays and help smooth sunburned skin. Spermine acts as a free radical scavenger and a natural antioxidant when applied to the skin.

The Benefits of Snake VenomThere are several products on the market that incorporate a synthetic version of snake venom. For example, Sonya Dakar’s Ultra Luxe-9 Age Control Complex ($185) utilizes a synthetic version of snake venom that works to diminish the appearance


of fine lines and deep wrinkles while leaving skin smooth and hydrated. Another product, KumaaraOvernight Repair Complex, also uses snake venom peptide to improve the appearance of the face. Syn-Ake is a skin care ingredient supplied by DSM. It mimics the paralyzing effects of snake venom and softens wrinkles at least temporarily.

Biocutis Bioskincare Cream contains more than 70% snail secretion, which reportedly helps stimulate germinal cells, which aid in the regeneration of scar tissue and the reduction of acne scars. Snail secretion is rich in natural mineral calcite, which snails use to repair their shells. This slimy secretion is said to improve the texture of skin too. It may also have some potential in the treatment of bone fractures since it has powerful bonding properties.

In 2009 Michael Todd Cosmetics introduced Knu Anti-aging Tri-Complex, which includes a 90% concentration of real snail goo. The company claims the purified secretion has excellent regenerative properties and helps prevent and correct wrinkles and loss of firmness. Naturopathica’s Green Tea Wasabi Mask helps activate cellular repair, which increases circulation and reduces puffiness. Japanese horseradish contains powerful isothiocyanates that help kill parasites and germs. This enzyme also has antioxidant properties and helps combat carcinogens. Because of its anti-inflammatory properties, it helps treat acne and rosacea; it is priced at $56.

Bizarre Spa TreatmentsFor years, adventurous consumers have applied mayonnaise to their hair, and oats and honey to their faces. But now, some spa owners are taking weird ingredients to a whole new level. Here’s a look at some of the more bizarre spa treatments and the science behind them.

For centuries, geishas have applied nightingale droppings to their faces to detoxify their pores and brighten discolorations. Now, for a few hundred dollars, spa enthusiasts can enjoy the modern version of this ancient treatment. The droppings are sterilized via UV light and applied during a facial. The natural enzymes of the droppings break down dead skin cells. Some spas also mix droppings with rice bran to enhance the exfoliation effects. Bull semen is used for damaged hair. Sometimes it is mixed with katera root from an Iranian plant to treat and revitalize all types of hair especially colored, over-processed and dry, frizzy hair.

For all-over healthy skin, the town of Chodova Piana in the Czech Republic offers a soothing hot bath containing healing mineral water and a dark bathing beer. This curative therapy claims to have rejuvenating effects. Reportedly beer has antioxidant rich polyphenols that works wonders on dry skin and hair. There is also bath side bar where you can sip beer while soaking in it.

The Hershey Hotel in Hershey, PA offers skin nourishing aromatic chocolate soaks, massages and chocolate wraps. If beer and chocolate aren’t your thing, you can try an Egyptian mud facial. Egypt- ian mud is supposedly very rich in vitamin A, E, and essential fatty acids. It is usually mixed with shea butter and applied on the face. It is said that extremely smooth facial skin feel that is generated, lasts for two to three weeks. Gold leaf facials use 24-carat gold to tighten the face and help produce collagen. But dermatologist Leslie Bowmann warns that gold can cause severe rashes because it is an allergen and is terrible to put on your face. For the sports-minded, a softball facial is an anti-wrinkle treatment that involves rolling softballs to massage, tone and stretch skin. After several soothing sessions, facial muscles tighten to give sagging areas a boost.


Fish FoodThe next time you want a pedicure, toss the pumice stones and nail files and soak your feet in a fish tank so that tiny carp can nibble away rough skin and calluses leaving your feet soft and smooth. Taking the concept of these pisces pedicures to a whole new level, in Malayasia, you can lounge in a heated pool while swarms of nibbling fish snack away at rough spots and deep clean your pores while feeding. Reportedly, nibbling fish exude an enzyme that slows acne and other skin problems.

Looking for a bit more beauty help from live animals? How about a slithering snake massage? In this treatment, snakes of various sizes are placed on your back and left to writhe up and down the spine, creating a unique kneading sensation. If you opt for tiny garden snakes, a 15-minute massage costs just $80. Reportedly this treatment helps with tight muscles and headaches.

Last year, the Academic Journal of Bioresource Technology reported that when bullfrog peptide was added to human cells walls, it reduced the effects of oxidization by 73%. This peptide is extremely effective at attacking free radicals. This material is water soluble, which would make its use possible in beauty products of all kinds.

ConclusionsMost cosmetics contain ingredients that are promoted with exaggerated claims of beauty or long lasting effects to create an image. Slowing aging is no longer science fiction…it is a reality! Creative and bizarre treatments create attention and awareness. Recent celebrity endorsements to these regimens have increased their appeal to masses. These products and treatments may sound strange and seem extreme, but remember, Botox was also considered weird when it was first introduced into the mainstream beauty market!

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Chapter 25

SIFTING THROUGH AN ALPHABET OF TOPICAL ANTIOXIDANTS

ANTIOXIDANTS NEUTRALIZE free radicals before they attack cell membranes. They are found in a majority of antiaging products because they have shown efficacy in preventing photo-aging and protecting DNA

damage. Their use is predominant among all other cosmeceuticals. According to Freedonia Group, U.S. cosmeceutical product sales will increase 7.2% a year to $8.2 billion in 2012. This column introduces various antioxidants, their mechanism of action and benefits.

Assorted Antioxidants

Mechanism of ActionWe all know that antioxidants are free radical scavengers. Understanding the entire antioxidant cascade would be helpful in understanding their skin benefits. Just watch an apple turn brown after you have sliced it; the free radical theory of aging is based on a similar mechanism of oxidation. In oxidation, there is the donation of electrons by complete transfer from one molecule (donor) to another (receptor). The donor molecule is oxidized while the receptor is reduced.

Antioxidants are any substance that interferes with oxidation either by blocking or by reversing the action. Free radicals, or ROS, are believed to be responsible for wrinkles, sagging, dryness, age spots, inflammation and skin cancer. Because they contain an unpaired electron, they are highly unstable and react with other molecules. It is not easy to detect the presence of free radicals in the cell. Its half-life is very short and can be picked out only with sophisticated instruments rather than a routine test. There are four types of free radicals namely: superoxide (02), trichloromethyl (CCL3), nitric oxide (N0), and mercapto (RS) radicals.

Blocking the ReactionFree radical scavengers are any substance that terminates or blocks the free radical chain reaction. The use of topically applied antioxidants seems promising. Newer studies suggest that combinations of different antioxidants seem to have synergistic effects and hence better efficacy when compared to a single antioxidant use, as has been shown for the combination of vitamins E and C. Antioxidants prevent and

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188 Sifting Through an Alphabet of Topical Antioxidants

repair free radical damage from sun and pollution. Topically applied, they keep wrinkles, brown spots and other signs of aging at bay. Furthermore, antioxidants reduce damage caused by ultraviolet radiation, reduce or eliminate erythema and reduce cell damage. They play a role in a wide variety of actions including reducing irritation, controlling sensitivity, stimulating collagen synthesis and enhancing the immune system.

It is important to note, however, that there is no assurance that the percentage of antioxidant in a cream is high enough to make any difference in the skin. In reality, antioxidants may be present only in token amounts in the formula merely to retard product degradation. Also, both vitamins C and E are very large molecules, therefore it is difficult to get them through the epidermis using a common cream or lotion unless the pH and delivery system is optimized.

Consumers are aware that antioxidants are beneficial and this awareness has grown considerably during the past few years. New research on antioxidants should bring to light more promising ingredients that may provide new or better benefits.

Today, cosmetic chemists have so many antioxidant raw materials to choose from for delivering specific end benefits to broad range of consumers that there is enormous opportunity for antioxidant raw material suppliers to serve the cosmetic industry and dermatological researchers.

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Chapter 26

THE ANTI-AGING BENEFITS OF HYALURONIC ACID

Getting older doesn’t necessarily mean looking old. The idea of growing old just doesn’t creep into the minds of many baby boomers, who are under pressure to look good all the time. New anti-aging actives formulated in creams and

serums make consumers feel increasingly more youthful than their actual age as their outer appearances reflect their inner youthfulness. The ever-increasing growth in new products designed to prevent the skin from aging has attracted consumers in droves to the vibrant anti-aging market.

This column will detail the benefits of hyaluronic acid, which is found naturally in our own skin cells. I’ll answer two key questions, namely: how do we keep our skin youthful looking and how can we undo the damage of time?

Hyaluronic acid’s name is derived from the Greek word for glass (hyalos), which accurately describes its transparent glassy appearance. Hyaluronic acid (HA), is the most abundant glycosaminoglycan (GAG) found in human dermis. It was originally discovered in 1934 by Karl Meyer and John Palmer who isolated it from bovine vitreous humor.1

In young skin, HA is found at the periphery and at interfaces of collagen and elastin fibers. It is thought to help hold together collagen and elastin in the proper configuration. Studies have shown that these connections with HA are absent in aged skin, which may help explain the disorganization of collagen and elastin fibers.2

HA structure is identical irrespective of its source of origin, which could range from bacterial culture, animals or humans. It is a viscous carbohydrate fluid present in connective tissue as synovial fluid, which is responsible for lubricating and cushioning joints.

DermatologicalsHA is non-toxic and non-sensitizing, and therefore can be safely used for all skin types and carries no risk of allergic reactions. Dermal fillers enable dermatologists to inject these naturally- occurring components back into the dermis to restore skin’s volume and minimize the appearance of wrinkles. They mimic the natural materials found in our cells and are injected into skin folds, and deep wrinkles to lift and reshape the face. They are the most popular cosmetic procedures because they produce natural looking results. They are reasonable in cost ($450-600 per syringe), efficient and are instantly transforming.

190 The Anti-Aging Benefits of Hyaluronic Acid

In fact, injections are the fastest growing non-surgical aesthetic procedures.Patients see the results immediately after just one injection treatment. The effects

are temporary but they can last up to six months. Side effects are rare, but they include redness, swelling and bruising. Fillers help skin regenerate natural collagen. It is important to maintain a strong moisture barrier in the top layer of the skin.

More DetailsThere are many different types of fillers and each one has different benefits, usage parameters and duration of effectiveness. In order to develop a gel-like viscosity that could possess an increased residence time, HA is crosslinked. Untreated HA is rapidly broken down by hyaluronidase enzyme. Its half-life is no longer than one day. The most popular cross-linking agent is 1,4-butanediol diglycidyl ether. This process results in HA gels of different viscosity grades.Commercial dermatological preparations are:

Fillers: These are typically HA derived from rooster combs. Another available grade is Hylaform Plus, called Captique. It is similar to Hylaform except it is derived from bacteria. This product has been withdrawn from US market. Restylane is a hyaluronic acid product that is also derived from bacteria. Juvederm, both ultra and ultra plus grades, are non-animal derived dermal fillers consisting of a smooth gel. The ultra plus grade is stronger, giving dermatologists the ability to better treat deeper folds and wrinkles. It also lasts a little longer.

Topicals: HA is important for tissue repair and maintaining skin hydration. 3 HA binds water up to 500 times its weight. Hyaluronic acid does not penetrate the skin because of its large molecular size.4 HA, and its derivative sodium HA, are used in cosmetic formulations for their strong water-binding capabilities. It brings moisture up to the top layer of the skin and keeps skin hydrated. When it is formulated in creams and serums, it provides skin moisturization lasting for few days.

HA has the ability to pull moisture from the atmosphere and trap it on the surface of the skin only, because it can’t penetrate the stratum corneum and enter the epidermis.5 It has been shown that soy isoflavones can increase levels of GAG and specifically HA in aging skin, although the exact mechanism is not known.6

Hyaluronic acid is responsible for maintaining skin water balance, providing hydration, lubrication and cellular function as well as imparting a cushion effect between the joints. It provides a reservoir of water within the skin. In aging skin marked by dehydration, sagging, and wrinkles, a remarkable improvement is demonstrated when skin’s HA levels are boosted.

ConclusionsThe loss of hyaluronic acid in the human body is one of the causes of wrinkles. Hyaluronic acid-injected fillers make skin look younger and improve its tone, making it smooth and supple. Effective active ingredients such as retinoids, peptides and HA are gaining credibility in high-end anti-aging preparations. Regular use of skin care products containing such actives can undo the damage of time.

However, the effectiveness of hyaluronic acid oral supplementation remains some what controversial.

References:1. J. Biol. Chem. 107:629-34, 19342. Int. J. Derm.33(2):119-22, 19443. Sudel KM etal - Photochem. Photobiol. 2005; 81:581-5874. Zettersten EM, etal. J. Am. Derm. 1997; 37:4035. Cosmetics & Toiletries, 113 (3) 35-42., 1998 Hyaluronic acid has strong water-

binding properties,

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Chapter 27

PROBIOTICS PLAY A KEY ROLE IN MAINTAINING SKIN HEALTH

Probiotics are “body-friendly” bacteria that help balance our “good” and “bad” bacteria to help strengthen the immune system and support the body’s ability to remain healthy. Probiotics are live bacterial culture that, when applied

topically, influence the composition of skin microflora. The first mention of topical probiotics as a therapeutic treatment for skin conditions appeared in the medical literature in 1912, and was termed “topical bacteriotherapy.” It was not until 1999 that researchers were able to hone-in on exactly how probiotic application to the skin might improve dermatological health. They found that S. thermophilus, a species of probiotic typically found in yogurt increased ceramide production in keratinocytes, the cells that create our skin, strengthening the lipid barrier of the skin and make it more resilient to dryness.1

The cosmetic industry studied probiotic technology for nearly 15 years; finally, in 2017, researchers understand how it can help skin, according to New York City-based dermatologist Whitney Bowe MD. Recently there have also been an increasing number of skin care products entering the market touting probiotics. In this column, we will briefly review the science supporting the use of topical probiotics in skin care products.

Clinical StudiesResearch has shown that the bacteria in our gut interacts with the immune system, which results in changes in skin. Harmful bacteria in the gut can lead to inflammation like redness, acne and rosacea. It is advisable to incorporate foods and drinks that are rich in probiotics, like yogurt, miso soup, sauerkraut and Kombucha (fermented tea).

Some prefer to take a probiotic supplement, too. Using a topical probiotic is beneficial, as it offers a protective shield and triggers the production of natural moisturizers in the skin. The October issue of Journal of Microbiology and Biotechnology published research findings that middle-aged adults showed improved skin hydration and elasticity and reduced wrinkles after taking a clinical dosage of oral probiotic supplement Lactobacillus plantarum for 12 weeks.

“Scientists are just starting to discern what constitutes a normal, healthy skin microbiome,” said Alan C. Logan, an independent researcher and co-author of “Your Brain on Nature.”

192 Probiotics Play a Key Role In Maintaining Skin Health

It is clear, however that the microbes residing on healthy skin make important contributions to the proper barrier maintenance. They also interact with the immune system and protect against harmful bacteria. A cream containing the lysate of S. thermophiles was found to significantly increase stratum corneum ceramide levels in healthy females after two weeks of application.2 Skin hydration was also improved following use of probiotic lysatecontaining cream.

Through the fermentation process, probiotic bacteria produce acidic compounds like lactic acid, reducing the pH of the skin. The skin microbiome is influenced by pH, sebum content, barrier function and hydration.3 A slight acidic pH favors the growth of proprionbacterium, it discourages the growth of most pathogens. Probiotic strains produce potent antimicrobials such as bacteriocidins, organic acids that prevent pathogen adhesion while more alkaline pH encourages the majority of resident species.

Proprionbacterum species are more plentiful where sebaceous glands are present. Dry areas of the skin have the greatest diversity of species while having the lowest absolute number of bacteria. Furthermore, extrinsic factors such as geographic location, occupation and the use of antibiotics or cosmetics can influence skin microbiodata.4

Studies indicate that alterations in skin microflora play a significant role in conditions such as atopic dermatitis, psoriasis, acne and skin cancer.5 Researchers6 demonstrated that a cream containing 10% B. Longum lysate improved sensitive skin after two months compared to vehicle control. There was a reduction in stinging after lactic acid, as well as an improvement in clinical dryness. In vitro studies on B. Longum lysate suggest, that it may reduce skin sensitivity by reducing neuron reactivity and neuron accessibility.7

Products and BenefitsAlthough probiotic bacteria have documented skin benefits, live cultures are generally not preferred in cosmetics. Rather than including live bacteria cultures, many of the probiotic skin care formulae use bacteria fragments or metabolites. The reason is that there is not currently any science developed to support the idea that live cells are any more effective when applied to the skin than these fragments. In near future, some brands using live bacteria might emerge.

In 2013, the American Academy of Dermatology proposed the use of probiotics in the treatment of rosacea.8 Prebiotics are nondigestible, plant-based carbohydrates that discourage the growth of pathogens while preserving beneficial bacteria. Prebiotics can be incorporated into skin care products and are an excellent alternative to live bacteria.9 Bacterial lysates are also used in cosmetic formulations. Bacterial cell lysates provide broad biologic activity that can be harnessed to provide skin benefits. Skin care products containing these are well positioned for treating conditions characterized by an altered microflora. Cosmetics containing probiotics may also be helpful for improving skin health and beauty.10

According to Dr. Erin Gilbert MD, Ph.D., probiotics are one of the most cutting edge concepts in skin care today. Probiotics based topical products address and correct a multitude of skin conditions including premature aging, acne, hypersensitivity, dullness, rosacea and inflammation. Probiotics when taken internally help with the health of digestive and immune system. It is beneficial in all skin types. Probiotics have proven themselves to be a powerful tool to achieve healthy, balanced and radiant skin.

Yun Company just launched (April 2017) to the European market two products contain live probiotics: ACN and ACN + creams with probiotic microcapsules. The probiotic bacteria are first deactivated and then stabilized by microencapsulation.

193 Probiotics Play a Key Role In Maintaining Skin Health

Encapsulating the bacteria provide protection against the adverse environmental conditions in cosmetic formulations, thereby improving viability. The performance of the probiotic ingredient can be negatively affected by the preservative and emulsification system in the cosmetic product. Microcapsules provide protection. When product is applied topically, the microcapsules burst and deliver the probiotic. These products are packaged in airless tubes to prevent oxidative damage and are proven to last between six months to a year with no chemicals added to preserve the formulation. All products are biome friendly and they do not need refrigeration.

More and more companies are now entering the probiotic market including L’Oréal and Estée Lauder. Clinique’s Redness Solutions foundation, for example features lactobacillus to reduce flushing by balancing the skin’s pH. The British brand Aurelia is built around bifidobacteria, which is said to strengthen the skin’s barrier, and Elizabeth Arden’s SuperStart Renewal Booster contains a probiotic blend believed to boost skin’s natural defenses.

More Study AheadIn cosmetics, there is no standardized definition of probiotics and this makes it very difficult for consumers to really understand what to expect from a cosmetic product carrying a probiotic label. The health of our skin comes from deep within us. In recent years, study of the microbiome has led to innovations in medicine and health, including dermatology. The clinical studies conducted with topical prebiotics, probiotics and bacterial cell lysates do provide demonstrable skin benefits. It appears that more studies are warranted to confirm these skin benefits.

References1 Bockmuhl D. et al IFSCC 20006:9:1-52 Dr. Marzio et al. Increase of skin ceramide lev els in aged subjects. Int. Jr.

Immunopathology Pharmacol. 2008, 21(1) : 137-1433 Zeeuwen PL et al. J. Microbiome and skin dis eases Curr Opin allergy Clin immune

2013, 13 : 420-514.4 Holland KR et al. Cosmetics- what is their in fluence on skin microflora ? Am. Jr.

Clin. Derm. 2002, 3(7) 445-4495 Salva A. et al. Role of the skin microbiome in atopic dermatitis. Clin. Transl. Allergy

2014: 4:336 Gueniche A. et al, Exptal, Derm. 2009, 19 :e1-e87 Di Marzio et al Invest. Derm. 113(1),98-106.8 SharmaD et al Antiaging effects of probiotics Jr. Drugs Derm. 2016:15(1) 9-12.9 Vermuri R-C et al. Intnl. Jr. of Medical Science 12(5) 387- 396Derm. Times, Aug.8, 2016. Dr. P. Ferris)

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Chapter 28

QUESTIONS ARISE OVER PLANT STEM CELLS

STEM cells are found in both plants and animals. They divide and can differentiate into a range of cell types. It is this regenerative property of plant stem cells that has captured the imagination of cosmetic researchers. In this column, we will

briefly review if plant stem cells have anti-aging efficacy, when they are formulated into topical products.

The plant stem cell market for cosmetics is growing at a CAGR of 15.9% and expected to exceed $4.8 billion by 2022, according to Credence Market Research Company. The key players in this market are L’Oréal, Estée Lauder, My Chelle Dermaceuticals, Juice Beauty and Intelligent Nutrients.1

Several years back, stem cells were the marquee ingredients in the flourishing US anti-aging market. But, recent regulatory crackdowns and class action lawsuits have weighed on the industry.

Human-based CellsStem cells are trendy in cosmetic procedures. They are injected along with fat to plump up the skin. In addition to their presence in many skin care formulations, stem cells are touted as an age-reversing ingredient in officebased treatments. However, the US Food and Drug Administration (FDA) recently issued warning letters to three physician-owned stem cell treatment centers in California, Florida and New York. These centers were extracting patient’s own fat, isolating the stem cells and re-injecting them into the patient. All three doctors received the warning letters from the FDA to stop performing these unapproved procedures immediately. Stem cell therapy for anti-aging has not been approved or been deemed safe or effective by the FDA. Furthermore, its use outside of clinical research is prohibited. In recent years, researchers have conducted extensive research on embryonic stem cells which have shown potential to repair damaged tissues and organs. As a result, scientists researched using stem cells in skin care products to help repair wrinkles, and restore and maintain skin firmness and elasticity. However, it is not possible to use live human embryonic stem cells in skin care products, so skin care companies have turned to plant stem cells.

Plant-based Stem CellsLike humans, plants have stem cells, too. In theory, these cells can protect the human epidermal stem cells from damage and deterioration and they can stimulate them to renew the skin. Primarily, botanical stem cells are used in cosmetic products in order to avoid the sourcing and extracting controversies associated with animal- and

195 Questions Arise Over Plant Stem Cells

human-derived stem cells. Grape, raspberry, lilac, rose and edelweiss are common botanical sources.

The most promising stem cell so far has come from an apple from the tree known as Uttwiler Spatlaube, cultivated in Switzerland more than 300 years ago. These apples formed a protective film made of stem cells on the surface when the apple is cut. Liposome encapsulated apple stem cells topical cream in a clinical study, reduced wrinkle depth by an average of 15% after 4 weeks Armed with these results, skin care companies swarmed Mibelle Group, a Swiss company that developed this wonderful active. Numerous products containing this active, were launched several years ago in the market at premium prices. These products claimed to protect longevity of skin cells and combat skin aging.

However, some biologists are skeptical about these particular claims. Renowned plant biologist Professor Liam Dolan of Oxford University, observed that he does not see how plant stem cells could react with human cells. According to Dolan, the stem cells found in skin care products are plant-based not human-based; humans cannot synthesize chlorophyll, so plant stem cells offer no benefit to humans.

Living plant stem cells are not found in beauty products, and even if they were, they would not have the capability to differentiate into specialized human skin cells, plaintiffs assert in a proposed class action against PhytoCellTec user G.M. Collin Company. Evidence that plant stem cells in cosmetic products translate to an improved appearance is tenuous at best, according to Tyler Holling M.D., Stamford Medical Center.

Almost all cosmetic products promoted for their stem cell content actually contain stem cell extracts—not live stem cells. Extracts from stem cells cannot act in the same way as live stem cells. To gain all the true benefits from stem cells and to let them work according to the label directions, they must be incorporated as live cells and should remain so in the formulated cosmetics.

There are other issues as well. Plant stem cells are simply too large to penetrate the skin and cannot live in the cream while it stays on the shelf for months or even years according to Leslie Baumann MD.

According to another dermatologist, Richard Hope MD, stem cells in topical skin care products are of no value at this point. The stem cells are plant derived, dead and basically have no activity in human skin.

ConclusionIt is clear at this stage in the game that cosmetics manufacturers using plant stem cell ingredients are severely limited in what they can safely claim without potentially drawing unwanted attention from federal authorities and/or plaintiff’s lawsuits.1

Furthermore, according to a leading dermatologist, Leslie Baumann MD, the stem cells will become part of fight against skin ageing one day, but until then, let us keep the human-based stem cells in the lab and the stem cell skincare products off the shelves.3 The University of Miami is a leader in this field, so it will continue to monitor the research conducted there, and the cosmetic industry will be informed when stem cells are ready to promote skin health and beauty.

References:1. R. Nelson, Executive Summary, R. Sheet 6/15/17.2. SOFW Journal 2008:134 (5): 30-5. Stem cells don’t work in topical anti-aging

products.3. Leslie Baumann MD, Miami Herald 2/23/16

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Chapter 29

UNDERSTANDING HOW COLLAGEN HELPS HEALTHY LOOKING SKIN

Global sales of collagen products are expected to reach $9.3 billion by 2023 and the market for nutricosmetics will be worth $7.4 billion by 2020 driven, in part, by an aging population and a growing acceptance of functional foods,

according to a report by Transparency Market Research Company. This column will briefly review benefits of collagen for skin.

The word collagen comes from two Greek terms: kola meaning “glue” and gen meaning “producing.” Collagen has gluelike properties; think of it as the building block that keeps skin firm and resilient. The dermis has plenty of collagen and elastin. As we age, our skin produces less collagen; the lack of collagen is the main cause of wrinkles. The body’s natural collagen production declines mostly due to genetic factors along with lifestyle factors such as stress, sun, poor diet, pollution etc. Initial breakdown of collagen depends on members of the collagenase family that are capable of cleaving naïve triple helical collagen. If you never stopped making collagen and never damaged collagen, you would hardly get a wrinkle, your pores would stay small, you would never get a scar and your skin would stay nice and tight. Collagen is the key

Collagen’s Make-UpThere are different types of collagens. Some are derived from animal bones or skin, and others from animal cartilage. Either way, collagen is a protein and it is very rich in two amino acids: proline and hydroxyproline. Its structure is complicated. The amino acids link together to form long chains called peptides. Peptides are smaller molecule proteins, and thus can penetrate the dermis more easily than regular collagen. The deeper penetration of peptides into the skin improves the quality and beauty of the skin. The five most commonly used peptides in antiaging skin care are Palmitoyl pentapeptide-3, Palmitoyl tetrapeptide-7, Acetyl Hexapeptide-3, Palmitoyl Oligo peptide, and Matrixyl 3000.

Peptides form even longer chains called polypeptides. Three polypeptides wrap around each other to form a bundle that is called pro-collagen. Pro-collagen then turns into tropocollagen which then is called a single collagen fiber. The fibers are very well organized. Older skin has less collagen and elastin, which deteriorates and hence do not provide the fill and support that they do in young skin. Its destruction plays a role in the aging of the body.

197 UNDERSTANDING HOW COLLAGEN HELPS HEALTHY LOOKING SKIN

Depending upon how amino acids are combined, you can generate 28 or 29 different types of collagen. Collagen is a long chain amino acid and the most abundant protein in the body. It is composed of amino acids glycine, proline, hydroxyproline and arginine. In nature, collagen is found exclusively in animal tissues, especially bone and connective tissues. There are marine sources but there are no vegetable sources or synthetic sources of true collagen.

You can rub collagen on your skin in lotion form, you can swallow it as a dietary supplement, or you can have it injected directly into your skin. It is an insoluble fiber that is responsible for giving skin elasticity and hair its strength. Soluble collagen is thought to penetrate skin better. Naïve collagen is essentially a fully formed, mature version. It has a very high molecular weight and it is a very large molecule. Hydrolyzed collagen, generally referred to as enzymatically-processed collagen, is most commonly used in cosmetics. Here, a mature collagen is chemically chopped off in very tiny bits. It is generally well absorbed on hair, increasing its tensile strength and elongation. It is also used in soaps to impart a soft texture to skin. The most abundant collagen in the body are Type 1, Type 2 and Type 3. Type 3 is the most stable and longest lasting.

Leiden University Medical Center in The Netherlands made the first direct link between the amount of sugar circulating in the blood and how sugar molecules permanently bond to collagen proteins in your skin. Collagen becomes crosslinked from long-term exposure to the destructive linear sugars. When glycation occurs in skin, the sugar molecules attach themselves to collagen fibers. Extensive cross-linking of collagen causes the loss of skin elasticity, resulting in wrinkled sagging skin. This is a process known as glycation, and it produces compounds called Advanced Glycation End Products (AGEs) that cross-link with proteins and consequently tissues become stiff and inflexible, skin becomes tougher and permanently sags. Glycated collagen is the unseen enemy within. Glycation reduces Type 3 collagen into Type 1, which is more fragile and is less stable than Type 2 and Type 3. When this happens, skin looks and feels less supple and is more prone to wrinkling.

Topical TopicsPricey moisturizers contain collagen, which reportedly replaces the collagen lost during the aging process. This claim is unfounded. Collagen has a molecular weight of 15,000 to 50,000 daltons. Only substances with molecular weight of 5,000 daltons or less can penetrate the stratum corneum.1 These products are usually labeled as firming creams as well as moisturizers, although they have little to no effect on transepidermal water loss.2

Collagen gives skin plumpness, yet its molecules are too large to make it through the skin, it won’t supplement collagen deficiencies. Collagen is the main structural protein that keeps the skin tight and elastic. The loss of collagen results in loss of facial volume causing crow’s feet, nasolabial folds, and jowls on the chin and jaw line areas of the face. To stimulate production of new collagen in the skin, a cosmetic formula must incorporate ingredients that efficiently penetrate deeply and work together to rebuild collagen.

Vitamin C in the form of L-ascorbic acid with concentrations between 5 and 15% was proven to have a skin anti-aging effect by inducing the production of collagen Type 1 and Type 3 (Dermatoendocrinol. 2012). The main action of vitamin C on the skin is direct stimulation of collagen synthesis. It is an essential co-factor for the two enzymes required for collagen synthesis: prolyl hydroxylase and lysyl hydroxylase.3

Topical application of tretinoin can improve the appearance of photo-aged skin by stimulating new collagen production in the dermal layer of the skin (Clin. Interv. Aging 2006). In general, vitamin A derivatives encourage the skin to generate


collagen, increase cell-turnover, and reduce hyperpigmentation. It smooths skin while promoting the growth of collagen and elastin—proteins that keep face firm and supple.

The Role of SupplementsThey are often combined with other vitamins and ingredients such as Type 2 hydrolysates and glucosamine for joint health; for example, low molecular weight Bio Cell is combined with proline hydroxyproline and vitamin C for healthy skin and hair.The body produces less collagen with age; food makers are marketing collagen supplements as a way to boost your body’s level of it. Meanwhile, research has also linked collagen supplements to improved skin elasticity and moisture. Studies report that taking collagen peptides regularly improves skin moisture level and smoothness as well as helps to fight the effects of skin aging.4

Another study showed that individuals taking a daily supplement containing collagen peptides reported a significant reduction in eye wrinkle depth.5 Study participants also showed improvement in their skin’s collagen and elastin after eight weeks of taking the supplement. Marine collagen peptides can have a profound effect on the biological regulation of the skin and have been shown to boost new collagen production.However, these studies are either small in scope, short in duration or not yet replicated by follow up experiments, according to Dr. Mark Moyad MD, MPH, The University of Michigan Medical Center. Furthermore, there is no clear evidence that eating collagen increases your body’s level of it. There are also concerns regarding contaminants in collagen supplements and foods. Since it comes primarily from ground up animal parts, it is better to check for its heavy metal and creatinine content. Harmful heavy metals like copper and arsenic have turned up in supplements. There are also side effects such as nausea, diarrhea and other GI issues. Moreover, it is not clear how much collagen or exactly which type is most effective.

In terms of collagen supplements offering skin and hair benefi ts, Adam Friedman MD, an Associate Professor of Dermatology at George Washington University, says simply “no way.” He insists, “Collagen is going to be digested by your GI tract, because it is not built to survive the massive pH change in the gut.”

A 2002 study in the International Journal of Clinical Pharmacological Research reported that digestive enzymes and hydrochloric acid break down hydrolyzed collagen, which is the type found in most collagen peptide powders. The same study, also found that collagen Type 2 may be able to slip through your gut without losing its chemical structure.

Medical ProceduresThere are in-office procedures to boost collagen. GentleMax Pro Laser is a thermal collagen stimulator that creates new collagen cells leaving skin plump and firm. There is no downtime or pain and it offers facial firmness. Pro-Peel is a face and neck treatment. Results last from 12 to 18 months. Similar to chemical peels, laser treatments can stimulate collagen production by producing a controlled injury to the skin.

Clear+ Brilliant laser promotes collagen production to smooth away the appearance of fi ne lines, wrinkles, uneven skin tone and texture. AMP MD Microexfoliating Roller is easy to use and gently removes dead skin cells and smooths skin’s surface by tearing into it via tiny needles. The process of wounding the skin triggers its


repair by producing new collagen to help smooth wrinkles, according to Dr. Neil Sadick of Cornell Medical College, New York.

ConclusionsCollagen is the key protein in maintaining skin elasticity and structural integrity. For better or worse, they have been used in creams for many years, even though they are too big to penetrate the skin. Still they are good moisturizers.

References:1. Wehr RF Krochmal, Cutis 1987, 89512.2. Cosmetic Dermatology, Leslie Baumann MD3. Kivirikko Ki et al. Acad Sci 1996:3831.4. True Marine Collagen, Research Institute of Biomatrix, Tokyo, Japan.5. Proksch E, et al. Oral intake of specifi c bioactive collagen peptides reduces skin

wrinkles and increases dermal matrix synthesis. Skin Pharmacol Physiol 2014; 27:113-119

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Chapter 30

CANNABIDIOL GETS HIGH MARKS FOR COSMETICS FORMULAS

Cannabis products are gaining momentum in the beauty industry. Cannabidiol (CBD) is a nonpsychoactive cannabis compound that won’t get you high—that’s the job of tetrahydrocannabinol (THC)—but the stuff does get high

marks from cosmetic chemists. This column will briefly examine CBD oil-based cosmeceuticals and nutraceuticals.

Collagen molecules are too big to penetrate the stratum corneum, but that doesn’t keep chemists from incorporating these proteins into creams and lotions.

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201 Cannabidiol Gets High Marks For Cosmetics Formulas

The CBD market is exploding, and expected to increase seven-fold to $2.15 billion by 2021 from roughly $292 million in 2016, according to Brightfield Group, a market research firm specializing in cannabis. Five leading Canadian marijuana company’s market value has catapulted from less than $4 billion to nearly $40 billion in the past year alone. With these growth rates, one can expect the US Congress to pass legislation enabling US companies to accelerate their efforts to sell hemp-derived products including CBD.

CBD oil is extracted from cannabis and is used in topical and oral preparations sold for its relaxation and pain control properties and to even treat diseases. Right now, CBD is being marketed as a cosmetic and supplement ingredient. CBD oil is not to be confused with hemp oil, which is extracted from a different part of the plant and contains little to no CBD or THC. CBD has become one of the most intriguing and notable compound in the field of natural health. It is responsible for the vast majority of the health benefits cannabis has to offer. Some motivated consumers are drawn to CBD topical products largely for their pain relieving properties. The Cannabis plant come in several varieties and has dozens of uses including making of food products, oils, paper, ropes and textiles. Hemp oil has long been available in health food store.

Personal Care UsesCannabis is branching out into skin care; balms, lotions, oils and creams created from hemp are legal in all 50 states. The material has the ability to repair the skin barrier, according to dermatologist Sejal Shah MD, who maintains that CBD oil is ideal for eye cream and serum, because its fatty acids are very moisturizing. In skin care, the oil is tapped for its “antioxidant and neuro-protective properties.”For these and other reasons, CBD has become a key ingredient for many niche skin care brands. Perricone MD’s CBx for Men reduces inflammation, according to Chris Caires, chief innovation officer. Meanwhile, Cindy Capobianco, founder of Lord James Company, says CBD can improve skin conditions like eczema, psoriasis, rosacea and acne. According to Vertly Company Founder Claudia Mata, the brand’s lip balm has gained a devoted following.

CBD is being added to everything from gum drops to beverages, as marketers claim benefits such as pain relief and stress reduction. However, large retailers such as Target and Walmart are staying away from offering CBD oil products. They are sold in health food stores such as Cambridge Naturals, boutiques and regional store chains such as CV Sciences and Barleans. Leading CBD oil infused cosmeceutical products companies are Apothecana, Charlotte’s Web, Ildi Pekar, Isodiol, Shen Beauty, Lord Jones, Myaderm, Cannuka, Khus & Khus, Leef Organics, Vertly, Malin & Goetz.

Grow Your OwnFormulated products come in many forms; some can be mixed into different foods or drinks or taken with a pipette or dropper. Others are available in capsules or as thick pastes to massage into skin. Skin care products containing CBD targets CB1 and CB2 receptors. CBD does not attach directly to either of them; instead, it directs the body to use more of its own cannabinoids. CB1 receptors are present throughout the body, but many are in the brain. CB2 receptors are more common in the immune system. The three most common routes of administration are: sublingual, inhalation and topical. They affect inflammation and pain.

Some products are available as sprays to be administered under the tongue. Several CBD oils with different applications are currently available for purchase on line. Consumers take or apply CBD to treat a variety of symptoms, but its use


is controversial. Most of them are designed to help skin surface issues such as eczema. Dixie Botanicals, a line of CBD supplements, is legal and available in the US and in more than 40 countries worldwide. Lord Jones CBD gum drops, caramels, “veggimins”, chocolate bars, and coffee are the latest in the nutraceutical field.

TrialsThe Journal of the American Academy of Dermatology’s recent review of published studies concluded that cell receptors respond well to CBD-infused products, leaving patients with skin that is less reactive and itchy. Jeff Chen, director of UCLA Cannabis Research Initiative admits that much is still unclear regarding the science behind CBD’s purported effects. The knowledge of unique group of compounds found in cannabis, which interacts with brain and body receptors, may contribute to self-reported effects such as anxiety relief and inflammation reduction. Until recently the best-known compound in cannabis was delta-9 tetrahydrocannabinol (THC). This is the most active ingredient in marijuana. Marijuana contains both THC and CBD, and these compounds have different effects. THC creates a mind-altering “high” when smoked or consumed. This is because THC breaks down when it is heated and introduced in the body.

CBD is different. Unlike THC, it is not psychoactive. It has medical and health benefits. CBD oil contains all 21 known amino acids, plus it is rich in essential fatty acids such as omega 3 and omega 6 which are vital for our internal body and skin. CBD oil is an antioxidant that is even more powerful than vitamin A, C, E, or omega-3 fatty acid. The least processed form of cannabis plant is hemp, and it contains the most CBD. Hemp and marijuana come from the same plant, Cannabis sativa, but the two are very different. According to Dermatologist Jeanette Jacknin MD, affecting the endocannabinoid system with CBD can help the skin look more radiant and youthful. CBD slowed the visible signs of aging in mice. CBD is also said to work on warts, moles and even HPV outbreaks because it is thought to cause cell death in these abnormally growing cell groups.

According to Dr. Tamas Biro, professor of Immunology, University of Debrecen, Hungary, CBD contains anti-inflammatory actives, which are helpful for conditions such as acne, psoriasis and eczema. He also conducted cell model research proving CBD inhibited sebum production while normalizing overactive sebaceous gland cells, one of the main causes of acne. And yet, a study published in the Journal of the American Medical Association found widespread mislabeling of CBD products sold online. The problem is that there is no study which indicates the proper dose. According to dermatologist Dendy Engelman MD, CBD might be the ticket to a clear skin too. Many small scale studies have looked into CBD safety. Researchers have found no significant side effects on the central nervous system. The most common side effect was tiredness. Also, some people reported diarrhea and changes in appetite or weight.

Regulators Weigh InThe US Food and Drug Administration recently approved an epilepsy drug featuring cannabidiol. Many states have moved toward legalization of marijuana, which has pushed cannabis into the mainstream. CBD cannot be sold in dietary supplements or added to foods being sold between states. The FDA considers hemp oil and its derivative CBD to be a dietary supplement (not a medication). One does not need a doctor’s prescription and can legally purchase and consume CBD in any state. FDA is concerned about the proliferation and illegal marketing of unapproved CBD-containing products with unproven medical claims, according to FDA Commissioner Scott Gottlieb.


According to Melvin Patterson, a spokesman for the US Drug Enforcement Administration, products that are appearing on the shelves are illegal, but enforcement is not a priority for the agency, which is currently focused on the opioid crisis. DEA considers cannabis an illegal schedule 1 drug, one with “high potential” for abuse and with no currently accepted medical treatment use. According to the US Department of Agriculture, CBD extracted from hemp is legal.

The legality of selling CBD to minors is also an unresolved issue. There is generally a minimum age requirement of 18 to 21 for purchasing in states where cannabis is legal. Federal law, for years have regulated hemp alongside marijuana as a “controlled substance,” making it illegal to sell certain extracts or derivatives. However, Federal Farm Bill of 2014, permits states to initiate pilot programs to study cannabis growth, cultivation and marketing of hemp. CBD derived from hemp can be distributed nationally.

Consumers credit CBD with benefits such as anxiety relief and inflammation reduction, but researchers say it’s unclear what causes these effects or even whether they are real. And yet, so many of CBD’s benefits are well known. We can only conclude that there have not been any large scale studies done on CBD. All evidence is anecdotal or is based on animal research or small, short term human studies. Nevertheless, as CBD oil goes mainstream, it is not easy to tell which products will hold up to scrutiny. In the meantime, it is important for consumers to make sure that the CBD they are considering comes from a reputable source.

COSMECEUTICALS - 7 Con

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