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Herbs–Are they Safe Enough? An OverviewDivya Singh a , Rajiv Gupta a & Shubhini A. Saraf aa Faculty of Pharmacy, Babu Banarasi Das National Institute of Technology and Management,Dr. Akhilesh Das Nagar, Lucknow, India

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Critical Reviews in Food Science and Nutrition, 52:876–898 (2012)Copyright C©© Taylor and Francis Group, LLCISSN: 1040-8398 / 1549-7852 onlineDOI: 10.1080/10408398.2010.512426

Herbs–Are they Safe Enough?An Overview

DIVYA SINGH, RAJIV GUPTA, and SHUBHINI A. SARAFFaculty of Pharmacy, Babu Banarasi Das National Institute of Technology and Management, Dr. Akhilesh Das Nagar,Lucknow, India

Drugs based on herbs have become a common form of therapy as well as for prophylaxis because they are often perceived asbeing natural and therefore harmless. Today they are one of the hottest trends and most sought after in the field of nutrition orherbal therapeutics. As the use of complementary medicine grows, so does the knowledge that many compounds in commonuse not only have a significant effect on the body but may also interact with pharmaceuticals and also with other alternativeproducts. Concurrent use of herbs with drugs may mimic, magnify, or oppose the effect of drugs leading to herb-druginteractions. Currently, there is very little information published on herb-herb or herb-drug interactions as compared to theuse of herbs which is progressively growing across the world. Many reports of herb-drug interactions are sketchy and lacklaboratory analysis of suspect preparations. Health-care practitioners should caution patients against mixing herbs andpharmaceutical drugs. The article reviews the recent literature on the adverse effects of herbal remedies including the mostwidely sold herbal medicinal products, like liquorice, garlic, ginger, green tea, and turmeric, etc., and reinforce the safetyaspect of herbal products, which are considered to be relatively safe by common people.

Keywords hazard, interaction, contraindication, adverse effects

INTRODUCTION

Herbs have been used for medicinal purposes since the be-ginning of recorded time. Although most people believe thatherbs are harmless plants, about one-third of our drugs (includ-ing digitalis, morphine, atropine, and several chemotherapeuticagents) were developed from plants. So, indeed, herbs can be po-tent products (Tables 1 and 2). Herbs can affect body functions;therefore, when herbs are taken concurrently with drugs, in-teractions are possible (Table 5) (Mohammad and Mohammad,2009). In a survey involving medically advanced countries likethe United States, U.K., Germany, etc., it was observed that peo-ple’s perception regarding health and fitness was primarily basedon diet and not exercise or hereditary factors as it was earlierbelieved. After the initial development in the 1980s, countrieslike Japan first gave the definition of “physiologically functionalfoods.” Later on, a world renowned authority such as FDA alsogave definition like medical foods itself proves the significanceof herbs in retaining health in human life (Hardy, 2000). Fromthe earliest times, herbs have been prized for their healing abili-ties. Because the use of herbal therapies in the U.S. is escalating,

Address correspondence to Rajiv Gupta, Faculty of Pharmacy, Babu Ba-narasi Das National Institute of Technology and Management, Dr. AkhileshDas Nagar, Lucknow 227 105, (U.P.), India. E-mail: rajiv961@rediffmail.com

it is essential to be aware of clinical and adverse effects, doses,and potential drug-herb interactions. A consumer poll indicatedthat one-third of the respondents use botanical remedies, andnearly one in five taking prescription medications also usedherbs, high-dose dietary supplements, or both. An estimated15 million adults are at risk for potential adverse interactionsinvolving prescription medications and herbs or vitamin sup-plements, yet most practicing physicians have little knowledgeof herbal remedies or their effects (Valli and Giardina, 2002).Many of the thousands of plant species growing throughout theworld have medicinal uses, containing active constituents thathave a direct pharmacological action on the body. The risks ofusing herbal remedies, considered “natural,” should not be disre-garded, as some have serious side effects and some interact withand influence conventional medical therapeutics. The effect maybe pharmacokinetic by altering absorption or metabolism, andmay be pharmacodynamic, by changing the final effect of thedrug (Goldstein et al., 2006). They are not entirely free of sideeffects or adverse drug interactions as believed by a large sec-tion of society. The availability of herbal products as “over-the-counter” drugs and their increasing usage in the United Statesand Canada have caused concern at the US FDA, since theseproducts are not currently monitored for their safety, efficacy,and quality (Tables 3 and 4). The manufacturers of these prod-ucts are not required to submit proof of safety and efficacy to the

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U.S. FDA before marketing. For this reason, the adverse effectsand drug interactions associated with herbal remedies are largelyunknown (Cupp, 1999). Reliable information on these aspectsof the products is not available. Most of the clinical trials carriedout to date have been lacking in scientific design, data collectionand interpretation, and systematic toxicological evaluation.

Some Commonly used Herbs, their Adverse Effects, andContraindications

Acorus calamus (Araceae) Commonly known as Sweet Flag

Calamus has been identified as an unsafe herb. Calamus maycause stomach upset and skin rashes. Calamus is not recom-mended for pregnant or breastfeeding women due to a lack ofavailable scientific evidence. Individuals with a known allergy orhypersensitivity to calamus must avoid it (Klepser and Klepser,1999; Healthline, 2010).

Aesculus hippocastanum (Hippocastanaceae) Commonlyknown as Horse Chestnut

The use of horse chestnut in cultural and traditional settingsmay differ from concepts accepted by current Western medicine.Although uncommon, allergic reactions to horse chestnut havebeen reported such as difficulty in breathing, closing of thethroat, swelling of the lips, tongue, or face, or hives), bleeding(gums, nose, skin, stool, urine), decreased amounts of urine,joint or muscle pain, skin rash, or unusual bruising (Popp et al.,1992; eMedicineHealth, 2010). Other less serious side effectshave also been reported like stomach upset or heartburn, orburning or stinging where cream or gel is applied. Horse chestnutshould not be used without first consulting a doctor if the personhas had a history of blood clots, colitis, or other stomach orintestine related illnesses, diabetes, heart disease, low bloodpressure, kidney disease, liver disease, or poor blood circulation(Popp et al., 1992).

Allium sativum (Liliaceae) Commonly known as Garlic

Side effects of garlic include headache, itching, garlic odoron breath and skin, occasional allergic reactions, stomach dis-orders, decrease in serum protein and calcium levels, associa-tion with bronchial asthma, and contact dermatitis (Zhion.com,2008; Argento et al., 2000; Heck et al., 2000; Izzo and Ernst,2001; Abebe, 2002; Vaes and Chyka, 2000).

Aloe vera (Liliaceae)

Aloe vera is a natural product that is now a day frequentlyused in the field of cosmetology. There are various indicationsfor its use. Aloe vera has some adverse effects, it can causedamage to intestinal mucosa, which may be irreversible, painfulintestinal spasms, severe hemorrhagic diarrhoea, kidney dam-age, reddish urine (with frequent use), accumulation of blood

in the pelvic region (with large doses), fluid and electrolyteloss from frequent use, hypokalemia, contact dermatitis delayedwound healing because of reduced oxygen permeability (top-ical forms), spontaneous abortion or premature birth (duringthe third trimester of pregnancy), and oral mucositis (Ferreiraet al., 2007; Shoji, 2006; Krishnakumar et al., 2009; aloe re-search.com, 2007). External aloe preparations are contraindi-cated in patients known to be hypersensitive to aloe or in thosewith a history of allergic reactions to plants in the Liliaceaefamily (garlic, onions, and tulips). Internal use is also con-traindicated in patients known to be hypersensitive to aloe aswell as during menstruation, in children, and in patients with re-nal or cardiac disease because of the potential for hypokalemiaand, possibly, disturbance of cardiac rhythm. Oral aloe is notrecommended during pregnancy due to theoretical stimulationof uterine contractions, and in breastfeeding mothers, it maysometime causes gastrointestinal distress in the nursing infant(aloe research.com, 2007; Surjushe et al., 2008).

Ananas comosus (Bromeliaceae) Commonly known asPineapple

The stem and the fruit of Pineapple plant contains a pro-teolytic digestive enzyme, Bromelain. Bromelain may causenausea, vomiting, diarrhea, metrorrhagia, and hypermenorrhea.It may cause drowsiness or sedation. Caution must be used inpatients with coagulation disorders, liver or kidney disease, andin hypertension patients. Allergic reactions, including skin reac-tions and asthma, may occur if the patient is allergic to pineap-ples (Bradbrook, 1978; Tinozzi and Venegoni, 1978; Gutfreundet al., 1978; Integrative Medicine, 2000).

Angelica sinensis (Apiaceae)

Angelica is generally believed to be nontoxic. Angelica is ac-cepted as being safe as a food additive in the United States andEurope but its safety in medicinal doses is not known. Some sideeffects have rarely been reported with angelica taken alone orin combination with other herbs. These include headache, light-headedness/dizziness, sedation/drowsiness, insomnia, irritabil-ity, fever, sweating, weakness, abnormal heart rhythms, bloodpressure abnormalities, wheezing/asthma, hot flashes, worsen-ing premenstrual symptoms, reduced menstrual flow, increasedmale breast size, kidney problems, or skin rash (Medline Plus,2009; Goh and Loh, 2001). Using angelica may pose a can-cer risk (Best-home-remedies.com, 2010). Angelica is not rec-ommended during pregnancy due to possible hormonal andanticoagulant/anti-platelet properties (Medline Plus, 2009).

Apium graveolens (Umbelliferae) Commonly known as Celery

Celery is responsible for a number of skin reactions. When itcomes into contact with the skin, it can make the skin sen-sitive to sunlight. Celery contains furanocoumarins, includ-ing xanthotoxin, bergapten, and 5-methoxypsoralen, which are

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chemicals that react with sunlight (Finkelstein et al., 1994).There have been reports of allergic contact dermatitis, acuteurticaria, angio-edema and anaphylaxis due to celery (Pauliet al., 1985; Ballmer-Weber et al., 2000). Celery root is alsoknown causes of acute food-induced allergy (Ballmer-Weber etal., 2000).

Arctostaphylos uva-ursi (Ericaceae) Commonly known asBearberry

Uva ursi is generally well tolerated in short-term, traditionaldoses, but available human trial data is limited. Uva ursi maycause tachycardia, cardiac arrhythmias, skin irritations, nau-sea, vomiting, diarrhoea, stomach upset, greenish-brown urinecolor, irritation and inflammation of the urinary tract, mucousmembranes, increase in urine flow, hepatotoxicity, insomnia,convulsions, seizures, irritability, motor restlessness, cyanosis(bluish skin discoloration due to lack of oxygen in the blood),headaches, shortness of breath, or tinnitus (ringing in the ears)(Livestrong.com, 2010; Beaux et al., 1999; Bentley-Phillips andBayles, 1975). Long term ingestion of uva ursi has caused bilat-eral bull’s-eye maculopathy, and may be considered a potentialretinal toxic herb. Persons suffering from renal or hepatic dys-function (due to risk of inflammation of the urinary tract andhepatoxicity), with gastrointestinal distress (because the prepa-ration can be irritating to the mucous membrane of the stomachand the intestine due to high amounts of tannins), from gallstonesand persons on diuretics (may promote electrolyte imbalance)must use Uva ursi with caution (Livestrong.com, 2010).

Areca catechu (Arecaceae) Commonly known as Betel Palm

Both benign and malignant diseases can be induced by betelnut chewing. Betel causes reddish discoloration of teeth, pe-riodontitis, and buccal mucositis. Among malignant diseasesinduced by betel quid, oral squamous cell cancer is the mostimportant but esophageal cancer and hepatocellular cancer canalso be observed (Wollina et al., 2002). Oral diseases associatedwith Betel palm chewing are oral submucous fibrosis (OSF),oral leukoplakia (OL), and oral cancer (Zhang and Reichart,2007; Reichart and Nguyen, 2008). Areca catechu causes bron-choconstriction in asthmatic patients and may aggravate asthma(Taylor et al., 1992; Kiyingi, 1991). It also causes verrucouslesions (Chung et al., 2005). Betel chewing may predispose tocolonization with H. pylori in the digestive tract through swal-lowing the quid or during betel chewing (Fernando et al., 2009).Areca-induced lichenoid lesions appear mainly on buccal mu-cosa or tongue and produce a cariostatic effect (Howden, 1984).In chronic chewers a condition known as betel chewer’s mucosa,a discolored areca nut-encrusted change is developed (Trivedyet al., 2002).

Arnica montana (Asteraceae)

Allergic reactions may occur when taking arnica in fullstrength preparations or when handling the plant (Hausen, 1980;Reider et al., 2001; Paulsen, 2002; Werner, 2007). Reactions in-cluding Sweet’s syndrome, facial eczema, oral lesions, itchyerythema (reddening of the skin) of the legs, trunk (torso), andface, and dermatitis have been reported. Consumption of Arnicamontana-containing extracts has caused severe gastroenteritisdue to mucosal irritation, nervousness, nausea, and vomiting.Arnica may also cause muscle weakness, collapse, and death.High doses may impair urine flow and damage the kidneysand liver (Andersen, 2001; Healthline, 2010; Spettoli et al.,1998). There is also the potential for organ damage, coma, anddeath with the internal use of arnica. Internal use of arnica isnot recommended in pregnancy due to the potential for uterinestimulation and toxicity (Healthline, 2010).

Artemisia vulgaris (Compositae) Commonly known asMugwort

Mugwort may cause liver damage, nausea, and convulsions.Some people develop contact dermatitis, or allergic skin rash,if they are in contact with mugwort and certain other spices.This food allergy has been called the mugwort-spice syndrome(Anliker et al., 2002; Jensen-Jarolim et al., 1997; Subiza et al.,1989). In addition, mugwort pollen has been reported to causeasthma in susceptible children. Mugwort should be avoided dur-ing pregnancy and lactation. The herb is a uterine stimulant.Women should avoid its use during lactation as the chemicalconstituent thujone may be passed to the baby through themother’s milk. Mugwort should not be ingested if uterine in-flammation or pelvic infection is present (Answers.com, 2010).

Astragalus membranaceus (Fabaceae) Commonly known asMilk-vetch

Astragalus may cause Bloating, diarrhoea, gas, nausea, stom-ach upset. Severe allergic reactions (rash, hives, itching, diffi-culty breathing, tightness in the chest, swelling of the mouth,face, lips, or tongue), bloody or black stools, difficult or painfulswallowing, failure to have a bowel movement, stomach or ab-dominal pain (Drugs.com, 2010).

Azadirachta indica (Meliaceae)

It is important to know that while taking Azadirachta, sideeffects may occur even though the supplement is a “natural”product. Potential side effects include low or no urine produc-tion, yellowing of the skin, and an allergic reaction (symptomsmay include itching or hives) (eMedTV, 2010). Azadirachta oilcan cause dermatitis (Reutemann and Ehrlich, 2008). There havealso been reports of very serious side effects of Azadirachta inchildren, including seizures, loss of consciousness, and coma(eMedTV, 2010).

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Berberis aquifolium (Berberidaceae) Commonly known asOregon grape, Barberry

The use of the Berberis aquifolium and other traditional Chi-nese medicines containing a high proportion of berberine isbest avoided in jaundiced neonates and pregnant women (Chan,1993). Adverse effect of Berberis aquifolium are abdominal dis-comfort, abdominal distention, abortion, alterations in gut flora,bradycardia, cardiac arrest, cardiac damage, death, decrease inblood glucose, diarrhoea, dyspnea, eye irritation, facial flush-ing, faintness, flu-like symptoms, giddiness, headache, hemor-rhagic nephritis, hepatotoxicity, hyperbilirubinemia, hyperten-sion, hypotension, and increased serum total (Livestrong.com,2010).

Berberis vulgaris (Berberidaceae) Commonly known asBarberry

Adverse reactions associated with Barberry are CNS de-pression, paralysis, paresthesias, seizures, asystole bradycar-dia, heart block, mouth ulcers, abdominal cramps and pain,diarrhoea, nausea, vomiting, respiratory depression, and con-tact dermatitis (Articlesbase.com, 2008). Berberis Vulgaris cansuppress as well as intensified the processes of lipid perox-idation (Ryzhikova et al., 1999). It is contraindicated in pa-tients with heart problems, particularly arrhythmias, heart fail-ure, or hypertension, and in pregnant patients (Articlesbase.com,2008).

Boswellia serrata (Bruseraceae) Commonly known as IndianOlibanum Tree

Boswellia extract has been associated with dermatitis, mildgastrointestinal upset, abdominal fullness, epigastric pain, gas-troesophageal reflux symptoms, diarrhoea, and nausea. Reportsin the Indian literature suggest that resin from boswellia is anemmenagogue and may induce abortion (About.com, 2009).

Calendula officinalis (Asteraceae) Commonly known asMarigold

Calendula may cause contact dermatitis, or an anaphylacticor eczematous allergic reaction (Reider et al., 2001). Peoplewith allergies to plants in the Aster/Compositae family suchas ragweed, chrysanthemums, and daisies are more likely tohave an allergic reaction to calendula. Calendula is associatedwith a fatal reduction in blood glucose, decreased in serumlipids and protein, eye irritation. It is not clear if calendulais safe for use during pregnancy or breastfeeding. In animalstudies, calendula had effects on the uterus, and calendula hastraditionally been thought to have harmful effects on sperm andto cause abortions. However, it is not clear if these effects occurwith use of calendula on the skin (MedlinePlus, 2009).

Camellia sinensis (Theaceae) Commonly known as Green Tea

Tea may cause the following symptoms due to its caffeinecontent: restlessness, irritability, sleeping problems, tremor,heart palpitations, loss of appetite, upset stomach, nausea, fre-quent urination, and skin rash. Green tea contains caffeine, cat-echins, and tannic acids, and all three substances have beenlinked to pregnancy risks. In addition, drinking a large amountmay cause neural tube birth defect in babies (AmazingGreen-Tea.com, 2010).

Caffeine can interfere with many prescription medicationscausing adverse reactions or dangerous interactions. Green teahas been associated with documented reports of potential inter-actions with warfarin (Heck et al., 2000). Results suggest thatconsumption of tea affect the human status of niacin, thiamin,iron, and protein (Thankachan et al., 2008; Nelson and Poulter,2004; Temme and Van Hoydonck, 2002; Zijp et al., 2000).

Cassia angustifolia (Leguminosae)

Cassia is likely safe for most adults and children over age2 when used short-term. Cassia is an FDA-approved nonpre-scription medicine. Cassia can cause some side effects in-cluding stomach discomfort, cramps, and diarrhoea (WebMD,2009). Results from some of the studies suggest that compo-nents of Cassia products, particularly emodin, aloe-emodin,anthraquinone sennoside B, and rhein have genotoxic activity(Brusick and Mengs, 1997; Mukhopadhyay et al., 1998). Cassiashould not be used for more than two weeks because longer usecan cause the bowels to stop functioning normally and mightcause dependence on laxatives. Long-term use can also changethe amount or balance of some chemicals in the blood (elec-trolytes) that can cause heart function disorders, muscle weak-ness, and other harmful effects. Cassia should not be used bypeople with abdominal pain, intestinal blockage, Crohn’s dis-ease, ulcerative colitis, appendicitis, stomach inflammation, analprolapse, or hemorrhoids. Cassia poisoning may leads to hepato-myoencephalopathy in children (Vashishtha et al., 2007; 2007).In a study performed to evaluate the potential carcinogenic activ-ity of Cassia for the rat colon, it was concluded that Cassia mightbehave as weak promoters in rat colon carcinogenesis (Meretoet al., 1996). Unintentional ingestion of Cassia-containing lax-atives in young children may potentially cause severe diaperrash, blisters, and skin sloughing (Spiller et al., 2003). Inges-tion of large doses of Cassia laxatives may expose people to therisk of hepatotoxicity (Vanderperren et al., 2005). Chronic useof Cassia may rarely be associated with portal vein thrombosis(Soyuncu et al., 2008).

Caulophyllum thalictroides (Berberidaceae) Commonly knownas Blue cohosh

Blue cohosh is not safe for adults or children. It can cause di-arrhoea, stomach cramps, chest pain, increased blood pressure,increased blood sugar, and other severe side effects (WebMD,

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2009). When taken by the mother late in pregnancy, blue cohoshcan cause severe heart problems including acute myocardial in-farction associated with profound congestive heart failure andshock in the newborn baby (Jones and Lawson, 1998). If usedas an abortifacient it can produce symptoms like tachycardia,diaphoresis, abdominal pain, vomiting, and muscle weakness,and fasciculations (Rao and Hoffman, 2002).

Centella asiatica (Apiaceae)

Centella asiatica is an herb that is commonly used in tra-ditional Chinese and Ayurvedic medicine. Centella asiatica ispossibly safe when taken orally or applied topically appropri-ately (Naturalhealthweb.com, 2003). However, there is concernthat Centella asiatica might cause liver damage in some peo-ple or make liver problems worse (Jorge and Jorge, 2005).It can also cause other side effects including stomach upset,nausea, and itching. Too much Centella asiatica might alsocause drowsiness (Naturalhealthweb.com, 2003; Veerendra Ku-mar and Gupta, 2002).

Cimicifuga racemosa (Ranunculaceae) Commonly known asBlack cohosh

The safety profile of black cohosh is positive (McKenna etal., 2001). Adverse events with black cohosh are allergic reac-tions like skin rash, itching or hives, swelling of the face, lips,or tongue, difficulty breathing, shortness of breath, or wheez-ing, easy bruising, fast heartbeat, slow heartbeat, or palpita-tions, high blood pressure, nausea, vomiting, headache, dizzi-ness, mastalgia, weight gain, unusually weak or tired, heart-burn, and gastrointestinal upsets (Healthline, 2010; Mahady etal., 2002; Huntley and Ernst, 2003). Black cohosh may causehepatic failure (Whiting et al., 2002). The estrogenic effects ofblack cohosh are controversial, and the more recent data in-dicate that black cohosh extracts may have an anti-estrogenicactivity. Owing to potential effects on sex hormones, however,black cohosh should not be administered to children or duringpregnancy and lactation (Mahady et al., 2002).

Cinnamomum aromaticum (Lauraceae)

Cinnamon is possibly safe for most people in amounts usedfor medicine. These amounts are slightly higher than amountsfound in food. However, cinnamon is possibly unsafe whentaken in large amounts. The cinnamon oil can be irritating to theskin and mucous membranes, including the stomach, intestine,and urinary tract. It can cause side effects such as diarrhoea,vomiting, dizziness, asthma, allergic contact dermatitis, andstomatitis (bullous eruption, oral erythema multiforme, hyperk-eratosis, chronic lichenoid mucositis with plasmacytic infiltra-tion, marked chronic perivasculitis, oral leukoplakia, squamouscell carcinoma of the tongue), drowsiness, loss of hair, smartingof eyes, and loss of weight. Cinnamon might decrease bloodsugar. So people on diabetes medications should take precau-

tions (Uragoda et al., 1984; Drake and Maibach, 1976; Goh andNg, 1988; Cohen and Bhattacharyya, 2000; Miller et al., 1992;Endo and Rees, 2006; Tremblay and Avon, 2008; De Rossi andGreenberg, 1998; Mihail, 1992; Westra et al., 1998).

Citrus aurantium (Rutaceae) Commonly known as Bitterorange

Bitter orange has generally been recognized as safe (GRAS)for the use in foods in the United States. Despite the lack ofsystematic study on the safety and efficacy of bitter orange,there are several theoretical side effects that may occur fromthe use of bitter orange (Healthline, 2010). For instance, bit-ter orange may cause adverse cardiovascular effects becauseit contains synephrine and N-methyltyramine (Nykamp et al.,2004). Theoretically, bitter orange may worsen narrow-angleglaucoma (Penzak et al., 2001). It may also trigger migraineor cluster headaches. The plant must be used with care in pa-tients with hyperthyroidism because it may worsen the condi-tion due to its synephrine content. It is a potential photosensi-tizer (Healthline, 2010). Ischemic colitis associated with use ofbitter orange-containing dietary weight-loss supplements (Sul-tan et al., 2006). Avoid using in patients with intestinal colicbased on reports of convulsion and death in children who con-sume large amounts of bitter orange peel. Also, avoid using inpatients taking QT-interval prolonging drugs or with long QTinterval syndrome. Theoretically, bitter orange might increasethe risk of ventricular arrhythmias (Healthline, 2010). Severehypertension, tachyarrhythmias, and monoamine oxidase in-hibitor recipients should avoid consumption. Persons takingdecongestant-containing cold preparations should also refrainfrom intake (Penzak et al., 2001). There is some possible as-sociation of acute lateral-wall myocardial infarction and bitterorange supplement (Nykamp et al., 2004).

Coleus forskohlii (Labiatae) Commonly known as Coleous

Individuals with allergy to Coleus forskohlii should avoidcoleus products. There are reports of skin rash (airborne), con-tact dermatitis with exposure to some species of coleus, suchas Coleus blumei and Coleus scutellarioides (Bryld, 1997). Atrecommended doses, coleus is generally regarded as safe, withfew reports of side effects. There have been reports of skin rash,a milky film over the eyes (when used as an eyedrop), and in-creased heart rate and flushing (coleus.net, 2010). Coleus maylower blood pressure (Lindner et al., 1978). In animal stud-ies, coleus has caused sedation. Large doses of coleonol havea depressant action on the central nervous system (Dubey etal., 1981). In theory, coleus may increase the risk of bleeding,so avoid taking coleus before some surgeries and dental proce-dures. Coleus should not be used by people with active bleeding,such as peptic ulcer or intracranial bleeding. Coleus may stim-ulate the thyroid and should be used cautiously by people withthyroid disorders. Caution should be used in patients with acidreflux or other gastric acid problems. Forskolin has been found

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to stimulate acid formation. Coleus is not recommended duringpregnancy and breast-feeding. There is some evidence in an-imals that coleus may increase the risk of miscarriage duringpregnancy.

Commiphora mukul (Burserceae)

Crude Commiphora extracts can cause side effects suchas skin rashes, diarrhoea, hiccups, restlessness, apprehension.Commiphora is considered as an emenogogue and a uterinestimulant, and should not be used during pregnancy. It stimu-lates the thyroid gland (Tripathi et al., 1984). Caution is rec-ommended with patients who are on prescribed medications forcardiovascular disease (Miller, 1998).

Crataegus oxyacantha (Rosaceae) Commonly known asHawthorn

The most frequent adverse events were dizziness/vertigo,gastrointestinal complaints, headache, migraine and palpitation,nausea, fall, circulation failure, and erythematous rash (Danieleet al., 2006).

Curcuma longa (Zingiberaceae) Commonly known asTurmeric

Even though it is a “natural” product, turmeric may cause sideeffects. Turmeric side effects included nausea and diarrhoea.When applied to the skin, turmeric can cause irritation and al-lergic contact dermatitis reactions. Consuming high amount ofturmeric may produce liver problems. There is also some con-cern that turmeric could make preexisting gallbladder problemsworse. (eMedTV, 2010; Heck et al., 2000; Hata et al., 1997).

Cymbopogan citrates (Gramineae) Commonly known asLemongrass

Lemongrass oil was listed as having a high reactivity in sen-sitive patients (Frosch et al., 2002). Lemongrass may cause skinreactions, irritation, and burning if not properly diluted whenused on the skin in some individuals (Bleasel et al., 2002; Health-line, 2010). In general, a common side effect of lemongrass oilis rash. Lemongrass may lower blood sugar levels. Patients withdiabetes and hypoglycemia and in those taking drugs, herbs,or supplements that affect blood sugar must be careful whiletaking lemongrass. Serum glucose levels may need to be moni-tored. Lemongrass may cause slight increases in liver functiontests, particularly bilirubin, or an increase in pancreatic tests,particularly amylase. It is not recommended during pregnancyor breastfeeding due to lack of sufficient human data. Early sci-entific evidence is conflicting and some chemical compoundsfound in lemongrass (beta-myrcene) may cause decreased birthweight, increased perinatal mortality, and delay in development.Lemongrass may have respiration-inhibitory effects (Inouyeet al., 1998).

Datura stramonium (Solanaceae) Commonly known as Jimsonweed, Thorn apple

Datura is unsafe. It is poisonous and can cause many toxiceffects including dry mouth and extreme thirst, dilated pupils,blurred vision, nausea, vomiting, fast heart rate, tachycardia,hallucinations, combative behavior, difficulty urinating, hightemperature, seizures, confusion, loss of consciousness, breath-ing problems, and death. Children are more sensitive than adultsto the toxic effects of jimson weed. Even a small amount can killthem (WebMD, 2009; Dewitt et al., 1997; Fraunfelder, 2004).Inappropriate consumption of any part of the plant can result insevere anticholinergic toxicity (Phua et al., 2008; Marc et al.,2007; Nakamura et al., 2008; Koevoets and van Harten, 1997;Guharoy and Barajas, 1991; Al-Shaikh and Sablay, 2005). In astudy performed on albino rat, a marked reduction was notedin the protein, DNA, and RNA contents of Datura administeredrats (Hasan and Kushwaha, 1987).

Digitalis purpurea (Scrophulariaceae) Commonly known asFoxglove

Digitalis purpurea can cause poisioning after ingestion,symptoms of poisoning include nausea, vomiting, diarrhoea,abdominal pain, cardiovascular shock with sinus, bradycardiacatrial fibrillation, flickering in eyes and palpitations, dyspnea, or-thopnea, and appetite loss (Lacassie et al., 2000; Brustbauer andWenisch, 1997; Yamada et al., 1999; Medicinenet.com, 2005).

Dioscorea villosa (Dioscoreaceae) Commonly known as Wildyam, Colic root

Dioscorea villosa (wild yam) induces chronic kidney injuryvia pro-fibrotic pathways (Wojcikowski et al., 2008). Wild yamis believed to cause uterine contractions, and therefore its use isdiscouraged during pregnancy.

Echinacea purpurea (Compositae) Commonly known as Coneflower

When taken orally echinacea usually does not produce sideeffects. However, some people experience allergic reactions,including rashes, increased asthma, urticaria/angioedema, andanaphylaxis. In clinical trials, gastrointestinal side effects weremost common. People are more likely to experience allergicreactions to echinacea if they are allergic to related plants inthe daisy family, which includes ragweed, chrysanthemums,marigolds, and daisies. Also, people with asthma or atopymay be more likely to have an allergic reaction while tak-ing Echinacea (NCCAM, 2008; Mullins and Heddle, 2002;Mullins, 1998). Echinacea can cause ocular side effects (Fraun-felder, 2004). There is some possibility that pharmaceuticalscontaining Echinacea purpurea might influence fetal develop-ment in humans also because they may interfere with embrional

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angiogenesis, and should not be recommended for pregnantwomen (Barcz et al., 2007).

Ephedra gerardiana (Ephedraceae)

Adverse effect related to Ephedra gerardiana are hyper-tension, insomnia, arrhythmia, nervousness, tremor, headache,seizure, cerebrovascular event, myocardial infarction, kidneystones, anxiety, confusion, dizziness, psychosis, restlessness,seizure, cardiac arrest, hypersensitivity myocarditis myocardialinfarction, constipation (caused by tannin content), urine re-tention, uterine contractions, and exfoliative dermatitis (Cupp,1999; Home-Remedies.Info, 2010; Wettach and Falvey, 2002;Samenuk et al., 2002; Kaberi-Otarod et al., 2002). Ephedra canexacerbate seizures in people with epilepsy (Spinella, 2001; Ver-duin and Labbate, 2002). Leber hereditary optic neuropathy isassociated with the use of ephedra alkaloids (Warner and Lee,2002). Ephedra is contraindicated in pregnant women becauseof the risk of uterine stimulation (Home-Remedies.Info, 2010).Patients should be advised not to use ephedrine-containing sup-plements if they have cardiovascular disease, hyperthyroidism,diabetes mellitus, benign prostatic hypertrophy, or glaucoma(Cupp, 1999).

Equisetum arvense (Equisitaceae) Commonly known asHorsetail, Bottle-brush

Side effects of horsetail include electrolyte imbalance, skinirritation from topical use, seborrhoeic dermatitis, thiamine de-ficiency from long-term use, and symptoms of nicotine poison-ing and toxicity including nausea and vomiting, muscle weak-ness, abnormal pulse rate, fever, and ataxia. Use of horsetailwith benzodiazepines, disulfiram, or metronidazole may causea disulfiram-like reaction. Horsetail may increase digitalis toxi-city as a result of potassium loss with diuretic effect. When it isused with potassium-wasting drugs (including corticosteroids,diuretics, and laxative stimulants), there is an increased risk ofhypokalemia. Overuse of licorice with horsetail may increasepotassium depletion and risk of cardiac toxicity. Excessive al-cohol consumption while horsetail is being used may lead tothiamine deficiency (Sudan, 1985; EzineArticles.com, 2008).

Eucalyptus globulus (Myrtaceae) Commonly known as BlueGum Tree

Eucalyptus can cause dermatological side-effects (Ernst,Schaller and Korting, 1995). Other adverse reactions of Eu-calyptus oil may include nausea, vomiting, diarrhoea, andasthma-like attacks. Signs of eucalyptus poisoning might in-clude stomach pain and burning, dizziness, muscle weakness,small eye pupils, feelings of suffocation. Eucalyptus supplemen-tation is inadvisable for older or chronically ill people, pregnantwomen, or women who are breastfeeding, and anyone with lowblood pressure, kidney problems, stomach problems, intestinalor biliary inflammation, or liver disorders (NutraSanus, 2010;

EzineArticles.com, 2008). The herb is not recommended forchildren too because it can cause seizure, depression of con-scious state, drowsiness, unconsciousness, vomiting, or ataxia.Ingestion of eucalyptus oil caused significant morbidity in in-fants and young children (Gouin and Patel, 1996; Tibballs,1995).

Eugenia caryophyllus (Myrtaceae) Commonly known as Clove

Clove may cause contact dermatitis (Kanerva et al., 1996).Oral administration of clove oil may result in central nervoussystem depression, urinary abnormalities, and a large anion-gap acidosis (Lane et al., 1991). Clove cigarettes may be haz-ardous to health (Schydlower et al., 1991). The smoking of clovecigarettes cause pharyngolaryngeal anesthesia that may resultin aspiration pneumonia (Guidotti et al., 1989).

Euphrasia officinalis (Scrophulariaceae) Commonly known asEyebright

Eyebright has been associated with pruritus, redness andswelling of the eye, vision changes, and photophobia. Other ad-verse effects reported include toothache, confusion, headache,sneezing, yawning, insomnia, raised ocular pressure, lacrima-tion, cough, dyspnoea, nasal congestion, hoarseness, nausea,constipation, expectoration, polyuria, and diaphoresis. (Jeffrey,1996; Wellness.com, 2010).

Foeniculum vulgare (Apiaceae) Commonly known as Fennel

Fennel may cause an allergic reaction, occupational allergicrhinoconjunctivitis, and asthma (Jensen-Jarolim et al., 1997;Schwartz et al., 1997). It may also affect estrogen level inthe body (Malini et al., 1985; Albert-Puleo, 1980; Drugs.com,2009). It may cause photodermatitis, contact dermatitis, andcross reactions (Drugs.com, 2009).

Fucus vesiculosus (Fucaceae) Commonly known as Bladderwrack, Seaweed, kelp

Bladderwrack is generally safe, though there are three poten-tial problems with its consumption: acne, thyroid dysfunction,and heavy-metal contamination. Iodine in any form includingfrom bladderwrack and other seaweeds-can cause or aggravateacne in some people. Excessive iodine ingestion can cause ei-ther hypothyroidism or hyperthyroidism and should be avoided.Bladderwrack and other seaweeds that grow in heavy-metal-contaminated waters may contain high levels of these toxins(particularly arsenic and lead), leading to nerve damage, kidneydamage, or other problems. Fucus vesiculosis cause changes inskin thickness and mechanical properties (Peacehealth, 2009;Phaneuf et al., 1999; Norman et al., 1988; Eliason, 1998; deSmet et al., 1990; Fujimura et al., 2002).

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Ginkgo biloba (Gingkoaceae) Commonly known as SilverApricot, Maidenhair-tree

It should not be used by patients on oral anticoagulant and/orantiplatelet therapy (Argento et al., 2000; Bone, 2008; Heck etal., 2000). Ginkgo biloba changes the levels of various aminoacids, reduces blood pressure, causes hemorrhage and hyphema,exacerbates seizures, produces gastrointestinal complaints, andcauses ocular side effects (Sasaki et al., 2002; Jezova et al.,2002; Schneider et al., 2002; Pubmed, 2008; Spinella, 2001;Kohler et al., 2004; Fraunfelder, 2004). Ginkgo should be usedwith caution during pregnancy, particularly around labor whereits anti-platelet properties could prolong bleeding time (Dugouaet al., 2006).

Glycyrrhiza glabra (Leguminosae) Commonly known asLiquorice

Liquorice can cause fluid retention, high blood pressure, andloss of Potassium if more than 3 g per day is taken for morethan six weeks. Individuals with high blood pressure, heart dis-ease, diabetes, or kidney disease are advised to avoid liquorice.Heavy glycyrrhizin exposure was associated with preterm de-livery (Strandberg et al., 2002). It may cause rhabdomyolysis,arterial hypertension, and ocular side effects (Fraunfelder, 2004;Sardi et al., 2002).

Hypericum perforatum (Hypericaceae) Commonly known asSt. John’s Wort, Goatweed

St. John’s wort causes gastrointestinal disturbances, allergicreactions, fatigue, dizziness, confusion, dry mouth, and pho-tosensitivity (Cupp, 1999; Nierenberg et al., 1999; Neuman,2002). Mania and hypoglycaemia are also associated with itsuse (Ioannides, 2002; Schulz, 2001). The herb has the potentialto alter medication pharmacokinetics and the seizure threshold(Spinella, 2001).

Hyssopus officinalis (Labiatae) Commonly known as Hyssop

Hyssop can cause human intoxication (Millet et al., 1981).The essential oil contains the ketone pino-camphone, which inhigh doses can cause convulsions/seizure (Millet et al., 1981;Burkhard et al., 1999). Other adverse conditions of Hyssopare nausea, upset stomach, diarrhoea, dizziness, tightness inthe chest, and disturbances of the central nervous system. Itshould be avoided during pregnancy and by people sufferingfrom epilepsy (HealthCare Tips, 2010).

Inula helenium (Compositae) Commonly known asElecampane

Elecampane was one of the plants causing occupational con-tact dermatitis, anaphylactic reactions, and sensitization. Theknown chemical allergens causing dermatitis were tuliposide-A

and sesquiterpene lactones, such as alantolactones and partheno-lide (Lamminpaa et al., 1996; Pazzaglia et al., 1995; Gay-Crosieret al., 2000). It also leads to gastrointestinal side effects (Ioanaand Flamm, 1999).

Lactuca sativa (Asteraceae) Commonly known as Lettuce,Cos, Romaine

Lactuca sativa can cause anaphylaxis reactions (Vila et al.,1998; San Miguel-Moncin et al., 2003; Franck et al., 2000).

Larrea mexicana (Zygophyllaceae)

Larrea has been identified as an unsafe herb (Klepser andKlepser, 1999). Larrea has been associated with multiple seri-ous and potentially fatal adverse effects in humans. In humans,Larrea has been associated with severe liver injury, includingacute to chronic irreversible liver damage, cholestastic liver in-jury and even cirrhotic transformation and liver failure, kidneycysts, and kidney cancer (Stickel et al., 2000; Sheikh et al., 1997;Katz and Saibil, 1990; Alderman et al., 1994; Batchelor et al.,1995; Gordon et al., 1995). Human case reports note rash andfever with use of chaparral. Based on an animal study, Larreamay lower blood sugar levels. Caution is advised in patients withdiabetes or hypoglycemia, and in those taking drugs, herbs, orsupplements that affect blood sugar. Aggravation of hypothy-roidism may occur. Larrea may inhibit ovulation and decreasethe chance that women will become pregnant.

Leonurus sibiricus (Lamiaceae) Commonly known asMotherwort

One article in the Journal of Clinical Pharmacy & Therapeu-tics lists motherwort among herbs containing the blood thinningcompound coumarin. This would make the herb contraindi-cated for persons who take blood thinning drugs, nonsteroidalanti-inflammatory drugs (NSAIDs), and other herbs containingcoumarins such as Chamomile, horse chestnut, fenugreek, andred clover (Herbalist.com, 2010) may cause a decrease in bloodpressure (Milkowska-Leyck et al., 2002). It also has a stimulat-ing action on the uterus, so it should be taken with care at thetime of pregnancy (Chang et al., 1995).

Linum usitatissimum (Linaceae) Commonly known as Flax,Linseed

It might cause gastrointestinal (GI) side effects such as bloat-ing, gas, abdominal pain, constipation, diarrhea, stomachache,and nausea. Higher doses are likely to cause more GI side ef-fects. Flaxseed might slow clotting, so it could increase the riskof bleeding in people with bleeding disorder. Because flaxseedcontains hormone estrogen, there is some concern that flaxseedmight make hormone-sensitive conditions worse or may af-fect pregnancy (WebMD, 2009; Stark and Madar, 2002; Con-nor, 2010). It possesses inflammatory potential and can induce

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respiratory and allergic diseases: from upper respiratory tractinfections to asthma. Flax seed dust when inhaled producesimmunologic reactions (Ye et al., 1998; Jaber, 2002).

Lobelia inflata (Campanulaceae) Commonly known asLobelia, Pukeweed, Indian tobacco

Lobelia is considered a potentially toxic herb (Mazur et al.,2001). It leads to vomiting (Kowalczyk-Bronisz, 1980). Signsof lobelia poisoning may include weakness, heartburn, weakpulse, difficulty in breathing, and collapse. People with highblood pressure, heart disease, tobacco sensitivity, paralysis, andseizure disorder should not take lobelia (Vitamin SupplementsGuide, 2006). It possesses an antidepressant and sedative actionwhich could interfere with medication (Subarnas et al., 1992;1993). Lobelia is not recommended for women who are pregnantor breastfeeding (Vitamin Supplements Guide, 2006).

Matricaria recutita (Asteraceae) Commonly known asChamomile

Use of Chamomile is generally considered safe and non-toxic. Side effects are rare. Tincture or essential oil versionof Chamomile should be avoided during pregnancy (VitaminSupplements Guide, 2006). It causes gastrointestinal disorders(Jeschke et al., 2009). Anaphylactic reactions were reported af-ter the ingestion of chamomile tea (Subiza et al., 1989). Thosewho are allergic to ragweed or other plants in the Asteraceaefamily should avoid chamomile. Chamomile may cause drowsi-ness in some individuals. In large doses, chamomile can causevomiting (Vitamin Supplements Guide, 2006; Heck et al., 2000).Chamomile can cause ocular side effects (Fraunfelder, 2004).Chamomile tea eye washing can induce allergic conjunctivitis(Subiza et al., 1990).

Medicago sativa (Fabaceae) Commonly known as Alfalfa,Lucerne, Buffalo herb

Alfalfa appears to be well tolerated by most individuals, al-though rare serious adverse effects have been reported. Mildgastrointestinal symptoms may occur, such as stomach discom-fort, diarrhea, gas, or larger/more frequent stools. Dermatitis hasbeen reported, and may be due to alfalfa allergy. Blood sugar lev-els may be reduced. Caution is advised in patients with diabetesor hypoglycemia, and in those taking drugs, herbs, or supple-ments that affect blood sugar level. Serum glucose levels mayneed to be monitored by a healthcare provider, and medicationadjustments may be necessary. Lupus-like effects have been as-sociated with alfalfa use, including antinuclear antibodies in theblood, muscle pains, fatigue, abnormal immune system func-tion, and kidney abnormalities. Therefore, people with a historyof lupus (systemic lupus erythematosus), or family history oflupus should avoid alfalfa supplements. Other rarely reportedadverse effects include abnormal blood cell counts (pancytope-nia) and lowered potassium levels. In theory, thyroid hormone

levels may be increased, gout flares may be stimulated, andestrogen-like effects may occur (Malinow et al., 2005; 1981;HCV Advocate, 2009).

Melaleuca alternifolia (Myrtaceae) Commonly known as TeaTree

Tea tree oil is a potential toxic herb (Jacobs and Hornfeldt,1994). Symptoms of toxicity are ataxia, unresponsiveness, anddrowsiness (Morris et al., 2003; Del Beccaro, 1995). Tea treeoil taken orally is associated with potentially severe reactions,like rash, reduced immune system function, abdominal pain,diarrhea, lethargy, drowsiness, inflammation of the corners ofthe mouth, slow or uneven walking, confusion, or coma, nausea,unpleasant taste, burning sensation, and bad breath associatedwith tea tree oil use (Healthline, 2010). It also produces hyper-sensitivity reactions and allergic contact dermatitis (Fritz et al.2001; Khanna et al., 2000; Rutherford et al., 2007; Knight andHausen, 1994).

Mentha piperita (Labiatae) Commonly known as Peppermint

The possible side effects of mint are allergic symptoms, suchas flushing, headache, heart burn, irritated mucous membranes,muscle tremors, and skin rash (Best-home-remedies.com,2010). Gastrointestinal/stomach irritation has been reported insome individuals (Wallace et al., 2008).

Myristica fragrans (Myristicaceae) Commonly known asNutmeg, Mace

In low doses, nutmeg produces no noticeable physiologicalor neurological response (Wikipedia, 2010). High dosage cancause bizarre behavior and visual, auditory, and tactile hallu-cinations along with nausea, gagging, hot/cold sensations, andblurred vision followed by numbness, double, and “triple” vi-sion, headache, and drowsiness (Sangalli and Chiang, 2000).An overdose of nutmeg can be fatal (Stein et al., 2001). Use ofnutmeg as a recreational drug is unpopular due to its unpleas-ant taste and its possible negative side effects, including dizzi-ness, flushes, dry mouth, accelerated heartbeat, temporary con-stipation, difficulty in urination, nausea, and panic (Wikipedia,2010). A risk in any large-quantity ingestion of nutmeg is theonset of “nutmeg poisoning,” which may be due to myristicin,it could also result in an acute psychiatric disorder marked bythought disorder, a sense of impending doom/death, and agi-tation (Wikipedia, 2010; McKenna et al., 2004; Hallstrom andThuvander, 1997; Beyer et al., 2006). If consumed in largequantities during pregnancy it may affect the fetus due to itshallucinogenic contents (Wikipedia, 2010). A case of acute an-ticholinergic hyperstimulation in a pregnant woman was asso-ciated with excessive ingestion of nutmeg (Lavy, 1987).

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Panax ginseng (Araliaceae)

The most commonly experienced adverse events of Ginsengare headache, sleep, and gastrointestinal disorders (Coon andErnst, 2002).

Paullinia Cupana (Sapindaceae)

Paullinia Cupana supplements can result in an increase inheart rate and blood pressure and unfavorable actions on glu-cose and potassium homeostasis. Such effects could be detri-mental in persons with hypertension, atherosclerosis, or glucoseintolerance, conditions that are strongly associated with obe-sity (Haller et al., 2005). Paullinia Cupana may cause nausea,vomiting, stomach upset, increased urination dizziness, shaking,mental/mood changes, serious allergic reactions including rashitching/swelling (especially of the face/tongue/throat), severedizziness and trouble breathing (HealthSquare.com, 2007). Itmay lead to acute renal and hepatic failure (Vagasi et al., 2007).

Phyllanthus niruri (Euphorbiaceae) Commonly known asCatnip

Acute exposure to catnip increased stereotyped behavior andsusceptibility to seizures, did not interfere with haloperidol-induced catalepsy, and decreased sleeping time after sodiumpentobarbital administration. Long-term exposure induced tol-erance to stereotypic behavior, catalepsy and sleeping time, andincreased the susceptibility to seizures induced by picrotoxinand strychnine. An amphetamine-like effect of catnip was sug-gested to explain the acute effects, while dispositional and func-tional adaptative changes were considered involved with thelong-term effects (Massoco et al., 1995). After consumption,Phyllanthus niruri may cause central nervous system depres-sion (Osterhoudt et al., 1997).

Piper methysticum (Piperaceae) Commonly known as Kava

Kava users were more likely to complain of poor health anda “puffy” face, and were more likely to have a typical scaly rashknown as “kava dermopathy,” and slightly-increased patellar re-flexes (PubMed, 1998). Very heavy users of kava were 20% un-derweight and their levels of gamma-glutamyl transferase wereincreased greatly. Albumin, plasma protein, urea, and bilirubinlevels were decreased in kava users and high-density lipopro-tein cholesterol levels were increased. Kava users were morelikely to show haematuria, and to have urine which was poorlyacidified and of low specific gravity. The use of kava was alsoassociated with an increased red-cell volume, with a decreasedplatelet volume and with a decreased lymphocyte count. Short-ness of breath in kava users was associated with tall P waves on aresting electrocardiogram, which provided suggestive evidenceof pulmonary hypertension. There was evidence of decreasedlung volumes and a high carriage rate of hepatitis B surface anti-gen (Mathews et al., 1988; PubMed, 1998; Sticke et al., 2003).

Kava causes sedation, oral and lingual dyskinesia, torticollis,oculogyric crisis, exacerbation of Parkinson’s disease, painfultwisting movements of the trunk, rash (Cupp, 1999). Heavy kavadrinkers acquire a reversible ichthyosiform eruption (Gounder,2006). Extracts of kava induce acute anxiolytic-like behavioralchanges in mice (Garrett et al., 2003). Four lactones in kava havebeen found to have significant analgesic and anesthetic effectsvia non-opiate pathways. In vitro kava has been found to blocknorepinephrine uptake (PubMed, 1998).

Serenoa repens (Arecaceae) Commonly known as SawPalmetto

The most frequent adverse events after Saw Palmetto admin-istration are mild, infrequent, and reversible, and include ab-dominal pain, diarrhoea, nausea, fatigue, headache, decreasedlibido, and rhinitis (Agbabiaka et al., 2009).

Symphytum officinale (Boraginaceae) Commonly known asComfrey, Slippery-root

Comfrey has been applied for inflammatory disorders such asarthritis, thrombophlebitis and gout, and as a treatment for diar-rhoea. Only recently the use of comfrey leaves was recognizedas a substantial health hazard with hepatic toxicity in humansand carcinogenic potential in rodents. These effects are mostlikely due to various hepatotoxic pyrrolizidine alkaloids suchas lasiocarpine and symphytine, and their related N-oxides. Themain liver injury caused by comfrey is a veno-occlusive disease,a non-thrombotic obliteration of small hepatic veins leading tocirrhosis and eventually liver failure. Patients may present witheither acute or chronic clinical signs with portal hypertension,hepatomegaly, and abdominal pain as the main features (Stickeland Seitz, 2000; Abbott, 1998).

Tanacetum parthenium (Asteraceae) Commonly known asFeverfew

Feverfew is associated with only mild and transient adverseeffects like abdominal pain, bitter taste, contact dermatitis, di-arrhoea, fatigue, flatulence, GI symptoms, and indigestion, in-flammation of lips or tongue, joint pain, loss of taste, mouthulceration, nausea /vomiting, nervousness, and swollen lips. Itmay produce contraindications in children under 12 years andin case of pregnancy or lactation (Ernst and Pittler, 2000).

Taraxacum officinale (Compositae) Commonly known asDandelion

Possible internal and external allergic reactions like allergiccontact dermatitis to dandelion were reported (Mark et al., 1999;Jovanovic and Poljacki, 2003). Dandelion juice extracted fromthe stem or roots can induce nausea, vomiting, stomach pain,diarrhoea and increased urination. This is mainly due to its di-uretic properties, so it may interact with diuretic medications.

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Table 1 Some published doses of herbs for which adverse effects have been studied

Herb Dose Symptoms produced References

Aristolochia debilis > 3–6 g/day Toxic Complementary and Alternative Healing University, 2010Artemisia argyi 20–30 g orally Induction of seizure Complementary and Alternative Healing University, 2010Catharanthus roseus 9–15 g Toxic Complementary and Alternative Healing University, 2010Ephedra geradiana 4 to 20 mg/day Life threatening adverse reactions Cupp, 1999Ginkgo biloba 50 mg 3 times a day for 6 months Intracerebral hemorrhage Cupp, 1999Ginkgo biloba 40 mg 2 times a day for 1 week Bleeding from the iris into the

anterior chamber of the eyeCupp, 1999

Hypericum perforatum 600 mg/kg/day for 10 days Nausea, weakness and fatigue Cupp, 1999Panax ginseng < 15 g/d Depersonalization and confusion Dasgupta, 2003Panax ginseng >15 g/d Depression Dasgupta, 2003Piper methysticum 100–450 mg/day Extrapyramidal effects Dasgupta, 2003Syzygium aromaticum > 1–3g Toxic Complementary and Alternative Healing Uni- versity, 2010

People on diabetes medications should also be aware that dan-delion or any dandelion supplement might increase the bloodsugar lowering effects of those pharmaceutical drugs. Peoplewith gallbladder conditions and gallstones must exercise cautionbefore starting on dandelion remedies (All4NaturalHealth.com,2010). Acute allergic reactions were reported after ingestion ofdandelion pollen (Cohen et al., 1979).

Turnera diffusa (Turneraceae) Commonly known as Damiana

In general, few adverse effects have been reported for dami-ana, including diarrhoea, headaches, mood changes, eroticdreams, insomnia, and hallucinations. As damiana contains lowlevels of cyanide-like compounds, excessive doses may be dan-gerous. Patients with psychiatric disorders, those taking medica-

tions for diabetes or to control blood sugar levels, or those witha history of breast cancer should use the herb with caution. Theuse of damiana should be avoided in patients with Alzheimer’sdisease, or Parkinson’s disease, as ethanol extracts of the leavesand stem have shown central nervous system depressant activity.Traditionally, damiana has been used as an abortifacient and iscontraindicated during pregnancy. Excessive dosage may causeone to feel disoriented and lightheaded or experience headache(Healthline, 2010; Alarcon-Aguilara, 1998).

Tussilago farfara (Compositae) Commonly known as Coltsfoot

Coltsfoot has been identified as an unsafe herb (Klepser andKlepser, 1999). Coltsfoot contains potentially liver-damagingpyrrolizidine alkaloids (MaineHealth, 2009). Animal studies

Table 2 Median lethal dose values of some of the herbs

Herb LD50 values References

Acorus calamus 417 mg/kg (oral) and 310 mg/kg (IP) in mice Drugs.com, 2009Allium sativum > 30 mL/kg (oral) in rats and mice MDidea.com, 2010Aloe vera > 5 g/kg in rats. Yagi et al., 2009Angelica sinensis Aqueous extract: 100 g/Kg (i.v.) in mice, 50% ethanolic extract > 40 g/Kg (p.o.)in mice Encyclopedia of dietary supplements, 2005Apium graveolens 150 mg/kg (i.p.) in mice and 125 mg/kg (i.p.) in rats. MDidea.com, 2010Arnica montana 123 mg/Kg (oral) and 31 mg/kg (i.p.) in mice and > 5 g/kg (oral) in rats. The essential guide to herbal safety, 2005Astragalus membranaceus 40 g/kg (i.p.) in mice Astragalus monograph, 2003Azadirachta indica 14.1 ml/kg bw for rats and showing similar symptoms, 24.0 mL/kg bw for rabbits Sara et al., 2004Boswellia serrata Acute oral and i.p. LD50 was greater than 2 g/kg in mice and rats. Xtend-Life, 2010Calendula officinalis Aqueous extract: 375 mg/kg (i.v.) in mice. Aqueous ethanolic extracts (drug/extract

ratio 1 : 1 and 0.5 : 1, 30% ethanol): 45 mg/mouse (s.c.) and 526 mg/100 g(i.v.) in rat.Hecapedia, 2006

Cassia angustifolia 5000 mg/kg (oral) in rat and mice Morales et al., 2009Centella asiatica Alcoholic extract:1930 mg/Kg (i.p.) and hydroalcoholic extract (leaf): 675 mg/kg (p.o.)

in ratCentella asiatica extract, 2009

Commiphora mukul 3708.7 mg/kg in rats and 471.2 mg/kg in mice Ezekiel et al., 2010Ginkgo biloba 7.73 g/kg (oral) and 1.1 g/kg (i.v.) in mice MDidea.com, 2010Taraxacum officinale 36.8 g/kg for the root and 28.8 g/kg for herb in mice. MDidea.com, 2010Urtica dioica 3.5 g/kg (i.p.) in rat Bnouham et al., 2003Vaccinium myrtillus > 5.0 g/kg(oral) and > 2.0 g/kg (dermal) chemcas.org, 1970Valeriana officinalis Valerian oil: 15,000 mg/kg (oral) in rats, ethanolic extract: 3300 mg/kg (i.p.) in mice,

valerian constituents: ∼62 mg/kg (i.p.),Information Review Document for

Valerian (Valeriana officinalis L.), 2009Viburnum opulus 5.447 g/kg in mice Altun et al., 2010Vicum album 417.5 mg/kg. (i.p.) in mice Eno et al., 2004Withania somnifera 1260 mg/Kg Body Wt in Wistar rat Sharadaa et al., 1993Zingiber officinale 458 µg/mL in mice Raji et al., 2002

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Table 3 Herbal drugs categorized as hazardous by USFDA (GoutCure.com,2009)

Name of the Herbal drug Description

Acorus calamus Commonly known as Sweet Flag. Rats fed variedlevels of this sweet flag developed heart and liverabnomalities within a few months and laterintestinal tumors. For this reason “sweet flag” isbanned from all products intended for humanconsumption in the United States in 1968.

Aristolochic acid It is a constituent of Aristolochia, Birthwort,Snakeroot, Snakeweed, Snagree root, Sangrel,Serpentary, and Wild ginger. FDA lists this ashaving caused documented human cancers, islinked to kidney failure, and is also listed as verylikely hazardous. It is banned in other countries,has an FDA warning, and shows adverse effect instudies.

Citrus aurantium Commonly known as Bitter orange. High bloodpressure, increased risk of heart arrhythmias,heart attack, and stroke are risks associated withuse.

Ephedra sinica FDA find that Ephedra present an unreasonable riskof illness and or injury to the consumers.Substance raises blood pressure and stresses theheart. On February 6, 2004, the FDA issued arule banning the sale of all dietary supplementscontaining ephedra in the United States.

Hedeoma pulegioides Commonly known as Pennyroyal oil, Mosquitoplant, Pudding grass, Tickweed. Liver and kidneyfailure, nerve damage, convulsions, abdominaltenderness, burning of the throat are risks; deathshave been reported.

Larrea divaricata Commonly known as Chaparral, Creosote bush,Greasewood. Abnormal liver function has beenlinked to use.

Lobelia inflate Commonly known as Indian tobacco, Pukeweed,Vomit wort, Wild tobacco. Difficulty breathingand rapid heart rates are thought to be associatedwith this.

Pausinystalia yohimbe Commonly known as Yohimbe. Blood pressurechanges, heart beat irregularities, and heartattacks have been reported.

Piper methysticum Commonly known as Kava, Intoxicating pepper.Abnormal liver function has been linked to use.

Scutellaria lateriflora Commonly known as Scullcap, Helmet flower,Hoodwort, Mad weed, Mad-dog herb. Abnormalliver damage.

Symphytum officinale Commonly known as Comfrey, Ass ear, Black root,Blackwort. Cause abnormal liver function ordamage, often irreversible; deaths reported.

Teucrium chamaedrys Commonly known as Germander, Wall germander,Wild germander. Abnormal liver function hasbeen linked to use.

using amounts of coltsfoot hundreds of times higher than thoseused as medicine have shown these alkaloids can cause cancerin animals. The carcinogenicity of coltsfoot is most probablydue to senkirkine, a hepatotoxic pyrrolizidine alkaloid (Hironoet al., 1976). A single case of an infant who developed liverdisease and died after the mother drank tea containing coltsfootduring pregnancy has been reported. This eventually led to thebanning of coltsfoot in Germany in 1992 (Klepser and Klepser,

1999). Coltsfoot produces a stimulating effect on the growth ofCandida albicans (Baronets et al., 2001).

Uncaria tomentosa (Bignoniaceae) Commonly known as Cat’sClaw

Possible side effects of the herb include stomach discomfort,nausea, diarrhea, slow heartbeats or altered rhythm of heartbeats,kidney disease, acute kidney failure, neuropathy, decreases inestrogen or progesterone levels and an increased risk of bleed-ing. Cat’s claw should be avoided during pregnancy or breast-feeding (Aetna InteliHealth, 2005).

Urtica dioica (Urticanceae) Commonly known as Nettle,Stinging nettle

Stinging nettle is probably safe with limited side effects; how-ever, the plant extract seems to have a toxic effect at the higherdose. A frequent cause of contact urticaria is skin exposure tothe common stinging nettle. The urticaria is accompanied by astinging sensation lasting longer than 12 h (Zhion.com, 2008;Tahri et al., 2000). Urtica dioica may produce an Atropine poi-soning like effect (Scholz et al., 1980).

Vaccinium macrocarpon (Ericaceae) Commonly known asCranberry

Cranberry as dietary supplements may increase the risk ofnephrolithiasis (Terris et al., 2001). Drinking cranberry juice inlarge quantities can cause diarrhea and stomach upset (Vitamins& Health Supplements Guide, 2006).

Valeriana officinalis (Valerianaceae) Commonly known asGarden valerian

Long-term use of valerian may cause psychological depres-sion, damage to the liver, or damage to the central nervoussystem. High short-term doses of valerian have been reportedto cause headaches, muscle spasms, dizziness, digestive upsets,insomnia, and confusion. Some people taking valerian may ex-perience a paradoxical effect; that is they may feel agitated orjittery instead of being relaxed or sleepy (Encyclopedia of Men-tal Disorders, 2010).

Viscum album (Loranthaceae) Commonly known as Mistletoe,Devil’s Fuge

All the parts of Mistletoe are toxic. Mistletoe used withoutproper instruction can produce toxic effects such as vomiting,diarrhea, contraction of the pupils, muscle spasm, exhaustion,coma, convulsions, and death, particularly when its leaves andberries are ingested. Fatalities have been reported following in-gestion of the fresh berries. Children frequently suffer epilepti-form convulsions following ingestion of the berries. It containsviscotoxin, a mixture of toxic proteins that apparently affect

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Table 4 Herbal Drug product banned by USFDA (dietblog, 2010)

Products claiming“Natural/Herbal” ingredients Main ingredients present

Phyto shape Sea Algae, Bladderwrack, Ivy, Horse-Chestnut, Southern Wood, Grape Seed Oil, Macadamia Nut Oil, Liquorice, and AlfalfaPerfect slim 5x Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural substancesProslim plus Lingzhi, Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural

substancesRoyal slimming formula Lingzhi, Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural

substancesSlim 3 in 1 Green Tea Extract, Lotus Leaf, Hemp Seed, Alismatis, Fructus crataeg and othersSlim express 360 Glossy ganoderma, Gynosyemma pentaphyllum, Ginkgo leaf, Cassia seed, Tea polyphenols, France roseFat loss sliming Bamboo vinegar, Gynostemma pentaphylla, Lotus leaf, Haw, Polygonum multiflorum thumb, Fomes japonica, Licorice flavorVenom hyperdrive 3.0 Cocoa Extract, Hoodia Gordonii, Guarana, 5-HTP, R-ALA, Guggul Extract, Rhodiola Rosea extract, L- Tyrosine, and

L-Carnitine2 Day diet Lingzhi, Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural

substances3X Slimming power Lingzhi, Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural

substancesJapan lingzhi 24 hours diet Lingzhi, Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural

substances5X Imelda perfect slim Lingzhi, Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural

substances3 Day diet Not available7 Day herbal slim Seville orange flower, Lingzhi, Sweet potato fiber, Konjak, Cassia seed, Lotus leaf, Koala nut, Slight grass, Rose extract,

Cane sugar ester, etc.999 Fitness essence Lotus Leaf, Bush-Cheery Seed, Chinese Yam, and Hawthorn FruitExtrim plus Lingzhi, Ebony, Fox-nut, Tuckahoe (Peltandra virginica), Semen Pruni, Dioscorease, Wheat Germ, and other natural

substancesImelda perfect Slim Ebony, Fox-Nut, Tuckahoe, Seman Pruni, Dioscoreae, Wheat Germ, and other natural substancesLida daidaihua Bitter Orange, Mulberry Leaf Extract, Cassia seed, Job’s-tearsPerfect slim Ebony, Fox-nut, Tuckahoe, Semen Pruni, Ginseng, Dioscorease, Wheat Germ, and other natural substancesMiaozi slim capsules Semen cassiae, Radix polygoni multiflori. Gingko and Folium neiumbinis7 Diet Day/Night Formula Not available8 Factor Diet Not availableGmp Not availableSlimtech Not availableSomotrim Not availableSuperslim Not availableTripleSlim Not available

RNA and DNA synthesis. Mistletoe injections are not recom-mended as they can cause skin reactions such as swelling anddead skin. Other side effects include chills, fever, headache,chest pain, low blood pressure, and allergic reactions includinganaphylactic reactions after therapeutic injection of mistletoe(Viscum album L.) (Florahealth.com, 2010). Mistletoe must beavoided in patients having tuberculosis, AIDS, hyperthyroidism,an inflammatory disease, or brain or spinal cord tumors (ViableHerbal Solutions, 2010).

Vitex agnus castus (Vefrbenaceae) Commonly known asChasteberry

Chasteberry is a well tolerated herb and adverse effects thatare reported are minor including gastrointestinal complaints,dizziness, dry mouth, nausea, headache, menstrual disorders,acne, pruritus, and erythematous rash. Use of chasteberry shouldbe avoided during pregnancy or lactation (Roemheld-Hamm,2005; Daniele et al., 2005; Cahill et al., 1994).

Withania somnifera (Solanaceae)

Withania somnifera in large dose acts as an abortifacient andcan cause heaviness in abdomen, nausea, vomiting, and diar-rhoea (Holistic-Herbalist.com, 2005). The herb must be avoidedduring severe and acute inflammatory conditions except in de-generative disorders like arthritis, rheumatoid arthritis, and gout.It should not be taken alone in case of gastric and duodenal ulcer.

Zingiber officinale (Zingiberaceae) Commonly known asGinger

Ginger should not be taken in case of gallstones or anyother disease of the gallbladder, if the person is a diabetic,has any heart problems, bleeding, or blood clotting disorders(Drugs.com, 2009). In an animal study it was found that inutero exposure to ginger tea results in increased early embryoloss with increased growth in surviving fetuses. Thus it shouldbe taken with caution at the time of pregnancy (Wilkinson,2000).

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Table 5 Interactions reported with herbal drugs

Herbs Interactions References

Apiumgraveolens

It may increase the risk of bleeding or potentiate the effects of warfarin therapy Heck et al., 2000

Aloe vera The effects of antiarrhythmics, cardiac glycosides, loop diuretics, other potassium-wasting drugs,corticosteroids, thiazide diuretics will be increased when taken with aloe. When taken orally, aloemay increase the laxative properties of agents such as senna and may cause diarrhoea. Aloe alsoadds to the effects of blood sugar lowering herbs. Latex of aloe increases the potassium-loweringeffects of other herbs such as liquorice.

aloe research.com, 2007

Angelicasinensis

Angelica may increase the risk of bleeding due to anticoagulant and anti-platelet effects, so it shouldnot be taken with blood thining agents like Warfarin, there are chances that it may increase theeffects of drugs such as digoxin, beta-blockers, calcium channel blockers, antidepressant, andantioxidants.

Heck et al., 2000; Medline Plus, 2009

Arnicamontana

Arnica may increase the toxicity and decreases the effectiveness of any drug. Use of Arnica withother pain-relieving medication increases their analgesic effects. It decreases the protein bindingproperties of drugs that are highly protein bound Arnica may increase the risk of bleeding orpotentiate the effects of warfarin therapy.

Spettoli et al., 1998; Heck et al., 2000;HerbalRemediesInfo.com, 2010

Astragalusmem-branaceus

Astragalus may interact with medications that suppress the immune system. Astragalus may potentiatehyperglycemic and hyperuremic effects of glucose elevating agents. Caution should be exercisedwhen used with CNS depressants or stimulants. That interacts with dopamine receptor agonists.

Dietaryfiberfood.com,2007;Questhealthlibrary.com, 2000

Ananascomosus

It may increase the absorption of some antibiotics, notably amoxicillin and tetracycline, and increasetheir level in the body. It may increase the amount of drowsiness caused by some drugs.

Bradbrook, 1978; Tinozzi andVenegoni, 1978; Gutfreund et al.,1978; Integrative Medicine, 2000

Acoruscalamus

Calamus interacts with immunostimulating, hypnotics, antispasmodic antifungals, antibacterials,amphetamines, cholesterol-lowering, anti-inflammatories, anticholinergics, or antioxidant drugs,herb, and supplements.

Klepser and Klepser, 1999; Healthline,2010

Areca catechu Betel Palm increases the effects of alcohol, beta-blockers, cardiac glycosides and MAO inhibitors.When combined with neuroleptics, cause extrapyramidal symptoms and decrease the action ofantiglaucoma agents.

Connor, 2010

Artemisiavulgaris

Artemisia contains coumarin derivatives, which may increase the risk of bleeding when taken withdrugs like aspirin, anticoagulants, anti-platelet drugs, and non-steroidal anti-inflammatory drugs.

Healthline, 2010

Aesculus hip-pocastanum

Aesculus should not be taken with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) oranticooagulants. These drugs may increase the risk of bleeding while using with Aesculus.

Popp et al., 1992; Heck et al., 2000

Allium sativum Garlic reinforces warfarin action. Garlic changes pharmacokinetic variables of paracetamol andproduces hypoglycaemia when taken with chlorpropamide.

Argento et al., 2000; Heck et al., 2000;Izzo and Ernst, 2001; Abebe, 2002;Vaes and Chyka, 2000

Berberisvulgaris

It interact with anticoagulants, antihypertensives, beta blockers, calcium channel blockers, digoxin,CNS depressants.

Articlesbase.com, 2008

Boswelliaserrata

Boswellia may potentiate the actions of pharmaceutical leukotriene inhibitors such as zafrilukast andmontelukast which are used in the treatment of asthma and it also interact with anti-proliferativeagents, non-steroidal anti-inflammatory drugs, and antifungals.

Wellness.com, 2010

Berberisaquifolium

It interacts with acetylcholine, antiarrhythmics, antibiotics, anticoagulants, antihyperglycemic drugs,antihyperlipidemic drugs, antihypertensives, anti-inflammatory drugs, antineoplastics, COX-2inhibitors, cyclosporine, drugs metabolized through cytochrome P450 3A4 enzymes.

Livestrong.com, 2010

Coleusforskohlii

Increase the risk of bleeding when used with anticoagulants or antiplatelet drugs, have an additiveeffect if taken with drugs used to treat asthma, high blood pressure or glaucoma or if taken withdrugs that increase heart rate or heart function, such as digoxin (Lanoxin). It may also interact withantihistamines, thyroid agents, and antidepressants.

coleus.net, 2010

Commiphoramukul

Concomitant oral administration with propranolol (Inderal) or diltiazem (Cardizem) can reduce theirbioavailability and might reduce their therapeutic effects.

Dalvi et al., 1994

Crataegusoxyacantha

May interfere with either digoxin pharmacodynamically or with digoxin monitoring. It affects theaction of CNS depressants, beta-blockers, calcium channel blockers, medications for male sexualdysfunction, and nitrates.

Miller, 1998; Connor, 2010; Webmd,2009

Cymbopogancitrates

It may interact with antihypertensive drugs, anti-hyperglycemics, and P450 enzyme affecting drugs,herbs, and supplements with similar effects.

Livestrong.com, 2010

Cimicifugaracemosa

Female hormones like estrogens or progestins, birth control pills, medicines for blood pressure anddiabetes, interacts with Cimicifuga.

Healthline, 2010

Caulophyllumthalictroides

Caulophyllum may interact with medications for diabetes and high blood pressure by decreasing theireffectiveness. It contains chemicals that work similarly like nicotine, so taking Caulophyllum withnicotine might increase the effects and side effects of nicotine.

WebMD, 2009

Calendulaofficinalis

It interacts with benzodiazepines, barbiturates, narcotics, antidepressants, alcohol, and blood pressurelowering agent. Other possible interactions includes, increase in the activity of hypoglycemic(diabetic) medications, or agents that decrease lipids and triglycerides.

MedlinePlus, 2009

Cassiaangustifolia

Cassia interacts with Digoxin, Warfarin, and diuretic drugs. WebMD, 2009

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Table 5 Interactions reported with herbal drugs (Continued)

Herbs Interactions References

Curcuma longa Curcuma may increase the risk of bleeding or potentiate the effects of warfarin therapy. Heck et al., 2000Camellia

sinensisCaffeine antagonizes the actions of alcohol. Fudin and Nicastro, 1988; Mackay et

al., 2002; Fillmore, 2003; Liguori andRobinson, 2001

Citrusaurantium

Ulcer medications, anti-anxiety medication, blood pressure medications, cholesterol medications,fungal medications, HIV medication, sedation medication, anti-nausea medication, and weight lossmedication interacts with Citrus.

The Herbal Resource, 2006

Daturastramonium

Datura interacts with Anticholinergic drugs, antihistamines and medications for depression. WebMD, 2009

Dioscoreavillosa

It produces interactions with anti-hyperglycemics, anti-inflammatory agents, cholesterol-loweringmedications, and hormonal therapies.

MedlinePlus, 2009

Digitalispurpurea

It interacts with clarithromycin which induce digoxin toxicity by three different mechanisms,including reduction of renal excretion of digoxin, alteration of intestinal flora, and inhibition ofcytochrome P-450 in the liver. Coadministration of digoxin with itraconazole induces digoxintoxicity. It also interacts with Verapamil in a non competitive way.

Xu and Rashkow, 2001; Mathis andFriedman, 2001; Ito et al., 1993

Eucalyptusglobulus

Enhanced effects may be noted when administered with antidiabetics. Eucalyptus oil inducesdetoxification enzyme systems in the liver; therefore, the oil may affect any drug that the livermetabolizes. When given with other herbs that cause hypoglycemia, decreased blood glucose levelsmay be observed.

NutraSanus, 2010; EzineArticles.com,2008

Ephedragerardiana

It interacts with beta blockers, MAO inhibitors, Caffeine, decongestants, stimulants. The combinationtherapy of Ephedra and Loxoprofen caused gastric lesions in mice.

Cupp, 1999; Home-Remedies.Info,2010; Cho et al., 2002

Echinaceapurpurea

If used beyond 8 weeks, Echinacea could cause hepatotoxicity and therefore should not be used withother known hepatoxic drugs, such as anabolic steroids, amiodarone, methotrexate, andketoconazole. Incidences of hepatotoxicity and nephrotoxicity may be augmented byacetaminophen when concomitantly used with Echinacea.

Miller, 1998; Abebe, 2002

Equisetumarvense

With Benzodiazepines, disulfiram, or metronidazole it may cause a disulfiram-like reaction. It mayincrease digitalis toxicity as a result of potassium loss with diuretic effect. With potassium-wastingdrugs there is an increased risk of hypokalemia. Alcohol consumption with Equisetum leads tothiamine deficiency.

Sudan, 1985; EzineArticles.com, 2008

Foeniculumvulgare

Fennel interacts with ciprofloxacin and affects it absorption, distribution and elimination and it alsointeracts with birth control pills.

Zhu et al., 1999; Malini et al., 1985;Albert-Puleo, 1980; Drugs.com, 2009

Ginkgo biloba Rinforces warfarin action, interacts with aspirin and Trazodone, and with Trazodone it can causecoma. It raises blood pressure when combined with a thiazide diuretic, has potential interactionswith garlic and vitamin E.

Heck et al., 2000; Dergal et al., 2002;Izzo and Ernst, 2001; Cupp, 1999

Glycyrrhizaglabra

It may interfere with corticosteroid treatment; long-term use of liquorice may be dangerous if one ison cardiac glycosides because it may interfere with either digoxin pharmacodynamically or withdigoxin monitoring. Liquorice may increase the risk of bleeding or potentiate the effects ofwarfarin therapy.

Questhealthlibrary, 2000; Miller, 1998;Heck et al., 2000

Hypericumperforatum

It decreased the blood concentrations of amitriptyline, cyclosporine, digoxin, fexofenadine, indinavir,methadone, midazolam, nevirapine, phenprocoumon, simvastatin, tacrolimus, theophylline andwarfarin, decreased the plasma concentration of omeprazole and the active metabolite SN-38 incancer patients receiving irinotecan treatment. It decreased cyclosporine blood concentrationleading to organ rejection, caused breakthrough bleeding and unplanned pregnancies when usedconcomitantly with oral contraceptives, also produce serotonin syndrome when coadministeredwith selective serotonin-reuptake inhibitors. St. John’s wort extract has a clear inhibitory effect onthe neuronal uptake not only of serotonin, noradrenaline, and dopamine but also ofgamma-aminobutyric acid (GABA) and L-glutamate.

Schulz, 2001; Muller, 2003; Sardi et al.,2002; Zhou et al., 2004; Ernst, 2002;Izzo and Ernst, 2001; Wang et al.,2004

Linum usitatis-simum

Flax may cause a decrease in the absorption of all oral medications if taken concurrently with it.There is some evidence that flaxseed can lower blood sugar levels and might increase the bloodsugar-lowering effects of some medicines used for diabetes.

Salvaggio et al., 1986; WebMD, 2009

Larreamexicana

Use of Larrea with other agents known to alter kidney and liver function, or induce toxicity should beavoided, including sulfa antibiotics, aminoglycoside antibiotics, COX-2 inhibitors, NSAIDs,amiodarone, carmustine, danazol, fluoxymesterone, isoniazid, ketoconazole, mercaptopurine,methotrexate, methyltestosterone, oxandrolone, oxymetholone, plicamycin, stanozolol, tacrine,testosterone, and valproic acid.

eNotAlone, 2010

Matricariarecutita

The concomitant use of opioid analgesics with Matricaria, may lead to increased central nervoussystem depression. It may potentiate the effects of antiepileptic medications, increasing theirsedative and cognitive effects. Matricaia can interfere with blood clotting, should not be usedtogether with aspirin, warfarin, or other substances that possess anticoagulant action.

Abebe, 2002; Spinella, 2001; VitaminSupplements Guide, 2006; Heck etal., 2000

Menthapiperita

Peppermint has the potential to interact with medications such as blood pressure drugs, calciumchannel blockers, and antacids.

Unger and Frank, 2004

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Table 5 Interactions reported with herbal drugs (Continued)

Herbs Interactions References

Ocimumsanctum

Basil may increase the hypoglycemic effects of insulin and oral antidiabetics. Connor et al., 2010

Pipermethysticum

It may potentiate the effects of antiepileptic medications. Increases “off” periods in Parkinsonpatients taking levodopa and can cause a semicomatose state when given concomitantly withalprazolam. Incidences of hepatotoxicity and nephrotoxicity may be augmented by acetaminophenwhen concomitantly used with it. The concomitant use of opioid analgesics with it may lead toincreased CNS depression. It has also been known to potentiate other medications such asbarbiturates and Xanax.

Izzo and Ernst, 2007; Miller, 1998;Abebe, 2002; Escher et al., 2001;Connor, 2010; PubMed, 1998

Passifloraincarnata

Passionflower may increase the risk of bleeding or potentiate the effects of warfarin therapy. Heck et al., 2000

Piper nigrum Black pepper should not be taken along with drugs metabolized by cytochrome P-450. Connor, 2010Panax ginseng The herb lowers the blood concentrations of alcohol and warfarin, and induces mania if used

concomitantly with phenelzine. The analgesic effect of opioids may be inhibited by ginseng.Izzo and Ernst, 2001; Heck et al., 2000;

Abebe, 2002Scutellaria

baicalensisScutellaria baicalensis may increase sedation of CNS depressants and decrease the effects of

immunosuppressants.Connor, 2010

Spiraeaulmaria

Spiraea may increase the risk of bleeding or potentiate the effects of warfarin therapy. Heck et al., 2000; Abebe, 2002

As it contains salicylate, so with acetaminophen it may augment the incidences of hepatotoxicity andnephrotoxicity.

Serenoa repens Serenoa may increase the effects off anticoagulants, antiplatelets and NSAID’s, antagonize hormonetherapy, and increase or decrease the effect of immunostimulants.

Connor, 2010

Salix alba It should not be taken with heparin as it contains a substance that is converted by the body into asalicylate similar to aspirin and combining aspirin with heparin increases the risk of abnormalbleeding. Salix alba may adversely interact with alcohol, anticoagulants, antiplatelet agents,anti-inflammatory agents, sulfonamide drugs, methotrexate, metoclopramide, phenytoin,probenecid, spironolactone and other potassium-sparing diuretics, and valproate.

Connor, 2010

Trifoliumpratense

Trifolium pratense may increase the risk of bleeding or potentiate the effects of warfarin therapy. Heck et al., 2009

Turnera diffusa Damiana may affect blood sugar levels so caution is advised when using it with medications thatlower blood sugar. Damiana may interact with progestin drugs.

Healthline, 2010; Alarcon-Aguilara,1998

Tanacetumparthenium

Effect of Feverfew is reduced when taken with NSAIDs. Feverfew may increase the risk of bleedingor potentiate the effects of warfarin therapy.

Miller, 1998; Heck et al., 2000.

Uncariatomentosa

May increase the risk of bleeding when used with anticoagulants or antiplatelet drugs, as it possessanti-inflammatory property, so it should be used with caution with other anti-inflammatorymedications.

Aetna InteliHealth, 2005; Hardin, 2007

Urtica dioica It possesses acute hypotensive action, diuretic and natriuretic effects, so along with it medicationshaving similar properties should be used with caution.

Tahri et al., 2000

Vacciniummacrocar-pon

The juice of vaccinium may decrease the effectiveness of antacid medications and may increase theabsorption of proton pump inhibitors.

Vitamins & Health Supplements Guide,2006

Viburnumopulus

Alter the effects of sedative, blood pressure medications, antibiotics, antioxidant, antiulcer,antispasmodic agents, astringent agents, and immunomodulators.

Healthline, 2010

Vacciniummyrtillus

Mildly inhibits platelet aggregation and should not be taken along with anticoagulants or antiplateletagents. Caution must be taken while taking Vaccinium with antidiabetics and NSAIDs, as it mayincrease the actions of these drugs.

Connor, 2010; Abebe, 2002

Viscum album There may be interactions with Viscum and prescription antihypertensives, antiarrhythmics (i.e.,Digoxin) due to its negative inotropic property.

Viable Herbal Solutions, 2010

Valerianaofficinalis

Valerian may cause an adverse interaction with lorazepam and haloperidol. The herb may potentiatethe effects of antiepileptic medications. Valerian should not be used concomitantly withbarbiturates because excessive sedation may occur. The concomitant use of opioid analgesics maylead to increased central nervous system depression.

Dergal et al., 2002; Dalla Corte et al.,2008; Spinella, 2001; Miller, 1998;Abebe, 2002

Vitex agnuscastus

It has dopaminergic effect and show additional pharmacological actions via opioid receptors, sopeople taking dopamine-related medications, such as selegiline, amantadine, and levodopa, shouldavoid using it.

Meier et al., 2000

Withaniasomnifera

The herb is found to potentiate the effects of Barbiturates and it should not be taken in combinationwith sedatives and anti-anxiety drugs.

Bhattacharya et al., 2000

Zingiberofficinale

Zingiber officinale may increase the risk of bleeding or potentiate the effects of warfarin therapy. Heck et al., 2000

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CONCLUSION

Contrary to popular belief that “natural is safe,” herbalmedicines can cause significant toxic effect, drug interaction,and even morbidity or mortality. This article is not a bias againstherbal medicines, but an attempt to put forth various publisheddata of national/international repute, to critically analyze it tocreate awareness amongst common masses, and also a readyreference/reckoner for pharmacognosist/herbal practitioners re-garding the use of herbal medicines. Worldwide, there is resur-gence of herbal remedies due to their high potential for healthbenefits. The point of thought is as to why common peopleare reverting back to use the Ayurvedic, Chinese, and otherherbal medicines. The reasons are their easy accessibility, noexpert consultation required, are considered safe, economical touse, and also because primary health care services in developingcountries fall short of peoples need both in qualitative and quan-titative terms. All these easily marketed herbal medicines mustbe Government/FDA/regulatory approved and people must beaware about their pros and cons while using them. We all knowthat the practice of herbal remedies is as old as civilization.However, it should be remembered that argument about the useof herbal remedies by ancestors since time immemorial cannotbe a substitute for compiled data on their safety or efficacy.Herb-drug and herb-herb interactions do occur and controlledscientific studies are the need of the hour to clarify and fullyexplore the clinical significance of herb-drug interactions andrediscover the classical procedures mentioned in old traditionaltexts. The common belief that anything natural is safe is not trueand this must be revolutionized.

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