3 L Int . J. Vi tam. Nutr. Res.,80 (1),2010,32-44

0r ig i na I Commu n ica t ion

Plasma and Associat ionwith Socio-Demographic and

DietaryFree- l iv ing 0 lder

Cather ine Féart1, Aisha Siewel , Céci l ia Samier i l , Evelyne Peuchant2,Cather ine Helmer ' , Serge Al fos3,

Véronique Pal let3 and Pascale Barberger-Gateaul1 INSERI\4, U897, UnivVictorSegalen Bordeaux, BORDEAUX, France; 'z INSERIV, U876, Laborato i re de Biochimie;UnivVictorSegalenBordeaux, B0RDEAUX, France; 3 Univ Bordeaux et Victor Segalen Bordeaux, EA 2975, Unité de Nutrit ion et Ne uroscienc*,t^i:).a.|

Received for publication: September 16,2008; Accepted for publication: February 7,2009

Abstract: The objective was to describe retinol plasma concentration and its association with socio-demographic characteristics and dietary habits in French older persons. The study population consistedof,1664 subjects aged 65 + from Bordeaux (France), included in the Three-City cohort. Retinol plasmaconcentration was determined in fasting blood samples. Dietary assessment was performed by a foodfrequency questionnaire allowing estimation of weekly intake of dietary sources of vitamin A orprovitamin A. The weekly number of glasses of alcohol was also recorded. Age, sex, marital status,educational and income levels, body-mass index (BMI), and smoking were registered. Cross-sectionalanalysis of the association between plasma retinol and socio-demographic characteristics and dietaryhabits was performed by multilinear regression. Mean plasma retinol was close to the homeostaticallyregulated concentration of 2.0 prnol/L but ranged from 0.35 to 637 pmol/L. It was higher in women anddivorced or separated individuals, and increased with income but not with age or educational level.

ofthe

Ret inol

Bordeaux

Ch aracteristicsPersons:

Sample of theThree-City Study

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C. Féart et al: Vitamin A in Older Persons

Plasma retinol was positively and independently associated with the frequency of offal consumption andto the number of glasses of alcohol consumed per week. These results allow targeting older individualswho are at risk of either excessive or deficient vitamin A status and who should benefit from dietarvcounseling.

Key words: Vitamin A, age, socio-demographic characteristics, diet, alcohol.

J J

In t roduct ion

The role of vitamin A in aging is still poorly under-stood and probably underestimated. Indeed, recentfindings suggest that vitamin A is involved in thepathophysiology of Alzheimer's disease (AD), acondition whose incidence sharply increases withaging [1-a].

On the other hand, vitamin A may also cause toxiceffects and older persons may be at significantlygreater risk of toxicity than are younger adults [5].

Although plasma retinol is generally considered tobe tightly regulated around 2 pnollL [6], little isknown about the distribution of vitamin A plasmalevels, and their determinants, in the free-livingelderly population. Most of the few published studiesare based on rather small or highly selective samplesof older persons 11-1,51.

Very low or very high plasma retinol may reflectinadequate vitamin A dietary intake or liver store,respectively [6,16]. Dietary vitamin A is obtainedfrom retinyl esters in animal foods and from provi-tamin A carotenoids in plant sources [5]. To ourknowledge, dietary patterns influencing plasma ret-inol have been examined in middle-aged adults113,1'7,181 but not in older persons, except for astudy of total vitamin A intake in a small sample ofolder persons attending a preventive medicine center

179,201, and for one study included in the EuropeanProspective Investigation into Cancer and Nutrition(EPIC) study, the latter limited by its sample size andthe Greek geographical characteristics of the sample

l2rl.Serum retinol is also linked to alcohol consump-

tion in adults [11, 77,22). Alcohol is a non-negligiblecompound of the diet in some populations. In theFrench Three-City (3C) study, alcohol intake ac-counted for L5 % of total energy intake in older menand 3.17o in women 1231. Chronic alcoholism inadults induces damages on liver storage and metab-olism of retinol and related compounds l2a-26].^1oour knowledge, two studies have assessed anddetermined a positive association between plasmaretinol and alcohol consumption in large samples of

older persons but they did not adjust for specific ortotal dietary sources of retinol [19,271. In a cross-sectional study in older persons aged 65 and over,alcohol intake was also directly correlated to plasmaretinol, although this association disappeared afteradjustment for total retinol intake [28].

Besides the role of aging on the retinoid pathway,socio-demographic factors such as gender, maritalstatus, and income are also determinants of dietarybehavior and may therefore have an indirect effect onvitamin levels. Other potential confounding factorslinked to both serum retinol concentrations in adultsand dietary behavior include BMI [18,22] and smok-ing [8,17,1B,20].

The objective of this study was to describe plasmaretinol concentrations in a large sample of Frenchelderly community-dwellers and to assess their asso-ciations with socio-demographic characteristics anddietary habits (foods rich in retinyl esters or beta-carotene and alcohol), taking these potential con-founders into account.

M ethods

Part icipants

This analysis is based on the Bordeaux sample of the3C study. The 3C study is a large ongoing prospectivecohort study of vascular risk factors for dementia,which included 9294 community dwellers in Bor-deaux (n:2I04),Dijon (n :4931), and Montpellier (n:2259), France, at baseline in 1999-2000. Themethods of the study and baseline characteristics ofthe participants are described in detail elsewhere

[29]. The protocol of the 3C study has been approvedby the Consultative Committee for the Protection ofPersons participating in Biomedical Research(CCPPRB) of the Kremlin-Bicêtre University Hos-pital (Paris) [29]. All the participants signed aninformed consent. In Bordeaux, a particular interestwas given to nutritional factors and complementarybiological variables were recorded as describedbelow. The present study is based on 1664 Bordeaux

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34 C. Féart et al: Vitamin A in Older PersonstWH\W$"lMiiK&imi'$fi iffi h$lffi ,S$llù:U'iirilliiii

participants with dietary data and plasma retinolassessment, after exclusion of one participant with anextremely high, aberrant plasma retinol concentra-tion (72.1pmol/L).

We did not intend to be representative of the whole3C cohort but of the Bordeaux sample.

Only 12 participants were taking dietary supple-ments at the time of blood sampling. Given that theirplasma retinol values (mean 1.95 pmol/L, standarddeviation (SD) 0.45 p.mol/L, range1.29 -3.04 prnolil)did not differ significantly from those of the rest of thesample, they were not excluded.

Plasma ret ino l determinat ion

Plasma retinol was determined in fasting bloodsamples by high-performance liquid chromatography(HPLC) as described elsewhere [30]. Values areexpressed in grnol/L (1.0 mg/L : 3.5 Urnol/L). Therange of serum retinol concentration under normalconditions is 1-3 pmol/L [5]. The deficiency ortoxicity of vitamin A is difficult to determine at thecirculating level and usually requires the evaluationof the hepatic vitamin A storage [16]. However,individuals with a retinol concentrations lower than0.70 trunol/L are considered as likely at risk ofinadequate vitamin A status in the literature and inFrench recommended dietary allowances [22,31]. Assuggested by Hallfrisch et al., we considered that aretinol plasma concentration over 3.5 ;rmol/L was theupper safe limit [9].

Die tary var iab les

A brief food frequency questionnaire was adminis-tered at baseline to assess the dietary habits of theparticipants for broad categories of aliments: meatand poultry, offal (including liver, a major source ofdietary retinol), fish (including seafood), eggs, milkand dairy products, cereals, raw fruits, raw vegetables,cooked fruits or vegetables, and pulses. Frequency ofconsumption was recorded in six classes: never, lessthan once a week, once a week,2-3 times a week,4-6 times a week, and daily. Participants indicatedthe dietary fats that they used at least once a week fordressing, cooking, or spreading. V/e considered as"regular users" those citing the corresponding dietaryfat. The number of glasses of wine, spirits, and othersources of alcohol consumed per week was recorded.Dietary habits of the whole 3C cohort have beendescribed elsewhere [32].

Other var iab les

Socio-demographic information recorded at baselineincluded age, gender, marital status, educational level(in four classes: primary or secondary or high school,and university level), and income in four predeter-mined classes expressed in euros (less than 750 euros,750 to L500 euros, 1500 to 2200 euros, more than 2200euros per month) as shown in Tâble 1. We excluded 13participants whose educational level was unknownand 117 who did not wish to report their income forthe corresponding analyses. Body-mass index (BMI)was computed as the weight/height2 ratio expressedin kg/m'. BMI was available in 1486 participants.Three classes of BMI were used accordins to theWHO definjtion: < 25kglm2 (reference calegory),from 25 to 299 kg/m2 (overweight) and ) 30 kg/m2(obesity). The 1563 participants who answered thequestion about smoking were classified as present,former, or never smokers based on their self-reports.Plasma triglycerides and total cholesterol were alsomeasured at baseline.

Statist ical analyses

Socio-demographic and dietary characteristics ofsubjects with available plasma retinol assessmentwere compared to those of subjects without plasmaretinol determination to ensure the representative-ness of the studied sample. Plasma retinol concen-tration was described for the studied population by itsmean and standard deviation. The cross-sectionalassociations of plasma retinol with socio-demograph-ic characteristics and biological variables were as-sessed by univariate linear regression. Statisticallysignificant difference was accepted at p<0.05. Wealso examined the association between frequency ofconsumption of each main dietary source of vitaminA (offal, fish, dairy products, eggs, butter) or carote-noid sources of provitamin A (fruits and vegetables)and plasma retinol by univariate linear regression.Since margarine brands widely differ according totheir vitamin A content, we did not analyze theassociation between margarine intake and plasmaretinol. The dietary variables were entered as dummyexplanatory variables. In order to achieve at leastabout 30 individuals in each consumption category,we grouped some contiguous classes. For totalalcohol intake, we used 6 classes ranging from zeroto 28 glasses per week (i. e. 4 glasses or more per day).We first performed a multivariate socio-demographicmodel with all socio-demographic variables associ-

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C. Féart et al: Vitamin A in Older Persons 35

èe0)NCh

O

.^lr

(t)

r.2

Plasma Retinol (pmol/L)Figure 1:Distribution of plasma retinol (pmol/L). The Bordeaux sample of the Three-City study, France, 1999-2000.

Resu lts

Compared with subjects with available plasma retinolassessment, subjects with missing plasma retinol(N:439) had lower income (p:0.016), had lowerweekly consumption of fish (p:0.0:0) and eggs(p:0.010) and higher weekly consumption of rawvegetables (p:0.011). As these foods were notassociated with plasma retinol in univariate analysis,we considered that the study sample (N:1664) wasrepresentative of the initial sample (N:210a).

The study sample included 646 men and 1018women; their mean age was 74.7 years. Table Idisplays the descriptive statistics of plasma retinol inthe sample studied and according to socio-demo-graphic characteristics of the participants. The plas-ma retinol appeared normally distributed (Figure 1).Plasma retinol ranged from 0.35 to 6.77 Frnol/L in thewhole sample. Nine subjects (0.5a%) had a concen-tration lower than 0.70 pmol/L. Forty subjects (2.4%)had a concentration at which toxicity symptoms mayappear (plasma retinol > 3.5 prnolil). Among them,none was a supplement user. Half of them (2Lsubjects) were regular alcohol drinkers (at least 14drinks per week).

6.45 .65 .24.03.6J . L2.82.01.60.80.4

ated with plasma retinol at p <0.20 in univariatemodels (sex, marital status, and income) and age asexplanatory variables (Model 1). The significant(pSO.ZO; dietary variables were then introduced asexplanatory variables (alcohol, offal, and cookedvegetables or fruits) and we performed stepwisebackward regression to identify the variables inde-pendently associated with the variation in plasmaretinol. At this step, we cancelled adjustment forcooked vegetables or fruits (p:0.25). Model 2included adjustments for age, sex, marital status,income, alcohol, and offal consumption. We addi-tionally adjusted for BMI and smoking status, andfinally for plasma triglycerides and total cholesterol(Model 3). A statistical interaction between alcoholconsumption and sex has been tested and was notfound (p:Q.lJ).

Statistical analyses were performed with StatisticalAnalysis Systems (SAS) statistical software packageversion 9.1 (SAS Institute, Cary, NC, USA).

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36 C. Féart et al: Vitamin A in Older Persons

Table I: Association between socio-demographic characteristics of the participants and plasma retinol. The Bordeauxsample of the Three-City study, France, 1999-2000

Retinol (prnol/L)

Mean SD p coefficief,t

Total population

Sex

Men

Women

Age (years)

65-69

70-74

75-79

80-84

> 8 5

Marital status

Single

Married

Divorced/Separated

Widowed

Educational level

Primary school

Secondary school

High school

University

Monthly income (euros)

< 7 5 0

750 - 1500

1.500-2200

> 2200

BMI (kg/m'z)

Normal

Overweight

Obese

Smoking

1664

1664

646

1018

1664

369

490

22240

1664

110

961

122

471

1651

613

425

335

278

1544

157

560

382

445

1486

782

562

142

1563

2.08

1..94

0.69

0.60

0.64

0.63

0.66

0.s9

0.7L

0.54

<0.0001

0.23

-0.14

0.r20.26

0.07

0.08

0.04

0,04

Ref.

<0,0001

2.00

0.39

1.97

2.02

1..97

2.05

r.99

0.0s

0.00

0.08

0.02

Ref.

0.23

0.94

0.14

0.86

0.02

1.89

2.01

2.15

l.vo

t.87

1..97

2.04

2.02

r .96

2.04

2.00

2.00

0.67

0.65

0.65

0.61

0.63

0.64

0.63

0.64

Ref.

0.07

0.002

0.38

Ref.

0.04

0.39

0.37

Ref.

0.09

0.004

0.009

Ref.

0.013

0.98

0.63

0.63

0.67

0.64

0.02

r.962.05L .96

0.62

0.64

0.64

0.100.r70.15

0.09

0.00

0.04

Int. J. Vitam. Nutr. Res., 80 (1),2010, @ Hogrefe & Huber Publishers

0.002

C. Féart et al: Vitamin A in Older Persons ) J

Frirlf"!"S$1fr EB'iijûâ'tiffiTSiXêirffi fillHilT"#RiHHfS:&

'Iable I: Association between socio-demographic characteristics of the participants and plasmâ retinol. The Bordeauxsample of the Three-City study, France, 1999-2000 (Continued)

Retinol (prnol/L)

Mean B coefficienlSD

Never smoker

Former smoker

Current smoker

1028

440

95

1.95

2.07

2.04

0.61

0.6s0.79

0.r20.09

Ref.

0.0006

0.18

* p-value for the linear regression comparing mean plasma retinol.Age and each significant (p < 0.20) socio-demographic characteristic were introduced in multivariate analysis (Table 3)

Women had significantly lower mean concentra-tions than men (Table I). There was no significantvariation with age or education. Marital status wassignificantly linked with plasma retinol, with divorcedor separated individuals having the highest meanvalues. Mean plasma retinol tended to increase withincreasing income. BMI and smoking were bothassociated with plasma retinol since overweightsubjects, but not the obese, and former smokers hadsignificantly higher mean concentrations. Moreover,plasma triglycerides and total cholesterol were bothpositively associated with plasma retinol in univariateanalysis (F:0.21, SD:0.02, p<0.0001 and B:9.65,SD:0.02, p:0.017 respectively).

Associations between dietary and drinking habitsand plasma retinol are presented in Table II. Plasmaretinol was positively associated with the frequencyof offal consumption. Indeed, frequent offal consum-ers (at least once a week) had significantly highermean retinol concentration than non-consumers. Theoverall association with frequency of consumption ofcooked fruits or vegetables was of bôrderline signifi-cance (p:Q.07). There was no significant associationwith frequency of consumption of any other foodconsidered as a dietary source of vitamin A orprovitamin A (fish, milk, eggs, butter, raw vegetables,and raw fruits). Alcohol drinking was strongly andpositively associated with plasma retinol.

Age, sex, marital status, and income remainedindependently associated with the variation in plasmaretinol in multivariate analysis (Table III, Model 1).When frequency of consumption of offal, cookedfruits and vegetables, and alcohol drinking wereadded to the model, the associationwith cookedfruitsand vegetables became nonsignificant and this vari-able was therefore excluded from the model (TableIII, Model2). Mean plasma retinol remained signifi-cantly higher in weekly offal consumers and alcoholdrinkers above 14 glasses per week, after adjustmentfor potential socio-demographic confounders. This

model explained 3.3% of the variance of plasmaretinol (adjusted R-square).

When smoking and BMI were added to Model2,their association with plasma retinol became non-significant. The association of plasma retinol withoffal and alcohol consumption was virtually un-changed when additional adjustment for plasmatriglycerides and total cholesterol was considered(Table III, Model 3 adjusted for age, sex, maritalstatus, income, offal and alcohol consumption, BMI,smoking status, triglycerides and cholesterol concen-trations). This last model explained 7.60/" of thevariance of plasma retinol.

DiscussionIn this sample of French older community-dwellers,plasma retinol was higher in men, divorced orseparated persons, those with higher income, andwas positively associated with frequency of offalconsumption and alcohol drinking.

Range of p lasma ret ino l

Although mean plasma retinol was very close to thehomeostatically regulated concentration of 2 prnolil-in our sample as expected, we observed a greatvariability exceeding by far the "normal" range of1 - 3 pnol/L that has been previously suggested [33] .This finding indicates that a non-negligible propor-tion of this population might be at risk of inadequatevitamin A status. However, plasma retinol reflectsonly very low or very high liver vitamin A stores andgives little information about the functionality ofthese stores 16,1'6,341. The plasma retinol variabilityobserved in this study may be in part explained bymodifications of the metabolism of vitamin A in olderpersons, linked to impaired chylomicron blood trans-port to the liver, or reduced ability of the liver to store

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38 C. Féart et al: Vitamin A in Older Persons

Table II: Association between dietary and drinking habits and plasma retinol. The Bordeaux sample of the Three-Citystudy, France ,1999 -2000

Retinol (prnol/L)

Mean SD 13 coeJficienln *r

Food and number of servinss

Offal

Never

< l, /week

> l iweek

Cooked fruits or vegetables

<2 lweek

2-3 lweek

4-6 lweek

> 1. lday

1657

924

618

115

1658

44

151

225

1238

L.9 l

2.00

2.78

2.07

Z,TI

L .94

1..99

0.62

0.62

0.84

0.004

0.07

0.03

0.2r

0.04-0.13

-0.08

Ref.

0.39

0.0009

Ref.

0.75

0.20

0.39

0.67

0.75

0.60

0.63

Beverage

Number of glasses of alcohol per week

None

1 - 6

I _ T J

14-20) 1 _ )1

> 2 8

1652

362

347

407

z /o

97

163

<0.0001

1.89

1..99

L .93

2.10

2. t7

z.t3

0.63

0.63

0.56

0.65

0.11.

0.76

0.10

0.04

0.2L

0.28

0.24

Ref.

0.04

0.39

<0.0001

0.0001

<0.0001

* p-value for the linear regression comparing mean plasma retinol.There was no significant association between plasma retinol and frequency of consumption of fish (p:0.12), milk (p:0.50),eggs (p:0.31), butter (p:O.gf ), raw vegetables (p:0.26), and raw fruits (p:0.95).The same positive trend between alcohol and plasma retinol was observed with wine drinking (p<0.0001).Offal, cooked fruits, or vegetables and alcohol were first introduced in multivariate analysis (Table 3). Finally, the "cookedfruits and vegetables" variable was not associated to plasma retinol and was then excluded for the multivariate analysis(Table 3, Model2).

dietary vitamin A [35-37]. Furthermore, retinol-binding protein (RBP), which is the specific carrierprotein of retinol in blood, may decrease with agingdue to malnutrition, infection, or inflammation lead-ing to a decrease of plasma retinot [38 -40]. However,almost 4o/o of the participants had a fasting plasmaretinol under 1.05 grnol/L, a threshold assumed toindicate a moderate risk of vitamin A deficiency [17],while only 0.54% really seemed to be at risk ofvitamin A deficiency (plasma retinol <0.70 pmol/L)

122,311. This may have potential consequences sincelow retinol serum concentration has been reported indemented patients compared to controls [41-43] andis sisnificantlv associated to frailtv svndrome in older

women [ a]. On the other hand, older persons mayalso be at greater risk of vitamin A toxicity thanyounger ones [5] , although the toxicity of vitamin A isgenerally evaluated by total dietary intake of vitaminA and supplements rather than plasma retinol

[45,46].

Comparison to mean plasma retinol found in otherstudies of older persons

Mean plasma retinol observed in the present studywas close to that reported by another study in a smallsample of 87 older Italians [7]. In other studies inolder persons, mean serum retinol was slightly higher

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C. Féart et al: Vitamin A in Older Persons

Table III: Influence of socio-demographic characteristics and dietary habits on plasma retinol in multilinear regressionmodels. The Bordeaux sample of the Three-Citv studv. France. 1999-2000

Model 1 (n:l1aa) Model2 (n:1530) Model3 (rz:1308)

39

B coeffi-,cient B coeffi- p*

cientB coeffi- p*cient

nr<r

Socio-demographic data

Age (years)

Sex (women)

Marital status

Single (Ref.)

Married

Divorced

Widowed

Income (euros)

< 750 (Ref.)

750- 1500

1500-2200

> 2200

Dietary data

Offal

Never (Ref.)

< 1 /week

)1 /week

Number of glasses of alcohol perweek

None (Ref.)

t - o

t - 1 3

14-20a 1 a 1

> 2 8

BMI (kg/m'z)

< 25 (Ref.)

25*29.9

> 3 0

Smoking status

never (Ref.)

former

current

0.005-0.148

-0.004

0.228

0.048

0.r17

<0.001

0.006

0.952

0.008

0.484

0.036

0.059

0.005

0.012

0.087

0.012

0.010

0.918

0.011

0.5s6

0.042

0.043

0.004

0.020

0.006-0.08s

0.007

0.209

0.043

0.069

0.t'73

0.111

0.018

0.618 0.005

0.005 0.230

0.006

0.069 0.085

0.804 0.032

0.012 0.131

0.003 0.243

0.023 0.1.41.

0.018-0.066

0.023

0.011

0.074

0.069

0,034

0.9r7

0.022

0.563

0.054

0.283

0.015

0.124

0.888

0.001

0.027

0.108

0.528

0.022

0.003

0.004

0.402

0.636

0.283

0.879

0.005-0.100

-0.007

0.2r50.040

0.110

0.L82

0.165

0.118

0.185

0.1.54

0.004

0.017

0.188

0.090

0.012

0.138

0.230

0.156

0.611

0.885

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40 C. Féart et al: Vitamin A in Older PersonsI'L$fôÊltf#"&W:.*ii,$;i.ilrlirïi.lÈSillËi&1tf$liliriti:bi.ïlii$litfiùM

Table III: Influence of socio-demographic characteristics and dietary habits on plasma retinol in multilinear regressionmodels. The Bordeaux sample of the Three-City study, France, 1999-2000 (Continued)

Model I (n:1544) Model2 (n:1530) Model3 (n:1308)

p coefficlent

p coeffi-cient

p coeffi-crent

6 *r1)* n'Fr

Plasma triglycerides (mmol/L)

Plasma cholesterol (mmol/L)

* p-value for the multilinear regression comparing mean plasma retinol.Model L: Adjustment for age, sex, marital status and incomeModel 2: Model 1 plus additional adjustment for offal and alcohol consumpttons.Model 3: Model 2 plus additional adjustment for BMI, smoking status, plasma triglycerides and total cholesterol

0.187

0.029

<0.0001

0.108

(2.12 to 2.43 pmollL) [14,19] or lower (from 1.30 to1.86 prnol/L) 121,,47). Our sample is much larger andmay better reflect true values for the general Frencholder population. A larger range of plasma retinolIevels was observed in the SENECA study across tenEuropean countries and one town in the US (range ofthe means from 1.4 to 2.0 prnol/L in men and women)

l2Tl.Higher mean values are provided by US studies,rnaybe because of their higher proportion of supple-ment users. The 619 older participants in the Wom-en's Health and Aging Study I had higher meanplasma retinol Ievels (2.60 plnolil-) [15]. In theNHANES III, serum retinol concentration medianvalue was 2.13 pmol/L for non-Hispanic whitepersons aged 71 and over [22].

Effect of socio-demographic factors

We did not find any variation of plasma retinol withage in this sample of older persons aged 65 and over,as also mentioned by several authors 119,47,481.However, controversial results exist as well sinceHaller et al. found a significant decrease of plasmaretinol with aging over a five-year time span in acohort of older persons f27), whercas others haveshown a higher retinol concentration in youngersubjects [17] or in healthy centenarians [a9].

In most studies conducted in middle-aged adults,as in the present study, mean plasma retinol wassignificantly higher in men 19,13,17,2I,41] althoughthis association was not always established [47 ,48].This association was in part explained by morefrequent alcohol or cigarette consumption in men inone study [19]. In our study this association persisteddespite adjustment for alcohol intake and smokingwhich were more frequent in men.

Few studies examined the relationship betweenplasma retinol and other socio-demographic charac-teristics, whereas we showed strong significant inde-pendent associations. To our knowledge, only one

study in 415 adults over 35 years of age mentionedthat married men had higher levels of plasma retinol

[B]. The association between divorce or separationand higher plasma retinol was rather unexpected.

The association between income and plasmaretinol was already assessed in the NHANES IIIStudy with inconsistent results l22l.In our study, thehigher plasma retinol found in higher income classeswas independent of dietary habits. Older persons withlow income are at risk for malnutrition as well [23].Residual confounding may also explain this unex-pected association. Indeed, all these socio-demo-graphic characteristics may also be markers ofunmeasured particular lifestyle variables that wouldinfluence plasma retinol.

Contrarily to other studies in middle-aged adults

[8,17], we did not find any association betweenplasma retinol and smoking status in our sample ofolder persons, as already observed in the EPIC study

[21]. Indeed, smoking was strongly associated withalcohol drinking. The association between plasmaretinol and smoking was therefore totally explainedby higher alcohol consumption of current and formersmokers. Controversial results about the associationbetween plasma retinol and smoking exist as well inolder persons 1I9,471.

Correlates of plasma retinol with food intake

Most previous investigations studied the associationbetween overall dietary intakes of vitamin A orsupplements, expressed as Retinol Equivalents, andplasma retinol, but they did not analyze specificdietary sources of vitamin A or carotenoid provita-min A. Indeed, the ZENITH study described thedietary intake and vitamin A status of a sample of 387healthy volunteers aged 55-87 years participating ina multicenter intervention study in France, Ireland,and ltaly, but they did not publish correlationsbetween these data [1a]. In healthy middle-aged

Int. J. Vitam. Nutr. Res., 80 (1), 2010, O Hogrefe & Huber Publishers

C. Féart et al: Vitamin A in Older Persons 4T

adults included in the SUVIMAX study, serumretinol was not associated with "estimated dietaryintake of retinol" [17]. The association betweenweekly consumption of offal and plasma retinol,highlighted in the present study, has thus far neverbeen mentioned in the literature- Since liver is theorgan of vitamin A storage, the association betweenconsumption of offal and plasma retinol may beexpected, knowing the age-related impairment ofvitamin A metabolism already suggested. The rela-tion between fruits or vegetables, sources of l3-carotene and so of provitamin A, and plasma retinolwas not found in this sample as in healthy olderItalians ll, 211. Conversely, intake of non-fruityvegetables was associated with increased plasmaretinol in the EPIC study [21].

The positive association between alcohol intakeand plasma retinol found in our sample was alreadymentioned by other authors in different age groups

117,L9,27,47). This association was independent offood sources of vitamin A intake in our study,contrary to results reported by Walmsley et al. l29l.An increased mobilization of vitamin A from the liverto other organs by ethanol may in part explain thisassociation [50]. Although many confounding fac-tors, including the lack of control for dietary intake ofanti-oxidants and other potentially protective nu-trients, may explain this association, although apositive impact of moderate alcohol drinking onvitamin A status cannot be excluded.

Lim i ta t ions

Several potential limitations to our results musthowever be considered. First, a selection bias cannotbe dismissed. Indeed, significant differences betweensubjects with and without plasma retinol data werefound. However, this may have had little influence onour findings since these differences concerned con-sumption of foods not associated with plasma retinolin univariate analyses. Second, some of the significantassociation or unexpected significant results found bymultiple comparisons performed in this large samplecould be due to chance finding.

Third, repeated measurements should improve theprecision of the estimates and strengthen the ob-served associations as well. Although our studyshowed a good correlation between the frequencyof offal consumption and plasma retinol, otherbiomarkers may be useful in evaluating the risk forchronic vitamin A toxicity resulting from the inges-tion of high amounts of pre-formed vitamin A for

months or years [5] . Moreover, \rye cannot excludethat part of the variability observed in the measuresof plasma retinol may be due to the techniqueemployed [51]. More sensitive biomarkers, such asthe molar ratio RBP-to- transthyretin (RBP:TTR)

[52], have been suggested to indirectly assess vitaminA status, but this ratio seems to be less reliable inolder persons [53].

Thanks to this population-based study, it waspossible to demonstrate that the homeostatic regu-lation of plasma retinol around 2.0 gnol/L in humanswas influenced by sex, income, and marital status, inaddition to specific dietary patterns such as intake ofoffal or alcohol drinking. These results may havepotential implications in terms of prevention ofvitamin A-related diseases in older persons. Theresults of this study may be used to identify olderindividuals who are at risk of either excessive ordeficient vitamin A status and those who couldbenefit from dietary counseling.

Acknowledgments

We thank Mélanie Le Goff who contributed to thestatistical analyses.

Source of funding

C. Samieri benefited from a grant from the Associ-ation Internationale pour la Recherche sur la Mal-adie d'Alzheimer (AIRMA). C. Féart benefited froma grant from the Regional Council of Aquitaine. Thebiological assays were funded by the RegionalCouncil of Aquitaine. The Three-City Study isconducted under a partnership agreement betweenthe Institut National de la Santé et de la RechercheMédicale (INSERM), the Institut de Santé Publiqueet Développement of the Victor Segalen Bordeaux 2University, and Sanofi-Aventis. The Fondation pourla Recherche Médicale funded the preparation andinitiation of the study. The 3C Study is also supportedby the Caisse Nationale Maladie des TiavailleursSalariés, Direction Générale de Ia Santé, MutuelleGénérale de I'Education Nationale, Institut de laLongévité, Regional Councils of Aquitaine andBourgogne, Fondation de France, and Ministry ofResearch - INSERM Programme "Cohortes etcollections de données biologiques." The nutritionalpart of the 3C study is included in the COGINUT(COGnition, anti-oxidants, fatty acids: an interdisci-plinary approach of the role of NUTiition in brain

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À a C. Féart et al: Vitamin A in Older PersonsFdiiiù$&i-4i&f$#,$Nffi$$Sil$If$.Wf$Trg{i}S!${,îiiiÏilrtl$d,ril$iJ$Hir.tlir,, ,$lirli;&il[r$t$i{:#,$rhjÉ1!t

aging) research program, which has benefited from a3-year grant from the French National Agency forResearch since 2007.None of the authors had anv financial or personalconflict of interest.

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Pascale Barberser-Gateau

INSERMu897Univ Victor Segalen Bordeaux 2F-33076 BordeauxFranceFax: -t- 33 5 57 57 14 86E-mail : Pascale.Barberger-Gateau@isped.u-borde auxZ.ft

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