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Department ofEpidemiology andPublic Health, INSERM744, Institut Pasteurde Lille and Universityof Lille Nord de France,

Lille, France(L. Dauchet,P. Amouyel,

J. Dallongeville).

Correspondence:J. Dallongeville,Department ofEpidemiology andPublic Health, INSERM744, Institut Pasteurde Lille, 1 rue du PrCalmette, 59019 Lille,France

[email protected]

Fruits, vegetables and coronary heart diseaseLuc Dauchet, Philippe Amouyel and Jean Dallongeville

Abstract | Diet plays an important part in the maintenance of optimal cardiovascular health. This Review

summarizes the evidence for a relationship between fruit and vegetable consumption and the occurrence of

coronary heart disease. This evidence is based on observational cohort studies, nutrition prevention trials with

fruit and vegetables, and investigations of the effects of fruit and vegetables on cardiovascular risk factors.

Most of the evidence supporting a cardioprotective effect comes from observational epidemiological studies;

these studies have reported either weak or nonsignificant associations. Controlled nutritional prevention

trials are scarce and the existing data do not show any clear protective effects of fruit and vegetables on

coronary heart disease. Under rigorously controlled experimental conditions, fruit and vegetable consumption

is associated with a decrease in blood pressure, which is an important cardiovascular risk factor. However,

the effects of fruit and vegetable consumption on plasma lipid levels, diabetes, and body weight have not

yet been thoroughly explored. Finally, the hypothesis that nutrients in fruit and vegetables have a protective

role in reducing the formation of atherosclerotic plaques and preventing complications of atherosclerosis

has not been tested in prevention trials. Evidence that fruit and vegetable consumption reduces the risk of

cardiovascular disease remains scarce thus far.

Dauchet, L. et al. Nat. Rev. Cardiol. 6, 599608 (2009); published online 4 August 2009; doi:10.1038/nrcardio.2009.131

Introduction

Interest in the role of diet in maintaining optimal healthstems from observations that rates of diseases differbetween cultures; dietary variation seems an obviousfactor that contributes to such differences. By the endof the 1980s, findings from laboratory, clinical andepidemiological studies indicated that consumption

of fruit and vegetables prevents several major diseases,such as cancer and heart disease,18prompting healthauthorities to promote consumption of these foods.9,10This Review summarizes the evidence for a relationshipbetween consumption of fruit and vegetables and theoccurrence of coronary heart disease (CHD), through ananalysis of observational cohort studies, nutritional pre-vention trials, and investigations of the effects of fruit andvegetable consumption on cardiovascular risk factors.We focused our analysis on studies that used fruit andvegetables as a nutritional exposure variable, as publichealth recommendations are usually expressed in termsof fruit and vegetable intake.

Observational epidemiological studies

The proposed relationship between fruit and vegetableconsumption and prevention of CHD is based in largepart on observational epidemiological studies,28,1113which can have an ecological, casecontrol, or prospec-tive cohort design. Ecological studies are designed toexplore relationships between environmental factorsand diseases in human populations. They do not provideprecise information about individuals in a populationand are subject to many uncontrolled biases. By contrast,in casecontrol studies, individuals diagnosed with CHD

Competing interests

The authors, the Journal Editor B. Mearns and the CMEquestions author C. P. Vega declare no competing interests.

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Learning objectives

Upon completion of this activity, participants should be able to:

1 Identify the results and limitations of observational

epidemiologic studies of fruit and vegetable consumption

and cardiovascular disease.

2 Describe results of prospective trials in regard to fruit

and vegetable consumption in the prevention

of cardiovascular disease.

3 Specify cardiovascular risk factors most improved with

higher intakes of fruit and vegetables.

4 Summarize the results of research on fruit and vegetable

nutrients in the prevention of cardiovascular disease.

2009 Macmillan Publishers Limited. All rights reserved
mailto:[email protected]:[email protected]://www.nature.com/doifinder/10.1038/nrcardio.2009.131http://www.medscape.com/cme/ncphttp://www.medscape.com/cme/ncphttp://www.medscape.com/cme/ncphttp://www.medscape.com/cme/ncphttp://www.nature.com/doifinder/10.1038/nrcardio.2009.131mailto:[email protected]:[email protected]


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are compared with disease-free individuals. Casecontrolnutrition studies rely on retrospective assessment of anindividuals diet and are, therefore, particularly subject toselection and recall bias. In prospective cohort studies,the diets of people who are assumed to be healthy areassessed and the group is followed over a period of time.

During the follow-up period, some individuals willdevelop CHD. Because measurements are made beforeany disease is diagnosed, cohort studies are not subjectto recall bias. In this section, we focus on prospectivestudies because they offer the most useful methodo-logical compromise for studying associations betweennutritional factors and CHD. The clinical end points ofthese studies were fatal and nonfatal CHD, CHD-relatedmortality (fatal coronary events only) and cardiovasculardisease (CVD) events, which include a variety of com-bined end points associating CHD-related fatal and non-fatal events and other vascular end points, such as stroke,heart failure, and sudden death.

Table 1 shows cohort studies from North America,Northern Europe and Japan, published between 1992and 2009.14,1550These studies vary considerably in theirinclusion criteria, recruitment methods, sample size,duration of follow-up, definition of events and adjust-ment factors, and presentation of results. Dietary assess-ment methodssuch as dietary history, 24-h recall,food-frequency questionnaires, and 3-day or 7-day fooddiariesalso varied between studies. The reliability andaccuracy of these methods to assess long-term nutri-tional habits is limited and was not always properly vali-dated. This heterogeneity complicates the estimation ofthe magnitude of effects, and the comparison of results

between studies.

CHD events

Of the eight prospective studies that have evaluated therelationship between fruit and vegetable consumptionand CHD, only three recorded more than 1,000 ischemiccoronary events,28,35one recorded 5001,000 events,37andfour recorded fewer than 500 events16,29,33,42(Table 2). TheHealth Professionals Follow-up Study (HPFS)28showeda statistically significant inverse relationship betweenfruit and vegetable intake and fatal and nonfatal isch-emic coronary events. An increase in fruit and vegetable

Key points

Consumption of fruit and vegetables is weakly associated with reduced riskof coronary heart disease in cohort studies

Prevention trials have failed to show clear effects of fruit and vegetableconsumption on the occurrence of coronary heart disease

Consumption of fruit and vegetables is associated with decreases in bloodpressure, but effects on other cardiovascular risk factors have not been clearly

established

Prevention trials have failed to confirm the hypothesis that vitamins and otherindividual nutrients in fruit and vegetables prevent coronary heart disease

Evidence that fruit and vegetable consumption prevents cardiovascular diseaseremains scarce thus far

consumption by one serving a day was associated witha 4% decrease in r isk of CHD (relative risk [RR] 0.96,95% CI 0.930.99). A pooled analysis of the HPFS andthe Nurses Health Study (NHS)28showed a decreasein risk with an additional serving of either fruit (RR0.94, 95% CI 0.900.98) or vegetables (RR 0.95, 95%CI 0.920.99).

Four other studies failed to show a statistically signifi-cant inverse relationship between fruit and vegetableconsumption and CHD events.29,35,37,42Other cohortstudies failed to show a statistically significant effect ofeither fruit16,29,42or vegetable29,33,42intake in reducing riskof ischemic coronary events, although in some of thesestudies, a trend towards a beneficial effect of fruit andvegetable intake was observed.

CHD-related mortality

The relationship between fruit and vegetable consump-tion and risk of CHD-related mortality has beeninvestigated in ten studies (Table 3). However, only the

Alpha-Tocopherol, Beta-Carotene Cancer Prevention(ATBC) study showed a significant inverse relationshipbetween intake of fruits and berries and CHD-relateddeaths.21The ATBC Study,21the Baltimore LongitudinalStudy of Aging (BLSA),45and the Japan CollaborativeCohort Study for Evaluation of Cancer Risk (JACC)50all reported a significant inverse relationship betweenvegetable intake and CHD-related deaths.

CVD events

Twelve studies have shown a relationship between fruitand vegetable consumption and CVD events (Table 4).A significant inverse relationship between fruit and veg-

etable intake and CVD events was observed in four ofseven studies.35,40,44,47Of the eleven studies24,2931,44,4750that assessed the protective effects of fruit on CVD,five30,31,44,47,49showed a significant correlation betweenfruit consumption and decreased risk of CVD events.Nine studies24,29,30,44,4750assessed the relationship betweencardiovascular protection and vegetable intake but onlytwo24,48reported a significant correlation.

Interpretation of observational studies

Epidemiological evidence for causality is controversial.51Many studies have reported a trend towards an inverserelationship between fruit and vegetable intake and

CHD, but few have produced statistically significantresults. The risk reduction estimates from cohort studiesare, therefore, less impressive than initially observed inecological or casecontrol studies, both of which can besubject to methodological bias.1Several factors couldexplain the limited associations between fruit and veg-etable intake and CHD risk. First, these studies cover aperiod of more than 50 years, during which the ratio ofpolyunsaturated to saturated fatty acids has improved inthe general population; this could affect the outcomesof prospective follow-up. Second, diet was assessed bya variety of methods, some of which did not provide



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sufficient information or did not adequately assess long-term dietary habits. Thus, the lack of comparability ofthe assessment instruments combined with inaccuratemeasurements make it difficult to detect associationsor weaken these associations. Third, although meta-analyses report relative risks indicative of a protectiveeffect of fruit and vegetables,6,8they also show substantialinter-study heterogeneity, which might be explained by

methodological issues or publication bias. Furthermore,meta-analyses of observational nutritional studies (incontrast to meta-analyses of clinical trials) have beencriticized because of difficulties in defining exposurevariables and because many different nutritional assess-ment methods are used. Given the extreme variability ofnutrition assessment methods and large measurementerrors in food intake, trend analyses of doseresponse

Table 1 | Description of cohorts concerning fruit and/or vegetable consumption and the risk of CHD and CVD*

Cohort Study area Population characteristics Number

(men/women)

Age (years) Years of

follow-up

Recruitment

dates

Dietary

assessment

AdventistHealth Study16

USA (California) Caucasian Adventists 10,003/16,740 >25 6 1976 FFQ

MCFSI18 Finland Healthy volunteers 2,748/2,385 3069 1216 19661972 Dietary history

Framingham19

USA (Framingham) Framingham residents 832/ 4565 20 19661969 24-h recallHFSS25 UK Vegetarians and HC 4,336/6,435 >16 16.8 19731979 FFQ

MCFSI22 Finland Healthy volunteers 2,748/2,385 3069 26 19661972 FFQ

ATBC21 Southwest Finland Smokers from a lung cancerprevention trial

21,930/ 5069 6.1 1993 FFQ

BC24 USA (Massachusetts) Volunteers 254/471 60101 912 19811984 3-day food diary

OVS26 UK Vegetarians and HC 4,102/6,700 1679 13.3 19801984 FFQ

HPFS27 USA Healthcare professionals 38,683/ 4075 8 1986 FFQ

NHS27 USA Nurses /75,596 3459 14 1980 FFQ

BHLS31 UK Residents of the UK 1,422/1,826 3575 7 19841985 FFQ

ATBC32 Southwest Finland Smokers from a lung cancerprevention trial

26,497/ 50 69 6.1 1993 Dietary history

WHS29 USA Healthcare professionals /39,127 54 (average) 5 1993 FFQ

MB 191330 Sweden (Gteborg) Men born in 1913 730/ 54 26 1967 FFQ

HPFS28 USA Healthcare professionals 42,148/ 4075 8 1986 FFQ

NHS28 USA Nurses /84,251 3459 14 1980 FFQ

PHS33 USA American physicians 15,220/ 40 84 12 1982 FFQ

HFSS34 UK Vegetarians and HC 4,325/6,416 >16 1824 19731979 FFQ

NHANES35 USA Population sample 3,684/5,924 2574 19 19711975 FFQ

DDCHS39 Denmark Healthy volunteers 27,177/29,876 50 64 3.09 19931997 Semi-quantitative FFQ

KIHD40 Finland (Kupio) Population sample 1,950/ 4260 12.8 19841989 4-day food diary

HNLS41 Japan Population sample 14,966/23,471 35103 16 19781981 FFQ

ARIC37 USA Residents of 4 geographical

areas

5,171/ 6,669 45 64 11 19871989 Semi-quantitative FFQ

PRIME42 France and Ulster Healthy volunteers 8,087/ 5059 5 1991 FFQ

Odyssey43 USA (Washington) Healthy volunteers 6,151 30 93 13 19741989 FFQ

NHS andHPFS44

USA Healthcare professionalsand nurses

37,725/71,910 3475 13 19841986 FFQ

Boyd Orr46 England, Scotland Children 4,028 7.5 37 19371939 7-day inventory

BLSA45 USA Men 80 years and older 501/


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relationships do not often reveal statistically signifi-

cant associations. Thus uncertainty remains about thereal magnitude of the relationship between fruit andvegetable intake and the occurrence of CHD.

Regardless of methodological issues related to cohortstudies, interpretation of the results requires caution.Consumers of fruit and vegetables have specific social,economic, and behavioral characteristics that couldinfluence CVD risk. For example, Joshipura et al.27foundthat individuals who consumed large quantities of fruitand vegetables were less likely to smoke and tended touse vitamin supplements. Social and behavioral factorscannot always be measured precisely, or might not be

appropriately considered in statistical analyses, and theirconfounding effects in studies of fruit and vegetableconsumption might not be fully appreciated. Fruit andvegetable intake might simply be a surrogate for reducedintake of undesirable nutrients, such as saturated fats.Thus, the observation of a favorable association betweenfruit and vegetable consumption and CHD risk does not

necessarily indicate causality. A careful approach to thedesign and analysis of observational studies, to accountfor potential confounding factors and reduce or preventmeasurement errors, is necessary to accurately estimatethe strength of the association.52

Prevention trials

Randomly assigning individuals to a prescribed dietensures comparability between groups, and minimizesthe effects of confounding factors, which are not alwaysadequately controlled in observational studies. However,although randomized nutritional prevention trialsprovide the most robust estimate of causal effects, they are

difficult to perform and not always feasible. The successof these studies relies on compliance of the participantsfor the duration of the study, which can be several years.Even with appropriate interventions, changes in fruit andvegetable intake are generally modestbarely one addi-tional portion per day on average according to publishedtrials.53Strict interventions could potentially be enforcedin a medical environment or for individuals with chronicdiseases,53but these conditions might not be feasible oreasily extrapolated to public-health settings.

Not surprisingly, given these difficulties, few rando-mized prevention trials have been conducted to evalu-ate the effect of high fruit and vegetable intake on the

incidence or recurrence of CHD.5456

In the Diet AndReinfarction Trial (DART) II,54recommendations aimedat promoting increased consumption of fruit, vegetables,fiber, and orange juice had no effect on cardiac death inpatients with angina pectoris. However, the small dif-ference in fruit and vegetable intake between study andcontrol participants20 g per daycould certainly havecontributed to the lack of significance.55,57In the WomensHealth Initiative (WHI) Randomized Controlled DietaryModification Trial,29dietary advice was provided forpostmenopausal women aged 5070 years, with the goalof reducing their intake of lipids and increasing con-sumption of fruit, vegetables, and grains. After 6 years,

fruit and vegetable intake in the group that receivednutritional advice had increased only slightly (by 1.2servings per day), compared with the control group.56The two groups did not, however, differ significantly inthe rate of major CHD events;56nutritional advice wasassociated with a 7% reduction in risk among womenwith no history of CVD. Post hoc analyses of fruit andvegetable levels showed that women who achieved thehighest level of consumption (6.5 servings per day) hadan 11% lower risk of CHD than the control group, butthis difference was not statistically significant. However,post hoc analyses are subject to residual confounding

Table 2 | Fruit and vegetable consumption and CHD events

Cohort Exposure End points Events Results

RR (95% CI)*

Test

for trend

Fruit & vegetables

WHS29 Q5 versus Q1 Fatal ornonfatal MI

126 0.63(0.381.17)

0.21

HPFS28

1 additionalserving daily Fatal ornonfatal MI 1,063 0.96(0.930.99) NA

NHS28 2 additionalservings daily

Fatal ornonfatal MI

1,127 0.97(0.931.00)

NA

NHANES35 3 times dailyversus 2 servings dailyversus


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factors and are not as strong or robust as randomizedcontrolled trials. The Lyon study58,59showed major bene-fits of a Mediterranean diet but given the complexity ofthis diet and the use of margarines rich in -linolenicfatty acid, these benefits cannot be attributed to fruit andvegetable consumption alone.

Nutritional prevention trials reported thus far have notprovided conclusive evidence for a cardioprotective effectof fruit and vegetable consumption. However, the difficul-ties in modifying long-term fruit and vegetable intake onthe basis of nutritional advice alone should be taken intoaccount when interpreting these disappointing results.

Risk factors for CVD

Analysis of the effects of fruit and vegetable intake onestablished CVD risk factors is an important step in deter-mining the biological plausibility of a causal relationshipbetween fruit and vegetable consumption and CHD-related events. At present, blood pressure and LDL chol-esterol are the only surrogate end points of CHD that arerecognized by health authorities. Studies of these endpoints are, therefore, more relevant than other biologicalexperiments in assessing cause-and- effect relationships.The effect of fruit and vegetable intake per se has not

always been adequately documented. In this section, wefocus on clinical studies that have tested the ef fects offruit and vegetable intake on principal cardiovascularrisk factors.

Hypertension

Findings of observational population studies6063andclinical trials64,65support the hypothesis that fruitand vegetable consumption can affect blood pressureregulation. The Dietary Approaches to Stop Hyper-tension (DASH) study,66which was conducted understrictly controlled experimental conditions, showed that

fruit and vegetable consumption was associated with asignificant decrease in blood pressure over an 8 weekperiod (systolic and diastolic blood pressure decreasedby 2.8 mmHg and 1.1 mmHg, respectively). The effectwas more pronounced in hypertensive patients thanin normotensive participants.6668 In another study,community-dwelling individuals who were encouragedto consume five portions of fruit and vegetables per dayfor 6 months had lower blood pressure values than thecontrol group (the between group differences for changein systolic and diastolic blood pressure were 3.4 mmHgand 1.4 mmHg, respectively).69Similarly, increased fruit

Table 3 | Fruit and/or vegetable consumption and CHD-related mortality

Cohort Exposure End points Events RR (95% CI)* Test for trend

Fruit & vegetables

NHANES35 3 daily versus 2 daily versus 2 daily versus


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and vegetable consumption combined with reduced fatintake has produced a very modest decrease in bloodpressure in some,56but not all,70prevention trials despite

large differences in fruit and vegetable intake betweenthe intervention and control groups. Consumption offruit and vegetables has, therefore, been shown to be

Table 4 | Fruit and/or vegetable consumption and CVD events

Cohort Exposure End points Events RR (95% CI)* Test for trend

Fruit & vegetables

WHS29 Q5 versus Q1 Fatal or nonfatal MI,PTCA, CABG

418 0.85 (0.611.17) 0.45

NHANES35 3 daily versus 26 years offollow-up: 32% versus 25.8%

NS

NHS & HPFS44 3 additional servingsdaily

Fatal or nonfatal MIand stroke

3,864 0.87 (0.800.94) NA

Takayama48 Q4 versus Q1 Cardiovascular mortality Men: 200Women: 184

Men: 1.20 (0.801.79)Women: 1.01 (0.671.53)

0.490.52

EPIC diabetic47 80 g daily supplement Cardiovascular mortality 517 0.88 (0.810.95) NA

JPHC49 Q4 versus Q1 Fatal or nonfatal MIand stroke

1,386 0.81 (0.67-0.97) 0.01

JACC50 Q4 versus Q1 Cardiovascular mortality 1,207 0.85 (0.641.14) NS

Vegetables

BC24 T3 versus T1 Cardiac mortality 101 0.51 (0.27 0.95) 0.04

WHS29 Q5 versus Q1 Fatal or nonfatal MI,PTCA, CABG

418 0.85 (0.611.19) 0.21

MB 191330 01 versus 67 intakesper week

Cardiovascular mor tality 226 >26 years of follow-up:35.5% versus 26.9%

NS

MB 191330 01 versus 67 intakesper week

Cardiovascular mor tality 209 >26 years of follow-up:29.8% versus 24.6%

NS

NHS & HPFS44 3 additional servingsdaily

Fatal or nonfatal MIand stroke

3,864 0.93 (0.861.00) NA

Takayama48 Q4 versus Q1 Cardiovascular mortality Men: 200

Women: 184

Men: 0.91 (0.601.36)

Women: 0.68 (0.441.07)

0.93

0.02EPIC diabetic47 80 g daily supplement Cardiovascular mortality 517 0.85 (0.681.07) NA

MB 191349 Q4 versus Q1 Fatal or nonfatal MIand stroke

1,386 0.97 (0.821.15) 0.66

JACC50 Q4 versus Q1 Cardiovascular mortality 1,207 0.96 (0.841.10) NS

*RR corresponds to the exposure variables presented in the articles (right column). Abbreviations: CVD, cardiovascular disease events; MI, myocardialinfarction; NA, Pvalue not available in the paper; NS, not statistically significant; OR, odds ratio; PTCA, percutaneous transluminal coronary angioplasty; Q5 andQ1, 5th and 1st quintile; Q4 and Q1, 4th and 1st quartile; RR, relative risk; T1, 1st tertile; T3, 3rd ter tile.



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associated with decreased blood pressure under con-trolled conditions, particularly in hypertensive individ-uals. Additional studies are necessary to validate thesefindings in the long term.

Hypercholesterolemia

Several components of fruit and vegetables have cho-

lesterol-lowering properties.71Dietary fiber promoteselimination of cholesterol through the feces by modify-ing biliary physiology and the enterohepatic cholesterolcycle.72Similarly, ingestion of large quantities of phy-tosterols (>2 g per day) lowers plasma LDL-cholesterollevels.73Several studies have reported effects of fruitand vegetable consumption on lipid profiles.70,74Mosthave shown little or no effect;68,69,7577however, not allwere specifically designed to test the effects of fruit andvegetable consumption in patients with hypercholester-olemia. In cancer prevention trials, interventions aimedat increasing fruit and vegetable intake and reducing lipidintake decreased levels of both LDL cholesterol and HDL

cholesterol.56,7880Thus, the lack of appropriately designedstudies has led to a situation where there is little evidencefor an effect of fruit and vegetable consumption on LDL-cholesterol levels.

Obesity

Fruit and vegetable are low in fat and have high water andnondigestible fiber content; increasing fruit and vegetableintake, therefore, lowers the energy density of meals. Inthe generally energy-abundant diets prevalent in westernsocieties, replacing energy-dense foods with fruit andvegetables could help to decrease calorie intake and,therefore, body weight.81,82Short-term investigations have

confirmed this hypothesis, but long-term regulation ofsatiety seems more complex, particularly for those livingin the community (that is, noninstitutionalized individu-als).83,84The effect of fruit and vegetable consumption onweight control has been thoroughly reviewed.8587In anambulatory setting, promoting fruit and vegetable con-sumption has not had a substantial effect on body weightor BMI.76,88However, these studies did not specificallytarget overweight or obese individuals. Other studieshave shown that decreased fat intake combined withincreased fruit and vegetable intake results in greaterweight loss when compared with low-fat diets.78,89,90Accumulating evidence indicates that the combination

of increased fruit and vegetable intake, together withother dietary recommendations, might promote satietyand weight loss in overweight individuals.

Diabetes

Several cohort studies have reported that componentsof fruit and vegetablessuch as antioxidants, fiberand magnesiumseem to lower the risk of type IIdiabetes.9193The relationship between fruit and vegetableintake and the risk of type II diabetes has not, however,been established and other cohort studies have producedconflicting results.9395The discrepancies between studies

could be explained by confounding factors, includingeducation level, social condition, physical activity, andby the possible antagonistic effects of the sugars, fiber,and antioxidants in fruit and vegetables. Randomizedprevention trials have demonstrated the effectivenessof complex lifestyle interventions (including promotionof fruit and vegetable intake, physical activity, and body

weight reduction) on reducing the risk of diabetes,96,97but the contribution of fruit and vegetablesper se in thesestudies is difficult to estimate given the complexity of theinterventions. Nutrition trials have not shown that fruitand vegetable intake affects either the risk of diabetes,98or levels of glycemia and insulin sensitivity.78,99101Thus,studies published to date do not provide clear evidencethat consumption of fruit and vegetables reduces the riskof type II diabetes.

Biological plausibility

The effects of nutrients on the biological processesleading to atherosclerosis have been tested in animal

models and in vitrocell culture systems.102In chronicpathologies, such as atherosclerosis, that have multiplepathophysiological causes occurring at different timepointsoften with years of latency before clinical man-ifestationdetermining the contribution of differentpathways to the final event is complicated. Thus, identi-fying the mechanisms of the proposed protective role offruit and vegetable consumption in multifactorial diseaseprocesses is difficult. To further complicate matters, theinteractions between the variety of nutrients found infruit and vegetables are rarely evaluated in biologicalexperiments. Moreover, different varieties of fruit andvegetables, growing techniques, industrial processing,

and storage and cooking conditions can strongly affectthe composition and properties of the nutrients. Giventhese variables, determining biological plausibility ofthe association observed between fruit and vegetableintake and CHD is particularly challenging and beyondthe scope of this Review. Nevertheless, in the followingsection we briefly discuss clinical trials that have inves-tigated the effects of individual components or combina-tions of components derived from fruit and vegetableson CVD end points.

Of the many nutrients in fruit and vegetables, onlyvitamins have been evaluated in clinical preventiontrials. Despite the abundance of biological evidence72and

observational epidemiological data103105

supporting theirrole in atherosclerosis prevention, meta-analyses of trialswith folate, carotenoids, and vitamin C have failed todemonstrate convincingly that these vitamins have a rolein preventing CVD and mortality.106112A meta-analysisevaluating the effects of combinations of multivitaminand mineral supplements on prevention of cardiovas-cular disease113found no evidence of a protective effect.Methodological issues, however, require that these trialsbe interpreted with caution. Factors that might haveaffected the results include inappropriate dosing or insuf-ficient duration of intake, both of which could influence



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effectiveness.114Perhaps the most effective combinationof vitamins or the optimal biochemical structure forsynthetic molecules for CVD prevention was not identi-fied. A further possibility is that CVD prevention trialsmight have recruited participants not likely to benefitfrom treatment, such as those with advanced lesions orwith satisfactory vitamin status. These limitations should

be taken into account in the design of future CVD pre-vention trials if we are to translate our knowledge of themolecular and cellular mechanisms of atherosclerosismore effectively into clinical benefit.

The use of biological and genetic markers as surro-gate end points in future studies should help to clarifywhether a causal relationship indeed exists betweenfruit and vegetable intake and CVD preventionso farthis relationship has only been inferred. For example,a randomized clinical trial published in 2009 supportsepidemiological observations by showing that in hyper-tensive patients, fruit and vegetable intake resultedin a dose-dependent improvement in endothelium-

dependent forearm blood flowan integrated markerof vascular function with known prognostic value.115

Conclusions

Evidence that fruit and vegetable consumption has aprotective effect against CVD comes mainly from obser-vational epidemiological studies. Most of these studiesshow a decrease in the risk of CHD and CVD with fruitand vegetable consumption. However, as fruit and veg-etable intake is associated with particular social, cul-tural, and lifestyle characteristics that might also conferprotection against CVD and, as these confounders arenot adequately controlled in observational studies, the

conclusion that a causal relationship exists betweenfruit and vegetable intake and CVD prevention is notjustif ied. Controlled, nutritional prevention trials arestill scarce, and the results so far have not shown con-clusively that fruit and vegetable intake protects againstCVD, in part because the dietary interventions have notbeen intensive enough to enable optimal analysis of theirputative effects.

Under rigorously controlled experimental condi-tions, fruit and vegetable consumption is associatedwith a decrease in blood pressurean important CVDrisk factor. The effects of fruit and vegetables on plasmalipid levels, diabetes, and body weight have not yet beenthoroughly explored. The hypothesis that componentsof fruit and vegetables decrease atheroma formation and

prevent its complications has been explored in animalmodels, in vitrocell culture systems and in human studiesusing integrated end points. In view of the complexity offruit and vegetable composition and of disease patho-physiology, the relevance of these models to biologicalplausibility of the association between fruit and vegetableconsumption and CHD remains debatable.

In conclusion, fruit and vegetables should be eatenas part of a balanced diet, as a source of vitamins, fiber,phytochemicals, and water. Substitution of harmful foodswith fruit and vegetables might reduce CVD events andprovide a basis for public health recommendations.Confirmation that fruit and vegetablesper se have a pro-

tective effect against CVD awaits further evidence fromnutritional prevention trials and clinical interventions oncardiovascular risk factors. In particular, the quantitiesof fruit and vegetables necessary for optimal preventionand target population are yet to be defined.

Review criteria

We selected studies that assessed the relationship

between coronary heart disease, or risk factors for this

condition, and consumption of fruit and vegetables,

separately and combined. We focused on CHD (angina andmyocardial infarction), but some studies that we examined

have looked more broadly at cardiovascular disease

(CHD and other vascular events such as stroke and heartfailure). We restricted our analysis to cohort studies or

trials that used fruit and vegetable intake as a nutritionalexposure variable and excluded studies of specific fruits,

vegetables, micronutrients or macronutrients. We also

excluded studies with complex interventions, such as the

Mediterranean diet. MEDLINE and EMBASE publicationswere searched up to June 2009.

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2. Law, M. R. & Morris, J. K. By how much doesfruit and vegetable consumption reduce the risk

of ischaemic heart disease? Eur. J. Clin. Nutr.52,549556 (1998).

3. Hu, F. B. Plant-based foods and prevention ofcardiovascular disease: an overview.Am. J. Clin.Nutr.78, 544S551S (2003).

4. Bazzano, L. A. Dietary intake of fruit andvegetables and risk of diabetes mellitus andcardiovascular diseases. World HealthOrganisation[online],http://www.who.int/dietphysicalactivity/publications/ f&v_cvd_diabetes.pdf(2005).

5. Dauchet, L., Amouyel, P. & Dallongeville, J. Fruitand vegetable consumption and risk of stroke:a meta-analysis of cohort studies. Neurology65,11931197 (2005).

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Acknowledgments

Charles P. Vega, University of California, Irvine, CA, isthe author of and is solely responsible for the contentof the learning objectives, questions and answers ofthe MedscapeCME-accredited continuing medicaleducation activity associated with this ar ticle.
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