Vegetarian diet: panacea for modern lifestyle diseases? From the Department of Medicine, Northern Territory Clinical School of Medicine of FlindersUniversity, Alice Springs, and 1Department of Medicine, Flinders University, Adelaide, Australia We review the beneficial and adverse effects of suggested. Consumption of fruits and vegetables, vegetarian diets in various medical conditions. Soy- especially spinach and collard green, was associated bean-protein diet, legumes, nuts and soluble fibre with a lower risk of age-related ocular macular significantly decrease total cholesterol, low-density degeneration. There is an inverse association lipoprotein cholesterol and triglycerides. Diets rich between dietary fibre intake and incidence of colon in fibre and complex carbohydrate, and restricted and breast cancer as well as prevalence of colonic in fat, improve control of blood glucose concentra- diverticula and gallstones. A decreased breast cancer tion, lower insulin requirement and aid in weight risk has been associated with high intake of soy control in diabetic patients. An inverse association bean products. The beneficial effects could be due has been reported between nut, fruit, vegetable and to the diet (monounsaturated and polyunsaturated fibre consumption, and the risk of coronary heart fatty acids, minerals, fibre, complex carbohydrate, disease. Patients eating a vegetarian diet, with com- antioxidant vitamins, flavanoids, folic acid and phy- prehensive lifestyle changes, have had reduced fre- toestrogens) as well as the associated healthy life- quency, duration and severity of angina as well as style in vegetarians. There are few adverse effects, regression of coronary atherosclerosis and improved mainly increased intestinal gas production and a coronary perfusion. An inverse association between fruit and vegetable consumption and stroke has been IntroductionLifestyle diseases such as obesity, diabetes mellitus, and cholesterol, with higher fibre and folate content hyperlipidaemia, hypertension, coronary artery dis- than a normal mixed diet. These result in lower body ease and cancer are common in industrialized coun- weight, blood pressure and plasma lipid levels than tries. There is considerable epidemiological evidence in omnivores. The vegetarian diet has beneficial suggesting that a vegetarian lifestyle is associated effects on the renal haemodynamic response to with a lower risk for these diseases. The beneficial protein, progressive renal disease, proteinuria and effects could be due to the diet as well as the healthy glomerulosclerosis, blood pressure and hyperlipidae- lifestyle, which includes desirable weight, regular mia in nephrotic syndrome. We now review the physical activity, and abstinence from smoking, alco- beneficial and adverse effects of vegetarian diets on hol and illicit drugs.1 We have already reviewed the primary hyperlipidaemia, diabetes mellitus, cardio- different types of vegetarian diets and their relevance vascular disease, stroke, dementia, neural-tube to renal disease.2 Briefly, vegetarian diets are lower defects, age-related macular degeneration, gastrointe- in energy and their percentage of energy from fat Address correspondence to Dr M. Segasothy, NT Clinical School of Medicine of Flinders University, Alice Springs Hospital,Box 2234, Alice Springs, NT 0871, Australia. e-mail: [email protected] cardiac death (4 vs. 7), compared to a control diet.15 Complications such as angina pectoris, electrocardio- Diets rich in fibre and complex carbohydrate and graphic changes after exercise, left ventricular hyper- restricted in fat improve control of blood glucose trophy, and ventricular ectopics (>8/min) were concentration,3 delay glucose absorption,4 lower significantly decreased in the group eating a veget- insulin requirements,5 increase peripheral tissue insu- arian diet, compared with those eating the control lin sensitivity,6 decrease serum cholesterol and tri- diet. After 1 year follow-up, cardiac events (non-fatal glyceride values,3,5 aid in weight control7 and lower acute myocardial infarction, fatal acute myocardial blood pressure in diabetic patients.8 Studies using infarction, and sudden cardiac deaths) occurred high-carbohydrate and high-fibre diets reported an significantly less often in the intervention group than average 40% reduction of insulin doses,9–11 a 6–27% in the control group (50 vs. 82, p<0.001).16 The reduction in fasting serum glucose values9,11 and a mean age, sex, mean body weight, blood pressure, 10–32% reduction in serum cholesterol values.9–11 lipoproteins, risk factors, complications, electrocar-diographic changes, initial level of cardiac enzymes,drug therapy and dietary intake (mean energy, totalfat calories, polyunsaturated/saturated fat ratio, diet- ary cholesterol, fibre and salt) were similar in both Studies have shown an inverse association between fruit, vegetable and fibre consumption and the risk In four patients who had severe angina pectoris, for coronary heart disease. Inverse relations between the angina resolved within 3–18 months on institut- vegetable consumption and myocardial infarction ing a vegan diet. When the health of vegans and (odds ratio, OR, 0.79 for the highest tertile) and age- and sex-matched omnivore controls using the angina pectoris (OR 0.89) were seen in an epidemiol- Cornell Medical Index was assessed, female vegans ogical study of 46 693 subjects in Italy.12 Two had fewer symptoms of cardiovascular disease.17 In epidemiological studies suggest that frequent con- a short-term (24 days) study, stress management sumption of nuts may provide some protection training (stretching/relaxation exercise and medita- against coronary heart disease. In the Adventist tion) and a vegan diet produced improvements in 23 Health Study, which was a prospective cohort investi- patients with ischaemic heart disease when com- gation of 31 208 Seventh-Day Adventists, subjects pared with a non-intervention control group. There who consumed nuts more than four times per week, was a 44% mean increase in duration of exercise, a had fewer definite fatal coronary heart disease events 55% mean increase in total work performed (bicycle (relative risk, RR, 0.52) and definite non-fatal ergometry), improved left ventricular regional wall myocardial infarction (RR 0.49), when compared motion and ejection fraction during exercise (exercise with those who consumed nuts less than once per radionuclide ventriculography) and a 91% mean week. This was independent of traditional coronary reduction in frequency of anginal episodes.18 In two risk factors such as blood pressure and relative prospective randomized, controlled trials, 50 patients weight, and other foods that were available for who were subjected to comprehensive lifestyle analysis, and was seen in both stratified and propor- changes (low fat, vegetarian diet, stopping smoking, tional hazards multivariate analyses.13 The nuts con- stress management training and moderate exercise) sumed were peanuts (32%), almonds (29%), walnuts for 1 year showed significant overall regression of (16%) and other nuts (23%). In the Iowa Women’s coronary atherosclerosis as measured by quantitative Health Study, 41 837 postmenopausal women were coronary arteriography. Degree of adherence was studied. Coronary mortality was inversely associated directly correlated with changes in percentage dia- with nut intake in these women (RR 0.43 in women meter stenosis. In contrast, patients in the usual-care consuming nuts 2–4 times per week) after adjusting control group showed significant overall progression for multiple factors such as age, energy intake, body of coronary atherosclerosis.19,20 There were also mass index, waist-hip ratio, presence of hypertension reductions in the frequency (91%), duration (42%) and diabetes, smoking status, use of hormonereplacement therapy, alcohol intake, and level of and severity (28%) of angina in the experimental group. In contrast, control group patients reported a In a randomized, single-blind prospective inter- rise in frequency (165%), duration (95%) and severity ventional trial in 406 patients subjected to dietary (39%) of angina.19 The design of the three studies18– intervention for 6 weeks, 24–48 h after acute 20 does not allow the determination of the relative myocardial infarction, a vegetarian diet resulted in contribution of each component of the intervention.
significant decrease (34.5%) in total cardiac end There were significant reductions in total cholesterol points, including non-fatal (17 vs. 25) and fatal (8 (20.5–24.3%), LDL cholesterol (37.4%) and triglycer- vs. 12) acute myocardial infarction, and sudden ides (15.5%) in the intervention group compared to the control group, suggesting a significant dietary ( p<0.05). The role of folic acid will be discussed in the section on cardiovascular disease.
Although serum cholesterol is a major determinant of atherosclerosis, its role in the pathogenesis ofstroke is unclear. However, recent trials of statins for secondary prevention of coronary artery disease have Mortality from stroke has been declining for many consistently shown that lowering lipid levels results decades in Europe and North America. This decline in lower risk of stroke as well as coronary events.30–32 in mortality has been attributed to multiple factors, Epidemiological studies indicate an inverse associ- including the increased consumption of fruits and ation between dietary intake of fat and saturated fat, vegetables.21 An inverse association between fruit and risk of stroke, supporting a beneficial effect.33,34 and vegetable consumption and stroke has been The vegetarian diet, which includes fruits, vegetables, suggested.22–24 In a population-based longitudinal complex carbohydrates, soy bean, legumes, nuts and study of 832 middle-aged men over 20 years of soluble fibre, could thus lower the risk of cardiovas- follow-up, for each increment of three servings of cular disease through multiple mechanisms such as fruit and vegetable per day, there was a 22% lowering of cholesterol and the beneficial effect of decrease in the risk of all stroke.24 Similar results antioxidant vitamins, folic acid, linolenic acid and were observed for transient ischaemic attack and completed stroke, both ischaemic and haemorrhagic.
The protective effect of fruit and vegetables may be related to their potassium, antioxidant, a-linolenic acid and folate content, as well as their ability to lower serum cholesterol and blood pressure. Thevegetarian diet has a blood-pressure-lowering effect.2 At least part of the beneficial effects of vegetarian Increased potassium intake may decrease risk of diet, with or without other lifestyle changes, probably stroke by lowering blood pressure as well as by results from a hypolipidaemic effect. In addition, mechanisms independent of its effect on blood vegetarian diets reduce weight and blood pressure, pressure, as indicated by animal studies.25 The further improving primary and secondary prevention.
inverse association of low plasma carotene, vitaminC levels and vitamin C intake with risk of stroke,26,27 and preliminary data from the Nurses’ Health Study28both suggest a protective role for dietary antioxidant Vegetable proteins are useful for the treatment of vitamins. A prospective study over 12 years invol- human hyperlipidaemia. A soy-bean-protein diet ving 2974 middle-aged men in Switzerland showed lowered the serum cholesterol to a greater degree that men with low plasma concentrations of both than did a low-cholesterol, low-saturated-fat diet ascorbic acid and b-carotene had four times the risk containing an equivalent amount of protein of animal of dying of stroke.26 In a cohort study of 730 elderly origin.35–37 Substantial decreases were observed in men and women in the UK followed for 20 years, both serum cholesterol (21% after 3 weeks) and stroke among those in the highest tertile of vitamin triglycerides, in patients with type IIa and IIb hyperli- C intake (mean >45 mg per day) was significantly poproteinaemia, including some with familial hyper- reduced (RR reduction, RRR, 50%) compared to the cholesterolaemia.35,36 A recent meta-analysis of 38 lowest tertile (mean <28 mg per day). A similar human studies derived from 29 articles with a total gradient of risk was present for plasma ascorbic acid of more than 740 subjects showed that the consump- concentration (RRR 30%).27 In 87 245 US female tion of soy protein resulted in significant decreases nurses, the RR of ischaemic stroke was 0.55 in in total cholesterol (0.60 mmol/l; 9.3%), low-density women in the highest quintile of antioxidant vitamin lipoprotein (LDL) cholesterol (0.56 mmol/l; 12.9%) score compared with those in the lowest. Carotene and triglycerides (0.15 mmol/l; 10.5%).38 There were intake was the predominant contributor to the no significant changes in high-density lipoprotein reduced risk, with modest contributions from vit- (HDL) cholesterol or very-low-density lipoprotein (VLDL) cholesterol concentrations. The magnitude of Analysis of the Multiple Risk Factor Intervention the lipid changes was greatest in those with the Trial (MRFIT) suggests that higher levels of a-linolenic highest initial plasma cholesterol concentrations. Soy acid are independently associated with lower risk of protein intake averaged 47 g per day. It was estimated stroke in middle-aged men at high risk for cardiovas- that the ingestion of 25 or 50 g of soy protein per cular disease.29 A standard deviation increase day could decrease serum cholesterol by 8.9%.38 An (0.13%) in the serum level of a-linolenic acid was intake of 30 g soy protein can be obtained by associated with a 37% decrease in the risk of stroke drinking two cups of soy milk and consuming one serving of meat analogue. The mechanisms of the of 20 trials using oat products revealed that about hypocholesterolaemic effect of soy protein are 3 g per day of soluble fibre from oat products (28 g unknown. It has been suggested that the beneficial oat bran) can lower total cholesterol levels by effect of soy may be the result of the amino-acid 0.13–0.16 mmol/l, and the reduction is greater in pattern and peptide structure of the soy protein39 as those with initially higher blood cholesterol levels.53 well as from non-protein compounds such as isofla- Oat bran is more effective in lowering cholesterol vones or phytoestrogens and saponins.38–40 than wheat bran or oatmeal, as it contains morewater-soluble fibre b-glucan.54 A high intake ofsoluble fibre can further reduce plasma cholesterol even after marked reductions in dietary saturated fat Leguminous seeds lower serum cholesterol in man.41–44 and cholesterol have been achieved. A crossover Substitution of chick peas for wheat flour decreased study in 43 volunteers with hyperlipidaemia sub- serum cholesterol levels by 22% by the end of 55 jected to a metabolic diet high in soluble fibre, but weeks.41 Consumption of 30 g dried legumes daily low in saturated fat and cholesterol, demonstrated a over a 3-month period resulted in a 16% decrease fall in total cholesterol by 4.9% and LDL cholesterol in serum cholesterol in hyperlipidaemia patients, by 4.8% during the soluble-fibre period.55 compared to a 8.7% decrease in normal volunteersstudied under similar conditions.42 Substitution ofabout 140 g dried beans (kidney, pinto, chick pea, green and red lentils) daily for other sources of starch Vegetarian diets are lower in energy and percentage over a 4-month period in hyperlipidaemic patients of energy from fat and cholesterol, and vegetarians resulted in a 7% decrease in total serum cholesterol have lower body weight than omnivores.56–58 There and a 25% reduction in serum triglycerides. There is evidence that a low-energy diet can modulate were no significant changes in LDL and HDL choles- blood lipids59 and reduce atherosclerosis and coron- ary deaths,60 and weight reduction may be associatedwith reduction in coronary artery disease and all its risk factors.61,62 With a fat-modified diet, even modestweight reduction (4.5 kg) by obese people results in Nuts are rich in protein, monounsaturated fatty acids a 30% or 40% greater fall in the level of cholesterol (oleic acid), vitamins (vitamin E, B6, folic acid and than that resulting from the qualitative change in fat niacin), minerals and fibre.45 Walnuts are, however, intake alone.63,64 Weight reduction may also reduce rich in polyunsaturated fatty acids (linoleic and a- cardiac enlargement, left ventricular strain, post- linolenic acids). Nuts are classified as part of arrhythmias,61,65 possibly by reducing myocardial Alternate Group and in the Mediterranean and Asian oxygen requirements and having other beneficial diet pyramids, have been placed on the same level Walnuts,46,47 macadamia,48 almonds,47,49 and hazelnuts46 have cholesterol-lowering properties, and a beneficial effect on the lipoprotein profile. In The beneficial effect of vegetarian diet on cardiovas- controlled, randomized, crossover study in 18 norm- cular disease could also be due to the presence of ocholesterolaemic men, diets rich in walnuts antioxidant vitamins such as vitamin E, vitamin C and b-carotene and flavanoids as well as folic acid, 12.4%), LDL cholesterol (0.47 mmol/l; 16.3%) linolenic acid and fibre in fruits and vegetables.
and triglycerides (0.11 mmol/l; 8.3%). Although Oxidation of LDL cholesterol is an important step in HDL cholesterol was lowered by 4.9%, the LDL the pathogenesis of atherosclerosis.66 Vitamin E,67 cholesterol to HDL cholesterol ratio was lowered vitamin C,68 b-carotene69 and flavanoids70 prevent significantly by 12.0%. Likewise, a randomized the oxidation of LDL cholesterol. Four large prospect- controlled, crossover-designed study in 30 healthy ive epidemiological studies found that high doses of subjects showed a macadamia-nut-based, high- vitamin E intake or supplementation were associated monounsaturated-fat diet lowered serum total choles- with a significant reduction in cardiovascular dis- terol and LDL cholesterol within 4 weeks.
eases.71–74 The relative risk reductions (RRR) rangedfrom 31% to 65%. Studies involving b-carotene and vitamin C gave less consistent reductions in cardio- Soluble fibres are abundant in fruits, dried beans, vascular disease, the RRR ranging from −2% to legumes, guar gums, barley, psyllium and oat cereals 46%, and −25% to 51%, respectively.71–73,75–77 and can lower blood lipid levels.50–52 A meta-analysis Three other epidemiological studies have suggested a role for flavanoids, especially quercetin, in the thrombosis in patients with systemic lupus eryth- prevention of coronary artery disease.78–81 However, all82–89 but one90 prospective randomized trial did The predominant cause for elevated homocysteine not show reductions in cardiovascular disease with blood concentrations is inadequate blood folate.101 vitamin E, vitamin C or b-carotene supplementation.
Folic acid supplementation has been shown to be However, the prospective trials were designed to highly effective in reducing plasma homocysteine study cancer, not cardiovascular disease (fatal or levels.96 Total homocysteine concentrations reach a non-fatal cardiovascular disease outcomes) and prob- reduced plateau when the folate intake approaches 400 mg/day.101 It has been estimated that a folic acid Furthermore, the prospective studies were of limited increase of about 200 mg/day results in an average duration (usually a few years) and usually com- reduction of 4 mmol/l in total homocysteine concen- menced in middle age when atherosclerosis may be tration and an increase in folic acid intake of 350 mg well established, in contrast to epidemiological stud- per day in men and 280 mg per day in women ies where intake is protracted (several years or would potentially prevent 30 500 and 19 000 deaths decades) and started at a much younger age when from vascular causes per year, respectively, in the atherosclerosis is in the early stages.91 Ongoing large-scale and planned long-term randomized trials Results from the Nurses’ Health Study demon- designed specifically to evaluate effects on cardiovas- strated a significant inverse relation between dietary cular disease will help to resolve this controversy.
intake of folate and vitamin B6, and mortality and morbidity from cardiovascular disease during afollow-up of 80 082 women over a 14-year period.102 The RR of coronary heart disease between extreme An elevated plasma homocysteine concentration is quintiles were 0.69 for folate and 0.67 for vitamin an independent risk factor for atherosclerosis of B and 0.55 for both folate and vitamin B . The coronary, cerebral and peripheral vessels92 and for magnitude of the inverse association for folate was deep-vein thrombosis.93 One study found that similar to their parallel study among male health 28–42% of patients with premature vascular disease professionals.103 Each 100 mg/day increase in folate had hyperhomocysteinaemia.94 In the Physicians’ was associated with a 5.8% lower risk of coronary Health Study, 14 916 male physicians were prospect- heart disease.102 In a retrospective cohort study ively followed for about 5 years.95 Men with plasma of 5056 men and women aged 35–79 years, there homocysteine concentrations that were 12% above was a 69% increased risk of coronary mortality the upper limit of normal had about a three-fold among those in the lowest quartile as compared with increase in the risk of myocardial infarction, as the highest quartile of serum folate.104 In a small compared with those with lower levels, even after uncontrolled study of 38 patients with atherosclerosis correction for other risk factors. A meta-analysis of the carotid arteries, supplementation with folic of 27 studies indicated that 10% of the risk of acid, pyridoxine and vitamin B was associated with coronary artery disease in the general population is regression of plaque after a mean follow-up of 4.4 attributable to homocysteine.96 An increase of years.105 Prospective, randomized, controlled trials 5 mmol/l in the plasma homocysteine concentration will be necessary to determine the effect of folic raised the risk of coronary artery disease by as much acid supplementation on cardiovascular mortality.
as an increase of 0.52 mmol/l in the cholesterolconcentration.96 A prospective study involving 587 patients with angiographically-documented coronaryartery disease showed a graded association between An inverse association between linolenic acid intake plasma homocysteine concentrations and overall and coronary heart disease has been observed in mortality.97 In a cross-sectional study of 1041 elderly several studies.106–108 In 43 757 US health profes- subjects in the Framingham Heart Study, high plasma sionals followed-up for 6 years, intake of linolenic homocysteine concentrations and low concentrations acid was inversely associated with risk of myocardial of folate and vitamin B were associated with an infarction.107 The RR for a 1% increase in linolenic increased risk of extracranial carotid artery stenosis.98 acid intake was 0.53 after adjustment for standard There was a graded relation between plasma homo- risk factors and intake of fibre, and 0.41 after further cysteine and the risk of carotid stenosis. Likewise a adjustment for intake of total fat. In a prospective graded increase in the relative risk of stroke with secondary prevention trial, a Mediterranean a- increasing serum homocysteine concentration was linolenic-acid-rich diet was associated with lower seen in a nested case-control study.99 Total plasma cardiac deaths and non-fatal myocardial infarction.108 homocysteine concentration was also found to be The risk ratio for both these endpoints combined an independent risk factor for stroke and arterial was 0.27. The incidence of coronary disease is low in Japan, where the diet is rich in linolenic acid.109 up study of 921 elderly men and women in the UK, Foods rich in a-linolenic acid include green leafy cognitive impairment was associated with lower vegetables, soybean products, grapeseed oil, canola vitamin C intakes (OR 1.7) and lower plasma ascorbic oil, purslane, walnuts, hazelnuts and flax seed. The levels (OR 1.6).119 However, as these studies were cardioprotective effects of a-linolenic acid may be cross-sectional, the lower vitamin C status could be due to its beneficial effects on platelet reactivity110 a consequence rather than a cause of cognitive impairment. Low vitamin E levels were associatedwith dementia both in older people and in subjectswith Down’s syndrome.120 In 341 patients with moderately severe Alzheimer’s disease treatment with In a prospective cohort study of 43 757 US male selegeline (10 mg/day) or a-tocopherol (2000 IU/day) health professionals followed-up for 6 years, the age- for 2 years slowed the progression of disease.121 The adjusted RR for total myocardial infarction was 0.59 increase in median survival was 230 days for the among men in the highest quintile of total dietary patients receiving a-tocopherol, 215 days for those fibre intake compared with men in the lowest receiving selegeline, and 145 days for those receiving quintile.112 The inverse association was strongest for both, as compared with patients receiving placebo.
fatal coronary disease (RR 0.45). A 10 g increase in These studies suggest that increased consumption of total dietary fibre corresponded to an RR for total antioxidants such as vitamins C and E may delay myocardial infarction of 0.81. The main contributors for fibre intake were cereal (cold breakfast cereal),fruits (apples, bananas and oranges) and vegetables(peas, cooked carrots and tomato sauces). An inverse association between fibre and coronary disease has Age-related macular degeneration is the leading also been reported by previous smaller studies.113–115 cause of irreversible blindness in persons over the In a new analysis of the Finnish a-tocopherol, b- age of 65 years.122 Serum levels of carotenoids have carotene (ATBC) cancer prevention study in which been significantly inversely related to the risk of age- 21 930 men were followed-up for 6 years, a high- related macular degeneration.123 People with low fibre diet significantly reduced morbidity and mortal- intake of fruits and vegetables rich in vitamin A had ity from coronary heart disease in middle-aged men a significantly higher risk for age-related macular who smoke.116 For men in the highest quintile of degeneration compared with those whose consump- total dietary fibre intake, the RR for coronary death tion was high.124 Adults in the highest quintile of was 0.69 compared with men in the lowest quintile carotenoid intake had a 43% lower risk of age- of intake. A 10 g greater daily intake of fibre appeared related macular degeneration, compared with adults to lower the risk of coronary death by 17%. Cereal in the lowest quintile of intake.125 Among the carot- fibre had a stronger association with reduced coron- enoids, lutein and zeaxanthin were most strongly ary death than vegetable or fruit fibre. In the food associated with a reduced risk for age-related macu- group analysis, intake of rye products, potatoes, lar degeneration. Consumption of spinach and col- vegetable and fruit were inversely associated with lard greens, which are rich in lutein and zeaxanthin, coronary death. The RR in the highest quintile of were associated with a dose-dependent reduction in vegetable consumption compared with the lowest risk of age-related macular degeneration. Lutein and was 0.60. A 100 g greater daily intake of vegetables zeaxanthin form the yellow pigment in the macula, was associated with a 26% lower risk of coronary and may prevent photic damage by absorbing blue light.126 These pigments are found in green leafyvegetables, as well as fruits and vegetables of othercolours such as maize, orange pepper, kiwi fruit, grapes, spinach, orange juice, zucchini and differentkinds of squash.127 Cognitive impairment has been associated with lowervitamin C intakes and lower plasma ascorbic acidlevels.117–119 In 260 men and women aged >60 years in the US, those with low blood levels ofvitamin C, folic acid, riboflavin or vitamin B Dietary fibre is protective against colorectal cancer.
significantly lower scores on tests of memory and A review of 40 epidemiological studies described abstract thinking.117 In 418 elderly men and women in 55 original reports indicated an inverse association in China, low blood levels of vitamin C, riboflavin between total dietary fibre intake and the incidence and folic acid were associated with low scores on of colon cancer in 32 of the 40 studies.128 These the Hodkinson mental test.118 In a 20-year follow- studies were performed on vegetarians as well as non-vegetarians, and the main sources of fibre were Mechanisms by which fibre may aid in reducing fruits, vegetables, cereals, pulses and wheat.128 breast cancer include lowering circulating levels of Mechanisms for the inhibitory role of fibre in colorec- oestrogens.148 Soy beans contain several classes of tal carcinogenesis include reducing faecal mutagen potentially important chemopreventing agents such concentrations by increasing faecal bulk, reducing as phytosterols, sitosterols, phytoestrogens, saponins, the exposure of colonic mucosa to faecal mutagens Bowman Birk inhibitor and chymostatin.149 There by reduced faecal transit time, and inhibiting faecal are two principal varieties of phytoestrogens, namely mutagen synthesis through fibre-induced changes in isoflavones and lignans. Isoflavones genistein and colonic pH or bacterial metabolism.129 Fibre intake diadzein are found predominantly in soy products,150 may influence colonic cell proliferation and the whilst lignans are found in the fibre present in whole development of polyps in high-risk populations.130 grains, berries, fruits, vegetables and flax seed.151 There is an inverse relation between dietary con- Daily ingestion of soy protein lengthens the menstrual centration of cereal fibre and the prevalence of cycle and suppresses the usual midcycle surge in colonic diverticula, both in a lifespan study of rats131 pituitary gonadotropins,152 effects that are beneficial and in matched groups of vegetarians and non- in decreasing risk of breast cancer. Phytoestrogens vegetarians.132 Vegetarians consuming 41.5 g fibre may exert an antioestrogenic effect by competing per day had an incidence of asymptomatic divertic- with estradiol for oestrogen receptors in breast ular disease (12%) that was significantly lower than tissue;153 cell-culture studies and animal experiments that in non-vegetarians (33%) who consumed 21.4 g show that they are tumour-inhibitory.142 Animal fibre per day.132 Dietary fibres shorten gastrointestinal studies also suggest that short-term exposure to transit time,133 and increase stool weight,134 fre- dietary isoflavones neonatally or prepubertally quency135 and water content135 thereby reducing decreases carcinogen induced breast cancer.154 constipation. An association between cholelithiasis These studies suggest that the protective effect of the and a diet low in protein, fat and crude fibre intake Southeast Asian diet occurs early in life,155 and has been reported.135 Intake of fibre is negatively infants there are exposed to soy food early in associated with gallstones.136 The fibre content of the diet influences bile salt metabolism and theconcentrations of biliary lipids in bile.137,138 Epidemiological studies indicate that people whoconsume higher dietary levels of fruits and vegetables have a lower risk of certain types of cancer158 suchas breast,159 lung, oral, pancreas, larynx, oesophagus, bladder and stomach.160 Certain subgroups of the The protective role of dietary fibre against colorectal American population, such as the Mormons and cancer has already been discussed. Epidemiological Seventh-day Adventists, who are vegetarians, have a studies also suggest that the risk of breast cancer significantly lower cancer rate.161,162 The reduced may be lowered by increasing the intake of dietary risk of cancer associated with the consumption of fibre and other dietary components associated with fruits and vegetables has been postulated to be due high intakes of whole grains, vegetables and fruits.139 to the presence of antioxidants such as vitamins E An inverse association between breast cancer risk and C and b-carotene, and this has been well and consumption of fibre and fibre-rich foods has reviewed in many publications.129,163–165 been reported,140,141 and there is a lower frequency Several correlational and case-control studies sug- of breast and prostate tumours in Asian countries, gest that the consumption of vitamin C containing where soy foods, which are a rich source of fibre foods is associated with lower risk of certain cancers, and phytoestrogens, are commonly consumed.142 particularly gastric, pancreatic, oesophageal, oral and Five case-control studies of diet and breast cancer laryngeal cancers.129,163–165 Epidemiological, animal showed decreased cancer risk to be associated with and clinical data suggest that vitamin E reduces oral high intake of soy bean products.143–146 Three of the carcinogenesis.165 Supplementation with vitamin E studies found a significantly reduced risk for pre- has been reported to protect against lung cancer in menopausal breast cancer143–145 and one a reduced non-smokers. Supplementation with vitamin E and risk for postmenopausal breast cancer.146 A case- b-carotene has been associated with a reduced control study showed that increased excretion of prostate cancer incidence and mortality by one-third some phytoestrogens was associated with substantial in men who smoke167,168 and combined vitamin E, reduction in breast cancer risk.147 Colon cancer rates b-carotene and selenium supplementation decreased are low in Japan and China, where intake of soy total mortality by reducing the rate of stomach cancer. The prevalence of esophageal cancer was also reduced.169,170 Epidemiological studies show Trans-unsaturated vegetable fats have adverse that increased intake of vegetables, fruits and caroten- effects on cholesterol profiles, and could increase oids and elevated blood levels of b-carotene are the risk of coronary heart disease.186 The Health consistently associated with reduced risk of lung Professionals Follow-up Study187 and the Alpha- cancer.156,157,171,172 Carotenoids may also reduce the risk of other cancers, such as breast, cervical, stom- Study188 showed a RR for coronary heart disease of ach and oropharyngeal, although the evidence is 1.4 and 1.39, respectively, for men in the upper less extensive and consistent.172 An inverse associ- quintile of dietary trans-fat intake. The Framingham ation between breast cancer and the total intake of Study found that after the first decade of follow-up, vitamin A (preformed vitamin A and carotenoids) the RR of coronary heart disease was 1.1 for each was seen in several case-control studies173 and in additional teaspoon of margarine eaten per day.189 The Nutrition Committee of the American Heart Recent long-term, large scale prospective trials, Association concluded that trans fat should be however, failed to demonstrate any beneficial effect replaced when possible by monounsaturated or poly- unsaturated oils in foods, because of its adverse supplementation on cancer risk in populations with essentially normal intake,159,167,175,176 and have raised Although serum cholesterol is a major determinant concern about harmful effects of these antioxidants of atherosclerosis, there are conflicting reports of its under certain conditions.167,176 In addition, two role in the pathogenesis of stroke. Two ecological smaller trials of b-carotene supplementation failed studies from Japan showed correlations between to demonstrate significant benefit in the prevention increased fat intake and decreased cerebrovascular of recurrent skin cancer177 and colon polyps.178 The mortality.191,192 A cohort study of Japanese men failure of supplementation with b-carotene and vit- living in Hawaii showed inverse association between amins A, C and E to reduce cancer risk may be total fat and saturated fat intake and all-stroke explained by these vitamins being markers for other mortality.33 In the Framingham Heart Study, which nutrients present in fruits and vegetables. b-Carotene was a population-based cohort study, intakes of fat, is one of 600 carotenoids that include lycopene, saturated fat and monounsaturated fat but not polyun- lutein and zeaxanthin, which are even more antioxid- saturated fat were associated with reduced risk of ant than b-carotene in laboratory studies.179 Similarly, ischaemic stroke in men.34 Low serum cholesterol there are many other plant compounds including has been shown to be a risk factor for haemorrhagic more than 4000 flavanoids that may be responsible stroke.193,194 These data imply that vegetarians have for beneficial (antioxidant) effects. The beneficial a higher risk for stroke as their intake of total fat and effects may be the result of a complex interaction saturated fat is low, and their serum cholesterol level between all the potential cancer-preventing sub- is low. However, a recent analysis of all published stances (carotenoids, flavanoids, folic acid, vitamins randomized trials of statin drugs showed that large A, C and E, selenium and fibre) in physiological reductions in cholesterol were associated with signi- doses rather than pharmacological doses of a single The major side effects of vegetarian diets that are high in fibre and leguminous seeds is increasedintestinal gas production, resulting in more flatulenceand eructations.43,189 Soy bean has a bland but somewhat beany aftertaste that may make it unap- diets56,180 and deficiencies in this vitamin have beenreported in vegetarians, especially vegans,56,181 andin breastfed infants of vegans.182–184 Most vegetable oils are low in saturated fatty acids. Coconut, palm and palm kernel oil, in contrast A well-balanced vegetarian diet chosen from a wide to other vegetable oils, are rich in saturated fatty variety of foods such as fresh fruits, vegetables, acids. Coconut and palm kernel oils are more whole grains, cereals, nuts, seeds, legumes, beans saturated than animal fats; palm oil has similar and soy bean is rich in monounsaturated and polyun- proportions of saturated fatty acids to those of animal saturated fatty acids (a-linolenic acid), minerals, fats.185 High intakes of saturated fatty acids have fibre, complex carbohydrate, antioxidant vitamins been associated with elevated plasma cholesterol [vitamins E, C and carotenoids (600; b-carotene, levels, and concern has been expressed about the lycopene, lutein, zeaxanthin)], flavanoids (4000), ‘atherogenicity’ of coconut and or palm oil in food folic acid and phytoestrogens, and is restricted in saturated fat. Substitution of plant sources of protein 12. Vecchia CL, Decarli A, Pagano R. Vegetable consumption for animal protein effectively decreases fat intake and risk of chronic disease. Epidemiology 1998; 9:208–10.
while increasing consumption of complex carbo- 13. Fraser GE, Sabate J, Beeson WL, Strahan TM. A possible protective effect of nut consumption on risk of coronary The burden of modern lifestyle diseases is enorm- heart disease. Arch Intern Med 1992; 152:1416–24.
ous when the costs of investigation, diagnosis, treat- 14. Prineas RJ, Kushi LH, Folsom AR, Bostick RM, Wu Y.
ment and primary and secondary prevention are Walnuts and serum lipids (Letter). N Engl J Med 1993; included. Thus, dietary intervention with a vegetarian diet seems to be a cheap, physiological and safe 15. Singh RB, Rastogi SS, Verma R, Bolaki L, Singh R. An approach for the prevention, and possibly manage- Indian experiment with nutritional modulation in acute ment of modern lifestyle diseases. Ideally, it should myocardial infarction. Am J Cardiol 1992; 69:879–85.
be complemented with other healthy lifestyle prac- 16. Singh RB, Rastogi SS, Verma R, Laxmi B, Singh R, Ghosh S, et al. Randomised controlled trial of cardioprotective diet tises such as regular exercise and abstinence from in patients with recent acute myocardial infarction: results of one year follow up. Br Med J 1992; 304:1015–19.
Recognizing these benefits, the US Public Health 17. Ellis FR, Sanders TAB. Angina and vegan diet. Am Heart J Service has recommended a national dietary goal of increasing overall per capita consumption of fruits 18. Ornish DM, Scherwitz LW, Doody RS, Kesten D, and vegetables in the American diet to at least five McLanahan SM, Brown SE, et al. Effects of stress servings a day by the year 2000 to improve health management training and dietary changes in treating ischemic heart disease. JAMA 1983; 249:54–9.
19. Ornish D, Brown SB, Scherwitz LW, Billings JH, Armstrong WT, Ports TA, et al. Can lifestyle changes reverse coronaryheart disease? Lancet 1990; 336:129–33.
20. Gould KL, Ornish D, Kirkeeide R, Brown S, Stuart Y, Buchi M, et al. Improved stenosis geometry by quantitative 1. Position of the American Dietetic Association: Vegetarian coronary arteriography after vigorous risk factor diets-technical support paper. J Am Diet Assoc 1988; modification. Am J Cardiol 1992; 69:845–53.
21. Verlangieri AJ, Kapeghian JC, El-Dean S, Bush M. Fruit and 2. Segasothy M, Bennett WM. Vegetarian diet: Relevance in vegetable consumption and cardiovascular disease renal disease. Review Article. Nephrology 1997; mortality. Med Hypotheses 1985; 16:7–15.
22. Acheson RM, Williams DRR. Does consumption of fruit 3. Simpson HCR, Simpson RW, Lousley S, Carter RD, and vegetables protect against stroke? Lancet 1983; Geekie M, Hockaday TD, et al. A high carbohydrate leguminous fiber diet improves all aspects of diabetic 23. Manson JE, Willett WC, Stampfer MJ, Colditz GA, Speizer control. Lancet 1981; 1:1–5.
FE, Hennekens CH. Vegetable and fruit consumption and 4. Jenkins DJA, Goff DV, Leeds AR, Alberti KGMM, incidence of stroke in women. Circulation (Abstract) 1994; Wolever TMS, Gassull MA, et al. Unabsorbable carbohydrate and diabetes: Decreased post-prandial 24. Gillman MV, Cupples LA, Gagnon D, Posner BM, hyperglycemia. Lancet 1976; 2:172–4.
Ellison RC, Castelli WP, et al. Protective effect of fruits and 5. Anderson JW. High fiber diets in diabetes and vegetables on development of stroke in men. JAMA 1995; hypertriglyceridemia. Can Med Assoc J 1980; 123:975–9.
6. Hjollund E, Pedersen O, Richelsen B, Beck-Nielsen H, 25. Tobian L, Lange JM, Johnson MA, MacNeill DA, Wilke TJ, Sorensen N. Increased insulin binding to adipocytes and Ulm KM, et al. High-K diets markedly reduce brain monocytes and increased insulin sensitivity of glucose hemorrhage and infarcts, death rate and mesenteric transport and metabolism in adipocytes from noninsulin arteriolar hypertrophy in stroke-prone spontaneously dependent diabetes after a low fat, high starch/high fiber hypertensive rats. J Hypertens 1986; 4 (Suppl 5):205–7S.
diet. Metabolism 1983; 32:1067–75.
26. Gey KF, Stahelin HB, Eichholzer M. Poor plasma status of 7. Anderson JW. High fiber diets for obese diabetic men on carotene and vitamin C is associated with higher mortality insulin therapy: short-term and long-term effects. In: from ischemic heart disease and stroke: Basel prospective Vahouny GV, ed. Dietary Fiber and Obesity. New York, study. Clin Investig 1993; 71:3–6.
27. Gale CR, Martyn CN, Winter PD, Cooper C. Vitamin C 8. Anderson JW. Plant fiber and blood pressure. Ann Intern and risk of death from stroke and coronary heart disease in cohort of elderly people. Br Med J 1995; 310:1563–6.
9. Kiehm TG, Anderson JW, Ward K. Beneficial effects of a 28. Manson JE, Stampfer MJ, Willett WC, Colditz GA, Speizer high carbohydrate, high fiber diet on hyperglycemic FE, Hennekens CH. Antioxidant vitamin consumption and diabetic men. Am J Clin Nutr 1976; 29:895–9.
incidence of stroke in women. Circulation (Abstract) 1993;87:678.
10. Anderson JW, Ward K. High carbohydrate, high fiber diets for insulin-treated men with diabetes mellitus. Am J Clin 29. Simon JA, Fong J, Bernert JT, Browner WS. Serum fatty acids and risk of stroke. Stroke 1995; 26:778–82.
11. Anderson JW, Chen WJL, Sieling B. Hypolipidemic effects 30. Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, of high carbohydrate, high fiber diets. Metabolism 1980; Rutherford JD, Cole TG, et al, for the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction Comparison of lipid levels in humans on a macadamia nut in patients with average cholesterol levels. N Engl J Med based high monounsaturated fat diet to their levels on a moderate fat diet and a high fat ‘typical American’ diet.
Presented at the American Heart Association’s Scientific 31. The Lipid Study Group. Design features and baseline Conference on Efficacy of Hypocholesterolemic Dietary characteristics of the LIPID (Long-Term Intervention with Interventions, 3–5 May 1995, San Antonio, Texas.
Pravastatin in Ischemic Disease) Study: a randomized trialin patients with previous acute myocardial infarction 49. Spiller GA, Jenkins DJA, Cragen LN, Gates JE, Bosello O, and/or unstable angina pectoris. Am J Cardiol 1995; Berra K, et al. Effect of a diet high in monounsaturated fat from almonds on plasma cholesterol and lipoproteins.
J Am Coll Nutr 1992; 11:126–30.
32. Scandinavian Simvastatin Survival Study Group: Randomized trial of cholesterol lowering in 4444 patients 50. Anderson JW, Story L, Sieling B, Chen WJ, Petro MS, with coronary heart disease: The Scandinavian Simvastatin Story J. Hypocholesterolemic effects of oat-bran or bean Survival Study (4S). Lancet 1994; 344: 1383–9.
intake for hypercholesterolemic men. Am J Clin Nutr 1984;40:1146–55.
33. McGee D, Reed D, Stemmerman G, Rhoads G, Yano K, Feinleib M. The relationship of dietary fat and cholesterol 51. Newman RK, Lewis SE, Newman CW, Boik RJ, to mortality in 10 years: the Honolulu Heart Program. Int Ramage RT. Hypocholesterolemic effect of barley foods on J Epidemiol 1985; 14:97–105.
healthy men. Nutr Rep Int 1989; 39:749–60.
34. Gillman MV, Cupples LA, Millen BE, Ellison RC, Wolf PA.
52. Federation of American Society for Experimental Biology.
Inverse association of dietary fat with development of Physiological effects and health consequences of dietary ischemic stroke in men. JAMA 1997; 278:2145–50.
fiber. Washington DC, Department of Health and Human 35. Sirtori CR, Agradi E, Mantero O, Cotti F, Gatti E. Soybean protein diet in the treatment of type II hyperlipidemia.
53. Ripsin CM, Keenan JM, Jacobs DR, Elmer PJ, Welch RR, Van Horn L, et al. Oat products and lipid lowering: a 36. Sirtori CR, Gatti E, Mantero O, Conti F, Agradi E, meta-analysis. JAMA 1992; 267:3317–25.
Tremoli E, et al. Clinical experience with the soybean 54. Davidson MH, Dugan LD, Burns JH, Bova J. The protein diet in the treatment of hypercholesterolemia. Am hypocholesterolemic effects of beta-glucan in oatmeal and J Clin Nutr 1979; 32:1645–58.
oat bran: a dose-controlled study. JAMA 1991; 265:833–9.
37. Goldberg AP, Lim A, Kolar JB, Grundhauser JJ, Steinke FH, 55. Jenkins DJA, Wolever TMS, Rao V, Hegele RA, Mitchell SJ, Schonfeld GS. Soybean protein independently lowers Ransom TPP, et al. Effect on blood lipids of very high plasma cholesterol levels in primary hypercholesterolemia.
intakes of fiber in diets low in saturated fat and cholesterol.
Atherosclerosis 1982; 43:355–67.
N Engl J Med 1993; 329:21–6.
38. Anderson JW, Johnstone BM, Cook-Newell ME. Meta- 56. Abdulla M, Andersson I, Asp N-G, Berthelsen K, analysis of the effects of soy protein intake on serum lipids.
Birkhed D, Dencker I, et al. Nutrient intake and health N Engl J Med 1995; 333:276–82.
status of vegans. Chemical analyses of diet using duplicate 39. Carroll KK, Kurowska EM. Soy consumption and portion sampling technique. Am J Clin Nutr 1981; cholesterol reduction; review of animal and human studies. J Nutr 1995; 125 (Suppl):594–7S.
57. Sanders TAB. The health and nutritional status of vegans.
40. Potter SM. Overview of proposed mechanisms for the Plant Foods Man 1978; 2:181–93.
hypocholesterolemic effect of soy. J Nutr 1995; 125 58. Miller DS, Mumford P. The nutritive value of Western vegan and vegetarian diets. Plant Foods Human Nutr 41. Mathur KS, Khan MA, Sharma RD. Hypocholesterolemic effect of Bengal gram. Br Med J 1968; 1:30–1.
59. Woods PD, Stafanick ML, Dreon DM, Hewitt BF, 42. Bingwen L, Zhaofeny W, Wanshen L, Rongjue Z. Effects of Garay SC, William PT, et al. Changes in plasma lipids and bean meal on serum cholesterol and triglycerides. Chinese lipoproteins in overweight men during weight loss through dieting as compared with exercise. N Engl J Med 1988;319:1173–8.
43. Jenkins DJ, Wong GS, Patten R, Bird J, Hall M, Buckley GL, et al. Leguminous seeds in the dietary management of 60. Schettler G. Cardiovascular diseases during and after hyperlipidemia. Am J Clin Nutr 1983; 38:567–73.
World War II: a comparison of Federal Republic of 44. Grande F, Anderson JT, Keys A. Effect of carbohydrates Germany with other European countries. Prev Med 1979; and leguminal seeds, wheat and potatoes on serum cholesterol concentration in man. J Nutr 1965; 86:313–7.
61. Wong ND, Cupples A, Ostfeld AM, Levy D, Kannel WB.
45. Dreher ML, Maher CV, Kearney P. The traditional and Risk factors for long term coronary prognosis after initial emerging role of nuts in healthful diets. Nutr Rev 1996; myocardial infarction: The Framingham Study. Am J Epidemiol 1989; 130:469–80.
46. Sabate J, Fraser GE, Burke K, Knutsen S, Bennett H, 62. Bagatell CA, Heymafield SB. Effect of meal size on Lindsted KD. Effects of walnuts on serum lipid levels and myocardial oxygen requirements: implications for blood pressure in normal men. N Engl J Med 1993; postmyocardial infarction diets. Am J Clin Nutr 1984; 47. Abbey M, Noakes M, Belling GB, Nestel PJ. Partial 63. National Diet-Heart Study Research Group: The National replacement of saturated fatty acids with almonds or Diet-Heart Study final report. Circulation 1968; 37 walnuts lowers total plasma cholesterol and low-density- lipoprotein cholesterol. J Clin Nutr 1994; 59:995–9.
64. Cagguila A, Christakis G, Farrand M, Hulley S, Johnson R, 48. Curb JD, Wergowski G, Dobbs J, Abbott RD, Huang B.
Lasser N, et al. The Multiple Risk Factor Intervention Trial (MRFIT): IV, Intervention on blood lipids. Prev Med 1981; flavanoids and coronary heart disease risk (Letter). Lancet 65. Kannel WB. New perspectives of cardiovascular risk 82. The effect of vitamin E and beta carotene on the incidence factors. Am Heart J 1987; 147:213–19.
of lung cancer and other cancers in male smokers. Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group.
66. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum N Engl J Med 1994; 330:1029–35.
JL. Beyond cholesterol: modification of low densitylipoprotein that increase its atherogenecity. N Engl J Med 83. Blot WJ, Li JY, Taylor PR, Guo W, Dawsey S, Wang GQ, et al. Nutrition intervention trials in Linxian, China:Supplementation with specific vitamin/mineral 67. Jessup W, Rankin SM, De Whalley CV, Hoult JR, Scott J, combinations, cancer incidence and disease-specific Leake DS. Alphatocopherol consumption during low- mortality in the general population. J Natl Cancer Int 1993; density lipoprotein oxidation. Biochem J 1990; 68. Sato K, Niki E, Shimasaki H. Free radical-mediated chain 84. Greenberg ER, Baron JA, Stukel TA, Stevens MM, oxidation of low density lipoproteins and its synergistic Mandel JS, Spencer SK, et al. A clinical trial of beta inhibition of vitamin E and vitamin C. Arch Biochem carotene to prevent basal-cell and squamous-cell cancers of the skin. The Skin Cancer Prevention Study Group. NEngl J Med 1990; 323:789–95.
69. Jialal I, Norkus EP, Cristol L, Grundy SM. beta-Carotene inhibits the oxidative modification of low-density 85. Wilson TS, Datta SB, Murrell JS, Andrews CT. Relation of lipoprotein. Biochem Biophys Acta 1991; 1086:134–8.
vitamin C levels to mortality in a geriatric hospital: a studyof the effect of vitamin C administration. Age Aging 1973; 70. De Whalley CV, Rankin SM, Hoult JRS, Jessup W, Leake DS. Flavanoids inhibit the oxidative modification oflow density lipoproteins by macrophages. Biochem 86. Rapola JM, Virtamo J, Haukka JK, Heinonen OP, Pharmacol 1990; 39:1743–50.
Albanes D, Taylor PR, et al. Effect of vitamin E and betacarotene on the incidence of angina pectoris. JAMA 1996; 71. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the riskof coronary disease in women. N Engl J Med 1993; 87. Rapola JM, Virtamo J, Ripatti S, Huttenen JK, Albanes D, Taylor PR, et al. Randomised trial of a-tocopherol and b-carotene supplements on incidence of major coronary 72. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, events in men with previous myocardial infarction. Lancet Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 1993;328:1450–6.
88. Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-term 73. Knekt P, Reunanen A, Jarvinen R, Seppanen R, supplementation with beta carotene on the incidence of Heliovaara M, Aromaa A. Antioxidant vitamin intake and malignant neoplasms and cardiovascular disease. N Engl coronary mortality in a longitudinal population study. Am J Epidemiol 1994; 139:1180–90.
89. Omenn GS, Goodman GE, Thornquist MD, Balmes J, 74. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick Cullen MR, Glass A, et al. Effects of a combination of beta RM. Dietary antioxidant vitamins and death from coronary carotene and vitamin A on lung cancer and cardiovascular heart disease in postmenopausal women. N Engl J Med disease. N Engl J Med 1996; 334:1150–5.
90. Stephens NG, Parsons A, Schofield PM, Kelly F, 75. Gey KF, Moser UK, Jordan P, Stahelin HB, Eichholzer M, Cheeseman K, Mitchinson MJ, et al. Randomised Ludin E. Increased risk of cardiovascular disease at controlled trial of vitamin E in patients with coronary suboptimal plasma concentrations of essential disease: Cambridge Heart Antioxidant Study (CHAOS).
antioxidants: an epidemiological update with special attention to carotene and vitamin C. Am J Clin Nutr 1993;57 (Suppl 5):787–97S.
91. Jha P, Flather M, Lonn E, Farouh M, Yusuf S. The antioxidant vitamins and cardiovascular disease. A critical 76. Morris DL, Kritchevsky SB, Davis LE. Serum carotenoids review of epidemiologic and clinical trial data. Ann Intern and coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study.
JAMA 1994; 272:1439–41.
92. Stampfer MJ, Malinow MR. Can lowering homocysteine 77. Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and levels reduce cardiovascular risks? N Engl J Med 1995; mortality among a sample of the United States population.
Epidemiology 1992; 3:194–202.
93. den Heijer M, Blom HJ, Gerrits WBJ, Rosendaal FR, Haak 78. Hertog MG, Feskens EJ, Hollman PC, Katan MB, HL, Wijermans PW, et al. Is hyperhomocysteinemia a risk Kromhout D. Dietary antioxidant flavanoids and the risk of factor for recurrent venous thrombosis. Lancet 1995; coronary heart disease: the Zutphen elderly study. Lancet 94. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, 79. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Fowler B, et al. Hyperhomocysteinemia: an independent Buzina R, Fidanza F, et al. Flavanoid intake and long-term risk factor for vascular disease. N Engl J Med 1991; risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 1995; 155:381–6.
95. Stamper MJ, Malinow R, Willett WC, Newcomer LM, 80. Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavanoid Upson B, Ullman D, et al. A prospective study of plasma intake and coronary mortality in Finland: a cohort study.
homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992; 268:877–8.
81. Hertog MGL, Feskens EJM, Kromhout D. Antioxidant 96. Boushey CJ, Beresford SAA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk 114. Khaw KT, Barrett-Connor E. Dietary fiber and reduced factor for vascular disease. JAMA 1995; 274:1049–57.
ischemic heart disease mortality rates in men and women:a 12-year prospective study. Am J Epidemiol 1987; 97. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vellset SM. Plasma homocysteine levels andmortality in patients with coronary artery disease. N Engl 115. Humble CG, Malarcher AM, Tyroler HA. Dietary fiber and coronary heart disease in middle-agedhypercholesterolemic men. Am J Prev Med 1993; 98. Selhub J, Jacques PF, Boston AG, D’Agastino RB, Wilson PWF, Belanger AJ, et al. Association between plasmahomocysteine concentrations and extracranial carotid- 116. Pietinen P, Rimm EB, Korhonen P, Hartman AM, Willett artery stenosis. N Engl J Med 1995; 332:286–91.
WC, Albanes D, et al. Intake of dietary fiber and risk ofcoronary heart disease in a cohort of Finnish men. The 99. Perry IJ, Refusm H, Morris RW, Ebrahim SB, Ueland PM, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Shaper AG. Prospective study of serum total homocysteine Study. Circulation 1996; 94:2720–7.
concentration and risk of stroke in middle-aged Britishmen. Lancet 1995; 436:1395–8.
117. Goodwin JS, Goodwin JM, Garry PJ. Association between nutritional status and cognitive functioning in a healthy 100. Petri M, Roubenoff R, Dallal GE, Nadeau MR, Selhub J, elderly population. JAMA 1983; 249:2917–21.
Rosenberg IH. Plasma homocysteine as a risk foratherothrombotic events in systemic lupus erythematosus.
118. Woo J, Ho SC, Mak YT, Swaminathan R. Association between mental and nutritional status in a healthy elderlyChinese population. Res Comm Psychol, Psychiat Behav 101. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH.
Vitamin status and intake as primary determinants ofhomocysteinemia in an elderly population. JAMA 1993; 119. Gale CR, Martyn CN, Cooper C. Cognitive impairment and mortality in a cohort of elderly people. Br Med J 1996;312:608–11.
102. Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, et al. Folate and vitamin B from diet and 120. Jackson CVE, Holland AJ, Williams CA, Dickerson JWT.
supplements in relation to risk of coronary heart disease Vitamin E and Alzheimer’s disease in subjects with Down’s among women. JAMA 1998; 279:359–64.
syndrome. J Mental Def Res 1988; 32:479–84.
103. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Willett 121. Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, WC. Dietary folate, vitamin B6, and vitamin B12 intake and Grundman M, et al. A controlled trial of selegiline, alpha- risk of CHD among a large population of men (Abstract).
tocopherol or both as treatment for Alzheimer’s disease. N Engl J Med 1997; 336:1216–22.
104. Morrison HI, Schaubel D, Desmeules M, Wigle DT. Serum 122. Klein R, Klein B, Linton KLP. Prevalence of age-related folate and risk of fatal coronary heart disease. JAMA 1996; maculopathy: the Beaver Dam Study. Opthalmology 1992; 105. Peterson JC, Spence JD. Vitamins and progression of 123. The Eye Disease Case-Control Study Group. Antioxidant atherosclerosis in hyper-homocyst(e)inaemia (Letter).
status and neovascular age-related macular degeneration.
Arch Ophthalmol 1993; 111:104–9.
106. Dolecek TA. Epidemiological evidence of relationship 124. Goldberg J, Flowerdew G, Smith E, Brody JA, Tso MOM.
between dietary polyunsaturated fatty acids and mortality Factors associated with age-related macular degeneration: in the multiple risk factor intervention trial. Proc Soc Exp an analysis of data from the First National Health and Nutrition Examination Survey. Am J Epidemiol 1998; 107. Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett C. Dietary fat and risk of coronary 125. Seddon JM, Ajani UA, Sperduto RD, Hiller R, Blair N, heart disease in men: cohort follow up study in the United Burton TC, et al. for the Eye Disease Case-Control Study States. Br Med J 1996; 313:84–90.
Group. Dietary carotenoids, vitamin A, C and E and 108. De Lorgeril M, Renaud S, Mamelle N, Salen P, Martin J-L, advanced age-related macular degeneration. JAMA 1994; Monjaud I, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease.
126. Schalch W. Carotenoids in the retina: a review of their possible role in preventing or limiting damage caused by 109. Kardinal AFM, Kok FJ, Ringstad J, Gomez-Aracena J, light and oxygen. In: Emerit I, Chance B, eds. Free Radicals Mazaev VP, Kohlmeier L, et al. Antioxidants in adipose and Aging. Basel, Birkhauser Verlag, 1992:280–98.
tissue and risk of myocardial infarction: the Euramic study.
127. Sommerburg O, Keunen JEE, Bird AC, van Kuijk FJGM.
Fruits and vegetables that are sources for lutein and 110. Renaud S, Nordoy A. Small is beneficial: a-linolenic acid zeaxanthin: the macular pigment in human eyes. Br and eicosapentaenoic acid in man. Lancet 1983; i:1169.
J Ophthalmol 1998; 82:907–10.
111. Burr ML, Fehily AM, Gilbert JF, Rogers S, Holliday RM, 128. Greenwald P, Lanza E, Eddy GA. Dietary fiber in the Sweetman PM, et al. Effects of changes in fat, fish, and reduction of colon cancer risk. J Am Diet Assoc 1987; fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989; 334:757–61.
129. Greenwald P. The future of nutrition research in cancer 112. Rimm EB, Ascherio A, Giovannucci E, Spiegelman D, prevention. In: Laidlaw W, ed. Vitamins and Cancer: Stampfer MJ, Willett WC. Vegetable, fruit, and cereal fiber Prevention, chap 9. New York, Wiley-Liss, 1991:111–27.
intake and risk of coronary heart disease among men.
130. Greenwald P, Clifford C. Dietary prevention. In: Greenwald P, Kramer BS, Weed DL, eds. Cancer 113. Morris JN, Marr JW, Clayton DG. Diet and heart: a prevention and control, chap 18. New York, Marcel postscript. Br Med J 1977; 2:1307–14.
131. Fisher N, Berry CS, Fearn T, Gregory JA, Hardy J. Cereal 150. Dwyer JT, Goldin BR, Saul N, Gaultieri L, Barakat S, dietary fiber consumption and diverticular disease: a Adlercreutz H. Tofu and soy drinks contain lifespan study in rats. Am J Clin Nutr 1985; 42:788–804.
phytoestrogens. J Am Diet Assoc 1994; 94:739–43.
132. Gear JSS, Ware A, Furdson P, Mann JI, Nolan DJ, Brodribb 151. Thompson LU, Robb P, Serraino M, Cheung P.
AJM, et al. Symptomless diverticular disease and intake of Mammalian lignan production from various foods. Nutr dietary fibre. Lancet 1979; 1:511–14.
133. Cummings JH, Southgate DAT, Branch W, Houston H, 152. Cassidy A, Bingham S, Setchell KDR. Biological effects of Jenkins DJA, James WPT. Colonic response to dietary fibre soy protein rich in isoflavones on the menstrual cycle of from carrot, cabbage, apple, bran and guargum. Lancet premenopausal women. Am J Clin Nutr 1994; 60:333–40.
153. Rose DP. Dietary phytoestrogens and breast cancer.
134. Ornstein MH, Littlewood ER, Baird IM, Fowler J, North WRS, Cox AG. Are fiber supplements really necessary in 154. Murrill WB, Brown NM, Zhang J-Y, Manzolillo PA, diverticular disease of the colon? A controlled clinical trial.
Barnes S, Lamartiniere CA. Prepubertal genistein exposure suppresses mammary cancer and enhances gland 135. Smith DA, Gee MI. A dietary survey to determine the differentiation in rats. Carcinogenesis 1996; 7:1451–7.
relationship between diet and cholelithiasis. Am J Clin 155. Colditz GA, Frazier AL. Models of breast cancer show that risk is set by events of early life: prevention efforts must 136. Scragg RKR, McMichael AJ, Baghurst PA. Diet, alcohol and switch focus. Cancer Epidem Biomarker Prevent 1995; relative weight in gall stone disease: A case-control study.
Br Med J 1984; 288:1113–19.
156. Peto R, Doll R, Buckley JD, Sporn MB. Can dietary beta- 137. Jenkins DJA, Hill MS, Cummings JH. Effect of wheat fibre carotene materially reduce human cancer rates? Nature on blood lipids, fecal steroid excretion and serum iron. Am J Clin Nutr 1975; 28:1408–11.
157. National Research Council. Diet, nutrition, and cancer.
138. Pomare EW, Heaton KW, Low-Beer TS, Espiner HJ. The Washington DC, National Academy Press, 1982.
effect of wheat bran upon bile salt metabolism and upon 158. Block G, Patterson B, Subar A. Fruits, vegetables, and lipid composition of bile in gallstone patients. Am J cancer prevention: a review of the epidemiology evidence.
139. National Academy of Sciences, National Research 159. Hunter DJ, Manson JE, Colditz GA, Stampfer MJ, Rosner B, Council, Commission on Life Sciences, Food and Nutrition Hennekens CH, et al. A prospective study of the intake of Board. Diet and Health: Implications for Reducing Chronic vitamins C, E and A and the risk of breast cancer. N Engl Disease Risk. Washington DC, National Academy 160. Steinmetz KA, Poiter JD. Vegetable, fruit, and cancer I: 140. Shanker S, Lanza E. Dietary fiber and cancer prevention.
epidemiology. Cancer Causes Control 1991; 2:325–58.
Hematol Oncol Clin North Am 1991; 5:25–41.
161. Lyon JL, Klauber MR, Gardner JW, Smart CR. Cancer 141. Von’t Veer P, Kolb CM, Verhoef P, Kok FJ, Schouten EG, incidence in Mormons and non-Mormons in Utah, Hermus RJJ, et al. Dietary fiber, beta-carotene and breast 1966–70. N Engl J Med 1976; 294:129–33.
cancer: results from a case-control study. Int J Cancer1990; 45:825–8.
162. Newberne PM, Suphakarn V. Nutrition and Cancer: A review with emphasis on the role of vitamins C and E and 142. Herman C, Adlercreutz T, Goldin BR, Gorbach SL, selenium. Nutr Cancer 1983; 5:107–19.
Hockerstedt KAV, Watanabe S, et al. Soybeanphytoestrogen intake and cancer risk. J Nutr 1995; 163. Chen LH, Boissonneault GA, Glauert HP. Vitamin C and vitamin E and Cancer (Review). Anticancer Res 1988;8:739–48.
143. Lee HP, Gourley L, Duffy SW, Esteve J, Day WE. Dietary effects on breast-cancer risk in Singapore. Lancet 1991; 164. Carpenter MP. Vitamins E and C in Neoplastic Development. In: Laidlaw W, ed. Vitamins and CancersPrevention, chap 6. New York, Wiley-Liss, 1991:61–90.
144. Hirose K, Tajima K, Hamajima N, Inoue M, Takezaki T, Kuroisha T, et al. A large-scale hospital-based case-control 165. Lippman SM, Hong WK, Benner SE. The chemoprevention study of risk factors of breast cancers according to of cancer. In: Greenwald P, Kramer BS, Weed DL, eds.
menopausal status. Jpn J Cancer Res 1995; 86:146–54.
Cancer prevention and control, chap 19. New York, 145. Yuan J-M, Wang Q-S, Ross RK, Henderson BE, Yu MC.
Diet and breast cancer in Shanghai and Tianjin, China. Br 166. Mayne ST, Janerich DT, Greenwald P, Chorost S, Tuccic C, Zaman MB, et al. Dietary beta carotene and lung cancer 146. Wu AH, Ziegler RG, Horn-Ross PL, Nomura AMY, risk in US nonsmokers. J Natl Cancer Inst 1994; 86:33–8.
West DW, Kolonel LN, et al. Tofu and risk of breast cancer 167. The Alpha-Tocopherol, Beta Carotene Cancer Prevention in Asian-Americans. Cancer Epidemiol Biomarkers Prev Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male 147. Ingram D, Sanders K, Kolybaba M, Lopez D. Case-control smokers. N Engl J Med 1994; 330:1029–35.
study of phyto-oestrogens and breast cancer. Lancet 1997; 168. Heinonen OP, Albanes D, Virtamo J, Taylor PR, Huttenen JK, Hartman AM, et al. Prostate cancer and 148. Adlercreutz H. Western diet and Western diseases: Some supplementation with a-tocopherol and b-carotene: hormonal and biochemical mechanisms and associations.
Incidence and mortality in a controlled trial. J Natl Cancer Scand J Clin Lab Invest 1990; 50:3–23.
149. Messina M, Barnes S. The role of soy products in reducing 169. Blot W, Li JY, Taylor PR, Guo W, Dawsey S, Wang GQ, risk of cancer. J Natl Cancer Inst 1991; 83:541–6.
et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral 183. Anonymous. Vitamin B12 deficiency in the breastfed infant combinations, cancer incidence and disease-specific of a strict vegetarian. Nutr Rev 1979; 37:142–4.
mortality in the general population. J Natl Cancer Inst 184. Higginbottom MC, Sweetman L, Nyhan WL. A syndrome of methylmalonic aciduria, homocystinuria, megaloblasticanemia and neurologic abnormalities in a vitamin B12- 170. Taylor PR, Li B, Dawsey SM, Li J-Y, Yang CS, Guo W, et al. deficient breast-fed infant of a strict vegetarian. N Engl Prevention of eosophageal cancer: the nutrition intervention trials in Linxian, China. Linxian NutritionIntervention Trials Study Group. Cancer Res 1994; 54 185. Council report. Saturated fatty acids in vegetable oils.
171. Shekelle RB, Lepper M, Liu S, Maliza C, Raynor WJ, Rossof 186. Byers T. Hardened fats, hardened arteries? N Engl J Med AH, et al. Dietary vitamin A and risk of cancer in the Western Electric Study. Lancet 1981; 2:1185–90.
187. Ascherio A, Rimm EB, Giovannucci EL, Spiegelman D, Stampfer M, Willett WC. Dietary fat and risk of coronary 172. Ziegler RG, Subar AF, Craff NE, Ursin G, Patterson BH, heart disease in men: cohort follow up study in the United Graubard BI. Does b-carotene explain why reduced States. Br Med J 1996; 313:84–90.
cancer risk is associated with vegetable and fruit intake?Cancer Res 1992; 52 (Suppl):2060–6S.
188. Pietinen P, Ascherio A, Korhonen P, Hartman AM, Willett WC, Albanes D, et al. Intake of fatty acids and risk of 173. Howe GR, Hirohata T, Hislop TG, Iscovich JM, Yuan J-M, coronary heart disease in a cohort of Finnish men: the Katsouyanni K, et al. Dietary factors and risk of breast Alpha Tocopherol, Beta-Carotene Cancer Prevention cancer: combined analysis of 12 case-control studies.
Study. Am J Epidemiol 1997; 145:876–87.
J Natl Cancer Inst 1990; 82:561–9.
189. Gillman MV, Cupples LA, Gagnon D, Millen BE, 174. Peganini-Hill A, Chao A, Ross RK, Henderson BE. Vitamin Ellison RC, Castelli WP. Margarine intake and subsequent A, b-carotene and the risk of cancer: a prospective study.
coronary heart disease in men. Epidemiology 1997; J Natl Cancer Inst 1987; 79:443–8.
175. Hennekens CH, Buring JE, Manson JE, Stampfer M, 190. Lichtenstein AH. Trans fatty acids, plasma lipid levels and Rosner B, Cook NR, et al. Lack of effect of long-term risk of developing cardiovascular disease: a statement for supplementation with beta carotene on the incidence of healthcare professionals from the American Heart malignant neoplasms and cardiovascular disease. N Engl Association. Circulation 1997; 95:2588–90.
191. Kimura N. Changing patterns of coronary heart disease, 176. Omens GS, Goodman GE, Thornquist MD, Balmes J, stroke and nutrient intake in Japan. Prev Med 1983; Cullen MR, Glass A, et al. Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular 192. Omura T, Hisamatsu S, Takizawa Y, Minowa M, disease. N Engl J Med 1996; 354:1150–5.
Yanagawa H, Schigematsu I. Geographical distribution of 177. Greenberg ER, Baron JA, Stukel TA, Stevens MM, cerebrovascular disease mortality and food intakes in Mandel JS, Spencer SK, et al. A clinical trial of beta Japan. Soc Sci Med 1987; 24:401–7.
carotene to prevent basal-cell and squamous-cell cancers 193. Committee on Diet and Health, Food and Nutrition Board, of the skin. N Engl J Med 1990; 323:789–95.
National Research Council. Diet and Health: Implicationsfor Reducing Chronic Disease Risk. Washington DC, 178. Greenberg ER, Baron JA, Tosteson TD, Freeman DH, Beck GJ, Bond JH, et al. A clinical trial of antioxidantvitamins to prevent colorectal adenoma. N Engl J Med 194. Neaton JD, Wentworth DN, Cutler J, Stamler J, Kuller L.
Risk factors for death from different types of stroke. AnnEpidemiol 1993; 3:493–9.
179. Palozza P, Krinksy NI. Antioxidant activity of carotenoids 195. Hebert PR, Gaziano M, Chan KS, Hennekens CH.
in vivo and in vitro: an overview. Meth Enzymol 1992; Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials. JAMA 180. Abdulla M, Aly K-O, Andersson I, Asp N-G, Birkhed D, Denker I, et al. Nutrient intake and health status of 196. Anderson JW, Gustafson NJ, Bryant CA, Tietyen- lactovegetarians. Chemical analyses of diet using duplicate Clark J. Dietary fiber and diabetes: A comprehensive portion sampling technique. Am J Clin Nutr 1984; review and practical application. J Am Diet Assoc 1987; 181. Sanders TA, Ellis FR, Dickerson JWT. Hematological 197. Public Health Service. Healthy People 2000. National studies on vegans. Br J Nutr 1978; 40:9–15.
Health Promotion and Disease Prevention Objectives— 182. Frader J, Reibman B, Turkewitz D. Vitamin B Full report, with commentary DHHS Publ (PHS ) 91-50212.
in strict vegetarians (Letter). N Engl J Med 1978; 299:1319.
Washington DC, US Dept Health Hum Serv, PHS, 1991.

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1. MacKerell, Jr., A.D., Vallari, R.C. and Pietruszko, R., Human mitochondrial aldehyde dehydrogenase inhibition by diethyldithiocarbamic acid methanethiol mixed disulphide: A derivative of disulfiram., FEBS Letters 179:77-81, 1985 2. MacKerell, Jr., A.D., Blatter, E.E. and Pietruszko, R., Human aldehyde dehydrogenase: Kinetic identification of the isozymes for which biogenic aldehydes and a

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