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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: 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. 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Recipe: name of dish

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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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