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Micronutrients: dietary intake v. supplement use

Published online by Cambridge University Press:  07 March 2007

Jayne V. Woodside ,
Damian McCall ,
Claire McGartland  and
Ian S. Young
Jayne V. Woodside*
Affiliation:
Nutrition and Metabolism Group, Centre for Clinical and Population Science, Mulhouse Building, Grosvenor Road, Belfast BT12 6BJ, UK
Damian McCall
Affiliation:
Nutrition and Metabolism Group, Centre for Clinical and Population Science, Mulhouse Building, Grosvenor Road, Belfast BT12 6BJ, UK
Claire McGartland
Affiliation:
Nutrition and Metabolism Group, Centre for Clinical and Population Science, Mulhouse Building, Grosvenor Road, Belfast BT12 6BJ, UK
Ian S. Young
Affiliation:
Nutrition and Metabolism Group, Centre for Clinical and Population Science, Mulhouse Building, Grosvenor Road, Belfast BT12 6BJ, UK
*
*Corresponding author: Dr Jayne Woodside, fax +44 28 90235900, email j.woodside@qub.ac.uk
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Abstract

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Whilst clinical deficiency of micronutrients is uncommon in the developed world, a suboptimal intake of certain micronutrients has been linked with an increased risk of chronic diseases such as CVD and cancer. Attention has therefore focused on increasing micronutrient status in order to theoretically reduce chronic disease risk. Increasing micronutrient status can involve a number of approaches: increasing dietary intake of micronutrient-rich foods; food fortification; use of supplements. Observational cohort studies have demonstrated an association between high intakes of micronutrients such as vitamin E, vitamin C, folic acid and β-carotene, and lower risk of CHD, stroke and cancer at various sites. However, randomised intervention trials of micronutrient supplements have, to date, largely failed to show an improvement in clinical end points. The discordance between data from cohort studies and the results so far available from clinical trials remains to be explained. One reason may be that the complex mixture of micronutrients found, for example, in a diet high in fruit and vegetables may be more effective than large doses of a small number of micronutrients, and therefore that intervention studies that use single micronutrient supplements are unlikely to produce a lowering of disease risk. Studies concentrating on whole foods (e.g. fruit and vegetables) or diet pattern (e.g. Mediterranean diet pattern) may be more effective in demonstrating an effect on clinical end points. The present review will consider the clinical trial evidence for a beneficial effect of micronutrient supplements on health, and review the alternative approaches to the study of dietary intake of micronutrients.

Keywords

MicronutrientsDiseaseSupplementationDietary intake
Type
Symposium on ‘Micronutrients through the life cycle’
Information
Proceedings of the Nutrition Society , Volume 64 , Issue 4 , November 2005 , pp. 543 - 553
Copyright
Copyright © The Nutrition Society 2005

References

Age-Related Eye Disease Study Research Group (2001) A randomised, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta-carotene, and zinc for age-related macular degeneration and vision loss. Archives of Ophthalmology 119, 1417–1436.CrossRefGoogle Scholar
Albert, CM, Hennekens, CH, O'Donnell, CJ, Ajani, UA, Carey, VJ, Willett, WC, Ruskin, JN & Manson, JE (1998) Fish consumption and risk of sudden cardiac death. Journal of the American Medical Association 279, 23–28.CrossRefGoogle ScholarPubMed
Alpha-Tocopherol, Beta Carotene Cancer Prevention Trial Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New England Journal of Medicine 330, 1029–1035.CrossRefGoogle Scholar
Alpha-Tocopherol, Beta Carotene Cancer Prevention Trial Study Group (2004) Incidence of cancer and mortality following alpha-tocopherol and beta-carotene supplementation: a postintervention follow-up. Journal of the American Medical Association 290, 476–485.Google Scholar
Ambring, A, Friberg, P, Axelsen, M, Laffrenzen, M, Taskinen, MR, Basu, S & Johansson, M (2004) Effects of a Mediterranean-inspired diet on blood lipids, vascular function and oxidative stress in healthy subjects. Clinical Science 106, 519–525.CrossRefGoogle ScholarPubMed
Appel, LJ, Moore, TJ, Obarzanek, E, Vollmer, WM, Svetkey, LP, Sacks, FM et al. . (1997) A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. New England Journal of Medicine 336, 1117–1124.CrossRefGoogle ScholarPubMed
Aviram, M & Fuhrman, B (1998) Polyphenolic flavonoids inhibit macrophage-mediated oxidation of LDL and attenuate atherogenesis. Atherosclerosis 137, S45–S50.CrossRefGoogle ScholarPubMed
Baker, F, Picton, D & Blackwood, S (2002) Blinded comparison of folic acid and placebo in patients with ischemic heart disease: an outcome trial. Circulation 106, II741S.Google Scholar
Balder, HF, Goldbohm, RA & van den Brandt, PA (2005) Dietary patterns associated with male lung cancer risk in the Netherlands Cohort Study. Cancer Epidemiology Biomarkers and Prevention 14, 483–490.CrossRefGoogle ScholarPubMed
Bazzano, LA, He, J, Ogden, LG, Loria, CM, Vapputuri, S, Myers, L & Whelton, PK (2002) Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. American Journal of Clinical Nutrition 76, 93–99.CrossRefGoogle ScholarPubMed
Bjelakovic, G, Nikolova, D, Simonetti, RG & Gluud, C (2004) Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet 364, 1219–1228.CrossRefGoogle ScholarPubMed
Boaz, M, Smetana, S, Weinstein, T, Matas, Z, Gafter, U, Iaina, A, Knecht, A, Weissgarten, Y, Brunner, D, Fainaru, M & Green, MS (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial. Lancet 356, 1213–1218.CrossRefGoogle ScholarPubMed
Bostom, AG & Garber, C (2000) Endpoints for homocysteine-lowering trials. Lancet 355, 511–512.CrossRefGoogle ScholarPubMed
Boushey, CJ, Beresford, SA, Omenn, GS & Motulsky, AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. Journal of the American Medical Association 274, 1049–1057.CrossRefGoogle ScholarPubMed
Brouwer, IA, van Dusseldorp, M, West, CE, Meyboom, S, Thomas, CMG, Duran, M, van het Hof, KH, Eskes, TKAB, Hautvast, JGAJ & Steegers-Theunissen, RPM (1999) Dietary folate from vegetables and citrus fruit decreases plasma homocysteine concentrations in humans in a dietary controlled trial. Journal of Nutrition 129, 1135–1139.CrossRefGoogle Scholar
Brown, AJ (1963) Regional differences in coronary heart disease in Britain: do antioxidant nutrients provide the key? Asia Pacific Journal of Clinical Nutrition 2, Suppl. 1. 33–36.Google Scholar
Brown, BG & Crowley, J (2005) Is there any hope for vitamin E? Journal of the American Medical Association 293, 1387–1390.CrossRefGoogle ScholarPubMed
Caballero, B (2003) Fortification, supplementation and nutrient balance. European Journal of Clinical Nutrition 57, S76–S78.CrossRefGoogle ScholarPubMed
Cao, G, Booth, SL, Sadowski, JA & Prior, RL (1998) Increases in human plasma antioxidant capacity after consumption of controlled diets high in fruit and vegetables. American Journal of Clinical Nutrition 68, 1081–1087.CrossRefGoogle ScholarPubMed
Chopra, M, O'Neill, ME, Keogh, N, Wortley, G, Southon, S & Thurnham, DI (2000) Influence of increased fruit and vegetable intake on plasma and lipoprotein carotenoids and LDL oxidation in smokers and non-smokers. Clinical Chemistry 46, 1818–1829.CrossRefGoogle Scholar
Daviglus, ML, Stamler, J, Orencia, AJ, Dyer, AR, Liu, K, Greenland, P, Walsh, MK, Morris, D & Shekelle, RB (1997) Fish consumption and the 30-year risk of fatal myocardial infarction. New England Journal of Medicine 336, 1046–1053.CrossRefGoogle ScholarPubMed
de Lorgeril, M, Renaud, S, Mamelle, N, Salen, P, Martin, JL, Monjaud, I, Guidollet, J, Touboul, P & Dleaye, J (1994) Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 343, 1454–1459.CrossRefGoogle ScholarPubMed
de Lorgeril, M, Salen, P, Martin, J-L, Monjaud, I, Boucher, P & Mamelle, N (1998) Mediterranean dietary pattern in a randomised trial. Prolonged survival and possible reduced cancer rate. Archives of Internal Medicine 158, 1181–1187.CrossRefGoogle Scholar
de Lorgeril, M, Salen, P, Martin, J-L, Monjaud, I, Delaye, J & Mamelle, N (1999) Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction. Final report of the Lyon Diet Heart Study. Circulation 99, 779–785.CrossRefGoogle ScholarPubMed
de Stefani, E, Boffetta, P, Ronco, AL, Correa, P, Oreggia, F, Deneo-Pellegrini, H, Mendilaharsu, M & Leiva, J (2005) Dietary patterns and risk of cancer of the oral cavity and pharynx in Uruguay. Nutrition and Cancer 51, 132–139.CrossRefGoogle ScholarPubMed
Dragsted, LO, Pedersen, A, Hermetter, A, Basu, S, Hansen, M, Haren, GR et al. . (2004) The 6-a-day study: effects of fruit and vegetables on markers of oxidative stress and antioxidative defense in healthy non-smokers. American Journal of Clinical Nutrition 79, 1060–1072.CrossRefGoogle Scholar
El-Kadiki, A & Sutton, AJ (2005) Role of multivitamins and mineral supplements in preventing infections in elderly people: systematic review and meta-analysis of randomised controlled trials. British Medical Journal 330, 871–876.CrossRefGoogle ScholarPubMed
Esposito, K, Marfella, R, Ciotola, M, di Palo, C, Giugliano, F, Giugliano, G, d'Armiento, M, d'Andrea, F & Giugliano, D (2004) Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome. A randomised trial. Journal of the American Medical Association 292, 1440–1446.CrossRefGoogle Scholar
Esposito, K, Nappo, F, Giugliano, F, Giugliano, G, Marfella, R & Giugliano, D (2003) Effect of dietary antioxidants on post-prandial endothelial dysfunction induced by a high fat meal in healthy subjects. American Journal of Clinical Nutrition 77, 139–143.CrossRefGoogle ScholarPubMed
Fairfield, KM & Fletcher, RH (2002) Vitamins for chronic disease prevention in adults. Journal of the American Medical Association 287, 3116–3126.CrossRefGoogle ScholarPubMed
Fawzi, WW, Msamanga, GI, Spiegelman, D, Wei, R, Kapiga, S, Villamor, E, Mwakagile, D, Mugusi, F, Hertzmark, E, Essex, M & Junter, DJ (2004) A randomised trial of multivitamin supplements and HIV disease progression and mortality. New England Journal of Medicine 351, 23–32.CrossRefGoogle ScholarPubMed
Fuentes, F, Lopez-Miranda, J, Sanchez, E, Sanchez, F, Paez, J, Paz-Rojas, E, Marin, C, Gomez, P, Jimenez-Peraperez, J, Ordovas, JM & Perez-Jimenez, F (2001) Mediterranean and low-fat diets improve endothelial function in hypercholesterolemic men. Annals of Internal Medicine 134, 1115–1119.CrossRefGoogle ScholarPubMed
Fung, TT, Hu, FB, Holmes, MD, Rosner, BA, Hunter, DJ, Colditz, GA & Willett, WC (2005) Dietary patterns and the risk of postmenopausal breast cancer. International Journal of Cancer 116, 116–121.CrossRefGoogle ScholarPubMed
Fung, TT, Rimm, EB, Spiegelman, D, Rifai, N, Tofler, GH, Willett, WC & Hu, FB (2001) Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk. American Journal of Clinical Nutrition 73, 61–67.CrossRefGoogle ScholarPubMed
Gardner, CD, Coulston, A, Chatterjee, L, Rigby, A, Spiller, G & Farquhar, JW (2005) The effect of a plant-based diet on plasma lipids in hypercholesterolemic adults: a randomized trial. Annals of Internal Medicine 142, 725–733.CrossRefGoogle ScholarPubMed
GISSI-Prevenzione Trial Group (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 354, 447–455.CrossRefGoogle Scholar
Goodman, GE, Thornquist, MD, Balmes, J, Cullen, MR, Meyskens, FL, Omenn, GS, Valanis, B, Williams, JH Jr (2004) The Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. Journal of the National Cancer Institute 96, 1743–1750.CrossRefGoogle ScholarPubMed
Heart Protection Study Collaborative Group (2002) MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet 360, 23–33.CrossRefGoogle Scholar
Hogg, R & Chakravarthy, U (2004) AMD and micronutrient antioxidants. Current Eye Research 29, 387–401.CrossRefGoogle ScholarPubMed
Homocysteine Studies Collaboration (2002) Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. Journal of the American Medical Association 288, 2015–2022.CrossRefGoogle Scholar
Hu, FB (2002) Dietary pattern analysis: a new direction in nutritional epidemiology. Current Opinion in Lipidology 13, 3–9.CrossRefGoogle ScholarPubMed
Hu, FB, Rimm, EB, Stampfer, MJ, Ascherio, A, Spiegelman, D & Willett, WC (2000) Prospective study of major dietary patterns and risk of coronary heart disease in men. American Journal of Clinical Nutrition 72, 912–921.CrossRefGoogle ScholarPubMed
Hung, HC, Joshipura, KJ, Jiang, R, Hu, FB, Hunter, D, Smith-Warner, SA, Colditz, GA, Rosner, B, Spiegelman, D & Willett, WC (2004) Fruit and vegetable intake and risk of major chronic disease. Journal of the National Cancer Institute 96, 1577–1584.CrossRefGoogle ScholarPubMed
Huxley, RR, Lean, M, Crozier, A, John, JH & Neil, HAW (2004) Effect of dietary advice to increase fruit and vegetable consumption on plasma flavonol concentrations: results from a randomised controlled intervention trial. Journal of Epidemiology and Community Health 58, 288–289.CrossRefGoogle ScholarPubMed
Johansen, JS, Harris, AK, Rychly, DJ & Ergul, A (2005) Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovascular Diabetology 4, 5–16.CrossRefGoogle ScholarPubMed
John, JH, Ziebland, S, Yudkin, P, Roe, LS & Neil, HA (2002) Effects of fruit and vegetable consumption on plasma antioxidant concentrations and blood pressure: a randomised controlled trial. Lancet 359, 1969–1974.CrossRefGoogle ScholarPubMed
Joshipura, KJ, Ascherio, A, Manson, JE, Stampfer, MJ, Rimm, EB, Speizer, FE, Hennekens, CH, Spiegelman, D & Willett, WC (1999) Fruit and vegetable intake in relation to risk of ischaemic stroke. Journal of the American Medical Association 282, 1233–1239.CrossRefGoogle Scholar
Joshipura, KJ, Hu, FB, Manson, JE, Stampfer, MJ, Rimm, EB, Speizer, FE, Colditz, G, Ascherio, A, Rosner, B, Spiegelman, D & Willett, WC (2001) The effect of fruit and vegetable intake on risk for coronary heart disease. Annals of Internal Medicine 134, 1106–1114.CrossRefGoogle ScholarPubMed
Kerver, JM, Yang, EJ, Bianchi, L & Song, WO (2003) Dietary patterns associated with risk factors for cardiovascular disease in healthy US adults. American Journal of Clinical Nutrition 78, 1103–1110.CrossRefGoogle ScholarPubMed
Key, TJ, Fraser, GE, Thorogood, M, Appleby, PN, Beral, V, Reeves, G et al. . (1999) Mortality in vegetarians and nonvegetarians: detailed findings from a collaborative analysis of 5 prospective studies. American Journal of Clinical Nutrition 70, 516S–524S.CrossRefGoogle ScholarPubMed
Kim, MK, Sasaki, S, Otani, T & Tsugane, S (2005) Dietary patterns and subsequent colorectal cancer risk by subsite: a prospective cohort study. International Journal of Cancer 115, 790–798.CrossRefGoogle ScholarPubMed
Knoops, KTB, de Groot, LCPGM, Kromhout, D, Perrin, A-E, Moreiras-Varela, O, Menotti, A & van Staveren, WA (2004) Mediterranean diet, lifestyle factors, and 10-year mortality in elderly European men and women. The HALE Project. Journal of the American Medical Association 292, 1433–1439.CrossRefGoogle ScholarPubMed
Kris-Etherton, P, Eckel, RH, Howard, BV, St Jeor, S & Bazzarre, TL (2001) Lyon diet heart study. Benefits of a Mediterranean-style, national cholesterol education program/American Heart Association Step I dietary pattern on cardiovascular disease. Circulation 103, 1823–1825.CrossRefGoogle ScholarPubMed
Lanzillotti, JS & Tang, AM (2005) Micronutrients and HIV disease: a review pre- and post-HAART. Nutrition and Clinical Care 8, 16–23.Google ScholarPubMed
Leaf, A (1999) Dietary prevention of coronary heart disease: the Lyon Diet Heart Study (editorial; comment). Circulation 99, 733–735.CrossRefGoogle Scholar
Liem, AH, van Boven, AJ, Veeger, NJ, Withagen, AJ, Robles, de, Medina, RM, Tijssen, JG & van Veldhuisen, DJ (2004) Folic Acid on Risk Diminishment After Acute Myocardial Infarction Study Group. Efficacy of folic acid when added to statin therapy in patients with hypercholesterolemia following acute myocardial infarction: a randomised pilot trial. International Journal of Cardiology 93, 175–179.CrossRefGoogle Scholar
Liu, S, Manson, JE, Lee, I-M, Cole, SR, Hennekens, CH, Willett, WC & Buring, JE (2000) Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study. American Journal of Clinical Nutrition 72, 922–928.CrossRefGoogle ScholarPubMed
Lock, K, Pomerleau, J, Causer, L, Altmann, DR & McKee, M (2005) The global burden of disease attributable to low consumption of fruit and vegetables: implications for the global strategy on diet. Bulletin of the World Health Organization 83, 100–108.Google ScholarPubMed
Lonn, E, Bosch, J, Yusuf, S, Sheridan, P, Pogue, J, Arnold, JM, Ross, C, Arnold, A, Sleight, P, Probstfield, J & Dagenais, GR (2005) Effect of long-term vitamin E supplementation on cardiovascular events and cancer. A randomised controlled trial. Journal of the American Medical Association 293, 1338–1347.Google Scholar
Lopez-Garcia, E, Schulze, MB, Fung, TT, Meigs, JB, Rifai, N, Manson, JE & Hu, FB (2004) Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. American Journal of Clinical Nutrition 80, 1029–1035.CrossRefGoogle Scholar
Michaud, DS, Skinner, HG, Wu, K, Hu, F, Giovannucci, E, Willett, WC, Colditz, GA & Fuchs, CS (2005) Dietary patterns and pancreatic cancer risk in men and women. Journal of the National Cancer Institute 97, 518–524.CrossRefGoogle ScholarPubMed
Miller, ER, Pastor-Barriuso, R, Dalal, D & Riemersma, RA (2005) Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Annals of Internal Medicine 142, 37–46.CrossRefGoogle ScholarPubMed
MRC Vitamin Study Research Group (1991) Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 338, 131–137.CrossRefGoogle Scholar
Napoli, C, Williams-Ignarro, S, De Nigris, F, Lerman, LO, Rossi, L, Guarino, C et al. . (2004) Long-term combined beneficial effects of physical training and metabolic treatment on atherosclerosis in hypercholesterolemic mice. Proceedings of the National Academy of Sciences USA 101, 8797–8802.CrossRefGoogle ScholarPubMed
Ness, A, Egger, M & Powles, J (1999) Fruit and vegetables and ischaemic heart disease: systematic review or misleading meta-analysis? European Journal of Clinical Nutrition 53, 900–904.CrossRefGoogle ScholarPubMed
Nigdikar, SV, Williams, NR, Griffin, BA & Howard, AN (1998) Consumption of red wine polyphenols reduces the susceptibility of LDL to oxidation in vivo. American Journal of Clinical Nutrition 8, 258–265.Google Scholar
Omenn, GS, Goodman, GE, Thornquist, MD, Balmes, J, Cullen, MR, Glass, A et al. . (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. New England Journal of Medicine 334, 1150–1155.CrossRefGoogle ScholarPubMed
Osler, M, Heitmann, BL, Gerdes, LU, Jorgensen, LM & Schroll, M (2001) Dietary patterns and mortality in Danish men and women: a prospective observational study. British Journal of Nutrition 85, 219–225.CrossRefGoogle ScholarPubMed
Peto, R, Doll, R, Buckley, JD & Sporn, MB (1981) Can dietary beta-carotene materially reduce human cancer rates? Nature 290, 201–209.CrossRefGoogle ScholarPubMed
Rapola, JM, Virtamo, J, Ripatti, S, Huttunen, JK, Albanes, D, Taylor, PR & Heinonen, OP (1997) Randomised trial of α-tocopherol and β-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 349, 1715–1720.CrossRefGoogle ScholarPubMed
Rimm, EB, Stampfer, MJ, Ascherio, A, Giovannucci, E, Colditz, GA & Willett, WC (1993) Vitamin E consumption and the risk of coronary heart disease in men. New England Journal of Medicine 328, 1450–1456.CrossRefGoogle ScholarPubMed
Rimm, EB, Willett, WC, Hu, FB, Sampson, L, Colditz, GA, Manson, JE, Hennekens, C & Stampfer, MJ (1998) Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. Journal of the American Medical Association 279, 359–364.CrossRefGoogle ScholarPubMed
Ros, E, Nunez, I, Perez-Heras, A, Serra, M, Gilabert, R, Casals, E & Deulofeu, R (2004) A walnut diet improves endothelial function in hypercholesterolaemic subjects: a randomised crossover trial. Circulation 109, 1609–1614.CrossRefGoogle Scholar
Sacks, FM, Svetkey, LP, Vollmer, WM, Appel, LJ, Bray, GA, Harsha, D et al. . (2001) DASH-Sodium Collaborative Research Group. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. New England Journal of Medicine 344, 3–10.CrossRefGoogle Scholar
Schnyder, G, Roffi, M, Pin, R, Flammer, Y, Lange, H, Eberli, FR, Meier, B, Turi, ZG & Hess, OM (2001) Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. New England Journal of Medicine 345, 1593–1600.CrossRefGoogle ScholarPubMed
Segasothy, M & Phillips, PA (1999) Vegetarian diet: panacea for modern lifestyle diseases? Quarterly Journal of Medicine 92, 531–544.CrossRefGoogle ScholarPubMed
Serdula, MK, Byers, T, Mokdad, AH, Simoes, E, Mendlein, JM & Coates, RJ (1996) The association between fruit and vegetable intake and chronic disease risk factors. Epidemiology 7, 161–165.CrossRefGoogle ScholarPubMed
Singh, RB, Dubnov, G, Niaz, MA, Ghosh, S, Singh, R, Rastogi, SS, Manor, O, Pella, D & Berry, EM (2002) Effect of an Indo-Mediterranean diet on progression of coronary artery disease in high risk patients (Indo-Mediterranean Diet Heart Study): a randomised single-blind trial. Lancet 360, 1455–1461.CrossRefGoogle ScholarPubMed
Singh, RB, Rastogi, SS, Niaz, MA, Ghosh, S, Singh, R & Gupta, S (1992a) Effect of fat-modified and fruit-enriched and vegetable-enriched diets on blood lipids in the Indian Diet Heart Study. American Journal of Cardiology 70, 869–874.CrossRefGoogle Scholar
Singh, RB, Rastogi, SS, Verma, R, Laxmi, B, Singh, R, Ghosh, S & Niaz, MA (1992b) Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of a one year follow up. British Medical Journal 304, 1015–1019.CrossRefGoogle ScholarPubMed
Slattery, ML, Jacobs, DR, Dyer, A, Benson, J, Hilmer, JE & Caan, BJ (1995) Dietary antioxidants and plasma lipids: the CARDIA study. Journal of the American College of Nutrition 14, 635–642.CrossRefGoogle ScholarPubMed
Sommer, A, Tarwotjo, I, Djunaedi, E, West, KP, Loeden, AA & Tilden, R (1986) Impact of vitamin A supplementation on childhood mortality. Lancet i, 1169–1173.CrossRefGoogle Scholar
Sondergaard, E, Moller, JE & Egstrup, K (2003) Effect of dietary intervention and lipid-lowering treatment on brachialvasoreactivity in patients with ischaemic heart disease and hypercholesterolaemia. American Heart Journal 145 E19.CrossRefGoogle Scholar
Stampfer, MJ, Hennekens, CH, Manson, JE, Colditz, GA, Rosner, B & Willett, WC (1993) Vitamin E consumption and the risk of coronary heart disease in women. New England Journal of Medicine 328, 1444–1449.CrossRefGoogle Scholar
Toole, JF, Malinow, MR, Chambless, LE, Spence, JD, Pettigrew, LC, Howard, VJ, Sides, EG, Wang, CH & Stampfer, M (2004) Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. Journal of the American Medical Association 291, 565–575.CrossRefGoogle ScholarPubMed
Trichopoulou, A, Costacou, T, Bamia, C & Trichopoulos, D (2003) Adherence to a Mediterranean diet and survival in a Greek population. New England Journal of Medicine 348, 2599–2608.CrossRefGoogle Scholar
Trichopoulou, A, Orfanos, P, Norat, T, Bueno-de-Mesquita, B, Ocke, MC, Peeters, PH et al. . (2005) Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study. British Medical Journal 330, 991–998.CrossRefGoogle ScholarPubMed
Tucker, KL, Chen, H, Hannan, MT, Cupples, LA, Wilson, PWF, Felson, D & Kiel, DP (2002) Bone mineral density and dietary patterns in older adults: the Framingham Osteoporosis Study. American Journal of Clinical Nutrition 76, 245–252.CrossRefGoogle ScholarPubMed
Tucker, KL, Hallfrisch, J, Qiao, N, Muller, D, Andres, R & Fleg, JL (2005) The combination of high fruit and vegetable and low saturated fat intakes is more protective against mortality in ageing men than is either alone: the Baltimore Longitudinal Study of Ageing. Journal of Nutrition 135, 556–561.CrossRefGoogle Scholar
Tunstall-Pedoe, H, Kuulasmaa, K, Mahonen, M, Tolonen, H, Ruokokoski, E & Amouyel, P (1999) Contribution of trends in survival and coronary-event rate to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations: monitoring trends and determinants in cardiovascular disease. Lancet 353, 1547–1557.CrossRefGoogle ScholarPubMed
Vermeulen, EJ, Stehouwer, CA, Twisk, JR, van den, Berg, M, de, Jong, SC, Mackaay, AJ, van Campen, CM, Visser, FC, Jakobs, CA, Bulterjis, EJ & Rauwerda, JA (2000) Effect of homocysteine-lowering treatment with folic acid plus vitamin B-6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial. Lancet 355, 517–522.CrossRefGoogle ScholarPubMed
Vivekananthan, DP, Penn, MS, Sapp, SK, Hsu, A & Topol, EJ (2003) Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 361, 2017–2023.CrossRefGoogle ScholarPubMed
Vogel, RA, Corretti, MC & Plotnick, GD (2000) The postprandial effect of components of the Mediterranean diet on endothelial function. Journal of the American College of Cardiology 36, 1455–1460.CrossRefGoogle ScholarPubMed
Voutilainen, S, Rissanen, TH, Virtanen, J, Lakka, TA, Salonen, JT & Kuopio Ischemic Heart Disease Risk Factor Study (2001) Low dietary folate intake is associated with an excess incidence of acute coronary events: The Kuopio Ischemic Heart Disease Risk Factor Study. Circulation 103, 2674–2680.CrossRefGoogle ScholarPubMed
Wald, DS, Law, M & Morris, JK (2002) Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. British Medical Journal 325, 1202.CrossRefGoogle ScholarPubMed
Walker, M, Aronson, KJ, King, W, Wilson, JW, Fan, W, Heaton, JP, MacNeily, A, Nickel, JC & Morales, A (2005) Dietary patterns and risk of prostate cancer in Ontario, Canada. International Journal of Cancer 116, 592–598.CrossRefGoogle ScholarPubMed
Wise, JA, Morin, RJ, Sanderson, R & Blum, K (1996) Changes in plasma carotenoid, alpha-tocopherol, and lipid peroxide levels in response to supplementation with concentrated fruit and vegetable extracts – a pilot study. Current Therapeutic Research Clinical and Experimental 57, 445–461.CrossRefGoogle Scholar
Zino, S, Skeaff, M, Williams, S & Mann, J (1997) Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants. British Medical Journal 314, 1787–1791.CrossRefGoogle ScholarPubMed
Zureik, M, Galan, P, Bertrais, S, Mennen, L, Czernichow, S, Blacher, J, Ducimetiere, P & Hercberg, S (2004) Effects of long-term daily low-dose supplementation with antioxidant vitamins and minerals on structure and function of large arteries. Arteriosclerosis, Thrombosis, and Vascular Biology 24, 1485–1491.CrossRefGoogle ScholarPubMed