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  • Review Article
  • Published:

Dietary supplements and disease prevention — a global overview

Key Points

  • In developing countries, limited access or adaptation to a healthful, well-balanced diet can cause micronutrient malnutrition, with irreversible health consequences affecting morbidity and mortality

  • Deficiencies in vitamin A and/or iron are prevalent among reproductive-aged women, infants and children in developing countries, with therapeutic doses required for treatment

  • In developing and developed countries, reproductive-aged women or those who are pregnant must ensure adequate intakes of folic acid, iron, calcium and iodine, which might require supplementation

  • In developed countries, adequate nutrient intake can usually be achieved through a well-balanced diet and supplementation might not confer additional health benefits (except among individuals with increased requirements)

  • Postmenopausal women and elderly men could benefit from a combination of low-dose calcium and vitamin D for bone health

  • Use of a multivitamin supplement with low levels of essential vitamins and minerals could be linked to reductions in the incidence of cancer and cataracts among men

Abstract

Dietary supplements are widely used and offer the potential to improve health if appropriately targeted to those in need. Inadequate nutrition and micronutrient deficiencies are prevalent conditions that adversely affect global health. Although improvements in diet quality are essential to address these issues, dietary supplements and/or food fortification could help meet requirements for individuals at risk of deficiencies. For example, supplementation with vitamin A and iron in developing countries, where women of reproductive age, infants and children often have deficiencies; with folic acid among women of reproductive age and during pregnancy; with vitamin D among infants and children; and with calcium and vitamin D to ensure bone health among adults aged ≥65 years. Intense debate surrounds the benefits of individual high-dose micronutrient supplementation among well-nourished individuals because the alleged beneficial effects on chronic diseases are not consistently supported. Daily low-dose multivitamin supplementation has been linked to reductions in the incidence of cancer and cataracts, especially among men. Baseline nutrition is an important consideration in supplementation that is likely to modify its effects. Here, we provide a detailed summary of dietary supplements and health outcomes in both developing and developed countries to help guide decisions about dietary supplement recommendations.

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References

  1. World Health Organization. World health statistics 2012. [online] http://apps.who.int/iris/bitstream/10665/44844/1/9789241564441_eng.pdf, (2012).

  2. Bjelakovic, G., Nikolova, D., Gluud, L. L., Simonetti, R. G. & Gluud, C. Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases. Cochrane Database Syst. Rev. 3, CD007176 (2012).

    Google Scholar 

  3. Fortmann, S. P., Burda, B. U., Senger, C. A., Lin, J. S. & Whitlock, E. P. Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: an updated systematic evidence review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 159, 824–834 (2013).

    PubMed  Google Scholar 

  4. International Food Policy Research Institute. 2014 global nutrition report: actions and accountability to accelerate the world's progress on nutrition. [online] http://ebrary.ifpri.org/utils/getfile/collection/p15738coll2/id/128484/filename/128695.pdf, (2014).

  5. World Health Organization. World health statistics 2014. [online] http://apps.who.int/iris/bitstream/10665/112738/1/9789240692671_eng.pdf, (2014).

  6. World Health Organization. Global action plan for the prevention and control of noncommunicable diseases 2013–2020. [online] http://apps.who.int/iris/bitstream/10665/94384/1/9789241506236_eng.pdf, (2013).

  7. International Food Policy Research Institute. 2015 global nutrition report: actions and accountability to advance nutrition and sustainable development. [online] http://www.fao.org/fileadmin/user_upload/raf/uploads/files/129654.pdf, (2015).

  8. World Health Organization. The global prevalence of anaemia in 2011. [online] http://apps.who.int/iris/bitstream/10665/177094/1/9789241564960_eng.pdf, (2015).

  9. Rasheed, S. & Woods, R. T. Malnutrition and quality of life in older people: a systematic review and meta-analysis. Ageing Res. Rev. 12, 561–566 (2013).

    PubMed  Google Scholar 

  10. Bailey, R. L. et al. Dietary supplement use in the United States, 2003–2006. J. Nutr. 141, 261–266 (2011).

    CAS  PubMed  Google Scholar 

  11. Shakur, Y. A., Tarasuk, V., Corey, P. & O'Connor, D. L. A comparison of micronutrient inadequacy and risk of high micronutrient intakes among vitamin and mineral supplement users and nonusers in Canada. J. Nutr. 142, 534–540 (2012).

    CAS  PubMed  Google Scholar 

  12. Lee, J. S. & Kim, J. Factors affecting the use of dietary supplements by Korean adults: data from the Korean National Health and Nutrition Examination Survey III. J. Am. Diet. Assoc. 109, 1599–1605 (2009).

    PubMed  Google Scholar 

  13. Lentjes, M. A., Welch, A. A., Keogh, R. H., Luben, R. N. & Khaw, K. T. Opposites don't attract: high spouse concordance for dietary supplement use in the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study. Publ. Health Nutr. 18, 1060–1066 (2015).

    Google Scholar 

  14. Messerer, M., Johansson, S. E. & Wolk, A. Sociodemographic and health behaviour factors among dietary supplement and natural remedy users. Eur. J. Clin. Nutr. 55, 1104–1110 (2001).

    CAS  PubMed  Google Scholar 

  15. Li, K., Kaaks, R., Linseisen, J. & Rohrmann, S. Consistency of vitamin and/or mineral supplement use and demographic, lifestyle and health-status predictors: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort. Br. J. Nutr. 104, 1058–1064 (2010).

    CAS  PubMed  Google Scholar 

  16. Pouchieu, C. et al. Sociodemographic, lifestyle and dietary correlates of dietary supplement use in a large sample of French adults: results from the NutriNet-Sante cohort study. Br. J. Nutr. 110, 1480–1491 (2013).

    CAS  PubMed  Google Scholar 

  17. Skeie, G. et al. Use of dietary supplements in the European Prospective Investigation into Cancer and Nutrition calibration study. Eur. J. Clin. Nutr. 63, S226–S238 (2009).

    CAS  PubMed  Google Scholar 

  18. Gaziano, J. M. et al. Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 308, 1871–1880 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Hercberg, S. et al. The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals. Arch. Intern. Med. 164, 2335–2342 (2004).

    CAS  PubMed  Google Scholar 

  20. Galan, P. et al. Antioxidant status and risk of cancer in the SU.VI.MAX study: is the effect of supplementation dependent on baseline levels? Br. J. Nutr. 94, 125–132 (2005).

    CAS  PubMed  Google Scholar 

  21. Blot, W. J. et al. Nutrition intervention trials in Linxian, China: supplementation with specific vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J. Natl Cancer Inst. 85, 1483–1492 (1993).

    CAS  PubMed  Google Scholar 

  22. Chowdhury, R. et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ 348, g1903 (2014).

    PubMed  PubMed Central  Google Scholar 

  23. Bjelakovic, G. et al. Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst. Rev. 6, CD007469 (2014).

    Google Scholar 

  24. LaCroix, A. Z. et al. Calcium plus vitamin D supplementation and mortality in postmenopausal women: the Women's Health Initiative calcium-vitamin D randomized controlled trial. J. Gerontol. A Biol. Sci. Med. Sci. 64, 559–567 (2009).

    PubMed  Google Scholar 

  25. Wactawski-Wende, J. et al. Calcium plus vitamin D supplementation and the risk of colorectal cancer. N. Engl. J. Med. 354, 684–696 (2006).

    CAS  PubMed  Google Scholar 

  26. Chlebowski, R. T. et al. Calcium plus vitamin D supplementation and the risk of breast cancer. J. Natl Cancer Inst. 100, 1581–1591 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Avenell, A. et al. Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D3 and/or calcium (RECORD trial). J. Clin. Endocrinol. Metab. 97, 614–622 (2012).

    CAS  PubMed  Google Scholar 

  28. Lappe, J. M., Travers-Gustafson, D., Davies, K. M., Recker, R. R. & Heaney, R. P. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am. J. Clin. Nutr. 85, 1586–1591 (2007).

    CAS  PubMed  Google Scholar 

  29. Manson, J. E. et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp. Clin. Trials 33, 159–171 (2012).

    CAS  PubMed  Google Scholar 

  30. Manson, J. E. & Bassuk, S. S. Vitamin D research and clinical practice: at a crossroads. JAMA 313, 1311–1312 (2015).

    CAS  PubMed  Google Scholar 

  31. Pradhan, A. D. & Manson, J. E. Update on the Vitamin D and OmegA-3 trial (VITAL). J. Steroid Biochem. Mol. Biol. 155, 252–256 (2016).

    CAS  PubMed  Google Scholar 

  32. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet 354, 447–455 (1999).

  33. Yokoyama, M. et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet 369, 1090–1098 (2007).

    CAS  PubMed  Google Scholar 

  34. The Risk and Prevention Study Collaborative Group. n-3 fatty acids in patients with multiple cardiovascular risk factors. N. Engl. J. Med. 368, 1800–1808 (2013).

  35. The ORIGIN Trial Investigators. n-3 fatty acids and cardiovascular outcomes in patients with dysglycemia. N. Engl. J. Med. 367, 309–318 (2012).

  36. Kromhout, D., Giltay, E. J. & Geleijnse, J. M. n-3 fatty acids and cardiovascular events after myocardial infarction. N. Engl. J. Med. 363, 2015–2026 (2010).

    CAS  PubMed  Google Scholar 

  37. Andreeva, V. A. et al. B vitamin and/or ω-3 fatty acid supplementation and cancer: ancillary findings from the supplementation with folate, vitamins B6 and B12, and/or ω-3 fatty acids (SU.FOL.OM3) randomized trial. Arch. Intern. Med. 172, 540–547 (2012).

    CAS  PubMed  Google Scholar 

  38. Lippman, S. M. et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 301, 39–51 (2009).

    CAS  PubMed  Google Scholar 

  39. Ledesma, M. C. et al. Selenium and vitamin E for prostate cancer: post-SELECT (Selenium and Vitamin E Cancer Prevention Trial) status. Mol. Med. 17, 134–143 (2011).

    CAS  PubMed  Google Scholar 

  40. Klein, E. A. et al. Vitamin E and the risk of prostate cancer: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA 306, 1549–1556 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Marshall, J. R. et al. Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia: SWOG S9917. Cancer Prev. Res. (Phila.) 4, 1761–1769 (2011).

    CAS  Google Scholar 

  42. Gaziano, J. M. et al. Vitamins E and C in the prevention of prostate and total cancer in men: the Physicians' Health Study II randomized controlled trial. JAMA 301, 52–62 (2009).

    CAS  PubMed  Google Scholar 

  43. Meyer, F. et al. Antioxidant vitamin and mineral supplementation and prostate cancer prevention in the SU.VI.MAX trial. Int. J. Cancer 116, 182–186 (2005).

    CAS  PubMed  Google Scholar 

  44. Figueiredo, J. C. et al. Folic acid and prevention of colorectal adenomas: a combined analysis of randomized clinical trials. Int. J. Cancer 129, 192–203 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Zhang, S. M. et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on cancer risk in women: a randomized trial. JAMA 300, 2012–2021 (2008).

    PubMed  PubMed Central  Google Scholar 

  46. Song, Y. et al. Effect of combined folic acid, vitamin B6, and vitamin B12 on colorectal adenoma. J. Natl Cancer Inst. 104, 1562–1575 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Baron, J. A. et al. A trial of calcium and vitamin D for the prevention of colorectal adenomas. N. Engl. J. Med. 373, 1519–1530 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Grau, M. V. et al. Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J. Natl Cancer Inst. 95, 1765–1771 (2003).

    CAS  PubMed  Google Scholar 

  49. Vollset, S. E. et al. Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals. Lancet 381, 1029–1036 (2013).

    CAS  PubMed  Google Scholar 

  50. Druesne-Pecollo, N. et al. β-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int. J. Cancer 127, 172–184 (2010).

    CAS  PubMed  Google Scholar 

  51. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N. Engl. J. Med. 330, 1029–1035 (1994).

  52. Omenn, G. S. et al. Effects of a combination of β carotene and vitamin A on lung cancer and cardiovascular disease. N. Engl. J. Med. 334, 1150–1155 (1996).

    CAS  PubMed  Google Scholar 

  53. Cook, N. R., Le, I. M., Manson, J. E., Buring, J. E. & Hennekens, C. H. Effects of β-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States). Cancer Causes Control 11, 617–626 (2000).

    CAS  PubMed  Google Scholar 

  54. Kamangar, F. et al. Lung cancer chemoprevention: a randomized, double-blind trial in Linxian, China. Cancer Epidemiol. Biomarkers Prev. 15, 1562–1564 (2006).

    CAS  PubMed  Google Scholar 

  55. Lee, I. M., Cook, N. R., Manson, J. E., Buring, J. E. & Hennekens, C. H. β-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J. Natl Cancer Inst. 91, 2102–2106 (1999).

    CAS  PubMed  Google Scholar 

  56. Lin, J. et al. Vitamins C and E and β carotene supplementation and cancer risk: a randomized controlled trial. J. Natl Cancer Inst. 101, 14–23 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. The Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supplementation and cardiovascular events in high-risk patients. N. Engl. J. Med. 342, 154–160 (2000).

  58. Lee, I. M. et al. Vitamin E in the primary prevention of cardiovascular disease and cancer: the Women's Health Study: a randomized controlled trial. JAMA 294, 56–65 (2005).

    CAS  PubMed  Google Scholar 

  59. Sesso, H. D. et al. Vitamins E and C in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA 300, 2123–2133 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Schurks, M., Glynn, R. J., Rist, P. M., Tzourio, C. & Kurth, T. Effects of vitamin E on stroke subtypes: meta-analysis of randomised controlled trials. BMJ 341, c5702 (2010).

    PubMed  PubMed Central  Google Scholar 

  61. Lonn, E. et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N. Engl. J. Med. 354, 1567–1577 (2006).

    CAS  PubMed  Google Scholar 

  62. Bonaa, K. H. et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N. Engl. J. Med. 354, 1578–1588 (2006).

    CAS  PubMed  Google Scholar 

  63. Saposnik, G. et al. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke 40, 1365–1372 (2009).

    CAS  PubMed  Google Scholar 

  64. Toole, J. F. et al. 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. JAMA 291, 565–575 (2004).

    CAS  PubMed  Google Scholar 

  65. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group. Effects of homocysteine-lowering with folic acid plus vitamin B12 versus placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA 303, 2486–2494 (2010).

  66. Huo, Y. et al. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA 313, 1325–1335 (2015).

    CAS  PubMed  Google Scholar 

  67. Albert, C. M. et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA 299, 2027–2036 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Ebbing, M. et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA 300, 795–804 (2008).

    CAS  PubMed  Google Scholar 

  69. Schnyder, G., Roffi, M., Flammer, Y., Pin, R. & Hess, O. M. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial. JAMA 288, 973–979 (2002).

    CAS  PubMed  Google Scholar 

  70. Galan, P. et al. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ 341, c6273 (2010).

    PubMed  PubMed Central  Google Scholar 

  71. Prince, R. L. et al. Effects of ergocalciferol added to calcium on the risk of falls in elderly high-risk women. Arch. Intern. Med. 168, 103–108 (2008).

    CAS  PubMed  Google Scholar 

  72. Wang, L., Manson, J. E., Song, Y. & Sesso, H. D. Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Ann. Intern. Med. 152, 315–323 (2010).

    PubMed  Google Scholar 

  73. Hsia, J. et al. Calcium/vitamin D supplementation and cardiovascular events. Circulation 115, 846–854 (2007).

    CAS  PubMed  Google Scholar 

  74. Campbell, A., Price, J. & Hiatt, W. R. Omega-3 fatty acids for intermittent claudication. Cochrane Database Syst. Rev. 7, CD003833 (2013).

    Google Scholar 

  75. Gissi, H. F. et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 372, 1223–1230 (2008).

    Google Scholar 

  76. Rauch, B. et al. OMEGA, a randomized, placebo-controlled trial to test the effect of highly purified ω-3 fatty acids on top of modern guideline-adjusted therapy after myocardial infarction. Circulation 122, 2152–2159 (2010).

    CAS  PubMed  Google Scholar 

  77. Sesso, H. D. et al. Multivitamins in the prevention of cardiovascular disease in men: the Physicians' Health Study II randomized controlled trial. JAMA 308, 1751–1760 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Li, J. Y. et al. Nutrition intervention trials in Linxian, China: multiple vitamin/mineral supplementation, cancer incidence, and disease-specific mortality among adults with esophageal dysplasia. J. Natl Cancer Inst. 85, 1492–1498 (1993).

    CAS  PubMed  Google Scholar 

  79. Kokubo, Y. Prevention of hypertension and cardiovascular diseases: a comparison of lifestyle factors in Westerners and East Asians. Hypertension 63, 655–660 (2014).

    CAS  PubMed  Google Scholar 

  80. Sacks, F. M. et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N. Engl. J. Med. 344, 3–10 (2001).

    CAS  PubMed  Google Scholar 

  81. Juraschek, S. P., Guallar, E., Appel, L. J. & Miller, E. R. 3rd Effects of vitamin C supplementation on blood pressure: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 95, 1079–1088 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Burgaz, A., Orsini, N., Larsson, S. C. & Wolk, A. Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis. J. Hypertens. 29, 636–645 (2011).

    CAS  PubMed  Google Scholar 

  83. Witham, M. D. et al. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH randomized controlled trial. JAMA Intern. Med. 173, 1672–1679 (2013).

    CAS  PubMed  Google Scholar 

  84. Arora, P. et al. Vitamin D therapy in individuals with prehypertension or hypertension: the DAYLIGHT trial. Circulation 131, 254–262 (2015).

    CAS  PubMed  Google Scholar 

  85. Larsen, T., Mose, F. H., Bech, J. N., Hansen, A. B. & Pedersen, E. B. Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial. Am. J. Hypertens. 25, 1215–1222 (2012).

    CAS  PubMed  Google Scholar 

  86. Pfeifer, M., Begerow, B., Minne, H. W., Nachtigall, D. & Hansen, C. Effects of a short-term vitamin D3 and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J. Clin. Endocrinol. Metab. 86, 1633–1637 (2001).

    CAS  PubMed  Google Scholar 

  87. Beveridge, L. A. et al. Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA Intern. Med. 175, 745–754 (2015).

    PubMed  PubMed Central  Google Scholar 

  88. Seely, E. W. & Ecker, J. Chronic hypertension in pregnancy. Circulation 129, 1254–1261 (2014).

    PubMed  Google Scholar 

  89. Hofmeyr, G. J., Lawrie, T. A., Atallah, A. N., Duley, L. & Torloni, M. R. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst. Rev. 6, CD001059 (2014).

    Google Scholar 

  90. Nield, L., Summerbell, C. D., Hooper, L., Whittaker, V. & Moore, H. Dietary advice for the prevention of type 2 diabetes mellitus in adults. Cochrane Database Syst. Rev. 3, CD005102 (2008).

    Google Scholar 

  91. Song, Y., Cook, N. R., Albert, C. M., Van Denburgh, M. & Manson, J. E. Effects of vitamins C and E and β-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial. Am. J. Clin. Nutr. 90, 429–437 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Liu, S. et al. Vitamin E and risk of type 2 diabetes in the Women's Health Study randomized controlled trial. Diabetes 55, 2856–2862 (2006).

    CAS  PubMed  Google Scholar 

  93. Kataja-Tuomola, M. et al. Effect of α-tocopherol and β-carotene supplementation on the incidence of type 2 diabetes. Diabetologia 51, 47–53 (2008).

    CAS  PubMed  Google Scholar 

  94. Song, Y., Cook, N. R., Albert, C. M., Van Denburgh, M. & Manson, J. E. Effect of homocysteine-lowering treatment with folic acid and B vitamins on risk of type 2 diabetes in women: a randomized, controlled trial. Diabetes 58, 1921–1928 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Seida, J. C. et al. Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 99, 3551–3560 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Mooren, F. C. et al. Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects — a double-blind, placebo-controlled, randomized trial. Diabetes Obes. Metab. 13, 281–284 (2011).

    CAS  PubMed  Google Scholar 

  97. Guerrero-Romero, F. et al. Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Diabetes Metab. 30, 253–258 (2004).

    CAS  PubMed  Google Scholar 

  98. Rodriguez-Moran, M. & Guerrero-Romero, F. Oral magnesium supplementation improves insulin sensitivity and metabolic control in type 2 diabetic subjects: a randomized double-blind controlled trial. Diabetes Care 26, 1147–1152 (2003).

    CAS  PubMed  Google Scholar 

  99. Song, Y., He, K., Levitan, E. B., Manson, J. E. & Liu, S. Effects of oral magnesium supplementation on glycaemic control in type 2 diabetes: a meta-analysis of randomized double-blind controlled trials. Diabet. Med. 23, 1050–1056 (2006).

    CAS  PubMed  Google Scholar 

  100. Golden, N. H. & Abrams, S. A. & Committee on Nutrition. Optimizing bone health in children and adolescents. Pediatrics 134, e1229–e1243 (2014).

    PubMed  Google Scholar 

  101. Cashman, K. D. Calcium intake, calcium bioavailability and bone health. Br. J. Nutr. 87, S169–S177 (2002).

    CAS  PubMed  Google Scholar 

  102. Brouwer-Brolsma, E. M. et al. Vitamin D: do we get enough? A discussion between vitamin D experts in order to make a step towards the harmonisation of dietary reference intakes for vitamin D across Europe. Osteoporos. Int. 24, 1567–1577 (2013).

    CAS  PubMed  Google Scholar 

  103. Jackson, R. D. et al. Calcium plus vitamin D supplementation and the risk of fractures. N. Engl. J. Med. 354, 669–683 (2006).

    CAS  PubMed  Google Scholar 

  104. Dawson-Hughes, B., Harris, S. S., Krall, E. A. & Dallal, G. E. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N. Engl. J. Med. 337, 670–676 (1997).

    CAS  PubMed  Google Scholar 

  105. Di Daniele, N. et al. Effect of supplementation of calcium and vitamin D on bone mineral density and bone mineral content in peri- and post-menopause women; a double-blind, randomized, controlled trial. Pharmacol. Res. 50, 637–641 (2004).

    CAS  PubMed  Google Scholar 

  106. Chapuy, M. C. et al. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N. Engl. J. Med. 327, 1637–1642 (1992).

    CAS  PubMed  Google Scholar 

  107. Salovaara, K. et al. Effect of vitamin D3 and calcium on fracture risk in 65- to 71-year-old women: a population-based 3-year randomized, controlled trial — the OSTPRE-FPS. J. Bone Miner. Res. 25, 1487–1495 (2010).

    CAS  PubMed  Google Scholar 

  108. Meier, C., Woitge, H. W., Witte, K., Lemmer, B. & Seibel, M. J. Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. J. Bone Miner. Res. 19, 1221–1230 (2004).

    CAS  PubMed  Google Scholar 

  109. Grados, F. et al. Effects on bone mineral density of calcium and vitamin D supplementation in elderly women with vitamin D deficiency. Joint Bone Spine 70, 203–208 (2003).

    PubMed  Google Scholar 

  110. Karkkainen, M. et al. Effect of calcium and vitamin D supplementation on bone mineral density in women aged 65–71 years: a 3-year randomized population-based trial (OSTPRE-FPS). Osteoporos Int. 21, 2047–2055 (2010).

    CAS  PubMed  Google Scholar 

  111. Bischoff-Ferrari, H. A. et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N. Engl. J. Med. 367, 40–49 (2012).

    CAS  PubMed  Google Scholar 

  112. Wagner, C. L. & Greer, F. R. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 122, 1142–1152 (2008).

    PubMed  Google Scholar 

  113. Braegger, C. et al. Vitamin D in the healthy European paediatric population. J. Pediatr. Gastroenterol. Nutr. 56, 692–701 (2013).

    CAS  PubMed  Google Scholar 

  114. Spiro, A. & Buttriss, J. L. Vitamin D: an overview of vitamin D status and intake in Europe. Nutr. Bull. 39, 322–350 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Mosekilde, L. Vitamin D requirement and setting recommendation levels: long-term perspectives. Nutr. Rev. 66, S170–S177 (2008).

    PubMed  Google Scholar 

  116. Lerch, C. & Meissner, T. Interventions for the prevention of nutritional rickets in term born children. Cochrane Database Syst. Rev. 4, CD006164 (2007).

    Google Scholar 

  117. Cheung, A. M. et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 5, e196 (2008).

    PubMed  Google Scholar 

  118. Bolton-Smith, C. et al. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J. Bone Miner. Res. 22, 509–519 (2007).

    CAS  PubMed  Google Scholar 

  119. Braam, L. A. et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif. Tissue Int. 73, 21–26 (2003).

    CAS  PubMed  Google Scholar 

  120. Binkley, N. et al. Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J. Bone Miner. Res. 24, 983–991 (2009).

    CAS  PubMed  Google Scholar 

  121. Knapen, M. H., Drummen, N. E., Smit, E., Vermeer, C. & Theuwissen, E. Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos. Int. 24, 2499–2507 (2013).

    CAS  PubMed  Google Scholar 

  122. Knapen, M. H., Schurgers, L. J. & Vermeer, C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos. Int. 18, 963–972 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Emaus, N. et al. Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos. Int. 21, 1731–1740 (2010).

    CAS  PubMed  Google Scholar 

  124. Koitaya, N. et al. Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone metabolism and prevents forearm bone loss in postmenopausal Japanese women. J. Bone Miner. Metab. 32, 142–150 (2014).

    CAS  PubMed  Google Scholar 

  125. World Health Organization. Universal eye health: a global action plan 2014–2019. [online] http://www.who.int/blindness/AP2014_19_English.pdf, (2013).

  126. Christen, W. G. et al. A randomized trial of beta carotene and age-related cataract in US physicians. Arch. Ophthalmol. 121, 372–378 (2003).

    CAS  PubMed  Google Scholar 

  127. Christen, W., Glynn, R., Sperduto, R., Chew, E. & Buring, J. Age-related cataract in a randomized trial of beta-carotene in women. Ophthalmic Epidemiol. 11, 401–412 (2004).

    PubMed  Google Scholar 

  128. Christen, W. G. et al. Age-related cataract in a randomized trial of vitamins E and C in men. Arch. Ophthalmol. 128, 1397–1405 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Christen, W. G., Glynn, R. J., Chew, E. Y. & Buring, J. E. Vitamin E and age-related cataract in a randomized trial of women. Ophthalmology 115, 822–829.e1 (2008).

    PubMed  Google Scholar 

  130. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E and beta carotene for age-related cataract and vision loss: AREDS report no. 9. Arch. Ophthalmol. 119, 1439–1452 (2001).

  131. Age-Related Eye Disease Study 2 (AREDS2) Research Group. Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4. JAMA Ophthalmol. 131, 843–850 (2013).

    CAS  PubMed  Google Scholar 

  132. Clinical Trial of Nutritional Supplements and Age-Related Cataract Study Group. A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities: clinical trial of nutritional supplements and age-related cataract report no. 3. Ophthalmology 115, 599–607 (2008).

  133. Milton, R. C., Sperduto, R. D., Clemons, T. E. & Ferris, F. L. 3rd & Age-Related Eye Disease Study Research Group. Centrum use and progression of age-related cataract in the Age-Related Eye Disease Study: a propensity score approach. AREDS report No. 21. Ophthalmology 113, 1264–1270 (2006).

    PubMed  Google Scholar 

  134. Christen, W. G. et al. Effects of multivitamin supplement on cataract and age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 121, 525–534 (2014).

    PubMed  Google Scholar 

  135. Newsome, D. A., Swartz, M., Leone, N. C., Elston, R. C. & Miller, E. Oral zinc in macular degeneration. Arch. Ophthalmol. 106, 192–198 (1988).

    CAS  PubMed  Google Scholar 

  136. Age-Related Eye Disease Study Research Group. A randomized, 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: AREDS report no. 8. Arch. Ophthalmol. 119, 1417–1436 (2001).

  137. Chew, E. Y. et al. Long-term effects of vitamins C and E, β-carotene, and zinc on age-related macular degeneration: AREDS report no. 35. Ophthalmology 120, 1604–1611.e4 (2013).

    PubMed  Google Scholar 

  138. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and ω-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 309, 2005–2015 (2013).

  139. Christen, W. G., Glynn, R. J., Chew, E. Y., Albert, C. M. & Manson, J. E. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Arch. Intern. Med. 169, 335–341 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Christen, W. G. et al. Vitamins E and C and medical record-confirmed age-related macular degeneration in a randomized trial of male physicians. Ophthalmology 119, 1642–1649 (2012).

    PubMed  Google Scholar 

  141. Christen, W. G., Glynn, R. J., Chew, E. Y. & Buring, J. E. Vitamin E and age-related macular degeneration in a randomized trial of women. Ophthalmology 117, 1163–1168 (2010).

    PubMed  Google Scholar 

  142. World Health Organization. Vitamin A supplementation in pregnant women [online] http://www.who.int/nutrition/publications/micronutrients/guidelines/vas_pregnant/en/, (2011).

  143. World Health Organization. Vitamin A Supplementation in Infants & Children 6–59 Months of Age WHO [online] http://www.who.int/nutrition/publications/micronutrients/guidelines/vas_6to59_months/en/, (2011).

  144. Gogia, S. & Sachdev, H. S. Vitamin A supplementation for the prevention of morbidity and mortality in infants six months of age or less. Cochrane Database Syst. Rev. 10, CD007480 (2011).

    Google Scholar 

  145. World Health Organization. WHO recommendation on the management of diarrhoea and pneumonia in HIV-infected infants and children: intergrated management of childhood illness (IMCI). [online] http://www.unicef.org/aids/files/hiv_diarrhoea_and_pneumonia.pdf, (2010).

  146. Hathcock, J. N. et al. Evaluation of vitamin A toxicity. Am. J. Clin. Nutr. 52, 183–202 (1990).

    CAS  PubMed  Google Scholar 

  147. World Health Organization. Global update on the health sector response to HIV, 2014. [online] http://www.who.int/hiv/pub/global-update.pdf, (2014).

  148. Irlam, J. H., Siegfried, N., Visser, M. E. & Rollins, N. C. Micronutrient supplementation for children with HIV infection. Cochrane Database Syst. Rev. 10, CD010666 (2013).

    Google Scholar 

  149. McDonald, C. M. et al. Daily zinc but not multivitamin supplementation reduces diarrhea and upper respiratory infections in Tanzanian infants: a randomized, double-blind, placebo-controlled clinical trial. J. Nutr. 145, 2153–2160 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  150. World Health Organization. World Health Organization guideline: optimal serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects, WHO guidelines approved by the Guidelines Review Committee. [online] http://apps.who.int/iris/bitstream/10665/161988/1/9789241549042_eng.pdf, (2015).

  151. Yi, Y., Lindemann, M., Colligs, A. & Snowball, C. Economic burden of neural tube defects and impact of prevention with folic acid: a literature review. Eur. J. Pediatr. 170, 1391–1400 (2011).

    PubMed  PubMed Central  Google Scholar 

  152. De-Regil, L. M., Fernandez-Gaxiola, A. C., Dowswell, T. & Pena-Rosas, J. P. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst. Rev. 10, CD007950 (2010).

    Google Scholar 

  153. Rofail, D., Colligs, A., Abetz, L., Lindemann, M. & Maguire, L. Factors contributing to the success of folic acid public health campaigns. J. Publ. Health (Oxf.) 34, 90–99 (2012).

    CAS  Google Scholar 

  154. Wolff, T., Witkop, C. T., Miller, T. & Syed, S. B. Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. Preventive Services Task Force. Ann. Intern. Med. 150, 632–639 (2009).

    PubMed  Google Scholar 

  155. Knudsen, V. K. et al. Low compliance with recommendations on folic acid use in relation to pregnancy: is there a need for fortification? Publ. Health Nutr. 7, 843–850 (2004).

    Google Scholar 

  156. de Jong- van den Berg, L. T. Monitoring of the folic acid supplementation program in the Netherlands. Food Nutr. Bull. 29, S210–S213 (2008).

    Google Scholar 

  157. Pouchieu, C. et al. Socioeconomic, lifestyle and dietary factors associated with dietary supplement use during pregnancy. PLoS ONE 8, e70733 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Crider, K. S. et al. Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis. Am. J. Clin. Nutr. 98, 1272–1281 (2013).

    CAS  PubMed  Google Scholar 

  159. World Health Organization. Guideline: daily iron and folic acid supplementation in pregnant women. [online] http://apps.who.int/iris/bitstream/10665/77770/1/9789241501996_eng.pdf, (2012).

  160. Pena-Rosas, J. P., De-Regil, L. M., Garcia-Casal, M. N. & Dowswell, T. Daily oral iron supplementation during pregnancy. Cochrane Database Syst. Rev. 7, CD004736 (2012).

    Google Scholar 

  161. De-Regil, L. M., Jefferds, M. E., Sylvetsky, A. C. & Dowswell, T. Intermittent iron supplementation for improving nutrition and development in children under 12 years of age. Cochrane Database Syst. Rev. 12, CD009085 (2011).

    Google Scholar 

  162. Cantor, A. G., Bougatsos, C., Dana, T., Blazina, I. & McDonagh, M. Routine iron supplementation and screening for iron deficiency anemia in pregnancy: a systematic review for the U.S. Preventive Services Task Force. Ann. Intern. Med. 162, 566–576 (2015).

    PubMed  Google Scholar 

  163. Pearce, E. N., Andersson, M. & Zimmermann, M. B. Global iodine nutrition: where do we stand in 2013? Thyroid 23, 523–528 (2013).

    CAS  PubMed  Google Scholar 

  164. Andersson, M. et al. Iodine deficiency in Europe: a continuing public health problem. World Health Organization [online] http://www.who.int/nutrition/publications/VMNIS_Iodine_deficiency_in_Europe.pdf, (2007).

    Google Scholar 

  165. Zhou, S. J., Anderson, A. J., Gibson, R. A. & Makrides, M. Effect of iodine supplementation in pregnancy on child development and other clinical outcomes: a systematic review of randomized controlled trials. Am. J. Clin. Nutr. 98, 1241–1254 (2013).

    CAS  PubMed  Google Scholar 

  166. De-Regil, L. M., Palacios, C., Lombardo, L. K. & Pena-Rosas, J. P. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst. Rev. 1, CD008873 (2016).

    Google Scholar 

  167. Saccone, G. & Berghella, V. Omega-3 long chain polyunsaturated fatty acids to prevent preterm birth: a systematic review and meta-analysis. Am. J. Obstet. Gynecol. 125, 663–672 (2015).

    CAS  Google Scholar 

  168. Zhang, P., Lavoie, P. M., Lacaze-Masmonteil, T., Rhainds, M. & Marc, I. Omega-3 long-chain polyunsaturated fatty acids for extremely preterm infants: a systematic review. Pediatrics 134, 120–134 (2014).

    PubMed  Google Scholar 

  169. Peter, S. et al. Nutrient status assessment in individuals and populations for healthy aging — statement from an expert workshop. Nutrients 7, 10491–10500 (2015).

    PubMed  PubMed Central  Google Scholar 

  170. Qiu, C. & Fratiglioni, L. A major role for cardiovascular burden in age-related cognitive decline. Nat. Rev. Cardiol. 12, 267–277 (2015).

    PubMed  Google Scholar 

  171. Stover, P. J. Vitamin B12 and older adults. Curr. Opin. Clin. Nutr. Metab. Care 13, 24–27 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  172. Dangour, A. D. et al. Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial. Am. J. Clin. Nutr. 102, 639–647 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  173. Jerneren, F. et al. Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial. Am. J. Clin. Nutr. 102, 215–221 (2015).

    CAS  PubMed  Google Scholar 

  174. van der Zwaluw, N. L. et al. Results of 2-year vitamin B treatment on cognitive performance: secondary data from an RCT. Neurology 83, 2158–2166 (2014).

    CAS  PubMed  Google Scholar 

  175. Cheng, D. et al. B vitamin supplementation improves cognitive function in the middle aged and elderly with hyperhomocysteinemia. Nutr. Neurosci. http://dx.doi.org/10.1179/1476830514Y.0000000136 (2014).

  176. Clarke, R. et al. Effects of homocysteine lowering with B vitamins on cognitive aging: meta-analysis of 11 trials with cognitive data on 22,000 individuals. Am. J. Clin. Nutr. 100, 657–666 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  177. de Jager, C. A., Oulhaj, A., Jacoby, R., Refsum, H. & Smith, A. D. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: a randomized controlled trial. Int. J. Geriatr. Psychiatry 27, 592–600 (2012).

    PubMed  Google Scholar 

  178. Aisen, P. S. et al. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA 300, 1774–1783 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Sun, Y., Lu, C. J., Chien, K. L., Chen, S. T. & Chen, R. C. Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients. Clin. Ther. 29, 2204–2214 (2007).

    CAS  PubMed  Google Scholar 

  180. Kwok, T. et al. A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people. Clin. Nutr. 30, 297–302 (2011).

    CAS  PubMed  Google Scholar 

  181. Kang, J. H. et al. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am. J. Clin. Nutr. 88, 1602–1610 (2008).

    CAS  PubMed  Google Scholar 

  182. Li, Y., Liu, S., Man, Y., Li, N. & Zhou, Y. U. Effects of vitamins E and C combined with β-carotene on cognitive function in the elderly. Exp. Ther. Med. 9, 1489–1493 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  183. Naeini, A. M. et al. The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double-blind, randomized, placebo-controlled trial. Eur. J. Nutr. 53, 1255–1262 (2014).

    PubMed  Google Scholar 

  184. Cetin, E. et al. Effect of vitamin E supplementation with exercise on cognitive functions and total antioxidant capacity in older people. J. Nutr. Health Aging 14, 763–769 (2010).

    CAS  PubMed  Google Scholar 

  185. Grodstein, F., Kang, J. H., Glynn, R. J., Cook, N. R. & Gaziano, J. M. A randomized trial of beta carotene supplementation and cognitive function in men: the Physicians' Health Study II. Arch. Intern. Med. 167, 2184–2190 (2007).

    CAS  PubMed  Google Scholar 

  186. Kang, J. H., Cook, N., Manson, J., Buring, J. E. & Grodstein, F. A randomized trial of vitamin E supplementation and cognitive function in women. Arch. Intern. Med. 166, 2462–2468 (2006).

    CAS  PubMed  Google Scholar 

  187. Kang, J. H. et al. Vitamin E, vitamin C, beta carotene, and cognitive function among women with or at risk of cardiovascular disease: the Women's Antioxidant and Cardiovascular Study. Circulation 119, 2772–2780 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Quinn, J. F. et al. Docosahexaenoic acid supplementation and cognitive decline in Alzheimer disease: a randomized trial. JAMA 304, 1903–1911 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  189. Sinn, N. et al. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: a 6-month randomised controlled trial. Br. J. Nutr. 107, 1682–1693 (2012).

    CAS  PubMed  Google Scholar 

  190. Shinto, L. et al. A randomized placebo-controlled pilot trial of omega-3 fatty acids and α lipoic acid in Alzheimer's disease. J. Alzheimers Dis. 38, 111–120 (2014).

    CAS  PubMed  Google Scholar 

  191. Mahmoudi, M. J. et al. Effect of low dose ω-3 poly unsaturated fatty acids on cognitive status among older people: a double-blind randomized placebo-controlled study. J. Diabetes Metab. Disord. 13, 34 (2014).

    PubMed  PubMed Central  Google Scholar 

  192. van de Rest, O. et al. Effect of fish oil on cognitive performance in older subjects: a randomized, controlled trial. Neurology 71, 430–438 (2008).

    CAS  PubMed  Google Scholar 

  193. Dangour, A. D. et al. Effect of 2-y n-3 long-chain polyunsaturated fatty acid supplementation on cognitive function in older people: a randomized, double-blind, controlled trial. Am. J. Clin. Nutr. 91, 1725–1732 (2010).

    CAS  PubMed  Google Scholar 

  194. Geleijnse, J. M., Giltay, E. J. & Kromhout, D. Effects of n-3 fatty acids on cognitive decline: a randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients. Alzheimers Dement. 8, 278–287 (2012).

    CAS  PubMed  Google Scholar 

  195. Chew, E. Y. et al. Effect of omega-3 fatty acids, lutein/zeaxanthin, or other nutrient supplementation on cognitive function: the AREDS2 randomized clinical trial. JAMA 314, 791–801 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  196. Dean, A. J. et al. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults — a randomised controlled trial. PLoS ONE 6, e25966 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Rossom, R. C. et al. Calcium and vitamin D supplementation and cognitive impairment in the Women's Health Initiative. J. Am. Geriatr. Soc. 60, 2197–2205 (2012).

    PubMed  PubMed Central  Google Scholar 

  198. Kesse-Guyot, E. et al. French adults' cognitive performance after daily supplementation with antioxidant vitamins and minerals at nutritional doses: a post hoc analysis of the Supplementation in Vitamins and Mineral Antioxidants (SU.VI.MAX) trial. Am. J. Clin. Nutr. 94, 892–899 (2011).

    CAS  PubMed  Google Scholar 

  199. McNeill, G. et al. Effect of multivitamin and multimineral supplementation on cognitive function in men and women aged 65 years and over: a randomised controlled trial. Nutr. J. 6, 10 (2007).

    PubMed  PubMed Central  Google Scholar 

  200. Grodstein, F. et al. Long-term multivitamin supplementation and cognitive function in men: a randomized trial. Ann. Intern. Med. 159, 806–814 (2013).

    PubMed  PubMed Central  Google Scholar 

  201. World Health Organization. Mental health action plan 2013–2020. [online] http://apps.who.int/iris/bitstream/10665/89966/1/9789241506021_eng.pdf, (2013).

  202. Cuijpers, P., Beekman, A. T. & Reynolds, C. F. 3rd Preventing depression: a global priority. JAMA 307, 1033–1034 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  203. Okereke, O. I. et al. Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women. Br. J. Psychiatry 206, 324–331 (2015).

    PubMed  PubMed Central  Google Scholar 

  204. Ford, A. H. et al. Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial. J. Clin. Psychiatry 69, 1203–1209 (2008).

    CAS  PubMed  Google Scholar 

  205. Walker, J. G. et al. Mental health literacy, folic acid and vitamin B12, and physical activity for the prevention of depression in older adults: randomised controlled trial. Br. J. Psychiatry 197, 45–54 (2010).

    PubMed  Google Scholar 

  206. Andreeva, V. A. et al. Supplementation with B vitamins or n-3 fatty acids and depressive symptoms in cardiovascular disease survivors: ancillary findings from the SUpplementation with FOLate, vitamins B-6 and B-12 and/or OMega-3 fatty acids (SU.FOL.OM3) randomized trial. Am. J. Clin. Nutr. 96, 208–214 (2012).

    CAS  PubMed  Google Scholar 

  207. Almeida, O. P. et al. B-vitamins reduce the long-term risk of depression after stroke: the VITATOPS-DEP trial. Ann. Neurol. 68, 503–510 (2010).

    CAS  PubMed  Google Scholar 

  208. Patrick, R. P. & Ames, B. N. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB J. 29, 2207–2222 (2015).

    CAS  PubMed  Google Scholar 

  209. Grosso, G. et al. Role of omega-3 fatty acids in the treatment of depressive disorders: a comprehensive meta-analysis of randomized clinical trials. PLoS ONE 9, e96905 (2014).

    PubMed  PubMed Central  Google Scholar 

  210. Bloch, M. H. & Hannestad, J. Omega-3 fatty acids for the treatment of depression: systematic review and meta-analysis. Mol. Psychiatry 17, 1272–1282 (2012).

    CAS  PubMed  Google Scholar 

  211. Shaffer, J. A. et al. Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosom. Med. 76, 190–196 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  212. Li, G. et al. Efficacy of vitamin D supplementation in depression in adults: a systematic review. J. Clin. Endocrinol. Metab. 99, 757–767 (2014).

    CAS  PubMed  Google Scholar 

  213. Macpherson, H., Rowsell, R., Cox, K. H., Scholey, A. & Pipingas, A. Acute mood but not cognitive improvements following administration of a single multivitamin and mineral supplement in healthy women aged 50 and above: a randomised controlled trial. Age 37, 9782 (2015).

    CAS  PubMed  Google Scholar 

  214. Harris, E. et al. The effect of multivitamin supplementation on mood and stress in healthy older men. Hum. Psychopharmacol. 26, 560–567 (2011).

    CAS  PubMed  Google Scholar 

  215. Smith Fawzi, M. C. et al. Multivitamin supplementation in HIV-positive pregnant women: impact on depression and quality of life in a resource-poor setting. HIV Med. 8, 203–212 (2007).

    CAS  PubMed  Google Scholar 

  216. World Health Organization. The ICD-10 classification of mental and behavioural disorders. [online] http://www.who.int/classifications/icd/en/bluebook.pdf, (2010).

  217. Gillies, D., Sinn, J., Lad, S. S., Leach, M. J. & Ross, M. J. Polyunsaturated fatty acids (PUFA) for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst. Rev. 7, CD007986 (2012).

    Google Scholar 

  218. Lobar, S. L. DSM-V changes for autism spectrum disorder (ASD): implications for diagnosis, management, and care coordination for children with ASDs. J. Pediatr. Health Care http://dx.doi.org/10.1016/j.pedhc.2015.09.005 (2015).

  219. Lyall, K., Schmidt, R. J. & Hertz-Picciotto, I. Maternal lifestyle and environmental risk factors for autism spectrum disorders. Int. J. Epidemiol. 43, 443–464 (2014).

    PubMed  PubMed Central  Google Scholar 

  220. Suren, P. et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 309, 570–577 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  221. James, S., Montgomery, P. & Williams, K. Omega-3 fatty acids supplementation for autism spectrum disorders (ASD). Cochrane Database Syst. Rev. 11, CD007992 (2011).

    Google Scholar 

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Acknowledgements

S.R. has received funding from COFAS 2 Marie Curie Fellowship, Stockholm, Sweden. J.E.M. has received grant or research support from the NIH (HL34594, CA138962 and HHSN268201100001C) for the for the VITamin D and OmegA-3 TriaL (VITAL) and other research studies. A.H.L has received funding from USDA 1950-51000-072-02S, USDA/NIFA/AFRI 2011-03389 and AHRQ/Contract HHSA290201200012I. H.D.S. has received grant support from the NIH (R01 HL102122) related to work on the VITamin D and OmegA-3 TriaL (VITAL).

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S.R. researched the data for the article. All authors provided a substantial contribution to discussions of the content. S.R., J.E.M., A.H.L. and H.D.S. contributed equally to writing the article. All authors contributed equally to review and/or editing of the manuscript before submission.

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Correspondence to JoAnn E. Manson.

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Competing interests

J.E.M. declares that she has received investigator-initiated grant support and/or donation of study pills from Mars Symbioscience, Pfizer Inc., PharmaViteProNova and BioPharma/BASF. H.D.S. declares that he has received investigator-initiated grant support (including donations of study pills) from the Council for Responsible Nutrition Foundation, Mars Symbioscience and Pfizer Inc. S.R. and A.H.L. declare no competing interests.

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Rautiainen, S., Manson, J., Lichtenstein, A. et al. Dietary supplements and disease prevention — a global overview. Nat Rev Endocrinol 12, 407–420 (2016). https://doi.org/10.1038/nrendo.2016.54

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