公衆衛生73巻1号

2009年01月発行

特集 健康食品をめぐって

サプリメントの有効性の疫学研究

著者： 下方浩史¹ 安藤富士子²

所属機関： ¹国立長寿医療センター研究所疫学研究部 ²愛知淑徳大学医療福祉学部医療貢献学科

ページ範囲：P.25 - P.30

栄養疫学とサプリメント

　明治時代，脚気は国民病であり，特に兵士の罹病，死亡例が多かった．当時の海軍軍医総監であった高木兼寛は白米と麦による動物飼育実験の結果などにより，西洋諸国で脚気が少ないことはパン食による麦の摂取のためであると考えた．遠洋航海での麦飯混合食の試行実験を実施し，脚気患者が1人も出なかったことから，明治18年，海軍の食事をすべて麦飯混合食へ切り替えた．その結果，海軍から脚気がなくなった．これは日本で最初の栄養疫学的な観察研究，介入研究であると言える．一方，陸軍では森鴎外が軍医総監であり，ドイツ流の病理学や細菌学を採用し，脚気は脚気菌によるものと考えていた．このため麦飯混合食は陸軍では採用されず，その結果，陸軍では多数の死亡者が出て，日清戦争では戦死者よりも脚気による病死者のほうが多かったと言われる．

　鈴木梅太郎が抗脚気因子であるオリザニン(ビタミンB₁)を発見するのは明治43年である．それまではなぜ麦飯が脚気を予防するのかわからず，森鴎外らによって「科学的根拠がない」として否定されたわけである．これは疫学的研究と病理学的研究の差を示すものであろう．疫学でははっきりとした理由がわからなくても，観察研究，コホート研究，介入研究などで関連性が明らかになれば，それは科学的事実として認め，予防に役立てていく．この結果，麦飯混合食で何万人もの人命が救われたのである．逆に「科学的根拠」があるとされる場合にも，疫学的研究で否定される場合もある．試験管での実験の結果で有効である根拠が示され，また動物実験でも有効であった成分が人ではまったく無効であったり有害であったりする．

参考文献

1) NIH State-of-the-Science Conference Statement on Multivitamin/Mineral Supplements and Chronic Disease Prevention. NIH Consensus State Science Statements 23(2):1-30, 2006

2) Imai T, et al:Dietary supplement use by community-living population in Japan:Data from the National Institute for Longevity Sciences Longitudinal Study of Aging(NILS-LSA). J Epidemiol 16(6):249-260, 2006

3) Foote JA, et al:Factors associated with dietary supplement use among healthy adults of five ethnicities;the Multiethnic Cohort Study. Am J Epidemiol 157(10):888-897, 2003

4) Fairfield KM, et al:Vitamins for chronic disease prevention in adults;Scientific Review. JAMA 287(23):3127-3129, 2002

5) Morrison HI, et al:Serum folate and risk of fatal coronary heart disease. JAMA 275:1893-1896, 1996

6) Rimm EB, et al:Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 279:359-364, 1998

7) Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements;meta-analysis of randomised trials. BMJ 316:894-898, 1998

8) Eikelboom JW, et al:Homocysteine and cardiovascular disease:a critical review of the epidemiologic evidence. Ann Intern Med 131:363-375, 1999

9) Bostom AG, et al:Endpoints for homocysteine lowering trials. Lancet 355:511-512, 2000

10) Giovannucci E, et al:Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 87:265-273, 1995

11) Giovannucci E, Stampfer MJ, Colditz GA, et al:Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 129:517-524, 1998

12) Su LJ, et al:Nutritional status of folate and colon cancer risk;evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol 11:65-72, 2001

13) Stampfer MJ, et al:Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 328:1444-1449, 1993

14) Rimm EB, et al:Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med 328:1450-1456, 1993

15) Rapola JM, et al:Randomised trial of alpha-tocopherol and beta-carotene supplements on incidence of major coronary events in men with previous myocardial infarction. Lancet 349:1715-1720, 1997

16) Rapola JM, et al:Effect of vitamin E and beta carotene on the incidence of angina pectoris;a randomized, double-blind, controlled trial. JAMA 275:693-698, 1996

17) Yusuf S, et al:Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 342:154-160, 2000

18) deGaetaro G, et al:Low-dose aspirin and vitamin E in people at cardiovascular risk;a randomised trial in general practice. Lancet 357:89-95, 2001

19) Stephens NG, et al:Randomised controlled trial of vitamin E in patients with coronary disease;Cambridge Heart Antioxidant Study(CHAOS). Lancet 347:781-786, 1996

20) Gann PH, et al:Lower prostate cancer risk in men with elevated plasma lycopene levels;results of a prospective analysis. Cancer Res 59:1225-1230, 1999

21) Chan JM, et al:Supplemental vitamin E intake and prostate cancer risk in a large cohort of men in the United States. Cancer Epidemiol Biomarkers Prev 8:893-899, 1999

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

23) Kushi LH, et al:Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med 334:1156-1162, 1996

24) Evans RW, Shaten BJ, Day BW, Kuller LH:Prospective association between lipid soluble antioxidants and coronary heart disease in men;the Multiple Risk Factor Intervention Trial. Am J Epidemiol 147:180-186, 1998

25) Omenn GS, et al:Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334:1150-1155, 1996

26) Blot WJ, 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

27) Hennekens CH, Buring JE, Manson JE, et al:Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 334:1145-1149, 1996

28) Greenberg ER, Baron JA, Karagas MR, et al:Mortality associated with low plasma concentration of beta carotene and the effect of oral supplementation. JAMA 275:699-703, 1996

29) van Poppel G, et al:Epidemiologic evidence for beta-carotene and cancer prevention. Am J Clin Nutr 62:1393S-1402S, 1995

30) Speizer FE, et al:Prospective study of smoking, antioxidant intake, and lung cancer in middle-aged women. Cancer Causes Control 10:475-482, 1999

31) Knekt P, et al:Role of various carotenoids in lung cancer prevention. J Natl Cancer Inst 91:182-184, 1999

32) Michaud DS, Feskanich D, Rimm EB, et al:Intake of specific carotenoids and risk of lung cancer in 2 prospective US cohorts. Am J Clin Nutr 72:990-997, 2000

33) Lee IM, et al:Beta-carotene supplementation and incidence of cancer and cardiovascular disease;the Women's Health Study. J Natl Cancer Inst 91:2102-2106, 1999

34) Giovannucci E, et al:Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 87:1767-1776, 1995

35) Mills PK, et al:Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 64:598-604, 1989

36) Cerhan J, et al:A cohort study of diet and prostate cancer risk[abstract]. Cancer Epidemiol Biomarkers Prev 7:175, 1998

37) Baldwin D, et al:The effect of nutritional and clinical factors upon serum prostate specific antigen and prostate cancer risk in a population of elderly California men[abstract]. Paper presented at:1997 Annual Meeting of the American Urological Association, April 12-17, 1997

38) Dawson-Hughes B, et al: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

39) LeppäläJM, et al:Controlled trial of alpha-tocopherol and beta-carotene supplements on stroke incidence and mortality in male smokers. Arterioscler Thromb Vasc Biol 20(1):230-235, 2000

40) Miller ER 3rd, et al:Meta-analysis;high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med 142:37-46, 2005

41) Lee IM, et al:Beta-carotene supplementation and incidence of cancer and cardiovascular disease;the Women's Health Study. J Natl Cancer Inst 91(24):2102-2106, 1999

42) Lee IM, et al:Vitamin E in the primary prevention of cardiovascular disease and cancer;the Women's Health Study;a randomized controlled trial. JAMA 294(1):56-65, 2005

43) 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(21):2335-2342, 2004

44) Huang HY, et al:Multivitamin/mineral supplements and prevention of chronic disease. Evid Rep Technol Assess 139:1-117, 2006

45) 食品安全委員会：大豆イソフラボンを含む特定保健用食品の安全性評価の基本的な考え方．pp49-50，2006

46) Kreijkamp-Kaspers S, et al:Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women;a randomized controlled trial. JAMA 292:65-74, 2004

47) White LR, et al:Brain aging and midlife tofu consumption. J Am Coll Nutr 19:242-255, 2000

48) Hogervorst E, et al:High tofu intake is associated with worse memory in elderly indonesian men and women. Dement. Geriatr Cogn Disord 26:50-57, 2008