DIETARY SUPPLEMENTS

VI. DIETARY SUPPLEMENTS

In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA). Through this legislation, dietary supplements have been defined as ‘‘a product, other than tobacco, intended to supplement the diet that contains at least one or more of the following ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, or extract or combination of any of the previously mentioned ingredients.’’ Dietary supplements are regulated as a special category of foods rather than as a category of drugs. Because these products are meant to supplement the diet by increasing the total dietary intake of a substance, manufacturers do not have to provide information to the FDA to get their product on the market. Once In 1994, the United States Congress passed the Dietary Supplement Health and Education Act (DSHEA). Through this legislation, dietary supplements have been defined as ‘‘a product, other than tobacco, intended to supplement the diet that contains at least one or more of the following ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, or a dietary substance for use to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, or extract or combination of any of the previously mentioned ingredients.’’ Dietary supplements are regulated as a special category of foods rather than as a category of drugs. Because these products are meant to supplement the diet by increasing the total dietary intake of a substance, manufacturers do not have to provide information to the FDA to get their product on the market. Once

Three types of claims can be made regarding dietary supplements: nutrient-content claims, disease claims, and nutrition support claims. A nutrient-content claim is based on the level of the nutrient in a food or dietary supplement. For example, a supplement that contains 12 mg of vitamin C could state that it is a ‘‘good source of vitamin C.’’ If there is a link between the food and a disease or health-related condition, a disease claim could

be made. For example, a product that contains folic acid can make a disease claim that the product decreases the risk of neural tube defects during pregnancy. A nutrient support claim can show a link between the nutrient and a deficiency disease as a result of a lack of the nutrient. For example, vitamin C prevents scurvy.

As of March 1999, dietary supplements must contain a ‘‘Supplement Facts’’ panel. Dietary supplements must be labeled as such and be sold in the form of pills, capsules, tablets, gelcaps, liquids, powders, or other forms, and not be represented for use as conven- tional foods. These products cannot be marketed as the only item in a meal or diet (222).

The dietary supplement industry continues to grow. In 1996, consumers spent an estimated $6.5 billion on supplements, double the expenditures in 1990–1991 (223). The Office of Dietary Supplements is a congressionally mandated office in the Office of the Director, National Institutes of Health (NIH). Through their efforts and those of the USDA Food and Nutrition Information Center, the International Bibliography Information on Dietary Supplements (IBIDS) database are available: http:/ /odp.od.nih.gov/ods/ databases/ibids.html .

REFERENCES Vitamin A

1. Ball, G. 1996. Determination of the fat-soluble vitamins in foods by high-performance liquid chromatography. In: Handbook of Food Analysis, Vol. 1, Physical Characterization and Nu- trient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 602–604. 2. Olson, J. A. 1994. Vitamin A, retinoids, and carotenoids. In: M. E. Shils, J. A. Olson, M. Shike (Eds.), Modern Nutrition in Health and Disease, 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 287–307. 3. Olson, J. A. 1996. Vitamin A. In: Present Knowledge in Nutrition, 7th ed., Ziegler, E. E., Filer, L. J., Jr. (Eds.). LSI Press, Washington, D.C., pp. 109–119. 4. Stephensen, C. B., Alvarez, J. O., Kohatsu, J., Hardmeier, R., Kennedy, J. I. Jr., Gammon, R. B. Jr. 1994. Vitamin A is excreted in the urine during acute infection. Am. J. Clin. Nutr. 60:388–392. 5. Duitsman, P. K., Cook, L. R., Tanumihardjo, S. A., Olson, J. A. 1995. Vitamin A inadequacy in socioeconomically disadvantaged pregnant Iowan women as assessed by the modified relative dose response (MRDR) test. Nutr. Res. 15:1263–1276. 6. Food and Nutrition Board. 1989. Recommended Dietary Allowances, 10th ed., National Academy Press, Washington, D.C. 7. Mahan, K. L., Escott-Stump, S. 1996. Krause’s Food Nutrition and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia.

dex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C. 9. FAO. 1996. Food fortification technology and quality control. FAO technical meeting, Rome. FAO Food and Nutrition Paper 60. 10. Hathcock, J. N., Hattan, D. G., Jenkins, M. Y., McDonald, J. T., Sundaresan, P. R., Wilken- ing, V. L. 1990. Evaluation of vitamin A toxicity. Am. J. Clin. Nutr. 52:183–202.

Carotenoids

11. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition & Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 12. FAO. 1996. Food fortification technology and quality control. FAO technical meeting, Rome. FAO Food and Nutrition Paper 60. 13. Olson, J. A. 1994. Vitamin A, retinoids, and carotenoids. In: Modern Nutrition in Health and Disease , 8th ed., Shils, M. E., Olson, J. A., Shike, M. Williams & Wilkins, Baltimore, pp. 287–307. 14. Ball, G. 1996. Determination of the fat-soluble vitamins in foods by high-performance liquid chromatography. In: Handbook of Food Analysis, Vol. 1, Physical Characterization and Nu- trient Analysis . Marcel Dekker, New York, pp. 602–604. 15. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemical Codex, 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Wash- ington, D.C.

Vitamin D

16. Holick, M. F. 1994. Vitamin D. In: Modern Nutrition in Health and Disease, 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 308–325. 17. Food & Nutrition Board. 1998. Dietary Reference Intakes. National Academy Press, Wash- ington, D.C. 18. Webb, A. R., Pilbeam, C., Hanafin, N., Holick, M. F. 1990. An evaluation of the relative contributions of exposure to sunlight and of diet to the circulating concentrations of 25- hydroxyvitamin D in an elderly nursing home population in Boston. Am. J. Clin. Nutr. 51: 1075–1081. 19. Holick, M. F. 1995. Environmental factors that influence the cutaneous production of Vitamin

D. Am. J. Clin. Nutr. 61(Suppl.):638S–645S. 20. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Co- dex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C. 21. FAO. 1996. Food fortification technology and quality control. FAO technical meeting, Rome. FAO Food and Nutrition Paper 60. 22. Norman, A. W. 1996. Vitamin D. In: Present Knowledge in Nutrition, 7th ed., Ziegler, E. E., Filer, L. J., Jr. (Eds.). ILSI Press, Washington, D.C., pp. 120–129.

Vitamin E

23. Sokol, R. J. 1996. Vitamin E. In: Present Knowledge in Nutrition, 7th ed., Ziegler, E. E., Filer, L. J., Jr. (Eds). ILSI Press, Washington, D.C., pp. 130–136. 24. Meydani, S. N., Barklund, M. P., Liu, S., Meydani, M., Miller, R. A., Cannon, J. G., Morrow,

F. D., Rocklin, R., Blumberg, J. B. 1990. Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am. J. Clin. Nutr. 52:557–563.

25. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed., W. B. Saunders, Philadelphia. 26. Stampfer, M. J., Hennekens, C. H., Manson, J. E., Colditz, G. A., Rosner, B., Willett, W. C. 1993. Vitamin E consumption and the risk of coronary disease in women. New Engl. J. Med. 328:1444–1449. 27. Rimm, E. B., Stampfer, M. J., Ascherio, A., Giovannucci, E., Colditz, G. A. Willett, W. C. 1993. Vitamin E consumption and the risk of coronary heart disease in men. New Engl. J. Med . 328:1450–1456. 28. Ball, G. 1996. Determination of the fat-soluble vitamins in foods by high-performance liquid chromatography. In: Handbook of Food Analysis, Vol. 1, Physical Characterization and Nu- trient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 602–604. 29. Food and Nutrition Board. 1989. Recommended Dietary Allowances, 10th ed. National Acad- emy Press, Washington, D.C. 30. FAO. 1996. Food fortification technology and quality control. FAO technical meeting, Rome. FAO Food and Nutrition Paper 60. 31. Committee on Food Chemical Codex Food & Nutrition Board. 1996. Food Chemical Codex, 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Wash- ington, D.C.

Vitamin K

32. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition, and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 33. Olson, R. E., 1994. Vitamin K. In: Modern Nutrition in Health and Disease Eighth Edition, Shils, M. E., Olson J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 342–358. 34. Ferland, G., Sadowski, J. A., O’Brien, M. E. 1993. Dietary induced subclinical vitamin K deficiency in normal human subjects. J. Clin. Invest. 91:1761–1768. 35. Binkley, N. C., Suttie, J. W. 1995. Vitamin K nutrition and osteoporosis. J. Nutr. 125:1812– 1821. 36. Suttie, J. W. 1996. Vitamin K. In: Present Knowledge in Nutrition, 7th ed., Ziegler, E. E., Filer, L. J. (Eds.). ILSI Press, Washington, D.C., pp. 137–145. 37. Food and Nutrition Board. 1989. Recommended Dietary Allowances, 10th ed. National Acad- emy Press, Washington, D.C. 38. Ball, G. F. M. 1996. In: Handbook of Food Analysis, Vol. 1 Physical Characterization and Nutrient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 601–647. 39. Booth, S. L., Davidson, K. W., Sadowski, J. A. 1994. Evaluation of an HPLC method for the determination of phylloquinone (vitamin K1) in various food matrices. J. Agricult. Food Chem . 42:295–300. 40. Committee on Food Chemicals Codex, Food and Nutrition Board. 1997. Food Chemicals Codex: First Supplement to the Fourth Edition . Institute of Medicine, National Academy of Science. National Academy Press, Washington, D.C.

Vitamin C

41. Pauling, L. 1970. Vitamin C and the Common Cold. W. H. Freeman, San Francisco. 42. Food and Nutrition Board. 1989. Recommended Dietary Allowances, 10th ed., National Academy Press, Washington, D.C. 43. Levine, M., Rumsey, S., Wang, Y., Park, J., Kwon, O., Xu, W., Amano, N. 1996. Vitamin

C. In: Present Knowledge in Nutrition, 7th ed., Ziegler, E. E., Filer, L. J. Jr. (Eds.). ILSI Press, Washington, D.C., pp. 146–159.

44. Levine, M., Dhariwal, K. R., Welch, R. W., Wang, Y., Park, J. B. 1995. Determination of optimal vitamin C requirements in humans. Am. J. Clin. Nutr. 62(Suppl):1347S–1356S. 45. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 46. Vanderslice, J. T., Higgs, D. J. 1991. Vitamin C content of foods: sample variability. Am. J. Clin. Nutr . 54:1323S–1327S. 47. Jacob, R. A. 1994. Vitamin C. In: Modern Nutrition in Health and Disease, 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 432–448.

Thiamin

48. Mahan, L. K. & Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 49. Rindi, G., Patrini, C., Laforenza, U., Mandel, H., Berant, M., Viana, M. B., Poggi, V., Zarra,

A. N. F. 1994. Further studies on erythrocyte thiamin transport and phosphorylation in seven patients with thiamin-responsive megaloblastic anaemia. J. Inherited Metabolic Disease, 17: 667–677. 50. Rindi, G. 1996. Thiamin. In: Present Knowledge in Nutrition, 7th ed. Ziegler, E. E. Filer, L. J., Jr. (Eds.) ILSI Press, Washington, D.C., pp. 160–166. 51. Food and Nutrition Board. 1998. Dietary Reference Intakes for Thiamin Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C. 52. Russell, L. F. 1996. Water-soluble vitamins. In: Handbook of Food Analysis, Vol. 1, Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 649–713. 53. Committee on Food Chemicals Codex Food and Nutrition Board. 1996. Food Chemicals Codex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Riboflavin

54. Rivlin, R. S., Dutta, P. 1995. Vitamin B2 (riboflavin) relevance to malaria and antioxidant activity. Nutrition Today. 30:62–67. 55. McCormick, D. B. 1994. Riboflavin. In: Modern Nutrition in Health and Disease, 8th ed. Shils, M. E., Olson, J. A., Shike M. (Eds.). Williams & Wilkins, Baltimore, pp. 366–375. 56. Food & Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C. 57. Boisvert, W. A., Mendoza, I., Castaneda, C., De Portocarrero, L., Solomons, N. W., Gershoff, S. N., Russell, R. M. 1993. Riboflavin requirement of healthy elderly humans and its relation- ship to macronutrient composition of the diet. J. Nutr. 123:915–925. 58. Russell, L. F. 1996. In: Handbook of Food Analysis, Vol. 1, Physical Characterization and Nutrient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 649–713. 59. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Co- dex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Niacin

60. Jacob, R. A., Swendseid, M. E. 1996. In: Present Knowledge in Nutrition, 7th ed. Ziegler,

61. Food & Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C. 62. Krishnan, P. G., Mahmud, I., Mathees, D. P. 1996. Postcolumn fluorimetric HPLC procedure for determination of niacin content of cereals. Cereal Chem. 76(4):512–518. 63. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Co- dex . 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Vitamin B 6

64. Russell, L. F. 1996. Water-soluble vitamins. In: Handbook of Food Analysis, Volume 1 Physi- cal Characterization and Nutrient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 649–713. 65. Mahan, L. K. & Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 66. Rall, L. C., Meydani, S. N. 1993. Vitamin B6 and immune competence. Nutr. Rev. 51:217– 225. 67. Compton, M. M., Cidlowski, J. A. 1986. Vitamin B6 and glucocorticoid action. Endocrine Rev . 7:140–148. 68. Leklem, J. E. 1994. Vitamin B6. In: Modern Nutrition in Health and Disease, 8th ed., Shils M. E., Olson, J. A., Shike M. (Eds.). Williams & Wilkins, Baltimore, pp. 383–394. 69. Food & Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C. 70. Driskell, J. A. 1994. Vitamin B6 requirements of humans. Nutr. Res. 14:293–324. 71. Leklem, J. E. 1990. Vitamin B6: A status report. J. Nutr. 120:1503–1507. 72. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Co- dex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Pantothenic Acid

73. Plesofsky-Vig, N. 1996. Pantothenic Acid. In: Present Knowledge in Nutrition, 7th ed., Ziegler E. E., Filer, L. J., Jr. (Eds.) ILSI Press, Washington, D.C., pp. 237–244. 74. Plesofsky-Vig, N., Brambl, R. 1988. Pantothenic acid and coenzyme A in cellular modifica- tion of proteins. Ann. Rev. Nutr. 8:461–482. 75. Plesofsky-Vig, N. 1994. Pantothenic acid and coenzyme A. In: Modern Nutrition in Health and Disease , 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 395–401. 76. Food and Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C. 77. Tahiliani, A. G., Beinlich, C. J. 1991. Pantothenic acid in health and disease. Vitamin Hor- mone . 46:165–228. 78. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Codex 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Wash- ington, D.C.

Characterization and Nutrient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 649–713.

Folate

80. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 81. Czeizel, A. E. 1995. Folic acid in the prevention of neural tube defects. J. Pediatr. Gastroen- terol. Nutr . 2:4–16. 82. MRC Vitamin Study Research Group. 1991. Prevention of neural tube defects: results of the medical research council vitamin study. Lancet 338:131–137. 83. Herbert, V., Das, K. C. 1994. Folic acid and vitamin B12. In: Modern Nutrition in Health and Disease , 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 402–425. 84. Food and Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C. 85. Russell, L. F. 1996. Water-soluble vitamins. In: Handbook of Food Analysis, Vol. 1, Physical Characterization and Nutrient Analysis , Nollet L. M. L. (Ed.). Marcel Dekker, New York, pp. 649–713. 86. Seyoum, E., Selhub, J. 1993. Combined affinity and ion pair column chromatographies for the analysis of food folate. J. Nutr. Biochem. 4:488–494. 87. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Co- dex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Vitamin B 12

88. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed. W.B. Saunders, Philadelphia. 89. Rauma, A.-L., Torronen, R., Hanninen, O., Mykkanen, H. 1995. Vitamin B12 status of long- term adherents of a strict uncooked vegan diet (‘‘living food diet’’) is compromised. J. Nutr. 125:2511–2515. 90. Herbert, V. 1994. Staging vitamin B12 (cobalamin) status in vegetarians. Am. J. Clin. Nutr. 59(Suppl.):1213S–1222S. 91. Nygard, O., Vollset, S. E., Refsum, H., Stensvold, I., Tverdal, A., Nordrehuag, J. E., Ueland, P. M., Kvoale, G. 1995. Total plasma homocysteine and cardiovascular risk profile. JAMA 274:1518–1525. 92. Herbert, V. 1996. Vitamin B-12. In: Present Knowledge in Nutrition, 7th ed. Ziegler, E. E., Filer, L. J., Jr. (Eds.). ILSI Press, Washington, D.C., pp. 191–205. 93. Food and Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C. 94. Herbert, V. 1994. Vitamin B12 and elderly people. Am. J. Clin. Nutr. 59:1093–1094 (Letter). 95. Herbert, V., Das, K. C. 1994. Folic acid and vitamin B12. In: Modern Nutrition in Health and Disease , 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 402–425. 96. Russell, L. F. 1996. Water-soluble vitamins. In: Handbook of Food Analysis, Vol. 1, Physical Characterization and Nutrient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York,

97. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Co- dex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Biotin

98. Mock, D. M. 1996. Biotin. In: Present Knowledge in Nutrition, 7th ed., Ziegler, E. E., Filer, L. J., Jr. (Eds.). ILSI Press, Washington, D.C., pp. 220–235. 99. Velazquez, A., Martin-del-Campo, C., Baez, A., Zamudio, S., Quiterio, M., Aguilar, J. L., Perez-Ortiz, B, Sanchez-Ardines, Guzman-Hernandez, J., Casanueva, E. 1989. Biotin defi- ciency in protein-energy malnutrition. Eur. J. Clin. Nutr. 43:169–173.

100. Velazquez, A., Teran, M., Baez, A., Gutierrez, J., Rodriguez, R. 1995. Biotin supplementa- tion affects lymphocyte carboxylases and plasma biotin in severe protein-energy malnutrition. Am. J. Clin. Nutr . 61:385–391.

101. Russell, L. F. 1996. Water-soluble vitamins. In: Handbook of Food Analysis, Vol. 1, Physical Characterization and Nutrient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 649–713.

102. Food and Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C.

103. Dakshinamurti, K. 1994. Biotin. In: Modern Nutrition in Health and Disease, 8th ed., Shils,

M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 426–431. 104. Committee on Food Chemicals Codex Food & Nutrition Board. 1996. Food Chemicals Co- dex , 4th ed., Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Choline

105. Savendahl, L., Mar, M.-H. Underwood, L. E., Zeisel, S. H. 1997. Prolonged fasting in humans results in diminished plasma choline concentrations but does not cause liver dysfunction. Am. J. Clin. Nutr . 66:622–625.

106. Anderson, K. N., Anderson, L. E., Glanze, W. D. 1994. Mosby’s Medical, Nursing, and Allied Health Dictionary , 4th ed., Mosby-Year Book, St. Louis. 107. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed., W. B. Saunders, Philadelphia. 108. Zeisel, S. H., DaCosta, K.-A. Franklin, P. D., Alexander, E. A., Lamont, J. T., Sheard, N. F.,

Beiser, A. 1991. Choline, an essential nutrient for humans. FASAB. 5:2093–2098. 109. Zeisel, S. H. 1994. Choline. In: Modern Nutrition in Health and Disease, 8th ed., Shils,

M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 449–458. 110. Food and Nutrition Board. 1998. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin and Choline . Committee on the Scientific Evaluation of Dietary Reference Intakes. National Academy Press, Washington, D.C.

111. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex . 4th ed., Institute of Medicine, National Academy of Science. National Academy Press, Washington, D.C.

112. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex . 4th ed., Institute of Medicine, National Academy of Science. National Academy Press, Washington, D.C.

113. Whitney, E. N., Rolfes, S. R. 1996. Understanding Nutrition, 7th ed., West Publishing, St.

Carnitine

114. Anderson, K. N., Anderson, L. E., Glanze, W. D. 1994. Mosby’s Medical, Nursing and Allied Health Dictionary , 4th ed. Mosby-Year Book, St. Louis. 115. Borum, P. R. 1996. Changing perspective of carnitine function and the need for exogenous carnitine of patients treated with hemodialysis. Am. J. Clin. Nutr. 64:976–977. 116. Chen, W., Huang, Y.-C., Shultz, T. D., Mitchell, M. E. 1998. Urinary, plasma, and erythro- cyte carnitine concentration during transition to a lactoovovegetarian diet with vitamin B6 depletion and repletion in young adult women. Am. J. Clin. Nutr. 67:221–230.

117. Harper, P., Wadstrom, C., Backman, L., Cederblad, G. 1995. Increased liver carnitine content in obese women. Am. J. Clin. Nutr. 61:18–25. 118. Broquist, H. P. 1994. Carnitine. In: Modern Nutrition in Health and Disease, 8th ed., Shils,

M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 459–465. 119. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 120. Whitney, E. N., Rolfes, S. R. 1996. Understanding Nutrition, 7th ed., West Publishing, St. Paul, MN.

Inositol

121. Aukeman, H. M., Holub, B. J. 1994. Inositol and pyrroloquinoline quinone. In: Modern Nutri- tion in Health and Disease 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore, pp. 466–472.

122. Fux, M., Levine, J., Aviv, A., Belmaker, R. H. 1996. Inositol treatment of obsessive-compul- sive disorder. Am. J. Psychiatry 153:1219–1221. 123. Benjamin, J., Levine, J., Fux, M., Aviv, A., Levy, D., Belmaker, R. H. 1995. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. Am. J. Psychiatry 152:1084–1086.

124. Levine, J., Barak, Y., Gonzalves, M., Szor, H., Elizur, A., Kofman, O., Belmaker, R. H. 1995. Double-blind, controlled trial of inositol treatment of depression. Am. J. Psychiatry 152:792–794.

125. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex . 4th ed., Institute of Medicine, National Academy of Science. National Academy Press, Washington, D.C.

Amino Acids

126. Baxter, J. H. 1996. Amino Acids. In: Handbook of Food Analysis Vol. 1, Physical Character- ization and Nutrient Analysis , Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 197– 228.

127. Polge, A., Bancel, E., Bellet, H., Strubel, D., Poirey, S., Peray, P., Carlet, C., Magnan de Bornier, B. 1997. Plasma amino acid concentrations in elderly patients with protein energy malnutrition. Age and Aging 26:457–463.

128. Obarzanek, E., Velletri, P. A., Cutler, J. A. 1996. Dietary protein and blood pressure. JAMA 275:1598–1603. 129. American Dietetic Association. 1999. In the news high-protein/low-carbohydrate diets. http:/ /www.eatright.org/news. Accessed July 5, 1999 . 130. Zeman, F. J., Ney, D. M. 1996. Applications in Medical Nutrition Therapy, 2nd ed. Prentice Hall, Upper Saddle River, NJ. 131. Committee on Food Chemicals Codex, Food & Nutrition Board. 1996. Food Chemicals Co- dex , 4th ed., Institute of Medicine, National Academy of Sciences. National Academy Press,

132. Committee on Food Chemicals Codex, Food & Nutrition Board. 1997. Food Chemicals Co- dex: First Supplement to the Fourth Edition . Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

133. Crim, M. C., Munro, H. N. 1994. Proteins and Amino Acids. In: Modern Nutrition in Health and Disease , 8th ed., Shils, M. E., Olson, J. A., Shike, M. (Eds.). Williams & Wilkins, Baltimore.

Fatty Acids

134. Andersen, K. N., Anderson, L. E., Glanze, W. D. 1994. Mosby’s Medical, Nursing, and Allied Health Dictionary , 4th ed. Mosby-Year Book, St. Louis. 135. Mahan, L. K., Escott-Stemp, S. 1996. Krause’s Food, Nutrition & Diet Therapy, 9th ed., W. B. Saunders, Philadelphia. 136. Rowe, P. M. 1995. Fat of the land and of the lab. Lancet 346:46. 137. Walling, A. D. 1998. Linolenic acid and calcium for prevention of preeclampsia. Am Family

Physician , 58:252. 138. Hu, F. B., Stampfer, M. J., Manson, J. E., Rimm, E. B., Wolk, A., Colditz, G. A., Hennekens, C. H., Wilett, W. C. 1999. Dietary intake of (alpha)-linolenic acid and risk of fatal ischemic heart disease among women. Am. J. Clin. Nutr. 69:890. 139. Willett, W. C. 1997. Specific fatty acids and risks of breast and prostate cancer: dietary intake. Am. J. Clin. Nutr. 66:1557S–1563S. 140. Ascherio, A., Willett, W. C. 1997. Health effects of trans fatty acids. Am. J. Clin. Nutr. 66: 1006S–1010S. 141. ASCN/AIN Task Force on Trans Fatty Acids. 1996. Position paper on trans fatty acids. Am. J. Clin. Nutr . 63:663–670. 142. Committee on Food Chemicals Codex, Food and Nutrition Board. 1997. Food Chemicals Codex , 4th ed., Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D. C.

143. Mossoba, M. M., Firestone, D. 1996. New methods for fat analysis in foods. Food Testing Anal. 24–32. 144. Sempore, B. G., Bezard, J. A. 1996. Analysis of Neutral Lipids: Fatty Acids. In: Handbook of Food Analysis , Vol. 1 Physical Characterization and Nutrient Analysis, Nollet, L. M. L. (Ed.). Marcel Dekker, New York, pp. 331–394.

Vitamins and Trace Minerals

145. Food and Nutrition Board. 1998. Recommended Dietary Allowances, 11th ed. National Acad- emy Press, Washington, D.C. 146. Abrams, S. A., Grusak, M. A. Stuff, J., O’Brien, K. O. 1997. Calcium and magnesium balance in 9–14-year-old children. Am J. Clin. Nutr. 66:1172–1177. 147. Harel, Z. 1998. Adolescents and calcium: what they do and do not know and how much they consume. JAMA 279:1678F. 148. Perman, J. A., Dudley, B. S. 1998. Dairy products: try them—you’ll like them? Am. J. Clin. Nutr . 68:995–996. 149. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

150. Committee on Food Chemicals Codex, Food and Nutrition Board. 1997. Food Chemicals Codex First Supplement to the Fourth Edition . Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

Phosphorus

152. Larson Duyff, R. 1998. The American Dietetic Association’s Complete Food & Nutrition Guide . Chronimed Publishing, Minneapolis, MN. 153. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition, & Diet Therapy. 9th ed. W. B. Saunders, Philadelphia. 154. Dalton, M. A., Sargent, J. D., O’Connor, GT, Olmstead, E. M., Klein, R. Z. 1997. Calcium and phosphorus supplementation of iron-fortified infant formula: no effect on iron status of healthy full-term infants. Am. J. Clin. Nutr. 65:921–926.

155. Boaz, M., Smetana, S. 1996. Regression equation predicts dietary phosphorus intake from estimate of dietary protein intake. J Am Dietetic Assoc 96:1268–1270. 156. Food and Nutrition Board. 1998. Recommended Dietary Allowances, 11th ed. National Acad- emy Press, Washington, D.C. 157. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

158. Pennington, J. A. T. 1996. Intakes of minerals from diets and food: is there a need for con- cern? J Nutr. 126:2304S–2308S. 159. Bercowy, GM, Peile, R. 1996. GFAA determination of phosphorus in food oils. Food Testing Anal. Aug.–Sept.:10,15,41.

Magnesium

160. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition, and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 161. Wood, R. J. Suter, P. M., Russell, R. M. 1995. Mineral requirements of elderly people. Am. J. Clin. Nutr . 62:493–505. 162. Schuck, P., Gammelin, G., Resch, K. L. 1998. Magnesium and phosphorus. Lancet 1474. 163. Nelson, J. K., Moxness, K. E., Jensen, M. D., Gastineau, C. F. 1994. Mayo Clinic Diet

Manual 7th ed. Mosby-Year Book, St. Louis. 164. Larson Duyff, R. The American Dietetic Association’s Complete Food and Nutrition Guide. Chronimed Publishing, Minneapolis, MN. 165. Food and Nutrition Board. 1998. Recommended Dietary Allowances, 11th ed. National Acad- emy Press, Washington, D.C. 166. Committee on Food Chemicals Codex, Food and Nutrition Board. 1997. Food Chemicals Codex . Institute of Medicine, National Academy of Sciences. National Academy Press, Washington D.C.

167. Pomeranz, Y., Meloan, C. E. 1994. Food Analysis, Theory and Practice, 3rd ed. Chapman & Hall, New York. 168. Pennington, J. A. T. Intakes of minerals from diets and foods: is there a need for concern? J Nutr 126:2304S–2308S.

Potassium, Sodium, and Chloride

169. Gennari, F. J. 1998. Hypokalemia. New Eng J Med 339:451–458. 170. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals

Codex . 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington D.C.

171. Pennington, JAT. 1996. Intakes of minerals from diets and foods: is there a need for concern? J Nutr 126:2304S–2308S. 172. Pomeranz, Y., Meloan C. E. 1994. Food Analysis, Theory and Practice, 3rd ed. Chapman

173. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition, and Diet Therapy. 9th ed. W. B. Saunders, Philadelphia. 174. Duyff, R. L. 1998. The American Dietetic Association’s Complete Food & Nutrition Guide. Chronimed Publishing, Minneapolis, MN. 175. Engstrom, A., Tobelmann, R. C., Albertson, A. M. 1997. Sodium intake trends and food choices. Am. J. Clin. Nutr. 65:704S–707S. 176. Kotchen, T. A., Kotchen, J. M. 1997. Dietary sodium and blood pressure: interactions with other nutrients. Am. J. Clin. Nutr. 65:708S–711S. 177. Weinberger, M. H. 1997. More spice on the salt debate. Arc Inter Med 157:2407–2409. 178. Luft, F. C. 1996. Salt, water and extracellular volume regulation. In: Present Knowledge in

Nutrition , 7th ed. Ziegler, E. E., Filer, L. J., Jr. (Eds.). ILSI Press, Washington, D.C. pp. 265– 271.

179. Welsh, M. J., Smith, A. E. 1995. Cystic fibrosis. Scientific American 273:52–60. 180. Sojo, A. 1995. Chloride deficiency as a presentation or complication of cystic fibrosis. JAMA

273:441. 181. Helrich, K. 1990. Official Methods of Analysis, Vol. 1, 15th ed. Association of Official Ana- lytical Chemists, Arlington, VA.

Iron

182. Duyff, R. L. 1998. American Dietetic Association’s Complete Food and Nutrition Guide. Chronimed Publishing, Minneapolis, MN. 183. Food and Nutrition Board. 1989. Recommended Dietary Allowances, 10th ed. National Acad- emy Press, Washington, D.C. 184. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition, and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia. 185. Yip, R., Dallman, P. R. Iron. 1996. In: Present Knowledge in Nutrition, 7th ed., Ziegler, E. E., Filer, L. J., Jr. (Eds). ILSI Press, Washington, D.C., pp. 277–292. 186. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

187. Hong, J. H., Yasumoto, K. 1996. Near-infrared spectroscopic analysis of heme and nonheme iron in raw meats. J. Food Comp. Analy. 9:127–134.

Zinc

188. Andrews, M., Gallagher-Allred, C. 1999. The role of zinc in wound healing. Advances in Wound Care 12:137–138. 189. Fortes, C. et al. The effect of zinc and vitamin A supplementation on immune response in an older population. JAMA 279:726h (Abstract). 190. Mossad, S. B., Macknin, M. L., Medendorp, S. V., Mason, P. 1996. Zinc gluconate lozenges for treating the common cold. Ann. Intern. Med. 125:81–88. 191. Macknin, M. L., Piedmonte, M., Calendine, C., Janosky, J., Wald E. 1998. Zinc gluconate lozenges for treating the common cold in children. JAMA 279:1962–1967. 192. Nicoara-Kasti, G. L., Lockey, R. F. 1998. Disease prevention:which nutritional supplements, vitamins, and medications may help? Consultant Feb.:397–400. 193. Food and Nutrition Board. 1989. Recommended Dietary Allowances, 10th ed. National Acad- emy Press, Washington, D.C. 194. Duyff, R. L. 1998. American Dietetic Association’s Complete Food and Nutrition Guide. Chronimed Publishing, Minneapolis, MN. 195. Wood, R. J., Zheng, J. J. 1997. High dietary calcium intakes reduce zinc absorption and

196. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex . 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington DC.

197. Pomeranz, Y., Meloan, C. E. 1994. Food Analysis, Theory and Practice. Chapman & Hall, New York.

Copper

198. Olivares, M., Uauy, R. 1996. Copper as an essential nutrient. Am. J. Clin. Nutr. 63:791S– 796S. 199. Lonnerdal, B. 1996. Bioavailability of copper. Am. J. Clin. Nutr. 63:821S–829S. 200. Uauy, R., Olivares, M., Gonzalez, M. 1998. Essentiality of copper in humans. Am. J. Clin.

Nutr . 67(Suppl):952S–959S. 201. Anderson, K. N., Anderson, L. E. 1998. Mosby’s Medical, Nursing and Allied Health Dic- tionary , 5th ed. Mosby-Year Book, St. Louis. 202. Food and Nutrition Board. 1989. Recommended Dietary Allowances, 10th ed. National Acad- emy Press, Washington, D.C. 203. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy Press, Washington, D.C.

204. Pomeranz, Y., Meloan, C. E. 1994. Food Analysis, Theory and Practice, 3rd ed. Chapman & Hall, New York.

Iodine

205. Delange, F. 1998. Risks and benefits of iodine supplementation. Lancet 351:923–924. 206. Tiwari, B. D., Godbole, M. M., Chattopadhyay, N., Mandal, A., Mithal, A. 1996. Learning

disabilities and poor motivation to achieve due to prolonged iodine deficiency. Am. J. Clin. Nutr . 63:782–786.

207. Levander, O. A., Whanger, P. D. 1996. Deliberations and evaluations of the approaches, endpoints and paradigms for selenium and iodine dietary recommendations. J. Nutr. 126: 2427S–2434S.

208. Khan, L. K., Li, R., Gootnick, D., Peace Corps Thyroid Investigation Group. 1998. Thyroid

abnormalities related to iodine excess from water purification units. Lancet 352:1519. 209. Duyff, R. L. 1998. The American Dietetic Association’s Complete Food & Nutrition Guide. Minneapolis, MN: Chronimed Publishing. 210. Schilling, J. S. 1997. Hyperthyroidism: diagnosis and management of graves’ disease. The Nurse Practitioner. 22:72–95. 211. Food and Nutrition Board. 1989. Recommended Dietary Allowances. 10th Ed. Washington, D.C.: National Academy Press. 212. Committee on Food Chemicals Codes, Food and Nutrition Board, Institute of Medicine, National Academy of Sciences. 1996. Food Chemicals Codex. 4th Ed. Washington, D.C.: National Academy Press.

213. Sadecka, J., Polonsky, J. 1999. Determination of inorganic ions in food and beverages by capillary electrophoresis. J. Chromatogr. A. 834:401–417.

Manganese

214. Mahan, L. K., Escott-Stump, S. 1996. Krause’s Food, Nutrition and Diet Therapy, 9th ed. W. B. Saunders, Philadelphia.

proaches, endpoints and paradigms for manganese and molybdenum dietary recommenda- tions. J. Nutr. 126:2435S–2440S.

216. Food and Nutrition Board. Recommended Dietary Allowances, 10th ed. National Academy Press, Washington, D.C. 217. Barceloux, D. G. 1999. Manganese. J. Toxicol. Clin. Toxicol. 37:293. 218. Fell, J. M. E., Reynolds, A. P., Meadows, N., Khan, K., Long, S. G., Quaghebeur, G., Taylor,

W. J., Milla, P. J. 1996. Manganese toxicity in children receiving long-term parenteral nutri- tion. Lancet. 347:1218–1221.

219. Committee on Food Chemicals Codex, Food and Nutrition Board. 1996. Food Chemicals Codex , 4th ed. Institute of Medicine, National Academy of Sciences. National Academy, Press, Washington, D.C.

220. Pomeranz, Y., Meloan, C. E. 1994. Food Analysis, Theory and Practice, 3rd ed. Chapman & Hall, New York.

Dietary Supplements

221. Kurtzweil, P. 1999. An FDA guide to dietary supplements. In: Nutrition, 11th ed., Cook- Fuller, C. C. (Ed.). Dushkin/McGraw-Hill, Guilford, CT, pp. 27–34. 222. Camire, M. E., Kantor, M. A. 1999. Dietary supplements: nutritional and legal considerations. Food Tech . 53:87–96. 223. Kurtzweil, P. 1998. An FDA guide to dietary supplements. FDA Consumer 32:28–35.

Essential Fatty Acids as Food Additives

DAVID J. KYLE

Martek Biosciences Corporation, Columbia, Maryland