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Micronutrient Information Center

References: L-Carnitine


1.  Rebouche CJ. Carnitine. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. 10th ed. Philadelphia: Lippincott, Williams & Wilkins; 2006:537-544.

2.  Fraenkel G, Friedman S. Carnitine. Vitam Horm. 1957;15:73-118.

3.  De Grandis D, Minardi C. Acetyl-L-carnitine (levacecarnine) in the treatment of diabetic neuropathy. A long-term, randomised, double-blind, placebo-controlled study. Drugs R D. 2002;3(4):223-231.  (PubMed)

4.  Seim H, Eichler K, Kleber H. L(-)-Carnitine and its precursor, gamma-butyrobetaine. In: Kramer K, Hoppe P, Packer L, eds. Nutraceuticals in Health and Disease Prevention. New York: Marcel Dekker, Inc.; 2001:217-256. 

5.  Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. 2004;1033:30-41.  (PubMed)

6.  Rebouche CJ. Carnitine function and requirements during the life cycle. FASEB J. 1992;6(15):3379-3386.  (PubMed)

7.  Rebouche CJ. Ascorbic acid and carnitine biosynthesis. Am J Clin Nutr. 1991;54(6 Suppl):1147S-1152S.  (PubMed)

8.  Lombard KA, Olson AL, Nelson SE, Rebouche CJ. Carnitine status of lactoovovegetarians and strict vegetarian adults and children. Am J Clin Nutr. 1989;50(2):301-306.  (PubMed)

9.  Rebouche CJ, Chenard CA. Metabolic fate of dietary carnitine in human adults: identification and quantification of urinary and fecal metabolites. J Nutr. 1991;121(4):539-546.  (PubMed)

10.  Gross CJ, Henderson LM, Savaiano DA. Uptake of L-carnitine, D-carnitine and acetyl-L-carnitine by isolated guinea-pig enterocytes. Biochim Biophys Acta. 1986;886(3):425-433.  (PubMed)

11.  Rebouche CJ, Lombard KA, Chenard CA. Renal adaptation to dietary carnitine in humans. Am J Clin Nutr. 1993;58(5):660-665.  (PubMed)

12.  Foster DW. The role of the carnitine system in human metabolism. Ann N Y Acad Sci. 2004;1033:1-16.  (PubMed)

13.  McGrane MM. Carbohydrate metabolism--synthesis and oxidation. In: Stipanuk MH (ed). Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co; 2000:158-210. 

14.  Olson AL, Nelson SE, Rebouche CJ. Low carnitine intake and altered lipid metabolism in infants. Am J Clin Nutr. 1989;49(4):624-628.  (PubMed)

15.  American Academy of Pediatrics, Committee on Nutrition. Soy protein-based formulas: recommendations for use in infant feeding. Pediatrics. 1998;101(1):148-152.  (PubMed)

16.  Nezu J, Tamai I, Oku A, et al. Primary systemic carnitine deficiency is caused by mutations in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet. 1999;21(1):91-94.  (PubMed)

17.  Stanley CA. Carnitine deficiency disorders in children. Ann N Y Acad Sci. 2004;1033:42-51.  (PubMed)

18.  Kerner J, Hoppel C. Genetic disorders of carnitine metabolism and their nutritional management. Annu Rev Nutr. 1998;18:179-206.  (PubMed)

19.  Pons R, De Vivo DC. Primary and secondary carnitine deficiency syndromes. J Child Neurol. 1995;10 Suppl 2:S8-24.  (PubMed)

20.  Gregory MJ, Schwartz GJ. Diagnosis and treatment of renal tubular disorders. Semin Nephrol. 1998;18(3):317-329.  (PubMed)

21.  Calvani M, Benatti P, Mancinelli A, et al. Carnitine replacement in end-stage renal disease and hemodialysis. Ann N Y Acad Sci. 2004;1033:52-66.  (PubMed)

22.  Winter SC, Szabo-Aczel S, Curry CJ, Hutchinson HT, Hogue R, Shug A. Plasma carnitine deficiency. Clinical observations in 51 pediatric patients. Am J Dis Child. 1987;141(6):660-665.  (PubMed)

23.  Food and Nutrition Board, Institute of Medicine. Vitamin C. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington D.C.: National Academy Press; 2000:95-185.  (National Academy Press)

24.  Costell M, O'Connor JE, Grisolia S. Age-dependent decrease of carnitine content in muscle of mice and humans. Biochem Biophys Res Commun. 1989;161(3):1135-1143.  (PubMed)

25.  Hagen TM, Ingersoll RT, Wehr CM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci U S A. 1998;95(16):9562-9566.  (PubMed)

26.  Pesce V, Fracasso F, Cassano P, Lezza AM, Cantatore P, Gadaleta MN. Acetyl-L-carnitine supplementation to old rats partially reverts the age-related mitochondrial decay of soleus muscle by activating peroxisome proliferator-activated receptor gamma coactivator-1alpha-dependent mitochondrial biogenesis. Rejuvenation Res. 2010;13(2-3):148-151.  (PubMed)

27.  Gomez LA, Heath SH, Hagen TM. Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart. Mech Ageing Dev. 2012;133(2-3):99-106.  (PubMed)

28.  Hagen TM, Liu J, Lykkesfeldt J, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A. 2002;99(4):1870-1875.  (PubMed)

29.  Liu J, Head E, Gharib AM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99(4):2356-2361.  (PubMed)

30.  Muthuswamy AD, Vedagiri K, Ganesan M, Chinnakannu P. Oxidative stress-mediated macromolecular damage and dwindle in antioxidant status in aged rat brain regions: role of L-carnitine and DL-alpha-lipoic acid. Clin Chim Acta. 2006;368(1-2):84-92.  (PubMed)

31.  Kumaran S, Panneerselvam KS, Shila S, Sivarajan K, Panneerselvam C. Age-associated deficit of mitochondrial oxidative phosphorylation in skeletal muscle: role of carnitine and lipoic acid. Mol Cell Biochem. 2005;280(1-2):83-89.  (PubMed)

32.  Kumaran S, Subathra M, Balu M, Panneerselvam C. Supplementation of L-carnitine improves mitochondrial enzymes in heart and skeletal muscle of aged rats. Exp Aging Res. 2005;31(1):55-67.  (PubMed)

33.  Savitha S, Panneerselvam C. Mitochondrial membrane damage during aging process in rat heart: potential efficacy of L-carnitine and DL alpha lipoic acid. Mech Ageing Dev. 2006;127(4):349-355.  (PubMed)

34.  Savitha S, Sivarajan K, Haripriya D, Kokilavani V, Panneerselvam C. Efficacy of levo carnitine and alpha lipoic acid in ameliorating the decline in mitochondrial enzymes during aging. Clin Nutr. 2005;24(5):794-800.  (PubMed)

35.  Sethumadhavan S, Chinnakannu P. Carnitine and lipoic Acid alleviates protein oxidation in heart mitochondria during aging process. Biogerontology. 2006;7(2):101-109.  (PubMed)

36.  Sundaram K, Panneerselvam KS. Oxidative stress and DNA single strand breaks in skeletal muscle of aged rats: role of carnitine and lipoicacid. Biogerontology. 2006;7(2):111-118.  (PubMed)

37.  Sethumadhavan S, Chinnakannu P. L-carnitine and alpha-lipoic acid improve age-associated decline in mitochondrial respiratory chain activity of rat heart muscle. J Gerontol A Biol Sci Med Sci. 2006;61(7):650-659.  (PubMed)

38.  Tamilselvan J, Jayaraman G, Sivarajan K, Panneerselvam C. Age-dependent upregulation of p53 and cytochrome c release and susceptibility to apoptosis in skeletal muscle fiber of aged rats: role of carnitine and lipoic acid. Free Radic Biol Med. 2007;43(12):1656-1669.  (PubMed)

39.  Aliev G, Liu J, Shenk JC, et al. Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and lipoic acid to aged rats. J Cell Mol Med. 2009;13(2):320-333.  (PubMed)

40.  Lopaschuk G. Regulation of carbohydrate metabolism in ischemia and reperfusion. Am Heart J. 2000;139(2 Pt 3):S115-119.  (PubMed)

41.  Davini P, Bigalli A, Lamanna F, Boem A. Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Res. 1992;18(8):355-365.  (PubMed)

42.   Xue YZ, Wang LX, Liu HZ, Qi XW, Wang XH, Ren HZ. L-carnitine as an adjunct therapy to percutaneous coronary intervention for non-ST elevation myocardial infarction. Cardiovasc Drugs Ther. 2007;21(6):445-448.  (PubMed)

43.  Iyer R, Gupta A, Khan A, Hiremath S, Lokhandwala Y. Does left ventricular function improve with L-carnitine after acute myocardial infarction? J Postgrad Med. 1999;45(2):38-41.  (PubMed)

44.  Colonna P, Iliceto S. Myocardial infarction and left ventricular remodeling: results of the CEDIM trial. Carnitine Ecocardiografia Digitalizzata Infarto Miocardico. Am Heart J. 2000;139(2 Pt 3):S124-130.  (PubMed)

45.  Iliceto S, Scrutinio D, Bruzzi P, et al. Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: the L-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) Trial. J Am Coll Cardiol. 1995;26(2):380-387.  (PubMed)

46.  Tarantini G, Scrutinio D, Bruzzi P, Boni L, Rizzon P, Iliceto S. Metabolic treatment with L-Carnitine in acute anterior ST segment elevation myocardial infarction. A randomized controlled trial. Cardiology. 2006;106(4):215-223.  (PubMed)

47.  Trupp RJ, Abraham WT. Congestive heart failure. In: Rakel RE, Bope ET, eds. Conn's Current Therapy. 54th ed. New York: W.B. Sunders Company 2002:306-313. 

48.  Rizos I. Three-year survival of patients with heart failure caused by dilated cardiomyopathy and L-carnitine administration. Am Heart J. 2000;139(2 Pt 3):S120-123.  (PubMed)

49.  Anand I, Chandrashekhan Y, De Giuli F, et al. Acute and chronic effects of propionyl-L-carnitine on the hemodynamics, exercise capacity, and hormones in patients with congestive heart failure. Cardiovasc Drugs Ther. 1998;12(3):291-299.  (PubMed)

50.  Study on propionyl-L-carnitine in chronic heart failure. Eur Heart J. 1999;20(1):70-76.  (PubMed)

51.  Serati AR, Motamedi MR, Emami S, Varedi P, Movahed MR. L-carnitine treatment in patients with mild diastolic heart failure is associated with improvement in diastolic function and symptoms. Cardiology. 2010;116(3):178-182.  (PubMed)

52.  Cacciatore L, Cerio R, Ciarimboli M, et al. The therapeutic effect of L-carnitine in patients with exercise-induced stable angina: a controlled study. Drugs Exp Clin Res. 1991;17(4):225-235.  (PubMed)

53.  Cherchi A, Lai C, Angelino F, et al. Effects of L-carnitine on exercise tolerance in chronic stable angina: a multicenter, double-blind, randomized, placebo controlled crossover study. Int J Clin Pharmacol Ther Toxicol. 1985;23(10):569-572.  (PubMed)

54.  Iyer RN, Khan AA, Gupta A, Vajifdar BU, Lokhandwala YY. L-carnitine moderately improves the exercise tolerance in chronic stable angina. J Assoc Physicians India. 2000;48(11):1050-1052.  (PubMed)

55.  Bartels GL, Remme WJ, Pillay M, Schonfeld DH, Kruijssen DA. Effects of L-propionylcarnitine on ischemia-induced myocardial dysfunction in men with angina pectoris. Am J Cardiol. 1994;74(2):125-130.  (PubMed)

56.  Mills JL. Peripheral arterial disease. In: Rakel RE, Bope ET, eds. Conn's Current Therapy. 54th ed. New York: W.B. Sunders Company; 2002:340-343. 

57.  Brevetti G, Perna S, Sabba C, Martone VD, Condorelli M. Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study. J Am Coll Cardiol. 1995;26(6):1411-1416.  (PubMed)

58.  Brevetti G, Diehm C, Lambert D. European multicenter study on propionyl-L-carnitine in intermittent claudication. J Am Coll Cardiol. 1999;34(5):1618-1624.  (PubMed)

59.  Hiatt WR. Carnitine and peripheral arterial disease. Ann N Y Acad Sci. 2004;1033:92-98.  (PubMed)

60.  Santo SS, Sergio N, Luigi DP, et al. Effect of PLC on functional parameters and oxidative profile in type 2 diabetes-associated PAD. Diabetes Res Clin Pract. 2006;72(3):231-237.  (PubMed)

61.  Brevetti G, Perna S, Sabba C, et al. Superiority of L-propionylcarnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease: an acute, intravenous, double-blind, cross-over study. Eur Heart J. 1992;13(2):251-255.  (PubMed)

62.  Cipolla MJ, Nicoloff A, Rebello T, Amato A, Porter JM. Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism. J Vasc Surg. 1999;29(6):1097-1103.  (PubMed)

63.  Loffredo L, Marcoccia A, Pignatelli P, et al. Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J. 2007;28(5):608-612.  (PubMed)

64.  Guarnieri G, Situlin R, Biolo G. Carnitine metabolism in uremia. Am J Kidney Dis. 2001;38(4 Suppl 1):S63-67.  (PubMed)

65.  Hurot JM, Cucherat M, Haugh M, Fouque D. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol. 2002;13(3):708-714.  (PubMed)

66.  Vesela E, Racek J, Trefil L, Jankovy'ch V, Pojer M. Effect of L-carnitine supplementation in hemodialysis patients. Nephron. 2001;88(3):218-223.  (PubMed)

67.  Kazmi WH, Obrador GT, Sternberg M, et al. Carnitine therapy is associated with decreased hospital utilization among hemodialysis patients. Am J Nephrol. 2005;25(2):106-115.  (PubMed)

68.  Weinhandl ED, Rao M, Gilbertson DT, Collins AJ, Pereira BJ. Protective effect of intravenous levocarnitine on subsequent-month hospitalization among prevalent hemodialysis patients, 1998 to 2003. Am J Kidney Dis. 2007;50(5):803-812.  (PubMed)

69.  Clinical practice guidelines for nutrition in chronic renal failure. K/DOQI, National Kidney Foundation. American Journal of Kidney Diseases. 2000;35(6 Suppl 2):S1-140.  (PubMed)

70.  Eknoyan G, Latos DL, Lindberg J. Practice recommendations for the use of L-carnitine in dialysis-related carnitine disorder. National Kidney Foundation Carnitine Consensus Conference. Am J Kidney Dis. 2003;41(4):868-876.  (PubMed)

71.  Schreiber B. Safety of oral carnitine in dialysis patients. Semin Dial. 2002;15(1):71-72.  (PubMed)

72.  Pettegrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging. 1995;16(1):1-4.  (PubMed)

73.  Spagnoli A, Lucca U, Menasce G, et al. Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology. 1991;41(11):1726-1732.  (PubMed)

74.  Sano M, Bell K, Cote L, et al. Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol. 1992;49(11):1137-1141.  (PubMed)

75.  Thal LJ, Carta A, Clarke WR, et al. A 1-year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology. 1996;47(3):705-711.  (PubMed)

76.  Thal LJ, Calvani M, Amato A, Carta A. A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. Neurology. 2000;55(6):805-810.  (PubMed)

77.  Brooks JO, 3rd, Yesavage JA, Carta A, Bravi D. Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. Int Psychogeriatr. 1998;10(2):193-203.  (PubMed)

78.  Moretti S, Alesse E, Di Marzio L, et al. Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood. 1998;91(10):3817-3824.  (PubMed)

79.  Moretti S, Famularo G, Marcellini S, et al. L-carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine. Antioxid Redox Signal. 2002;4(3):391-403.  (PubMed)

80.  Arrigoni-Martelli E, Caso V. Carnitine protects mitochondria and removes toxic acyls from xenobiotics. Drugs Exp Clin Res. 2001;27(1):27-49.  (PubMed)

81.  Scarpini E, Sacilotto G, Baron P, Cusini M, Scarlato G. Effect of acetyl-L-carnitine in the treatment of painful peripheral neuropathies in HIV+ patients. J Peripher Nerv Syst. 1997;2(3):250-252.  (PubMed)

82.  Osio M, Muscia F, Zampini L, et al. Acetyl-l-carnitine in the treatment of painful antiretroviral toxic neuropathy in human immunodeficiency virus patients: an open label study. J Peripher Nerv Syst. 2006;11(1):72-76.  (PubMed)

83.  Youle M, Osio M. A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV Med. 2007;8(4):241-250.  (PubMed)

84.  Hart AM, Wilson AD, Montovani C, et al. Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. Aids. 2004;18(11):1549-1560.  (PubMed)

85.  Herzmann C, Johnson MA, Youle M. Long-term effect of acetyl-L-carnitine for antiretroviral toxic neuropathy. HIV Clin Trials. 2005;6(6):344-350.  (PubMed)

86.  Jeulin C, Lewin LM. Role of free L-carnitine and acetyl-L-carnitine in post-gonadal maturation of mammalian spermatozoa. Hum Reprod Update. 1996;2(2):87-102.  (PubMed)

87.  Vitali G, Parente R, Melotti C. Carnitine supplementation in human idiopathic asthenospermia: clinical results. Drugs Exp Clin Res. 1995;21(4):157-159.  (PubMed)

88.  Costa M, Canale D, Filicori M, D'Lddio S, Lenzi A. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia. 1994;26(3):155-159.  (PubMed)

89.  Matalliotakis I, Koumantaki Y, Evageliou A, Matalliotakis G, Goumenou A, Koumantakis E. L-carnitine levels in the seminal plasma of fertile and infertile men: correlation with sperm quality. Int J Fertil Womens Med. 2000;45(3):236-240.  (PubMed)

90.  Lenzi A, Lombardo F, Sgro P, et al. Use of carnitine therapy in selected cases of male factor infertility: a double-blind crossover trial. Fertil Steril. 2003;79(2):292-300.  (PubMed)

91.  Lenzi A, Sgro P, Salacone P, et al. A placebo-controlled double-blind randomized trial of the use of combined l-carnitine and l-acetyl-carnitine treatment in men with asthenozoospermia. Fertil Steril. 2004;81(6):1578-1584.  (PubMed)

92.  Balercia G, Regoli F, Armeni T, Koverech A, Mantero F, Boscaro M. Placebo-controlled double-blind randomized trial on the use of L-carnitine, L-acetylcarnitine, or combined L-carnitine and L-acetylcarnitine in men with idiopathic asthenozoospermia. Fertil Steril. 2005;84(3):662-671.  (PubMed)

93.  Siliprandi N, Di Lisa F, Pieralisi G, et al. Metabolic changes induced by maximal exercise in human subjects following L-carnitine administration. Biochim Biophys Acta. 1990;1034(1):17-21.  (PubMed)

94.  Vecchiet L, Di Lisa F, Pieralisi G, et al. Influence of L-carnitine administration on maximal physical exercise. Eur J Appl Physiol Occup Physiol. 1990;61(5-6):486-490.  (PubMed)

95.  Dragan GI, Vasiliu A, Georgescu E, Dumas I. Studies concerning chronic and acute effects of L-carnitine on some biological parameters in elite athletes. Physiologie. 1987;24(1):23-28.  (PubMed)

96.  Marconi C, Sassi G, Carpinelli A, Cerretelli P. Effects of L-carnitine loading on the aerobic and anaerobic performance of endurance athletes. Eur J Appl Physiol Occup Physiol. 1985;54(2):131-135.  (PubMed)

97.  Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr. 2000;72(2 Suppl):618S-623S.  (PubMed)

98.  Smith WA, Fry AC, Tschume LC, Bloomer RJ. Effect of glycine propionyl-L-carnitine on aerobic and anaerobic exercise performance. Int J Sport Nutr Exerc Metab. 2008;18(1):19-36.  (PubMed)

99.  Natali A, Santoro D, Brandi LS, et al. Effects of acute hypercarnitinemia during increased fatty substrate oxidation in man. Metabolism. 1993;42(5):594-600.  (PubMed)

100.  Barnett C, Costill DL, Vukovich MD, et al. Effect of L-carnitine supplementation on muscle and blood carnitine content and lactate accumulation during high-intensity sprint cycling. Int J Sport Nutr. 1994;4(3):280-288.  (PubMed)

101.  Vukovich MD, Costill DL, Fink WJ. Carnitine supplementation: effect on muscle carnitine and glycogen content during exercise. Med Sci Sports Exerc. 1994;26(9):1122-1129.  (PubMed)

102.  Trappe SW, Costill DL, Goodpaster B, Vukovich MD, Fink WJ. The effects of L-carnitine supplementation on performance during interval swimming. Int J Sports Med. 1994;15(4):181-185.  (PubMed)

103.  Brass EP, Hoppel CL, Hiatt WR. Effect of intravenous L-carnitine on carnitine homeostasis and fuel metabolism during exercise in humans. Clin Pharmacol Ther. 1994;55(6):681-692.  (PubMed)

104.  Brass EP. Carnitine and sports medicine: use or abuse? Ann N Y Acad Sci. 2004;1033:67-78.  (PubMed)

105.  Rebouche CJ. Carnitine. In: Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Philadelphia: Lippincott, Williams & Wilkins; 1999:505-512.

106.  Brass EP, Hiatt WR. The role of carnitine and carnitine supplementation during exercise in man and in individuals with special needs. J Am Coll Nutr. 1998;17(3):207-215.  (PubMed)

107.  In: Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc.; 2001.