-------------------------------------------------------------------------------- Requirements/Sources Choline is widespread in the foods we eat. The average diet provides about 500 to 1,000 mg of choline per day.4,5 Lecithin, a fatty constituent in foods, is a major source of choline; it is comprised mostly of a type of choline called phosphatidylcholine (PC). (Lecithin and PC have been studied separately as treatments for a variety of illnesses; for more information on these supplements, see the full article on lecithin.) According to U.S. and Canadian guidelines, the recommended daily intake of choline is as follows: Infants 06 months, 125 mg 712 months, 150 mg Children 13 years, 200 mg 48 years, 250 mg 913 years, 375 mg Males 14 years and older, 550 mg Females 1418 years, 400 mg 19 years and older, 425 mg Pregnant women, 450 mg Nursing women, 550 mg Tolerable upper intake level (UL) for adults, 3.5 g* *The "tolerable upper intake level" can be thought of as the highest daily intake over a prolonged time known to pose no risks to most members of a healthy population. -------------------------------------------------------------------------------- Therapeutic Dosages Most studies of choline as a treatment for diseases have used between 1 and 30 g of choline or choline-containing supplements per day. This wide range is due to the existence of several different types of choline supplements, all with varying amounts of the active ingredient. -------------------------------------------------------------------------------- Therapeutic Uses Choline, as well as phosphatidylcholine, lecithin, and a special form of choline called citicoline (or CDP-choline) has been studied quite extensively in people with Alzheimer's disease and other conditions involving the brain. As noted above, this research is based on the fact that an important neurotransmitter, acetylcholine, is made from choline. We know that eating a lot of choline raises blood levels of choline, but we don't know the degree to which this enhances acetylcholine levels and, ultimately, brain function.614 Choline alone does not appear to diminish Alzheimer's symptoms in studies of people diagnosed with the disease.1519 In other areas of brain function, two studies showed some benefit from lecithin or pure choline in people with mania or bipolar disorder respectively, but these studies were small and poorly controlled.51,52 Two other small double-blind placebo-controlled studies examined the effects of lecithin in people with tardive dyskinesia but found no substantial improvement in symptoms.53,54 One very large (899 participant) double-blind placebo-controlled trial evaluated citicoline for the treatment of strokes, but found no evidence of benefit.56 Choline's reputation as a cholesterol-lowering agent has been extensively studied in trials involving lecithin. Studies showing a positive effect from choline were poorly controlled and lacked a placebo group;27,28 well-designed studies do not support the claim that choline can reduce cholesterol levels.29,30 However, preliminary evidence suggests cholinein concert with other methyl donors like folate, methionine, and vitamins B12 and B6may help to lower homocysteine levels, which could in turn help prevent heart disease.31,32 Evidence suggests that individuals with HIV who are low in choline may experience more rapid disease progression.33 Numerous studies have found that diets very low in choline lead to impaired liver function.3439 But these diets are contrived: one would have to work very hard to get so little choline in the diet! To what degree additional choline may benefit people with pre-existing liver damage is an area of ongoing research. In one study, liver function improved in people with hepatitis who were given choline supplements,40 but in another study, the same supplement failed to show improvements in individuals with hepatitis.41 A study of malnourished hospitalized people with cirrhosis showed an improvement in several important measurements of liver function when choline supplements were given.42 Finally, there are theoretical reasons to believe that choline might have cancer-preventive properties. The notion stems from its function as a methyl donor. Methyl units are essential for RNA and DNA replicationa process ongoing in every cell of the body. The theory goes like this: diets lacking sufficient methyl donors (such as choline) may cause an error in RNA or DNA synthesis, leading to a mutated gene and, hypothetically, to cancer initiation.43,44 Indeed, in rats fed diets very low in choline and other methyl donors, cancer rates increased.45,46 However, as noted above in the discussion of liver disease, it is a long step from the effects of an artificially low-choline diet to taking choline supplements. -------------------------------------------------------------------------------- What Is the Scientific Evidence for Choline? Alzheimer's Disease Note: Many of the studies below used PC or lecithin instead of choline. However, because these substances break down to form choline, they are discussed here as well. Several studies in the early 1980s examined supplemental lecithin in people diagnosed with Alzheimer's disease.47,48,49 Although the groups studied were small (from 11 to 37 people), these were all double-blind placebo-controlled trials. After 3 to 6 months, no differences in cognitive function could be detected in those getting choline compared to placebo. More promising may be choline in combination with other drugs. A 1989 Canadian study combined lecithin with tetrahydroaminoacridine (THA), a drug that effectively improves symptoms associated with Alzheimer's disease but is toxic to the liver at high doses.50 By combining THA with lecithin (3.4 g per day), researchers were able to use lower doses of the drug and achieve comparable improvements in symptoms of Alzheimer's. Finally, studies in rats and mice found enhanced brain function in animals fed supplemental choline.55,56 But in studies of healthy adults given lecithin as well as in observational trials evaluating dietary choline intake, little to no benefit was seen.57,58 -------------------------------------------------------------------------------- Safety Issues When taken at nutritional doses as recommended above (see Requirements/Sources), choline supplementation is safe. In higher dosages, minor but annoying side effects may occur, such as abdominal discomfort, diarrhea, and nausea. Maximum safe dosages for young children, pregnant or nursing women, or those with severe liver or kidney disease have not been determined. -------------------------------------------------------------------------------- References 1. Zeisel SH. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr. 1992;11:473481. 2. Zeisel SH, Da Costa KA, Franklin PD, et al. Choline, an essential nutrient for humans. FASEB J. 1991;5:20932098. 3. Jacob RA, Jenden DJ, Allman-Farinelli MA, et al. Folate nutriture alters choline status of women and men fed low choline diets. J Nutr. 1999;129:712717. 4. Zeisel SH, Da Costa KA, Franklin PD, et al. Choline, an essential nutrient for humans. FASEB J. 1991;5:20932098. 5. [No authors listed]. Choline: a conditionally essential nutrient for humans. Nutr Rev. 1992;50:112114. 6. Leathwood PD, Schlosser B. Phosphatidylcholine, choline and cholinergic function. Int J Vitam Nutr Res Suppl. 1986;29:4967. 7. Sanchez CJ, Hooper E, Garry PJ, et al. The relationship between dietary intake of choline, choline serum levels, and cognitive function in healthy elderly persons. J Am Geriatr Soc. 1984;32:208212. 8. Zeisel SH. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr. 1992;11:473481. 9. Davis KL, Berger PA. Pharmacological investigations of the cholinergic imbalance hypotheses of movement disorders and psychosis. Biol Psychiatry. 1978;13:2349. 10. Hirsch MJ, Growdon JH, Wurtman RJ. Relations between dietary choline or lecithin intake, serum choline levels, and various metabolic indices. Metabolism. 1978;27:953960. 11. Wood JL, Allison RG. Effects of consumption of choline and lecithin on neurological and cardiovascular systems. Fed Proc. 1982;41:30153021. 12. Russell RW. Continuing the search for cholinergic factors in cognitive dysfunction. Life Sci. 1996;58:19651970. 13. Wurtman RJ, Growdon JH. Dietary enhancement of CNS neurotransmitters. Hosp Pract. 1978;13:7177. 14. Zeisel SH. Dietary influences on neurotransmission. Adv Pediatr. 1986;33:2347. 15. Heyman A, Schmechel D, Wilkinson W, et al. Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease. J Neural Transm Suppl. 1987;24:279286. 16. Weintraub S, Mesulan MM, Auty R, et al. Lecithin in the treatment of Alzheimer's disease. Arch Neurol. 1983;40:527528. 17. Etienne P, Dastoor D, Gauthier S, et al. Alzheimer disease: lack of effect of lecithin treatment for 3 months. Neurology. 1981;31:15521554. 18. Gauthier S, Bouchard R, Bacher Y, et al. Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. Can J Neurol Sci. 1989;16:543546. 19. Leathwood PD, Schlosser B. Phosphatidylcholine, choline and cholinergic function. Int J Vitam Nutr Res Suppl. 1986;29:4967. 20. Sanchez CJ, Hooper E, Garry PJ, et al. The relationship between dietary intake of choline, choline serum levels, and cognitive function in healthy elderly persons. J Am Geriatr Soc. 1984;32:208212. 21. Harris CM, Dysken MW, Fovall P, et al. Effect of lecithin on memory in normal adults. Am J Psychiatry. 1983;140:10101012. 22. Stoll AL, Sachs GS, Cohen BM, et al. Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients. Biol Psychiatry. 1996;40:382388. 23. Cohen BM, Lipinski JF, Altesman RI, et al. Lecithin in the treatment of mania: double-blind, placebo-controlled trials. Am J Psychiatry. 1982;139:11621164. 24. Gelenberg AJ, Dorer DJ, Wojcik JD, et al. A crossover study of lecithin treatment of tardive dyskinesia. J Clin Psychiatry. 1990;51:149153. 25. Domino EF, May WW, Demetriou S, et al. Lack of clinically significant improvement of patients with tardive dyskinesia following phosphatidylcholine therapy. Biol Psychiatry. 1985;20:11891196. 26. Davis KL, Berger PA. Pharmacological investigations of the cholinergic imbalance hypotheses of movement disorders and psychosis. Biol Psychiatry. 1978;13:2349. 27. Brook JG, Linn S, Aviram M, et al. Dietary soya lecithin decreases plasma triglyceride levels and inhibits collagen- and ADP-induced platelet aggregation. Biochem Med Metab Biol. 1986;35:3139. 28. Wojcicki J, Pawlik A, Samochowiec L, et al. Clinical evaluation of lecithin as a lipid-lowering agent. Phytotherapy Res. 1995;9:597599. 29. Oosthuizen W, Vorster HH, Vermaak WJ, et al. Lecithin has no effect on serum lipoprotein, plasma fibrinogen and macro molecular protein complex levels in hyperlipidaemic men in a double-blind controlled study. Eur J Clin Nutr. 1998;52:419424. 30. Zeisel SH, Da Costa KA, Franklin PD, et al. Choline, an essential nutrient for humans. FASEB J. 1991;5:20932098. 31. Olszewski AJ, Szostak WB, Bialkowska M, et al. Reduction of plasma lipid and homocysteine levels by pyridoxine, folate, cobalamin, choline, riboflavin, and troxerutin in atherosclerosis. Atherosclerosis. 1989;75:16. 32. Dudman NP, Wilcken DE, Wang J, et al. Disordered methionine/homocysteine metabolism in premature vascular disease. Its occurrence, cofactor therapy, and enzymology. Arterioscler Thromb. 1993;13:12531260. 33. Bogden JD, Kemp FW, Han S, et al. Status of selected nutrients and progression of human immunodeficiency virus type 1 infection. Am J Clin Nutr. 2000;72:809815. 34. Misra S, Ahn C, Ament ME, et al. Plasma choline concentration in children requiring long-term home parenteral nutrition: a case control study. JPEN J Parenter Enteral Nutr. 1999;23:305308. 35. Buchman AL, Dubin M, Jenden D, et al. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology. 1992;102:13631370. 36. Zeisel SH, Da Costa KA, Franklin PD, et al. Choline, an essential nutrient for humans. FASEB J. 1991;5:20932098. 37. Tayek JA, Bistrian B, Sheard NF, et al. Abnormal liver function in malnourished patients receiving total parenteral nutrition: a prospective randomized study. J Am Coll Nutr. 1990;9:7683. 38. Zeisel SH. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr. 1992;11:473481. 39. Burt ME, Hanin I, Brennan MF, et al. Choline deficiency associated with total parenteral nutrition. Lancet. 1980;2:638639. 40. Niederau C, Strohmeyer G, Heintges T, et al. Polyunsaturated phosphatidyl-choline and interferon alpha for treatment of chronic hepatitis B and C: a multi-center, randomized, double-blind, placebo-controlled trial. Leich Study Group. Hepatogastroenterology. 1998;45:797804. 41. Guan R, Ho KY, Kang JY, et al. The effect of polyunsaturated phosphatidyl choline in the treatment of acute viral hepatitis. Aliment Pharmacol Ther. 1995;9:699703. 42. Chawla RK, Wolf DC, Kutner MH, et al. Choline may be an essential nutrient in malnourished patients with cirrhosis. Gastroenterology. 1989;97:15141520. 43. Zeisel SH. Choline: an important nutrient in brain development, liver function and carcinogenesis. J Am Coll Nutr. 1992;11:473481. 44. Newberne PM. Lipotropic factors and oncogenesis. Adv Exp Med Biol. 1986;206:223251. 45. Wainfan E, Poirier LA. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res. 1992;52:S2071S2077. 46. Rogers AE. Methyl donors in the diet and responses to chemical carcinogens. Am J Clin Nutr. 1995;61:S659S665. 47. Heyman A, Schmechel D, Wilkinson W, et al. Failure of long term high-dose lecithin to retard progression of early-onset Alzheimer's disease. J Neural Transm Suppl. 1987;24:279286. 48. Weintraub S, Mesulan MM, Auty R, et al. Lecithin in the treatment of Alzheimer's disease. Arch Neurol. 1983;40:527528. 49. Etienne P, Dastoor D, Gauthier S, et al. Alzheimer disease: lack of effect of lecithin treatment for 3 months. Neurology. 1981;31:15521554. 50. Gauthier S, Bouchard R, Bacher Y, et al. Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease. Can J Neurol Sci. 1989;16:543546. 51. Stoll AL, Sachs GS, Cohen BM, et al. Choline in the treatment of rapid-cycling bipolar disorder: clinical and neurochemical findings in lithium-treated patients. Biol Psychiatry. 1996;40:382388. 52. Cohen BM, Lipinski JF, Altesman RI, et al. Lecithin in the treatment of mania: double-blind, placebo-controlled trials. Am J Psychiatry. 1982;139:11621164. 53. Gelenberg AJ, Dorer DJ, Wojcik JD, et al. A crossover study of lecithin treatment of tardive dyskinesia. J Clin Psychiatry. 1990;51:149153. 54. Domino EF. Monoamine oxidase, tobacco smoking, and psychiatric disorders. Biol Psychiatry. 1996;40:433434. 55. Bartus RT, Dean RL, Goas JA, et al. Age-related changes in passive avoidance retention: modulation with dietary choline. Science. 1980;209:301303. 56. Meck WH, Williams CL. Simultaneous temporal processing is sensitive to prenatal choline availability in mature and aged rats. Neuroreport. 1997;8:30453051. 57. Sanchez CJ, Hooper E, Garry PJ, et al. The relationship between dietary intake of choline, choline serum levels, and cognitive function in healthy elderly persons. J Am Geriatr Soc. 1984;32:208212. 58. Harris CM, Dysken MW, Fovall P, et al. Effect of lecithin on memory in normal adults. Am J Psychiatry. 1983;140:10101012. 59. Clark WM, Wechsler LR, Sabounjian LA, et al. A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients. Neurology. 2001;57:1595-1602. |
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