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Choline

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Choline

Choline has only recently been recognized as an essential nutrient. Choline is part of the neurotransmitter acetylcholine, which plays a major role in the brain; for this reason, many studies have been designed to look at choline's role in brain function.
Choline functions as a part of a major biochemical process in the body called methylation; choline acts as a methyl donor. Until recently, it was thought that the body could use other substances to substitute for choline, such as folate , vitamins B 6 and B 12 , and the amino acid methionine . But recent evidence has finally shown that, for some people, adequate choline supplies cannot be maintained by other nutrients and must be obtained independently through diet or supplements. 1-3

Requirements/Sources

Choline is widespread in the foods we eat. The average diet provides about 500 mg to 1,000 mg of choline per day. 2,4 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 US and Canadian guidelines, the recommended daily intake of choline is as follows:
  • Infants
    • 0-6 months: 125 mg
    • 7-12 months: 150 mg
  • Children
    • 1-3 years: 200 mg
    • 4-8 years: 250 mg
    • 9-13 years: 375 mg
  • Males
    • 14 years and older: 550 mg
  • Females
    • 14-18 years: 400 mg
    • 19 years and older: 425 mg
  • Pregnant Women : 450 mg
  • Nursing Women : 550 mg

Therapeutic Dosages

Most studies of choline as a treatment for diseases have used between 1-30 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

A form of choline called choline alfoscerate has shown promise for Alzheimer's disease . 5
A substance related to choline called CDP-choline (or citicoline) may be slightly helpful for enhancing recovery from strokes . 6
Slight evidence hints that lecithin or pure choline may be helpful for people with bipolar disorder . 7,29 Lecithin has failed to prove effective for tardive dyskinesia . 8,9 Lecithin has also failed to prove effective for improving cholesterol profile levels. 2,10
Some evidence suggests that individuals with HIV who are low in choline may experience more rapid disease progression. 11 However, there is no direct evidence that choline supplements offer any benefit for people with HIV.
Numerous studies have found that diets very low in choline lead to impaired liver function. 1,2,12-15 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 a double-blind study , use of phosphatidylcholine enhanced the effect of interferon in people with chronic hepatitis C, but not those with chronic hepatitis B. 16Open studies have yielded mixed results. 17,18
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 replication—a 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. 1,19 Indeed, in rats fed diets very low in choline and other methyl donors, cancer rates increased. 20,21 However, again it is a long step from the effects of an artificially low-choline diet to taking choline supplements.   
Choline as phosphatidylcholine may reduce homocysteine levels. 30 This, in turn, might reduce heart disease risk, although the proposed homocysteine-heart disease connection remains far from proven. (See the High Homocysteine article for more information.)

What Is the Scientific Evidence for Choline?

Alzheimer's Disease

In a 6-month, double-blind, placebo-controlled trial , 261 people with mild to moderate Alzheimer’s disease were given either placebo or choline alfoscerate (a special form of choline) at a dose of 400 mg 3 times daily. 5 The results indicated that people receiving the supplement improved slightly over the course of the trial, while those given placebo worsened.
Weak evidence from highly preliminary studies hint that CDP-choline may improve mental function in Alzheimer’s disease. 22-25 Double-blind trials using lecithin as a source of choline failed to find benefit. 26-28

Strokes

Four double-blind, placebo-controlled studies enrolling a total of 1,372 people have evaluated the potential effectiveness of CDP choline in the treatment of strokes . 6 Overall, the evidence suggests that use of CDP-choline in the immediate period following a stroke slightly improves the chances of full recovery.

Safety Issues

The tolerable upper intake of choline has been set at 3.5 g daily for adults. Tolerable upper intake is defined as: the highest daily intake over a prolonged time known to pose no risks to most members of a healthy population.
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;11:473-481.

2 Zeisel SH, Da Costa KA, Franklin PD, et al. Choline, an essential nutrient for humans. FASEB J . 1991;5:2093-2098.

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;129:712-717.

4 [No authors listed]. Choline: a conditionally essential nutrient for humans. Nutr Rev . 1992;50:112-114.

5 De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: A multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther . 2003;25:178-193.

6 Davalos A, Castillo J, Alvarez-Sabin J, Oral citicoline in acute ischemic stroke: an individual patient data pooling analysis of clinical trials. Stroke. 2002;33:2850-2857.

7 Cohen BM, Lipinski JF, Altesman RI, et al. Lecithin in the treatment of mania: double-blind, placebo-controlled trials. Am J Psychiatry. 1982;139:1162-1164.

8 Gelenberg AJ, Dorer DJ, Wojcik JD, et al. A crossover study of lecithin treatment of tardive dyskinesia. J Clin Psychiatry. 1990;51:149-153.

9 Domino EF, May WW, Demetriou S, et al. Lack of clinically significant improvement of patients with tardive dyskinesia following phosphatidylcholine therapy. Biol Psychiatry. 1985;20:1189-1196.

10 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;52:419-424.

11 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;72:809-815.

12 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;23:305-308.

13 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;102:1363-1370.

14 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;9:76-83.

15 Burt ME, Hanin I, Brennan MF, et al. Choline deficiency associated with total parenteral nutrition. Lancet . 1980;2:638-639.

16 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;45:797-804.

17 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;9:699-703.

18 Chawla RK, Wolf DC, Kutner MH, et al. Choline may be an essential nutrient in malnourished patients with cirrhosis. Gastroenterology. 1989;97:1514-1520.

19 Newberne PM. Lipotropic factors and oncogenesis. Adv Exp Med Biol . 1986;206:223-251.

20 Wainfan E, Poirier LA. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res. 1992;52:S2071-S2077.

21 Rogers AE. Methyl donors in the diet and responses to chemical carcinogens. Am J Clin Nutr. 1995;61:S659-S665.

22 Alvarez XA, Mouzo R, Pichel V, et al. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion. Methods Find Exp Clin Pharmacol. 1999;21:633-644.

23 Franco-Maside A, Caamano J, Gomez MJ, et al. Brain mapping activity and mental performance after chronic treatment with CDP-choline in Alzheimer's disease. Methods Find Exp Clin Pharmacol. 1994;16:597-607.

24 Cacabelos R, Alvarez XA, Franco-Maside A, et al. Effect of CDP-choline on cognition and immune function in Alzheimer's disease and multi-infarct dementia. Ann N Y Acad Sci . 1993;695:321-323.

25 de la Morena E. Efficacy of CDP-choline in the treatment of senile alterations in memory. Ann N Y Acad Sci. 1991;640:233-236.

26 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;24:279-286.

27 Weintraub S, Mesulan MM, Auty R, et al. Lecithin in the treatment of Alzheimer's disease. Arch Neurol. 1983;40:527-528.

28 Etienne P, Dastoor D, Gauthier S, et al. Alzheimer disease: lack of effect of lecithin treatment for 3 months. Neurology. 1981;31:1552-1554.

29 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;40:382-388.

30 Olthof MR, Brink EJ, Katan MB, et al. Choline supplemented as phosphatidylcholine decreases fasting and postmethionine-loading plasma homocysteine concentrations in healthy men. Am J Clin Nutr. 2005;82:111-7.

Revision Information

This content is reviewed regularly and is updated when new and relevant evidence is made available. This information is neither intended nor implied to be a substitute for professional medical advice. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with questions regarding a medical condition.

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