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by Jack Norris, RD &
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Choline

by Jack Norris, RD | Last updated April, 2013

Contents

Summary

Choline is found in a wide range of plant foods in small amounts. Eating a well-balanced vegan diet with plenty of whole foods should ensure you are getting enough choline. Soymilk, tofu, quinoa, and broccoli are particularly rich sources.

The Dietary Reference Intake (DRI) for choline is 550 mg/day for men and 425 mg/day for women. It is based on only one study comparing those amounts to 50 mg/day, with no intermediary amounts examined. Eating less than 50 mg/day can result in liver damage, but it is very unlikely that a vegan would have such a low intake.

Some people have genetic mutations that increase the need for choline; it is not clear how much choline such people need but the DRI is probably adequate for almost everyone. If you suspect any sort of liver dysfunction, it might be worth talking to your physician about boosting your choline intake or supplementing with it in moderate amounts.

The data on choline and chronic disease (cardiovascular disease, dementia, and cancer) is somewhat mixed. Ideal amounts appear to be about 300 mg per day. Most vegans probably get about that much from the foods they eat.

Vegan women who are considering getting pregnant should make sure they are meeting the DRI for choline to reduce the risk of neural tube defects, and might need a modest supplement.

Introduction

The Food and Nutrition Board, of the Institute of Medicine, considers choline to be an essential nutrient (i.e, a nutrient that must be obtained from the diet). Choline can appear in food in many forms, including as just choline (also known as free choline), phosphatidylcholine (also known as lecithin), sphingomyelin, glycerophosphocholine, and phosphocholine). Choline is found in a wide range of foods, although animal products tend to be the richest sources.

There is another molecule, betaine, that is involved in the choline story. The body can turn choline into betaine, and betaine is also found in range of foods. Getting plenty of betaine in your diet can somewhat reduce the need for choline.

Choline has a number of functions:

  • Most choline is used for the synthesis of phosphatidylcholine, the principle phospholipid in cell membranes (15).
  • Along with betaine, choline functions as a methyl donor. Like many other molecules including folate, vitamin B12, and s-adenosylmethionine (SAMe), methyl donors are involved in keeping homocysteine levels low, among many other functions.
  • Choline is needed to synthesize low-density lipoproteins (LDL).
  • Choline is needed to synthesize the neurotransmitter, acetylcholine.

The need for choline was discovered when it was found that people on total parenteral nutrition (being fed through a catheter directly into the blood and bypassing digestion) for long periods of time were developing fatty livers. The fatty livers resolved upon adding choline to the feeding regimen (2, 3, 4). The fatty livers were caused by an accumulation of triglycerides as a result of the liver's inability to synthesize and release very-low-density lipoprotein (VLDL) particles because of a reduced synthesis of phosphatidylcholine (15).

Table 1. DRI for Choline26
AgeFemale
(mg)
Male
(mg)
0-6 mos125125
7-12 mos150150
1-3 yrs200200
4-8 yrs250250
9-13 yrs375375
14-18 yrs400550
≥ 19 yrs425550
Pregnant450 
Breastfeeding550 

In 1998, for the first time, the Institute of Medicine (IOM) set a Dietary Reference Intake (DRI) for choline (26). There was not enough evidence to create a Recommended Dietary Allowance (RDA), but based on the only study available at the time, a 1991 study out of the University of North Carolina (UNC), Chapel Hill, that had purposefully induced choline deficiency in humans (25), the IOM created an Adequate Intake (AI) of 550 mg/day for men and 425 mg/day for women (both equivalent to 7 mg/day per kg body weight).

Average Choline Intakes

There has been little data on average choline intakes in the population because the choline content of foods has not been included in major nutrient databases until recently. In 2004, the USDA added choline to their database for about 150 foods. Using this information, in 2005, researchers from UNC Chapel Hill determined the average choline intake of 16 adult men and 16 adult women, ages 18 to 67 (13). Daily total choline intake per kg of body weight was 8.4 ± 2.1 mg for men and 6.7 ± 1.3 mg for women. These amounts were 120% and 96% of the AI, or about 660 mg for men and 408 mg for women. From this survey, it appeared that people were generally meeting the AI.

In 2008, the USDA added significantly more data on the choline content of foods, and it is likely that earlier analyses somewhat underestimated choline intakes.

Induced Choline Deficiency

Since the 1991 study mentioned above, five more studies inducing choline deficiency have come out of UNC Chapel Hill (8, 11, 9, 14, 18). They all follow a very similar pattern. Subjects are fed a diet with plenty of choline for a short period after which they are given a diet of about 50 mg or less per day for six weeks or until they develop markers of dysfunction (whichever comes first). The markers include increased liver enzymes, a fatty liver, or elevated creatine phosphokinase (CPK) (8) which indicates muscle deterioration.

In all studies, a large proportion of subjects develop markers of dysfunction during the six weeks, indicating that few people can stay healthy on < 50 mg/day of choline. They found some differences between groups:

  • Premenopausal women develop choline deficiency-associated organ dysfunction at a rate of about 50%, whereas men and postmenopausal women develop it at a rate of about 75% (11, 9).
  • There are a number of genetic variations among people that increase or decrease the likelihood of getting choline deficiency. Estrogen protects against the effects of at least one of these genes (over a six week period, anyway) (9, 14).

After inducing choline deficiency, the researchers put the subjects on diets that included the DRI for choline and almost all the subjects' organ dysfunction returned to normal. It should be noted that the organ dysfunction did not present itself to the subjects in any noticeable way. Unfortunately, by returning the subjects to the DRI for choline, there was no way to know if less choline was required to arrest the organ dysfunction. There was one exception in which 10 days of 138 mg/70 kg of body weight returned CPK to normal in four men studied (8). So, 138 mg/70 kg of body weight per day might be enough choline, but the problems with drawing conclusions from this study are the small number of people measured, that they were only men, and that liver dysfunction wasn't measured. In another study, a whopping 825 mg/day per 70 kg of body weight of choline was required to normalize liver function for some people (11).

Looking at the research above, it is hard to know how much choline people need. It could be as little as 138 mg per day for some, but others might require quite a bit more. But there is more to the story than just preventing liver and muscle dysfunction. Choline intake or levels have also been studied in relation to heart disease, cancer, neural tube defects, and dementia, with some interesting findings.

Heart Disease

A 2007 UNC, Chapel Hill study, the Atherosclerosis Risk in Communities study, followed subjects for 14 years (1). They found no significant associations between choline intake and heart disease events. Intake categories ranged from about 300 to 500 mg/day.

A 2006 cross-sectional report from the Framingham Offspring Study of 920 men and 1,040 women found the average choline intakes to be about 313 mg/day (5). Higher intakes, above 339 mg/day were significantly associated with slightly lower homocysteine levels.

A 2008 report from a Dutch arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) found that high choline (365 mg versus 239 mg/day) and folate intakes, but not betaine, were associated with modestly lower homocysteine levels (10). However, there was no association with cardiovascular disease.

A 2008 cross-sectional study from Greece found that those with choline intakes > 310 mg had lower markers of inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor), than those eating < 250 mg (11). Betaine intakes of > 350 mg resulted in lower homocysteine and tumor necrosis factor than < 260 mg.

Gut Microbes, Choline, and Cardiovascular Disease

In 2011, an interesting report on choline and heart disease was released by researchers from the Cleveland Clinic and University of California at Los Angeles (20). Plasma was taken from stable patients undergoing an elective heart evaluation who subsequently experienced a heart attack, stroke or death over the ensuing three-year period. Their plasma was compared to age- and gender-matched subjects who did not suffer such problems.

They analyzed the plasma for any molecules that might be different between the groups. They found 18 molecules that were higher in the cases, and of those 18, they determined that three of them were choline, betaine, and trimethylamine N-oxide (TMAO). They then determined that, at least in mice, TMAO is a byproduct of gut microbe metabolism of choline and betaine. The pathway goes like this: Phosphatidylcholine is turned into choline. Microbes turn the choline into the gas, trimethylamine (TMA). The liver then turns TMA into TMAO.

The researchers then looked at levels of choline, betaine, and TMAO in members of the ongoing study, the Learning and Validation Cohorts, and found that all three molecules showed a dose-dependent association with the presence of cardiovascular disease. The association held true after adjustments for traditional cardiac risk factors and medication usage.

Update: In 2013, the research group from the Cleveland Clinic showed that humans given lecithin from eggs increase TMAO production (21). They also prospectively followed patients undergoing elective coronary angiography and found that higher TMAO levels in the blood were associated with an increase in major adverse cardiac events.

As an aside, some people have defects in the enzymes for converting TMA to TMAO, and TMA accumulates in their system and produces a fishy odor (know as trimethylaminuria). The authors noted that, "In fact, individuals with trimethylaminuria often become vegans, as reducing the ingestion of dietary animal products rich in lipids decreases TMA production and the associated noxious odour."

Breast Cancer

A 2007 report from the Nurses’ Health Study II found no correlation between choline intake and breast cancer among 90,663 pre-menopausal women after 12 years of follow-up (6). Average intake in each quintile was 263, 301, 327, 354, and 397 mg/day.

A 2009 case-control study from the Long Island Breast Cancer Study Project found that higher free choline intakes were associated with a lower risk of developing breast cancer (23). Following the breast cancer cases forward showed that higher betaine, phosphocholine, and free choline intakes were associated with reduced all-cause and breast cancer mortality in a dose-dependent fashion. This study was mostly a re-analysis of the same study published the year before (23), but with updated USDA nutrient data regarding the choline content of food. The lowest and highest quintiles of choline Intake were ≤ 123 and ≥ 247 mg/day, respectively.

Colon Cancer

A 2007 report from the Nurses’ Health Study found that higher choline intakes were associated with an increased risk of colon cancer in women (7). A choline intake of 383 mg/day had a risk of 1.45 (1.27 - 1.67) compared to the lowest intake group of 293 mg/day. Results were adjusted for energy intake, alcohol, folate, fiber, calcium, and red meat.

In the same study, betaine was associated with a lower risk of colon cancer.

A 2010 report from the Health Professionals Follow-up Study found that after 18 years of follow-up, there was no relation between choline or betaine intake and colorectal cancer in men (19). The choline amounts were not given.

Prostate Cancer

A 2009 nested case-control from the Northern Sweden Health and Disease Cohort analyzed plasma concentrations of betaine, choline, cysteine, methionine, methylmalonic acid (MMA), vitamin B2, and vitamin B6 in 561 cases and 1,034 controls (17). Elevated MMA levels indicate vitamin B12 deficiency.

The relative risks for a doubling in concentration were 1.46 (1.04-2.05) for choline, 1.11 (1.00-1.23) for vitamin B2, and 0.78 (90.63-0.97) for MMA. In other words, choline, vitamin B2, and vitamin B12 were all associated with an increased the risk of prostate cancer.

Neural Tube Defects

In 2004, a case control study on neural tube defects (NTD) was reported from the California Birth Defects Monitoring Program (22). There is a concern that because choline is involved in some of the same metabolic pathways as folate, choline deficiency in pregnant women, along with folate deficiency, might be a risk for a NTD.

In this study, there were 424 cases of a NTD and 440 controls. Quartiles of choline intake were ≤ 290, 290–372, 372–499, and ≥ 499. The risks for NTD for the 2nd, 3rd, and 4th quartile compared to the lowest were 0.63 (0.42-0.99), 0.65 (0.39-1.07), and 0.51 (0.25-1.07) respectively. Average choline intake for cases was 377 vs. 409 mg/day for controls.

The risks for a NTD were lowest for women whose diets were in the 75th percentile for choline, betaine, and methionine (compared to those below the 25th percentile) with a very low risk of 0.17 (0.04-0.76).

In other words, getting at least 290 mg/day of choline, as well as plenty of betaine and methionine, possibly reduces the risk of having a baby with a NTD.

Table 2. Choline Intake for One Day's Diet Diary
FoodServingsServing SizeCholine
(mg)
Soymilk, original and vanilla, unfortified1 1.00 - cup57.3
Bananas, raw1 1.00 - medium (7" to 7-7/8" long)11.6
Cereals, oats, instant, fortified, plain, prepared with water (boiling water added or microwaved)1 1.00 - cup, cooked16.6
Raisins, seedless0.33 50.00 - raisins1
Oranges, raw, all commercial varieties1 1.00 - large (3-1/16" dia)15.5
Bread, whole-wheat, commercially prepared2 1.00 - slice14.8
Hummus, commercial3 1.00 - tbspNR
Snacks, corn-based, extruded, chips, unsalted1 10.00 - chips3.3
Sauce, salsa, ready-to-serve0.25 1.00 - cup7.6
Lettuce, cos or romaine, raw1 1.00 - leaf inner0.6
Oil, grapeseed1 1.00 - tablespoonNR
Dates, medjool4 1.00 - date, pitted9.5
Apples, raw, with skin1 1.00 - large (3-1/4" dia)7.6
Peanut butter, chunk style, without salt0.6 2.00 - tbsp11.8
Nuts, almonds, dry roasted, without salt added0.5 1.00 - oz (22 whole kernels)7.4
Nuts, walnuts, english0.33 1.00 - oz (14 halves)3.7
Raisins, seedless0.1 50.00 - raisins0.3
Carrot juice, canned0.5 1.00 - cup11.7
Tofu, firm, prepared with calcium sulfate and magnesium chloride (nigari)1 0.50 - cup35.4
Spaghetti, cooked, enriched, without added salt1.5 1.00 - cup13.4
Tomato sauce, no salt added0.5 1.00 - cup14.8
Squash, summer, zucchini, includes skin, cooked, boiled, drained, without salt0.5 1.00 - cup, sliced8.5
Broccoli, cooked, boiled, drained, with salt1 0.50 - cup, chopped31.3
Beans, pinto, mature seeds, cooked, boiled, without salt0.5 1.00 - cup30.2
Lettuce, cos or romaine, raw1.5 1.00 - cup shredded7
Avocados, raw, all commercial varieties0.2 1.00 - cup, cubes4.3
Tomatoes, red, ripe, raw, year round average0.33 1.00 - plum tomato1.4
Celery, raw0.2 1.00 - cup chopped1.2
Carrots, raw0.1 1.00 - cup grated1
Oil, canola1 1.00 - tbsp0
Seeds, sesame butter, tahini, from roasted and toasted kernels (most common type)0.5 1.00 - tbsp1.9
Potatoes, boiled, cooked in skin, flesh, with salt1 0.50 - cup10.5
Nuts, coconut cream, canned, sweetened1.75 1.00 - tbsp2.2
Total342
NR - not reported

Dementia

In 2004, The Cochrane Collaboration updated their extremely thorough literature review on lecithin supplementation and cognition (16). They conclude:

On the basis of the published studies there is no evidence to support the use of lecithin in the treatment of patients with dementia. A single trial has produced dramatic results in favour of lecithin for people with memory complaints (brain organic psychosyndrome), but this needs to be replicated before conclusions can be drawn.

In other words, the bulk of the evidence indicates that lower levels of choline do not cause dementia.

Recommended Choline Intakes

To summarize the information above on choline intakes:

  • 50 mg/day is clearly not enough.
  • Although I am unaware of any vegan woman having a baby with a NTD, vegan women who might become pregnant should try to get 450 mg/day (the AI) to be safe.
  • Choline might help lower homocysteine levels, but it's not clear that this has any benefit for health. The concern for vegans regarding homocysteine continues to be to avoid the very high homocysteine levels that occur with vitamin B12 deficiency.
  • There is reason to think that choline in large amounts might contribute to heart disease. Keeping levels not much higher than the AI is a prudent choice at this time. It might even be better to keep levels closer to 300 mg/day.
  • Research on choline and cancer indicates that a moderate amount of choline (~300 mg/day) could reduce breast cancer compared to lower amounts, but too much could increase the risk of colon and prostate cancer.

The amount of research on choline and chronic disease is fairly minimal at this time. But taking all of it into account, it appears that a choline intake of 300 mg per day is probably adequate for most people except possibly for women trying to become pregnant who should try to meet the DRI.

How Much Choline do Vegans Get?

There has been no study determining the amount of choline in the average vegan diet. If you look at the choline amounts of foods in the USDA Database for the Choline Content of Common Foods, Release 2 (2008), you will see that there are somewhat small, but consistent amounts across a range of plant foods. Legumes, tofu, green vegetables, potatoes, nuts, grains, and fruit all contain some choline. It is not clear how much choline is in more processed vegan foods because it has not been measured.

One thing to note about the USDA database is that, per 100 grams, wheat germ and uncooked quinoa appear to be extremely high sources of choline. However, a serving of wheat germ is only two tablespoons, which contains 25 mg of choline; a decent, but not extremely high amount.

Uncooked quinoa provides 119 mg per per cup. Assuming no choline is lost in cooking, a cup of cooked quinoa would provide 42 mg of choline. This still makes quinoa one of the best sources of choline among plant foods, though it would be good to find out if cooking results in a significant loss.

Soymilk also has a decent amount of choline at 57 mg per cup.

Table 2 shows the amount of choline this author consumed in a day, which came to 342 mg. That is short of the AI of 550 mg, but the Institute of Medicine recognizes that the AI is a very rough estimate. It does, however, surpass the 300 mg per day I recommend.

On the day depicted in Table 2, I consumed 2,716 calories, which is more than most people will eat. Eating significantly fewer calories will make it hard to get 300 mg of choline. I personally would not worry about this, but adding more quinoa, soymilk, and broccoli to your diet can boost choline intake by quite a bit. For anyone who is especially worried, there are choline supplements. Based on the research above, I would recommend not going much above the AI without a physician's approval.

Sources of Betaine

Although betaine is not an essential nutrient, as it can be made from choline, some of the research above indicates that it might be a good idea to make sure you're getting higher than average amounts in your diet.

Quinoa, spinach, sweet potatoes, beets, and wheat-based breads, crackers, breakfast cereals, and pasta appear to be much higher in betaine than other plant foods. See the USDA Database for the Choline Content of Common Foods, Release 2 (2008) for more details.

Vitamin B12 Deficiency

Vitamin B12 deficiency interferes with production of choline and choline-containing phospholipids (27).

References

1. Bidulescu A, Chambless LE, Siega-Riz AM, Zeisel SH, Heiss G. Usual choline and betaine dietary intake and incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. BMC Cardiovasc Disord. 2007 Jul 13;7:20. Link

2. Buchman AL, Dubin MD, Moukarzel AA, Jenden DJ, Roch M, Rice KM, Gornbein J, Ament ME. Choline deficiency: a cause of hepatic steatosis during parenteral nutrition that can be reversed with intravenous choline supplementation. Hepatology. 1995 Nov;22(5):1399-403. Link (Abstract)

3. Buchman AL, Dubin M, Jenden D, Moukarzel A, Roch MH, Rice K, Gornbein J, Ament ME, Eckhert CD. Lecithin increases plasma free choline and decreases hepatic steatosis in long-term total parenteral nutrition patients. Gastroenterology. 1992 Apr;102(4 Pt 1):1363-70. Link (Abstract)

4. Buchman AL, Ament ME, Sohel M, Dubin M, Jenden DJ, Roch M, Pownall H, Farley W, Awal M, Ahn C. Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial. JPEN J Parenter Enteral Nutr. 2001 Sep-Oct;25(5):260-8. Link (Abstract)

5. Cho E, Zeisel SH, Jacques P, Selhub J, Dougherty L, Colditz GA, Willett WC. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr. 2006 Apr;83(4):905-11. Link

6. Cho E, Holmes M, Hankinson SE, Willett WC. Nutrients involved in one-carbon metabolism and risk of breast cancer among premenopausal women. Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2787-90. Link

7. Cho E, Willett WC, Colditz GA, Fuchs CS, Wu K, Chan AT, Zeisel SH, Giovannucci EL. Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst. 2007 Aug 15;99(16):1224-31. Link

8. da Costa KA, Badea M, Fischer LM, Zeisel SH. Elevated serum creatine phosphokinase in choline-deficient humans: mechanistic studies in C2C12 mouse myoblasts. Am J Clin Nutr. 2004 Jul;80(1):163-70. Link

9. da Costa KA, Kozyreva OG, Song J, Galanko JA, Fischer LM, Zeisel SH. Common genetic polymorphisms affect the human requirement for the nutrient choline. FASEB J. 2006 Jul;20(9):1336-44. Link

10. Dalmeijer GW, Olthof MR, Verhoef P, Bots ML, van der Schouw YT. Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women. Eur J Clin Nutr. 2008 Mar;62(3):386-94. Link

11. Detopoulou P, Panagiotakos DB, Antonopoulou S, Pitsavos C, Stefanadis C. Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. Am J Clin Nutr. 2008 Feb;87(2):424-30. Link

12. Fischer LM, daCosta KA, Kwock L, Stewart PW, Lu TS, Stabler SP, Allen RH, Zeisel SH. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 2007 May;85(5):1275-85. Link

13. Fischer LM, Scearce JA, Mar MH, Patel JR, Blanchard RT, Macintosh BA, Busby MG, Zeisel SH. Ad libitum choline intake in healthy individuals meets or exceeds the proposed adequate intake level. J Nutr. 2005 Apr;135(4):826-9. Link

14. Fischer LM, da Costa KA, Kwock L, Galanko J, Zeisel SH. Dietary choline requirements of women: effects of estrogen and genetic variation. Am J Clin Nutr. 2010 Nov;92(5):1113-9. Link

15. Hollenbeck CB. The importance of being choline. J Am Diet Assoc. 2010 Aug;110(8):1162-5. Link

16. Higgins JPT, Flicker L. Lecithin for dementia and cognitive impairment. Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No.: CD001015. DOI: 10.1002/14651858.CD001015. Review content assessed as up-to-date: 5 May 2004. Link

17. Johansson M, Van Guelpen B, Vollset SE, Hultdin J, Bergh A, Key T, Midttun O, Hallmans G, Ueland PM, Stattin P. One-carbon metabolism and prostate cancer risk: prospective investigation of seven circulating B vitamins and metabolites. Cancer Epidemiol Biomarkers Prev. 2009 May;18(5):1538-43. Link

18. Kohlmeier M, da Costa KA, Fischer LM, Zeisel SH. Genetic variation of folate-mediated one-carbon transfer pathway predicts susceptibility to choline deficiency in humans. Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16025-30. Epub 2005 Oct 18. Link

19. Lee JE, Giovannucci E, Fuchs CS, Willett WC, Zeisel SH, Cho E. Choline and betaine intake and the risk of colorectal cancer in men. Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):884-7. Link

20. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. Link

21. Tang WHW, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk. N Engl J Med 2013(April 25, 2013);368:1575-1584. | link

22. Shaw GM, Carmichael SL, Yang W, Selvin S, Schaffer DM. Periconceptional dietary intake of choline and betaine and neural tube defects in offspring. Am J Epidemiol. 2004 Jul 15;160(2):102-9. Link

23. Xu X, Gammon MD, Zeisel SH, Bradshaw PT, Wetmur JG, Teitelbaum SL, Neugut AI, Santella RM, Chen J. High intakes of choline and betaine reduce breast cancer mortality in a population-based study. FASEB J. 2009 Nov;23(11):4022-8. Epub 2009 Jul 27. Link

24. Xu X, Gammon MD, Zeisel SH, Lee YL, Wetmur JG, Teitelbaum SL, Bradshaw PT, Neugut AI, Santella RM, Chen J. Choline metabolism and risk of breast cancer in a population-based study. FASEB J. 2008 Jun;22(6):2045-52. Epub 2008 Jan 29. Link

25. Zeisel SH, Da Costa KA, Franklin PD, Alexander EA, Lamont JT, Sheard NF, Beiser A. Choline, an essential nutrient for humans. FASEB J. 1991 Apr;5(7):2093-8. Link

26. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic A Report of the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes and its Panel on Folate, Other B Vitamins, and Choline and Subcommittee on Upper Reference Levels of Nutrients, Food and Nutrition Board, Institute of Medicine. 1998:390-422. Link

27. Cherqaoui R, Husain M, Madduri S, Okolie P, Nunlee-Bland G, Williams J. A reversible cause of skin hyperpigmentation and postural hypotension. Case Rep Hematol. 2013;2013:680459. doi: 10.1155/2013/680459. Epub 2013 Jun 11. | link

Reviewed

Caudill MA. Pre- and postnatal health: evidence of increased choline needs. J Am Diet Assoc. 2010 Aug;110(8):1198-206. Link

da Costa KA, Gaffney CE, Fischer LM, Zeisel SH. Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am J Clin Nutr. 2005 Feb;81(2):440-4. Link

da Costa KA, Niculescu MD, Craciunescu CN, Fischer LM, Zeisel SH. Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am J Clin Nutr. 2006 Jul;84(1):88-94. Link

Savendahl L, Mar MH, Underwood LE, Zeisel SH. Prolonged fasting in humans results in diminished plasma choline concentrations but does not cause liver dysfunction. Am J Clin Nutr. 1997 Sep;66(3):622-5. Link