Evidence-Based Nutrient Recommendations

Choline

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Contents

Introduction

Choline is an essential nutrient needed for brain function, fat metabolism, and the health of cell membranes.

Humans make small amounts of choline in their liver but it’s not enough to meet needs and most choline comes from the diet. Foods contain choline in a number of different forms which include free choline, lecithin (also called phosphatidylcholine), sphingomyelin, glycerophosphocholine, and phosphocholine.

Although plant foods are generally lower in choline than animal foods, it’s found in small amounts in a wide range of plant foods. A vegan diet that emphasizes whole foods can provide enough choline.

Vegan women who are considering getting pregnant should choose a prenatal supplement that includes choline since inadequate intakes may be linked to the risk of neural tube defects.

Functions of Choline

Choline is involved in metabolic processes and in maintaining the structure of cells.

  • Most choline is used for synthesis of phospholipids which are an essential component of all cell membranes.
  • Like the B vitamins folate and vitamin B12, choline functions as a methyl donor. These compounds are important in many steps of metabolism.
  • Choline is needed to synthesize the lipoproteins involved in fat transport.
  • Choline is needed to synthesize acetylcholine, a neurotransmitter involved in mood, memory, and muscle control.

Choline Requirements

The requirement for choline was discovered in the 1990s in people on total parenteral nutrition (TPN), which delivers nutrition directly to the blood, bypassing digestion. Patients who were on TPN for long periods of time developed nonalcoholic fatty liver disease which resolved when choline was added to their feeding regimen (1, 2, 3). Without choline, the patients were unable to synthesize phosphatidylcholine, a compound needed for fat metabolism and transport (4).

The recommendation for choline is specified as an Adequate Intake (AI) which means that there is too little information to establish an RDA. The AI for choline is 550 mg/day for men and 425 mg/day for women but these numbers are based on very limited data. They are derived from a 1991 study at the University of North Carolina at Chapel Hill (5). When subjects consumed 50 mg or less of choline per day, they experienced markers of deficiency such as increased liver enzymes, a fatty liver, or elevated creatine phosphokinase (CPK) which indicates muscle deterioration. The deficiency symptoms resolved when the subjects were given supplements providing 500 mg of choline per day. The study didn’t look at the effects of choline intakes between 50 and 500 mg.

Since this study was published, five more studies on choline deficiency have been conducted at UNC Chapel Hill (6, 7, 8, 9, 10). In all these studies, deficiency was induced with diets that provided about 50 mg or less of choline. A large proportion of subjects developed markers of dysfunction within six weeks, indicating that few people can stay healthy on less than 50 mg/day of choline.

In one of these studies, just 138 mg of choline per 170 pounds of body weight was enough to return CPK function to normal, but the study involved a very small number of subjects, all of whom were men. And the study did not look at liver function (6). In contrast, in another of the studies, it took 825 mg per 170 pounds of body weight to normalize liver function (7). These differences may reflect the fact that there are a number of genetic variations that increase or decrease the need for choline.

Premenopausal women were much less likely to develop choline deficiency-associated organ dysfunction. This might be explained by the fact that estrogen protects against the effects of a genetic mutation that raises choline requirements (8, 9).

Choline can also be turned into betaine, another compound that acts as a methyl donor. Betaine can also be obtained directly from the diet and it may somewhat reduce the need for dietary choline.

It’s worth noting for vegans that vitamin B12 deficiency can interfere with production of choline and choline-containing phospholipids (11).

Given the uncertainty about choline requirements, aiming for the recommended choline intakes listed in Table 1 is a good idea.

Table 1. DRI for Choline12
Age Female
(mg)
Male
(mg)
0-6 mos 125 125
7-12 mos 150 150
1-3 yrs 200 200
4-8 yrs 250 250
9-13 yrs 375 375
14-18 yrs 400 550
≥ 19 yrs 425 550
Pregnant 450
Breastfeeding 550

Excessive choline intake is associated with fishy body odor, nausea, low blood pressure, and liver toxicity. The safe upper limit for choline intake is 3,500 mg per day.

Choline and Chronic Disease

Although recommendations for choline intake were established to protect against liver dysfunction, there has been a considerable amount of research looking at possible effects of choline on risk for cardiovascular disease, cancer, and dementia.

Choline and Heart Disease

Researchers have proposed that choline may protect against heart disease based on its functions in lipid metabolism and as a methyl donor. Methyl donors like choline, vitamin B12, and folate help lower homocysteine levels. Elevated homocysteine may be a risk factor for heart disease.

In the Framingham Offspring Study of 920 men and 1,040 women, higher intakes of choline (above 339 mg/day vs an average intake of 313 mg/day) were significantly associated with slightly lower homocysteine levels (13). And in a cross-sectional study from Greece, subjects with choline intakes above 310 mg had lower markers of inflammation (C-reactive protein, interleukin-6, and tumor necrosis factor), than those consuming less than 250 mg (14). Betaine intakes above 350 mg resulted in lower homocysteine and tumor necrosis factor compared to intakes below 260 mg.

In the Dutch arm of the European Prospective Investigation into Cancer and Nutrition (EPIC), higher choline (365 mg versus 239 mg/day) and folate intakes, but not betaine intake, were associated with modestly lower homocysteine levels. But they weren’t associated with incidence of cardiovascular disease (15).

There was no relationship between higher intakes of choline (which ranged from 300 to 500 mg per day) and heart disease events in the Atherosclerosis Risk in Communities study, which followed more than 14,000 adult subjects for 14 years (16). Finally, an analysis of 72,348 women in the Nurses’ Health Study and 44,504 men in the Health Professionals Follow-up Study found no association between choline intake and peripheral artery disease (17).

Despite its effects on homocysteine levels and possibly on markers of inflammation, there is little evidence to suggest a protective effect of choline against cardiovascular disease.

Choline as a Risk Factor for Heart Disease

While most research has focused on potential impacts of inadequate choline, it’s also been suggested that high intakes of choline could raise the risk for heart disease through its conversion to trimethylamine N-oxide (TMAO). Choline is converted to trimethylamine (TMA) by intestinal bacteria and this in turn is absorbed and converted by the liver to TMAO. Some research has linked TMAO to risk for cardiovascular disease (18, 19, 20).

Researchers from the Cleveland Clinic and University of California at Los Angeles (21) compared compounds in plasma taken from people who experienced death or a heart attack or stroke in the three years following an elective heart evaluation. They compared it to the compounds in plasma taken from age- and gender-matched subjects who did not experience these events. There were 18 compounds that were higher in plasma from the first group, including choline, betaine, and TMAO.

The researchers reported that all three of these compounds showed a dose-dependent association with cardiovascular disease in a large clinical study, the Learning and Validation Cohorts. Further research found that lecithin from eggs increased TMAO production and that higher TMAO blood levels were associated with an increase in major adverse cardiac events (22).

In contrast, a 2017 meta-analysis of six prospective studies did not find an association between choline or betaine intake and cardiovascular disease (23). Since the relationship of TMAO to cardiovascular disease risk isn’t yet completely clear, it’s too soon to draw any conclusions about high intake of choline as a risk factor (20).

Choline and Cancer

Numerous studies have looked for correlations between choline and various cancers but nothing can be concluded without significantly more evidence (24, 25, 26, 27, 28, 29).

Choline in Pregnancy and Infancy

Choline is required for the development of the central nervous system and plays other important roles in pregnancy (30). Because of choline’s importance, the American Medical Association recommends that prenatal supplements should include choline. Low choline intake during and immediately prior to pregnancy has been linked to an increased risk for neural tube defects and cleft palate in some studies (31, 32, 33).

A report from the California Birth Defects Monitoring Program (31) found that women with higher intakes of choline, betaine, and methionine in the three months prior to and the three months post-conception had a lower, but statistically weak, risk for having a baby with a neural tube defect. In this study, there were 424 cases of an NTD and 440 controls. Quartiles of choline intake were ≤ 290, 290–372, 372–498, and ≥ 498. 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.

More recent research does not find a strong association between maternal choline status and risk of a neural tube defect (34).

There is also research to suggest that higher choline intake or better maternal status in pregnancy is linked to enhanced cognitive development in infants and may even have benefits that last into school age, (35, 36, 37) although not all studies support these findings (38, 39) .

Although a woman’s choline intake may affect levels in breast milk (40), a study of 74 healthy lactating women found no difference in levels of water-soluble choline (the predominant form of choline in breast milk) among women following vegan, vegetarian, and non-vegetarian diets (41).

Choline Cognitive Function in Adults

In the Framingham Offspring Study, higher intakes of choline were associated with better verbal and visual memory among adults (42). But a 2015 systematic review of 13 studies found no improvements in cognitive function of healthy adults when they took choline supplements (43). In addition, a 2004 Cochrane review of clinical studies that looked at lecithin supplementation in people with memory loss, Alzheimer’s Disease, or Parkinson dementia found no clear benefits (44).

At this time, there is no evidence to suggest that lower choline intakes are a risk for dementia or that supplements of lecithin or other choline compounds are useful for preventing dementia.

Recommended Choline Intakes

Based on the limited research, 300 mg per day of choline may be adequate for most adults. But given the uncertainty, we recommend intakes that come closer to meeting the AI for this nutrient, especially for pregnant and nursing women.

Because choline is toxic at very high intakes and even moderately high intakes may be linked to cardiovascular disease, if you choose to take choline supplements, stick with a low dose and aim to get most of your choline from food.

Average U.S. Choline Intakes

Estimates of choline intakes are based on a USDA database that includes more than 630 food items. Based on food intake data from the National Health and Nutrition Examination Survey (NHANES), estimated usual choline intakes among non-pregnant, non-lactating adults is found to be just over 300 mg of choline per day (45). The findings indicate that only 10% of Americans and 8% of pregnant women meet choline recommendations.

An older study by researchers from the University of North Carolina at Chapel Hill found much higher intakes (46). Among their small study of 32 adults, average intake of choline was close to recommended intakes for women and exceeded those recommendations for men.

No studies have looked at choline intake of vegetarians or vegans.

Sources of Choline for Vegans

While we don’t have studies of choline intake among vegans, we do know that a vegan diet can provide adequate choline. The USDA database of the choline content of foods shows that there are small, but consistent amounts across a range of plant foods. Plant foods that are especially rich in choline include tofu, soynuts, soymilk, cruciferous vegetables, cooked dried beans, quinoa, peanuts, and peanut butter. It’s not clear how much choline is in more processed vegan foods because this hasn’t been measured. See a list of vegan foods and their choline content in table 2, as well as a sample vegan menu in table 3.

In addition, plant foods can be good sources of betaine, a compound that can stand in for choline as a methyl donor in some cases. Betaine is named after beets, and supplements of this compound are often a byproduct of sugar beet processing. 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.

Note that the USDA database shows the amount of choline per 100 g of food, which may not always be a typical serving size of the food. For example, 100 g of wheat germ provides 180 mg of choline. But that would be more than ¾ cup of wheat germ. A more usual 2-tablespoon serving of wheat germ provides around 27 mg of choline.

Despite the lower choline content of plant foods overall, you can feel confident that you’re meeting needs by eating legumes, including soyfoods and peanuts, and plenty of cruciferous vegetables.

Table 2. Food Sources of Choline47
Food Choline
(mg)
Shiitake mushrooms, cooked, ½ cup 58
Soymilk, original and vanilla, unfortified, 1 cup 57.3
Roasted soynuts, ¼ cup 53
Wheat germ, 2 tbsp 27
Kidney beans, canned, ½ cup 45
Quinoa, cooked, 1 cup 43
Tofu, firm, prepared with calcium sulfate and magnesium chloride (nigari), ½ cup 35.4
Brussels sprouts, boiled, ½ cup 32
Broccoli, boiled, ½ cup 31.3
Pinto beans, cooked, ½ cup 30.2
Soy protein powder, 1 oz 24
Peanuts, dry roasted, ¼ cup 24
Cauliflower, boiled, ½ cup 24
Peas, boiled, ½ cup 24
Peanut butter, smooth, 2 tbsp 20
Orange, 1 large 15.5
Almonds, dry roasted, 1 oz 15
Tomato sauce, ½ cup 12.2
Carrot juice, canned, ½ cup 11.7
Banana, raw, 1 medium 11.6
Oatmeal, instant, fortified, plain, prepared with water, 1 cup 11
Walnuts, English, 1 oz 11
Potatoes, boiled, with skin, ½ cup 10.5
Dates, medjool, 4 9.5
Bread, whole-wheat, commercially prepared, 1 slice 8.7
Zucchini, boiled, ½ cup 8.5
Spaghetti, cooked, enriched, 1 cup 8
Apples, raw, with skin, 1 large 7.6
Tahini, 2 tbsp 7.6
Lettuce, cos or romaine, 1 ½ cups 7
Avocado, ¼ cup cubes 5.4

Table 3. Choline in a 2,000-Calorie Vegan Menu47
Breakfast Choline (mg) Calories
1 cup oatmeal, cooked in water 17.3 166
2 tablespoons chopped English walnuts 5.8 96
1 tablespoon wheat germ 25.3 54
1 banana 11.6 105
1 cup soy milk 57 104
Total 117 525
Snack
1 navel orange 11.8 69
1/4 cup dry-roasted almonds 18 206
Total 29.8 275
Lunch
2 corn tortillas 6.4 104
1 cup pinto beans 60.4 245
1/2 cup cooked sliced portobello mushrooms 19.9 18
1/4 cup sliced avocado 5.2 59
1/4 cup sliced tomatoes 3 8
Total 94.9 434
Snack
1/2 cup raw sliced carrots 5.35 25
1/2 cup raw cauliflower florets 23.7 13
1/4 cup hummus 17.1 109
Total 46.15 147
Dinner
1 cup cooked quinoa 42.6 222
1 cup cooked broccoli 62.6 55
1 cup tofu 71.4 188
1/4 cup peanut sauce (includes 2 tablespoons peanut butter) 20.2 191
Total 196.8 656
Daily Total 485 2,037

 

References

Last updated March 2020

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45. Wallace TC, Fulgoni VL, 3rd. Assessment of Total Choline Intakes in the United States. J Am Coll Nutr 2016;35:108-12.

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47. U.S. Department of Agriculture, Agricultural Research Service. FoodData Central, 2019.

Reviewed

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

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.

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.

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.

Wallace TC, Blusztajn JK, Caudill MA, Klatt KC, Natker E, Zeisel SH, Zelman KM. Choline: The Underconsumed and Underappreciated Essential Nutrient. Nutr Today 2018;53:240-253.

Wiedeman AM, Barr SI, Green TJ, Xu Z, Innis SM, Kitts DD. Dietary Choline Intake: Current State of Knowledge Across the Life Cycle. Nutrients 2018;10

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