Lesson 27: Choline


Choline is a nutrient commonly grouped with B-vitamins. Choline has a variety of functions: It is part of cell membranes, helps nerves function properly, plays a role in liver function, is linked to our memory and mood, and may work with folic acid during pregnancy for the development of a baby’s brain and nervous system.Choline is an essential nutrient that is naturally present in some foods and available as a dietary supplement. Choline is a source of methyl groups needed for many steps in metabolism. The body needs choline to synthesize phosphatidylcholine and sphingomyelin, two major phospholipids vital for cell membranes. Therefore, all plant and animal cells need choline to preserve their structural integrity. In addition, choline is needed to produce acetylcholine, an important neurotransmitter for memory, mood, muscle control, and other brain and nervous system functions [1-3]. Choline also plays important roles in modulating gene expression, cell membrane signaling, lipid transport and metabolism, and early brain development.

Humans can produce choline endogenously in the liver, mostly as phosphatidylcholine, but the amount that the body naturally synthesizes is not sufficient to meet human needs. As a result, humans must obtain some choline from the diet. Premenopausal women might need less choline from the diet than children or other adults because estrogen induces the gene that catalyzes the biosynthesis of choline [4]. When a diet is deficient in folate, a B-vitamin that is also a methyl donor, the need for dietary choline rises because choline becomes the primary methyl donor.

The most common sources of choline in foods are the fat-soluble phospholipids phosphatidylcholine and sphingomyelin as well as the water-soluble compounds phosphocholine, glycerolphosphocholine, and free choline. When these choline-containing compounds are ingested, pancreatic and mucosal enzymes liberate free choline from about half of the fat-soluble forms and some water-soluble forms [5]. Free choline, phosphocholine, and glycerophosphocholine are absorbed in the small intestine, enter the portal circulation, and are stored in the liver, where they are subsequently phosphorylated and distributed throughout the body to make cell membranes. The remaining fat-soluble phospholipids (phosphatidylcholine and sphingomyelin) are absorbed intact, incorporated into chylomicrons, and secreted into the lymphatic circulation, where they are distributed to tissues and other organs, including the brain and placenta.

Choline status is not routinely measured in healthy people. In healthy adults, the concentration of choline in plasma ranges from 7 to 20 mcmol/L. According to one study, the range is 7–9.3 mcmol/L in fasting adults . Plasma choline levels do not decline below 50% of normal, even in individuals who have not eaten for more than a week. This may be due to the hydrolysis of membrane phospholipids, a source of choline, to maintain plasma choline concentrations above this minimal level, or to endogenous synthesis.

Meeting Your Daily Choline Requirement

The recommended amounts listed in the chart to the right meets the needs of individuals. Women who want to become pregnant should include choline- rich foods in order to reduce the risk of neural tube defects.

Food Sources of Choline

The body naturally makes choline in the liver, but it is not enough to meet our recommended intake. Eating a well-balanced vegetarian diet with a wide variety of whole foods should will help you get most of the nutrients your body needs. Although eggs and meat tend to be the highest sources of choline, it is found in a wide range of plant foods in smaller amounts. It is important for vegans to carefully consider prioritizing foods that are good sources of Choline.

*Ensuring daily intake of some of the following : beans, soy products such as tofu, soy milk, miso, natto and tempeh, broccoli, peas, quinoa, nuts and oranges. And of course ensuring adequate intake of folate , B12 and amino acid methionine ( found in oats, sunflower seeds and Brazil nuts) so the body can also produce choline.*

Choline Deficiency

Choline deficiency can cause muscle damage, liver damage, and nonalcoholic fatty liver disease (NAFLD or hepatosteatosis). Although most people in the United States consume less than the AI of choline, frank choline deficiency in healthy, nonpregnant individuals is very rare, possibly because of the contribution of choline that the body synthesizes endogenously

Choline and Health

This section focuses on three conditions in which choline might play a role: cardiovascular and peripheral artery disease, neurological disorders, and NAFLD. Choline is involved in functions that overlap with those of folate and other B vitamins. Many studies do not assess the status of all B vitamins, which can confound results and obscure the true relationship between choline and the observed outcome.

Cardiovascular and peripheral artery disease

Some researchers have suggested that choline might protect cardiovascular health by reducing blood pressure, altering lipid profiles, and reducing levels of plasma homocysteine. Other research suggests that higher dietary choline might increase cardiovascular disease risk because some choline and other dietary ingredients, such as carnitine, are converted to trimethylamine (TMA) by intestinal bacteria. The TMA is then absorbed and converted by the liver into trimethylamine-N-oxide (TMAO), a substance that has been linked to a higher risk of cardiovascular disease.

Despite the hypothesis that choline might affect heart health, several large observational studies have found no significant associations between choline intakes and cardiovascular or peripheral artery disease risk. An analysis of 72,348 women in the Nurses’ Health Study and 44,504 men in the Health Professionals Follow-up Study showed no association between choline intake and risk of peripheral artery disease in men or women. Similarly, a prospective study in 14,430 middle-aged adults in the Atherosclerosis Risk in Communities Study found that over 14 years, risk of coronary heart disease was not significantly different in the highest choline intake quartile compared to the lowest quartile. Choline intakes also had no association with cardiovascular disease risk in a study of 16,165 women participating in the European Prospective Investigation into Cancer and Nutrition.

However, a more recent analysis of data on 80,978 women from the Nurses’ Health Study and 39,434 men from the Health Professionals Follow-Up Study found an increased risk of mortality in those consuming higher levels of choline. The authors suggest that the higher risk might be due to increased production of TMAO, although they did not directly measure TMAO. Additional research is needed to determine the relationship between choline intakes and cardiovascular and peripheral artery disease as well as the potential risks and benefits of choline supplementation to reduce the risk of these diseases.

Neurological disorders

People with Alzheimer’s disease have lower levels of the enzyme that converts choline into acetylcholine in the brain. In addition, because phosphatidylcholine can serve as a phospholipid precursor, it might help support the structural integrity of neurons and thus might promote cognitive function in elderly adults [8]. Some experts have therefore theorized that consuming higher levels of phosphatidylcholine could reduce the progression of dementia in people with Alzheimer’s disease. However, little research conducted to date supports this hypothesis, as described below.

A few observational studies have shown a link between cognitive performance in adults and both higher choline intakes and plasma concentrations. In one observational study in 2,195 adults aged 70–74 years in Norway, participants with plasma free choline concentrations lower than 8.4 mcmol/L (20th percentile of concentrations in the study population) had poorer sensorimotor speed, perceptual speed, executive function, and global cognition than those with choline concentrations higher than 8.4 mcmol/L. A second study in 1,391 adults aged 36–83 years from the Framingham Offspring study who completed food frequency questionnaires from 1991 to 1995 and again from 1998 to 2001 found that those with higher choline intakes had better verbal memory and visual memory. Furthermore, higher choline intakes during the earlier period were associated with smaller white matter hyperintensity volume (a high volume is a sign of small-vessel disease in the brain).

Some small randomized intervention trials have shown that choline supplements improve cognitive performance in adults . However, a 2015 systematic review of 13 studies on the relationship between choline levels and neurological outcomes in adults found that choline supplements did not result in clear improvements in cognition in healthy adults . Similarly, a 2003 Cochrane review of 12 randomized trials in 265 patients with Alzheimer’s disease, 21 with Parkinsonian dementia, and 90 with self-identified memory problems found no clear clinical benefits of lecithin supplementation for treating Alzheimer’s disease or Parkinsonian dementia. Future studies are needed to clarify the relationship between choline intakes and cognitive function and determine whether choline supplements might benefit patients with Alzheimer’s disease or other forms of dementia.

Nonalcoholic fatty liver disease

NAFLD involves the accumulation of lipids in the livers of people who consume less than 20 g/day ethanol and who have no other known causes of steatosis. (A single drink [e.g., 12 oz beer, 5 oz wine, or 1.5 oz hard liquor] contains about 12–14 g alcohol.) It is the most common chronic liver disorder, present in up to 65% of overweight individuals and 90% of those with obesity. Although it is often benign, NAFLD can lead to steatohepatitis, fibrosis, cirrhosis, liver failure, and liver cancer. Choline, especially phosphatidylcholine, is essential for transporting lipids from the liver. Therefore, in choline deficiency, fat accumulates in the liver, which can result in NAFLD. Although most women of childbearing age are resistant to NAFLD because of their high estrogen levels, at least 40% have a polymorphism that makes them insensitive to activation of the gene by estrogen; adequate consumption of dietary choline is particularly important for this population.

Data from a single large observational study support a link between choline deficiency and risk of NAFLD. Specifically, a cross-sectional study of 56,195 Chinese adults aged 40–75 years found an inverse relationship between dietary choline intakes and risk of NAFLD based on 24-hour dietary recall. The risk of NAFLD was 32% lower in women in the highest quintile of choline intake (412 mg/day) compared to the lowest (179 mg/day) and 25% lower in men in the highest (452 mg/day) quintile compared to those in the lowest quintile (199 mg/day). However, choline intake was associated with NAFLD in normal-weight women only and not in those who were overweight or obese. This difference by weight status was not observed in men.

In a cross-sectional study of 664 adults and children from the Nonalcoholic Steatohepatitis Clinical Research Network, postmenopausal women who had nonalcoholic steatohepatitis (an extreme form of NAFLD involving liver inflammation and fibrosis) and a choline intake less than 50% of the AI had more severe fibrosis, but the results showed no relationship between choline intake and degree of liver steatosis.

Only limited data are available on the use of choline to treat NAFLD. For example, in a study of 57 adults who consumed a diet that included less than 50 mg choline per 70 kg body weight per day (<10% of the AI) for up to 42 days, 37 of the participants developed liver dysfunction. Liver function returned to normal in 29 participants in this study after they were fed a diet containing 25%–75% of the choline AI and in 8 who consumed an ad libitum diet. A pilot study in 15 adults on TPN found that NAFLD resolved completely in all patients who received their usual TPN regimen with an additional 2 g choline and in none of the patients who received their usual TPN regimen only. Adequate choline intake is needed for proper liver function and to prevent NAFLD, but more research is needed to further clarify the role of choline in preventing or treating NAFLD