Choline: The Brain Nutrient Most People Are Missing

Short answer: Choline is needed to make acetylcholine, a messenger for memory and attention, and only about 7 percent of US adults reach the adequate intake. Eggs are the best common source. Whether more choline improves memory or thinking in healthy adults has not been shown. Pregnant women and vegans are most likely to fall short.

Most adults eat less choline than the adequate intake, but there is no trial evidence that eating more improves memory or thinking in healthy adults. The evidence that extra choline helps the brain is preliminary. It comes from small or single trials in people with dementia, cognitive impairment or stroke, one small trial in healthy women, and observational studies.

The practical step is to eat choline-rich foods, especially eggs, and to pay attention if you are pregnant, breastfeeding or vegan.

How much choline you need

The National Academy of Medicine (formerly the Institute of Medicine), which recognized choline as an essential nutrient in 1998, sets these Adequate Intakes (AI), from food and supplements combined:

These are not ambitious targets. They are the intake judged enough to prevent organ damage, especially liver damage, which is one of the earliest signs of choline deficiency. The AI is not an estimated requirement, so falling below it does not mean you are deficient.

Even so, the shortfall is widespread. In US national survey data from 2009–2012, only 10.8 percent of Americans aged 2 and over, and 6.6 percent of adults, reached the AI (Wallace and Fulgoni 2016). Women fared worse than men. An earlier review of US data found mean intakes far below the AI for older children, men, women and pregnant women (Zeisel and da Costa 2009).

Part of the reason is that the richest sources, eggs and liver, are foods that decades of cholesterol advice told people to limit. Choline also doesn’t have to appear on most nutrition labels (in the US, listing it is voluntary), and many dietary guidelines don’t mention it.

Best food sources of choline

Values from USDA FoodData Central:

• Eggs: The most practical source. Nearly all the choline is in the yolk. Two whole eggs give more than half the AI for women, plus protein, lutein, zeaxanthin and some vitamin D. See our page on eggs and the brain and the choline-rich egg scramble.
• Liver: The most concentrated common source; one serving gives about 65 percent of the AI for men and over 80 percent for women. It is also very high in vitamin A, so pregnant people are usually advised to avoid it.
• Soy: The best plant source, though far below eggs or liver. Tofu, tempeh and edamame all help.
• Chicken, fish and vegetables: Smaller amounts that add up over a day. Fish also brings omega-3 fats.

Without eggs, liver or a supplement, reaching the AI is hard. On a vegan diet, soy, cruciferous vegetables and quinoa would need to be eaten in large amounts every day.

What choline does in the brain

• Acetylcholine: Choline is the raw material for acetylcholine, the messenger of the brain network that handles memory, attention and learning. In Alzheimer’s disease, acetylcholine-making neurons are among the first to die. That is a loss of neurons, not a shortage of dietary choline, and low choline intake has not been shown to cause it.
• Cell membranes: Choline is part of phosphatidylcholine, the largest single class of phospholipid in most cell membranes. The body can make some phosphatidylcholine itself, but this route is limited and uses up methyl groups needed elsewhere. Sphingomyelin, another choline-containing fat, is a major part of the myelin sheath that insulates nerve fibers. Whether low dietary choline affects myelin in adults is not known.
• Methylation: Through its breakdown product betaine, choline supplies methyl groups, chemical tags used to control genes and make neurotransmitters. Folate does similar work, and enough of one can partly make up for low intake of the other, but they are not fully interchangeable. In adults, low choline intake can raise homocysteine, which is linked to heart disease and cognitive decline in observational studies.

Three Alzheimer’s drugs (donepezil, rivastigmine, galantamine) work by blocking the enzyme that breaks down acetylcholine. Giving extra choline or lecithin to raise acetylcholine was tried early on. Well-controlled trials did not confirm a benefit in Alzheimer’s disease (as summarized by De Jesus Moreno Moreno 2003).

Who needs to pay more attention

Pregnant and breastfeeding women

Choline needs rise in pregnancy and breastfeeding. The developing brain uses choline for membranes and for setting up gene-control patterns, and the hippocampus, the memory center, is especially sensitive to it.

Animal research, mainly from Steven Zeisel’s lab at the University of North Carolina, has consistently shown that extra choline in pregnancy improves offspring memory and learning. The effects last into adulthood. Human evidence is limited.

In a small randomized feeding trial (Caudill 2018), 26 women in their third trimester ate either 480 mg or 930 mg of choline a day. Infants in the 930 mg group had faster reaction times, averaged across tests at 4, 7, 10 and 13 months. The Egg Nutrition Center and the Beef Checkoff partly funded the trial.

Many prenatal vitamins contain little or no choline. Pregnant people can ask their midwife or doctor about choline intake.

Vegans and vegetarians

Plant sources contain far less choline per serving than eggs or liver, so many vegans fall below the AI without planning. Choline belongs on a vegan’s short list of nutrients to manage, alongside vitamin B12, omega-3 DHA and vitamin D. More in our guide to vegan diets and brain health. A dietitian can advise on whether a supplement makes sense.

Older adults

Aging is linked to declining function of acetylcholine neurons. Older adults are also more likely to take medicines that block acetylcholine, including some antihistamines, bladder medicines and tricyclic antidepressants; do not stop any medication without talking to your doctor.

Whether extra choline protects cognition in older adults has not been shown in trials. In the Framingham Offspring cohort, people with higher choline intake scored better on memory tests (Poly 2011), but this was observational.

APOE4 carriers

APOE4 is the strongest common genetic risk factor for late-onset Alzheimer’s disease. Some researchers have proposed that carriers handle phospholipids differently, but there is no trial evidence that choline matters more for them. In the Kuopio cohort, APOE4 status did not change the (null) link between egg intake and dementia (Ylilauri 2017).

Choline supplements

Supplements are an option if food falls short. They have not been shown to improve cognition in healthy people.

Choline bitartrate is the cheapest form. It raises blood choline and prevents the fatty liver of choline deficiency. Few studies have looked at cognition, and it is not known whether it affects brain acetylcholine.

Alpha-GPC occurs naturally in the brain, and animal studies suggest it can raise brain acetylcholine. A multicenter trial enrolled 261 people with mild to moderate Alzheimer’s dementia (De Jesus Moreno Moreno 2003).

Over six months, 1,200 mg a day (400 mg three times a day) improved several cognitive and global scores compared with placebo. This was a single trial, and alpha-GPC is not an approved Alzheimer’s treatment. A large Korean health-insurance cohort linked alpha-GPC use with a higher rate of stroke.

Citicoline breaks down into choline and cytidine, which the body converts to uridine, another building block for nerve cell membranes. It has the most studies of the three:

• A Cochrane review of 14 short, varied trials (Fioravanti and Yanagi 2005) covered older people with chronic brain disorders. It found some evidence of benefit on memory and behavior, but none on attention. Citicoline was well tolerated in these trials.
• In a small randomized trial in 60 healthy women aged 40–60 (McGlade 2012), 250 or 500 mg a day for 28 days reduced errors on an attention test. Several authors worked for the manufacturer.
• An open-label randomized study followed 347 people after a first ischemic stroke (Alvarez-Sabín 2013). Taking 1 g a day for 12 months was linked to better attention, executive function and orientation.

There are no good head-to-head trials. For a fuller comparison, see alpha-GPC vs citicoline.

Safety. The doses above are research doses, not recommendations. Choline supplements can interact with medicines, and alpha-GPC has been linked to higher stroke risk in one large cohort study. Ask a doctor or pharmacist before taking any of them, especially if you are pregnant, breastfeeding, take medication or have a health condition.

The Tolerable Upper Intake Level (UL) for choline is 3,500 mg a day for adults. Above it, choline can cause a fishy body odor, heavy sweating, stomach upset, low blood pressure and, in extreme cases, liver toxicity. At usual supplement doses these effects are uncommon.

Eggs and cholesterol: what changed

A large egg yolk contains about 186 mg of cholesterol. From the 1960s, guidelines advised limiting cholesterol to 300 mg a day, which effectively capped eggs at one a day or fewer for many Americans. For most people, dietary cholesterol has a fairly modest effect on blood cholesterol, because the liver makes less when more is eaten. Some people respond more strongly.

The 2015–2020 Dietary Guidelines for Americans dropped the 300 mg limit. But they added that this “does not suggest that dietary cholesterol is no longer important”. People should eat as little as possible within a healthy eating pattern.

A meta-analysis of 22 cohorts from 16 prospective studies (Shin 2013) compared one or more eggs a day with less than one a week. Eggs were not linked to heart disease or stroke in the general population. But they were linked to a 42 percent higher risk of type 2 diabetes, and to higher cardiovascular risk in people who already had diabetes.

The Finnish Kuopio study followed 2,497 men for about 22 years (Ylilauri 2017). Neither egg nor cholesterol intake was linked to a higher risk of dementia or Alzheimer’s disease. In a subgroup of 480 men, higher egg intake was linked to better scores on some tests of executive function. These are observational findings.

For most healthy people, eating up to about one egg a day was not linked to heart disease in cohort studies. People with diabetes, familial hypercholesterolemia or existing heart disease should ask their doctor or dietitian how many eggs suit them.

Frequently Asked Questions

What are the symptoms of choline deficiency?

Diagnosed deficiency is uncommon, though low intake is widespread. Overt deficiency shows up as fatty liver, muscle damage and raised liver enzymes. The liver is often affected first because it needs choline to export fat. Whether long-term low intake affects the adult brain is not known.

Does choline raise TMAO and heart risk?

Gut bacteria turn some choline into trimethylamine N-oxide (TMAO), which is linked to heart risk in some observational studies. How much TMAO from moderate choline intake matters is debated. Most researchers in the field consider the benefits of adequate choline to outweigh this theoretical concern.

Sources

• Zeisel, S. H., & da Costa, K. A. (2009). Choline: an essential nutrient for public health. Nutrition Reviews, 67(11), 615–623. doi:10.1111/j.1753-4887.2009.00246.x

• Wallace, T. C., & Fulgoni, V. L. 3rd. (2016). Assessment of total choline intakes in the United States. Journal of the American College of Nutrition, 35(2), 108–112. doi:10.1080/07315724.2015.1080127

• Institute of Medicine. (1998). Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press. doi:10.17226/6015

• Caudill, M. A., Strupp, B. J., Muscalu, L., Nevins, J. E. H., & Canfield, R. L. (2018). Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. The FASEB Journal, 32(4), 2172–2180. doi:10.1096/fj.201700692RR

• De Jesus Moreno Moreno, M. (2003). 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. Clinical Therapeutics, 25(1), 178–193. doi:10.1016/s0149-2918(03)90023-3

• McGlade, E., Locatelli, A., Hardy, J., Kamiya, T., Morita, M., Morishita, K., Sugimura, Y., & Yurgelun-Todd, D. (2012). Improved attentional performance following citicoline administration in healthy adult women. Food and Nutrition Sciences, 3(6), 769–773. doi:10.4236/fns.2012.36103

• Fioravanti, M., & Yanagi, M. (2005). Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database of Systematic Reviews, (2), CD000269. doi:10.1002/14651858.CD000269.pub3

• Alvarez-Sabín, J., Ortega, G., Jacas, C., Santamarina, E., Maisterra, O., Ribo, M., Molina, C., Quintana, M., & Román, G. C. (2013). Long-term treatment with citicoline may improve poststroke vascular cognitive impairment. Cerebrovascular Diseases, 35(2), 146–154. doi:10.1159/000346602

• Shin, J. Y., Xun, P., Nakamura, Y., & He, K. (2013). Egg consumption in relation to risk of cardiovascular disease and diabetes: a systematic review and meta-analysis. The American Journal of Clinical Nutrition, 98(1), 146–159. doi:10.3945/ajcn.112.051318

• U.S. Department of Health and Human Services & U.S. Department of Agriculture. (2015). 2015–2020 Dietary Guidelines for Americans. 8th Edition. dietaryguidelines.gov (PDF)

• Ylilauri, M. P., Voutilainen, S., Lönnroos, E., Mursu, J., Virtanen, H. E., Koskinen, T. T., Salonen, J. T., Tuomainen, T. P., & Virtanen, J. K. (2017). Association of dietary cholesterol and egg intakes with the risk of incident dementia or Alzheimer disease: the Kuopio Ischaemic Heart Disease Risk Factor Study. The American Journal of Clinical Nutrition, 105(2), 476–484. doi:10.3945/ajcn.116.146753

• Poly, C., Massaro, J. M., Seshadri, S., Wolf, P. A., Cho, E., Krall, E., Jacques, P. F., & Au, R. (2011). The relation of dietary choline to cognitive performance and white-matter hyperintensity in the Framingham Offspring Cohort. The American Journal of Clinical Nutrition, 94(6), 1584–1591. doi:10.3945/ajcn.110.008938