Choline Supplements Review (Including Phosphatidylcholine, CDP-Choline, and Alpha-GPC)
Initial Posting: 1/28/17 Last Update:12/3/2019
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- What is it? Choline is a component of cell membranes and the neurotransmitter acetylcholine, which is essential for proper brain function, and it helps remove fat from the liver (see What It Is). The body naturally produces some choline and the rest can be obtained from the diet, but some people are not able to produce sufficient choline, particularly postmenopausal women and people with certain genetic traits, putting them at risk for choline deficiency.
- What does it do? Getting adequate choline from the diet helps prevent fatty liver (which can lead to reduced liver function) and muscle damage and, during pregnancy, may reduce the risk of birth defects. Supplemental choline has shown potential benefit with respect to stroke recovery, cognition, Alzheimer's disease, asthma, and ulcerative colitis (see What It Does).
- How to get it? Many foods are good sources of choline, particularly egg yolks, meats, and legumes (see Getting It from Food). Supplements can also provide choline in a variety of forms.
- Which form? A problem when choosing a choline supplement is that the different forms provide vastly different amounts of choline — and these differences are not clearly labeled. (See Comparison of Choline Ingredients in Supplements). To avoid confusion, we've calculated the choline content in each product for you in the second column of the Results Table.
- How much to take? The typical dose for treating disease ranges from fifty to several thousand milligrams of specific forms of choline (see Dosage).
- Best choice? Many products passed our tests of quality (see What CL Found), but only a few represent CL's Top Picks.
- Cautions: Choline is generally safe, although gastrointestinal side effects may occur with higher doses. A small percentage of people may develop a fish odor from choline. Although cause-and-effect relationships have not been demonstrated, higher intake of choline has been associated with increased risk of colorectal cancer in women, and choline increases production of TMAO, which, itself, is associated with a higher risk of heart attack. (See Concerns and Cautions).
What It Is:
Choline is a component of cell membranes and the neurotransmitter acetylcholine, a nerve chemical essential for proper brain function, including memory-related functions. In developing fetuses, choline is important for brain and memory development and may decrease the risk of neural tube defects. Choline is also required for lipid transport from the liver. Inadequate choline intake can result in fatty liver or muscle damage, as well as atherosclerosis, and possibly, certain neurological disorders (Zeisel, Nutr Rev 2009).
Our bodies can produce choline as well as obtain it from the foods we eat, such as egg yolk, meats, and legumes (see Getting It from Food). However, some people have less ability to produce choline and, therefore, need to get more choline from their diets. This is why, since 1998, choline has been considered an essential nutrient. This reduced ability to produce choline occurs in postmenopausal women (due to reduced estrogen, which plays a role in choline production) and those with common genetic variations associated with choline metabolism. These people are more prone to organ dysfunction (particularly of the liver) associated with a low-choline diet (Fischer, Am J Nutr 2010; Corbin, Curr Opin Gastroenterol 2013).
Choline intake tends to decrease with age and one U.S. government survey found that adults ages 71 and older consumed an average of about 264 milligrams per day, about one-half of the adequate intake for choline (Zeisel, Nutr Rev 2009).
Choline in Supplements
For many years, the most common source of choline as a supplement was phosphatidylcholine from soy lecithin. However, only 13% to 14% of phosphatidylcholine is choline — and it's choline that is the likely active component.
Many supplements now contain other forms of choline with two to three times as much choline per gram. As shown in the comparison chart below, the ingredient known as CDP-choline has a concentration of choline of 21.4%, and other forms, such as alpha-GPC, choline citrate and choline bitartrate, have about 40% choline. This doesn't necessarily make these "better" sources of choline, but it means you can take less to obtain the same amount of choline. Most supplements only list the amount of ingredient and not the amount of choline, so you need to be aware of these substantial differences.
Be aware that consuming high doses of choline in the form of choline bitartrate has been associated with the development of kidney stones (see Concerns and Cautions).
Comparison of Choline-containing Ingredients in Supplements
*For phosphatidylcholine, % choline may vary by approximately 0.5% depending on the specific fatty acid composition.
|CDP-choline, citicoline, Cognizin®
||Choline dihydrogen citrate
|Alpha-GPC, choline alfoscerate
||L-alpha glycerylphosphoryl choline
** Choline chloride does not appear to be currently available as a dietary supplement ingredient in the U.S., although it was generally recognized as safe by the FDA in 1975 and is used in animal feed.
What It Does:
Choline-containing ingredients have been used in clinical trials for a variety of disease, suggesting some potential benefits:
Fatty liver disease:
As noted earlier, inadequate choline from the diet can cause nonalcoholic fatty liver disease (NAFLD) and liver damage, and this risk may be increased in people with certain genetic types (affecting the enzymes choline dehydrogenase (CHDH) rs12676 and rs9001, methylene tetrahydrofolate dehydrogenase 1 (MTHFD1) (rs2236225), and PEMT (rs12325817) (Corbin, Curr Opin Gastroenterol 2013). Given intravenously, choline has been shown to be effective for treating total parenteral nutrition-associated hepatic steatosis in patients with choline deficiency (Buchman, Hepatology 1995). However, there do not appear to be studies on the effects of oral choline supplementation for the prevention or treatment of nonalcoholic fatty liver disease.
Treatment with CDP-choline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months by about 30%, according to an analysis of several clinical trials. The most effective dose appeared to be 2,000 mg daily of CDP-choline (428 mg of choline) (Davalos, Stroke 2002).
Memory and cognition:
Choline supplements have shown mixed results in studies to improve memory and/or cognition.
Studies showing CDP-choline to help to improve memory include one among older men and women (average age 67). Giving them 1,000 mg of CDP-choline twice daily for 2 months modestly improved short-term recall compared to placebo (Spiers, Arch Neurol 1996). A study among healthy middle-aged women (average age 47) given either 250 mg or 500 mg of CDP-choline daily for one month modestly improved certain measures of attention compared to placebo (McGlade, Food Nutr Sci 2012). Interestingly, those taking the lower dose had slightly better results than those taking the higher dose.
Studies showing less or no benefit include a small study among elderly adults given 2,000 mg of choline chloride four times daily for 21 days --- memory did not improve compared to placebo (Mohs, Neurobiol Aging 1980). A single, 2,000 mg dose of choline bitartrate taken with 25 mg of caffeine improved short-term memory and attention in middle-aged adults 40 minutes after ingestion compared to caffeine alone or placebo; however, there was no benefit when taking choline bitartrate with greater amounts of caffeine (50 mg or 100 mg) or taking choline bitartrate alone (Nagrecha, Clinic Pharmacol Biopharmaceut 2013). A single dose of choline bitartrate was also found to have no memory benefit in young adults one to two hours after ingestion (Lippelt, PLoS One 2016).
During Pregnancy and Lactation:
Choline plays important roles in brain and memory development in the fetus and appears to decrease the risk of the development of neural tube defects. Large amounts of choline are being delivered from the mother to the fetus during pregnancy and to the infant during lactation, which can deplete maternal choline levels (Zeisel, Nutr Rev 2009). A significant increase in choline intake during pregnancy may be beneficial to infants, as shown in a study of 24 women entering the third trimester of pregnancy. For 12 weeks they took a supplement containing either 100 mg or 550 mg of choline (as choline chloride) in addition to getting 380 mg of choline from their diet, as well supplementing with vitamins, minerals and 200 mg of DHA. When tested at 4 through 13 months of age, infants whose mothers had taken the 550 mg dose of choline had significantly faster information processing speeds than those whose mothers had taken 100 mg (Caudill, FASEB J 2017).
In June 2017, delegates at the American Medical Association annual meeting voted to support evidence-based amounts of choline in all prenatal vitamins, noting that mostprenatals currently contain little if any choline. As noted below, adequate intake of choline per day is 450 mg for women who are pregnant and 550 mg for those who are lactating (compared to 425 mg for other women). Considering that young women consume, on average, only 280 mg of choline per day (USDA NHANES 2013-2014), supplementing with about 200 to 400 mg of choline daily during pregnancy and about 300 to 600 mg during the third trimester and lactation would seem appropriate, depending on the amount of choline in one's diet.
Alzheimer's disease and dementia:
As with findings from studies on choline for memory and cognition, it appears that some forms and sources of choline may be beneficial in Alzheimer's disease, while others are not. High daily doses of lecithin (20 — 30 grams per day), a source of phosphatidylcholine, have generally not been found to be beneficial in people with Alzheimer's disease (Etienne, Neurology 1981; Little, J Neurol Neurosurg Psychiatry 1985).
However, a study among 261 men and women (ages 60 to 80) with a diagnosis of mild to moderate probable or possible Alzheimer's disease found that 400 mg of alpha-GPC taken in the morning, at lunch, and before dinner (total daily dose of 1,200 mg alpha-GPC) for six months modestly improved cognition and global function compared to placebo (Moreno, Clin Ther 2003). The same daily dose taken with 10 mg of donepezil (Aricept) for 2 years decreased depression, anxiety and apathy in patients with mild to moderate Alzheimer's disease in Italy, while donepezil taken with a placebo increased the severity and frequency of depression, anxiety and apathy. In addition, the combination of alpha-GPC and donepezil significantly decreased severity and stress of the patient's caregivers compared to donepezil with placebo (Carotenuto, J Alzheimers Dis 2016). Another study in Italy found that 1,000 mg of CDP-choline taken with either donepezil (Aricept), rivastigmine (Exelon), or galantamine (Razadyne) (drugs that inhibit the breakdown of acetylcholine) for nine months resulted in modest improvements in cognition compared to drug treatment alone (Gareri, J Alzheimers Dis 2016). There is also evidence that 1,000 mg of CDP-choline taken with galantamine (Razadyne) may slow the progression of Alzheimer's disease compared to treatment with galantamine alone (Castagna, Clin Drug Investig 2016).
A study among 75 healthy male adolescents (ages 13 to 18) who took either 250 mg or 500 mg of CDP-choline once daily for one month had slightly improved measures of attention, psychomotor speed and reduced impulsivity compared to those who took a placebo (McGlade, J Atten Disord 2015).
A small study among healthy, college-age men (average age 21) found that 600 mg of alpha-GPC for 6 days increased lower body isometric muscle strength, but did not increase upper body muscle strength, compared to placebo (Bellar, J Int Soc Sports Nutr 2015). However, another small study in healthy men found no improvement in physical or cognitive performance after exhaustive physical activity following a dose of choline (50 mg per kg of body weight) (Deuster, Mil Med 2002).
A study among 3,000 U.S. women found that breast cancer risk was reduced 24% among women with a high dietary intake of choline (> 488 mg/day) but was increased 30% among women homozygous for the minor allele of PEMT rs12325817, a gene of choline metabolism (Xu, FASB J 2008). However, there do not appear to be clinical trials investigating the effects of choline supplementation on breast cancer or breast cancer risk.
A study in India found that, compared to placebo, a dose of either 500 mg or 1,000 mg of choline citrate taken 3 times daily decreased symptoms and increased the number of asymptomatic days in patients with asthma (Gupta, Indian J Chest Dis Allied Sci 1997). Those taking the higher dose of choline citrate also had a decreased need for asthma medication compared to placebo. Another study in India found that 1,500 mg of choline chloride taken twice daily, in addition to standard medications (inhaled steroids and long-acting bronchodilators) for six months slightly improved bronchial reactivity and certain measures of immune inflammation, and reduced the use of medications, but did not decrease overall symptoms, compared to treatment with standard medication alone (Mehta, Immunobiology 2010).
People with ulcerative colitis may have insufficient amounts of phosphatidylcholine in the mucus lining of the colon; mucus phosphatidylcholine content may be reduced by as much as 70% in people with this condition (Stremmel, Dig Dis 2013). Some research suggests that supplementation with choline may be helpful. One study among 60 patients in Germany whose ulcerative colitis was poorly responsive to corticosteroids, for example, found that half of those who took 2,000 mg of phosphatidylcholine (from a 33% phosphatidylcholine enriched phospholipid delayed-release formula) daily for 3 months had a significant improvement of symptoms compared to just 10% of those who took a placebo; 80% of those who took phosphatidylcholine were also able to discontinue corticosteroid use without a flare-up, compared to 10% of those who took the placebo (Stremmel, Ann Intern Med 2007). However, this formulation does not appear to be available in the U.S.
There is preliminary evidence that citicholine (1,000 mg per day) may help slow the progression of primary open angle glaucoma (Grieb, Front Aging Neurosci 2016).
For more information about the clinical applications of choline, see the Choline article in the Encyclopedia on ConsumerLab.com.
Quality Concerns and What CL Tested For:
Neither the FDA nor any other federal or state agency routinely tests choline supplements for quality prior to sale. ConsumerLab.com, as part of its mission to independently evaluate products that affect health, wellness, and nutrition, purchased several dietary supplements sold in the U.S. claiming to contain various forms of choline. These were tested for their amounts of choline and, if they contained herbal ingredients, were also tested for potential contamination with heavy metals (lead, cadmium, and arsenic). Standard tablets and caplets were also tested for their ability to properly disintegrate ("break apart") as needed for absorption. See How Products Were Evaluated for more information about how products were evaluated.