Alpha-GPC or Choline Bitartrate: What's the Difference

The body needs choline to synthesize the neurotransmitter acetylcholine, membrane phospholipids and for the metabolism of methyl groups in the liver. In supplements it is most often offered in two forms — alpha-GPC (alpha-glycerylphosphorylcholine) and choline bitartrate. The price difference between them can be several-fold. The editorial team looked into how these molecules differ and whether such a difference is justified.

Chemistry: a salt versus a phospholipid metabolite

Choline bitartrate is a simple salt: a choline cation combined with a tartaric acid anion. In the gut the salt dissociates, and the body receives free choline — the same molecule that forms from food. This is the cheapest and most common form of choline in multivitamins and complex supplements.

Alpha-GPC has a more complex structure. It is a natural intermediate breakdown product of phosphatidylcholine — the main phospholipid of cell membranes. The molecule consists of a glycerol residue, a phosphate group and choline. In effect it is a “half-assembled” phospholipid that the body can use both to obtain choline and to rebuild membranes.

Interestingly, in terms of choline content per gram the two forms are close: in both choline bitartrate and alpha-GPC choline makes up about 40% of the mass. That is, 1 g of each form yields a comparable amount of choline. For comparison, in citicoline (CDP-choline) its share is much smaller — about 18%.

So the difference between the forms is not in “how much choline is in the capsule,” but in how the molecule behaves in the body: where it is broken down, how much choline reaches the tissues and what happens to the rest.

Absorption and the route to the brain

Free choline from bitartrate is absorbed quickly, but a significant part of it is intercepted while still in the gut and liver. The liver actively uses choline to synthesize phosphatidylcholine and oxidizes it to betaine — a methyl-group donor. As a result, a relatively small fraction reaches the brain, where choline is needed for acetylcholine.

Another nuance is the microbiota. The portion of free choline that is not absorbed in the small intestine becomes a substrate for bacteria that produce trimethylamine (TMA). In the liver TMA is converted into TMAO. The work of Hazen's group (Wang et al., 2011; Tang et al., 2013) linked high TMAO levels with cardiovascular risk, although the causality of this association is still being discussed.

Alpha-GPC is considered a form with better delivery of choline to the central nervous system. After absorption the molecule is broken down into choline and glycerophosphate, and the plasma choline concentration rises. Clinical data in patients with cognitive impairment became the basis for registering choline alfoscerate as a medicine in some countries.

At the same time, there are practically no direct comparative studies of “alpha-GPC versus bitartrate” in healthy people regarding the level of acetylcholine in the brain. Therefore the claims of a “many-fold superiority” of alpha-GPC that appear in advertising are regarded by the editorial team as an exaggeration: the advantage is plausible, but its scale has not been measured.

What is known from studies

The most substantial data on alpha-GPC were obtained in medicine. In a multicenter randomized study by De Jesus Moreno Moreno (2003), patients with mild to moderate Alzheimer's disease received 1200 mg of choline alfoscerate per day for 180 days and showed better results on cognitive tests than the placebo group.

In the sports context there are few studies. Bellar and colleagues (2015) reported an increase in isometric strength of the lower limbs after six days of taking alpha-GPC, and Ziegenfuss and colleagues (2008) reported an acute increase in the growth-hormone response and peak power in the bench press. The samples were small, so these results require confirmation.

For choline bitartrate the sports results are less impressive. In the study by Warber and colleagues (2000), taking choline bitartrate did not improve the endurance of service members during prolonged exertion, although the plasma choline level rose. Interest in the topic arose after a decrease in plasma choline was recorded in marathon runners after a race (Conlay et al., 1986).

But choline bitartrate performs its basic function well — covering the need for choline. Physiologically it does not matter from which form the choline will go toward the synthesis of phosphatidylcholine in the liver, so for closing a dietary deficiency the cheaper form is entirely suitable.

Safety and side effects

For choline overall, a tolerable upper intake level has been established — 3.5 g per day for adults (Institute of Medicine, 1998). Exceeding it leads to a characteristic “fishy” body odor (due to an excess of TMA), sweating, nausea, diarrhea and a drop in blood pressure. These effects apply equally to any form, if you count the choline itself.

Choline bitartrate more often causes gastrointestinal discomfort and a “fishy” odor, which is linked to the larger share of free choline available to gut bacteria. Alpha-GPC was well tolerated in studies; among the side effects, headache, heartburn and insomnia were described.

A separate issue is the long-term safety of alpha-GPC. The cohort study by Lee and colleagues (2021) in JAMA Network Open, based on Korean data, found an association between long-term intake of alpha-GPC and an increased risk of stroke. This is an observational study that does not prove causation, but it is an argument in favor of moderation.

• Both forms are not recommended to be combined with anticholinergic drugs without consulting a doctor.
• In kidney and liver diseases, the doses of choline should be determined by a doctor.
• People with cardiovascular diseases should discuss taking choline with a cardiologist.

Editorial conclusions

Alpha-GPC and choline bitartrate contain approximately the same share of choline, but behave differently in the body. Alpha-GPC is a phospholipid metabolite with better data on effects on cognitive function and a small sports evidence base. Bitartrate is a cheap source of free choline, suitable primarily for closing a dietary need.

The differences in absorption are plausible, but there is a lack of direct comparative studies in healthy people, so advertising claims about a many-fold superiority of alpha-GPC should be treated critically.

The upper limit of safe choline intake is the same for both forms, and caution regarding long-term intake of alpha-GPC is justified until better-quality data appear.

We examined the practical scenarios for choosing between these forms in the article “Alpha-GPC vs Choline Bitartrate: Which to Choose and for Whom.” The editorial team also recommends the materials on citicoline and on nootropic supplements for athletes.

References

1. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academy Press; 1998.
2. Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutr Rev. 2009;67(11):615–623.
3. De Jesus Moreno Moreno M. 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. Clin Ther. 2003;25(1):178–193.
4. Bellar D, LeBlanc NR, Campbell B. The effect of 6 days of alpha glycerylphosphorylcholine on isometric strength. J Int Soc Sports Nutr. 2015;12:42.
5. Warber JP, Patton JF, Tharion WJ, et al. The effects of choline supplementation on physical performance. Int J Sport Nutr Exerc Metab. 2000;10(2):170–181.
6. Wang Z, Klipfell E, Bennett BJ, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472(7341):57–63.
7. Tang WHW, Wang Z, Levison BS, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368(17):1575–1584.
8. Lee G, Choi S, Chang J, et al. Association of L-α glycerylphosphorylcholine with subsequent stroke risk after 10 years. JAMA Netw Open. 2021;4(11):e2136008.