Alpha-GPC for Women: Are There Any Particulars

Most studies of alpha-GPC in sport have been conducted in men, while women often take the supplement “by analogy.” The editorial team looked into how choline metabolism differs in the female body and what follows from this in practice.

Alpha-GPC in brief: what it is and why people take it

Alpha-GPC (alpha-glycerylphosphorylcholine, choline alfoscerate) is a compound that contains choline and serves as its source in the body. Choline is needed for the synthesis of the neurotransmitter acetylcholine, of the phospholipids of cell membranes, and for the metabolism of methyl groups. In a number of countries alpha-GPC is a prescription drug for treating cognitive disorders, and on the sports nutrition market it is sold as a supplement for focus and strength.

Women who train are usually interested in alpha-GPC for the same reasons as men: improving focus during training, the “mind–muscle connection” and a potential effect on strength performance. However, the question of “whether there are particulars for women” has a quite specific scientific basis, and it concerns primarily choline metabolism.

The female body processes choline differently from the male body, and this difference changes over the course of life: during the reproductive years, during pregnancy and breastfeeding, and after menopause. That is why a conversation about alpha-GPC for women should begin not with the supplement but with the need for choline in general.

At the same time it is important to acknowledge the limitations: most studies of alpha-GPC in sport have been conducted predominantly in men. There is virtually no direct data comparing the effect of the supplement in women and men, so some conclusions have to be drawn from the physiology of choline metabolism.

Sex differences in choline metabolism

The body can partly synthesize choline on its own — in the liver with the participation of the enzyme phosphatidylethanolamine-N-methyltransferase (PEMT). The activity of this enzyme’s gene is stimulated by estrogens. From this follows an important particularity: women of reproductive age have a more powerful “internal” pathway for obtaining choline.

This is well illustrated by the study of Fischer and colleagues (2007), published in the American Journal of Clinical Nutrition. Participants were placed on a diet very low in choline. Signs of deficiency — impaired liver or muscle function — developed in most men and postmenopausal women, but only in a fraction of premenopausal women.

The practical conclusion: on average a premenopausal woman is less vulnerable to insufficient dietary choline intake, but this “advantage” is not absolute. Genetic variants associated with folate and choline metabolism make some women more sensitive to deficiency.

After menopause, when estrogen levels fall, the need for dietary choline rises and approaches that of men. This is worth taking into account for older women who are considering choline supplements, including alpha-GPC.

Pregnancy and breastfeeding: a separate situation

Choline is critically important for fetal development, in particular the neural tube and the brain. That is why the intake recommendations for choline during pregnancy and lactation are higher than for other adult women. The review by Wiedeman and colleagues (2018) emphasizes that a significant proportion of pregnant women do not reach an adequate intake level.

However, it does not follow from this that pregnant women should take alpha-GPC. There are no safety studies of this particular compound during pregnancy, and in many countries choline alfoscerate is registered as a medicinal product whose instructions do not provide for such use without a doctor’s prescription.

The main sources of choline for pregnant and breastfeeding women should be foods: eggs, liver, meat, fish, dairy products, legumes. If the diet is insufficient, the question of a supplement (usually in the form of choline bitartrate or as part of prenatal formulas) is decided by a doctor.

During breastfeeding, alpha-GPC is also not recommended because of the lack of data on its passage into milk and its effect on the child. Any “sports” supplements are best postponed during this period.

• Eggs are one of the richest and most accessible sources of choline.
• Beef liver contains a great deal of choline, but its consumption in pregnant women is limited because of its vitamin A content.
• Fish, poultry, dairy products, soy and legumes are additional sources.

Sport: what is known and what is lacking

Studies of the effect of alpha-GPC in sport are few. Bellar, LeBlanc and Campbell (2015) reported an increase in isometric lower-limb strength after six days of taking 600 mg per day in young men. Kawamura and colleagues (2012) described the effect of glycerophosphocholine on growth hormone secretion and fat oxidation.

Can these results be transferred to women? Theoretically the mechanism — supplying choline for acetylcholine synthesis — is the same for both sexes. But the hormonal response to training, body composition and choline metabolism differ in women, so the effect may differ in magnitude.

Women considering alpha-GPC for training can realistically expect at most a small effect on focus or strength, which may not even appear. The supplement does not replace a training program, sufficient nutrition and recovery.

If a woman decides to try alpha-GPC, studies in healthy people used amounts from 250 to 600 mg before training. It is reasonable to start at the lower end, assessing tolerance, and not to combine several new supplements at once, so as to understand whether there is an effect.

Safety and special situations

Alpha-GPC is usually well tolerated. Among possible adverse effects, headache, heartburn, nausea, dizziness, insomnia or, conversely, drowsiness have been described. Some people note that a headache appears when combining choline supplements with other nootropics.

Women with migraine should be attentive: if choline supplements provoke a headache, it will be noticeable quickly, and it is better to stop taking them. It is also important to take into account medications that affect the cholinergic system — for example, drugs for treating dementia or some bladder medications with anticholinergic action.

Postmenopausal women with cardiovascular risk factors will find it useful to know about the observational study of Lee and colleagues (2021), which found an association between alpha-GPC use and stroke risk in a Korean cohort. A causal relationship has not been proven, but this is an argument in favor of consulting a doctor before long-term use.

Finally, during the period of planning a pregnancy it is logical to already think about dietary sources of choline and to discuss prenatal formulas with a doctor rather than sports supplements.

Editorial conclusions

The particulars of alpha-GPC for women are related primarily to choline metabolism: estrogens support the body’s own choline synthesis, so before menopause women are on average less vulnerable to its shortage, while after menopause the dietary need rises.

For pregnant and breastfeeding women, alpha-GPC is not recommended — choline is important during these periods, but it should be obtained from food and from supplements prescribed by a doctor.

Sports studies of alpha-GPC have been conducted predominantly in men, so women’s expectations regarding strength and focus should be moderate. Tolerance is usually good, but with migraine, medication use and cardiovascular risks a doctor’s consultation is needed.

We also recommend reading our articles “Alpha-GPC After 40,” “Alpha-GPC and Sleep” and “The History of Alpha-GPC: How the Supplement Became Popular.”

References

1. Fischer LM, daCosta KA, Kwock L, et al. Sex and menopausal status influence human dietary requirements for the nutrient choline. Am J Clin Nutr. 2007;85(5):1275–1285.
2. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington, DC: National Academies Press; 1998.
3. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Dietary Reference Values for choline. EFSA J. 2016;14(8):4484.
4. Wiedeman AM, Barr SI, Green TJ, et al. Dietary choline intake: current state of knowledge across the life cycle. Nutrients. 2018;10(10):1513.
5. Zeisel SH, da Costa KA. Choline: an essential nutrient for public health. Nutr Rev. 2009;67(11):615–623.
6. 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.
7. Kawamura T, Okubo T, Sato K, et al. Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults. Nutrition. 2012;28(11–12):1122–1126.
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.