Choline, α-GPC, and Cognitive Health Across the Lifespan
Research on choline and α-GPC continues to explore their role in cognitive function, neuroprotection, liver health, and aging-related neurological changes. Across clinical reviews, meta-analyses, and longitudinal studies, these compounds are being examined as part of broader integrative approaches to memory, metabolic health, and cognitive resilience across the lifespan.
People are always asking me about my personal protocols, so I thought I would begin sharing some of the practices and supplements I find invaluable, along with the reasons why I use them.
One thing I cannot do without is GPC choline. Choline is an essential nutrient involved in brain health, liver function, and the production of acetylcholine, the neurotransmitter associated with memory, focus, learning, and muscle control. I also eat two to three eggs a day because they are naturally rich in choline. Many people still worry that eggs increase cholesterol, but research examining the intake of three eggs daily found no adverse effects on cholesterol levels in healthy adults.
I want to retain what I learn, remember what I have always known, keep my liver free from fatty buildup, and support my strength training and recovery. Estrogen helps drive choline production in the body, which means that during menopause, when estrogen levels decline, women may become more vulnerable to choline deficiency and its cognitive and metabolic effects.
I use a liquid form of Alpha-GPC (L-α-glycerylphosphorylcholine) because it is highly bioavailable and readily crosses the blood–brain barrier. I keep it refrigerated and take a few squirts daily. I also recommend choline support to pregnant patients because of its role in fetal brain development. Extensive human studies on GPC have reported no severe adverse effects.
Some of you may remember Adele Davis, one of the pioneering voices of nutrition in the 1960s. She was a strong advocate for lecithin, which contains phosphatidylcholine and remains a valuable addition to foods such as smoothies and other nutrient-dense meals.
The first study examines the effects of different forms of choline supplementation, including alpha-GPC, lecithin, citicoline, and choline bitartrate. The authors describe these compounds as precursors to acetylcholine, the neurotransmitter involved in memory, focus, and cognitive processing, and discuss their growing use in nutritional and clinical approaches to cognitive support. The review also highlights lecithin as a source of phosphatidylcholine, connecting broader dietary practices with neurological and metabolic health.
The second study reviews the broader physiological effects and mechanisms of L-α-glycerylphosphorylcholine (GPC). In addition to its role in acetylcholine synthesis, the review discusses how GPC may influence neurogenesis, neurotrophic activity, inflammation, and cellular signaling pathways involved in brain and metabolic health.
The third study, a randomized cross-over intervention study, examines the effects of choline intake from whole eggs compared to a choline supplement in participants with metabolic syndrome. Researchers found that consuming three eggs per day increased plasma choline levels without increasing total or LDL cholesterol. Both eggs and choline supplementation reduced interleukin-6, a marker associated with inflammation, while egg consumption was also associated with reductions in C-reactive protein, insulin, and insulin resistance.
The fourth study examines whether L-α glycerylphosphorylcholine influences progression from mild cognitive impairment to dementia. Analyzing nationwide longitudinal data from more than 500,000 patients in South Korea, the researchers found that α-GPC users had a lower risk of developing both Alzheimer’s disease dementia and vascular dementia compared to non-users.
In this comprehensive review, we examine the main preclinical and clinical investigations assessing the effects of different forms of choline supplementation currently available, including choline alfoscerate (C8H20NO6P), also known as alpha-glycerophosphocholine (α-GPC, or GPC), choline bitartrate, lecithin, and citicoline, which are cholinergic compounds and precursors of acetylcholine. Extensively used as food supplements, they have been shown to represent an effective strategy for boosting memory and enhancing cognitive function.
Reference
Kansakar, U., Trimarco, V., Mone, P., Varzideh, F., Lombardi, A., & Santulli, G. (2023). Choline supplements: An update. Frontiers in endocrinology, 14, 1148166. https://doi.org/10.3389/fendo.2023.1148166
Unlocking the Potential of l-α-Glycerylphosphorylcholine: From Metabolic Pathways to Therapeutic Applications
Abstract
l-α-Glycerylphosphorylcholine (GPC), also known as choline alphoscerate or α-glycerophosphorylcholine, serves as both a pharmaceutical product and a dietary supplement. Through its metabolic pathways, GPC acts as the precursor not only of choline and acetylcholine but also of various phospholipids. Extensive preclinical and clinical evidence demonstrates that GPC effectively alleviates cognitive impairment associated with Alzheimer's disease, vascular dementia, cerebral ischemia, stress, and epilepsy, among other conditions. Additionally, GPC has beneficial effects on such conditions and measures as ischemic/hypoxic conditions, ionizing radiation-induced damage, exercise performance, growth hormone release, and liver damage. As well as facilitating cholinergic neurotransmission, evidence also indicates GPC, among other activities, also can promote γ-aminobutyric acid release, enhance protein kinase C activity, facilitate hippocampal neurogenesis, upregulate neurotrophic factors, and inhibit inflammation. In preclinical studies, results indicate that GPC is not genotoxic in vitro or in vivo. Extensive human studies indicate GPC causes no severe adverse effects. Possible risks of atherosclerosis and stroke await necessary validation. In this review, the GPC-related metabolic pathways, pharmacological effects, mechanisms of action, and safety evaluation are discussed with the aim of providing a comprehensive understanding of GPC.
Reference
Che, X., Zhao, Y., Xu, Z., Hu, Y., Ren, A., Wu, C., & Yang, J. (2025). Unlocking the Potential of l-α-Glycerylphosphorylcholine: From Metabolic Pathways to Therapeutic Applications. Nutrition reviews, 83(8), 1594–1620. https://doi.org/10.1093/nutrit/nuaf008
Choline Intake as Supplement or as a Component of Eggs Increases Plasma Choline and Reduces Interleukin-6 without Modifying Plasma Cholesterol in Participants with Metabolic Syndrome
Abstract
Metabolic syndrome (MetS) is characterized by low-grade inflammation and insulin resistance, which increase the risk of heart disease. Eggs have numerous nutrients including choline, carotenoids, and fat-soluble vitamins that may protect against these conditions. Egg phosphatidylcholine (PC) is a major contributor of dietary choline in the American diet. However, uncertainty remains regarding eggs due to their high concentration of cholesterol. In this study, we evaluated the effect of two sources of choline, whole eggs (a source of PC) and a choline supplement (choline bitartrate, CB), on plasma lipids, glucose, insulin resistance, and inflammatory biomarkers. We recruited 23 subjects with MetS to participate in this randomized cross-over intervention. After a 2-week washout, with no choline intake, participants were randomly allocated to consume three eggs/day or CB (~400 mg choline/d for both) for 4 weeks. After a 3-week washout period, they were allocated to the alternate treatment. Dietary records indicated higher concentrations of vitamin E and selenium during the egg period (p < 0.01). Interestingly, there were no changes in plasma total, low density lipoprotein (LDL)- or high density lipoprotein (HDL)-cholesterol, triglycerides, or glucose, compared either to baseline or between treatments. In contrast, interleukin-6 was reduced, with both sources of choline compared to baseline, while eggs also had an effect on lowering C-reactive protein, insulin, and insulin resistance compared to baseline. This study demonstrates that in a MetS population, intake of three eggs per day does not increase plasma LDL cholesterol, and has additional benefits on biomarkers of disease compared to a choline supplement, possibly due to the presence of other antioxidants in eggs.
Reference
DiBella, M., Thomas, M. S., Alyousef, H., Millar, C., Blesso, C., Malysheva, O., Caudill, M. A., & Fernandez, M. L. (2020). Choline Intake as Supplement or as a Component of Eggs Increases Plasma Choline and Reduces Interleukin-6 without Modifying Plasma Cholesterol in Participants with Metabolic Syndrome. Nutrients, 12(10), 3120. https://doi.org/10.3390/nu12103120
Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea
Abstract
Background: Alzheimer's disease and vascular dementia are two of the most common causes of dementia. While early diagnosis and intervention are crucial, available treatments and research concerning the mild cognitive impairment stage remain limited. This study aimed to evaluate the real-world effectiveness and safety of L-α glycerylphosphorylcholine in this context.
Objectives: To investigate the impact of L-α glycerylphosphorylcholine on the risk of conversion from mild cognitive impairment to Alzheimer's disease dementia and vascular dementia, as well as its influence on stroke risk
Design: A nationwide, population-based cohort study
Setting: Data from South Korea's National Health Insurance Service
Participants: Overall, 508,107 patients newly diagnosed with mild cognitive impairment between 2013 and 2016 were included.
Intervention: Patients were classified as users or non-users of L-α glycerylphosphorylcholine based on prescription records.
Measurements: The primary outcomes were the risk of progression to Alzheimer's disease dementia and vascular dementia. Stroke risk was examined as a secondary outcome. A time-dependent Cox regression analysis was used to adjust for demographic and clinical factors.
Results: Compared to non-users, L-α glycerylphosphorylcholine users had a lower risk of progression to Alzheimer's disease dementia (hazard ratio = 0.899, 95 % confidence interval: 0.882–0.918) and vascular dementia (hazard ratio = 0.832, 95 % confidence interval: 0.801–0.865) within 2,435,924 and 662,281.6 person-years, respectively. In patients under 65, L-α glycerylphosphorylcholine significantly reduced the risk of progression to Alzheimer's and vascular dementia. Stroke risk significantly decreased in patients who did not progress to dementia but not in those who did.
Conclusions: L-α Glycerylphosphorylcholine reduces dementia conversion and stroke risk in patients with mild cognitive impairment, making it a viable early intervention. Future large-scale randomized controlled studies should examine its effects on other dementia subtypes and long-term cognitive outcomes.
Reference
Kim, H. K., Park, S., Kim, S. W., Park, E. S., Hong, J. Y., Hong, I., & Baek, M. S. (2025). Association between L-α glycerylphosphorylcholine use and delayed dementia conversion: A nationwide longitudinal study in South Korea. The journal of prevention of Alzheimer's disease, 12(4), 100059. https://doi.org/10.1016/j.tjpad.2025.100059
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