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Alpha-GPC (choline alfoscerate)

  • Vitamins & Supplements
  • Updated March 16, 2020

Alpha-GPC is a supplement that may increase brain levels of acetylcholine, a neurotransmitter? that is important for memory and learning. Neurons that produce acetylcholine are some of the first neurons lost in Alzheimer’s disease, and theoretically, taking alpha-GPC may compensate for that loss. No studies have tested whether alpha-GPC improves cognition in healthy individuals. Although some studies suggest that alpha-GPC may improve cognition in dementia patients, many of these studies were conducted before widespread use of currently approved Alzheimer’s drugs that are designed to increase acetylcholine levels. It is still unclear whether alpha-GPC has additional benefits over approved Alzheimer’s medications. Alpha-GPC is a supplement with few mild side effects.

Evidence

No studies have examined whether alpha-GPC improves cognition in healthy individuals or prevents Alzheimer’s disease. Alpha-GPC may improve cognition in patients with dementia, though it is still uncertain whether it has additional benefits over approved drugs. Our search identified:

  • One open-label study in patients with mild cognitive impairment
  • Two randomized controlled trials in patients with mild to moderate Alzheimer’s/dementia
  • One review of previous trials in patients with dementia or cerebrovascular disease
  • Preclinical studies on the use of alpha-GPC

Potential Benefit

The loss of neurons that use the neurotransmitter acetylcholine is an early event in the development of Alzheimer’s disease [1]. However, no studies have examined whether alpha-GPC improves cognition in healthy individuals or prevents Alzheimer’s disease. In one open-label study, patients with mild cognitive impairment reported that alpha-GPC treatment slightly improved cognition over 90 days, and this effect appeared to be more pronounced in patients without APOE4, the genetic risk factor for Alzheimer’s disease [2]. However, because this was not a placebo-controlled study, the improvement may have been due to a “practice effect”.

Preclinical studies suggest that alpha-GPC increases the levels of acetylcholine in the brain and can improve cognition in models of memory impairment or brain aging [3; 4]. In a model of accelerated aging, alpha-GPC had no effect on brain levels of beta-amyloid, a biological marker of Alzheimer’s disease [5]. However, in a model of hypertension, alpha-GPC reduced inflammation around blood vessels in the brain, although it did not preserve the integrity of brain blood vessels [6].

APOE4 carriers: One open-label study in patients with mild cognitive impairment reported that alpha-GPC slightly improved cognition, and this effect may be more pronounced in patients without APOE4 [2]. For more information on what the APOE4 gene allele means for your health, read our APOE4 information page.

For Dementia Patients

One study reported that alpha-GPC improved cognition and function in patients with mild to moderate dementia over six months. However, the patients were not taking currently approved Alzheimer’s drugs which also increase levels of acetylcholine in the brain [4]. Another study suggested that alpha-GPC over two years further improved cognition and function in patients with mild to moderate Alzheimer’s disease who were also taking an Alzheimer’s drug that increases acetylcholine levels [7]. However, no further studies have confirmed there is value adding alpha-GPC to approved Alzheimer’s drugs or whether it would be safe. Finally, one review of studies conducted before the approval of current Alzheimer’s drugs reported that alpha-GPC improved cognition in patients with dementia and cerebrovascular disease [8].

Safety

Few studies have reported on the potential side effects of alpha-GPC. One study suggested it may be associated with mild side effects such as constipation and nervousness [4]. Other potential side effects include heartburn, headache, insomnia, dizziness, skin rash, and confusion [9]. Although alpha-GPC is a supplement, no large, long-term studies have examined alpha-GPC’s safety.

The only reported drug interaction for alpha-GPC is scopolamine, a drug used for motion sickness [9].

NOTE: This is not a comprehensive safety evaluation or complete list of potentially harmful drug interactions. It is important to discuss safety issues with your physician before taking any new supplement or medication.

How to Use

Alpha-GPC is available as a supplement in many vitamin stores. For Alzheimer’s trials, patients have taken 400mg three times per day (1200mg total) [4].

Learn More

  • Find more information on WebMD.

References

  1. Hampel H, Mesulam MM, Cuello AC et al. (2019) Revisiting the Cholinergic Hypothesis in Alzheimer's Disease: Emerging Evidence from Translational and Clinical Research. J Prev Alzheimers Dis 6, 2-15.
  2. Gavrilova SI, Kolykhalov IV, Ponomareva EV et al. (2018) [Clinical efficacy and safety of choline alfoscerate in the treatment of late-onset cognitive impairment]. Zh Nevrol Psikhiatr Im S S Korsakova 118, 45-53.
  3. Lopez CM, Govoni S, Battaini F et al. (1991) Effect of a new cognition enhancer, alpha-glycerylphosphorylcholine, on scopolamine-induced amnesia and brain acetylcholine. Pharmacol Biochem Behav 39, 835-840.
  4. 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. Clin Ther 25, 178-193.
  5. Matsubara K, Okuda M, Shibata S et al. (2018) The delaying effect of alpha-glycerophosphocholine on senescence, transthyretin deposition, and osteoarthritis in senescence-accelerated mouse prone 8 mice. Biosci Biotechnol Biochem 82, 647-653.
  6. Tayebati SK, Amenta F, Tomassoni D (2015) Cerebrovascular and blood-brain barrier morphology in spontaneously hypertensive rats: effect of treatment with choline alphoscerate. CNS Neurol Disord Drug Targets 14, 421-429.
  7. Amenta F, Carotenuto A, Fasanaro AM et al. (2014) The ASCOMALVA (Association between the Cholinesterase Inhibitor Donepezil and the Cholinergic Precursor Choline Alphoscerate in Alzheimer's Disease) Trial: interim results after two years of treatment. J Alzheimers Dis 42 Suppl 3, S281-288.
  8. Parnetti L, Amenta F, Gallai V (2001) Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev 122, 2041-2055.
  9. WebMD ALPHA-GPC. (accessed March 12, 2020)