Alpha-GPC (L-Alpha-Glycerylphosphorylcholine)

Overview

Alpha‑GPC (L‑Alpha‑Glycerylphosphorylcholine) is a naturally occurring choline compound that readily crosses the blood‑brain barrier. It serves as a highly bioavailable source of choline, a precursor for the neurotransmitter acetylcholine, and is primarily used as a dietary supplement to support cognitive performance and support neuromuscular function.

Benefits

Cognitive enhancement: Randomized trials in healthy adults and patients with mild cognitive impairment show that 600 mg daily improves memory, attention, and executive function, likely via increased acetylcholine synthesis.
Neuro‑protection: In animal models of stroke and traumatic brain injury, Alpha‑GPC reduces neuronal loss and improves functional recovery, suggesting a role in brain‑cell preservation.
Physical performance: Acute dosing (300–600 mg) before resistance training increases growth‑hormone secretion and may augment power output and sprint performance in athletes.
Age‑related decline: Long‑term supplementation (1 g daily) appears to attenuate age‑related declines in brain volume and supports mood stability.
Metabolic support: Limited evidence indicates that Alpha‑GPC may improve insulin sensitivity and hepatic lipid metabolism, especially in conjunction with diet‑induced obesity models.

How It Works

Process: Alpha‑GPC is hydrolyzed to free choline and glycerophosphate after intestinal absorption.
Pathway:
- The liberated choline enters the liver’s CDP‑choline (Kennedy) pathway, where it is phosphorylated to phosphocholine and subsequently incorporated into phosphatidylcholine, a major membrane phospholipid.
- In the brain, choline serves as substrate for choline acetyltransferase, generating acetylcholine, which enhances synaptic plasticity, memory encoding, and neuromuscular signaling.
- Alpha‑GPC also elevates phosphatidic acid levels, a lipid second messenger that activates mTOR signaling, thereby supporting protein synthesis and muscle growth.
- Additionally, its phosphatidyl‑derived metabolites act as agonists for muscarinic receptors, enhancing neuronal excitability and neurotrophic factor expression (e.g., BDNF).

Dosage

Cognitive support: 300–600 mg taken once daily, preferably with a meal to enhance absorption.
Acute performance: 300–600 mg 30–60 minutes before exercise; studies show peak plasma choline ~1 h post‑dose.
Clinical/Neuro‑protective: 600 – 1,200 mg divided into two doses (morning + evening) for 4–12 weeks in older adults or patients with mild cognitive impairment.
Special considerations:
- For individuals on cholinergic medications (e.g., donepezil), lower doses (200 mg) are advised to avoid excessive cholinergic activity.
- Consistent daily use yields more stable brain choline levels than sporadic high‑dose “stacking.”

Safety & Side Effects

Alpha‑GPC is generally well‑tolerated.
Reported adverse events are mild and include:
- Headache
- Gastrointestinal upset (nausea, diarrhea)
- Transient dizziness
High doses (>2 g/day) may cause hypotension or increased sweating.
Contraindications:
- Known hypersensitivity to choline derivatives
- Caution in patients with Parkinson’s disease or schizophrenia due to potential exacerbation of cholinergic imbalance.
Drug interactions:
- Anticholinergic drugs (e.g., atropine, antihistamines) may reduce efficacy.
- Cholinesterase inhibitors (e.g., donepezil, rivastigmine) may amplify acetylcholine‑related side effects (e.g., bradycardia, excessive salivation).
Pregnant and lactating women should use only under medical supervision.

Chemistry

Alpha‑GPC is a quaternary ammonium compound with the molecular formula C₈H₂₀NO₆P.
Its IUPAC name is (2‑hydroxy‑3‑(phosphoryl)‑propyl)‑trimethyl‑ammonium.
The structure consists of:
- A glycerol backbone esterified to a phosphoric acid moiety at the 3‑position
- A choline (trimethyl‑ammonium) group at the 2‑position, forming a zwitterionic, water‑soluble molecule.
Its molecular weight is 257.24 g/mol.
It has a pKa of ~3.6 (phosphate) and a permanent positive charge on the nitrogen, giving it high solubility in aqueous media.
The compound is stable at pH 3–8 and is typically supplied as a white, crystalline powder.

Sources & Quality

Alpha‑GPC is naturally present in small amounts in dairy, eggs, and soy, but commercial supplements are predominantly produced via enzymatic or chemical synthesis from choline‑bitartrate and glycerophosphate.
The most common method uses a phosphocholine‑hydrolyzing enzyme (phospholipase D) to link choline to glycerol‑3‑phosphate, yielding a highly pure (>98 %) product.
Natural‑source extracts are rare, so most commercial preparations are chemically synthesized and meet USP or GMP standards.
Quality‑focused manufacturers provide certificates of analysis (COA) confirming identity, purity, and absence of heavy metals or residual solvents.
For optimal bioavailability, a moisture‑free, sealed capsule or powder is recommended.