Alpha-GPC

NutraPedia - Evidence-Based Supplement Research

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Research Overview

Across the provided abstracts, α-glycerophosphocholine (Alpha‑GPC; also termed choline alfoscerate) has been studied most in two areas: (1) cognitive outcomes in Alzheimer’s disease (AD) as a cholinergic precursor, and (2) acute physiological/metabolic effects in healthy adults, particularly growth hormone (GH) responses and markers of lipid oxidation. A smaller, nutrition-focused line of research has examined Alpha‑GPC as a candidate “meat factor” that may enhance nonheme iron absorption, including mechanistic identification work and human isotope-based absorption studies in women.

The strongest evidence in these abstracts supports Alpha‑GPC’s ability to increase circulating choline after ingestion and to produce measurable short-term physiological changes under controlled conditions. In a small double-blind crossover study in young men, a single 1000 mg dose increased plasma free choline and was associated with a transient rise in GH and increases in circulating free fatty acids and ketone bodies (indices consistent with increased hepatic fat oxidation). For cognition, one multicenter, double-blind, randomized placebo-controlled trial in mild-to-moderate AD reported statistically significant improvements across multiple clinical scales over 180 days with 400 mg three times daily, suggesting potential symptomatic benefit and tolerability in that population; however, the broader historical context noted in the abstract (mixed results for cholinergic precursor “loading” approaches) implies that replication and comparison to contemporary standards of care are important for interpretation.

Key areas needing more research include confirmation and generalizability of cognitive benefits (e.g., independent replication, longer follow-up, functional outcomes, head-to-head comparisons or add-on designs with current AD therapies, and clearer characterization of responder subgroups and safety in older, comorbid populations). The acute GH/metabolic findings require larger samples, inclusion of women and older adults, dose–response testing, and evaluation of whether repeated dosing produces sustained, clinically meaningful effects (e.g., on body composition, strength, or metabolic health). For iron absorption, evidence is currently inconsistent: one human study found Alpha‑GPC increased nonheme iron absorption in a meal context, whereas a larger set of crossover absorption studies in inhibitory maize porridge did not detect a significant effect; resolving this discrepancy will likely require systematic testing across meal matrices, dosing, baseline iron status, and interactions with established enhancers (ascorbic acid, phytase, iron forms such as NaFeEDTA).

1. What conditions has Alpha-GPC been studied for?

  • Cognitive impairment due to mild-to-moderate Alzheimer’s disease (AD): Studied as choline alfoscerate (CA), which is Alpha-GPC, in a multicenter, double-blind, randomized, placebo-controlled trial over 180 days.

  • Acute endocrine/metabolic effects in healthy adults: Studied for growth hormone (GH) secretion and markers consistent with hepatic fat oxidation after a single 1000 mg dose in a double-blind randomized crossover study in young men.

  • Non-heme iron absorption (“meat factor”): Identified as L-alpha-glycerophosphocholine and tested as a meal additive to increase non-heme iron absorption in women with low iron stores.

  • Iron absorption in fortified complementary foods: Tested as an enhancer added to maize porridge with low-dose iron fortification; evaluated via stable-isotope iron absorption methods.

2. Does it work in treating those conditions? Summarize the evidence.

  • Alzheimer’s disease (cognitive symptoms): Evidence of benefit in one RCT.

    • In 261 patients with mild-to-moderate AD treated for 180 days, CA (Alpha-GPC) 400 mg three times daily was associated with improvement on multiple cognitive/clinical scales versus placebo.

    • ADAS-Cog: CA group decreased (improved) by 2.42 points at 90 days and 3.20 points at 180 days (both P < 0.001 vs baseline), while placebo worsened (increase of 2.90 points at 180 days; P < 0.001 vs baseline). Between-group differences were statistically significant at 90 and 180 days.

    • Other measures (MMSE, GDS, ADAS-Total, CGI) also showed statistically significant differences favoring CA at 90 and 180 days; ADAS-Behav and GIS differences were significant at 180 days.

    • Limitations: The abstracts provided do not describe longer-term outcomes, functional endpoints beyond scales, or comparisons to standard AD therapies; replication and modern comparative trials would strengthen confidence.

  • Acute GH secretion / metabolic markers: Evidence of short-term physiologic effects, not clinical treatment.

    • In 8 healthy young men, a single 1000 mg dose increased plasma free choline at 60 and 120 minutes and increased GH secretion at 60 minutes versus placebo.

    • Free fatty acids increased at 120 minutes, and ketone bodies (acetoacetate and 3-hydroxybutyrate) increased at 120 minutes, interpreted as increased hepatic fat oxidation.

    • Limitations: Very small sample, acute-only outcomes, and no demonstration of sustained body composition, performance, or clinical metabolic benefits.

  • Non-heme iron absorption: Mixed evidence depending on context.

    • In a human meal study (13 women with low iron stores), adding L-alpha-GPC to vegetarian lasagna increased non-heme iron absorption (P = 0.023), similar in direction to ascorbic acid (P = 0.010) under the tested conditions.

    • In a larger set of crossover absorption studies in women (n = 101) using maize porridge fortified with iron, adding L-alpha-GPC did not significantly increase iron absorption.

    • Interpretation: Alpha-GPC may enhance non-heme iron absorption in some meal matrices (e.g., the lasagna study) but not reliably across inhibitory staple meals (e.g., maize porridge). The effect appears context-dependent.

3. What health benefits does it have?

  • Cognitive/clinical benefit in mild-to-moderate AD (symptom-focused): In the 180-day RCT, Alpha-GPC (as choline alfoscerate) improved cognition and global clinical measures versus placebo (notably ADAS-Cog, MMSE, GDS, CGI, and ADAS-Total).

  • Acute increase in circulating choline: A single 1000 mg dose increased plasma free choline at 60 and 120 minutes in healthy young men.

  • Acute endocrine/metabolic signals: In the same acute study, Alpha-GPC increased GH at 60 minutes and increased free fatty acids and ketone bodies at 120 minutes (suggesting increased hepatic fat oxidation).

  • Potential enhancement of non-heme iron absorption in some settings: Identified as a “meat factor” component; increased iron absorption from a vegetarian meal in one small human study, though not confirmed in a larger fortification study using maize porridge.

4. Does it have any downsides or side effects?

  • Tolerability in AD trial: The AD RCT concludes Alpha-GPC (choline alfoscerate) was “tolerable,” but the abstract does not provide specific adverse event rates or types, so side-effect frequency/severity cannot be quantified from the provided text.

  • Acute study safety signals: The acute crossover study reports physiologic changes (increased GH, free fatty acids, and ketone bodies) but does not describe adverse events; absence of reported side effects in the abstract is not proof of no side effects.

  • Iron absorption implications (context-dependent): If Alpha-GPC increases non-heme iron absorption in some meals, it could theoretically be undesirable for individuals who must limit iron absorption (e.g., iron overload conditions). However, the evidence is inconsistent (no significant effect in the maize porridge fortification studies), and the abstracts do not evaluate clinical iron overload outcomes.

  • Overall limitation: The provided abstracts do not systematically report adverse events, so conclusions about downsides are limited to “appears tolerable” in one RCT and “no adverse events described” in the acute study.

5. Is it beneficial or harmful for any genetic variations (pharmacogenomics)?

The provided abstracts do not report analyses by genotype or genetic subgroups, and they do not evaluate pharmacogenomic interactions (e.g., variants affecting choline metabolism, acetylcholine signaling, or iron regulation). Therefore:

  • No pharmacogenomic conclusions can be drawn from these abstracts about Alpha-GPC being beneficial or harmful for specific genetic variants.

  • Any genotype-specific claims (for example, related to choline metabolism pathways or iron-handling genes) would require studies that explicitly stratify outcomes by genetic variation, which is not described here.

References

  1. 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
    Maria De Jesus Moreno Moreno (2003)
  2. Glycerophosphocholine enhances growth hormone secretion and fat oxidation in young adults
    Takashi Kawamura, Takeshi Okubo, Koji Sato, Satoshi Fujita, Kazushige Goto (2012)
  3. L-alpha-glycerophosphocholine contributes to meat's enhancement of nonheme iron absorption
    Charlotte N Armah, Paul Sharp, Fred A Mellon, Sandra Pariagh, Elizabeth K Lund (2008)
  4. Optimization of a phytase-containing micronutrient powder with low amounts of highly bioavailable iron for in-home fortification of complementary foods
    Barbara Troesch, Ines Egli, Christophe Zeder, Richard F Hurrell, Saskia de Pee (2009)


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