Overview
Polyglutamic acid, specifically in the form of polyglutamyl folic acid, refers to the naturally occurring form of folate found in foods, where glutamate chains are attached to the folate molecule. This polyglutamate structure must be deconjugated by intestinal enzymes (e.g., gamma-glutamyl hydrolase) to monoglutamyl forms before absorption, which limits its bioavailability compared to synthetic folic acid. Research shows that heptaglutamyl folic acid has lower bioavailability than monoglutamyl folic acid or synthetic folic acid, with significantly smaller increases in serum and erythrocyte folate concentrations after supplementation [1]. In contrast, PolyGlycopleX (PGX), a proprietary functional fiber composed of polyglutamic acid-containing polysaccharides, functions as a highly viscous soluble fiber that slows carbohydrate absorption, reduces postprandial glucose spikes, and may support weight management and metabolic health [2][9]. Doses of 2.5–5 g of PGX significantly reduce acute postprandial glycaemia when taken before meals, with optimal effects observed when consumed 15–30 minutes prior to eating [2]. PGX is well tolerated up to 10 g/day over 21 days, with minimal gastrointestinal side effects [10].
Dosage Guide
Therapeutic Doses
For treatment of specific conditions
Upper Intake Limit
Maximum safe daily intake
10 g— Maximum dose studied over 21 days; higher doses lack safety data
Clinical Notes
- PGX absorbs water and expands; must be taken with adequate fluid to prevent esophageal or gastrointestinal obstruction
- Start with lower doses (2.5 g) to assess tolerance and minimize bloating or gas
- May interfere with absorption of medications; take drugs at least 1 hour before or 2 hours after PGX
- Not a source of folate; despite structural similarity to polyglutamyl folate, PGX is a fiber, not a vitamin
Research
Heptaglutamyl folic acid has lower bioavailability than monoglutamyl folic acid in adults aged 50–75 years.
PGX (2.5–7.5 g) reduces postprandial glucose in a dose-dependent manner, with optimal timing 15–30 min before meals.
PGX is well tolerated at doses up to 10 g/day for 21 days in healthy adults.
Systematic review found PGX may support weight management and improve metabolic parameters, though evidence is limited to a few small RCTs.
Single-dose oral guanidinoacetic acid (GAA) shows dose-dependent pharmacokinetics, but this is not directly related to polyglutamic acid.
GAA supplementation does not increase brain GAA levels in healthy men, indicating safety regarding central nervous system accumulation.
GAA loading (3 g/day) reduces plasma GABA levels in healthy men, suggesting effects on neurotransmitter metabolism.
Highlights importance of phased clinical testing for supplements, relevant to development of PGX or similar agents.
PGX reduces postprandial glycaemia and supports satiety, with effects increasing with dose and proper timing.
No serious adverse events reported with PGX at up to 10 g/day for 21 days; good GI tolerance
