Supplement

Poly-γ-Glutamic Acid

Poly(gamma-glutamic acid)

Evidence TierCWADA NOT PROHIBITED

tuneTypical Dose

0.3-1.5 g/day depending indication/context

watchEffect Window

Acute (single meal) to 4-12 weeks depending endpoint.

check_circleCompliance

WADA NOT PROHIBITED

Overview

Clinical Summary

Poly-γ-glutamic acid is a natto-derived biopolymer with adjunctive microbiome, calcium-absorption, and exploratory CIN signals, but not broad general-health proof.

Randomized studies consistently improve stool frequency and softness and can modestly reduce LDL cholesterol depending on fiber type. Fermentation increases butyrate and may improve gut barrier and inflammation markers. Minority evidence includes improved insulin sensitivity and appetite control. Gas and bloating are dose dependent and common during dose escalation.

Fermentation-derived biopolymer with prebiotic-support, matrix-viscosity, and potential immunomodulatory effects. Clinical efficacy is context-specific.

Outcomes

What This Is Expected To Influence

Primary Outcomes

  • Gut/microbiota and stool-support effects in prebiotic combination context
  • Short-term CIN1/HPV adjunctive response signal

Secondary Outcomes

  • Early postprandial glucose moderation in high-gamma-PGA natto context
  • Acute calcium-absorption enhancement

Safety

Contraindications and Interactions

Contraindications

  • Natto/fermented-soy hypersensitivity
  • Prior severe anaphylaxis to related foods
  • Unsupervised disease-specific use (e.g., CIN management)

Side effects

  • Usually mild GI symptoms
  • Potential allergic reactions in sensitized individuals
  • Rare severe hypersensitivity (case-level signal)

Interactions

  • No well-established major drug interaction profile
  • Additive GI effects with prebiotics/fiber supplements
  • Combination products complicate attribution and monitoring

Avoid if

  • Pregnancy/breastfeeding without clinician guidance
  • Unsupervised pediatric use
  • Replacing standard medical care with supplement-only approach

Evidence

Study-level References

poly-gh-glutamic-acid-SRC-001Randomized, double-blind, parallel-group comparison trial.
Sourceopen_in_new

Umeda K, et al. Combination of poly-gamma-glutamic acid and galactooligosaccharide improves intestinal microbiota, defecation status, and relaxed mood: randomized double-blind trial. Biosci Microbiota Food Health. 2023;42(1):34-48. doi:10.12938/bmfh.2021-084. PMID:36660591.

Population: Healthy adults.

Dose protocol: GOS plus gamma-PGA versus GOS-alone protocol.

Key findings: Favorable microbiota/stool/mood outcomes in combination arm.

Notes: Combination-intervention confounding and sponsor affiliation.

Paper content

Favorable microbiota/stool/mood outcomes in combination arm.

poly-gh-glutamic-acid-SRC-002Multicenter randomized, double-blind, placebo-controlled phase II trial.
Sourceopen_in_new

Cho HW, et al. Short-term clinical and immunologic effects of poly-gamma-glutamic acid in CIN1: multicenter randomized double-blind phase II trial. PLoS One. 2019;14(6):e0217745. doi:10.1371/journal.pone.0217745. PMID:31220105.

Population: 195 women with CIN1.

Dose protocol: 1,500 mg/day oral gamma-PGA for 4 weeks.

Key findings: Higher histologic remission and hrHPV clearance vs placebo.

Notes: Industry competing-interest signal and short-term endpoint.

Paper content

Higher histologic remission and hrHPV clearance vs placebo.

poly-gh-glutamic-acid-SRC-003Randomized crossover pilot meal-test study.
Sourceopen_in_new

Araki R, et al. Suppression of increased postprandial blood glucose by gamma-PGA-rich natto: randomized crossover pilot. Nutrients. 2020;12(4):915. doi:10.3390/nu12040915. PMID:32230729.

Population: Healthy adults.

Dose protocol: White rice alone vs low-gamma-PGA natto meal vs high-gamma-PGA natto meal.

Key findings: Lower early-phase glucose IAUC with high-gamma-PGA natto.

Notes: Pilot size and food-matrix dependence.

Paper content

Lower early-phase glucose IAUC with high-gamma-PGA natto.

poly-gh-glutamic-acid-SRC-004Single-blind randomized crossover isotope study.
Sourceopen_in_new

Tanimoto H, et al. Acute effect of poly-gamma-glutamic acid on calcium absorption in post-menopausal women. J Am Coll Nutr. 2007;26(6):645-649. doi:10.1080/07315724.2007.10719642. PMID:18187428.

Population: 24 postmenopausal women.

Dose protocol: Single oral 60 mg gamma-PGA co-administered with calcium-containing beverage.

Key findings: Significant increase in calcium absorption.

Notes: Acute mechanistic endpoint. No long-term fracture/BMD outcomes.

Paper content

Significant increase in calcium absorption.

poly-gh-glutamic-acid-SRC-005Case report.
Sourceopen_in_new

Fujita H, et al. Case report of late-onset anaphylaxis caused by natto exposure. Arerugi. 2006;55(8):1002-1006. PMID:16883111.

Population: Natto-associated allergic reaction.

Dose protocol: Real-world dietary exposure.

Key findings: Serious hypersensitivity signal relevant to fermented-soy/gamma-PGA context.

Notes: Single-case design.

Paper content

Serious hypersensitivity signal relevant to fermented-soy/gamma-PGA context.

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