Outcome
    Moderate Evidence
    Effectiveness 2/5

    Glutathione for Phase II Detox Support

    Phase II detoxification depends on glutathione conjugation, and depleted glutathione measurably impairs it. The question is not whether glutathione matters but whether swallowing it raises tissue levels — and standard oral forms largely do not.

    Overview

    Phase II detoxification depends on glutathione conjugation, and depleted glutathione measurably impairs it. The question is not whether glutathione matters but whether swallowing it raises tissue levels — and standard oral forms largely do not.

    Verdict

    Mixed evidence

    Glutathione is genuinely central to phase II conjugation, but oral glutathione is a poor way to raise it. NAC supplies the rate-limiting precursor and has far better evidence.

    How It Works

    Glutathione S-transferases conjugate glutathione to electrophilic metabolites produced by phase I enzymes, rendering them water soluble for biliary and renal excretion. Synthesis is rate-limited by cysteine availability and glutamate-cysteine ligase, which is why precursor supply usually outperforms supplying the finished tripeptide.

    Dosing & Protocol

    Typical dose

    Recommended dose
    250-1,000 mg/day liposomal, or NAC 600-1,200 mg/day
    Expected timeframe
    4-12 weeks for biomarker change

    Protocol

    timing
    Empty stomach
    starting dose
    NAC 600 mg/day, or liposomal glutathione 250 mg/day
    typical range
    NAC 600-1,200 mg/day; liposomal glutathione 250-1,000 mg/day
    assessment point
    3 months

    Evidence

    What the studies say

    Intestinal gamma-glutamyltransferase cleaves oral glutathione into its constituent amino acids, and early pharmacokinetic work found no rise in plasma glutathione after large single oral doses. Later trials of sustained daily supplementation, and of liposomal formulations, have reported increases in body stores and in the reduced-to-oxidised ratio over one to six months, alongside changes in immune markers such as natural killer cell activity. These are biomarker outcomes rather than clinical ones. NAC by contrast reliably raises hepatic glutathione and is the established antidote in paracetamol poisoning, the clearest real-world demonstration that replenishing glutathione through its precursor supports phase II conjugation.

    Randomized controlled trial of oral glutathione supplementation on body stores of glutathione

    Score: 7/10
    2015
    rct
    n=54

    Richie JP, Nichenametla S, Neidig W +4 more

    Oral glutathione supplementation for six months resulted in increases in body stores of glutathione of 30-35% in blood and 260% in buccal cells at the higher dose.

    View source

    Safety

    Caveats

    Standard oral glutathione is largely degraded before absorption. Adequate protein, sulphur-containing vegetables and selenium matter more than any capsule.

    Less likely to help if

    People with adequate protein intake and no oxidative stress burden will not detect anything from this.

    Medical Disclaimer

    The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.

    Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.