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Glutathione bioavailability:New technology confronts old questions

By Kelly C. Heim, Ph.D.

Glutathione is a peptide comprised of the amino acids glutamine, cysteine and glycine. A universally acclaimed constituent of cellular defense systems, glutathione has been the subject of over 20,000 studies over the past 80 years. In its reduced form, glutathione serves as a powerful antioxidant in nearly every cell of the body. In the liver, it aids detoxification by interacting with toxins and promoting their excretion. In light of its widespread protective roles, glutathione is a prudent addition to any health and wellness protocol.‡

Significant antioxidant support and related health benefits have been demonstrated in animal and human studies of orally administered glutathione.1-4 Despite these outcomes, questions regarding bioavailability have evoked some controversy over the years. Since glutathione is a peptide, it is subject to degradation by peptidase enzymes in the digestive tract. Indeed, some evidence suggests that a fraction of an oral dose is broken down in this manner, yielding free glutamine, cysteine and glycine.3 The amino acids reassemble following absorption, affording considerable increases in plasma glutathione levels. However, other lines of evidence suggest that only a fraction of glutathione follows this course.‡

Absorption of intact glutathione through the intestinal epithelium has been clearly documented.4 In addition, special carrier proteins that occur in the intestine, heart, lungs, liver and brain enable intact glutathione to cross membranes throughout the body.3,4 Regardless of the route taken, the efficacy of orally administered glutathione is generally supported by cumulative body of evidence. However, enhancement of pharmacokinetic performance through various delivery technologies is an evolving area of glutathione research.‡5-8

Protection and transport: Two virtues of the liposome‡

For over four decades, liposomes have been studied, optimized and successfully applied as delivery vehicles for compounds that are poorly absorbed. Liposomes are tiny spheres composed of a phospholipid bilayer similar to a natural cell membrane (Figure 1). With glutathione loaded into its core, the liposomal structure enhances bioavailability by (1) protecting the peptide from degradation, and (2) transporting it across membranes.‡5-7



Figure 1. Structure of a liposome. A phospholipid membrane bilayer (blue) encloses a core filled with a bioactive, such as reduced glutathione (purple). The bilayer offers protection and enhances transport across many types of membranes.‡

Preclinical research on liposomal glutathione has demonstrated effective delivery across membranes.5 Comparison of liposomal glutathione with control liposomes in animal studies have elucidated superior support for markers of antioxidant defenses in vivo.6-8 While more clinical research is warranted, a robust proof of principle stems from a long history of liposomal-peptide systems in basic and clinical pharmacology research.‡

Liposomal Glutathione delivers highly pure, reduced glutathione, representing a considerable step forward in the field of nutraceutical delivery methods. By providing powerful support for antioxidant protection and detoxification, liposomal glutathione offers an advanced option suitable for many clinical applications.‡

References

  1. Hunjan MK, Evered DF. Absorption of glutathione from the gastrointestinal tract. Biochim Biophys Acta. 1985;815(2):184-8.
  2. Lomaestro BM, Malone M. Glutathione in health and disease: pharmacotherapeutic issues. Ann Pharmacother. 1995;29(12):1263-73.
  3. Favilli F, Marraccini P, Iantomasi T, Vincenzini MT. Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters. Br J Nutr. 1997;78(2):293-300.
  4. Kariya C, Leitner H, Min E, et al. A role for CFTR in the elevation of glutathione levels in the lung by oral glutathione administration. Am J Physiol Lung Cell Mol Physiol. 2007;292(6):L1590-7.
  5. Zeevalk GD, Bernard LP, Guilford FT. Liposomal-glutathione provides maintenance of intracellular glutathione and neuroprotection in mesencephalic neuronal cells. Neurochem Res. 2010;35(10):1575-87.
  6. Rosenblat M, Volkova N, Coleman R, Aviram M. Anti-oxidant and anti-atherogenic properties of liposomal glutathione: studies in vitro, and in the atherosclerotic apolipoprotein E-deficient mice.  Atherosclerosis. 2007;195(2):e61-8.
  7. Levitskaia TG, Morris JE, Creim JA, et al. Aminothiol receptors for decorporation of intravenously administered (60)Co in the rat. Health Phys. 2010;98(1):53-60.
  8. Kern JK, Geier DA, Adams JB, et al. A clinical trial of glutathione supplementation in autism spectrum disorders. Med Sci Monit. 2011;17(12):CR677-82.