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Glutathione and its many (dis)guises

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There is an on-going proliferation of alternative delivery systems for Glutathione (GSH) in the misguided attempt that one may be effective. This rather extended list includes oral, sublingual, liposomal, intranasal, inhalation, transdermal and intravenous applications; all of which have demonstrated the inadequacy of Glutathione (GSH) to increase cellular Glutathione (GSH). Most importantly, all these delivery systems ignore one fundamental fact: The concentration of Glutathione (GSH) inside the cell is much higher than outside the cell, no matter how much Glutathione (GSH) is consumed. In fact, it is about one thousand-fold higher, making diffusion across that kind of concentration gradient thermodynamically impossible [1]. So why keep trying when the laws of nature are firmly against you?

Before 2014, trialling the use of Glutathione (GSH) as a supplement was uncommon. Clinicians then were well aware of its limited use.  However, several companies started manufacturing and marketing Glutathione (GSH) as a supplement shortly after that, even though there was very little evidence at best to show that it had potential to increase cellular Glutathione (GSH). Nonetheless, this led to researchers testing Glutathione’s (GSH’s) potential, and today, the U.S. Clinical Trial Register has a long list of over 30 completed trials, none of which have published any positive results.

One type of delivery system that keeps appearing in the literature is liposomal Glutathione (GSH). This is simply Glutathione (GSH) encapsulated in a lipid (fatty) membrane. This approach is also doomed to fail for the same reason mentioned above, but one wonders if it is just clever marketing. This strategy can only work for some specific hydrophilic drugs that are not taken up easily by cells. The liposome is a “hack”, if you like, that helps the drug get transported across the cell membrane. But only because the concentration of the drug is higher outside the cell than inside, and thus the diffusion is thermodynamically favourable. Yet even with the potential benefits of liposomal drug delivery, there are very few successful examples on the market. Glutathione (GSH) is certainly not one of them.

References

  1. Wu, G., et al., Glutathione metabolism and its implications for health. Journal of Nutrition, 2004. 134(3): p. 489-92.

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