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Certain drugs, such as aspirin and ibuprofen, have been shown to deplete glutathione levels, impairing the body's ability to detoxify harmful substances and reducing the availability of SAMe for methylation

A majority of the trial participants had a body mass index above 30

46,7375 It is therefore suggested that metformin use may be an agent of iatrogenic potential inducing peripheral neuropathy exacerbation in individuals with T2DM who have depressed Vitamin B12, as a result of elevated fasting methylmalonic acid (MMA) and tHcy levels

This is the same mechanism targeted by topical brightening agents, delivered systemically instead, and the effect is best understood as a gradual, cumulative brightening support across a series rather than an overnight change