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KPV is reported to be selective for MC1R/MC3R and to lack the MC4R/MC5R activity responsible for pigmentation

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Metformin, through the induction of 5' AMP-activated protein kinase and subsequently insulin sensitivity, has been widely used as a therapeutic agent in various conditions, including type 2 diabetes mellitus, PCOS and gestational diabetes (Reference Rice, Elia and Jawad42)

This is why seasonal challenges often get progressively worse as spring continues

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I've also seen many families who have tried leucovorin or paid for it out of pocket, haven't noticed any benefit