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Additionally, ROS can upregulate HIF-1 expression, leading to activation of the Janus kinase (JAK) 2/STAT3 pathway, which promotes high RANKL expression and induces osteoclast differentiation (227)

Most multicellular and some unicellular eukaryotes, but not some insects such as Drosophila species, possess a mitochondrial proton-motive force-driven transmembrane transhydrogenase homologous to human NNT (Zhang et al., 2017), while bacteria can possess a transmembrane transhydrogenase, a soluble transhydrogenase, or rarely both (Sauer et al., 2004)

They are unlikely to improve with prolonged use, says Fishman