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In addition to direct antioxidant responses, it has also been shown that bilirubin can indirectly function to the alleviation of oxidative stress, examples including activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway through covalently binding to Kelch-like ECH-associated protein 1 (KEAP1) (54, 61) and thus acting as an antioxidant in the cell

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The MHRA advises checking B12 levels in patients taking metformin who develop symptoms of deficiency or have risk factors, with periodic monitoring in at-risk patients