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A 2026 retrospective population study of 84 million B12 measurements showed a 32 % increase in B12 deficiency-linked hospitalizations from 2016 to 2023

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53 Notably, there is bidirectional communication between mtDNA and the nuclear genome: nuclear-encoded mitochondrial proteins regulate mtDNA replication and packaging, whereas mitochondrial metabolites affect nuclear gene expression through epigenetic modification, forming a mitochondrial-nuclear feedback loop

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