Research shows that when using metformin alone, high doses may be required to see inhibitory effects on tumours [135], but high-dose administration of metformin may inhibit OXPHOS by targeting mitochondrial complex I (NADH dehydrogenase), leading to the accumulation and conversion of NADH and pyruvate into lactic acid and resulting in lactic acidosis in cancer cells, which promotes cancer progression. The gene discussed is ENSG00000254051; the disease is cancer.