MDH1 and heart failure: NR supplementation increases the levels of three rate-limiting TCA enzymes used for NADH production, including malate dehydrogenase 1 and 2 (MDH1, MDH2) and IDH3, which leads to an increase in mitochondrial ATP production, modulation of myocardial energy expenditure, and ultimately an improvement in heart failure in HFepEF mice [170].