Effects of L-malate on physical stamina and activities of enzymes related to the malate-aspartate shuttle in liver of mice

Abstract

L-malate, a tricarboxylic acid cycle (TCA) intermediate, plays an important role in transporting NADH from cytosol to mitochondria for energy production and may be involved in the beneficial effects of improving physical stamina. In the present study, we investigated the effects of L-malate on the performance of forced swimming time and blood biochemical parameters related to fatigue - blood urea nitrogen (BUN), glucose (Glc), creatine kinase (CK),total protein (TP) and lactic acid (LA). To investigate the effects of L-malate on the malate-aspartate shuttle and energy metabolism in mice, the activities of enzymes related to the malate-aspartate shuttle were measured. L-malate was orally administered to mice continuously for 30 days using a feeding atraumatic needle. The swimming time was increased by 26.1 % and 28.5 %, respectively, in the 0.210 g/kg and 0.630 g/kg L-malate-treated group compared with the control group. There were no differences in the concentrations of Glc, BUN and TP between the L-malate-treated groups and the control groups. However, the levels of CK were significantly decreased in the L-malate-treated groups. The results predict a potential benefit of L-malate for improving physical stamina and minimizing muscle damage during swimming exercise. The activities of cytosolic and mitochondrial malate dehydrogenase were significantly elevated in the L-malate-treated group compared with the control group. These enzymatic activities may be useful indicators for evaluating changes affecting the malate-aspartate shuttle and energy metabolism in the liver of mice.

A critical review of citrulline malate supplementation and exercise performance

“…Similarly, MDH yields oxaloacetate by dehydrogenating L-malate to increase overall rates of TCA flux and MAS. Support for these mechanisms can be found in Wu et al ( 2007 ), such that time to exhaustion swimming was improved in both the 0.2 g.kg −1 BM . day −1 g (+ 26.1%; 620 ± 141 s) group and 0.6 g.kg −1 BM .…”

“…A contemporary mechanism may be either through the increase in gene expression, or increased efficiency of the MAS, which is caused by elevations in PGC-1α in exercising musculature. These physiological changes can elevate aspartate and glutamate levels and increase the expression of glycolysis and MAS genes (Wu et al 2007 ; Agudelo et al 2019 ). As a result, increases in the transfer of fuel-derived electrons to mitochondrial respiration may occur, which in theory, should improve energy utilisation (Wu et al 2007 ; Fig.…”

“…These physiological changes can elevate aspartate and glutamate levels and increase the expression of glycolysis and MAS genes (Wu et al 2007 ; Agudelo et al 2019 ). As a result, increases in the transfer of fuel-derived electrons to mitochondrial respiration may occur, which in theory, should improve energy utilisation (Wu et al 2007 ; Fig. 2 ).…”

“…day −1 dose: 24.3 ± 3.5 vs. 0.6 g.kg −1 BM . day −1 dose: 26.4 ± 3.7) (Wu et al 2007 ). Mechanistically, as MDH is a rate-limiting enzyme for MAS, an increase in activity could suggest an increase in efficiency and therefore ATP supply.…”

“…Specifically, malate has been suggested to increase the rate of ATP production by mitigating lactate production during states of high flux; and by doing so allowing for continued pyruvate and energy production (Wax et al 2016 ). Furthermore, the malate-aspartate shuttle (MAS) may be more efficient following CM ingestion, thereby improving ATP availability (Wu et al 2007 ; Agudelo et al 2019 ). Based on these promising findings and additional mechanisms compared to L-citrulline supplementation alone, it is plausible to suggest CM supplementation could be a worthwhile ergogenic aid.…”