Short-Term Magnesium Supplementation Has Modest Detrimental Effects on Cycle Ergometer Exercise Performance and Skeletal Muscle Mitochondria and Negligible Effects on the Gut Microbiota: A Randomized Crossover Clinical Trial

Abstract

Background/Objectives: Although the importance of magnesium for overall health and physiological function is well established, its influence on exercise performance is less clear. The primary study objective was to determine the influence of short-term magnesium supplementation on cycle ergometer exercise performance. The hypothesis was that magnesium would elicit an ergogenic effect. Methods: A randomized, double-blind, placebo-controlled, two-period crossover design was used to study men and women who were regular exercisers. Fifteen participants ingested either a placebo or magnesium chloride (MgCl₂ 300 mg) twice per day, for 9 days, separated by a 3-week washout. During days 8 and 9, participants completed a battery of cycle ergometer exercise tests, and whole blood, vastus lateralis, and stools were sampled. The primary outcomes were the maximal oxygen uptake (VO_2max), a simulated 10 km time trial, and the sprint exercise performance. Additional outcomes included skeletal muscle mitochondrial respiration, and, on account of the known laxative effects of magnesium, the gut microbiota diversity. Results: Compared with a placebo, MgCl₂ supplementation increased the circulating ionized Mg concentration (p < 0.03), decreased the VO_2max (44.4 ± 7.7 vs. 41.3 ± 8.0 mL/kg/min; p = 0.005), and decreased the mean power output during a 30 s sprint (439 ± 88 vs. 415 ± 88 W; p = 0.03). The 10 km time trial was unaffected (1282 ± 126 vs. 1281 ± 97 s; p = 0.89). In skeletal muscle, MgCl₂ decreased mitochondrial respiration in the presence of fatty acids at complex II (p = 0.04). There were no significant impacts on the gut microbiota richness (CHAO1; p = 0.68), Shannon's Diversity (p = 0.23), or the beta-diversity (Bray-Curtis distances; p = 0.74). Conclusions: In summary, magnesium supplementation had modest ergolytic effects on cycle ergometer exercise performance and mitochondrial respiration. We recommend that regular exercisers, free from hypomagnesemia, should not supplement their diet with magnesium.

Keywords: dietary supplement; ergolytic; gastrointestinal microbiome; maximal oxygen uptake; time trial.

Figure 5

(A) Phyla-level relative abundances of taxa for each participant during the placebo or magnesium (Mag) intervention periods. (B) Bray–Curtis distances visualized in a Principal Coordinates Analysis (PCoA) showed no significant clustering by treatment group. A few taxa were differentially abundant between the treatment groups, as determined using the linear model in MaAsLin2. (C) Eubacterium siraeum increased with magnesium, and (D) Bifidobacterium and (E) Coprococcus decreased with magnesium.

Figure 6

No treatment differences in the maximal oxygen flux (Vmax) or ADP sensitivity (Km). We measured complex I-supported leak respiration (State 2_(PGM)) with the addition of glutamate, malate, and pyruvate. (A) Upon the acquisition of State 2_(PGM), we titrated progressively greater concentrations of ADP from 0.1 to 16 mM (State 3_(PGM)) to determine (B) the complex I-linked ADP V_max and (C) apparent K_m (the amount of ADP required to achieve ½ the V_max, a measure of the ADP sensitivity under complex I-supported respiration).

Figure 7

Treatment with magnesium decreased carbohydrate-and-fatty-acid-supported oxygen consumption. The second SUIT protocol was designed to assess carbohydrate-and-fatty-acid-supported oxygen consumption via titrations of glutamate, malate, pyruvate, octanoylcarnitine, and succinate (State 2 respiration). There were no treatment differences in State 2 respiration. To assess State 3 respiration, we added submaximal boluses of ADP. At all concentrations of ADP (A–C), the magnesium treatment group either tended to have lower respiration or was associated with significantly lower respiration compared to the placebo group. When we added rotenone to determine the maximal respiration in the absence of complex I (D), we found that respiration was significantly lower in the magnesium group compared to the placebo group (D). Finally, after FCCP was added to uncouple the electron transfer system from oxidative phosphorylation, respiration was significantly lower in the magnesium group compared to the placebo group (E).

Figure 1

Schematical overview of the experimental design. Blood was analyzed for the ionized magnesium concentration. Placebo/magnesium was ingested every 12 h. Only participants who consented to the procedure provided samples of their vastus lateralis. VO_2max: maximal oxygen uptake.

Figure 2

Consolidated Standards of Reporting Trials (CONSORT) flow diagram.

Figure 3

Short-term magnesium chloride supplementation decreased maximal oxygen uptake. White circles and connecting lines represent individual data (n = 15). Solid circles and errors bars represent mean and standard deviation.

Figure 4

Short-term magnesium chloride supplementation decreased mean power during 30 s cycle ergometer sprint. White circles and connecting lines represent individual data (n = 13). Solid circles and errors bars represent mean and standard deviation.