Ergogenic properties of metformin in simulated high altitude

Abstract

Metformin augments glucose/glycogen regulation and may acutely promote fatigue resistance during high-intensity exercise. In hypobaric environments, such as high altitude, the important contribution of carbohydrates to physiological function is accentuated as glucose/glycogen dependence is increased. Because hypoxia/hypobaria decreases insulin sensitivity, replenishing skeletal muscle glycogen in high altitude becomes challenging and subsequent physical performance may be compromised. We hypothesized that in conditions where glycogen repletion was critical to physical outcomes, metformin would attenuate hypoxia-mediated decrements in exercise performance. On three separate randomly ordered occasions, 13 healthy men performed glycogen-depleting exercise and ingested a low-carbohydrate dinner (1200 kcals, <10% carbohydrate). The next morning, in either normoxia or hypoxia (FiO =0.15), they ingested a high-carbohydrate breakfast (1225 kcals, 70% carbohydrate). Placebo (719 mg maltodextrin) or metformin (500 mg BID) was consumed 3 days prior to each hypoxia visit. Subjects completed a 12.5 km cycle ergometer time trial 3.5 hours following breakfast. Hypoxia decreased resting and exercise oxyhemoglobin saturation (P<.001). Neither hypoxia nor metformin affected the glucose response to breakfast (P=.977), however, compared with placebo, metformin lowered insulin concentration in hypoxia 45 minutes after breakfast (64.1±6.6 μU/mL vs 48.5±7.8 μU/mL; mean±SE; P<.001). Post-breakfast, pre-exercise vastus lateralis glycogen content increased in normoxia (+33%: P=.025) and in hypoxia with metformin (+81%; P=.006), but not in hypoxia with placebo (+27%; P=.167). Hypoxia decreased time trial performance compared with normoxia (P<.01). This decrement was similar with placebo (+2.6±0.8 minutes) and metformin (+1.6±0.3 minutes). These results indicate that metformin promotes glycogen synthesis but not endurance exercise performance in healthy men exposed to simulated high altitude.

Acute metformin administration increases mean power and the early Power phase during a Wingate test in healthy male subjects

“…In the animal model, 250 mg metformin chronic ingestion for ten days increased the anaerobic capacity of healthy rats (de Araujo et al, 2020). One possible explanation is that the use (4 days) of metformin (500‐100 mg) seems to have gluco‐regulatory properties, being able to increase the content of muscle glycogen in healthy subjects (Scalzo et al, 2017). However, our study utilised acute metformin intake, which seems insufficient to increase cell energy stores, and anaerobic capacity (Kristensen et al, 2019).…”

UIAA Medical Commission Recommendations for Mountaineers, Hillwalkers, Trekkers, and Rock and Ice Climbers with Diabetes

“…These data raised the hypothesis that metformin could increase exercise performance in hypoxic conditions. In healthy young men in acute normobaric hypoxia (F IO2 = 0.15), short-term metformin administration (1000 mg daily for 3 days) decreased insulin clearance in response to a high-carbohydrate meal, and promoted skeletal muscle glycogen synthesis, but did not influence endurance exercise performance (Scalzo et al, 2017 ). In addition, one study describes eight trekkers using metformin on a trekking trip to 4167 m without any adverse effects (de Mol et al, 2012 ).…”

Effects Of Acute Metformin Intake On Physiological Parameters And Performance Before, During And After High-intensity Interval Training Of Swimmers

“…The acute effect of metformin in healthy subjects not change the maximum oxygen uptake during a graded exercise test, but induces a lower level of blood lactate concentration on low-intensity exercise (10). Regarding performance, chronic metformin treatment (3 days) increased the muscle glycogen content, but was not enough to improve the endurance performance (13). On the other hand, the evidence of acute metformin effect on high-intensity exercise still not clear.…”