title: 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 (FiO2=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.
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Rebecca L
authors.identifier: http://orcid.org/0000-0001-9291-7390
authors.initials: RL
authors.lastname: Scalzo
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Hunter L
authors.initials: HL
authors.lastname: Paris
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Binns
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Janelle L
authors.initials: JL
authors.lastname: Davis
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Beals
authors.affiliation: Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO, USA.
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Melby
authors.affiliation: Heart Center of the Rockies, University of Colorado Health, Fort Collins, CO, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Luckasen
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Hickey
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Miller
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Karyn L
authors.initials: KL
authors.lastname: Hamilton
authors.affiliation: Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bell
mesh_terms: D000328:Adult; D000531:Altitude; D054874:Athletic Performance / Q000502:physiology*; D015444:Exercise / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D058573:Performance-Enhancing Substances / Q000494:pharmacology*
chemical_list: D058573:Performance-Enhancing Substances; D006003:Glycogen; D008687:Metformin
keywords: exercise; glucose; hypoxia; insulin; skeletal muscle glycogen