First Study to Demonstrate Ergogenic Effects of Metformin - 14% Increased Time to Exhaustion in Standardized Supra-Maximal Cycling Test With 500mg of Ordinary Metformin

With the publication of Learsi's latest paper the list of things metformin can do for you has just gotten been expanded with another item: Doping!
You will probably remember my article about the potential, but unproven ergogenic effects of AMPK mimetics (read it). Well, as it is often the case, a new study is released only days after you've published a review of the existing literature. Oftentimes that's not really relevant, but in the case of the latest study from the Federal University of Alagoas this may be different. After all, we are dealing with a human study in  ten healthy, physically active, but non-athletic subjects with a mean (±SD) maximal oxygen uptake (VO2max) o 38.6 ± 4.5 mL/kg per min who performed (i) an incremental test; (ii) six submaximal constant workload tests at 40%-90% V O2max; and (iii) two supramaximal tests (110% V O2max).

All tests were performed twice once with a placebo supplement and once with 500mg of metformin. Both, the placebo and the metformin supplement were ingested 60 minutes before the supramaximal test, in order to investigate the hypothesis that metformin would increase anaerobic capacity and performance during high-intensity, short-duration exercise.
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The authors, Learsi et al. (2015), based this hypothesis on the fact that metformin inhibits aerobic pathway energy production and so the glycolytic energy system could be overloaded during ATP production for muscle contraction.
Figure 1: Overview of the study design. The active / placebo treatment, i.e. 500mg of metformin or an identically looking placebo were administered 60 min before the supramaximal tests. The whole procedure was repeated twice, with at least 72h between the first and the second testing session (Learsi. 2015).
The aim was thus to to determine the effects of metformin on anaerobic capacity and to elucidate whether metformin has any ergogenic effect in intense, short-duration exercise in healthy, physically active men.
Is this really the first study? Yes, it is the first to prove metformin's ergogenic effects in humans. It's yet not the first human study to test the ergogenic effects of metformin. 2008 Johnson et al. made the mistake to assume that taking metformin would affect the VO2max, or ventilatory threshold. Just like Gudat et al. before them, Johnson et al. simply missed the most straight forward practical measure of exercise performance, i.e. total time to exhaustion, while focusing on things like VO2 (Johnson et al. 2008) or lactate (Gudat et al. 1997) which are nice to explain increases in performance, but - if we are honest - still irrelevant, when all that really counts is how fast you run, how long you cycle or how hard you hit.
While many of the variables they assessed didn't change, the already hinted at 14% increase in maximal endurance (see headline) is something that may make the difference between winning an Olympic medal and placing fourth or worse.
Figure 2: Changes in time to exhaustion and EPOC, both stat. significantly w/ metformin (Learsi. 2015).
What is also noteworthy is that the subjects excess post-exercise energy consumption, which was measured for (unfortunately) only 10 min, increased significantly, as well (see Figure 2, right). In contrast to what some bro-scientists may tell you that does not necessarily equal increased fat loss, but it's still interesting, because it may suggest that metformin improved the subjects' performance by increasing the supply of energy via the anaerobic alactic system, i.e. by boosting the efficacy of non-glucose- and thus non-lactic-acid-dependent energy pathways - in short: fat oxidation.
Alpha Lipoic Acid, GABA, Taurine, Green Tea, Gooseberry & Fenugreek. Plus: Metformin the No.1 Drug? Supplements to Improve and Restore Insulin Sensitivity - Read the First Installment of This Series | read more
Bottom line: This is the first human study to confirm that the AMPK-booster and frequently prescribed diabetes drug can trigger statistically and practically relevant increases in endurance performance during a supra-maximal VO2 max test. If we assume that a similar performance increase occurs in trained athletes, the Learsi study makes taking a bunch of grandma's metformin pills before the next race quite attractive. For the WADA, however, it means that they will have to watch and test for yet another commonly prescribed and readily available medication. And last but not least, for the "wonder-drug" metformin, it is yet another area of application: athletic performance enhancement or as we usually call it "doping" | Comment on Facebook!
  • Gudat, U., G. Convent, and L. Heinemann. "Metformin and exercise: no additive effect on blood lactate levels in healthy volunteers." Diabetic medicine 14.2 (1997): 138-142.
  • Johnson, S. T., et al. "Acute effect of metformin on exercise capacity in active males." Diabetes, Obesity and Metabolism 10.9 (2008): 747-754.
  • Learsi, et al. "Metformin improves performance in high-intensity exercise, but not anaerobic capacity." in healthy male subjects." Clin Exp Pharmacol Physiol. 2015 Aug 7. doi: 10.1111/1440-1681.12474. [Epub ahead of print]
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