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Unless you're planning to just sit, instead of cycle on your spinning bike, it is by no means sure if your performance well benefit or maybe even suffer from the use of AMPK mimetics and activators.

Recently someone asked me on Facebook, whether AMPK activators like Lipoic acid (ALA), Berberine, Metformin, AICAR & Co wouldn't make excellent performance boosters. I pondered that question for some time and said: "If you are about to compete in a highly glycolytic sport, the opposite is probably the case."

There's little question that supplements like lipoic acid are useful if you are an overweight type II diabetic. But let's be honest: How many of you fall into this category? As healthy, active individuals or even athletes, on the other hand, you should be aware that the ability of these agents to increase the glucose uptake and block the glyconeogenic pathways in the liver may easily make you run out of fuel during anaerobic activities like lifting or sprinting.
This does not negate the fact that AMPK activators, by their ability to increase the use of free fatty acids as a substrate, may be of interest to endurance runners or athletes competing in other sports, where the lion's share of the energy they use during their workouts and competitions are carboxylic acids with a long aliphatic tail (chain), i.e. fatty acids.

Against that backround it is hardly surprising that the few pertinent studies that exist are - at least in parts - contradictory. Shortly before the last Olympic Games in Beijing, for example, a study was published that showed that the research chemical and AMPK activator AICAR (5-amino-1-b-D-ribofuranosyl-imidazole-4-carboxamide) increased the running capacity of mice without any training. But let's be honest: Do you think athletes would be looking for agents that work without training... well, obviously they would, but AICAR - as potent as it may be - will never replace the blood, sweat and tears athletes have to invest to be successful. That's for sure.
Nevertheless, the observation Narkar et al. (2008) made was enough for the World Anti-Doping Agency (WADA) to include certain AMPK activators in the list of forbidden drugs - for all, not just endurance sports, obviously.

Table 1: Adenosine monophosphate-activated kinase activators and their impact on exercise capacity (Niederberger. 2015)

Actual experimental evidence of performance enhancing effects exists for several natural and synthetic AMPK mimetics and activators (see Table 1). If you look closely, however, you will notice that all those "enhacnements" and "increases" have been in rodent models and/or non-athletes.
In the absence of experimental evidence from both rodent and human studies that involve AMPK activators and anaerobic exercise, we have to use our brains to find out whether sprinters, bodybuilders, or weight lifters and athletes competing in team sports that have both an aerobic and an anaerobic component would benefit as well. In this case the extensive research on alpha lipoic acid (ALA) can help us, but we should not forget that the effects may differ from one agent to the other.

Due to the previously mentioned potentially negative effect on blood glucose in insulin sensitive individuals that is mediated primarily by increases in whole body glucose oxidation, increased glycolysis (wasting of the glycogen reserves| Barnes. 2004) and a reduced ability to produce new glucose "on demand" (via gluconeogenesis, which is AMPKs main of glucose control according to Zhang et al. 2009), athletes competing in anaerobic sports may in fact run the risk of running low on blood sugar and thus compromising their performance and/or being even more reliant on sugary high carbohydrate beverage.
If you don't care about blood glucose, you may be intrigued to hear that AMPK will not act on your glucose metabolism, alone. Increasing levels of AMPK will also suppress skeletal muscle protein synthesis (Figure 1), which is a side effect that's probably even worse than the remote risk of hypoglycemia, specifically in athletes competing in anaerobic sports.

Figure 1: Changes in p-AMPK and nutrient-induced protein synthesis in myotubes from the EDL muscle (Saha. 2010).

Now, some of you may argue that I personally wrote in an older article in the Intermittent Fasting Series that the rise in AMPK due to exercise would not be a problem.

If you'd read that article carefully, though, you'd also know that this is because exercise triggers the release of a specific form of AMPK that's different from the one that's released during fasting and in response to regular AMPK activators. It is thus not unlikely that high(er) intakes of ALA as they would probably be abused by athletes, who (falsely) believe they'd benefit from it, can impair the protein synthesis to a similar extent as it was observed by Saha et al. in their 2010 study in rodent EDL muscles.

Furthermore animal studies show that chronic administration of albeit very high doses of ALA, equivalent to ~5g/day for a human being, will actually trigger significant reductions in lean mass (Shen. 2005) - something almost every athlete who's competing in anaerobic sports will want to avoid.
References:

• Barnes, Brian R., et al. "The 5′-AMP-activated protein kinase γ3 isoform has a key role in carbohydrate and lipid metabolism in glycolytic skeletal muscle." Journal of Biological Chemistry 279.37 (2004): 38441-38447.
• Cuthbertson, Daniel J., et al. "5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men." Diabetes 56.8 (2007): 2078-2084.
• Hayashi, Tatsuya, et al. "Evidence for 5′ AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport." Diabetes 47.8 (1998): 1369-1373.
• Narkar, Vihang A., et al. "AMPK and PPARδ agonists are exercise mimetics." Cell 134.3 (2008): 405-415.
• Niederberger, Ellen, et al. "Activation of AMPK and its Impact on Exercise Capacity." Sports Medicine (2015): 1-13.
• Olesen, Jesper, et al. "Exercise training, but not resveratrol, improves metabolic and inflammatory status in skeletal muscle of aged men." The Journal of physiology 592.8 (2014): 1873-1886.
• Saha, Asish K., et al. "Downregulation of AMPK accompanies leucine-and glucose-induced increases in protein synthesis and insulin resistance in rat skeletal muscle." Diabetes 59.10 (2010): 2426-2434.
• Shen, Q. W., et al. "Effect of dietary α-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice." Journal of animal science 83.11 (2005): 2611-2617.
• Zhang, Bei B., Gaochao Zhou, and Cai Li. "AMPK: an emerging drug target for diabetes and the metabolic syndrome." Cell metabolism 9.5 (2009): 407-416.

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.
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.
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.
References:

• 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]