Newsletter #255

Hey y'all! This week, we are going to talk a little about some new research on our favorite drug: caffeine.

The performance-enhancing effects of caffeine for a broad range of physical activities have been well-established in numerous meta-analyses. A new review from researchers in Japan sheds a little more light on why exactly caffeine has this ergogenic impact. Importantly, this may also mean that caffeine could augment some of the health-promoting effects associated with physical activity as well.

But one dilemma associated with caffeine, that many people wonder about, is the potential for tolerance. Does using caffeine regularly make you habituated to its effects? Do you need to "save" it for the times when you really need it? A new meta-analysis might provide the answer. 👀

Finally, shameless plug: We are continuing to work on developing a kick-ass coaching program. If you’d like to be notified when we launch, please head to this link and take 30-ish seconds to fill out the short form. It also helps us know what y'all might be looking for in a coaching program, which in turn can guide our selection of both content and coaches.

The most obvious impact of physical exercise is the improvement of the function and health of your muscles. But of course, we now know that the beneficial effects of exercise are manifold, extending to remote tissues far beyond skeletal muscle. This is due, in part, to myokines. Myokines are small proteins that are released by skeletal muscle cells in response to muscular contractions. They are secreted into the blood, where they can circulate throughout the body. We have myokine receptors in our liver, pancreas, bone, heart, and even brain cells, so they can bind to and influence virtually every organ system. For example, certain myokines are linked to improvements in insulin sensitivity, immune function, and even cognition. As I said, contracting your muscles triggers the secretion of myokines. But myokine production is also promoted by changes in intracellular calcium concentration. And this is where caffeine enters the picture. Caffeine has long been known to facilitate the release of calcium ions from the sarcoplasmic reticulum (this is a big part of how it enhances exercise performance). Furthermore, myokines are released after the activation of an enzyme called adenosine monophosphate-activated protein kinase, or AMPK for short. AMPK is often characterized as a sort of cellular fuel gauge and tends to get ramped up in states of energy stress. Caffeine is also an AMPK activator. In effect, the researchers are suggesting that caffeine is able to amplify some of the beneficial effects of exercise by acting on the same pathways. They then go into a few of the specific myokines that caffeine can act upon. Interleukin-6 (IL-6) is maybe the best-known of the myokines. It plays an anti-inflammatory role in the body by inhibiting tumor necrosis factor-α (TNF-alpha), and it improves glucose tolerance. Caffeine supplementation has been shown to induce higher IL-6 levels in response to running. Preliminary research also suggests that caffeine could increase the secretion of brain-derived neurotrophic factor (BDNF), a myokine that plays a role in learning and memory. And muscle, a myokine that is linked to mitochondrial biogenesis and endurance adaptations, is responsive to changes in calcium concentrations, and caffeine administration could increase its expression. Taken together, this suggests that caffeine could function as an exercise mimetic. Not only does this make it a useful adjunct for athletes, it could also help boost levels of myokines, as well as lactate, in people who aren't able to engage in prolonged high-intensity exercise.

Researchers affiliated with the University of São Paulo in Brazil performed a systematic review of the literature investigating caffeine consumption and exercise performance. Importantly, they only included studies that provided information on habitual caffeine intake in the participants, meaning whether or not (and to what extent) they consumed caffeine on a regular basis. After this screening process, they conducted a meta-analysis of 60 randomized controlled trials, enrolling a total of 1,137 participants, which looked at the influence of habitual caffeine intake on exercise performance in various domains and populations. The researchers determined, to no surprise, that caffeine overall had a positive effect on performance when compared to a placebo. Benefits were universal to all forms of caffeine, including both pills and natural sources like coffee. Furthermore, both men and women benefited, as well as trained and untrained individuals, and all forms of exercise (endurance, power, strength) showed improvements, although longer-duration aerobic activity seems to benefit most strongly. Most importantly, no influence of relative habitual caffeine consumption was demonstrated. In other words, being a regular coffee drinker did not mean that participants got less of a performance payoff when they were given caffeine experimentally. When the researchers compared doses, they did find something slightly interesting — the ergogenic effects of caffeine were only shown when the caffeine dose was less than 6 mg per kg of body mass. With higher doses, (we're talking more than 500 mg of caffeine) the improvements in performance diminished and were no longer statistically significant. (My guess is that the unpleasant side effects of too much caffeine wind up overriding the performance-enhancing impact of the drug.) Obviously, this study is encouraging for those of us who are regular coffee drinkers and don't want to rein in our consumption. But it's also good news because the health-promoting effects of caffeine-containing beverages, like coffee and green tea, are generally only realized through regular use. Much as the title of this paper suggests, you really can have your coffee and drink it too.

Many humans rely on caffeine daily for its stimulant effects. Believe it or not, some bugs may respond to caffeine in a somewhat similar way.

The researchers believe that this caffeine method could be used to boost fruit yields by biasing pollinators toward specific crops.

Lead author Sarah Arnold, in a press release, said, “We generally know how coffee helps us concentrate and stay focused, as well as helping us remember complex information better, and what our limit is. We’ve shown that caffeine increases the bees’ enthusiasm and activity generally and it makes the memory formation stronger."

An ergogenic aid is simply a supplement that enhances physical performance. Dietary intake of these substances can, in theory, affect training adaptations in a couple of different ways. They can achieve this by simply increasing the exercise stimulus from a single training bout - basically just enabling an athlete to train longer or harder, or reducing perceived exertion. But they may also be able to affect gains in endurance by altering cellular responses to exercise-induced stress.

Importantly, these changes in cell signaling may not be universally beneficial from the standpoint of adaptation. For example, it is theoretically possible that a supplement could simultaneously make it easier for an athlete to exercise hard, but also have effects on cellular signaling that actually have a long-term negative impact on the adaptive response to training.

In this guide, we review some of the most rigorously researched supplements (including LactiGo), discuss how best to use them, and talk about why some supplements that sound like a good idea may actually not be helpful at all. If you are looking for a quick reference sheet of the latest evidence-based guidance on supplements to maximize your performance and adaptations, check it out! 👀

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