Newsletter #198

Happy weekend guys! As always, I hope everyone is doing well, wherever you are. So, this week, I decided to take a look at some of the research on creatine. But not for the purpose that you might be thinking of.

Of course, creatine is best known for its impact on acute exercise performance, and its effects in that domain are pretty impressive, especially for high-intensity activity that requires repeated bouts.

To explain why, let me step back and explain a little about how our cells generate energy to do stuff. For anaerobic activity, the body has to recruit from energy sources that are readily available, and this generally means ATP (adenosine tri phosphate). You’ve probably heard ATP referred to as the “energy currency of the cell,” and this is why. When the body needs fast energy, it breaks ATP into ADP (adenosine di phosphate). But this energy source runs out pretty fast when you are working hard, and it takes some time to restore ATP.

Okay here is where creatine comes in. The creatine stored in your muscles (creatine phosphate) can help replenish ATP by donating a phosphate group, enabling your muscle cells to produce more energy without needing to rest as much. Good stuff.

So, this is actually why creatine seems to be beneficial for the brain. You see, your brain needs quite a bit of energy as well. In fact, despite only making up only a small fraction of our total body mass, the brain represents the largest source of energy consumption - accounting for over 20% of total oxygen metabolism in an adult.

And it is well established that oral creatine supplementation increases concentrations of creatine in the brain, typically by 5-15%, leading to an increase in the brain’s high-energy phosphate pool. This, in turn, may help to buffer depletion of cellular energy, kind of like it does for skeletal muscle. This could be useful in a few different ways.

For one thing, it is thought that it could improve psychological conditions that are connected to altered brain energetics. For instance, major depression has been linked to a decreased pool of brain energy, and it’s not hard to imagine that increasing phosphocreatine levels in the brain could help reverse this. Additionally, some preliminary evidence suggests that boosting this energy pool could also offer benefits for aspects of cognition, which I personally find very intriguing. Who doesn’t want to be a little smarter?

Let’s take a look  👀

Researchers analyzed data from the 2005-2012 National Health and Nutrition Examination Survey (NHANES), a large representative cohort of American adults who provide detailed information on their dietary habits and health (n=22692). They calculated amounts of creatine in the diets of these subjects, then divided the participants into four groups based on levels of dietary creatine intake. After controlling for a variety of demographic and lifestyle variables, the odds of screening positive for depression was 31% lower in adults in the highest quartile of creatine consumption. The association was strongest in women (32% lower), participants between the ages of 20-39 years (48% lower), and in individuals not taking antidepressant or anxiolytic medications (42% lower).

Researchers in South Korea recruited 52 women with major depressive disorder, all of whom were taking the antidepressant Lexapro (escitalopram) during the trial. 25 of the women received 5 grams of creatine daily with the Lexapro, while the rest were given a placebo. This was a double blind trial, so neither the researchers nor the study participants knew who was in the placebo group. The group that received the creatine showed far better rates of improvement on tests of depressive symptoms compared to the placebo group at the 2-week mark (32% improvement rate vs 3.7%) and at the 4-week mark (68% vs 29%). This is key because faster response tends to predict better treatment outcomes in depression. Finally, at the 8-week mark, half of the participants in the creatine group had experienced remission from depression, compared to only around a quarter in the group that just took Lexapro.

The same research team who conducted the study described above wanted to get more insight into the mechanisms that underlie its apparent antidepressant effects. To that end, they had a subset of the participants in that study participate in brain MRI assessments at baseline and at the end of the study (week 8). They also had age-matched women without depression receive brain imaging at the same time intervals as a healthy comparison group. When examining the imaging, the researchers made three major observations. First, the participants with depression had lower levels of n-acetylaspartate (a measure of brain energetics) in their prefrontal cortex, and NAA levels seemed to predict severity of depression (meaning lower NAA = worse depression). Secondly, networks of the brain in the depressed individuals seemed to be less densely connected to one another, compared to the healthy subjects. Finally, depressed individuals whose treatment was augmented with creatine showed improvements in both brain energy metabolism (higher n-acetylaspartate levels) and in network organization (in the form of greater “rich club hub” connections).

We know that creatine prevents muscle fatigue for athletes. But what about mental fatigue? To explore this question, researchers in Japan recruited 24 healthy young volunteers and divided them into two groups: One group took 8 grams of creatine per day, and the other took a similar-looking placebo in the same dose and interval. To test mental fatigue, both groups underwent a test (before and after taking the supplement) in which they had to perform basic calculations using numbers randomly printed on a paper for 15 minutes, rest for 5 minutes, then do it again for another 15 minutes. Both groups got better at it when they did it the second time, as you’d probably expect, but the creatine group showed less mental fatigue in the second 15-min bout of calculations, as well as increased oxygen utilization in the brain.

If you look at the dietary sources of creatine, one thing you’ll notice right away is that it is principally found in animal products. Of course, your body can synthesize some too, but this does ultimately mean that vegetarians have less of it, and indeed muscle levels of creatine tend to be lower in people who do not eat meat. This also means that vegetarians/vegans might stand to benefit more from supplementing it. To explore this, researchers recruited 45 young vegetarians and had them take 5 grams of creatine (or placebo) daily for six weeks, in a double-blind crossover design. Sure enough, when the participants were taking creatine, they showed improvements in cognitive tasks that require fast processing (as you’d expect from a supplement that boosts brain energy). Specifically, they showed improvements in backward digit span, a test of working memory in which you try to recall a series of numbers that were briefly shown to you, and in Raven's Progressive Matrices, a non-verbal test used to gauge intelligence and abstract reasoning.

Mechanical gears are thought to have been invented around 300 BC by the Greeks. But in fact, natural selection produced this innovation way before us. The juvenile form of a tiny planthopper (Issus coleoptratus) actually has toothed gears on its joints that helps precisely synchronize their hind legs when jumping.

This coordination is critical because both legs need to push forward at the exact same time in order for them to leap in a straight line. If one leg were to extend even slightly sooner than the other, they would be steered off to the left or the right.

Researcher Gregory Sutton, who first reported this phenomenon, says, “These gears are not designed; they are evolved—representing high speed and precision machinery evolved for synchronization in the animal world.”

Honestly, the most cost-effective way to take creatine is through powder supplements containing creatine monohydrate, like this. However, if you don’t want to deal with measuring out powders (like if you’re traveling or something like that), these chews are a good alternative that I’ve used before. They taste fine and they have been lab-tested, so you know that you’re getting what you’ve paid for.

Thanks as always for reading - I hope you got some useful info out of this. Of course, if you're looking for more juicy health studies (and occasionally random science or memes), be sure to check us out on Twitter on @humanOS_me and @Natural_Fallacy

https://mailchi.mp/humanos.me/newsletter-198