Newsletter #284

More and more lately, I am hearing of people who are suffering lingering effects from COVID-19 (popularly known as long COVID). Perhaps you are as well. This shouldn’t be too surprising really, because it has been estimated that as many as 20-40% of infected individuals may develop some manifestation of post-COVID-19 fatigue, meaning that they experience symptoms at least one month after acute infection. Interestingly, a newly published study found that other upper respiratory infections, such as cold and flu, may carry a similar risk of long-term symptoms.

Is there anything we can do right now about this pervasive issue? Perhaps. There has been a little research into ways to accelerate the restoration of physical and mental function. One of these, according to a recent trial, is the supplement creatine. Furthermore, observational evidence indicates that maintaining a healthy lifestyle can substantially reduce the likelihood of you developing post-viral fatigue in the first place — which would be even better.

Inflammation has been implicated in various post-infection syndromes, including long COVID. Specifically, it has been suggested that systemic inflammation, as is often observed in chronic diseases and obesity, renders people more vulnerable to exaggerated cytokine release in response to infection. This not only increases risk for serious complications, but could also predispose individuals to long-term symptoms after the acute infection is cleared.

Notably, various lifestyle factors, such as sleep, nutrition, physical activity, etc., are all known to modulate systemic inflammation. To examine how lifestyle factors might affect long COVID, researchers at the Harvard School of Public Health analyzed data from 32249 women in the Nurse's Health Study II cohort, who had provided detailed information on their lifestyle habits in 2015 and 2017 (in other words, before the pandemic).

The healthy lifestyle factors that they focused on included:

Then, during the height of the pandemic (April 2020 to November 2021), the women were asked about COVID-19 infections, confirmed via testing. From there, the researchers zeroed in on a total of 1981 women who had a documented positive SARS-CoV-2 test. Among these, 871 (44%) developed some form of long COVID. Then, the researchers examined how their lifestyle habits before the pandemic associated with their risk of going on to develop long COVID.

After adjusting for sociodemographic factors, they determined that healthy lifestyle factors did indeed influence the risk of going on to develop long COVID in a dose-dependent manner — in other words, the more boxes you could check in the list above, the less likely you were to get long COVID.

Specifically, those with 5-6 healthy lifestyle factors had 49% lower risk, compared to those who had none of these. Further analyses suggested that healthy BMI and adequate sleep were responsible for most of the observed benefits.

Based on nationally representative data, they estimated that 36% of total long-COVID cases could be avoided if everyone adhered to 5-6 healthy lifestyle factors prior to infection.

A hallmark of long COVID is fatigue, or lack of energy, both physical and mental. But how does our body generate energy? When the body needs fast energy, it breaks ATP (adenosine triphosphate) into ADP (adenosine diphosphate). But eventually this energy source runs out, and this is where creatine enters the picture. Creatine stored in the body can help replenish ATP by donating a phosphate group. This enables your muscle cells to produce more energy without needing to rest as much, and it may also help buffer depletion of cellular energy in the brain (your brain is a very energy-hungry organ, relative to its mass). Creatine supplementation reliably boosts phosophocreatine levels in both muscle and in the brain, so there’s reason to think that it could be beneficial for addressing post-viral fatigue.

In a prior study, Serbian researchers found that patients with long COVID had lower tissue levels of creatine. To examine whether restoring creatine through supplementation could improve symptoms, they conducted a randomized placebo-controlled trial in 12 patients with post-COVID-19 fatigue, who were split evenly into experimental and control groups. The experimental group received 4 grams of creatine monohydrate per day, and controls received an equal dose of inulin. Before after the intervention, the researchers evaluated fatigue through a validated inventory, and they measured tissue levels of creatine in various regions of skeletal muscle and brain via proton magnetic resonance spectroscopy.

After six months, the creatine group showed a significant increase in tissue levels of creatine in their quadriceps, as well as in parts of the brain. The magnitude of uptake in some areas was remarkable, with an increase up to 33% for the right parietal white matter (typically you would see more like 5% for this dosage). The researchers suggest that a combination of creatine deficit as well as compromised blood brain barrier integrity may have led to unusually high uptake in this group.

This increase in tissue creatine levels was accompanied by improved cognitive performance. Difficulties concentrating fell by 77% after three months, and were totally abolished by the end of the study. They also saw improvements in lung function and body pain. It is worth noting that both placebo and creatine groups saw degrees of symptom improvement, as you would expect during a 6-month study, since these issues do tend to get better over time even without much intervention.

A British television series had 10 contestants try to go without sleep for seven whole days.

The reality show craze of the early 2000s generated a lot of surreal content — much of which, in retrospect, was pretty questionable.

One example was Shattered, a British show where ten people had to try to forgo sleep for a whole week while being constantly monitored. The grand prize was £100000. However, if a contestant closed their eyes for more than ten seconds, £1000 was deducted from the prize fund. You can imagine the interpersonal dynamics that must have emerged from that situation.

Due to sleep deprivation, the contestants became angry and irrational, and even suffered hallucinations. One person believed he was the Prime Minister of Australia at one point. The winner wound up staying awake for 178 hours straight.

As we have said before: There is perhaps no better and more cost-effective supplement than creatine. It is best known for its effects on exercise performance, but obviously confers other major payoffs. It may even enhance the ability of the immune system to fight cancer.

If you’d like to learn more about how creatine works, and some of its myriad benefits, I’d suggest checking out this pod from our good friend Tommy Wood, who I’m pretty sure is creatine’s #1 fan and advocate.

An ergogenic aid is simply a supplement that enhances physical performance. Creatine, of course, is one of them.

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.

In this guide, we review some of the most rigorously researched supplements, 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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