Taking a daily creatine supplement, 4g of creatine monohydrate per day.

Only 12 people in the study, this is a major limitation. 6 taking creatine and 6 placebo, with the age of participants of the placebo group being significantly lower 23.3 ± 2.0 than the treatment group. 31.7 ± 9.4. But matched well in other areas.

With multiple measurements of subjective levels of fatigue, it is like they are fishing for significance, more on this later. However, I do like that they included an objective measure with time to exhaustion.

Objective measure are always going to be more reliable that subjective ones, as they are less susceptible to bias. However, this is only how they can withstand short term excursion. The best method would be to attach smart watch/fitbits to all participants and measure the activity levels over the courser of the study.

Levels of creatine did go up, which you might think is hardly surprising when they are taking it every day for six months, but a lot of supplements don’t make it into your system because they are broken down during digestion. However, we don’t know that increases level of creatine is a good thing and if this actually helps anything including long Covid.

The study claims that there are significant decreases in general fatigue after 3 months of use, with the fatigue score going down from 12.0 to 11.3. However, the data clearly shows that the fatigue level clearly goes back up after six months, going above the starting level to 12.7. The placebo group also had a similar increase over 6months. This suggest that creatine does nothing for general fatigue. Hence the study claiming a significant reduction in fatigue is false, even by their own data. The drop after 3months is just random and is not significant as claimed in the paper.

To reiterate, this shows a only a temporary (probably random) decrease in perceived general fatigue over three months. However after six months no improvement is shown, and patients taking creatine got worse, and the same as the placebo group.

Here is where the study went wrong. They went p-hacking. If you don’t know what p hacking means. Researchers look for a p value of less that 0.05. This means there is a less than 5% chance of that result happening randomly. Therefore roughly 95% of the time that change would be do to the intervention and not just a random change.

This is ok if you measure one thing, 0.01 would be much better. However, here there are 24 different measurements of fatigue variation and only two of them are significant. Now if you have a 5% chance of a significant result, that is 1 in 20. Now make 24 attempts and it isn’t surprising that two came out to be significant. The chance of two or more things randomly coming out to be significant here is 34%. So 1 in 3 chance that this is just random. Not Significant at all. The researchers could ajust their data for multiple comparisons, but then they wouldn’t get an apparent positive result and they probably wouldn’t get it published.

The objective data did hint at some improvement, however, not enough to be statistically significant. Again a symtom of the small study size.

Other criticism in Medical news today highlight that the premise of using creating to improve Long covid is also not sound.
“There is no evidence for creatine deficiency in post-viral fatigue states or fibromyalgia or long COVID,” cautioned Prof. Lloyd.

Another big red flag, the person in charge of the study, co-owns patent “Supplements Based on Liquid Creatine” so I believe this would partly account for the bias and missrepresentation of their own data, since they are fishing for a positive result.

So in conclusion this data does not show that creatine improves Long Covid symptoms. Any claim that this study shows a benefit is simply not true. Outcomes over 6months were the same, anything else is down to random variations in the condition over time. So for now this is not good evidence to try creatine supplements.

References
https://onlinelibrary.wiley.com/doi/10.1002/fsn3.3597

https://www.medicalnewstoday.com/articles/can-creatine-supplements-help-people-with-long-covid#What-is-creatine?