Reading time: 8 minutes

Overview

1. Why researchers are studying creatine in long COVID
2. How the study was designed
3. The main results
4. Why more creatine was not better
5. How reliable are the findings?
6. What people with long COVID can take from the study
7. FAQ

Why researchers are studying creatine in long COVID

Fatigue is one of the most frequently reported symptoms of post-COVID syndrome, commonly known as long COVID. Many people experience persistent physical and mental exhaustion that improves little with sleep or rest and can make everyday activities considerably more difficult.

The underlying causes are not yet fully understood and are likely to differ between individuals. Researchers are investigating persistent changes in the immune system, inflammatory processes, impaired circulation and possible disruptions to cellular energy metabolism. Some people also experience post-exertional symptom exacerbation: even minor physical or mental effort may cause symptoms to worsen after a delay.

This is where scientific interest in creatine begins. Creatine is part of a natural system that helps cells provide energy at short notice. In the form of phosphocreatine, it can transfer a phosphate group to ADP, helping to restore ATP – the immediately usable energy carrier in our cells.

Earlier research provided initial indications that creatine concentrations in muscle and brain tissue may be lower in some people with long COVID. This led to the hypothesis that additional creatine could support the body’s energy system. The new study set out to determine whether supplementation could also produce measurable changes in symptoms.

How the study was designed

The Brazilian research team conducted a randomised, single-blind, placebo-controlled pilot study. Adults were eligible if they had experienced persistent fatigue for at least twelve weeks following a confirmed COVID-19 infection.

A total of 67 participants were randomly assigned to one of three groups:

• 6 g of creatine monohydrate per day
• 18 g of creatine monohydrate per day
• 6 g of maltodextrin per day as a placebo

Supplementation continued for 28 days. Fifty-eight participants completed the study protocol: 21 in the 6 g group, 19 in the 18 g group and 18 in the placebo group. The average age was 52, and approximately three quarters of the participants were women.

One detail is particularly important when interpreting the findings: all three groups completed the same rehabilitation programme, consisting of three sessions per week. The programme included aerobic, resistance, breathing, flexibility and balance exercises. The study therefore compared creatine plus rehabilitation with placebo plus rehabilitation – not creatine with complete inactivity.

The prespecified primary outcome was fatigue, measured using the Revised Piper Fatigue Scale. Participants answer 22 questions covering several aspects of fatigue, including its severity and physical, emotional and cognitive effects. Responses are summarised on a scale from 0 to 10, with a higher score indicating more severe fatigue. The researchers also measured handgrip strength, walking distance, respiratory muscle strength, lung function, body composition, quality of life, and symptoms of anxiety and depression.

The main results

Fatigue decreased more in the group taking 6 g of creatine per day than in the placebo group. The difference in change between the groups was 2.05 points on the 0–10 scale. In other words, after four weeks the 6 g group reported a greater reduction in fatigue than the participants who received placebo.

The difference was statistically significant. The calculated 95% confidence interval ranged from 0.63 to 3.47 points. Put simply, this interval describes the range within which the researchers estimate the true difference is likely to fall.

The 6 g group also performed better in the handgrip-strength assessment. Compared with placebo, the estimated difference in change was 4.40 kilograms-force. Handgrip strength does not represent every aspect of physical performance, but it is straightforward and reliable to measure and is often used as an indicator of general peripheral muscle strength.

Creatine did not provide a statistically significant advantage over placebo for most of the other measurements. This included the six-minute walk distance, respiratory muscle strength, lung function, body composition, quality of life, and anxiety and depression scores.

The findings therefore do not show that long-COVID symptoms improved as a whole. Instead, they provide an initial positive signal for two specific outcomes: participant-reported fatigue and measured handgrip strength.

Why more creatine was not better

One of the most notable findings is that only the lower dose produced a benefit. In the group taking 18 g per day, the change in fatigue was not significantly different from placebo.

The study cannot establish why. Possible explanations include differences in tolerability, adherence, body weight or individual response. The dose–response relationship may also be non-linear, meaning that a higher dose does not necessarily produce a larger effect. Given the small number of participants in each group, random variation may also have influenced the findings.

Digestive complaints were reported more frequently in the 18 g group. Nausea was reported by 42.8% of participants in this group, compared with 22.7% in the 6 g group and 4.7% in the placebo group. The differences between groups were not statistically significant, and all reported symptoms resolved without medical intervention.

Blood creatinine increased slightly in both creatine groups. In the absence of other clinical abnormalities, the researchers did not interpret this as evidence of clinically relevant impairment of kidney function. Creatinine is a breakdown product associated with creatine metabolism, so its concentration should be interpreted in context when someone takes creatine.

How reliable are the findings?

The randomised, placebo-controlled design is an important strength. The primary outcome was specified in advance, and the end-of-study assessments were conducted by an investigator who did not know which group each participant had joined.

Nevertheless, this was explicitly a pilot study, which brings several limitations:

• Each group contained only around 20 participants.
• The intervention lasted just four weeks.
• Participants did not know which group they were in, but the study was not fully double-blind.
• All groups exercised, so creatine can only be assessed as an addition to the rehabilitation programme.
• Participants’ usual dietary creatine intake was not examined in detail.
• Numerous secondary outcomes were assessed, increasing the possibility of chance findings.
• Results from one small sample cannot automatically be applied to everyone with long COVID.

What people with long COVID can take from the study

The results provide an initial indication that creatine may be of scientific interest for some people with long COVID. They do not, however, establish that creatine is an effective treatment or justify a general recommendation to start supplementation.

Creatine is not an approved treatment for long COVID, and the current evidence is insufficient to support a general treatment recommendation. Nor is there an authorised health claim stating that creatine relieves long-COVID symptoms.

Long COVID can vary considerably between individuals. In particular, people who experience post-exertional malaise should not interpret creatine supplementation as a reason to increase physical activity without appropriate guidance. Exercise and rehabilitation need to be adapted to the individual pattern of symptoms and should ideally be supervised by a qualified professional.

Anyone with an existing health condition, abnormal kidney markers, pregnancy, breastfeeding or regular medication use should seek medical advice before taking creatine. This is especially important when symptoms following COVID-19 are severe or persistent.

FAQ: creatine and long COVID

Does creatine help with long-COVID fatigue?

A small pilot study found a greater reduction in fatigue after four weeks with 6 g of creatine per day than with placebo. The result needs to be confirmed in larger studies and does not demonstrate a generally effective treatment.

Which creatine doses were studied?

The researchers tested 6 g and 18 g of creatine monohydrate per day. Only the 6 g group showed an advantage for fatigue and handgrip strength. The higher dose was not more effective.

How quickly did the change occur?

Participants were reassessed after approximately four weeks. The study cannot tell us exactly when the change began or whether it would persist over the longer term.

Is creatine safe for people with long COVID?

No serious adverse events occurred in the pilot study. Digestive complaints were more common with 18 g per day, however. Individual suitability should be assessed with a qualified healthcare professional, particularly for people with existing health conditions or regular medication use.

Can creatine replace medical treatment?

No. Creatine is not an approved treatment for long COVID. Persistent exhaustion, breathlessness, chest pain, circulatory symptoms or cognitive problems should be medically assessed.

Conclusion: an encouraging pilot signal with unanswered questions

The new study provides initial controlled evidence that 6 g of creatine per day, when added to a rehabilitation programme, could have a favourable effect on fatigue and handgrip strength in people with long COVID.

Several findings call for caution. The higher 18 g dose was not effective, most secondary outcomes did not change significantly, and the study was both small and short. An interesting biological idea has therefore not yet become an established treatment.

The appropriate conclusion is not “creatine treats long COVID”. Rather, the creatine–phosphocreatine system may be relevant for some people with the condition and deserves further investigation in larger, methodologically robust trials.

References

Important: This article is for general information only and is not a substitute for medical advice, diagnosis or treatment. Food supplements are not intended to treat long COVID.