Creatine Supplementation as a Potential Treatment for Post-COVID-19 Fatigue Syndrome


Post-viral fatigue syndrome (PVFS), previously known as chronic fatigue syndrome or myalgic encephalomyelitis, is a debilitating long-term neurological disorder characterized by profound fatigue, post-exertional malaise, and unrefreshing sleep.

PVFS typically lasts for more than six months and significantly impairs a person’s ability to engage in routine activities they could perform before falling ill.

While the exact cause of PVFS remains elusive, it is often associated with viral infections, including coronaviruses. With the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the subsequent COVID-19 pandemic, there has been a growing concern about the potential rise in cases of post-coronavirus disease 2019 fatigue syndrome, or Post-COVID-19 fatigue syndrome.

Recent studies have indeed shown a relatively high occurrence of PVFS-like symptoms in COVID-19 survivors, with up to 45% of them experiencing fatigue, post-exertional malaise, and unrefreshing sleep. This has underscored the importance of developing effective intervention strategies to alleviate the burden of Post-COVID-19 fatigue syndrome.

Among various potential approaches, dietary creatine supplementation has gained attention due to its documented benefits in rehabilitating various lung conditions.

Since PVFS is often associated with irregularities in creatine metabolism, replenishing creatine through dietary supplementation has emerged as a safe and cost-effective method of nutritional care for individuals experiencing post-COVID-19 fatigue syndrome.

This article discusses the results of a groundbreaking randomized controlled trial that evaluated the efficacy and safety of medium-term creatine supplementation in patients with post-COVID-19 fatigue syndrome. The study aimed to investigate the effects of creatine supplementation on patient-reported outcomes, tissue creatine levels, and overall fatigue in this specific patient population.

Efficacy of Creatine Supplementation in Post-COVID-19 Fatigue Syndrome

The study conducted to assess the impact of creatine supplementation on post-COVID-19 fatigue syndrome yielded promising results. It was the first human trial of its kind to investigate the effects of creatine supplementation on fatigue, tissue bioenergetics, and patient-reported outcomes in this particular patient group. The key findings of the study included:

  • Increased Tissue Creatine Levels: Creatine supplementation significantly increased total creatine levels in both brain and skeletal muscle tissue. The increase observed in some regions of the brain was particularly noteworthy, with up to a 33% rise in the right parietal white matter. Given that PVFS is associated with impaired tissue bioenergetics, this finding suggests that supplemental creatine may effectively support brain creatine levels in individuals with post-COVID-19 fatigue syndrome.
  • Improved Cognitive Function: Participants who received creatine reported a substantial improvement in concentration. The scores for concentration difficulties dropped by 77.8% at the 3-month follow-up and remained absent at the 6-month follow-up. This improvement in cognitive function is a significant outcome, as concentration difficulties are a common symptom in post-COVID-19 fatigue syndrome.
  • Reduction in Pain: Creatine supplementation led to a significant reduction in lung and body pain reported by participants. This is particularly noteworthy, as pain management is a crucial aspect of post-COVID-19 symptom relief.
  • Positive Impact on Other Symptoms: The study also noted improvements in various other post-COVID-19 symptoms, such as anosmia (loss of smell), ageusia (loss of taste), and breathing difficulties. This suggests that creatine supplementation may have a broader positive impact on the overall well-being of individuals recovering from COVID-19.

Potential Mechanisms of Action

The beneficial effects of creatine supplementation in post-COVID-19 fatigue syndrome may be attributed to several mechanisms:

  • Energy Replenishment: Creatine plays a crucial role in adenosine triphosphate (ATP) recycling, which supports energy metabolism in the brain and skeletal muscle. By replenishing cellular energy stores, creatine supplementation may help alleviate the fatigue experienced by individuals with post-COVID-19 fatigue syndrome.
  • Neuroprotection: Creatine has neuroprotective properties, which may safeguard against neurological damage or dysfunction associated with COVID-19 and post-viral fatigue.
  • Anti-Inflammatory and Antioxidant Activity: Creatine has anti-inflammatory and antioxidant properties, which can help mitigate the inflammatory response and oxidative stress often observed in post-COVID-19 patients.
  • Neuromodulation: Creatine may modulate neurotransmitter systems, such as glutamatergic pathways, contributing to improved cognitive function and symptom relief.


In summary, the results of this randomized controlled trial suggest that creatine supplementation can be a safe and effective intervention for individuals suffering from post-COVID-19 fatigue syndrome.

This study demonstrated that creatine not only increased tissue bioenergetics but also improved patient-reported outcomes, including cognitive function and pain relief. These findings offer hope for individuals grappling with the debilitating effects of post-COVID-19 fatigue syndrome.

While this study provides valuable insights, it is important to acknowledge its limitations, including the relatively small sample size and the need for further research to explore creatine’s effectiveness in different patient populations and over longer supplementation periods. Additionally, a more comprehensive analysis of biomarkers is required to uncover the underlying molecular pathways through which creatine exerts its therapeutic effects.

In conclusion, the potential role of creatine supplementation in alleviating the burden of Post-COVID-19 fatigue syndrome is a promising avenue for future research and may offer much-needed relief to those struggling with this debilitating condition.

Creatine is a naturally occurring compound found in the human body that plays a pivotal role in energy production, primarily in high-intensity, short-duration activities. It is one of the most widely researched and popular supplements in the fitness and sports industry. This comprehensive article aims to delve into the multifaceted world of creatine, covering its functions, chemistry, sources, benefits, dosages, and potential side effects.

I. Chemistry of Creatine

  • Molecular Structure: Creatine, chemically known as methylguanido-acetic acid, is a nitrogenous organic acid. Its chemical formula is C4H9N3O2. Creatine is a naturally occurring compound synthesized primarily in the liver, kidneys, and pancreas from amino acids, namely arginine, glycine, and methionine.
  • Phosphorylation: Creatine can exist in two forms in the body: free creatine and phosphocreatine (creatine phosphate). The latter is the more biologically active form. Creatine becomes phosphorylated by transferring a phosphate group from adenosine triphosphate (ATP) in a reversible reaction, creating phosphocreatine. This conversion stores potential energy in the form of high-energy phosphate bonds.

II. Functions of Creatine

  • ATP Regeneration: Creatine plays a crucial role in the regeneration of ATP, the primary energy currency of cells. During high-intensity activities like weightlifting or sprinting, ATP is rapidly depleted. Creatine donates its phosphate group to ADP (adenosine diphosphate), rapidly reforming ATP, allowing for sustained muscle contractions.
  • Enhanced Exercise Performance: Creatine supplementation has been extensively studied and shown to improve performance in activities that rely on short bursts of energy, such as weightlifting, sprinting, and jumping. This leads to increased strength, power, and endurance, enabling athletes to perform better.
  • Muscle Growth: Creatine supplementation can promote muscle growth, primarily by increasing water content in muscle cells and enhancing protein synthesis. It also appears to increase the expression of certain genes related to muscle growth.

III. Sources of Creatine

  • Dietary Sources: Creatine can be obtained through the diet, primarily from animal products such as red meat and fish. A typical diet provides about 1-2 grams of creatine per day.
  • Supplements: Creatine supplements, usually in the form of creatine monohydrate, are widely available and popular among athletes and bodybuilders. These supplements provide a convenient and concentrated source of creatine.

IV. Benefits of Creatine Supplementation

  • Improved Exercise Performance: Creatine supplementation has consistently demonstrated its ability to enhance performance in high-intensity, short-duration activities, benefiting athletes and fitness enthusiasts.
  • Muscle Growth and Hypertrophy: Creatine has been linked to increased muscle mass, especially in combination with resistance training. This is attributed to both increased water retention within muscle cells and enhanced protein synthesis.
  • Brain Health: Emerging research suggests that creatine may have neuroprotective properties and potential cognitive benefits. It may play a role in conditions like Alzheimer’s disease and depression.
  • Clinical Applications: Creatine has shown promise in various clinical conditions, including neuromuscular diseases like muscular dystrophy and in mitigating the side effects of cancer treatment.

V. Dosage and Safety

  • Dosage: A common dosing strategy involves a loading phase of 20 grams per day (divided into four doses) for 5-7 days, followed by a maintenance dose of 3-5 grams per day. Alternatively, individuals can skip the loading phase and take 3-5 grams daily from the start.
  • Safety: Creatine is generally considered safe for most people when used as recommended. Side effects are rare but can include stomach discomfort, diarrhea, and muscle cramps. Adequate hydration is essential when supplementing with creatine.

VI. Conclusion

Creatine is a fascinating compound with a profound impact on cellular energy production and exercise performance. Its chemistry, functions, sources, benefits, and safe usage have been extensively studied, making it a staple in the regimen of many athletes and individuals seeking to enhance their physical performance. While creatine offers numerous advantages, it’s crucial to use it responsibly and consult a healthcare professional if there are any concerns or pre-existing medical conditions. As research continues, creatine’s potential applications in various fields, including sports, medicine, and neuroscience, may continue to expand.

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