Melatonin treatment for ME CFS and Long Covid

Research: Melatonin as Possible Treatment for Long Covid and ME/CFS Symptoms

ME Association Comment

This is a useful and interesting review of the various ways in which melatonin could be used to treat Long Covid and ME/CFS.

We already know that a small but significant number of people with ME/CFS already use melatonin to help with sleep disturbance problems:

Results of MEA 2017 survey on Melatonin

Have you used melatonin to help with a sleep problem in ME/CFS? If so, was it helpful?

  • Very helpful (16%)
  • Of some help (14%)
  • No effect (11%)
  • Made worse (3%)
  • Made much worse (2%)
  • Not used melatonin (55%)
  • Total Voters: 541

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The review (below) is suggesting that melatonin could also be helpful in treating other symptoms, Cognitive Dysfunction (‘Brain Fog') in particular. Unfortunately, there have not been any proper clinical trials to assess whether melatonin is a safe and effective treatment for use in Long Covid or ME/CFS, but its use remains an interesting possibility.

  • The ME Association Ramsay Research Fund would welcome grant applications for a clinical trial of melatonin in ME/CFS and Long Covid. Please get in touch with head office for an initial conversation:

Melatonin and sleep

Melatonin is a natural hormone made by the body's pineal gland. This is a pea-sized gland located just above the middle of the brain. During the day the pineal is inactive. When the sun goes down and darkness occurs, the pineal is “turned on” by a special light sensitive centre in another part of the brain (the hypothalamus) and the pineal begins to actively produce melatonin, which is released into the blood.

Usually, the release of melatonin occurs around 9 pm. As a result, melatonin levels in the blood rise sharply and you begin to feel less alert. Sleep becomes more inviting. Melatonin levels in the blood stay elevated for about 12 hours – all through the night – before the light of a new day when they fall back to low daytime levels by about 9 am. Daytime levels of melatonin are barely detectable.

Melatonin is quite widely used to help relieve jet lag and adjust to new time zones or to help with sleep disorders. However, it is not licensed for general use here in the UK, and most doctors are reluctant to recommend it. As a result, people are often obtaining melatonin via the internet – where the quality of medical products is causing concern. 

For reasons that are difficult to understand, the 2007 NICE Guideline on ME/CFS stated that melatonin could be considered for use in children – but only under specialist supervision. Having reviewed the situation more recently, the 2019-2021 NICE Guideline committee decided there was insufficient evidence to recommend the use of melatonin for sleep disturbance or to help other symptoms in ME/CFS.

Article: NewsMedical Life Sciences By Dr Chinta Sidharthan

A recent review published in the journal Biomolecules discussed the potential uses of melatonin in treating brain fog and chronic fatigue syndrome or myalgic encephalomyelitis symptoms associated with long coronavirus disease (COVID).


An emerging concern associated with the coronavirus disease 2019 (COVID-19) pandemic is long COVID or clinical sequelae consisting of chronic fatigue, memory loss, muscle weakness, reduced pulmonary capacity during exertion, persistent fever, myalgia, epileptic seizures, stroke, and other cardiovascular complications. Patients who have recovered from severe COVID-19 experience these debilitating symptoms for months after recovery.

Furthermore, studies that examined vaccinated individuals who experienced breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections found a high incidence of long COVID symptoms such as deteriorated musculoskeletal, neurological, and mental health among these individuals after recovery. This indicates that vaccination provides only limited protection against long COVID.

Melatonin is a cryoprotective hormone and chemical that exhibits anti-inflammatory, antioxidant, and immunoregulatory activity and has been seen to impair viral infections, play a role in circadian rhythm maintenance, and be effective against diabetes mellitus and cardiovascular diseases. It is also involved in the activation of glutathione-synthesizing enzymes. Melatonin could potentially be a therapeutic agent in treating long COVID symptoms…

Research review: Abstract

Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, “long COVID”.

Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or “brain fog”), chronic fatigue, myalgia, and muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are of importance.

Melatonin may be particularly effective at reducing the signs and symptoms of SARS-CoV-2 infection due to its functions as an antioxidant, anti-inflammatory, and immuno-modulatory agent.

Melatonin is also a chronobiotic medication effective in treating delirium and restoring the circadian imbalance seen in COVID patients in the intensive care unit.

Additionally, as a cytoprotector, melatonin aids in the prevention of several COVID-19 comorbidities, including diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases.

This narrative review discusses the application of melatonin as a neuroprotective agent to control cognitive deterioration (“brain fog”) and pain in the ME/CFS syndrome-like documented in long COVID.

Further studies on the therapeutic use of melatonin in the neurological sequelae of SARS-CoV-2 infection are warranted.

Dr Charles Shepherd,
Trustee and
Hon. Medical Adviser
to the ME Association.

Dr Charles Shepherd
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