More research is coming out all the time that everyone might benefit from higher doses of vitamin D. Vitamin D deficiency seems to be relatively common in people with ME/CFS and Long-COVID (though the evidence is less than solid); people in the moderate and severe category and those who cannot be outside much are at higher risk. 

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Vitamin D deficiency has been linked with fatigue, headache, musculoskeletal pain, and weakness. At least 400 IU daily is usually recommended. While taking too much can cause toxicity, doses of up to 10,000 IU per day may be safe (but consult your doctor!).

People with GI (gastrointestinal) issues, including IBS (about 90% of folks with ME/CFS or long-COVID meeting ME diagnostic criteria) are at greater risk of magnesium deficiency, which may cause headache and other symptoms. 

Coenzyme Q10 deficiency, likely common in ME/CFS (and possibly in Long-COVID, but less known), has been shown to be related to fatigue, autonomic and neurocognitive symptoms. 

CoQ10 is one of the most frequently used supplements for the treatment of disorders (such as ME/CFS and Long-COVID) that may have suboptimal cellular energy metabolism because of its importance in the production of adenosine triphosphate (ATP), the cellular source of energy. In addition to reducing fatigue, CoQ10 may alleviate muscle weakness and pain. It is also one of the few supplements that may reduce cognitive dysfunction. Its role as a free radical scavenger may also lead to improvement in immune response.

CoQ10 has been noted as “a safe supplement with minimal side effects and low drug interaction potential”.

Carnitine (also known as L-carnitine, or as the acylated form Acetyl-L-Carnitine) is a naturally occurring amino acid nutrient in the body that is crucial for the transport of long-chain fatty acids into the mitochondria of cells, providing energy to skeletal and heart muscle. Carnitine deficiency produces fatigue, muscle weakness, malaise, exercise intolerance, heartbeat abnormalities, and tissue acidosis.

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ME patients have been found to have statistically significantly lower serum total carnitine, free carnitine, and acylcarnitine levels (citation 1, citation 2, citation 3). These serum levels correlate with clinical symptoms, with higher levels showing better functional capacity. Serum carnitine levels appear to return to normal during ME remission.

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 In studies in 1997, 2000, 2004 and 2011 (summaries here in “ME/CFS” section) , suggested that supplementation with L-Carnitine and Acytul-L-Cartnitine (possibly with Omega-3 fatty acids) may be beneficial for people with ME/CFS (and likely for people with Long-COVID for similar reasons).  

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L-carnitine was found to be very safe and to improve the clinical status of CFS patients in a 1997 study. It has, however, been noted that patients with hypothyroidism or Hashimoto’s disease should probably not take carnitine, but check with your doctor.

There are several small studies (example) that suggest that deficiencies in one or more of these vitamins may be relatively common in people with ME/CFS and Long-COVID., especially if you are on any sort of restrictive diet (plant-based, FODMAP, etc.).

Omega-3s have been suggested to alleviate some symptoms (fatigue, pain, muscle weakness, brain fog, headache). Lower zinc is related to defects in T cell activation, immune dysfunction and oxidative stress. Both Omega-3s and zinc are related to depression, a somewhat common comorbidity with ME/CFS and Long-COVID (citation 1, citation 2).

D-ribose is a precursor to ATP, a source of muscle energy. 

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Individuals with ME/CFS who take a D-ribose supplement may experience a reduction in brain fog and muscle or joint pain, and main gain energy and improve sleep. Some studies note “significantly reduced clinical symptoms.”

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See here for a good overall review of the evidence for D-Ribose for ME. Note that there are also strong suggestions that it would work in a similar fashion for Long-COVID.

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A note on dosage: While clinical studies are needed, it is commonly recommended  to try 5 gram doses 3 times a day (citation 1). But work with your doctor to determine whether you should try D-ribose, how much, and whether you should start at a low dose and work your way up.

An iron deficiency, somewhat common with poor appetite, restrictive diets and reproductive-age women, can lead to symptoms like fatigue, shortness of breath, and difficulty thinking, which can compound the challenges already faced by people with ME/CFS or Long-COVID. 

Caution: excess iron can be bad for heart health and even toxic, so it is highly recommended to check (blood test) for a deficiency before supplementing.