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Combating ‘Long COVID’

Combating ‘Long COVID’

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How mitochondrial nutrients may help with lingering effects of the virus

Viral infections can produce long-range symptoms well after the virus has passed through the body. Just ask the millions of people suffering from “long COVID” who are still struggling from fatigue and brain fog for months after contracting COVID-19.[1],[2]

Remarkably, long COVID doesn’t just affect people who were very ill with the virus, but also those who had seemingly mild cases of the virus initially.[3],[4] Many people who suffer from long COVID were previously healthy and are extremely frustrated by this lingering condition.

People’s descriptions of their long COVID experiences have several common themes:[5]

(1) The long COVID symptoms are numerous, hard to describe, and debilitating;
(2) All (or many) aspects of one’s day-to-day functioning are impacted;
(3) The affected individuals can no longer be physically active; and
(4) They keep asking for help but no one seems to be listening, and very little is helping.

A prospective study followed 96 individuals for a year after their COVID diagnosis and found that the majority of respondents still had at least one symptom after 12 months.[6] The symptoms of long COVID included reduced capacity for exercise (56%), fatigue (53%), breathing difficulties (37%), concentration problems (39%), problems finding words (32%), and poor sleep (26%).

Today we’ll discuss the role of the mitochondria in long COVID and the use of mitochondrial nutrients for nutritional support.

How the SARS-CoV-2 virus hijacks the mitochondria

Supplemental mitochondrial nutrients can help alleviate the fatigue associated with CFS, so they may be useful for long COVID as well.

To understand the mechanisms underlying this condition, one research team conducted cardiopulmonary (heart and lung) exercise tests in men and women with long COVID.[7] The results showed a reduction in fatty acid oxidation (one of the main sources of cellular energy) and an abnormal buildup of lactic acid, as compared to previously-tested controls. This points to a problem with the mitochondria, the cellular structures (organelles) that provide 95% of the body’s energy needs.

Viruses, including SARS-CoV-2, act as intracellular “parasites” that hijack mitochondrial pathways to drive viral replication.[8],[9],[10] Consequently, the infection depletes human cells of the antioxidants and mitochondrial cofactors they need for good health.[11],[12],[13],[14]

In fact, it’s becoming clear that mitochondrial dysfunction and antioxidant imbalance may explain most of the symptoms of long COVID, including fatigue and brain fog.[13],[15],[16],[17]

Some authors believe that long COVID syndrome is another form of chronic fatigue syndrome (CFS), since both conditions are very similar clinically.[18],[19],[20],[21] Viral infections can trigger CFS, although it is not exclusively considered a post-infectious illness.[13]

Supplemental mitochondrial nutrients can help alleviate the fatigue associated with CFS,[22] so they may be useful for long COVID as well.[19] The mitochondrial nutrients of interest for this purpose include Coenzyme Q10, carnitine, NADH, melatonin, and alpha-lipoic acid.

Coenzyme Q10

CoQ10 is produced in the body, but the amount produced is often insufficient to meet the demands during illnesses and infections.

Coenzyme Q10 (CoQ10, also known as ubiquinone or ubiquinol) is a mitochondrial cofactor that has both antioxidant and bioenergetic properties.[23],[24],[25] Although CoQ10 is produced in the body, the amount produced is often insufficient to meet the demands during illnesses and infections.[26],[27],[28]

In patients with CFS, lower levels of CoQ10 are associated with fatigue and with oxidative stress.[29],[30] Therefore, restoring normal antioxidant and CoQ10 levels may help alleviate chronic fatigue.[27],[31],[32],[33] In studies of CFS, CoQ10 (200 mg/day) has been used in conjunction with NADH (20 mg/day), as discussed later in this article.

Viral infections, including COVID-19, deplete CoQ10 and total antioxidant levels.[14],[26],[34] By correcting this deficit, supplemental CoQ10 may help support recovery after infections. According to preliminary studies, the use of CoQ10 (10 mg three times daily) in conjunction with standard treatments improved the recovery of cardiac function in patients with viral myocarditis (inflammation of the heart following viral infection).[35],[36]

Carnitine

Increasing skeletal muscle carnitine content increases whole-body fat oxidation during moderate-intensity exercise.

Carnitine is found in nearly all cells of the body. It enables fatty acids to enter the mitochondria where they can be burned to generate energy.[37],[38],[39] Supplemental carnitine (at a dose of 2-4 grams daily) has been shown to improve fatigue and exercise performance in healthy adults and in those suffering from chronic fatigue.[40],[41],[42],[43],[44]

Increasing skeletal muscle carnitine content increases whole-body fat oxidation during moderate-intensity exercise,[38],[43] suggesting that it may improve energy metabolism in people with long COVID as well.[45] People with naturally higher carnitine levels were found to have less severe outcomes from COVID-19 infections.[46]

Melatonin

Supplemental melatonin may improve fatigue and accelerate the return to baseline health.

Melatonin plays a key role in mitochondrial energy production, both at rest and during exercise.[47],[48],[49],[50],[51] It also activates the Nrf2 pathway, which regulates cell survival in response to injury and inflammation.[52],[53]

However, viruses that invade the mitochondria disrupt melatonin synthesis and impair these vital functions, leading to a buildup of dysfunctional mitochondria.[49],[54],[55] Controlled trials suggest that supplemental melatonin may improve fatigue and accelerate the return of patients to baseline health after COVID.[56],[57],[58] The suggested doses in these studies ranged from 3 to 12 mg/day, although far higher doses of 100 to 400 mg/day are being investigated for individuals with active infections.[50]

Alpha-lipoic acid

ALA is a powerful antioxidant that protects the brain and heart from oxidative damage.

Alpha-lipoic acid (ALA), a cofactor for four enzyme complexes exclusively located in mitochondria, is essential for energy production.[59] It is a powerful antioxidant that protects the brain and heart from oxidative damage during illness.[60],[61],[62],[63]  Oral doses of ALA generally range from 300 to 1200 mg/day in human studies.[60],[61]

Due the role played by oxidative stress in viral infections, supplemental ALA has been suggested as an adjunct to standard care during and after COVID.[64],[65] ALA may be particularly valuable for individuals with diabetes, who are highly susceptible to the effects of COVID.[66] Further clinical studies are needed to confirm these findings.

Nicotinamide adenine dinucleotide (NAD/NADH)

NADH and CoQ10 improved fatigue, mental clarity, and health-related quality of life for people with chronic fatigue.

Mitochondrial supplements often include nicotinamide adenine dinucleotide (NAD), another essential cofactor for energy production.[67] In a double-blind trial of people with CFS, supplementation with NADH relieved fatigue in 31% of cases, compared with only 8% of those in the placebo group.[68]

Three double-blind, placebo-controlled trials showed that supplemental NADH (20 mg per day) along with CoQ10 (200 mg per day) improved fatigue, mental clarity, and health-related quality of life for people with chronic fatigue.[69],[70],[71]

COVID-19 is associated with deficiencies in nicotinamide adenine dinucleotide (NAD+) and glutathione metabolism, so replenishing these cofactors may be helpful.[14],[72] A placebo-controlled trial assessed the effects of supplementation as an adjunct to standard care for individuals with mild to moderate COVID infections.[72] The supplement contained carnitine along with NADH (as nicotinamide riboside) and glutathione precursors. The combined nutrients helped relieve inflammation and oxidative stress, and hastened the recovery from the infection as compared to placebo.

 

In closing, viral infections such as COVID often deplete mitochondrial nutrients and antioxidants. This contributes to the clinical manifestations of the infection and is detrimental to healing processes. CoQ10, carnitine, melatonin, alpha-lipoic acid, and NADH are promising adjuncts for people recovering from COVID.[73],[74],[75],[76]

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