A broader approach to treating long COVID

This article addresses how fueling ATP and cellular energy with precursor molecules, such as nicotinamide riboside chloride, is an important part of a broad approach to treating long COVID.

Our patient population is suffering from an increasingly complex layering of health issues. One of those issues is long COVID, a very real health condition described in the medical literature and encompassing up to 200 diagnostic codes.¹ More than ever, a broadened functional medicine approach of supplementation, diet and lifestyle, along with a foundation of spinal care, is what more and more patients need to overcome challenges, such as long COVID. I share with my patients that fueling adenosine triphosphate (ATP) helps “all the ships in the harbor rise” with the tide of increased energetics.

Common long COVID symptoms

Long COVID is a chronic condition that develops after infection with the SARS-CoV-2 coronavirus. An estimated 10%-20% of COVID-19 survivors across all severity levels are impacted by long COVID.²

Long COVID is defined as symptoms persisting or emerging for at least three months post-SARS-CoV-2 infection and lasting for weeks to years.³ Rather than a single uniform disorder, it is characterized by overlapping symptom clusters that can include fatigue, neurocognitive impairment, respiratory/cardiopulmonary problems, autonomic symptoms and mood/sleep issues.

Common symptoms of long COVID may include:^4,5

• Fatigue
• Dyspnea after exercise
• Cognitive challenges
• Hair loss
• Problems exercising
• Headaches
• Sleep disturbances
• Mood alterations
• Chest tightness
• Persistent cough
• Palpitations
• Orthostatic intolerance (POTS)
• Musculoskeletal pain
• Myalgias
• Altered taste or smell
• Abdominal pain
• Diarrhea or constipation
• Rashes
• Swelling of the legs
• Anxiety and depression
• Foot problems

Fatigue occurring even with minimal exertion and worsening symptoms after exercise are hallmarks of long COVID. Cognitive symptoms, such as “brain fog,” reduced attention and memory and slowed mental processing occur frequently and often at the same time as headaches, sleep problems and mood changes. A patient’s status can change from day to day, and relapses can occur due to physical, mental or emotional stress.​

Certain people are at a higher risk of long COVID. These include people with asthma, type 2 diabetes, autoimmune diseases and mental health issues. Women are at a significantly higher risk of developing long COVID, particularly those who are perimenopausal and menopausal. In addition, inflammatory markers for D-dimer, C-reactive protein (CRP) levels and lymphopenia are associated with long COVID risk.

Mitochondrial impairment

The mitochondria, the batteries of the cells, play an essential role in energy production and are critical for maintaining cellular and systemic health. Mitochondrial dysfunction leads to a drop in energy production, elevated reactive oxygen species (ROS) production and upregulation of inflammatory pathways, which can all contribute to the development of many diseases, including long COVID. In fact, mitochondrial impairment and long COVID have a lot in common regarding similar symptoms.

People suffering from long COVID frequently have mitochondrial dysfunction, according to human evidence. For example, studies have found mitochondrial abnormalities in peripheral blood mononuclear cells (PBMCs) from long COVID patients.^6,7,8 These impairments indicate poor mitochondrial energy production, which may explain why long COVID patients experience fatigue and muscle weakness. Other studies of patients with long COVID observed changes in muscle tissue and the brain indicative of mitochondrial dysfunction.^9,10

The fact that long COVID patients have reactivated viruses, such as HHV-6 and EBV, which are known to damage the mitochondria and interfere with energy production, provides additional indication of mitochondrial dysfunction in long COVID.¹¹

How acute COVID-19 impairs NAD+

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme for many metabolic processes, including energy metabolism, DNA repair and stress response regulation. During SARS-CoV-2 infection, NAD+ metabolism is significantly dysregulated.¹² SARS-CoV-2 infection increases the activity of NAD+-consuming enzymes, while at the same time downregulating enzymes that synthesize NAD+. This decrease in cellular NAD+ is associated with disease progression and undesirable clinical results in COVID-19.¹³

Using NAD+

There are several mechanisms by which NAD+ supplementation can be beneficial in long COVID. NAD+ is essential for mitochondrial function due to being an electron carrier in the electron transport chain.¹⁴ NAD+ also acts as an essential substrate for sirtuins, a family of enzymes dependent on NAD+ for their actions in cellular defense and stress responses.¹⁵ Optimizing NAD+ levels allows cells to restore the capacity for energy generation and can trigger protective pathways.

Supporting the NAD+ pathway

Supporting healthy NAD+ levels can benefit both acute SARS-CoV-2 infection and long COVID. Supplementation with nicotinamide riboside (NR) is an effective way to boost NAD+ levels. In a randomized, double-blind, placebo-controlled clinical study sponsored by Niagen Bioscience and conducted by researchers at Massachusetts General Hospital, 58 non-hospitalized long COVID patients were randomized to receive 2,000 mg per day of NR or a placebo.¹⁶ The subjects were placed into a group that received only NR for 20 weeks or a placebo group that received only the placebo for 10 weeks, then the NR for another 10 weeks. NR concentrations were higher in the NR group compared with the placebo group, but there was no significant benefit of NR over placebo for cognition, fatigue, depression or sleep. However, within-group analyses revealed improvements in fatigue, sleep, depression and executive function, alongside confirmed increases in NAD+. These results warrant further long-term studies.

Studies using nicotinamide riboside in acute COVID-19

In a placebo-controlled, open-label Phase 2 study and a double-blinded Phase 3 clinical trial, patients with COVID-19 recovered faster after taking a combination of NR with N-acetyl-l-cysteine, L-serine and L-carnitine.¹⁷ After taking the combination of nutrients, the participants experienced significantly improved plasma levels of inflammatory proteins compared to the placebo.

According to other research, COVID-19 causes endothelial cell dysfunction, characterized by reduced nitric oxide (NO) production. The lower NO level correlates with greater reactive oxygen species (ROS) and a decline in NAD+. In one study, human aortic endothelial cells (HAECs) were treated with plasma from men and women age 18-85 years who were hospitalized and tested positive (34 participants) or negative (13 participants) for COVID-19.¹⁸ HAECs treated with plasma from COVID-19 patients also were co-incubated with NAD+ precursors including nicotinamide riboside (NR). NO production was 27% lower, and ROS bioactivity was 54% higher in HAECs exposed to plasma from patients with COVID-19. In addition, NAD+ concentrations were 30% lower in HAECs exposed to plasma from COVID-19 patients. Cells treated with NR stopped reductions in NO production and oxidative stress caused by COVID-19.

A broad approach

NAD+ optimization is not a stand-alone therapy, but used as part of a broader approach to the management of long COVID. In addition to impairing mitochondrial function and reducing NAD+ levels, COVID-19 can also cause other dysfunctions, including gut microbiome dysbiosis.¹⁹ COVID-19 affects the gastrointestinal tract through ACE2 receptors, which are extensively expressed in this area.²⁰ That’s why, in long COVID patients, an optimal approach is to maintain a healthy microbiota with probiotic supplementation together with NAD+ precursors such as NR. Other helpful approaches include immune support and lifestyle modifications such as mild to moderate exercise.

Final thoughts

Long COVID can be a debilitating condition that significantly interferes with the quality of life and well-being of patients. In addition to chiropractic adjustments, implementing a broad approach that includes NAD+ precursors such as nicotinamide riboside, probiotics, immune support and mild to moderate exercise can yield excellent results.

Chris D. Meletis, ND, is an educator, international author and lecturer. He is widely recognized as a world-renowned expert on the science of CBD and has authored 18 books and more than 200 national scientific articles. He served as dean of naturopathic medicine and chief medical officer for seven years at National University of Natural Medicine (NUNM). He has received numerous awards, including the prestigious Physician of the Year Award from the American Association of Naturopathic Physicians, an Excellence Award for his work treating and advocating for the medically underserved and most recently, the NUNM Hall of Fame Award.  Meletis is an independent educator on the role of nicotinamide riboside (Niagen®) and TruNiagen in clinical practice. He has free clinically focused videos available at pro.truniagen.com, covering topics such as cellular energetics, sports and muscular health, cognition, hormonal health and nearly a dozen others.

References

1. US Centers for Disease Control and Prevention. Long COVID signs and symptoms. Published 2025. https://www.cdc.gov/long-covid/signs-symptoms/index.html. Accessed March 22, 2026.
2. Abbas AH, et al. A multidisciplinary review of long COVID to address the challenges in diagnosis and updated management guidelines. Ann Med Surg (Lond).2025;87(4):2105-2117. https://pubmed.ncbi.nlm.nih.gov/40212158/. Accessed March 22, 2026.
3. A Long COVID Definition: A chronic, systemic disease state with profound consequences. Goldowitz I, Worku T, Brown L ed. Washington (DC): National Academies of Sciences; 2024. https://pubmed.ncbi.nlm.nih.gov/39110819/. Accessed March 22, 2026.
4. Molnar T, et al. Mitochondrial dysfunction in long COVID: Mechanisms, consequences, and potential therapeutic approaches. Geroscience. 2024;46(5):5267-5286. https://pubmed.ncbi.nlm.nih.gov/38668888/. Accessed March 22, 2026.
5. Long COVID: Post-COVID conditions (PCC). Yale Medicine. [Fact sheet]. https://www.yalemedicine.org/conditions/long-covid-post-covid-conditions-pcc. Accessed March 22, 2026.
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15. Libri V, et al. A pilot randomized, placebo controlled, double blind Phase I trial of the novel SIRT1 activator SRT2104 in elderly volunteers. PLoS One. 2012;7(12):e51395. https://pubmed.ncbi.nlm.nih.gov/23284689/. Accessed March 22, 2026.
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