Chronic fatigue: possible causes, cellular energy, and the role of NAD-H, vitamin D, and Coenzyme Q10

Chronic fatigue does not just mean "lack of motivation" or a simple transient state of exhaustion. For many people, it manifests as low energy in the morning, difficulty concentrating, unrefreshing sleep, muscle weakness, decreased physical and mental performance, or the feeling that the body is constantly "running on empty."

The causes can be multiple: vitamin D deficiency, anemia, thyroid disorders, insulin resistance, chronic inflammation, prolonged stress, sleep apnea, infections, side effects of some medications, or mitochondrial dysfunction. For this reason, persistent fatigue should be medically evaluated, especially if it lasts for weeks or months.

Chronic fatigue and cellular energy

The body's energy is mainly produced at the mitochondrial level, cellular structures that convert nutrients into ATP, the main energy source for cells. When mitochondrial function is impaired, a person may experience fatigue, lack of mental clarity, slow recovery after exertion, and decreased vitality.

Three very important nutrients in supporting cellular energy are vitamin D, Coenzyme Q10, and NAD-H. Each acts differently, but together they support essential processes for energy metabolism, muscle function, immunity, and mental clarity.

Vitamin D and fatigue

Vitamin D is best known for its role in bone health, but it also influences the immune system, muscle function, and overall well-being. Low vitamin D levels can be associated with fatigue, muscle weakness, diffuse pain, and decreased body resilience.

When fatigue persists, measuring 25(OH)D levels in the blood is one of the useful tests. Supplementation should be adjusted based on serum levels, weight, sun exposure, and individual medical context.

Coenzyme Q10 and mitochondria

Coenzyme Q10 is an essential molecule for energy production in mitochondria. It participates in the mitochondrial respiratory chain, the process by which cells produce ATP.

CoQ10 levels can decrease with age and may be influenced by certain medications, including statins. For this reason, Coenzyme Q10 is frequently used to support energy, cardiovascular function, and cellular performance.

NAD-H and ATP production

NAD-H is the reduced form of the coenzyme NAD+, an essential molecule in energy metabolism. NAD-H transfers electrons in the mitochondrial respiratory chain, directly contributing to ATP production.

In other words, NAD-H participates in the mechanism by which cells convert nutrients into usable energy. For this reason, it is studied in contexts such as persistent fatigue, mitochondrial function, mental clarity, and the body's resilience during demanding periods.

What tests can be useful in chronic fatigue?

• Complete blood count – for anemia or infections.
• Ferritin, serum iron, transferrin – for iron deficiency.
• TSH, FT4, FT3 – for thyroid function.
• 25(OH)D – for vitamin D status.
• Blood glucose, insulin, HbA1c – for insulin resistance and carbohydrate metabolism.
• CRP, ESR – for inflammation.
• Vitamin B12 and folate – for nervous system and energy.
• Transaminases, GGT, creatinine – for liver and kidney.

When should you see a doctor?

Persistent fatigue should be investigated if it lasts more than a few weeks, appears suddenly, progressively worsens, or is accompanied by weight loss, fever, night sweats, palpitations, shortness of breath, chest pain, significant dizziness, severe sleep disturbances, or neurological symptoms.

Useful supplements for supporting energy

Depending on the cause, supplements can play a supportive role but do not replace investigations and treatments recommended by a doctor. In persistent fatigue, the most useful approaches are correcting deficiencies, supporting mitochondria, and reducing oxidative stress.

• Vitamin D3 + K2 + Magnesium – for immunity, muscles, and vitamin D metabolism.
• Coenzyme Q10 – to support mitochondrial energy production.
• Liposomal NAD-H – for energy metabolism, ATP, and mental clarity.
• Alpha-lipoic acid – an antioxidant involved in glucose metabolism and mitochondrial function.
• Liposomal glutathione – for antioxidant protection and liver support.

What do the studies show?

A study published in Antioxidants & Redox Signaling (2015) evaluated oral administration of CoQ10 and NADH in patients with chronic fatigue syndrome. The randomized, double-blind, placebo-controlled study observed favorable effects on fatigue, biochemical markers, and oxidative stress.
See the study

A study published in Clinical Nutrition (2016) analyzed the effects of administering CoQ10 plus NADH for 8 weeks in people with chronic fatigue syndrome. The authors reported promising results regarding fatigue reduction and improvement of some functional parameters.
See the study

A study published in Antioxidants (2021) evaluated supplementation with CoQ10 and NADH in people with chronic fatigue syndrome and observed improvements in fatigue perception, quality of life, and sleep quality.
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A systematic review published in the Journal of Clinical Medicine (2023) analyzed the safety and efficacy of supplementation with forms of NAD and NADH in humans, discussing the role of these coenzymes in oxidative phosphorylation, ATP production, DNA repair, and gene expression.
See the analysis

An analysis published in Nature Reviews Molecular Cell Biology (2021) described the central roles of NAD metabolism in cellular processes such as energy metabolism, DNA repair, chromatin remodeling, and cellular senescence.
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A study published in the European Journal of Cardiovascular Medicine (2025) suggests a high prevalence of vitamin D deficiency in the general population, which is significantly associated with increased fatigue and reduced muscle strength. Routine screening and correction of vitamin D levels could help alleviate these symptoms and improve quality of life.
See the study

• Antioxidants & Redox Signaling, 2015 – CoQ10 plus NADH in chronic fatigue syndrome.
• Clinical Nutrition, 2016 – CoQ10 plus NADH and functional parameters in chronic fatigue.
• Antioxidants, 2021 – CoQ10 plus NADH and improvement of fatigue, quality of life, and sleep.
• Journal of Clinical Medicine, 2023 – Safety and efficacy of NAD/NADH as supplements in humans.
• Nature Reviews Molecular Cell Biology, 2021 – NAD metabolism and its roles in cellular processes during ageing.
• European Journal of Cardiovascular Medicine 2025 - Evaluation of Vitamin D Deficiency and Its Association with Fatigue and Muscle Weakness in the General Population

Frequently Asked Questions

Can chronic fatigue be caused by vitamin D deficiency?

Yes, low levels of vitamin D can be associated with fatigue, muscle weakness, and a general reduced state. However, vitamin D deficiency is only one of the possible causes, which is why tests and medical evaluation are useful.

Does Coenzyme Q10 help with energy?

Coenzyme Q10 participates in ATP production in mitochondria, being important for cellular energy metabolism. It can be especially useful for older adults, persistent fatigue, or those undergoing statin treatment.

What role does NAD-H play in fatigue?

NAD-H is directly involved in the mitochondrial respiratory chain and cellular energy production. For this reason, it is studied for supporting energy, mental clarity, and mitochondrial function.

Conclusion

Chronic fatigue should not be ignored. It can have simple causes, such as vitamin D deficiency or lack of sleep, but also metabolic, hormonal, inflammatory, or mitochondrial causes. A proper approach starts with investigations, correcting deficiencies, and supporting the natural mechanisms of energy production.

Vitamin D, Coenzyme Q10, and NAD-H can be three important components in supporting cellular energy, especially when integrated into a balanced lifestyle with good sleep, proper nutrition, exercise, and appropriate medical monitoring.

Dietary supplements do not cure diseases and cannot replace treatments prescribed by a doctor. If fatigue persists or worsens, it is important to consult a doctor for further investigations.