Conclusion

Supplements can play a supportive role in ME/CFS management, but expectations should be realistic:

• No supplement cures ME/CFS
• Effects are typically modest—10–20% symptom improvement is a good outcome
• Response varies enormously between individuals
• Cost adds up—prioritize based on evidence and your specific symptoms
• Foundation first: Electrolytes, magnesium, B vitamins, and vitamin D before exotic interventions

The following supplements have the strongest mechanistic rationale and/or limited clinical evidence, listed in approximate order of evidence strength:

• Electrolytes (especially if orthostatic symptoms)
• NADH + CoQ10 combination (ME/CFS RCT evidence: Castro-Marrero et al. 207-patient trial (Castro-Marrero et al. 2021))
• NAC (antioxidant, glutathione precursor; no ME/CFS-specific RCT)
• Magnesium (ubiquitous cofactor, often deficient; ME/CFS evidence is observational)
• NAD⁺ precursors (emerging mechanistic rationale; no completed ME/CFS RCT)

Work with a knowledgeable healthcare provider when possible, especially for higher-dose protocols or if taking multiple medications.

References

Castro-Marrero, Jesús, María José Segundo, Mónica Lacasa, Albert Martinez-Martinez, Ramon Sanmartín Sentañes, and José Alegre-Martin. 2021. “Effect of Dietary Coenzyme Q\(_{10}\) Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.” Nutrients 13 (8): 2658. https://doi.org/10.3390/nu13082658.