Cofactor Panel Evidence and Systematic Reviews

1 Joustra et al. 2017 β€” Systematic Review: Vitamins and Minerals in CFS/FM

Full Citation:: Joustra ML, Minovic I, Janssens KAM, Bakker SJL, Rosmalen JGM. Vitamin and mineral status in chronic fatigue syndrome and fibromyalgia syndrome: A systematic review and meta-analysis. PLoS ONE. 2017;12(4):e0176631. (Joustra et al. 2017) DOI:: 10.1371/journal.pone.0176631 Key Findings::

- Systematic review + meta-analysis; 45 studies (5 RCTs, 40 observational)
- Covered vitamins A, B1, B12, C, D, E and 13 minerals
- Little overall evidence for vitamin/mineral deficiency playing a role in CFS/FM
- Only vitamin E lower, but effect disappeared in high-quality studies
- *Critical omission:* CoQ10 and NAD^+^ excluded from primary analysis β€” the two cofactors with the strongest mechanistic rationale in the energy metabolism literature
- Riboflavin/FAD also not a primary focus
- *Certainty: 0.65* β€” rigorous methodology but the exclusion of the most mechanistically relevant cofactors limits its applicability to the G9 question

Relevance:: The best available systematic evidence synthesis for classical vitamins/minerals in CFS β€” and an object lesson in how selection of which cofactors to study shapes conclusions. The exclusion of CoQ10, NAD+, and riboflavin from primary analysis means the review answers the wrong question for the energy metabolism hypothesis. A future systematic review scoped to energy-relevant cofactors specifically is needed.

2 Dorczok et al. 2025 β€” Systematic Review: Dietary Supplementation in ME/CFS

Full Citation:: Dorczok M, et al. Dietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) β€” A Systematic Review. Nutrients. 2025;17(3):475. (Dorczok et al. 2025) DOI:: 10.3390/nu17030475 Key Findings::

- Systematic review; 14 studies ($n = 809$ total); heterogeneous designs
- CoQ10+NADH combination shows strongest signal for fatigue reduction
- One trial tested CoQ10 + alpha-lipoic acid + NAC + B vitamins combined β€” closest to a multi-cofactor intervention
- 9/14 studies included blood analyses, but cofactors measured in separate trials, never simultaneously
- No study measured all G9 cofactors at baseline
- *Certainty: 0.55* β€” moderate evidence base; heterogeneous designs prevent firm conclusions

Relevance:: Confirms that the supplementation literature has converged on CoQ10+NADH as the most promising combination but has never tested whether baseline cofactor status predicts response. The absence of pre-treatment comprehensive cofactor panels in all 14 studies means responder prediction is impossible β€” exactly the problem G9 would solve.

References

Dorczok, Marleen et al. 2025. β€œDietary Supplementation for Fatigue Symptoms in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) β€” a Systematic Review.” Nutrients 17 (3): 475. https://doi.org/10.3390/nu17030475.
Joustra, Maaike L, Isidor Minovic, Karin A M Janssens, Stephan J L Bakker, and Judith G M Rosmalen. 2017. β€œVitamin and Mineral Status in Chronic Fatigue Syndrome and Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis.” PLoS ONE 12 (4): e0176631. https://doi.org/10.1371/journal.pone.0176631.