A systematic review of nutraceutical interventions for mitochondrial dysfunctions in ME/CFS (Maksoud et al., 2021)


Senior Member
U.S., Earth
Another literature review from Staines and Marshall-Gradisnik:

A systematic review of nutraceutical interventions for mitochondrial dysfunctions in ME/CFS (Maksoud et al., 2021)

Maksoud et al 2021 said:
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness, characterised by persistent fatigue that is unrelieved by rest, in combination with a range of other disabling symptoms. There is no diagnostic test nor targeted treatment available for this illness. The pathomechanism also remains unclear. Mitochondrial dysfunctions have been considered a possible underlying pathology based on reported differences including structural and functional changes in ME/CFS patients compared to healthy controls. Due to the potential role that mitochondria may play in ME/CFS, mitochondrial-targeting nutraceutical interventions have been used to potentially assist in improving patient outcomes such as fatigue. The aim of this systematic review is to appraise literature assessing these nutraceuticals as a possible intervention for treating ME/CFS.

A systematic search of Pubmed, Embase, Medline (EBSCO host) and Web of Science (via Clarivate Analytics) for journal articles published between January 1995 and 10th November 2020 was conducted. Articles assessing nutraceutical interventions and ME/CFS patient outcomes were retrieved. Using specific inclusion and exclusion criteria, the list of articles was further refined. Quality was measured using the Rosendal scale.

Nine intervention studies were included in this review. The studies investigated patient symptom severity changes such as altered fatigue levels in response to mitochondrial-targeting nutraceuticals. Improvements in fatigue levels were observed in six of the nine studies. Secondary outcomes assessed include biochemical, psychological, and quality of life parameters.

There is insufficient evidence on the effectiveness of mitochondria- targeting nutraceuticals in ME/CFS patients. Future well-designed studies are required to elucidate both the involvement of mitochondria in the pathomechanism of ME/CFS and the effect of mitochondrial-modifying agents on illness severity.


Senior Member
"Mitochondrial dysfunctions have been considered a possible underlying pathology"

I'm just wondering how this wouldn't be the central focus?!?

Considered...possible? Neither seem definitive in determining a focus.
Below is a bullet listing of the supplements and outcomes.

Interventions on primary outcomes
Fatigue was the primary outcome measure in eight out of nine studies . From these studies, six found significant differences in fatigue levels following an intervention.
  • When receiving a combination treatment of CoQ10 and NADH a significant reduction in Fis-40 scores were reported in one study. (FIS: Fatigue Index Symptom)
  • Additionally, consumption of NADH alone, also resulted in significantly reduced fatigue scores compared to the placebo control group.
  • Combination treatments including: KPAX002 (methylphenidate hydrochloride accompanied by a mitochondrial modulator) and another range of mitochondrial targeting nutrients significantly reduced symptom scores .
  • One KPAX002 study found that the most significant response was with those who had higher symptom severity. ALC and propionyl-l-carnitine (PLC) significantly reduced mental fatigue and general fatigue, respectively.
What is KPAX002?

According to it’s manufacturer, “KPAX002 consists of two co-administered components – a low dosage of methylphenidate (generic Ritalin®) combined with a micronutrient formula specifically designed to support mitochondrial function. This proprietary micronutrient formula is designed to raise cellular energy production in order to improve the functioning of several bodily systems including the nervous, endocrine, and immune systems.”