NAD+ (nicotinamide adenine dinucleotide) in primary mitochondrial myopathy and bioenergetic disorders — evidence extract

§1Evidence extract: Primary mitochondrial myopathy and bioenergetic disorders

§1.1Question and anchor outcome

Population

Genetically determined impairment of oxidative phosphorylation producing myopathy, exercise intolerance or multisystem disease.

Intervention

NAD+ (nicotinamide adenine dinucleotide), intravenous infusion, subcutaneous or intranasal in research contexts; oral precursors are a separate matter

Comparator

As used in each contributing trial; reported per trial rather than pooled across comparator types

Anchor outcome

Six-minute walk distance

Additional outcomes the Institute extracts for this indication: Primary mitochondrial myopathy symptom assessment; Muscle phosphocreatine recovery kinetics.

§1.2Contributing trials

No trial has been identified for NAD+ (nicotinamide adenine dinucleotide) in primary mitochondrial myopathy and bioenergetic disorders. No certainty rating is issued where that is so, for the reason given at §1.3.

§1.3Why no certainty rating is issued

The Institute rates certainty in a body of evidence. Where no eligible study has been identified there is no such body, and the domain-by-domain assessment used elsewhere in this series is not rendered: an inconsistency judgement requires two estimates to be inconsistent with one another, and an imprecision judgement requires an interval. Neither exists here.

The outcome is therefore recorded as not assessed. It is listed in the certainty index under that heading rather than at the lowest rating, because a rating of very low certainty says that evidence was found and is weak, and that is not what has happened.

What would change this: a controlled study in the population stated at §1.1, reporting the anchor outcome, retrievable in a form the Institute can appraise. The evidence gaps recorded in the monograph at §9 state what such a study would need to measure.

§1.4What this extract does not establish

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 2015;21(3):443–454. doi:10.1016/j.cmet.2015.02.009 · PMID 25738459
2. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology 2014;171(8):2029–2050. doi:10.1111/bph.12461 · PMID 24117165
3. United States Pharmacopeial Convention. General Chapter ⟨85⟩ Bacterial Endotoxins Test. United States Pharmacopeia — National Formulary (USP–NF) 2024;USP 2024 Issue 1. identifier not held by the Institute

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.