Independent · non-commercial · publishes on a quarterly cycle|Current cycle 2026 Q3
Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Compound monograph · evidence extract

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

The Institute's graded assessment of NAD+ (nicotinamide adenine dinucleotide) for primary mitochondrial myopathy and bioenergetic disorders, with the contributing trials and the domain-by-domain certainty reasoning.

Document identifier
CEI-MN-045/EV-MITOCHONDRIAL
Series
Evidence extract
Version
2.1
Published
23 Aug 2026
Last reviewed
23 Aug 2026
Next review
23 Aug 2028
Identifier
10.71829/cei.mono.45
Certainty
Very low
Cycle
2026 Q3

§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. The rating below reflects that absence.

§1.3Certainty assessment

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasno downgradeInconsistencyno downgradeIndirectnessdowngrade two levelsImprecisiondowngrade one levelPublication biasno downgradeTotal downgrading: 3 levelsVery low certainty
Figure 2. Domain-by-domain certainty assessment for NAD+ (nicotinamide adenine dinucleotide) in primary mitochondrial myopathy and bioenergetic disorders. The starting rating for a body of randomised evidence is high; each serious concern reduces it by one level and each very serious concern by two.

Table 2. Reasoning recorded against each certainty domain.

DomainRatingReasoning
Risk of biasNo concernNo serious concern identified in this domain.
InconsistencyNo concernNo serious concern identified in this domain.
IndirectnessVery seriousThe enrolled population differs materially from the population of the assessment question.
ImprecisionSeriousThe event count falls below the optimal information size.
Publication biasNo concernNo serious concern identified in this domain.
Overall rating: Very low certainty. The Institute has very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate. In this series a very low rating most often reflects an absence of controlled human evidence rather than conflicting evidence.

§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.

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