Best for Mitochondrial function and metabolic-signaling research
Mitochondrial-health marketing combines nutritional precursors, approved drugs, experimental peptides, and preclinical enzyme inhibitors. This page separates human biomarker data from animal findings and untested therapeutic claims. It is an evidence curation, not guidance for use.
NAD+ / NMN / NR
The strongest human biomarker record in the group: NR and NMN can raise NAD-related measures, although broad anti-aging outcomes remain unproven.
Evidence level: Controlled human biomarker studies
Regulatory status: NR is marketed as a dietary supplement; NMN remains subject to an FDA DSHEA exclusion determination
Human studies show that NR or NMN supplementation can alter NAD-related biomarkers, and one controlled NMN study reported improved muscle insulin sensitivity in a specific prediabetic population. Clinical claims about energy, longevity, or disease prevention extend beyond the evidence.
MOTS-c
A mitochondria-derived signaling peptide directly relevant to mitochondrial-to-nuclear communication, with compelling animal data but no established human treatment effect.
Evidence level: Preclinical plus observational human research
Regulatory status: Not FDA-approved; regulatory watch
MOTS-c is encoded within mitochondrial DNA and has been studied as a metabolic signaling molecule. Mouse experiments reported improved insulin sensitivity and obesity resistance, while human observational work has examined exercise- and age-related associations.
Methylene Blue
An approved drug for methemoglobinemia with separate preclinical literature on mitochondrial electron cycling and cognition.
Evidence level: Approved drug for another indication; mitochondrial claims remain largely preclinical
Regulatory status: FDA-approved for methemoglobinemia; not approved as a mitochondrial or cognitive enhancer
Methylene blue has a defined pharmaceutical indication and a long research history. Low-dose mitochondrial and cognitive hypotheses come largely from preclinical or small experimental studies and should not be generalized to non-pharmaceutical products sold online.
5-Amino-1MQ
A research inhibitor of NNMT with metabolic effects in animal models and no published human clinical trials.
Evidence level: Preclinical only
Regulatory status: Not FDA-approved; research compound
5-Amino-1MQ inhibits nicotinamide N-methyltransferase in experimental systems. Mouse studies reported obesity-related metabolic effects, but the compound has no established human safety, pharmacokinetic, or efficacy record.
Improving a laboratory biomarker or animal metabolic endpoint is not the same as improving human health, performance, or lifespan. Regulatory categories also differ sharply across these compounds.
Source records are stored in the repo and linked from this page.
Randomized, double-blind trial (Dollerup et al.) showing that NR safely increased blood NAD+ in obese men but did not improve insulin sensitivity or body composition over 12 weeks, illustrating the biomarker-vs-outcome gap.
Randomized, placebo-controlled trial (Yoshino et al., including Shin-ichiro Imai) showing that 10 weeks of NMN supplementation increased muscle insulin sensitivity in prediabetic women. A key human proof-of-concept study.
FDA GRAS (Generally Recognized As Safe) notice response for nicotinamide riboside (NR) chloride, the ingredient in Tru Niagen, supporting its use as a dietary supplement ingredient.
FDA determination that NMN (nicotinamide mononucleotide) is excluded from the dietary supplement definition under DSHEA because it was first authorized for investigation as a new drug. This triggered marketplace disruption for NMN supplements.
Lee et al. (2015) landmark study (PMID 25754631) in Cell Metabolism identifying MOTS-c as a mitochondrial-derived peptide that regulates metabolic homeostasis, improves insulin sensitivity, and prevents obesity in mice fed a high-fat diet. Preclinical only.
Emerging research on MOTS-c in the context of exercise physiology and aging, including observational human studies showing MOTS-c levels change with exercise. No interventional human trials confirming therapeutic effects.
FDA advisory committee meeting notice listing multiple peptide bulk substances scheduled for discussion.