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Stack — Longevity

Mito Stack — MOTS-c + SS-31 + NAD+ · Tested together in people: none published

Gray market

Checked · 25 sources · 6 corrections on this page · No vendors · No affiliates · No one buys a word of it

MOTS-c: FDA panel said yes on July 23–24, 2026 — not legal yet

Sold as a research chemical. Some clinics and pharmacies still supply it; that’s their risk, not a change in the rule.

Not legal to compound — yet The FDA’s advisory committee recommended MOTS-c on July 23–24, 2026. Recommended is not legal — nothing changes until rulemaking is finished. See every change →

Built on: Mitochondrial Optimization & Longevity

The receipt

0 studies gave them to people together

Evidence on the combination
No data

None published

No study that gave them to people together is among the sources Kalios cites. Reports of people already taking both, registered trials, conference talks, patents and makers’ own tests don’t count.

What each does alone

Mechanism overlap · reasoning, not evidence

MOTS-c
Peptide — Mitochondrial-Derived Exercise Mimetic
NAD+
Coenzyme — Mitochondrial + Longevity
SS-31
Peptide — Cardiolipin-Targeted Mitochondrial Therapeutic

Reasoning, not evidence: what each is described to do says nothing about what they do together.

References

References cover the individual components (SS-31 FDA-approved as Forzinity; MOTS-c and NAD+ precursor RCTs) and the mechanistic framework. No trial has studied the three-compound combination.

  1. Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454. PMID: 25738459.
  2. Reynolds JC, Lai RW, Woodhead JST, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021;12(1):470. PMID: 33473109.
  3. Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029-2050. PMID: 24117165.
  4. Karaa A, Haas R, Goldstein A, Vockley J, Weaver WD, Cohen BH. Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy. Neurology. 2018;90(14):e1212-e1221. PMID: 29500292.
  5. Reid Thompson W, Hornby B, Manuel R, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. Genet Med. 2021;23(3):471-478. (TAZPOWER.) PMID: 33077895.
  6. Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. PMID: 29599478.
  7. Airhart SE, Shireman LM, Risler LJ, et al. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One. 2017;12(12):e0186459. PMID: 29211728.
  8. Elhassan YS, Kluckova K, Fletcher RS, et al. Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728. PMID: 31412242.
  9. Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229. PMID: 33888596.
  10. Grant R, Berg J, Mestayer R, et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD. Front Aging Neurosci. 2019;11:257. PMID: 31572171.
  11. Kim SJ, Mehta HH, Wan J, et al. Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging (Albany NY). 2018;10(6):1239-1256. PMID: 29886458.
  12. Yin Y, Li Y, Ma B, et al. Mitochondrial-Derived Peptide MOTS-c Suppresses Ovarian Cancer Progression by Attenuating USP7-Mediated LARS1 Deubiquitination. Adv Sci (Weinh). 2024;11(43):e2405620. PMID: 39321430.
  13. Gudiksen A, Hansen CC, van der Stede T, et al. MOTS-c improves intrinsic muscle mitochondrial bioenergetic health and efficiency in a PGC-1α/AMPK-dependent manner. Free Radic Biol Med. 2026;246:682-696. PMID: 41520850.
  14. Birk AV, Chao WM, Bracken C, Warren JD, Szeto HH. Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br J Pharmacol. 2014;171(8):2017-2028. PMID: 24134698.
  15. Butler J, Khan MS, Anker SD, et al. Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial. J Card Fail. 2020;26(5):429-437. PMID: 32068002.
  16. Karaa A, Bertini E, Carelli V, et al. Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial. Neurology. 2023;101(3):e238-e252. PMID: 37268435.
  17. Roshanravan B, Liu SZ, Ali AS, et al. In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial. PLoS One. 2021;16(7):e0253849. PMID: 34264994.
  18. Thompson WR, Manuel R, Abbruscato A, et al. Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER. Genet Med. 2024;26(7):101138. PMID: 38602181.
  19. Shirley M. Elamipretide: First Approval. Drugs. 2026;86(3):377-383. PMID: 41335372.
  20. Bassett DR Jr, Howley ET. Limiting factors for maximum oxygen uptake and determinants of endurance performance. Med Sci Sports Exerc. 2000;32(1):70-84. PMID: 10647532.
  21. Janssens GE, Grevendonk L, Perez RZ, et al. Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nat Aging. 2022;2(3):254-263. PMID: 37118369.
  22. Trętowicz MM, Scantlebery AML, Schomakers BV, et al. Human whole-blood NAD+ levels do not vary with age or lifestyle interventions. Nat Metab. 2026;8(6):1282-1290. PMID: 42135539.
  23. Yi L, Maier AB, Tao R, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. Geroscience. 2023;45(1):29-43. PMID: 36482258.
  24. Stealth Biotherapeutics Inc. FORZINITY (elamipretide) injection, for subcutaneous use — US prescribing information. Initial U.S. approval 2025; accelerated approval September 19, 2025 (NDA 215244). DailyMed SPL set id 146bf34c-76f2-48db-ac07-fb29cce2cd75. Read October 3, 2026.
  25. FDA. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the FD&C Act (503A categories list), versions updated April 15, April 22 and May 14, 2026. fda.gov/media/94155/download. Read October 3, 2026. (Notice that 12 peptides would leave Category 2 because their nominations were withdrawn; their removal; GHK-Cu, except injectable, back in Category 1.)

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Checked 13 Oct 2026