Metabolic Reset across Europe

This set pairs our MOTS-C 32 pen with our NAD+ 1000 pen. Both get called “mitochondrial”, and that shared adjective is why they are grouped, but the word is doing two different jobs: MOTS-c is a peptide that mitochondria themselves encode, while NAD+ is a coenzyme that mitochondria, and every other part of the cell, use.

Two meanings of “mitochondrial”

MOTS-c is a 16-amino-acid peptide encoded by a short open reading frame inside the mitochondrial 12S ribosomal RNA gene. Almost every peptide in our catalogue is encoded in nuclear DNA; MOTS-c is not, and that is why the 2015 paper describing it drew attention — it suggested mitochondria act as a signalling origin, not only as the cell’s power supply (Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 2015. PMID 25738459).

NAD+ (nicotinamide adenine dinucleotide) is not a peptide at all. It is a coenzyme that carries electrons in redox reactions, including the ones inside mitochondria that produce ATP. It does not bind a receptor and issue an instruction. One is a signal; the other is a piece of cellular machinery. The two molecules are set out side by side at mitochondrial peptides and compared directly at MOTS-c vs NAD+.

	MOTS-C 32	NAD+ 1000
What it is	16-amino-acid peptide, mitochondrially encoded	Coenzyme, not a peptide
Described role	Signal: AMPK activation via the folate–AICAR route	Substrate: electron carrier in redox reactions
Human trial evidence	None published	Mostly on the oral precursors NMN and NR

What the MOTS-c literature shows

The reported mechanism runs through skeletal muscle. MOTS-c inhibits the folate cycle and the de novo purine synthesis tethered to it, driving a more than twenty-fold rise in endogenous AICAR, which activates AMPK, a central metabolic sensor. In mice, treatment prevented age-dependent and high-fat-diet-induced insulin resistance and prevented diet-induced obesity (Lee et al., above; Wan W et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. J Transl Med 2023. PMID 36670507).

Every one of those results comes from cell culture or rodent models. No human efficacy trial of MOTS-c has been published, so there is no established human dose, no human safety dataset and no clinical outcome data. That is the most important fact about the MOTS-C 32 pen, and what is MOTS-c says it the same way.

What the NAD+ literature shows

NAD+ has a real human trial literature, but most of it concerns the oral precursors NMN and nicotinamide riboside rather than NAD+ itself, because NAD+ is comparatively large and poorly absorbed by mouth. Those trials are clear on one point: the precursors raise cellular NAD+ in a dose-dependent way, and long-term nicotinamide riboside was studied for safety in a randomised, placebo-controlled trial (Conze D et al. Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Sci Rep 2019. PMID 31278280; Dellinger RW et al. Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis 2017. PMID 29184669).

They are equivocal on the next point. A meta-analysis of randomised NMN trials found no significant effect on fasting glucose, fasting insulin, glycated haemoglobin or lipids across 250–2,000 mg/day (Chen F et al. Effects of nicotinamide mononucleotide on glucose and lipid metabolism in adults: systematic review and meta-analysis. Curr Diab Rep 2024. PMID 39531138), while a dose-ranging NMN trial in healthy middle-aged adults reported gains on physical-performance measures, six-minute walk distance among them (Yi L et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults. Geroscience 2023. PMID 36482258). The level rises reliably; the downstream endpoints do not follow it. Human data on injected NAD+ itself, the form in the NAD+ 1000 pen, is thinner still (what is NAD+).

Why they are grouped, and where the evidence stops

The grouping is mechanistic. AMPK activation (the MOTS-c story) and NAD+ availability (the coenzyme story) are both threads in how cells sense and respond to energy status, and the two are the pair most often filed together under energy and longevity. Buying them together is buying the two “mitochondrial” entries in our catalogue in one order. The word “reset” in the name is ours as well, like the pairing itself: nothing in either literature describes a metabolic state being reset, and we use it as a label for the pairing, not as a description of an effect.

What the grouping is not is a tested combination. No published trial has administered MOTS-c and NAD+ together, in humans or in animals, and measured anything. There is no interaction data, no additive-effect data and no safety data for the pair. Each pen is the same product sold on its own page; we do not tell you how to combine or sequence them.

Who typically chooses this set

You are usually looking at the energy or longevity goal, have read both product pages, and want both mitochondrial-story molecules rather than one. If your interest is weight rather than metabolic signalling, the Advanced Lean Stack pairs NAD+ with retatrutide, a compound that does have a published human phase 2 trial (Jastreboff AM, Kaplan LM, Frías JP et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med 2023. PMID 37366315).

Neither MOTS-c nor NAD+ holds a marketing authorisation as a medicine for this use; the oral NAD+ precursors are generally sold as food supplements. What we can stand behind is the contents of each pen: an independent laboratory tests every batch for identity, purity and sterility, and your lot’s certificate is reachable from the pen’s QR code or from the certificate index.