5-Amino-1MQ (oral)

5-Amino-1MQ is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the methyltransferase that clears nicotinamide. It is not a peptide; its small-molecule character is what confers oral stability and allows enteral administration. This entry covers the oral route.

It was developed at the University of Texas Medical Branch as an approach to obesity and metabolic dysfunction. In diet-induced obese mice, treatment produced substantial adipose loss with no change in food intake, the effect arising entirely from increased cellular energy expenditure — mechanistically distinct from incretin agonists such as semaglutide or retatrutide, which act principally through appetite suppression.

Mechanism: NNMT inhibition, removing the catabolic drain on nicotinamide in adipocytes; consequent elevation of intracellular NAD+ and SAM; SIRT1 activation; suppressed lipogenesis; and improved mitochondrial function and thermogenesis. CD38 inhibition has additionally been attributed to the compound under the NAD+ preservation heading.

Pharmacokinetics: Awosemo et al. (2021) established 38.4% oral bioavailability in rats with a terminal half-life of 6.90 hours.

Regulatory and evidential status: research compound, not FDA-approved, no published human clinical trials. All efficacy data derive from preclinical animal models and in vitro work, and long-term human safety data do not exist.

Route comparison: oral and subcutaneous dosing sit in the same 50 to 100 mg daily range, since subcutaneous administration bypasses first-pass losses and can therefore sit slightly lower for equivalent exposure. The site's separate injectable entry lists a 1 to 5 mg daily subcutaneous scale, so quoted figures for the injectable route are not consistent.

NAD+ functions as the electron carrier feeding the electron transport chain; reduction to NADH, subsequent re-oxidation, and continuous cycling underpin mitochondrial ATP synthesis. Roughly 80% of NAD+ is generated through the salvage pathway, in which nicotinamide is recycled to NAD+ by NAMPT.

NNMT competes for that same substrate, methylating nicotinamide to 1-methylnicotinamide (1-MNA) for excretion. It is a physiological clearance enzyme for excess vitamin B3, not a pathological entity. Hepatic tissue, where NNMT is strongly expressed, tolerates this because multiple NAD+ biosynthetic routes are available. Adipose tissue does not: adipocyte NAD+ synthesis relies primarily on the salvage pathway, and NNMT is the only catabolic enzyme for nicotinamide in fat.

Obesity drives NNMT overexpression in white adipose tissue, creating a drain on the single available NAD+ route. Kraus et al. (2014) identified NNMT as the most strongly reciprocally regulated gene in white adipose tissue in metabolic dysfunction models, with elevated expression in adipose and liver of obese and diabetic mice. The result is a self-reinforcing cycle: adiposity raises NNMT, NNMT depletes adipocyte NAD+, depleted NAD+ impairs oxidation and favours storage, and storage raises NNMT further.

5-Amino-1MQ inhibits NNMT, reducing 1-MNA generation and redirecting nicotinamide flux towards NAD+. Downstream consequences reported: increased intracellular NAD+ and SAM, SIRT1 activation, suppressed lipogenesis, reduced adipocyte size, and increased energy expenditure with no change in food intake. CD38 inhibition has also been attributed to the compound as a further NAD+-preserving route, and mitochondrial optimisation with thermogenesis and lipid oxidation is described.

A relevant kinetic caveat: NAMPT has 430 times higher affinity for nicotinamide than NNMT does, so under normal conditions nicotinamide preferentially flows towards NAD+ synthesis regardless. NNMT becomes a meaningful drain only when massively overexpressed, which is why the mechanism is adipose- and obesity-specific rather than a general NAD+ strategy.

Adipose: the primary effect. Neelakantan et al. (2018) reported approximately 35% reduction in white adipose tissue mass and 30% decrease in adipocyte size in diet-induced obese mice, with unchanged food intake and lowered plasma total cholesterol. Inhibition of adipocyte growth and reduction of existing fat deposits are described alongside suppressed lipogenesis.

Lean tissue: NNMT inhibition appears to preserve lean mass during fat loss, attributed to raised NAD+ and SIRT1 activation supporting protein retention and limiting catabolism — a contrast with caloric restriction alone.

Glycaemic: improved oral glucose tolerance and insulin sensitivity in animal models, with suppression of hyperinsulinaemia (Babula et al., 2024).

Hepatic: the same study reported improved liver pathology markers in obese mice, including fatty liver changes accompanying obesity.

Skeletal muscle regeneration: Neelakantan et al. (2019) found activation of senescent muscle stem cells in aged mice and improved regenerative capacity of aged skeletal muscle, with peak torque increased by approximately 70% versus controls — the first demonstration that NNMT inhibition rescues age-related muscle stem cell deficits.

Microbiome and diet interaction: Dimet-Wiley et al. (2022) combined treatment with a high-fat to low-fat diet switch and obtained body weight and fat mass indistinguishable from never-obese controls, which diet switch alone did not achieve, alongside increased Lactobacillus and decreased Erysipelatoclostridium.

NAD+ and longevity: age-related NAD+ decline is the longevity rationale, with CD38 inhibition cited as an additional NAD+-preserving route and possible contribution to mitochondrial biogenesis.

Neurological and performance: possible neuroprotection against age-related neurodegeneration via improved mitochondrial health and NAD+ availability, improved cerebral energy metabolism supporting cognition and reduced mental fatigue, and improved endurance and exercise capacity through enhanced mitochondrial activity and fat oxidation. Possible reduction in inflammation and oxidative stress is also described.

Appetite: no appetite suppression. Food intake was unaffected across the animal work, and users consistently note unchanged appetite. Earlier guidance on this page treated fasted administration as giving better appetite suppression; that is not supported by the mechanism or the preclinical data.

Patient selection dominates the expected response. NNMT overexpression correlates with adiposity rather than age (Kraus et al., 2014). The preclinical effect sizes came from diet-induced obese animals with already-elevated adipose NNMT, where inhibition corrected an existing dysfunction. In lean, metabolically healthy individuals, adipose NNMT sits at baseline and there is no pathological drain on the salvage pathway to relieve.

No human clinical data on timelines exist. The following is inferred from mechanism and from user reports, which do not carry the weight of published research.

Subtle increases in thermogenesis and baseline energy are commonly reported within the first 1 to 2 weeks, sometimes described as feeling slightly warmer or mildly more wakeful. Measurable fat loss, where it occurs, appears around weeks 3 to 4. At effective doses of 50 to 100 mg daily, users report modest but measurable loss over 4 to 6 week cycles, typically 3 to 6 pounds with diet and training held constant. The trajectory is gradual; the compound shifts energy expenditure at the cellular level and that takes time to register on body composition.

Appetite is unaffected, and users report this consistently — a direct confirmation of the mechanism and a point of contrast with incretin agonists. Reports from those co-administering retatrutide or tirzepatide suggest accelerated results, though the contribution cannot be isolated. Feedback from lean users has been markedly weaker, consistent with the selection logic above.

Microdose protocols of 150 to 600 mcg daily generate minimal to no reported effect. Any subjective improvement at that level is difficult to separate from placebo given the dose sits roughly 400 times below the IC50 threshold.

Practical oral protocol: 50 to 100 mg daily, morning only, initiating at 50 mg for the first week and escalating to 100 mg if tolerated. Oral bioavailability is approximately 38%. Morning-only administration is not arbitrary — increased cellular energy expenditure and raised NAD+ carry a stimulatory quality, and afternoon or evening dosing is the common cause of reported sleep disturbance. Fasting is not required.

Cycling: 4 to 6 weeks on, 2 to 4 weeks off, 2 to 3 cycles total with reassessment after each. Falling body fat reduces adipose NNMT overexpression, so successive cycles deliver diminishing returns; continuous inhibition may also provoke adaptive responses that erode effect.

Capsule strength is commonly 50 mg, mapping to one or two capsules daily. Earlier guidance on this page ran a three-tier ladder of 50, 100, and 150 mg, the upper two split across the day with the last dose by mid-afternoon; the current protocol consolidates dosing into the morning and caps at 100 mg.

Dose rationale. Published recommendations span 150 to 600 mcg daily (microdosing) to 50 to 150 mg daily — a 2,500-fold range. Meaningful pharmacology requires plasma concentrations sufficient to inhibit at least 50% of the target enzyme (IC50 coverage). Pharmacokinetic analysis using metformin as a structural analogue, matched on molecular weight, charge, oral bioavailability, and half-life, places 50% NNMT inhibition at roughly 50 to 100 mg daily and near-complete inhibition at 400 to 600 mg daily. Allometric scaling of the Neelakantan et al. (2018) mouse dose translates to approximately 400 mg daily in humans. Microdoses of 150 to 600 mcg sit roughly 400 times below the 50% inhibition threshold, and the lowest concentration producing any NAD+ increase in research was about 1,000 times higher than microdoses achieve.

A second argument against microdosing is substrate kinetics: NAMPT has 430 times higher affinity for nicotinamide than NNMT, so flux already favours NAD+ synthesis unless NNMT is massively overexpressed. Where NAD+ support is the actual goal, a direct precursor such as NMN or injectable NAD+ is the more coherent choice than a sub-threshold enzyme inhibitor.

The persistence of microdose protocols is economic: a 10 mg vial lasts about 66 days at 150 mcg daily and 2 days at 5 mg daily, so the effective dose is seldom tested outside funded trials.

Route note: subcutaneous dosing is given in the same 50 to 100 mg daily range, morning only, and can sit slightly lower than oral for similar or better results since it bypasses digestion. The site's injectable entry lists a 1 to 5 mg daily scale, so figures for that route differ.

No published human dose-finding studies exist; these protocols are extrapolated from animal data, pharmacokinetic modelling, and clinical practice patterns.

Strong preclinical dataset, zero human clinical evidence. 5-Amino-1MQ is an unapproved research compound developed at the University of Texas Medical Branch; all efficacy data derives from animal models and in vitro work.

Neelakantan et al. (2018), Biochemical Pharmacology — the foundational paper. 5-Amino-1MQ reduced intracellular 1-MNA, raised intracellular NAD+ and SAM, and suppressed lipogenesis in adipocytes. In diet-induced obese mice it significantly reduced body weight, white adipose mass, and adipocyte size, and lowered plasma total cholesterol, with no change in food intake and no observable adverse effects. Allometric translation of the dose used gives roughly 400 mg per day for a human.

Kraus et al. (2014), Nature — the biological foundation. NNMT is the most strongly reciprocally regulated gene in white adipose tissue in metabolic dysfunction models; knockdown prevented diet-induced obesity and improved insulin resistance, and NNMT expression was elevated in white adipose tissue and liver of obese and diabetic mice. This is the source of the claim that NNMT overexpression tracks adiposity rather than ageing.

Neelakantan et al. (2019), Biochemical Pharmacology — first demonstration that NNMT inhibition rescues age-related muscle stem cell deficits. Senescent muscle stem cells were activated and regenerative capacity of aged skeletal muscle improved, with peak torque up approximately 70% versus controls.

Dimet-Wiley et al. (2022), Scientific Reports — 5-Amino-1MQ plus a high-fat to low-fat diet switch normalised body weight and fat mass in obese mice to levels indistinguishable from never-obese controls, which diet switch alone did not achieve, alongside a favourable microbiome shift (increased Lactobacillus, decreased Erysipelatoclostridium).

Babula et al. (2024), Diabetes, Obesity and Metabolism — pharmacokinetics and metabolic effects: dose-dependent limitation of body weight and fat mass gain, improved oral glucose tolerance and insulin sensitivity, suppressed hyperinsulinaemia, improved liver pathology markers.

Awosemo et al. (2021), Journal of Pharmaceutical and Biomedical Analysis — 38.4% oral bioavailability in rats with a terminal half-life of 6.90 hours.

Supporting mechanism literature: Pissios (2017) on NNMT beyond vitamin B3 clearance, and Revollo et al. (2007) on NAMPT as the systemic NAD biosynthetic enzyme — relevant because NAMPT has 430 times higher affinity for nicotinamide than NNMT, so nicotinamide preferentially flows to NAD+ synthesis unless NNMT is massively overexpressed.

Limitations: no published human dose-finding work; practical protocols rest on allometric scaling, pharmacokinetic modelling using metformin as a structural analogue, and clinical practice patterns. No long-term human safety data.