Skip to content
PeptideAI
Animal data onlyfat lossmuscle growthenergylongevity

5-Amino-1MQ

A small-molecule NNMT inhibitor that raises intracellular NAD+ in fat cells and pushes them toward burning energy rather than storing it - popular precisely because it is an oral capsule.

Also known as 5A1MQ, 5-amino-1-methylquinolinium, NNMT inhibitor

Animal data only — Rodent or other animal studies. Dose translation to humans is genuinely uncertain.

The NNMT-obesity link is well documented and the mouse data are genuinely interesting - subcutaneous 5-amino-1MQ reduced adiposity in diet-induced obese mice without reducing food intake, with no adverse effects up to 60 mg/kg/day. But no human trial of any kind has been published, so effective human dosing, oral bioavailability and long-term safety are all unknown.

How it works

Nicotinamide N-methyltransferase methylates nicotinamide into 1-methylnicotinamide, consuming S-adenosylmethionine and diverting nicotinamide away from the NAD+ salvage pathway. NNMT is heavily overexpressed in the white adipose tissue of obese animals and humans. 5-Amino-1MQ is a substrate-site inhibitor with an IC50 around 1.2 micromolar; blocking the enzyme raises intracellular NAD+ and SAM in adipocytes, which increases sirtuin activity and lipolytic gene expression and shrinks fat cell size in diet-induced obese mice without changing food intake. Separate rodent work suggests NNMT inhibition also helps muscle regeneration after injury and improves the function of aged muscle stem cells, which is where the muscle claims come from. All of this is mouse data.

Targets: Nicotinamide N-methyltransferase (NNMT), NAD+ salvage pathway, S-adenosylmethionine pool, Sirtuins (indirectly)

Dosing

ProtocolDoseFrequencyRoute
Common oral protocolUsually morning, with or without food.50 mg – 150 mgonce dailyoral
Subcutaneous protocolMorning.10 mg – 50 mgonce dailysubcutaneous
  • · 50-150 mg per day (shown here as 50,000-150,000 mcg). Most people run 50 mg and increase only if nothing is happening. These are market conventions, not trial-derived doses.
  • · Less common than oral and offers no clear advantage given the compound is orally bioavailable. Rodent efficacy studies used 20 mg/kg/day subcutaneously, which does not translate directly to a human dose.

Titration

Start at 50 mg daily for two weeks before considering an increase.

Cycling

Typically run 8-12 weeks then taken off for a similar period. The rationale is caution about chronic methylation-pathway interference rather than any documented tolerance.

Work out your exact syringe units →

Pharmacology

Half-life
Not characterised in humans. It is orally bioavailable and dosed once daily in practice, which implies at least several hours.
Onset
Anecdotal reports describe appetite and energy changes within 1-2 weeks; any body composition change would take 8-12 weeks.
Routes
oral, subcutaneous
Molecule
Small-molecule quinolinium NNMT inhibitor (not a peptide)
Molecular weight
159.2 Da

Handling

Diluent
Bacteriostatic water (only if using an injectable vial)
Typical mix
1 or 2 mL
Vial sizes
50 mg
Lyophilised
Room temperature is acceptable for capsules; a cool dry place away from humidity.
Reconstituted
Refrigerated and used within about 30 days if using an injectable preparation.

Mixing

The oral capsule form needs no preparation and is how most people take it.

Side effects

  • commonNausea or mild GI upset— Usually settles or resolves by taking it with food.
  • commonHeadache
  • uncommonInsomnia or restlessness— More often reported with evening dosing.
  • uncommonFlushing
  • uncommonUnknown effects of chronic methylation-pathway inhibition— NNMT sits at the junction of NAD+ and methyl-group metabolism. Nobody has studied what blocking it for months does in humans.

Do not use if

  • Pregnancy and breastfeeding - no data at all.
  • Known methylation disorders or ongoing high-dose methyl-donor therapy, where interfering with SAM consumption is unpredictable.
  • Active malignancy - NNMT expression is altered in several cancers and the direction of effect is not consistent.

Combining it

  • synergynad — Both aim at raising cellular NAD+, from opposite directions - one supplies substrate, the other stops it being wasted.
  • synergysemaglutide — Commonly stacked in fat-loss protocols; no interaction data exist, and the combination is anecdotal.
  • synergymots-c — Frequently paired for metabolic effect; the rationale is mechanistic overlap, not evidence.

What to monitor

  • · Body composition by DEXA or consistent tape and scale measurements - this is a slow, modest-effect compound and subjective impressions are unreliable.
  • · Fasting glucose and a lipid panel if used for more than a couple of months.
  • · Liver function, since there is no human safety dataset.

Legal status

Not an approved drug. Sold as a research chemical and, increasingly, as a dietary-supplement-style capsule, which is a regulatory grey area rather than an endorsement.

References

  • Neelakantan et al. 2018, Biochemical Pharmacology - small-molecule NNMT inhibitor reduces adiposity in diet-induced obese mice (preclinical)
  • Preclinical studies of NNMT inhibition in muscle regeneration and aged muscle stem cell function (preclinical)
  • Reviews of NNMT in adipose tissue, NAD+ metabolism and metabolic disease (review)

Mechanism in depth

Nicotinamide N-methyltransferase takes nicotinamide and a methyl group from S-adenosylmethionine and produces 1-methylnicotinamide, which the cell then excretes. Two things are consumed in that reaction and both matter: nicotinamide, which would otherwise be salvaged back into NAD+ by NAMPT, and SAM, which is the cell's universal methyl donor. NNMT is expressed at high levels in adipose tissue and liver, and it is markedly upregulated in obesity, so in an obese adipocyte a substantial methyl and nicotinamide flux is being diverted into producing a molecule whose main job is to leave. Inhibit the enzyme and you get the results Neelakantan reported in cultured adipocytes: intracellular 1-methylnicotinamide falls, intracellular NAD+ rises, SAM rises, and lipogenesis is suppressed. The NAD+ rise is the interesting one because it feeds sirtuin activity, and SIRT1 and SIRT3 deacetylation of PGC-1alpha is a plausible route from a methyltransferase inhibitor to increased fat oxidation. In diet-induced obese mice, systemic administration of a potent NNMT inhibitor reduced body weight and white adipose mass, decreased adipocyte size and lowered plasma total cholesterol, with no change in food intake and no observable adverse effects. That last detail is the mechanistically important one - the weight loss was not appetite-mediated, which distinguishes it from essentially every effective obesity drug currently on the market. Sampson then showed that pairing NNMT inhibition with a reduced-calorie diet normalised body composition and enhanced the metabolic benefit beyond diet alone, which is the closest thing in the literature to the way people actually use it. All of this is mouse and cell work. There is no human trial of 5-amino-1MQ for anything.

What usually goes wrong

The evidential situation is the main thing to be honest about. Everything supporting 5-amino-1MQ is mouse and cell-culture work from essentially one research group and its collaborators, and there is no human trial, no human pharmacokinetics, no toxicology and no dose-response. The 50-150 mg oral doses in circulation were not derived from anything; the mouse studies used weight-based systemic dosing and nobody has published an allometric scaling for the human dose. Second, the SAM angle deserves more attention than it gets: inhibiting an enzyme that consumes SAM raises SAM, and SAM sits at the centre of the methionine cycle and of DNA and histone methylation. The chronic consequences of pushing that up in a healthy adult are unstudied in either direction. Third, NNMT expression is elevated in several cancers and has been reported to influence tumour metabolism, and the direction of that effect is not consistent across tumour types - which is a genuine unknown rather than a reflexive caution. Fourth, product identity: this is a cheap small molecule with no analytical standard in common use, and there is no published survey of what is in the capsules being sold.

Titration ladder

  1. 50 mgWeeks 1-2 — 50 mg daily, orally. This is the low end of the vendor range and there is no toxicology behind any of it, so starting at the bottom is the only defensible approach.
  2. 100 mgWeeks 3-6 — 100 mg daily. Liver enzymes checked before going higher.
  3. 150 mgWeek 7 onward — 150 mg daily is the top of the commonly used range. Nothing supports going beyond it and no human dose-response study exists at any dose.

Bloodwork worth running

MarkerWhenWhy it matters
Total cholesterol and full lipid panelBaseline and at eight to twelve weeks.Reduced plasma total cholesterol was one of the specific findings in the diet-induced obese mouse work, so it is the marker with the most direct preclinical support. It is also cheap and routine.Act if: No movement in lipids alongside no movement in body composition at twelve weeks means the compound is doing nothing for you.
Fasting glucose, insulin and calculated HOMA-IRBaseline and at twelve weeks.The whole mechanistic proposition is improved adipocyte metabolism and NAD+ availability. Insulin sensitivity is where that should show up, and HOMA-IR is more sensitive to it than glucose alone.Act if: A rising HOMA-IR on treatment is a reason to stop rather than to continue hopefully.
Liver enzymes - ALT, AST, GGTBaseline, at four weeks, then every twelve weeks.NNMT is expressed at high levels in liver, and the compound is being taken orally at doses of 50-150 mg daily by people with no toxicology data whatsoever. Liver is the tissue that would tell you first.Act if: Any transaminase rise above twice the upper reference limit means stop.
HomocysteineBaseline and at twelve weeks.This is the mechanistically specific one nobody checks. NNMT consumes SAM, so inhibiting it raises SAM, and SAM is a regulator of the methionine cycle - it activates cystathionine beta-synthase and inhibits MTHFR. Perturbing that cycle can move homocysteine, and homocysteine is a cardiovascular risk marker.Act if: A homocysteine above roughly 15 micromol/L that was normal at baseline is a genuine reason to stop and investigate.
DXA or at minimum consistent circumference and photographic trackingBaseline and at twelve weeks.The mouse effect was reduced white adipose mass and smaller adipocytes with no change in food intake. If that translates at all it will show as fat loss without appetite suppression, and scale weight alone will not distinguish it from anything else.Act if: No change in fat mass at twelve weeks means stop paying for it.

Pharmacokinetics

Metabolism
Not characterised. As a quaternary methylquinolinium it is not an obvious CYP substrate.
Elimination
Presumed renal. Not measured.

Receptor targets

  • Nicotinamide N-methyltransferase (NNMT) — Potency figures for the methylquinolinium series are reported in the low micromolar range in the primary literature; no single authoritative IC50 for 5-amino-1MQ was resolved in this session

    Competitive inhibition at the nicotinamide site. Reduces 1-methylnicotinamide production, raises intracellular NAD+ and SAM, suppresses lipogenesis in adipocytes.

  • Other SAM-dependent methyltransferases — Selective against them - Neelakantan tested structurally related methyltransferases and found the methylquinolinium analogues did not inhibit them

    None, which is the safety argument for the scaffold. Broad methyltransferase inhibition would be a serious problem.

  • NAD+ salvage pathway enzymes (NAMPT and related) — Not inhibited

    None directly. NAD+ rises because nicotinamide is spared for salvage, not because the salvage enzymes are stimulated.

What to expect, and when

Nothing acute or perceptible. In the mouse work the meaningful readouts - adipose mass, adipocyte size, plasma cholesterol - were measured over weeks of dosing. If you are going to try it, give it twelve weeks with a fixed diet and fixed training and measure body composition properly at both ends, because anything shorter or less controlled will tell you nothing.

Stacking and comparisons

The pairing with the best preclinical support is with a calorie deficit, which sounds trivial and is not - Sampson tested NNMT inhibition plus reduced-calorie diet specifically and found the combination normalised body composition where either alone did not. If you are running 5-amino-1MQ without a deficit you are testing a hypothesis nobody has tested. The stack that circulates alongside it is with NAD+ precursors, NMN or nicotinamide riboside, and the mechanistic logic is genuinely coherent: NNMT inhibition spares nicotinamide for salvage, precursors supply more substrate to the same pathway, and both converge on raising cellular NAD+. Nobody has tested it, but the reasoning is sound. Do not stack it with high-dose plain nicotinamide, which is the NNMT substrate - you would be loading substrate onto an inhibited enzyme, and high-dose nicotinamide has its own methyl-consumption problems. With GLP-1 agonists there is a real complementarity worth naming: the incretin suppresses appetite, and the mouse NNMT data showed fat loss without any change in food intake, so the mechanisms genuinely do not overlap.

Against SLU-PP-332, the other small-molecule metabolic compound in this class, the evidence bases are similar in quality - rodent and cell work only - but SLU-PP-332's is broader, spanning exercise capacity, metabolic syndrome, heart failure and kidney ageing across several independent groups. Against AICAR, which has been studied in humans for cardiac indications and therefore has some human safety exposure, 5-amino-1MQ has none at all. Against GLP-1 agonists, the comparison is not close on evidence and is interesting on mechanism: the incretins have phase 3 data and work through appetite, while NNMT inhibition produced weight loss in mice with no change in food intake, which if it translated would be a genuinely different kind of drug. It has not been shown to translate. Against the myostatin-pathway biologics in this class, 5-amino-1MQ is targeting fat rather than muscle and belongs in a different conversation.

Rough cost

$40–$120/month. Sold as capsules, typically 30-60 USD for a month at 50 mg daily and proportionally more at higher doses. It is one of the cheaper compounds in this class, which is part of why it spread so fast.

Genuinely uncertain

  • No human pharmacokinetic, safety or efficacy data exist for 5-amino-1MQ. Not a single human trial.
  • The 50-150 mg oral doses in circulation have no published derivation from the animal work.
  • No authoritative IC50 for 5-amino-1MQ against human NNMT was resolved in this session; the literature reports potency for the methylquinolinium series rather than a single canonical figure for this analogue.
  • Oral bioavailability has not been measured. The available data are cell permeability assays, which do not establish it.
  • The consequences of chronically raising intracellular SAM in a healthy adult are unstudied, including effects on the methionine cycle, homocysteine and epigenetic methylation.
  • NNMT is dysregulated in several cancers with inconsistent directionality, and what chronic inhibition does in that context is unknown.
  • Blood-brain barrier penetration is unknown; a permanently charged quaternary cation would not normally cross well, but this has not been tested.
  • There is no published analysis of what is actually in commercially sold 5-amino-1MQ capsules.

Papers