5-Amino-1MQ

What it is

Most of the substances discussed in this corner are peptides and have to be injected. 5-Amino-1MQ is something else: a small molecule from chemistry that crosses the cell membrane by itself and, in animal experiments, reaches the bloodstream after being swallowed. In rats, oral bioavailability was 38.4 percent, and the half-life after administration into the stomach was 6.90 hours compared with 3.80 hours after injection.

It was developed as a tool of pharmaceutical research: a research group was looking for inhibitors of the enzyme NNMT and worked through an entire series of substances, from which 5-Amino-1MQ emerged.

The enzyme and the two levers

NNMT stands for nicotinamide N-methyltransferase. At its core, the enzyme does one thing: it attaches a methyl group to nicotinamide, a building block of NAD+. This takes the building block out of the NAD+ cycle. NAD+, in turn, is involved in energy production and repair in every cell and declines with age.

The methyl group comes from SAM, the body’s central methyl currency. If NNMT is inhibited, both stay in the system: the building block for NAD+ and the methyl group. In cell experiments on fat cells, NAD+ and SAM then rose, and the formation of new fat decreased.

The difference from NMN or NR lies in the direction: they fill the tank; by this logic, 5-Amino-1MQ seals a leak. A combination is discussed in the scene, but it has not been tested.

The fat finding

The starting point of the field is a 2014 paper in Nature. It showed that NNMT is produced in increased amounts in the white adipose tissue and liver of obese and diabetic mice, and that turning the enzyme down in these tissues protected the animals from diet-induced obesity. The authors attribute this to an increased energy expenditure of the cells, mediated via SAM, NAD+ and polyamine metabolism.

Four years later came the step to an active substance. Obese mice received the inhibitor for 11 days and lost 2.0 grams, around 5.1 percent of their starting weight, while the control animals gained 0.6 grams. Abdominal fat decreased by about 35 percent, the fat cells became more than 30 percent smaller, and total blood cholesterol fell.

The interesting part is feeding behavior: it remained unchanged, 28.1 versus 26.2 grams of food. So the weight loss did not run through appetite, and in this the concept differs from the GLP-1 injections. Energy expenditure, however, was not measured here; the conclusion about it rests on the 2014 paper.

Muscle and age

The second finding concerns the muscles of old animals. Mice aged 24 months received the NNMT inhibitor after a muscle injury. The muscle stem cells divided more often again, the fiber cross-sections were almost twice as large as in the control group, and the peak force of the treated muscle was around 70 percent higher.

A 2024 paper then compared the active substance and training directly. Old mice that received only the inhibitor had around 40 percent more grip strength than untreated animals; the trained animals were at 20 percent. Both together resulted in around 60 percent. The effects thus added up rather than replacing each other.

The statement better than training therefore applies to aged mice in a laboratory experiment, and grip strength in animals is not everyday strength in humans. What remains interesting is that the combination was better than either part alone.

Why the target appeals to researchers

NNMT sits at a crossroads: it is linked to the NAD+ cycle and to methylation, two of the most discussed adjusting screws of aging. That is why several groups are working on inhibitors; another series of substances was presented in 2022 that improved insulin action in obese diabetic mice.

The same property is the reason for caution: NNMT is more active in many tumors. A central switch rarely acts at only one point, and nobody has studied what permanent inhibition means in humans.

What users report

In user circles the substance is described as a capsule and as well tolerated, with mild nausea as the most common side effect. A cycling pattern with breaks, adopted from peptide practice, is also reported. Such reports are observations without a comparison group and without laboratory testing of the product.

What the studies show

Kraus et al., Nature 2014

Mice in which NNMT was specifically downregulated in white adipose tissue and liver were protected against diet-induced obesity. NAD+ and SAM in adipose tissue, enzymes of polyamine metabolism, histone methylation and the oxygen consumption of the fat cells were measured. The paper establishes the target, but uses a genetic intervention, not an active substance.

Neelakantan et al., Biochemical Pharmacology 2018

Obese mice, 9 animals per group, 11 days of treatment with 5-Amino-1MQ versus saline. The treated animals lost 2.0 grams, the controls gained 0.6 grams; abdominal fat fell by about 35 percent, fat cell size by more than 30 percent, and plasma cholesterol dropped. The same amount of food was eaten. The primary study was an animal experiment with body composition as the endpoint, not a hard clinical measure.

Neelakantan et al., Biochemical Pharmacology 2019

Muscle injury in 24-month-old mice, followed by 1 to 3 weeks of treatment. The muscle stem cells divided more often, the fiber cross-sections were almost twice as large as in the controls, and the peak force of the muscle was around 70 percent higher. A regeneration model, not an everyday-strength endpoint.

Dimet-Wiley et al., Scientific Reports 2024

Old mice received the inhibitor, intensive training or both from month 22 to 24. Grip strength was around 40 percent above the sedentary control group with the active substance alone, 20 percent with training alone and around 60 percent with the combination. Muscle proteome and metabolites were also analyzed.

Where the data stop

There is no published study in humans, neither on efficacy nor on tolerability, and no ongoing clinical trial on 5-Amino-1MQ or on any other NNMT inhibitor can be found in the public trial registries. This removes any basis for statements such as so many kilos in so many weeks. The pharmacokinetics also come from rats; residence time and absorption in humans are unknown. Energy expenditure was not measured in the active-substance study, only the unchanged feeding behavior, which is why the mechanism of fat loss is inferred from the 2014 genetic study. Nothing exists on long-term safety, and because NNMT is more active in many tumors and is involved in several basic functions, that would be exactly the question a clinical trial would have to answer.

Status, approval and legal

5-Amino-1MQ is not an approved medicine and not an approved dietary supplement in Germany and the EU. It is sold as a research chemical, explicitly not for human use, and this label shifts responsibility to the buyer. What is in the vial or capsule is not manufactured to pharmaceutical standards, and two suppliers can deliver two different products. For competitive sport: a substance without approval falls under group S0 of the World Anti-Doping Agency and is therefore prohibited at all times, regardless of whether it enhances performance.

Safety

There is no safety profile in humans. In the animal studies, nothing conspicuous was observed at the amounts tested; one series of substances was additionally tested against a broad safety panel and was inactive there; that is a statement about animals and cells, not about humans. Users most often report mild gastrointestinal complaints. The weightiest point is the target itself: NNMT is more active in many tumors and intervenes in NAD+ metabolism and methylation, two systems that work everywhere in the body. What weeks of inhibition do in humans, for harm or for good, is open. Added to this is the product risk: with research chemicals, purity, content and admixtures are unverified. Anyone who wants to treat overweight, diabetes or muscle weakness has tested options, and those belong in the hands of a physician.

Sources

• Kraus et al., Nature 2014 — NNMT knockdown protects against diet-induced obesity
• Neelakantan et al., Biochemical Pharmacology 2018 — selective, membrane-permeable NNMT inhibitors reverse obesity in mice
• Neelakantan et al., Biochemical Pharmacology 2019 — NNMT inhibitor activates muscle stem cells of old mice
• Dimet-Wiley et al., Scientific Reports 2024 — NNMT inhibition and training in old mice
• Babula et al., Diabetes, Obesity and Metabolism 2024 — 28 days of 5A1MQ in obese mice, glucose tolerance and liver
• Awosemo et al., Journal of Pharmaceutical and Biomedical Analysis 2021 — pharmacokinetics and oral bioavailability of 5-Amino-1MQ in rats
• Ruf et al., Scientific Reports 2022 — another NNMT inhibitor series, insulin sensitivity in a mouse model
• Kannt et al., Molecules 2021 — NNMT as a target in metabolic diseases, expression in tumor cell lines
• ClinicalTrials.gov — search for 5-Amino-1MQ and NNMT inhibitors without a registered study