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Mitochondria

5-Amino + NAD+ (Oral)

Oral blend of an NNMT inhibitor plus an NAD+ precursor - both aim at the NAD+ and methylation metabolism. Evidence is preclinical.

4 min read 5 sources Titration Updated June 2026
Type
Oral blend (NNMT inhibitor + NAD+ precursor)
Target axis
NAD+ and methylation metabolism
Form
Tablets, 100 mg per tab, 60 tabs
Evidence
Preclinical (mouse), no human study on the blend

Getting started

Reported dosing (not established)

There is no clinically established human dose for this oral blend. The values listed here reflect common community use, not a validated study dose. The entire efficacy rationale comes from preclinical mouse data. Start low, observe, do not blindly titrate up.

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What is 5-Amino + NAD+ (Oral)?

This is an oral combination of two building blocks that both act on the same metabolic hub: the cell's NAD+ and methylation balance.

  • 5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of the enzyme nicotinamide N-methyltransferase (NNMT). The idea: less NNMT activity, more NAD+ and more methyl donor (SAM) inside the cell.
  • The NAD+ precursor supplies raw material the cell can build NAD+ from - NAD+ itself is poorly absorbed orally on its own, so research preparations work with precursors.

Both components come out of longevity and fat-loss research. Important up front: the entire rationale of this blend rests on preclinical mouse models. There is no human study on exactly this oral combination. We have separate entries for 5-Amino-1MQ and for NAD+ - look there for each component on its own. This information is for research and educational purposes only. No medical recommendations.

How it works

The mechanistic hook is the enzyme NNMT. NNMT consumes nicotinamide (vitamin B3, an NAD+ precursor) and a methyl donor (SAM) to make 1-methylnicotinamide. In the fat tissue and liver of obese mice, NNMT is upregulated.

  • Inhibiting NNMT means, preclinically: less nicotinamide gets "used up," more is left for NAD+ synthesis, and the methyl-donor pool rises. In mouse adipocytes, NNMT inhibitors raised intracellular NAD+ and SAM and dampened new fat formation (Neelakantan 2017).
  • Raising NAD+ is the second lever. NAD+ is a cofactor for energy metabolism and sirtuins. The NAD+ precursor in the blend supplies building material so the cell can refill its NAD+ pool - shown orally for nicotinamide riboside in humans (McDermott 2024).

The logic: both components push in the same direction (more NAD+), just via different levers. Whether that adds up in humans is open - it is a plausible hypothesis, not a proven synergy.

How to take it

Oral tablets, 100 mg per tablet. Common community use is 1 tablet daily, often in the morning.

  • Swallow with water, with or without food
  • Many report morning dosing, since the NAD+/energy focus fits the first half of the day
  • If your stomach is sensitive, start with half a tablet and step up over a few days

There is no established intake schedule from a study - this is experience-based, not a protocol.

Dosing

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What the research shows

The evidence is substantial - but almost entirely preclinical (mouse, cell culture). Keep that front of mind.

  • Foundation (Kraus 2014, Nature): knock down NNMT in mouse fat and liver and the animals are protected from diet-induced obesity - with higher energy expenditure and more NAD+ and SAM in tissue.
  • 5-Amino-1MQ scaffold (Neelakantan 2017): selective, membrane-permeable methylquinolinium-based NNMT inhibitors reversed obesity in high-fat-fed mice, lowering fat mass and cholesterol - without changing food intake and with no observable adverse effects in the study.
  • Muscle/aging (Neelakantan 2019, Dimet-Wiley 2024): in aged mice, NNMT inhibition activated quiescent muscle stem cells, improved muscle regeneration after injury and increased grip strength - partly additive to exercise.
  • NAD+ side in humans (McDermott 2024, NICE RCT): oral nicotinamide riboside raised NAD+ bioavailability in humans and improved walking distance in a randomized trial - proof that oral NAD+ precursors can actually lift the NAD+ pool.

The gap: there is no published human study on oral 5-Amino-1MQ and none on the exact blend. All fat-loss claims on the NNMT side come from mouse data.

Side effects

There is no systematic human safety dataset for 5-Amino-1MQ or this blend. What gets reported is anecdotal.

  • Occasional GI discomfort or mild nausea with oral intake - usually when ramping the dose too fast
  • Some report headaches or restlessness, often linked to the NAD+ component
  • NNMT is broadly active across the body (including liver, kidney, tumors) - the long-term consequences of chronic inhibition in humans are simply unknown

That is the honest crux: with a preclinical-only substance hitting such a central metabolic enzyme, the uncertainty is large. Think fail-closed: when in doubt, dose low and observe.

Practice

Practical framing if you work with the blend in a research context:

  • Get to know one component at a time - the standalone entries for 5-Amino-1MQ and NAD+ give you the per-component depth
  • Pick a consistent time of day (usually morning) so you can actually attribute any effects
  • Start low, change one variable, do not stack several preparations at once
  • Keep expectations realistic: this is longevity/metabolism research on a mouse foundation, not an established fat burner

If another preparation targets the same NAD+ pathway, you may be doubling up - keep that in view instead of blindly stacking.

Storage

Store tablets dry, cool and dark in a sealed container. Protect from moisture - oral active tablets otherwise draw water. Keep out of reach of children. No fridge needed as long as it stays dry and not too warm.

Evidence

Sources

  1. 1 Kraus et al. 2014, Nature - NNMT knockdown protects mice from diet-induced obesity, raises adipose NAD+ and SAM. Nature (PubMed, PMID 24717514)
  2. 2 Neelakantan et al. 2017, Biochem Pharmacol - selective, membrane-permeable NNMT inhibitors (methylquinolinium scaffold) reverse HFD obesity in mice without changing food intake. Biochemical Pharmacology (PubMed, PMID 29155147)
  3. 3 Neelakantan et al. 2019, Biochem Pharmacol - NNMT inhibitor activates senescent muscle stem cells and improves regeneration of aged muscle (mouse). Biochemical Pharmacology (PubMed, PMID 30753815)
  4. 4 Dimet-Wiley et al. 2024, Sci Rep - NNMT inhibition mimics and boosts exercise-mediated strength gains in aged mouse muscle. Scientific Reports (PubMed, PMID 38969654)
  5. 5 McDermott et al. 2024, Nat Commun (NICE RCT) - oral nicotinamide riboside raises human NAD+ bioavailability and improved walking distance in PAD. Nature Communications (PubMed, PMID 38871717)

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