NAD+ Precursors vs NAD+ Itself: NMN, NR and the IV Infusion Evidence

Three different things get sold under one name. NMN and NR are precursors, small molecules the body converts into NAD+. The third is the dinucleotide itself, the molecule found in vials and, since about 2018, in intravenous drips offered by private clinics. The trial record for each is very different, and this post sets it out.

The two precursors and how they differ

Nicotinamide riboside (NR) is a form of vitamin B3 found in trace amounts in milk. Nicotinamide mononucleotide (NMN) is one step further along the pathway: NR plus a phosphate group. Cells convert NR to NMN using the NRK enzymes, then NMN to NAD+.

Both became supplements because they are easier to handle than the final molecule, and because mouse studies from the Imai and Sinclair laboratories showed that feeding them restored tissue NAD+ in old animals. Human data arrived later and in much smaller quantities.

One complication came from the Mayo Clinic in 2016. Camacho-Pereira and colleagues found that CD38, the enzyme that rises with age and destroys NAD+, is also the main enzyme degrading NMN in vivo. The precursor is exposed to the same destruction as the product.

Martens 2018: the first chronic NR trial in people

Martens and colleagues at the University of Colorado Boulder published the first chronic dosing study of NR in Nature Communications in March 2018. It was a randomised, double-blind, placebo-controlled crossover trial in healthy men and postmenopausal women aged 55 to 79.

Thirty people were randomised and 24 completed both six-week arms. Participants received 1000mg of NR a day as Niagen, supplied by ChromaDex, or a matching placebo.

The compound was well tolerated and adherence was above 95%. The physiological results were exploratory: a trend towards lower blood pressure and lower aortic stiffness in people with raised baseline readings, and no change in exercise capacity. The authors called for larger trials aimed at blood pressure rather than claiming an effect.

Yoshino 2021: NMN and muscle insulin sensitivity

The best known NMN trial is from Washington University in St Louis. Yoshino, Baur, Imai and Klein's group published it in Science in April 2021 as a 10-week, randomised, placebo-controlled, double-blind study in postmenopausal women with prediabetes who were overweight or obese.

The dose was 250mg of NMN a day. The primary readout was insulin-stimulated glucose disposal measured by the hyperinsulinaemic-euglycaemic clamp, the reference method for insulin sensitivity.

Muscle insulin sensitivity rose by 25% in the NMN group and did not change on placebo. Muscle biopsies showed increased phosphorylation of AKT and mTOR and a shift in gene expression towards muscle remodelling. The authors compared the size of the effect to that seen after about 10% weight loss.

What the trial did not show matters too. There was no change in body weight, blood pressure, lipid profile or liver fat, and the registered trial covered a narrow population. Researchers wanting to follow up any of this in cell or animal models tend to work with the end product, which is why laboratories buy NAD+ in bulk rather than the precursor.

The FDA's 2022 ruling on NMN, and its 2025 reversal

In the United States, NMN was briefly removed from the supplement market by a regulatory technicality. On 4 November 2022, R. Philip Yeager of the FDA's Office of Dietary Supplement Programs signed a letter stating that NMN was excluded from the definition of a dietary supplement because it had been authorised for investigation as a new drug, and substantial clinical investigations had been made public.

The letter cited three registered trials of MIB-626, a pharmaceutical NMN from Metro International Biotech, in COVID-19 kidney injury, Alzheimer's disease and Friedreich's ataxia. Under US law, an ingredient that is first studied as a drug cannot later be marketed as a supplement unless it was sold as a food first.

The Natural Products Association sued the agency in August 2024. On 29 September 2025 the FDA responded to a citizen petition from the NPA and the Alliance for Natural Health and reversed its position, concluding that NMN "is not excluded from the definition of dietary supplement". A follow-up letter in December 2025 formally set aside the November 2022 letter and reinstated the earlier new dietary ingredient responses.

In Great Britain the question is different. NMN is treated as a novel food, and an application for its authorisation (reference RP-2116, from Effepharm) was still listed as "in progress" on the Food Standards Agency's register when checked in October 2026. NR, by contrast, already has novel food authorisation. Neither ruling touches NAD+ for research, which is sold for laboratory use and not as a food.

The IV NAD+ clinic trend

The third product is the molecule itself, given by drip. Clinics in the US, and increasingly in the UK, advertise infusions of several hundred milligrams over a few hours for fatigue, "longevity" and addiction recovery. The published human evidence for this is thinner than for either precursor.

The one controlled study is a pilot by Grant, Berg, Mestayer, Braidy and colleagues in Frontiers in Aging Neuroscience in 2019. Eleven healthy men aged 30 to 55 took part: eight received 750mg of NAD+ in saline over six hours, three received saline alone. The dose was chosen because it reflected a common clinic regimen; one co-author ran such a clinic in Louisiana.

The authors' reading was that infused NAD+ is "rapidly and completely removed from the plasma" for at least two hours, with a metabolite profile pointing to breakdown by NAD+ glycohydrolase and pyrophosphatase. Urine at six hours contained NAD+ and methylnicotinamide. No adverse events were recorded in the eight men.

That is the full published dataset on direct NAD+ infusion in people: one pilot, eight dosed participants, no clinical outcome measured. Any clinic claim beyond "it was tolerated and some of it reached the urine" is not supported by a trial.

What the 2025 reviews concluded

Two reviews in 2025 took stock. A Nature Metabolism review on NAD+ precursor supplementation in human ageing concluded that while preclinical studies support the strategy, "human clinical trials have shown limited efficacy". A Nature Aging review of September 2025 on targeting NAD+ in the clinic listed the open questions: which tissue, which precursor, which dose, and whether blood NAD+ tracks anything that matters.

That is the context for anyone who wants to buy NAD+ UK stock for a laboratory. The molecule's biology is well described. What it does when added back to an ageing human is not.

LynxLab stocks NAD+ for research use in 500mg vials at £49.99, tested to 99% purity with the lab report on the product page. Every batch has its certificate of analysis published, and the companion piece on why NAD+ falls with age covers the CD38, PARP and sirtuin story behind the precursor trials.

A final point on regulation. In the UK, nicotinamide adenine dinucleotide in a research vial is not a licensed medicine, not an authorised food and not a cosmetic. It is a laboratory reagent, and that is the only basis on which it is sold here.

Frequently asked questions

Is NMN better than NR for raising NAD+?

No head-to-head trial in people has settled this. Martens and colleagues (2018) raised blood cell NAD+ by about 60% with 1000mg of NR a day, and Yoshino and colleagues (2021) improved muscle insulin sensitivity with 250mg of NMN a day, but the two trials measured different things in different groups. Mouse data from the Mayo Clinic show CD38 degrades NMN, which complicates the comparison further.

Is NMN banned in the UK?

NMN is not banned, but it is regulated as a novel food in Great Britain and needs authorisation before it can be sold as a food or supplement. The Food Standards Agency register listed an NMN application (RP-2116) as still in progress in October 2026. NR has an existing novel food authorisation.

Does an NAD+ IV drip actually raise NAD+ levels?

In the only published controlled study, Grant and colleagues (2019) infused 750mg over six hours into eight men and saw no rise in plasma NAD+ for the first two hours, then a 398% rise at the end of the infusion. The molecule appeared to be cleared from plasma almost as fast as it entered. No clinical benefit was measured.

Why did the FDA say NMN could not be a supplement?

On 4 November 2022 the FDA ruled that NMN had been authorised for investigation as a new drug, with public trials of MIB-626, before it was marketed as a food, which excludes it under US law. The agency reversed that view on 29 September 2025 after a citizen petition and a lawsuit, and set aside the 2022 letter in December 2025.

Sources

• Chronic nicotinamide riboside supplementation in healthy middle-aged and older adults (Martens et al.), Nature Communications, 2018
• Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women, Science via PMC, 2021
• CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism, Cell Metabolism via PubMed, 2016
• FDA letter excluding NMN from the dietary supplement definition, FDA via regulations.gov, 2022
• FDA letter setting aside the November 2022 NMN exclusion, FDA via regulations.gov, 2025
• Application RP-2116, beta-Nicotinamide Mononucleotide as a novel food, Food Standards Agency, 2026
• A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ Metabolome During a 6 Hour Intravenous Infusion of NAD+, Frontiers in Aging Neuroscience via PMC, 2019
• NAD+ precursor supplementation in human ageing: clinical evidence and challenges, Nature Metabolism, 2025