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The precursor trials

NR, NMN and the NAD+ trial results

The most revealing experiments move from the blood tube to a muscle measurement or a walking course. Their results deserve individual names.

Nicotinamide riboside

The 8-week NR trial by Conze and colleagues has a pleasingly direct chemical result. Healthy overweight adults received 100, 300, or 1000 mg/day; whole-blood NAD+ rose 22%, 51%, and 142%, respectively. The elevation persisted through the study.

Adverse events did not differ significantly from placebo. The researchers reported no flushing or rise in LDL cholesterol. I appreciate the modesty of this experiment’s main achievement: it shows a reproducible relationship between the amount of a precursor and a blood measurement. The figure below makes that relationship easier to see.

Reading those percentages as improvements in energy, lifespan or memory would add outcomes this trial did not establish.

Three bars comparing the reported whole blood NAD+ increases after NR
Conze and colleagues: whole-blood NAD+ changes with oral NR in healthy overweight adults over 8 weeks. The bars show the reported percentages, without a health-benefit scale.

Nicotinamide mononucleotide

Yi and colleagues studied NMN for 60 days in healthy middle-aged adults, with groups receiving 300, 600, or 900 mg/day. Blood NAD+ increased at days 30 and 60 across the NMN groups. Walking distance and quality-of-life scores also improved versus placebo; the biological-age measure did not increase.

My curiosity tilts toward the walking test rather than the age estimate. A six-minute walk gives the claim a physical task to answer to. Even so, a short trial of healthy adults leaves the question of sustained function open. The authors favored the 600 mg/day result within their experiment; that judgment supplies no personal dose.

No safety issues were reported at the amounts tested. The longer view still needs longer observation.

NMN also has a contested supplement status. FDA has taken the position that NMN is excluded from the dietary-supplement definition because it was investigated as a drug. That marketplace dispute concerns its sales category; the trial’s tolerability observations answer a separate question.

Two research staff preparing a corridor walking course with cones and a stopwatch
An imagined preparation scene for a walking test, rather than a photograph of the NMN trial. The corridor makes the physical outcome tangible.

Insulin sensitivity in prediabetic women

The Yoshino trial in prediabetic, postmenopausal women tested NMN at 250 mg/day for 10 weeks. Muscle insulin sensitivity improved: insulin helped muscle handle glucose more effectively. Body composition and HbA1c, the longer-term blood-sugar measure, did not change.

I’d reserve the praise for the muscle measurement itself. The muscle finding is specific and interesting. Weight loss, diabetes treatment and a general feeling of extra energy would each need their own demonstration.

NAD+ vs NMN

NMN is one biochemical step from NAD+; NR can be converted to NMN along the way. The biosynthetic pathways explain why either precursor appears in experiments intended to raise NAD+.

Whole NAD+ has a different journey. In human skin fibroblasts grown in a dish, enzymes outside the cells broke extracellular NAD into smaller products before uptake. That experiment concerns cultured cells. It gives a concrete reason to ask about chemical form and route, while leaving the behavior of a whole person to human studies.

NAD+ benefits across the trials

The attractive findings are scattered across different populations and tasks: blood NAD+ with NR, walking with NMN, muscle insulin sensitivity in prediabetic women, and brain NAD+ in Parkinson’s disease. Combining them into a single list of benefits would conceal those differences.

Vinten and colleagues’ 2025 review describes limited human efficacy and a shortage of tissue-specific measurements. I share its appetite for more direct tissue work. My interest would sharpen considerably if tissue measurements and sustained function improved together in the same participants. The brain studies are already asking part of that question.