NAD+ research in muscle, walking and rare disease
A muscle biopsy, a blood-sugar experiment and a walking test ask different questions. The differences are the interesting part.
Muscle samples from 119 older men
The muscle-biopsy study across three populations found lower NAD+, fewer mitochondria and reduced capacity to make and recycle NAD+ in men with sarcopenia, the loss of muscle associated with ageing. Mitochondria are the structures inside cells that help release energy. The study examined muscle samples from 119 older men.
Sampling muscle places the finding close to the physical problem under investigation. The findings occurred together; the observational design leaves their causal order unsettled. A successful treatment experiment would have another job to do: change the problem and show that function improved.
Recycling NAD+ in mouse muscle
The NAMPT experiments in mouse muscle and cultured mouse muscle cells intervened more directly. Reducing the enzyme NAMPT lowered NAD+ and impaired maximal respiration, the cells’ capacity to use oxygen in energy production. NR restored NAD+ and increased maximal respiratory capacity in the cells.
The review of NAD+ metabolism places this recycling route alongside the enzymes that consume NAD+. CD38 supplies another part of the story: mice lacking CD38 were protected against age-related NAD+ decline and retained better mitochondrial function. These experiments help explain a shortage. Their animal and cell settings set the boundary around the findings.
The insulin experiment
The ten-week trial in postmenopausal women with prediabetes gave 250 mg/day of NMN. Researchers used a hyperinsulinemic-euglycemic clamp: insulin is supplied while blood sugar is held steady, allowing the response to insulin to be measured. Muscle insulin sensitivity improved.
Body composition and HbA1c stayed unchanged. I initially expected the result to spread across the metabolic measurements; the narrower outcome is more instructive. It suggests a particular response in a particular group, while leaving the larger claims about weight and long-term blood-sugar control unanswered. Calling it a weight-loss result would erase what was actually measured.
Walking distance
In the 60-day NMN trial, adults assigned to NMN walked farther than those assigned to placebo. The study tested 300, 600 and 900 mg/day and also recorded blood NAD+ and quality-of-life measures. Its biological-age measure did not increase during the trial. That measure is an estimate derived from body tests; it cannot establish that ageing stopped.
Walking is the outcome here that I most want followed for longer. It is recognisable outside a laboratory and gives the blood result somewhere concrete to lead.
Werner syndrome and a very small trial
The review of NR in rare DNA-repair diseases describes a 52-week Werner syndrome trial with 9 participants. Plasma NAD+ rose about 140%, alongside improvements in arterial stiffness, HDL and kidney function. The review also discusses ataxia-telangiectasia and Cockayne syndrome, conditions involving DNA-repair problems, and reports no moderate or severe adverse events across the reviewed trials.
These unusual diseases give the results an interest of their own. They may help identify circumstances in which restoring NAD+ matters most. Extending a result from Werner syndrome to ordinary ageing would require evidence from that other population. I would rather understand the small study on its own terms than make it carry everyone’s hopes for longevity.
Human ageing
The 2025 human-ageing review calls for more systemic and tissue-specific work. It finds limited efficacy in clinical trials and notes that consistent age-related decline has been observed in only a limited number of human studies. Tissue data remain sparse. Raising NAD+ has not been shown to reverse human ageing or produce a younger appearance.
That review tempered my starting assumption that the human story was already settled at the level of a universal shortage. The research is more local: particular tissues, diseases and measurements. The brain studies make the same subject look different again, especially when a placebo group enters the picture.