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NAD+ dosage: the subjects give the number meaning

A number detached from its participants and its outcome has lost the part that made it useful.

The oral trial register

A dose range as a headline loses me straight away. A range makes separate experiments look like options on one menu. These are amounts researchers gave their subjects, with the population and result still attached. They are not human dose recommendations.

NR, healthy overweight adults. 100, 300 or 1000 mg/day for eight weeks; whole-blood NAD+ rose 22%, 51% or 142%, respectively. No reported flushing or significant adverse-event difference from placebo.

NMN, healthy middle-aged adults. 300, 600 or 900 mg/day for 60 days; blood NAD+ and walking distance improved relative to placebo. The study's preferred 600 mg/day was attached specifically to its blood NAD+ endpoint.

NMN, prediabetic, postmenopausal women. 250 mg/day for ten weeks; muscle insulin sensitivity improved. Body composition and HbA1c did not.

NR, heart failure with reduced ejection fraction. 1000 mg twice daily for 21 days; blood NAD+ rose approximately 2-fold and inflammatory signaling in blood immune cells fell.

NR, blood-pressure research. 1000 mg/day for six weeks; lower systolic pressure and arterial stiffness were reported, most clearly with elevated starting pressure. The participants, endpoint and duration give the amounts their context.

Direct delivery, rapid plasma clearance

The source material describes a pilot IV NAD+ experiment using 3 micromoles per minute over six hours. Micromoles count molecules rather than their mass. It also reports near-complete removal of infused NAD+ from plasma during approximately the first two hours. Plasma is the liquid part of blood.

I had expected direct delivery to make the story simpler. The clearance finding makes it harder: arrival in a vein does not tell us where intact NAD+ ends up, how it is broken down, or whether the result helps a person. A rate measured during infusion cannot be turned here into a useful oral amount.

The review of the human NAD+ evidence leaves clinical efficacy limited, and the current research record for IV delivery is mostly small pilot or retrospective work. A compounded NAD+ infusion has no FDA approval. For heart health and safety, the next question is what the intervention changes in a person.

Raised blood NAD+ leaves molecular lifetime untimed

The NR trial maintained raised whole-blood NAD+ over eight weeks. The NMN trial measured increases on days 30 and 60. Those observations concern repeated oral precursor administration and the blood pool that resulted. They do not time the lifetime of one molecule of NAD+.

Nor does the rapid plasma clearance in IV pilot work establish how long a health benefit lasts. The health benefit would first need to be established. I would not join those very different observations into one NAD+ half-life.

Morning, night and the amount a person asks about

The NAD+ salvage machinery is connected to circadian rhythms, the daily biological cycle. That mechanism is interesting, but the human record here has not established an optimal morning-versus-evening schedule.

The question ‘How much NAD should I take?’ remains a personal medical question. These amounts cannot answer it. A trial's participants, health conditions, medicines, duration and monitoring all contributed to what that trial could observe; removing them leaves a number with no individual assessment attached.