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Does NAD⁺ actually decline with age?

It is the opening line of nearly every sales page. The largest community measurement — 1,518 people — found the decline in men only, and by less than the ordinary variation between two people the same age.

James Harper6 min read
1,518 people, one measurement eachMen34.5Women31.3Average whole blood NAD⁺, µmol/L. Population mean 33.0, SD 5.5.Decline with age: found in men onlySignificant only in the 60-and-over group, at −2.16 µmol/L.In women, no significant difference across five age groups.Cross-sectional: different people compared, not the same people followed.

Almost every page selling NAD⁺ opens the same way: your NAD⁺ declines as you age, and this product replaces it. The first half is presented as settled background rather than a claim.

It has been measured, in a community study of 1,518 adults [1], and the result is more interesting than either the marketing or the pushback.

It is worth having straight before you read a price, because the premise is what the price is attached to — what NAD⁺ actually does is the background if you want it first.

What the study did

Researchers recruited 1,518 adults from one community, all over 18 and free of cardiovascular disease and any cancer. Whole blood NAD⁺ was measured by cycling assay and liquid chromatography–mass spectrometry. Participants were split into five age groups, and the analysis was then repeated separately by sex [1].

Mean age was 43. Just over half were men. Average whole blood NAD⁺ across everyone was 33.0 µmol/L, with a standard deviation of 5.5 [1]. Hold onto that spread — it does more work than anything else here.

What it found

Across all participants, NAD⁺ declined with age up to about 50, reaching significance in the 40–49 group. After 50 the trend disappeared [1].

Then the part that is rarely quoted. The association differed by sex, and strongly so — the test for interaction came out at p = 0.003. In men, levels fell with age but reached significance only in the 60-and-over group, at about 2.16 µmol/L below the under-30s. In women, the level did not differ significantly across any of the five age groups, with no trend at all [1].

The authors’ own conclusion is that the loss of blood NAD⁺ with aging was observed only in males [1].

Why the spread matters more than the significance

A 2.16 µmol/L difference sounds like a lot until you set it against a population that averages 33.0 with a standard deviation of 5.5. The gap between older and younger men is smaller than the ordinary variation between two people of the same age.

It is a real, statistically detectable difference in a group average. It is not the picture the marketing implies, where a level falls off a cliff and a product restores it.

It is also worth setting against what a supplement can move: the doses trials used raised blood NAD⁺ substantially more than the age gap described here.

Three things this cannot tell you

It did not follow anyone. This is cross-sectional: different people of different ages, measured once each. It cannot show your level falling, only that older men in this sample averaged slightly less than younger ones. Diet, era and survivorship all sit inside that comparison — the study itself found a difference in meat consumption across NAD⁺ quartiles.

It measured blood. Whole blood NAD⁺ is what can be sampled easily. It is not the same as the level inside a muscle cell or a neuron, which is where the biology people care about happens.

It says nothing about supplements. A difference between age groups is not evidence that raising the number helps — that is a separate question with its own trials, and their results are narrower than the category implies.

What to do with it

If you are a man over 60, there is a measured basis for the premise, and it is modest. If you are a woman, the largest community measurement of this found no significant change across age groups at all — which is worth knowing before buying a product sold on age-related decline. That sits alongside the other finding about women in this field: the one good trial conducted entirely in women tested insulin sensitivity, not aging.

None of this means NAD⁺ is unimportant. It means the opening sentence of the sales page is doing more work than the evidence supports, and that the evidence is different for men and women — which almost nothing selling it acknowledges. If you are weighing a purchase, what the trials actually measured is the more useful page.

Frequently asked

Does NAD⁺ decline with age?
In a community study of 1,518 adults, whole blood NAD⁺ declined with age up to about 50 and the trend disappeared after that. Split by sex, the decline reached significance only in men aged 60 and over — about 2.16 µmol/L below men under 30. In women there was no significant difference across five age groups and no trend.
How big is the drop?
Smaller than it sounds. The men-over-60 difference was about 2.16 µmol/L against a population average of 33.0 with a standard deviation of 5.5 — so the gap between older and younger men is less than the ordinary variation between two people of the same age.
Does NAD⁺ decline with age in women?
This study did not find it. Whole blood NAD⁺ did not differ significantly across any of the five age groups in women, and showed none of the downward trend seen in men. The authors concluded the loss with aging was observed only in males, and that future NAD⁺ research should account for sex.
Does this mean supplements work?
No, and it is a separate question. A difference between age groups is not evidence that raising the number produces a benefit. That requires trials measuring outcomes, and what those found is narrower than the marketing suggests.

Sources

  1. [1] Yang F, Deng X, Yu Y, et al. (2022). Association of Human Whole Blood NAD⁺ Contents With Aging Frontiers in Endocrinology. PMID 35388296

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