NAD+ and the ageing brain: what the human trials show so far

The brain is one of the most energy-hungry organs in the body, and one of the busiest areas of NAD+ research. The big question is whether raising NAD+ levels can help the brain stay resilient as we age.

A new review from Professor Evandro Fang’s group at the University of Oslo, one of the leading NAD+ research teams, directly asks that question. Its title sums up where the science sits: NAD+ augmentation in brain ageing, hype, hope, or emerging reality? Their answer is somewhere in between. The early human results are encouraging, and the trials that could settle it are still under way.

Here’s a summary of what the review covers, plus a closer look at some of the studies behind it.

What NAD+ does in the brain

NAD+ (nicotinamide adenine dinucleotide) is found in every cell. In brain cells it plays a part in several processes that tend to falter with age:

• Energy production. Mitochondria, the cell’s power plants, need NAD+ to turn food into usable energy.
• DNA repair. Enzymes that fix everyday DNA damage use NAD+ as fuel.
• Mitochondrial clean-up. NAD+ supports mitophagy, the process that clears out worn-out mitochondria so healthy ones can take over.
• Body clock. NAD+ is involved in regulating the sleep-wake cycle.

Researchers have proposed that as NAD+ falls, these processes slip, which can lead to mitochondrial problems, inflammation and, over time, damage to brain cells. That idea is the reason NAD+ precursors such as NMN and NR (nicotinamide riboside) are being studied for brain ageing.

Does NAD+ in the brain fall with age?

In animals, the decline is clear. In people, the picture is less settled, mainly because NAD+ is hard to measure inside a living brain.

One study found signs that NAD+ in cerebrospinal fluid, the fluid around the brain and spinal cord, falls with age (although this is not a direct measurement of brain cells).

Blood is often used as a stand-in, but a large study published in Nature Metabolism in 2026 found that whole-blood NAD+ levels don’t change with age or with lifestyle changes such as diet and exercise. The review’s authors read this as a sign that NAD+ decline is likely to be tissue-specific. Some organs may lose more than others, and blood may not reflect what’s happening in the brain.

The clearest human evidence comes from ataxia-telangiectasia, a rare inherited condition that causes accelerated ageing and progressive damage to the nervous system. NAD+ depletion is a feature of the condition, and in Alzheimer’s and Parkinson’s disease, faltering NAD+ is linked to the same problems: poor mitochondrial clean-up, DNA damage and energy failure.

What the human trials show so far

The human studies are small and early, but several point in the same direction. All of the brain trials below used NR.

Who took part	Study	What was found
People newly diagnosed with Parkinson’s	NADPARK, a small randomised, placebo-controlled trial in Norway	NR raised NAD+ levels in the brain, measured by brain scans
Older adults with memory concerns or mild cognitive impairment	Wu et al., 2025	NR was linked to reductions in some blood markers of neurodegeneration
People with ataxia-telangiectasia	A two-year NR trial, one of the longest NAD+ trials in people	Improvements in coordination and eye movement

NADPARK has led to a much larger follow-up. A 400-person trial in Norway is now testing high-dose NR in early Parkinson’s. Most of the human trials now under way focus on Alzheimer’s and Parkinson’s, with growing interest in prevention in healthy older adults.

These results come from people with specific conditions, not from healthy adults taking a supplement for general brain health. They show NAD+ precursors can reach and affect the human brain, which is a necessary first step.

The latest lab work

Fang’s group also published a lab study in Alzheimer’s & Dementia in August 2026, looking at why this matters at the level of genes.

Working with AI company Insilico Medicine, they analysed gene activity from 12 human brain regions across 77 public datasets. Genes involved in NAD+ and mitochondrial clean-up were disrupted with normal ageing, and more severely in Alzheimer’s, Parkinson’s, Huntington’s disease and ALS.

The AI analysis singled out five genes, ULK1, OPA1, LAMP2, MFN1 and ATP6V0E1, that appear to help protect brain cells. In worms and in human cell models, these genes were linked to healthier ageing, better-functioning nerve cells and less build-up of tau, a protein that clumps in Alzheimer’s.

This study didn’t test any supplement. Its value is in mapping the machinery NAD+ supports, and the authors say work in more complex organisms is needed next.

NR or NMN?

NR and NMN are close relatives. Both are converted into NAD+ in the body, and NR becomes NMN along the way.

The brain trials so far have used NR, largely because it has been available for clinical research for longer. NMN has its own growing body of human trials, mostly looking at blood NAD+ levels, physical performance and metabolism, along with animal research on the brain. The two haven’t been compared head to head in the human brain.

Both have been shown to raise NAD+ blood levels by a similar amount.

What this means for you

• The biology is well established. NAD+ is central to energy, DNA repair and mitochondrial clean-up in brain cells.
• The human evidence is early but moving. NAD+ precursors can raise NAD+ in the human brain, and small trials have shown encouraging signals in specific conditions.
• The big answers are still to come. Longer, larger trials in Alzheimer’s and Parkinson’s, including the 400-person Norwegian study, will show whether NAD+ boosters change how the brain ages.
• The foundations still matter most. Regular exercise, good sleep, a varied diet and staying socially connected all support brain health, and supplements work alongside them.

If you have a diagnosed condition or take medication, talk to your GP before starting any new supplement. And if you’d like to talk through any of this with us, email or give us a call.

References

1. Wang HL, Zhang J, Fang EF. NAD+ augmentation in brain aging: hype, hope, or emerging reality? Trends in Endocrinology & Metabolism, 2026.
2. Lautrup S, et al. A combined artificial intelligence–wet lab approach identifies a pivotal role of the NAD+–mitophagy axis on aging and neurodegeneration. Alzheimer’s & Dementia, 2026.
3. Brakedal B, et al. The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson’s disease. Cell Metabolism, 2022.
4. Wu CY, et al. Cognitive and Alzheimer’s disease biomarker effects of oral nicotinamide riboside supplementation in older adults with subjective cognitive decline and mild cognitive impairment. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 2025.
5. Trętowicz MM, et al. Human whole-blood NAD+ levels do not vary with age or lifestyle interventions. Nature Metabolism, 2026.
6. Suaste V, et al. Transcriptional profiling shows dampening of interferon gene signatures by NAD+ augmentation in ataxia-telangiectasia. International Journal of Molecular Sciences, 2026.
7. Zhang J, et al. Emerging strategies, applications and challenges of targeting NAD+ in the clinic. Nature Aging, 2025.