A retired schoolteacher asked me the question directly last month. She had read our guide to NAD+ IV therapy, she had a daughter telling her it was a scam and a friend telling her it had changed her life, and she wanted a straight answer: does NAD+ therapy actually work? The honest answer is that it depends on what you mean by "work," and the clearest way I know to explain it is to walk through the three questions any treatment has to answer, in order, and show where NAD+ stands on each.
NAD+ therapy works in the sense that matters first: raising NAD+ in the body is well established in randomized trials, with oral precursors and with infusions. Whether raising NAD+ changes physiology has been shown in some tissues and some patients and not in others. Whether it changes how a person functions day to day is the question the field is still answering, and the evidence there is promising, uneven, and, for intravenous NAD+ specifically, still mostly clinical experience rather than controlled trials. That is not a reason to dismiss it. It is a reason to know which claim you are buying.
Question one: does it raise NAD+?
This is the easiest question, and the answer is yes, by every route that has been tested. In 2018, Christopher Martens and colleagues at the University of Colorado Boulder published a randomized, placebo-controlled crossover trial in Nature Communications in which 30 adults aged 55 to 79 were enrolled, 24 completed, and those who took 1,000 mg of nicotinamide riboside a day for six weeks saw NAD+ in their blood cells rise by about 60 percent. In 2022, a multicenter trial led by Lin Yi in GeroScience randomized 80 adults aged 40 to 65 to 300, 600, or 900 mg of nicotinamide mononucleotide a day or placebo for 60 days, and blood NAD+ rose in a dose-dependent way, with most of the rise already present by day 30 and no further gain from 900 mg over 600 mg.
For the infusion itself, the 2019 pilot by Ross Grant's group in Sydney, with co-authors from a Louisiana NAD+ clinic, infused 750 mg of NAD+ over six hours into eight men and found plasma NAD+ roughly five times baseline at the end, with the interesting wrinkle that nothing changed for the first two hours, the authors' explanation being that tissues were clearing it as fast as it arrived. A 2024 industry-sponsored pilot posted on medRxiv, not yet peer reviewed, compared 500 mg of intravenous nicotinamide riboside with 500 mg of intravenous NAD+ and oral NR in healthy adults and found the largest rise in blood NAD+ with the NR infusion, about 20 percent above baseline at three hours. So the first rung of the ladder is solid. If a clinic tells you NAD+ infusions do not raise NAD+, or that oral precursors do nothing, both statements are wrong.
Question two: does raising NAD+ change anything in the body?
Here the picture gets more interesting and more honest. The best-designed trial in this category is NADPARK, published in Cell Metabolism in 2022 by Brage Brakedal and colleagues at the University of Bergen. Thirty newly diagnosed, untreated Parkinson's patients took 1,000 mg of nicotinamide riboside or placebo for 30 days. Brain NAD rose on magnetic resonance spectroscopy in the treated group, and the patients whose brain NAD actually rose showed changes in cerebral glucose metabolism on PET imaging along with mild clinical improvement. The trial was small and the authors called it phase one, but it showed, for the first time in a randomized design, that an NAD+ precursor reaches the human brain and changes its metabolism in a neurological disease.
In metabolic tissue, the results split. Mihoko Yoshino and Samuel Klein's group at Washington University, publishing in Science in 2021, gave 250 mg of nicotinamide mononucleotide a day for ten weeks to 25 postmenopausal women with prediabetes and found that insulin's ability to drive glucose into skeletal muscle improved, along with the expression of muscle remodeling genes, while blood glucose, liver fat, blood pressure, and inflammatory markers did not change. Three years earlier, Ole Dollerup's group in Denmark, publishing in the American Journal of Clinical Nutrition, had given 2,000 mg of nicotinamide riboside a day for twelve weeks to 40 obese, insulin-resistant men and found no change in insulin sensitivity at all, measured by the gold-standard clamp. Same target, different precursor, different population, opposite result. Anyone who tells you the metabolic story is settled has not read both papers.
In the Martens trial, the blood pressure and arterial stiffness signals were encouraging but did not survive correction for multiple comparisons, which is why the authors flagged them for a larger trial rather than claiming them. In the Yi trial, the 600 and 900 mg groups walked about 150 meters farther in six minutes after two months, a large and clinically meaningful change in a functional test, although the trial was fully funded by the two companies that make the supplement and its first author is an employee of one of them, and that should be said clearly whenever the result is quoted.
Question three: does the person feel or function better?
This is the question my patient was really asking, and it is the one the literature answers least directly. No randomized trial has yet shown that NAD+, by any route, improves memory, attention, or processing speed in healthy adults. The functional signals that exist, the walking distance in the Yi trial, the quality-of-life scores in the same study, the mild clinical improvement in NADPARK, are real but come from single trials that need replication. For intravenous NAD+ specifically, the peer-reviewed record consists of safety and pharmacokinetic work: the Grant pilot found no adverse events, and a 2026 retrospective series of 14 patients at a commercial wellness clinic, published in Frontiers in Aging by the clinic's own staff, found no clinically meaningful change in liver, kidney, thyroid, or inflammatory markers over 30 days after four consecutive daily infusions of either NAD+ or nicotinamide riboside. Neither measured cognition as an endpoint, and neither was designed to. The two randomized trials of oral nicotinamide riboside in mild cognitive impairment raised NAD+ without improving test scores, which is worth knowing before anyone promises you a sharper memory.
What exists beyond the trials is clinical use that dates to the early 1960s, with two decades of continuous use in modern addiction clinics, and this is where I think the evidence conversation usually goes wrong in both directions. Skeptics treat the absence of a large trial as evidence of absence, which it is not. Enthusiasts treat testimonials as data, which they are not either. The accurate statement is that intravenous NAD+ sits where many physician-administered therapies sit: a sound mechanism, consistent safety data, a coherent biological rationale for the populations most likely to benefit, and outcome trials that no one has yet had the commercial incentive to fund, since NAD+ itself cannot be patented and the companies funding trials are testing their own branded precursors instead. In our own practice, patients receiving NAD+ alongside conventional detoxification have found the process easier to tolerate, with fewer cravings and less mood instability, and patients with afternoon cognitive fatigue have reported steadier energy across a series of infusions. I describe those observations as what they are, clinical experience, which is extremely useful evidence considering the large clinical experience that we, and many other clinics, are amassing.
How I read a claim about NAD+
When a patient brings me a headline, I ask three things. Which rung of the ladder does the study address: NAD+ levels, a physiological marker, or how the person functions? Who was in it, because a result in prediabetic women or newly diagnosed Parkinson's patients may not transfer to a healthy 50-year-old? And who paid for it, because a meaningful share of the NAD+ literature is funded by the companies that sell the precursors, which does not make the results wrong but does mean they need independent replication before they are treated as settled. A clinic that cannot answer those three questions about the study it is quoting is selling you the headline, not the finding.
The practical conclusion for my patient was the same one I reach with most people her age who are otherwise healthy. NAD+ therapy is a reasonable, low-risk intervention with a strong mechanistic case, more than half a century of adoption in clinics, and a growing database of human evidence, both in the literature and in the experience of clinicians and patients alike, best used as part of a workup that also looks for the common, treatable causes of fatigue and cognitive decline. If that describes you, our NAD+ IV therapy page explains how we dose and monitor it, and you can review our IV packages or book a consultation to talk through whether it fits your situation.
In the Neuroeconomy, the question is never whether a therapy is perfect. It is whether the evidence, read carefully, justifies the investment for the brain you are trying to protect. For NAD+, read carefully, it does, as long as you know which question each study was answering.
This article was drafted with the assistance of AI writing tools, then reviewed, edited, and approved by Dr. Sean C. Orr, M.D., who holds full editorial responsibility for its content.
Sources
- Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9:1286.
- Yi L, Maier AB, Tao R, et al. The efficacy and safety of β-nicotinamide mononucleotide (NMN) supplementation in healthy middle-aged adults: a randomized, multicenter, double-blind, placebo-controlled, parallel-group, dose-dependent clinical trial. GeroScience. 2023;45(1):29-43.
- Grant R, Berg J, Mestayer R, et al. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Front Aging Neurosci. 2019;11:257.
- Brakedal B, Dölle C, Riemer F, et al. The NADPARK study: a randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. 2022;34(3):396-407.e6.
- Yoshino M, Yoshino J, Kayser BD, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science. 2021;372(6547):1224-1229.
- Dollerup OL, Christensen B, Svart M, et al. A randomized placebo-controlled clinical trial of nicotinamide riboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am J Clin Nutr. 2018;108(2):343-353.
- Reyna K, Heinzen G, Patel N, et al. Intravenous infusion of nicotinamide adenine dinucleotide (NAD+) versus nicotinamide riboside (NR): a retrospective tolerability pilot study in a real-world setting. Front Aging. 2026;7:1652582.
- Hawkins J, Idoine R, Kwon J, et al. Randomized, placebo-controlled, pilot clinical study evaluating acute Niagen+ IV and NAD+ IV in healthy adults. medRxiv preprint, posted June 10, 2024; doi:10.1101/2024.06.06.24308565. Not peer reviewed; funded by ChromaDex.
- Alzheimer's Drug Discovery Foundation. Cognitive Vitality Reports: Nicotinamide Riboside (update). alzdiscovery.org, 2025. Summarizes the randomized trials of oral NR in mild cognitive impairment (including Orr et al., GeroScience 2024, NCT02942888).