Nicotinamide adenine dinucleotide (NAD) and its reduced form (NADH) therapy are dietary supplements that are promoted widely to support and treat a variety of conditions, from jet lag all the way to serious illnesses like Alzheimer’s disease and Parkinson’s disease. Back in 2021, I looked at the evidence base for this supplement. At that time I concluded that the evidence was weak and unconvincing, leaving this product unproven for any use. Now there are a few new papers that help us get a better picture of the potential value of this popular supplement.
What is NAD/NADH?
Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in every cell. It exists in oxidized (NAD+) and reduced (NADH) forms, and plays a central role in cellular metabolism and energy production. NAD is synthesized from niacin (vitamin B3), nicotinamide, and tryptophan through multiple biochemical pathways. Because NAD is involved in many cellular processes and has been thought to decline with aging and some diseases, there has been growing interest in its potential therapeutic and anti-aging effects. This is because research has suggested that NAD+ levels fall as people age, and that measuring NAD+ in blood could be a way to track aging or health status.
Back in 2021, the primary pitch for NAD was “cures cravings”. Today, the marketing seems to have shifted to “reverses aging,” with Hailey Bieber (who says she’s “never gonna age”) and Kendall Jenner as the influencers. The claims have progressed. How about the evidence?
New Evidence for Long-Standing Questions
A new systematic review by Cory Gallagher and Owoturo Oluwaseun Emmanuel, published in February 2026 in Ageing Research Reviews, gives us a comprehensive summary of the current evidence base. It included 113 intervention studies: 33 in humans and 80 in rodents. In animals, NAD-boosting interventions often improved metabolic, mitochondrial, inflammatory, vascular, and sometimes performance outcomes, but the results were inconsistent across models and endpoints. In humans, oral nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) usually increased blood or cellular NAD-related markers, which shows the supplements reach their biochemical target. However, improvements in meaningful outcomes were mixed: Some trials found small benefits in specific measures, while many found no clear effect on physical performance, insulin sensitivity, arterial stiffness, sleep, or other wellness outcomes. Nearly all of the trials were rated as having some risk of bias. Importantly, the review found no eligible controlled outcome trials of intravenous, intramuscular, or subcutaneous NAD itself for anti-aging or wellness indications. The authors concluded that NAD augmentation does seem to have biochemical effects, but the evidence that it works as an anti-aging therapy in people remains inconclusive. Interestingly, while the bulk of the (limited) evidence is for oral supplementation, the biggest hype is around expensive intravenous use, where there is virtually no clinical trial evidence.
The discussion section of the paper argues there could be biological constraints on NAD when given intravenously. NAD+ is a large, polar dinucleotide and so is not expected to cross cell membranes intact. Moreover, extracellular NAD+ is rapidly broken down into nicotinamide and ADP-ribose before any uptake can happen. The authors reference a small pilot study from 2019 that infused NAD+ intravenously and found early plasma clearance with a metabolite pattern consistent with this extracellular breakdown. The authors argue that any cellular uptake, if it does occur, is likely due to the retention of these NAD+ metabolites.
Overall, I found the systematic review interesting, but not conclusive. While it’s not a “gold standard” (I likely need to retire that phrase, given it’s been co-opted) systematic review, given the lack of registration, the declared conflict of interest, and other issues, the overall conclusions seem reasonable considering the evidence assessed:
In summary, oral NAD⁺ precursors (most commonly NR and NMN) consistently demonstrate biochemical target engagement in humans and appear generally well tolerated in the short term, but evidence for clinically meaningful anti-aging or wellness benefits remains heterogeneous and inconclusive across outcome domains. Preclinical studies provide broad biological plausibility yet do not reliably predict human efficacy. Evidence supporting parenteral NAD⁺ delivery for anti-aging/ wellness outcomes is currently absent among eligible controlled outcomes trials, and mechanistic considerations further underscore the need for rigorous pharmacokinetic/pharmacodynamic and clinical efficacy studies. Future trials with longer follow-up, standardized clinically meaningful endpoints, and prespecified analyses in appropriately selected populations are needed to define whether NAD⁺ augmentation offers measurable healthspan benefits and to clarify the role, if any, of parenteral approaches.
Is the premise for supplementing unjustified?
In another fascinating and informative paper published in May 2026 in Nature Metabolism, by Maria M. Trętowicz and colleagues, researchers measured NAD+ levels in blood samples from seven different groups of people using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). They first developed and validated a methodology to distinguish between genuine biological differences in samples and expected degradation due to handling/storage/freezing. They then looked at seven cohorts of patients large enough to detect actual differences, considering the sensitivity of the tests. If whole-blood NAD+ really does decline with age, or responds to lifestyle interventions, the effects should have been detectable here.
The researchers found that blood NAD+ levels were surprisingly stable. They did not consistently decrease with age, and they did not change meaningfully in response to lifestyle interventions such as diet or exercise programs. However, NAD+ levels did increase when people took nicotinamide riboside (NR), a supplement designed to raise NAD+ levels. This is a critical point – the analysis was able to detect supplementation when it occurred.
The consistency of these findings across the different cohorts raises an important question: If whole-blood NAD+ does not decline with age when measured under rigorous conditions, why have other, earlier studies suggested otherwise? This research suggests that those findings (and conclusions) could be an artifact of sample collection and storage, and not our biology. If correct, this calls into question the entire premise for administering NAD+, and it could explain why NAD supplementation doesn’t seem to show any meaningful treatment effects.
Manufacturing considerations
Because there are no FDA-approved commercial NAD+ intravenous formulations manufactured by traditional pharmaceutical companies, any consumer receiving an NAD+ infusion is receiving a compounded product. These are typically prepared by 503A compounding pharmacies or 503B outsourcing facilities, which operate under very different regulatory standards and quality control oversight than standard drug manufacturers.
This creates a challenging “buyer beware” environment. In 2024, the FDA issued a safety reminder warning that some compounders are utilizing cheap, food-grade NAD+—which is only intended for oral supplements—to manufacture sterile IV injections. When non-sterile, food-grade ingredients are injected into the bloodstream, they carry a high risk of microbial and endotoxin contamination. This is not a hypothetical hazard; the FDA has documented adverse event reports of severe chills, violent shaking, and vomiting requiring medical intervention—all classic signs of endotoxin poisoning. In 2025, the FDA issued a Class I recall for NAD+ for injection manufactured by GenoGenix LLC, following the detection of endotoxins.
In medicine, we routinely accept sometimes meaningful risks and potential side effects when a treatment or intervention has a critical, demonstrated therapeutic benefit. Accepting these same, highly preventable contamination risks for an expensive, unproven “wellness” treatment is far more difficult to justify.
Conclusion
The main takeaway from this newer research is that it raises questions about the whole rationale for monitoring and supplementing at all. It could be that blood NAD+ levels may not be a useful marker of aging or lifestyle-related health changes, despite claims to the contrary. It could also be that raising levels with supplementation has no meaningful medicinal or therapeutic effects. While this research alone doesn’t rule out the idea of NAD supplements, it does give us greater reason to question the relevance and usefulness of this supplement. Compared to where we were in 2021, I’m even more skeptical of the therapeutic potential for NAD.