A comprehensive review of clinical research and emerging evidence
Nicotinamide adenine dinucleotide (NAD+) is far more than just another supplement trend. It's a fundamental coenzyme present in every living cell, essential for converting nutrients into cellular energy and activating proteins that regulate critical biological functions.
NAD+ participates in over 500 enzymatic reactions in your body, making it one of the most important molecules for human health and longevity.
NAD+ serves several critical functions:
One of the most consistent findings in aging research is that NAD+ levels decline significantly as we age—in some tissues by as much as 10-80%.
Research identifies several mechanisms behind age-related NAD+ depletion:
Research Source: Covarrubias AJ, et al. "NAD+ metabolism and its roles in cellular processes during ageing." Nature Reviews Molecular Cell Biology, 2021. Read study →
The Promise: NAD+ is essential for mitochondrial ATP production. Restoring NAD+ levels may improve cellular energy metabolism.
The Evidence: Preclinical studies show that NAD+ boosting compounds improve mitochondrial function in aged animals. Clinical studies in humans demonstrate increased NAD+ blood levels following supplementation, though direct energy improvements require more research.
User Reports: Many individuals report sustained energy improvements within days to weeks of starting NAD+ injections.
The Promise: By activating sirtuins—proteins linked to longevity—NAD+ may slow cellular aging processes.
The Evidence: Emerging research indicates that elevating NAD+ levels may slow or even reverse aspects of aging. Studies show NAD+ modulation can extend healthspan and lifespan in animal models. Human longevity studies are ongoing but promising.
Research Source: Yoshino J, et al. "NAD+ intermediates: The biology and therapeutic potential of NMN and NR." Cell Metabolism, 2018. Read study →
The Promise: NAD+ supports neuronal health, neurotransmitter production, and protection against neurodegenerative diseases.
The Evidence: Research shows NAD+ plays a crucial role in neuronal function. Animal studies demonstrate neuroprotective effects. Clinical research in humans is still in early stages but shows promise for conditions like Alzheimer's and Parkinson's disease.
Research Source: Verdin E. "NAD+ in aging, metabolism, and neurodegeneration." Science, 2015. Read study →
The Promise: NAD+ improves insulin sensitivity, metabolic flexibility, and fat oxidation.
The Evidence: Studies show NAD+ precursors can improve metabolic markers in animal models and some human trials. Research indicates potential benefits for metabolic syndrome, diabetes, and obesity, though more clinical trials are needed.
The Promise: Enhanced mitochondrial function and reduced inflammation may improve exercise capacity and recovery.
The Evidence: Preliminary research suggests NAD+ supplementation may improve endurance and reduce exercise-induced inflammation. Athletes report faster recovery times, though controlled trials are limited.
The Promise: NAD+ is required for PARP enzymes that repair DNA damage and protect against cellular stress.
The Evidence: Strong preclinical evidence shows NAD+ is essential for DNA repair mechanisms. Clinical studies demonstrate promising results in rare genetic diseases with premature aging and DNA damage.
Research Source: Fang EF, et al. "Promising results with NAD supplementation in rare diseases with premature aging and DNA damage." Experimental Gerontology, 2025. Read study →
As of 2026, clinical studies examining NAD+ injections in humans remain relatively limited in scale and duration. A systematic review found that while many studies show increased NAD+ levels and improved clinical features, other studies have shown no measurable benefits. Large-scale, long-term clinical trials are ongoing.
Research Source: Mehmel M, et al. "Evaluation of safety and effectiveness of NAD in different clinical conditions: a systematic review." PubMed, 2023. Read review →
A pilot clinical study found that intravenous infusions of 500mg of NR (nicotinamide riboside) were safe with minor temporary side effects and no adverse events for up to 14 days post-infusion. Interestingly, NR IV increased NAD+ levels within 24 hours, which was not observed with direct NAD+ IV.
Research Source: Dahabiyeh LA, et al. "Randomized, placebo-controlled pilot clinical study evaluating acute Niagen+ IV and NAD+ IV in healthy adults." medRxiv, 2024. Read study →
NAD+ and its precursors can be delivered through several routes:
Pros: Convenient, well-studied, over-the-counter
Cons: Subject to digestive breakdown, variable absorption, requires higher doses
Pros: Direct delivery, bypasses digestion, potentially more bioavailable, lower doses
Cons: Requires injection, prescription needed, less research vs oral
Pros: Highest bioavailability, rapid effect
Cons: Most expensive, requires clinic visit, time-consuming
Injectable NAD+ offers a middle ground: more bioavailable than oral, more convenient than IV, and can be self-administered at home.
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