Is NAD therapy all it's cracked up to be? Here's the evidence

By Sarah Handzel, BSN, RN | Medically reviewed by Kristen Fuller, MD
Published October 7, 2022

Key Takeaways

  • Nicotinamide adenine dinucleotide (NAD) therapy is growing in popularity for treatment of various age-related illnesses and disorders, such as hearing loss, some cancers, and certain cardiovascular conditions.

  • NAD is actively involved in several cellular pathways impacting various biological processes, including DNA repair and energy metabolism.

  • To date, there are no large-scale human studies demonstrating the effectiveness and safety of NAD therapy.

Over the last decade or so, NAD therapy has grown in popularity among naturopaths, influencers, and celebrities.

Evidence suggests it may be effective, but further research is needed to understand its effects on the body.

Physicians have a responsibility to comprehensively educate patients about this treatment, including its benefits and potential harms.

NAD’s role in the body

As more Americans seek “health-boosting” supplements and treatments, NAD therapy is marketed as an especially effective treatment and preventative supplement for a variety of conditions, including age-related disorders, various forms of cancer, hearing loss, certain cardiovascular diseases, and even issues like addiction.[]

Levels of NAD in oxidized form (NAD+) steadily decline as we age, and as a result, we become more vulnerable to various aging processes.[]

According to research, NAD is involved in several cellular metabolic pathways.[] In both its oxidized (NAD) and reduced (NADH) forms, it helps transfer electrons and protons during enzymatic reactions. As a result, NAD is an important component of a variety of biological reactions, such as the citric acid cycle, glycolysis, and mitochondrial oxidative phosphorylation.

All of these processes are important for cell metabolism, DNA repair, cell signaling, immune function and mitochondrial fitness.

Fluctuations in NAD level may impact various biological processes, including DNA repair and transcriptional regulation. Inflammation, energy metabolism, stress resistance, and even circadian rhythm are also affected.[]

Various precursors aid in NAD synthesis, especially nicotinamide, a water-soluble form of niacin (vitamin B3) that’s primarily obtained from food sources, such as beef, cereal grains, eggs, fish, nuts, poultry, and some fortified foods.[] However, NAD may be also synthesized de novo from compounds like nicotinic acid and tryptophan.

Because NAD is involved in so many cellular processes, its supplementation, especially as levels decline, is the subject of continued research for the treatment of a number of medical conditions.

Conflicting evidence

While there have been studies examining the effectiveness of NAD supplementation, there have been no large-scale clinical trials or other major research efforts involving human beings. Instead, animal models suggest NAD’s effectiveness against age-related diseases.

According to an article published by Nature Portfolio, oral administration of nicotinamide mononucleotide (NMN), another precursor for NAD, enhances energy metabolism, suppresses age-related weight gain, improves insulin sensitivity, and prevents certain changes in gene expression typically related to age.[]

These results were noted in mice models; following treatment, older mice exhibited improved metabolism and energy levels resembling that of younger mice.

The article described how, in 2016, the first clinical study to assess the safety of NMN in humans was conducted using 10 healthy Japanese men. Each participant received between 100 and 500 mg doses of NMN, with no significant adverse effects reported.

Blood and urine samples showed fluctuations in various markers, including blood glucose, chloride, serum bilirubin levels, and serum creatinine.

However, these fluctuations were all within normal levels.

Additional research cited in the article described how 13 postmenopausal, prediabetic women who were classified as either overweight or obese, took 250 mg of NMN once daily for 10 weeks. Compared with a placebo group, there was an improvement in insulin muscle sensitivity. However, the benefits seen in rodent models didn’t translate to humans.

Additional benefits, drawbacks

Other studies suggest NAD upregulation via supplementation has benefits for aging, neurodegenerative diseases, cancer, diabetes, mitochondrial disorders, retinal degenerative diseases, hearing loss, and cardiovascular diseases.

Beyond these age-related problems, NAD therapy may benefit those suffering from jet lag, depression, candidiasis, and fatty liver disease. It may also have antioxidant and anti-inflammatory benefits, as well as the ability to improve endurance capacity of skeletal muscle.

However, evidence also suggests that high doses of supplemental NADH may promote anxiety, agitation, and sleeplessness.

Other research links excessive intake of NAD precursors nicotinamide and niacin to Parkinson’s disease and diabetes.[]

What this means for you

There’s evidence that NAD supplementation may improve or prevent a variety of age-related medical conditions, but it stems from animal models or small-scale studies in humans. Larger studies in human subjects are necessary to confirm these results and fully understand the impact of supplemental NAD. Physicians should caution patients that while anecdotal evidence may support the use of NAD, there is currently little to no data supporting those results.

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