NAD Supplements: Comprehensive Overview

Boosting NAD+ levels is at the top of the list for many interested in longevity and healthy aging. Nicotinamide adenine dinucleotide is often considered the 'everything molecule' as it is present in all our cells and is involved in numerous metabolic processes. However, because it begins to decline as we age, people are reaching for supplementation to help replenish NAD levels, aiming to regain their youth.

What is NAD?

NAD is a coenzyme found in every cell of the body. It is a key player in metabolism, helping to turn nutrients into energy and regulate other cellular functions. It’s also involved in DNA repair and modulating inflammation and mitochondrial function, which are all considered important factors in the 12 hallmarks of aging theory.

NAD has also been found to activate sirtuins known as the longevity genes, proposed to be essential in preventing age-related health decline. Studies done in animal models have linked increased sirtuin activity to increased health span and lifespan. While these findings are promising, further research is needed to determine if similar effects could occur in humans.

The decrease in cellular NAD+ levels has been linked to several diseases, including cognitive decline, cancer, metabolic disease, and frailty. Scientists have proposed that many of these age-related diseases may be slowed down and even reversed by restoring NAD+ levels.

How NAD supplements work

NAD supplements function primarily by providing precursors to the body that are necessary for the synthesis of NAD+. These supplements can include compounds such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), which the body converts into NAD+ through the NAD salvage pathway.

Another proposed way to boost NAD levels is directly with NAD+. These often include either NAD+ injections, NAD+ patches, capsules, or nasal sprays.

Types of NAD supplements reviewed

There are many ways you can supplement with either NAD precursors or NAD+ itself. From capsules and tablets to powder and formulation modifications such as liposomal delivery, supplement brands have formulated NAD boosters, aiming to meet anyone’s preference.

NAD+

NAD+ is known to be less stable than its precursors, NMN or NR, raising questions about its efficacy when taken orally. Its stability and ability to increase NAD+ levels in the bloodstream remain subjects for scientific research. Scientists note that NAD+ compound needs to be stored at freezing temperatures and has a limited stability window, which may affect its integrity and effectiveness by the time consumers use it.

While direct delivery methods like IVs and patches might offer higher bioavailability, the stability and actual NAD+ content at the time of use, require careful consideration and more validated research. When using the raw form of NAD+, IV infusion is the only administration method used to increase systemic NAD+ levels in pre-clinical models. However, the practical application and effectiveness of at-home NAD+ injections or patches are still uncertain and currently have not been evaluated in relevant clinical studies.

NMN

NMN is one of the precursors that our cells use to make NAD, the essential co-enzyme all of our cells use for optimal functioning. One of the ways that NAD+ is synthesized in the body is through the NAD salvage pathway, a biological route that helps maintain adequate levels of NAD+. Some preliminary research studies have shown that oral administration of NMN may lead to statistically significant increases in NAD+ levels. Considering the functions of NAD+ in the body, supplementation of its precursor, in turn, is proposed to support enhanced metabolic functions, improved mitochondrial efficiency, and better overall health outcomes.

Scientific research has also explored promising benefits, such as increased physical energy, improved cognitive function, and a potential slowdown in the physiological aspects of aging. However, more research is necessary.

NR

Nicotinamide riboside (NR) is a key building block of NAD+. It's been heavily studied as a compound that could help replenish NAD levels in the body. It’s also been proposed to have therapeutic potential for neurodegenerative, metabolic, and cardiovascular conditions. Some research suggests that it may be more bioavailable than NMN; however, there is still a lack of data to make any conclusions. Additionally, out of several precursors included in supplements, it’s the closest in structure to NAD, which is hypothesized to contribute to easier conversion.

Effectiveness of NAD supplements

Researchers continue to investigate the effectiveness of NAD boosters and the potential benefits they may evoke. Depending on individual needs and health status, consumers may experience varying effects when supplementing with NAD or its precursors. Additionally, there may be different outcomes whether you take NMN, NR, or a direct form of NAD+.

Research investigating the effectiveness of oral supplementation is ongoing. While supplements may not have a rapid acute impact on NAD+ levels, some preliminary data suggests that they may offer a more sustainable approach to increasing NAD+ baseline over time due to their continuous and gradual absorption.

While the majority of studies have been conducted in laboratory settings or on animal models, there’s an increasing number of recent and ongoing human clinical trials. One human study found that 250 mg of NMN supplementation increased NAD+ levels. However, the study also concluded that when participants stopped taking NMN at week 12, by week 16, their NAD levels went back to the baseline they had at the start of the study.

NAD supplement health benefits

Increasing NAD+ levels in the body has been proposed to have several health benefits, especially related to aging, inflammation, and metabolic processes.

May increase energy levels

Our cells use NAD+ to convert food into energy. By increasing NAD+ levels, the mitochondria, or cellular battery, may become more efficient in creating cellular ATP, our energy currency. Studies have noted that such increased cellular energy may support cognitive function, physical performance, and improved muscle functioning in older participants.

May support brain health

Declining NAD+ levels in the brain have shown an increased risk of brain aging and the progression of neurodegenerative disorders such as Alzheimer’s disease. NAD’s role in supporting mitochondrial function, reducing oxidative stress, and promoting mitochondrial biogenesis — the process of creating new mitochondria is proposed to help improve cognitive function and mitigate the effects of aging.

Studies have suggested that impaired mitochondria function and reduced autophagy may be risk factors for Alzheimer's disease or AD. With increased NAD levels, researchers have noted increased autophagy and mitochondrial function, potentially providing a therapeutic effect against AD. However, large randomized, double-blind, placebo-controlled studies on AD patients are necessary.

May increase lifespan

One of the most compelling areas of NAD+ research is its potential to affect the aging process. By supporting mitochondrial function, DNA repair, and reducing inflammation, NAD+ may address some of the fundamental processes that contribute to aging.

Studies on extending lifespan and health span have only been done in animal models but have shown that increased NAD+ levels may lead to longer lifespan and increased quality of life. This is believed to be due to the activation of sirtuins, also referred to as 'longevity genes,' which are linked to aging.

May improve sleep

NAD has been linked to circadian rhythm, our body’s internal clock that governs many physiological processes, including the sleep-wake cycle, metabolism, and hormonal homeostasis. If the circadian rhythm gets disrupted, it may impact both physical and mental health.

A 12-week study in 2022 reported that 250 mg NMN supplementation daily helped reduce drowsiness and fatigue in older adults. However, the investigators did point out that the study had several limitations, and there was no significant improvement in sleep quality as measured by the PSQI, a gold standard for subjective sleep measurement.

May improve insulin sensitivity

A 10-week study investigated the impact of supplementing with 250 mg of NMN in postmenopausal women with prediabetes and overweight or obesity. The protocol results showed improved insulin sensitivity and muscle insulin signaling, though no change in NAD+ levels was observed. These findings support the proposed potential therapeutic benefits of NAD+ supplementation in humans with prediabetes, although the precise mechanisms by which various NAD+ precursors may affect glucose metabolism still need further investigation.

May reduce inflammation

Chronic inflammation may contribute to various age-related diseases, including heart disease and diabetes. It’s also been recognized as one of the 12 hallmarks of aging. Scientists believe that increased inflammation may also be associated with depleted NAD levels, and supplementation may help decrease inflammatory markers.

Emerging research shows that both NMN and NR may help lower inflammation. However, human clinical trials are still lacking as most studies have been done on animal models or in cell cultures in a lab.

For example, in one study, researchers gave NMN to 24-month-old mice for one week and found a decrease in inflammation markers. Similarly, another study found that NR significantly reduced inflammation in a mouse model of autoimmune thyroiditis, showing promise in therapeutic effects in reducing inflammation.

A preclinical human study analyzed NAD+ metabolism in tissue samples of patients with rheumatoid arthritis (RA) and reported that RA patients had the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity compared to healthy donors. One of the effects they tested was the beneficial effects of NAD+ boosters on peripheral blood mononuclear cells (PBMCs). They found both increased NAD+ levels and reduced inflammatory and oxidative status.

Precautions when taking NAD supplements

While certain NAD supplements are generally regarded as safe and have not been associated with significant adverse effects, given the lack of long-term safety studies, individual reactions may vary. Research in humans has looked at NMN doses of up to 1,200 mg daily for six weeks and reported no adverse events.

The case is similar to NR. A randomized, placebo-controlled, double-blind, parallel-group study involving 140 healthy adults with overweight found that the supplementation of up to 1,000 mg of NR taken for eight weeks was generally well tolerated and not associated with flushing. Such redness to the skin has been found to be a common side effect of niacin, a form of vitamin B3 that’s also a precursor compound to NAD+.

However, potential side effects may include:

• Nausea
• Fatigue
• Headaches
• Gut discomfort

Although the safety profile of NAD boosters appears promising, more long-term studies are necessary to fully understand their broader impacts and long-term effects.

Additional precautions include:

• Allergic reactions. If you have allergies to different forms of vitamin B, make sure to consult with your healthcare provider before starting to take NAD boosters.
• Pregnancy and breastfeeding. Due to a lack of comprehensive safety data, make sure to consult with your healthcare provider before taking NAD+ supplements while pregnant or breastfeeding.

How to take NAD supplements for results

When it comes to NAD boosting, it’s recommended to apply a personalized approach. Considering your genetics, age, various lifestyle factors, and goals, your NAD supplementation may look different from the next person’s. Therefore, to optimize the potential benefits, it is key to tailor dosage, frequency, and timing of consumption to your specific needs.

• Dosage. Studies have shown effects in doses ranging from 250 mg to 1,000 mg per day.
• Frequency. A study has shown a significant increase in NAD levels after as much as four weeks of 250 mg daily NMN supplementation. There were increased levels throughout the 12-week study; however, after participants stopped taking the supplement, their NAD levels returned to baseline after 16 weeks.
• Timing. There are no definitive studies to conclude whether taking NAD boosters at a certain time of the day increases efficacy, so individual results may vary. Some studies have split up the dosage to be administered morning and evening, while others looked at only afternoon supplementation. Both have shown effects at varying degrees.

Where can you find NAD?

Supplementation is not the only way to increase your NAD levels. Dietary sources that contribute to its natural synthesis are crucial, as well as exercise, adequate sleep, and stress management.

• Nutrition. Foods rich in niacin (vitamin B3) may help directly contribute to the production of NAD+. You can find high levels of niacin in chicken breast, tuna, turkey, peanuts, and mushrooms.
• Physical activity. Exercise stimulates the production of an enzyme called NAMPT, which is essential for the biosynthesis of NAD+. This means that by maintaining a regular exercise regimen, you can enhance your body's ability to produce NAD+, contributing to improved energy metabolism and overall cellular health.
• Sleep and stress management. Lack of sleep and high stress levels have been found to deplete NAD. Conversely, diminished NAD levels have been linked to sleep disturbances and a decreased ability of the body to adapt to stressors. Adequate sleep and stress reduction techniques such as meditation, yoga, or deep breathing exercises may help maintain optimal NAD+ production.

Further reading on NAD supplements

To take a deeper dive into NAD+ and its implications for health and longevity, exploring the current literature may be beneficial. These research papers provide a comprehensive look at the scientific evidence supporting the use of NAD supplements and their potential benefits.

This study explores the effects of NMN in a randomized, double-blind, placebo-controlled trial to evaluate its safety and efficacy in increasing NAD+ levels in healthy human subjects over a period of 12 weeks.

This review discusses how NAD+ biosynthesis and its connection to SIRT1 may play a role in managing metabolism and circadian rhythms. Plus, it looks at how supplementing with NAD+ precursors may potentially reverse age-related cellular dysfunction and neurodegenerative diseases, offering a promising anti-aging strategy.

This comprehensive study tested if NMN supplementation in humans would result in similar positive effects on health span that have been observed in animals. This randomized, multicenter, double-blind, placebo-controlled trial involved 80 middle-aged healthy adults who were administered daily doses of either a placebo or 300 mg, 600 mg, or 900 mg of NMN over 60 days.

How to choose the best NAD supplements

When looking for NMN supplements, it’s recommended to approach these products with caution due to concerns about misleading claims. An investigation conducted by ChormaDex found that 64% of tested NMN supplements contained only 1% of the amount of active ingredient stated on the label. This discrepancy raises questions about the efficacy and value of the products being purchased.

Look for supplements from brands that provide a transparent look into their process for testing quality and purity. Even better if they provide a Certificate of Analysis to back up those analyses. Insights into where the brand sources its active ingredients may be also valuable in the decision-making process to ensure you’re choosing a brand with high-quality ingredients. Additional green flags to look for are third-party lab tests, studies investigating product efficacy done by independent organizations, and whether the company is listed as a Best Business Bureau brand and reviewed on Consumer Reports.

📝Healthnews editor's top picks

If you're thinking about adding NAD-boosting supplements to your routine, explore our carefully selected list of the top NAD supplements available, each rigorously reviewed by our experts.

Overall best NAD+ supplement with NR — Tru Niagen

• 300 mg of NR
• Made in GMP-certified facilities and NSF Certified for Sport
• FDA-recognized as GRAS

Try Tru Niagen now

Best NAD+ product from a quality supplier — partiQlar

• 500 mg of NMN
• 99% purity
• The provider gets the raw material from Efferpharm, a leading supplier in the U.S.

Try partiQlar now

Best NAD+ supplement formulation for cognition — Wonderfeel Youngr

• 900 mg of NMN
• 99% purity
• Lion's mane and porcini mushroom blend with vitamin D3 for mental clarity

Try Wonderfeel now