Nicotinamide Riboside (NR): Raise Your NAD+ Levels

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If you’ve been hearing a lot about anti-aging lately, it’s largely because of discoveries related to substances including nicotinamide riboside (NR) that are able to raise the levels of a critical energy production molecule called NAD. In this article, we discuss the ways you can raise your NAD levels both naturally, and through supplementation with NR.

What Is NR?

NR stands for nicotinamide riboside, which is a form of Vitamin B3. It is a molecule that can be converted into NAD+ (nicotinamide adenine dinucleotide) in the cells. NAD+ is a molecule that plays a vital role in cellular functions, including energy production and DNA repair.

NR is often used as a dietary supplement to increase NAD+ levels and support various biological processes. It is believed to have potential benefits for metabolism, energy levels, and overall cellular health. Ongoing research is being conducted to better understand the effects and potential uses of NR in promoting well-being.

What Are The Health Benefits of Nicotinamide Riboside?

Here are some of the notable health benefits associated with NR:

• Boosts NAD+ Levels: NR is an efficient way to increase NAD+ levels in the body. NAD+ is essential for energy metabolism, DNA repair, and cellular signaling, and its levels decline with age.
• Supports Healthy Aging: By increasing NAD+ levels, NR may help counteract some aspects of aging at the cellular level. This includes improving mitochondrial function, protecting against cellular damage, and possibly extending lifespan.
• Improves Metabolic Health: Some studies suggest that NR supplementation can improve metabolic markers, such as reducing insulin sensitivity and lowering blood sugar levels, which are beneficial for metabolic health and may help protect against metabolic syndrome and diabetes.
• Neuroprotection: NR may have neuroprotective effects, potentially supporting brain health by enhancing cognitive function, increasing brain NAD+ levels, and offering protection against neurodegenerative diseases.
• Enhances Muscle Function: Increasing NAD+ levels through NR supplementation could improve muscle function and endurance, potentially countering age-related muscle decline.
• Cardiovascular Health: There is emerging evidence that NR could support cardiovascular health by improving endothelial function, reducing oxidative stress, and lowering blood pressure in certain contexts.
• May Reduce Cancer Risk: Preliminary research suggests that boosting NAD+ levels through NR supplementation could play a role in cancer prevention and complement cancer treatment by enhancing the efficacy of certain therapies and reducing side effects.

It’s important to note that while NR shows promise for various health benefits, research is ongoing, and more studies are needed to fully understand its effects, optimal dosages, and long-term safety.

Can You Raise NAD Levels Without Supplements?

The answer is yes, and it’s simple but not necessarily easy. Diet and exercise. Here is the research on how this age-old advice works to raise your NAD levels.

Calorie Restriction

Calorie restriction (CR) is a dietary intervention that involves reducing daily caloric intake by 20-40% without causing malnutrition. It has been shown to extend lifespan, improve health, and delay age-related diseases in various organisms, including yeast, worms, flies, rodents, and potentially humans. One of the mechanisms through which calorie restriction exerts its beneficial effects is by boosting NAD (Nicotinamide Adenine Dinucleotide) levels in cells.

NAD is a crucial coenzyme that plays a vital role in many cellular processes, including metabolism, energy production, and DNA repair. It is also a substrate for enzymes like sirtuins, which are involved in regulating cellular aging and maintaining cellular health. Higher NAD levels have been associated with improved cellular function, increased stress resistance, and delayed aging.

Calorie restriction boosts NAD levels through several mechanisms:

• Enhanced NAD biosynthesis: Calorie restriction stimulates the expression of NAMPT (Nicotinamide phosphoribosyltransferase), an enzyme involved in the salvage pathway of NAD biosynthesis. Increased NAMPT activity results in higher NAD production, contributing to higher cellular NAD levels.
• Reduced NAD consumption: Calorie restriction reduces the activity of enzymes that consume NAD, like poly (ADP-ribose) polymerases (PARPs) and CD38. PARPs are involved in DNA repair and cellular stress response, while CD38 is a multifunctional enzyme associated with NAD degradation. By reducing their activity, CR conserves NAD levels in cells.
• Shift in energy metabolism: CR promotes a shift from glucose metabolism to fatty acid oxidation, which favors the production of ketone bodies. This metabolic shift increases the NAD+/NADH ratio, thereby making more NAD+ available for cellular processes, including the activation of sirtuins.
• Increased mitochondrial function: Calorie restriction enhances mitochondrial biogenesis and function, which can boost NAD+ levels. Improved mitochondrial function results in higher energy production, more efficient use of nutrients, and reduced oxidative stress, which together contribute to increased NAD+ levels.

In summary, calorie restriction boosts NAD levels through various mechanisms that involve enhancing NAD biosynthesis, reducing NAD consumption, shifting energy metabolism, and improving mitochondrial function. These changes promote cellular health and stress resistance, ultimately contributing to the lifespan-extending and health-promoting effects of calorie restriction.

Exercise

Exercise is another effective way to increase NAD levels in the body. Regular physical activity has numerous health benefits, including improved cardiovascular function, enhanced muscle strength, and reduced risk of chronic diseases. Several mechanisms are involved in the increase of NAD levels during and after exercise:

• Enhanced NAD biosynthesis: Exercise stimulates the expression of the enzyme NAMPT (Nicotinamide phosphoribosyltransferase), which is involved in the NAD salvage pathway. This pathway recycles nicotinamide (a form of vitamin B3) into NAD, thereby increasing its production. Higher NAMPT expression results in higher cellular NAD levels.
• Increased AMPK activation: Exercise leads to an increase in the cellular energy demand, which in turn results in the activation of AMP-activated protein kinase (AMPK). AMPK is a cellular energy sensor that helps maintain energy homeostasis by promoting catabolic processes and inhibiting anabolic processes. AMPK activation can upregulate NAD production by increasing the expression of NAMPT and promoting mitochondrial biogenesis.
• Improved mitochondrial function: Exercise enhances mitochondrial biogenesis, function, and efficiency, leading to an increase in cellular NAD+ levels. Enhanced mitochondrial function promotes better nutrient utilization and reduces oxidative stress, which can contribute to increased NAD+ levels.
• Shift in energy metabolism: Exercise promotes a shift in energy metabolism from glucose metabolism to fatty acid oxidation. This metabolic shift increases the NAD+/NADH ratio, making more NAD+ available for cellular processes, including sirtuin activation.
• Sirtuin activation: Sirtuins are a family of NAD+-dependent enzymes that play a significant role in regulating cellular aging and maintaining cellular health. Exercise-induced increases in NAD+ levels promote sirtuin activation, which in turn contributes to improved cellular function, stress resistance, and mitochondrial biogenesis.

To summarize, exercise can increase NAD levels through various mechanisms, including enhanced NAD biosynthesis, increased AMPK activation, improved mitochondrial function, a shift in energy metabolism, and sirtuin activation. Regular physical activity not only boosts NAD levels but also promotes overall health and well-being.

Is NR helpful For Aging Muscles and Inflammation?

Nicotinamide riboside (NR) supplements hold promise for addressing age-related muscle decline and inflammation. Studies suggest that NR supplementation may enhance muscle health in aging individuals by increasing molecules related to energy production in skeletal muscles. Although NR did not directly improve mitochondrial function, it improved the availability of essential energy-related molecules, potentially supporting muscle strength and mobility with age. Additionally, NR showed promise in reducing circulating inflammatory cytokines, indicating potential benefits for managing inflammation associated with aging and various inflammatory conditions. These findings underscore NR’s potential as a valuable supplement for promoting muscle health and addressing inflammation in aging individuals. PMC6702140

NR (nicotinamide riboside) May Be More Effective For People Near Their Ideal Weight

NR is degraded by an immune component called CD38. CD38 is higher in people who are at higher weights. This may be why NR is not found to increase NAD in studies with subjects carrying extra weight. But there’s an alternative. For people whose BMI numbers are above 30, it’s important to know that NMN supplementation has been shown to be effective in raising NAD levels in all groups studied. Visit our NMN page here.

[PMID: 29514064]

Is NR Safe?

Nicotinamide riboside (NR) is considered safe for most people when taken as a supplement within the recommended dosages. However, research on NR is still relatively limited, and more long-term studies are needed to fully understand its safety profile. Consult with a healthcare professional before starting NR supplementation, especially if you are pregnant, nursing, have pre-existing health conditions, or are taking medications, to ensure its safety and suitability for your individual needs.

What Other Supplements Interact with NR?

Nicotinamide riboside (NR) is a precursor of nicotinamide adenine dinucleotide (NAD+) and a popular supplement used to increase NAD+ levels. When considering supplements that interact with NR, it’s essential to keep in mind that interactions can be synergistic (complementary) or antagonistic (inhibiting).

Here are some supplements that can interact with NR:

• Synergistic interactions: Resveratrol: Resveratrol is a polyphenolic compound found in grapes, berries, and peanuts. It is known to activate sirtuins, which are NAD+-dependent enzymes involved in regulating cellular aging and maintaining cellular health. The combination of NR and resveratrol may provide synergistic effects on cellular health and longevity by increasing NAD+ levels and promoting sirtuin activation.b. Pterostilbene: Pterostilbene is a naturally occurring compound found in blueberries, which has a similar structure to resveratrol. It also activates sirtuins and may have synergistic effects when combined with NR.c. Quercetin: Quercetin is a flavonoid found in many fruits and vegetables, with antioxidant and anti-inflammatory properties. Quercetin has been shown to increase NAD+ levels and may work synergistically with NR to promote cellular health.
• Antagonistic interactions: Nicotinic acid (niacin): Nicotinic acid, also known as niacin, is another precursor of NAD+. High doses of niacin can compete with NR for the same metabolic pathways and enzymes, potentially limiting the effectiveness of NR supplementation. But, moderate doses of niacin may not have significant antagonistic effects on NR. Nicotinamide is a form of vitamin B3 and another precursor of NAD+. It can potentially compete with NR for the same enzymes, thus inhibiting the effectiveness of NR supplementation. Additionally, nicotinamide can inhibit sirtuin activity, which might counteract some of the benefits of increased NAD+ levels from NR supplementation.

What Medications and Supplements Interact With NR?

Nicotinamide riboside (NR) is a form of vitamin B3 and a precursor to nicotinamide adenine dinucleotide (NAD+). While NR is generally considered safe, there is limited research on potential interactions between NR and medications. However, some medications may interact with NR due to their effects on NAD+ metabolism or vitamin B3. Some possible interactions include:

• Blood Pressure Medications: NR has the ability to reduce arterial stiffness and improve systolic blood pressure. This is a very good thing, but if you are taking medication to lower your blood pressure, be sure to monitor for changes in blood pressure when taking NR. [PMC9127073]
• Anticonvulsant medications: Certain anticonvulsants, such as valproic acid and carbamazepine, can reduce the levels of NAD+ in the body. Supplementing with NR may counteract this effect by increasing NAD+ levels. It’s essential to consult with a healthcare professional before combining NR with anticonvulsants, as the interaction may affect the effectiveness of the medication.
• NR May Reduce Side Effects of Statins: Statins are medications used to lower cholesterol levels. Some studies suggest that statins can reduce NAD+ levels in cells, which might lead to muscle-related side effects. Combining NR with statins could potentially help restore NAD+ levels and alleviate some side effects. However, more research is needed to confirm this interaction, and it is crucial to consult a healthcare professional before using NR with statins.
• Niacin or nicotinic acid May Reduce the Benefit of NR: High doses of niacin or nicotinic acid, another form of vitamin B3, can compete with NR for the same metabolic pathways and enzymes. This competition may reduce the effectiveness of NR supplementation. If you are taking niacin for therapeutic purposes, it’s important to discuss with your healthcare provider before adding NR to your regimen.

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Dietary supplements are not designed to diagnose, treat, cure, or prevent any disease. The Supplement Sciences website seeks to provide comprehensive access to the most relevant supplement information along with convenient online ordering. We do not provide medical advice and cannot guarantee that every product suggested is completely without risk. Since each person is unique in their health history and medication use, it is important to discuss supplements with your personal physician. Specifically, pregnant women and individuals being treated for cancer or liver or kidney problems must consult their physician about every nutritional supplement they plan to take. People taking medications for the treatment of HIV or with a history of organ transplant must not take supplements without consulting with their physician.