Does NAD+ reduce inflammation? Unpacking the cellular mechanisms

December 26, 2025 •

4 min read

Chronic inflammation has been shown to reduce the body's NAD+ levels, creating a vicious cycle of cellular decline and persistent inflammatory signaling. In response, a growing body of research is exploring if boosting NAD+ levels can effectively counteract this process and if NAD+ reduce inflammation as a therapeutic strategy.

Quick Summary

NAD+ plays a critical role in modulating the body's inflammatory response by activating sirtuins, combating oxidative stress, and supporting mitochondrial health. This can help reduce chronic inflammation, which is linked to aging and various diseases. Evidence suggests a two-way relationship where inflammation depletes NAD+, and restoring NAD+ may offer anti-inflammatory benefits.

Key Points

NAD+ and Inflammation Cycle: Chronic inflammation depletes NAD+ levels, which in turn exacerbates inflammation via overactive NAD+-consuming enzymes like CD38, creating a detrimental feedback loop.
Sirtuin Activation: NAD+ boosts anti-inflammatory effects by serving as a cofactor for sirtuin enzymes, particularly SIRT1, which inhibits pro-inflammatory signaling proteins like NF-κB.
Combats Oxidative Stress: NAD+ supports the body's natural antioxidant systems by aiding in NADPH production, thereby reducing the cellular damage and inflammation caused by oxidative stress.
Supports Mitochondrial Health: By maintaining healthy mitochondrial function and energy production, NAD+ prevents the release of inflammatory signals from dysfunctional mitochondria.
NAD+ Precursors Show Promise: Supplements containing NAD+ precursors like NMN and NR have been shown in various studies to increase NAD+ levels, offering potential anti-inflammatory benefits, though more human data is needed.
Supports Cellular Repair: The coenzyme is vital for activating DNA repair mechanisms, and a decline in NAD+ can lead to accumulated cellular damage that triggers and sustains inflammation.
Evidence in Chronic Conditions: Research suggests that restoring NAD+ levels holds therapeutic potential for inflammatory diseases such as Inflammatory Bowel Disease and vascular dysfunction.

The Vicious Cycle: How Inflammation Depletes NAD+

Chronic, low-grade inflammation, often referred to as "inflammaging," is a key driver of age-related disease and is intrinsically linked to declining levels of nicotinamide adenine dinucleotide (NAD+). Research shows that an increase in inflammatory proteins, known as the senescence-associated secretory phenotype (SASP), promotes the proliferation of immune cells that overexpress the enzyme CD38. This enzyme is a major consumer of NAD+, and its hyperactivity effectively drains the body's NAD+ reserves, exacerbating cellular dysfunction and further promoting inflammation. This creates a negative feedback loop where inflammation leads to reduced NAD+, which in turn fuels more inflammation.

Core Mechanisms: How NAD+ Modulates the Inflammatory Response

Research has identified several key pathways through which NAD+ exerts its anti-inflammatory effects:

Sirtuin Activation: NAD+ acts as a required cofactor for sirtuins (SIRT1-7), a family of enzymes that regulate cellular health and inflammation. Specifically, SIRT1 has been shown to inhibit the activity of NF-κB, a central protein complex that drives the production of pro-inflammatory molecules. By activating SIRT1, NAD+ can help "turn down the volume" on excessive inflammatory signaling.
Oxidative Stress Reduction: An imbalance between free radicals (reactive oxygen species, ROS) and antioxidant defenses is a hallmark of inflammation. NAD+ is involved in the synthesis of NADPH, a molecule crucial for regenerating the body's antioxidants. By bolstering antioxidant defenses, NAD+ helps to mitigate the cellular damage and inflammation caused by oxidative stress.
Enhanced Mitochondrial Function: Mitochondria, the cell's energy factories, play a regulatory role in inflammation. Dysfunctional mitochondria can release signals that trigger an inflammatory response. By supporting mitochondrial health and energy production, NAD+ helps prevent this mitochondrial-driven inflammation.
Cellular and DNA Repair: Inflammation is often the result of cellular and DNA damage. NAD+ is essential for activating enzymes like PARPs, which are involved in repairing DNA. A decline in NAD+ impairs DNA repair, leading to the accumulation of damage that triggers and sustains inflammation.

The Role of NAD+ Precursors

Boosting NAD+ levels is a primary strategy for combating this NAD+-inflammation feedback loop. Since direct NAD+ supplementation is often inefficient due to poor absorption, precursors that the body can convert into NAD+ are used. Nicotinamide mononucleotide (NMN) and Nicotinamide Riboside (NR) are the most studied precursors.

NMN: A recent study showed NMN mitigating viral-mediated inflammation by preventing the elevation of pro-inflammatory proteins. Other research has found NMN to reduce inflammation in the gut and fat tissue, as well as brain inflammation in animal models. Human trials on NMN are ongoing and show promise in improving various metabolic markers, which are often linked to chronic low-grade inflammation.
NR: Clinical trials have shown NR to be safe and effective at increasing NAD+ levels. While direct evidence linking NR to inflammation reduction in humans is still limited, its ability to boost NAD+ suggests potential anti-inflammatory effects. Further research is exploring NR's impact on inflammatory markers in diverse populations.

Comparison of Anti-Inflammatory Mechanisms

To understand the full picture, it's helpful to compare the anti-inflammatory pathways of NAD+ boosters against traditional anti-inflammatory agents.


Feature	NAD+ Boosters (e.g., NMN, NR)	Traditional Anti-inflammatories (e.g., NSAIDs)
Mechanism of Action	Indirect modulation via boosting NAD+ to activate sirtuins, reduce oxidative stress, and enhance mitochondrial health.	Direct inhibition of inflammatory enzymes (e.g., COX-1 and COX-2) to block prostaglandin synthesis.
Inflammatory Target	Systemic, addresses underlying cellular dysfunction that drives chronic inflammation.	Localized and acute, primarily focused on symptomatic relief.
Effect on Cellular Function	Supports overall cellular repair, metabolism, and energy production, promoting healthier cellular aging.	Can have side effects on the gastrointestinal tract and kidneys with long-term use.
Metabolic Impact	Positive influence on metabolism by increasing cellular energy production and fat oxidation.	Does not directly address metabolic health or mitochondrial function.
Long-Term Implications	Focuses on addressing root causes of chronic inflammation, potentially reducing age-related disease risk.	Treats symptoms, but does not address the underlying causes of chronic inflammation.

Potential for IBD and Other Conditions

Beyond general aging, NAD+ has been investigated for its potential to reduce inflammation in specific diseases. Studies on Inflammatory Bowel Disease (IBD) show an upregulation of NAD+-consuming enzymes like CD38 and PARPs in inflamed tissue, correlating with reduced NAD+ levels. Restoring NAD+ levels through precursors has shown promise in animal models by promoting intestinal repair and restoring function. Similarly, in animal models of vascular dysfunction, increasing NAD+ levels reduced vascular inflammation and improved endothelial function. Research is also exploring NAD+'s role in neuroinflammation and metabolic diseases, where chronic inflammation is a significant factor. This suggests a broad therapeutic potential for NAD+ in various inflammatory conditions. For more information on the intricate connection between NAD+ and inflammatory diseases, you can refer to NAD+ Metabolism and Immune Regulation.

Lifestyle Interventions to Support NAD+ and Reduce Inflammation

While supplements offer a direct route, several lifestyle choices can support natural NAD+ levels and provide anti-inflammatory benefits:

Exercise: Regular physical activity is linked to higher NAD+ levels and improved mitochondrial function.
Caloric Restriction and Intermittent Fasting: These practices have been shown to increase NAD+ levels and activate sirtuins, contributing to anti-inflammatory effects.
Anti-inflammatory Diet: A diet rich in antioxidants and omega-3 fatty acids can support cellular health and reduce inflammation.

Conclusion

Does NAD+ reduce inflammation? While NAD+ is not a direct anti-inflammatory drug, research strongly supports its crucial role in modulating the body's inflammatory response. By addressing the root causes of chronic inflammation—including sirtuin activity, oxidative stress, and mitochondrial health—NAD+ helps restore cellular balance. Evidence from animal and human studies on its precursors like NMN and NR suggests significant therapeutic potential, especially for conditions where inflammation and NAD+ depletion create a negative feedback loop, such as in aging and certain chronic diseases. However, more extensive human clinical trials are needed to fully understand its efficacy and application. Lifestyle interventions that support healthy NAD+ levels can further enhance these effects, offering a holistic approach to managing inflammation and promoting overall cellular health.

Frequently Asked Questions

Chronic, low-grade inflammation, or 'inflammaging', is associated with a decline in NAD+ levels. The inflammatory process activates enzymes, particularly CD38, that consume NAD+ at an accelerated rate, thereby depleting cellular NAD+ reserves and further fueling the inflammatory response.

NAD+ supports anti-inflammatory pathways primarily by activating sirtuin enzymes, such as SIRT1. SIRT1 inhibits the activity of NF-κB, a key protein complex responsible for producing pro-inflammatory cytokines, effectively reducing inflammation at a cellular level.

While direct evidence in humans is still developing, studies on NAD+ precursors like Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NR) show promising anti-inflammatory effects, particularly in animal models. By increasing NAD+ levels, these precursors support cellular functions that help counteract inflammation.

Yes, several lifestyle interventions can naturally increase NAD+ levels, which can help reduce inflammation. These include regular exercise, caloric restriction, and intermittent fasting. Adopting an anti-inflammatory diet can also support these cellular processes.

Yes, NAD+ can help modulate immune function and cytokine production. By regulating inflammatory signaling through sirtuins, NAD+ helps balance the immune response. For example, some studies suggest that increased NAD+ levels can suppress the production of pro-inflammatory cytokines like IL-6 and TNF-α.

In diseases like arthritis and Inflammatory Bowel Disease (IBD), increased NAD+-consuming enzymes and reduced NAD+ levels are common. Restoring NAD+ through supplementation has shown potential to protect against inflammation, improve intestinal barrier function, and support joint health in preclinical and animal models.

NAD+ is not a direct replacement for traditional anti-inflammatories (NSAIDs). Instead of blocking inflammation acutely, it modulates underlying cellular pathways that cause chronic inflammation, making it a complementary approach for long-term cellular health rather than immediate symptom relief.