How Does NMN Affect Inflammation? A Comprehensive Look at the Mechanisms

November 23, 2025 •

4 min read

According to numerous animal and in-vitro studies, NMN supplementation can mitigate inflammation by restoring cellular nicotinamide adenine dinucleotide (NAD+) levels. The decline of NAD+ is a hallmark of aging and is closely linked with chronic inflammation, a state often called "inflammaging". Understanding how NMN affects inflammation at a molecular level is crucial for appreciating its therapeutic potential.

Quick Summary

NMN influences inflammation by increasing NAD+ levels, which in turn regulates key cellular processes involved in the inflammatory response. It suppresses pro-inflammatory cytokines like IL-6 and TNF-α while promoting anti-inflammatory signaling and combating oxidative stress, which together help mitigate both acute and age-related chronic inflammation in various tissues.

Key Points

Restores NAD+ Levels: NMN boosts cellular NAD+ levels, which are crucial for regulating inflammation and decline with age.
Suppresses Pro-Inflammatory Cytokines: NMN has been shown to reduce the production of key inflammatory signaling molecules, including IL-6, IL-1β, and TNF-α.
Modulates Macrophage Activity: It promotes the transition of macrophages from a pro-inflammatory (M1) to an anti-inflammatory (M2) state, helping to resolve inflammation.
Activates Anti-inflammatory Pathways: NMN influences specific cellular pathways, such as the kynurenine/AhR pathway, to suppress the inflammatory response.
Combats Oxidative Stress: By increasing NAD+ levels, NMN improves mitochondrial function and enhances antioxidant defenses, which reduces inflammation-fueling oxidative stress.
Addresses Chronic and Age-Related Inflammation: Evidence suggests NMN can help mitigate chronic, low-grade inflammation associated with aging, known as "inflammaging".
Acts Broadly on Cellular Mechanisms: NMN's effects go beyond a single target, influencing several molecular cascades that collectively contribute to a healthier inflammatory balance.

The Connection Between NMN, NAD+, and Inflammation

Nicotinamide mononucleotide (NMN) is a precursor to nicotinamide adenine dinucleotide (NAD+), a coenzyme vital for numerous cellular functions, including metabolism, DNA repair, and gene expression. A decline in NAD+ levels is a well-documented aspect of aging and is directly correlated with an increase in systemic, low-grade inflammation. This inflammatory state, known as 'inflammaging,' is a major contributor to many age-related diseases. By supplementing NMN, the body can increase NAD+ levels, thereby influencing inflammatory pathways and helping to restore a healthier cellular environment.

How NAD+ Levels Influence Inflammatory Responses

Inflammation triggers high consumption of NAD+ by enzymes like poly(ADP-ribose) polymerases (PARPs), which are involved in DNA repair and inflammatory signaling. As NAD+ levels drop, the body's ability to regulate inflammatory processes and other cellular functions is compromised. NMN counteracts this by replenishing NAD+ stores, allowing for proper regulation of these critical pathways.

Key mechanisms involved in NMN's anti-inflammatory action include:

Restoring NAD+ to power sirtuin (SIRT) activity, particularly SIRT1, which is known for its role in regulating inflammation.
Downregulating the expression of pro-inflammatory cytokines, which are signaling molecules that promote inflammation.
Suppressing key inflammatory pathways like the NF-κB and MAPK signaling cascades.

Cellular and Molecular Mechanisms of NMN's Anti-inflammatory Effects

NMN’s anti-inflammatory properties are not a single-action process but rather a complex series of molecular events. Research on animal and cell models has illuminated several of these key mechanisms.

Regulation of Cytokine Production: NMN has been shown to reduce the expression and secretion of powerful pro-inflammatory cytokines. In particular, studies have demonstrated a decrease in interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) after NMN supplementation. These cytokines are central to the inflammatory cascade, and their reduction is a primary way NMN helps mitigate inflammation.

Modulation of Macrophage Polarization: Macrophages are immune cells that can exist in different states, primarily pro-inflammatory (M1) and anti-inflammatory (M2). NMN has been observed to promote the shift of macrophages from the M1 to the M2 phenotype. This shift helps to resolve inflammation rather than perpetuate it, which is crucial for managing chronic inflammatory conditions like atherosclerosis.

Activation of the Kynurenine/AhR Pathway: A recent study identified a novel mechanism where NMN suppresses inflammatory responses by activating the indoleamine 2,3-dioxygenase (IDO)-kynurenine-aryl hydrocarbon receptor (AhR) pathway. NMN supplementation leads to an accumulation of kynurenine, which then activates the AhR. This cascade ultimately decreases the expression of the inflammatory enzyme COX-2, which is also a target for NSAIDs.

NMN vs. NSAIDs for Inflammation Management


Feature	NMN Supplementation	Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
Mechanism	Boosts NAD+ levels, modulates inflammation signaling pathways, reduces oxidative stress.	Block the activity of COX enzymes (COX-1 and COX-2) to reduce prostaglandin production.
Targeted Conditions	Broad range, including age-related inflammation, atherosclerosis, and metabolic disorders.	Symptom relief for pain and inflammation related to injuries, arthritis, and fever.
Long-Term Side Effects	Generally well-tolerated in studies, though more human data is needed for definitive safety profiles.	Can cause gastrointestinal side effects like bleeding, as well as kidney and cardiovascular issues with prolonged use.
Action on Inflammation	Addresses underlying metabolic and cellular drivers of inflammation, potentially mitigating root causes.	Primarily treats the symptoms by blocking an inflammatory enzyme, without addressing upstream issues.

Research Findings on NMN's Effects on Inflammation

Research on NMN and inflammation continues to provide compelling evidence for its therapeutic potential across different disease models. A study published in Free Radical Biology and Medicine showed that NMN significantly suppressed inflammation in mouse models by restoring NAD+ levels and downregulating the inflammatory enzyme COX-2. Another key finding from a study in Scientific Reports highlighted NMN's ability to mitigate inflammation induced by viral infections in human lung and coronary artery cells. The findings suggested NMN could aid in cellular defense against viruses by altering the activation of specific proteins.

In the context of atherosclerosis, a chronic inflammatory disease, an animal study demonstrated that NMN reduced the size of atherosclerotic plaques by decreasing pro-inflammatory cytokines and increasing anti-inflammatory factors in aortic tissue. This protective effect was also linked to NMN's ability to promote an anti-inflammatory macrophage phenotype. However, one study noted that NMN worsened inflammatory arthritis severity in rats by up-regulating NAMPT, indicating that NMN's effect may vary depending on the specific inflammatory condition and its underlying drivers. This highlights the need for careful consideration and further research, especially in human clinical trials.

For a deeper dive into the broader physiological effects of NMN, the National Institutes of Health has published a comprehensive review on the safety and anti-aging effects in humans and animals.

Conclusion

NMN exerts significant anti-inflammatory effects by acting as a precursor to NAD+, which is critical for cellular health and proper immune function. Through mechanisms like reducing pro-inflammatory cytokine production, shifting macrophage phenotypes, and activating specific signaling pathways such as kynurenine/AhR, NMN helps to mitigate both acute and chronic inflammation. While robust preclinical evidence supports NMN's role as a potent anti-inflammatory agent, especially in age-related conditions, it is important to acknowledge that some inflammatory conditions may respond differently. Further human clinical trials are essential to fully understand NMN's therapeutic scope and optimize its use for inflammation management.

Frequently Asked Questions

NMN's primary mechanism is acting as a precursor to Nicotinamide Adenine Dinucleotide (NAD+). By increasing intracellular NAD+ levels, NMN restores the proper function of key enzymes and signaling pathways that regulate inflammatory responses and cellular metabolism.

Yes, chronic, low-grade inflammation often associated with aging (known as "inflammaging") is linked to declining NAD+ levels. By restoring NAD+, NMN can help mitigate this process, as demonstrated in several preclinical studies.

Yes, NMN has been observed to significantly reduce the expression and secretion of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α in various cell and animal models.

NMN is not a direct antioxidant but can enhance the body's antioxidant capacity. By improving mitochondrial function and reducing oxidative stress, it helps create a cellular environment that is less prone to inflammatory damage.

Unlike non-steroidal anti-inflammatory drugs (NSAIDs), which primarily block specific inflammatory enzymes like COX-2, NMN addresses the upstream, metabolic causes of inflammation. NMN may offer a broader, potentially safer approach, especially for chronic conditions, though human research is still in progress.

Macrophages are immune cells involved in inflammation. NMN has been shown to modulate their function by promoting a shift from a pro-inflammatory (M1) to an anti-inflammatory (M2) phenotype, helping to resolve inflammation.

While most research suggests anti-inflammatory benefits, one animal study on inflammatory arthritis found NMN worsened the condition by upregulating NAMPT, a component of the NAD+ pathway. This highlights that effects can vary by condition, and more human clinical data is needed to confirm safety and efficacy for all inflammatory diseases.

Yes, studies have shown NMN's anti-inflammatory effects in various tissues. For instance, research has shown NMN can reduce lung inflammation in response to injury and alleviate vascular inflammation linked to atherosclerosis.