How NAD+ Can Influence Arthritis and Support Joint Health

Recent research has uncovered fascinating connections between a molecule called NAD+ and joint health.

For the millions who struggle with arthritis, this emerging area of study offers new insights into managing joint discomfort and supporting overall joint function.

What Is NAD+ and Why Does It Matter for Joint Health?

NAD+ (nicotinamide adenine dinucleotide) is a vital molecule found in every cell of your body. Think of it as a cellular fuel that helps your cells:

• Create energy from the food you eat
• Fight off harmful oxidative stress
• Repair damaged DNA
• Support your immune system
• Keep cells young and healthy

These functions are especially important for your joints, which need constant maintenance and protection.

Research shows that many factors can lower your NAD+ levels¹, including:

• Poor diet choices
• Infections
• Chronic diseases
• Aging

When NAD+ levels drop, inflammation often increases – which can be a problem for arthritis sufferers.

NAD+ Levels in Arthritis: What Science Tells Us

Several studies have documented alterations in NAD+ metabolism in patients with various forms of arthritis. Rheumatoid arthritis (RA) patients show significantly reduced plasma NAD+ levels compared to healthy individuals.

This NAD+ deficiency appears driven by multiple factors.

Research shows that genes involved in NAD+ consumption—including PARPs (poly-ADP-ribose polymerases), sirtuins (SIRTs), and CD38—are upregulated in rheumatoid arthritis.² Meanwhile, genes responsible for NAD+ biosynthesis are downregulated.

A multi-omics profiling study of collagen-induced arthritis in mice identified early metabolic changes characterized by oxidative stress and a significant drop in NAD+ levels. ³

This suggests that NAD+ depletion may precede and potentially contribute to the inflammatory cascade in arthritis, rather than merely being a consequence of inflammation.

How NAD+ Influences Inflammation and Joint Function

NAD+ impacts joint health through three key pathways:

The Sirtuin Anti-Inflammation Pathway

NAD+ powers proteins called sirtuins, which act as inflammation regulators in your body.

One sirtuin in particular, called SIRT1, works like a volume control for inflammation. When NAD+ levels are healthy, SIRT1 can help:

• Turn down excessive inflammation
• Regulate an important inflammation controller called NF-κB
• Restore balance to your immune response

Studies show that when NAD+ levels drop in arthritis, SIRT1 can’t do its job properly.⁴ This leads to unchecked inflammation and ongoing joint damage.

The CD38 Consumer Problem

CD38 is like a hungry enzyme that eats up NAD+ in your body. People with rheumatoid arthritis often have too much CD38 activity, which means:

• Less NAD+ available for important cellular functions
• More inflammation signals being produced
• Faster progression of joint damage

Research in mice shows that when CD38 is removed or blocked, arthritis symptoms improve significantly.⁵ A new compound called NTX-748 that blocks CD38 has shown promising results in reducing joint inflammation.

The Cellular Compartment Issue

NAD+ needs to be in the right place, not just at the right levels in your body.

Scientists discovered that in rheumatoid arthritis, NAD+ can build up abnormally in certain parts of cells due to a deficiency in an enzyme called QPRT.⁶ This leads to the release of harmful proteins that damage joints.

This finding shows that balancing NAD+ throughout all cellular compartments may be just as important as increasing NAD+ levels.

NAD+ Precursors: Promising Results in Arthritis Models

NAD+ precursors are compounds that the body can use to create NAD+. Several of these have shown promising effects in arthritis research:

Nicotinamide Riboside (NR) in Osteoarthritis

Nicotinamide riboside (NR), a potent NAD+ precursor, has shown promising effects in multiple animal models of osteoarthritis.

In a murine model of monoiodoacetate-induced knee osteoarthritis, NR treatment decreased blood and serum levels of oxidative stress biomarkers. It also reduced histological lesions in a manner comparable to hydrolyzed collagen, a commonly prescribed supplement.⁷

Another study investigating the mitochondrial unfolded protein response (UPRmt) in osteoarthritis found that enhancement of UPRmt with NR significantly improved mitochondrial function and reduced chondrocyte death. It also attenuated osteoarthritis pain and ameliorated disease progression.⁸

Dihydronicotinamide Riboside and Post-Traumatic Osteoarthritis

Research shows that dihydronicotinamide riboside (NRH), another orally bioavailable NAD+ precursor, significantly inhibited post-traumatic osteoarthritis development and associated pain in mice.⁹

Similarly, nicotinamide riboside supplementation has been found to modulate pro-fibrotic gene expression in a murine model of post-traumatic osteoarthritis, as has CD38 loss of function.

NAD+ Boosters in Rheumatoid Arthritis

In rheumatoid arthritis models, NAD+ boosters have shown potential as novel anti-inflammatory tools.

When peripheral blood mononuclear cells from active RA patients were treated ex vivo with NAD+ boosters—including nicotinamide (NAM) and NR—anti-inflammatory effects were observed.²

Interestingly, estrogen’s protective effects against rheumatoid arthritis may be partially mediated through alterations in nicotinamide metabolism.

A study investigating the impact of 17β-estradiol (E2) on the metabolome of synovial fibroblasts from RA patients found that nicotinate and nicotinamide metabolism was highly correlated with E2 treatment.¹⁰

Clinical Evidence: What We Know So Far

Despite promising preclinical findings, clinical evidence for the efficacy of NAD+ precursors in treating arthritis or supporting joint health in humans remains limited.

A comprehensive review of 25 published research articles on human nicotinamide riboside supplementation found that oral NR supplementation has displayed few clinically relevant effects overall.¹¹

However, the review noted that nicotinamide riboside may play a role in reducing inflammatory states and has shown some potential in the treatment of diverse severe diseases.

A twin study investigating long-term NR supplementation found that NR improved systemic NAD+ metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition.¹²

While this study did not specifically evaluate joint health, the improvements in mitochondrial function and systemic inflammation markers could indirectly benefit joint tissues.

Practical Considerations for NAD+ Supplementation

Currently, there are no official guidelines for NAD+ supplementation. The recommendations we have for vitamin B3 (a basic NAD+ building block) only focus on preventing deficiency diseases – not optimizing cellular health.

Scientists believe that NAD+ precursors like NR could become recommended supplements in the future¹³, but we more research will be helpful to determine:

• The most effective NAD+ dosages
• Who would benefit most
• The best timing and delivery methods
• Longer-term safety

Why might your response to NAD+ supplements differ from someone else’s? Several factors affect how your body uses these supplements:

• Your current NAD+ levels (which most people don’t know without testing)
• Your age and overall metabolic health
• Other health conditions you may have
• Medications you’re taking that might interact with NAD+ metabolism

If you have arthritis and are considering NAD+ supplementation, it’s best to:

• Work with a healthcare provider familiar with NAD+ science
• Consider testing your NAD+ levels before and after supplementation
• Monitor your symptoms and inflammation markers to see if the approach is working for you

The Jinfiniti Approach to NAD+ Optimization

At Jinfiniti Precision Medicine, we follow our TAO philosophy—Test, Act, Optimize—to support healthy NAD+ levels:

Test

Our Intracellular NAD® Test is the first step to understanding your personal NAD+ status:

• Simple finger-prick blood collection you can do at home
• Clinical-grade testing of your actual cellular NAD+ levels
• Personalized dosage recommendations based on your results

This test solves a critical problem: the same NAD+ dose that helps one person could be ineffective or even harmful for another.

Act

Based on your test results, you can choose from our science-backed NAD+ support options:

• Vitality↑® NAD Booster: Our premier supplement containing a precise blend of NAD+ precursors, creatine monohydrate, D-ribose, and niacinamide in a patent-pending formulation.
• Pure NMN Powder: A high-purity (99.5% verified) Nicotinamide Mononucleotide supplement for those who prefer a single-ingredient approach.

Optimize

To complete the cycle and ensure your supplementation is effective:

• NAD Optimization® Starter Package: This complete solution includes two NAD+ tests (before and after supplementation), our Vitality↑® NAD Booster, and a personalized consultation to help interpret your results.

The Future of NAD+ in Joint Health

The relationship between NAD+ metabolism and joint health is complex but increasingly well-understood. Dysregulation of NAD+ levels, often characterized by systemic depletion and altered expression of NAD+-synthesizing and -consuming enzymes, appears to be a feature of arthritis conditions.

NAD+ precursors and inhibitors of NAD+-consuming enzymes have shown promise in preclinical models of arthritis, suggesting potential therapeutic applications. However, clinical evidence in humans is still limited, indicating a need for further research to translate these findings into effective treatments.

By taking a personalized, data-driven approach to NAD+ optimization, individuals may be able to support their joint health and overall cellular function.

The Jinfiniti TAO methodology—Test, Act, Optimize—provides a framework for this personalized approach, allowing for targeted interventions based on individual biomarker results.

As research in this field continues to evolve, we remain committed to staying at the forefront of NAD+ science and bringing evidence-based solutions to those seeking to optimize their healthspan.

Referenced Citations:

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176364/ ↩︎
2. https://ard.eular.org/article/S0003-4967(24)64585-1/abstract ↩︎
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC9276706/ ↩︎
4. https://pubmed.ncbi.nlm.nih.gov/38638042/ ↩︎
5. https://ard.eular.org/article/S0003-4967(24)64574-7/abstract ↩︎
6. https://www.medrxiv.org/content/10.1101/2024.10.27.24316032v1 ↩︎
7. https://pmc.ncbi.nlm.nih.gov/articles/PMC10650314/ ↩︎
8. https://pmc.ncbi.nlm.nih.gov/articles/PMC9723171/ ↩︎
9. https://www.oarsijournal.com/article/S1063-4584(22)00474-5/fulltext ↩︎
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC11052502/ ↩︎
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC10361580/ ↩︎
12. https://pmc.ncbi.nlm.nih.gov/articles/PMC9839336/ ↩︎
13. https://cdn.nutrition.org/article/S2475-2991(23)11845-2/pdf ↩︎