What is the role of Nicotinamide adenine dinucleotide (NAD+) in reducing inflammation?

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Last updated: April 29, 2025View editorial policy

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From the Guidelines

NAD+ supplementation, specifically through its precursors nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), is recommended to lower inflammation, with suggested doses of 250-500mg daily for NR or 250-1000mg daily for NMN, based on the most recent evidence 1. When considering NAD+ for inflammation reduction, it's crucial to understand its role in energy metabolism and its impact on mitochondrial function, as highlighted in the study by Aytekin et al. 1. NAD+ plays a significant role in transferring hydride ions within dehydrogenase–reductase systems, which is essential for maintaining cellular energy homeostasis. The depletion of NAD+ can lead to a 'cellular energy crisis' caused by mitochondrial dysfunction, which in turn can result in increased oxidative stress and inflammation 1.

Key Considerations for NAD+ Supplementation

  • Dosing: The recommended doses are based on the premise of maintaining or increasing NAD+ levels to support mitochondrial function and reduce oxidative stress.
  • Administration: Taking NAD+ precursors in the morning with food may enhance absorption and efficacy.
  • Duration: A consistent regimen of 3-6 months is suggested to evaluate the effectiveness of NAD+ supplementation in reducing inflammation, as benefits may take time to manifest.
  • Lifestyle Integration: Combining NAD+ supplementation with anti-inflammatory lifestyle practices such as regular exercise, adequate sleep, stress management, and an anti-inflammatory diet rich in omega-3 fatty acids and antioxidants is likely to enhance results.

Mechanism of Action

NAD+ works by supporting mitochondrial function, activating sirtuins (proteins that regulate cellular health), and reducing oxidative stress—all processes that help combat chronic inflammation 1. The maintenance of cellular NAD+ levels is crucial for preventing the depletion of NAD+, which can lead to apoptotic events and increased inflammation.

Potential Side Effects and Precautions

Some individuals may experience mild side effects like flushing, fatigue, or headaches when starting NAD+ supplementation. Therefore, beginning with a lower dose and gradually increasing as needed is advisable. It's also important to consult with a healthcare professional before starting any new supplement regimen, especially for individuals with underlying health conditions or those taking medications.

From the Research

NAD+ and Inflammation

  • There is no direct evidence in the provided studies that links NAD+ to lowering inflammation in the context of rheumatoid arthritis or other inflammatory conditions.
  • The studies primarily focus on the efficacy of various disease-modifying antirheumatic drugs (DMARDs) and biologic agents in treating rheumatoid arthritis, without mentioning NAD+ as a potential therapeutic agent for reducing inflammation 2, 3, 4, 5.
  • One study discusses the efficacy of synthetic and biological DMARDs, but does not mention NAD+ as a factor in reducing inflammation 5.
  • Another study is unrelated to the topic of NAD+ and inflammation, as it discusses COVID-19 vaccines and their efficacy and safety 6.

Treatment of Inflammation

  • The provided studies suggest that various DMARDs and biologic agents, such as methotrexate, sulfasalazine, and tumor necrosis factor (TNF)-alpha antagonists, can be effective in reducing inflammation and treating rheumatoid arthritis 2, 3, 4, 5.
  • Combination therapies, such as triple therapy with methotrexate, sulfasalazine, and hydroxychloroquine, have also been shown to be effective in controlling disease activity and reducing inflammation 4.
  • However, these studies do not provide evidence on the use of NAD+ as a therapeutic agent for lowering inflammation.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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