NIH study shows elevating NAD+ with NR supplementation effectively reduces inflammation

A clinical study conducted by the National Institutes of Health (NIH), the agency responsible for biomedical and public health research for the US government has demonstrates that supplementation with nicotinamide riboside (NR), an NAD+ precursor, reduced inflammation in both healthy subjects and in cells derived from psoriasis patients [1].

The clinical trial was part of the ChromaDex External Research Program (CERP), which donated ChromaDex’s patented nicotinamide riboside (NR) ingredient, Niagen, for the advancement of this research; the results have been published in Cell Reports.

Longevity.Technology: This study builds on a growing body of evidence suggesting that NR defends against inflammation not only in individuals who are elderly or have inflammation-related disease, as they are associated with lower levels of NAD+ and higher inflammation markers, but may also provide anti-inflammatory benefits for healthy individuals. This is the third published human clinical study demonstrating that NR supplementation has a protective effect in healthy individuals and lays the foundation for future clinical research [2,3].

Revealing the connection between NAD+ and inflammation

Persistent chronic inflammation – also recognized as metaflammation or inflammaging – emerges as a consistent factor in ailing populations, in conditions correlated with age-related deterioration and even in ostensibly robust individuals. This phenomenon has been correlated with the onset of autoimmune disorders such as psoriasis and lupus, as well as chronic diseases including diabetes, cardiovascular disease, Alzheimer’s and Parkinson’s, among others. Investigations have substantiated that environmental and lifestyle variables such as smoking, a poor diet, physical inactivity and lack of or poor quality sleep can contribute to the perpetuation of chronic underlying inflammation.

Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme; vital for the functionality of all living cells, the preservation of intracellular NAD+ pools plays a crucial role in supporting cellular and metabolic processes. Key among these processes is the production of cellular energy, adenosine triphosphate (ATP), and DNA repair. Research indicates that a decrease in NAD+ levels is linked to compromised inflammatory responses and innate immune dysfunction. This implies that the levels of NAD+ may play a critical role in the operational efficacy of immune cells.

Research supporting anti-inflammatory effects of NR, the most efficient NAD+ precursor

NR is an efficient NAD+ precursor; clinically proven to increase NAD+ safely and effectively it has become a popular supplement, and there is a growing body of clinical evidence demonstrating the anti-inflammatory effects of NR supplementation (either alone or in combination with other ingredients) for healthy, older adults, or those with inflammation-related disorders [4]. Indeed, NR supplementation has potential for more robust effects among the elderly and diseased populations as they tend to have compromised NAD+ and a higher inflammatory status.

About the study

The first part of this clinical study analyzed the effects of ex vivo NR supplementation on adaptive immunity in CD4+ T cells, which play a vital role in regulating effective immune response to pathogens. CD4+ T cells were extracted from patients with mild-moderate psoriasis and age and gender-matched healthy controls (average age of 48).

The second part of the study analyzed the effects of oral NR supplementation on primary CD4+ T cell function using samples obtained from a prior pilot, randomized, double-blinded, placebo-controlled study in which 25 healthy subjects (average age of 24 and average BMI of 23) were supplemented with 1000mg NR or placebo daily for 7 days [5].

Study highlights

  • Ex vivo NR supplementation in CD4+ T cells in both healthy volunteers and patients with mild-moderate psoriasis reduced immune responsiveness, characteristic features in psoriasis, and depressed the secretion of pro-inflammatory factors observed in autoimmune disorders that contribute to overactive CD4+ T cells.
  • Genes related to antioxidant defense pathways were upregulated in CD4+ T cells in response to NR treatment.
  • NR decreased the production and activity of harmful reactive oxygen species (which causes damage to the building blocks of the cell including DNA), and reduced lipid peroxidation (a process by which oxidants attack healthy lipids, resulting in cell death) in CD4+ T cells.
  • Psoriatic T cells demonstrated both a reduction of NAD+ and upregulation of NAD+ consuming enzymes, as compared to the cells extracted from healthy individuals. These data suggest that psoriasis amplifies NAD+ consumption and that boosting NAD+ levels is necessary to blunt TH17 immune cell responsiveness.
  • In the in vivo analysis, oral NR supplementation in healthy participants reflected the immune-modulating effects of ex vivo NR supplementation. More specifically, oral NR reduced inflammatory biomarkers and enhanced antioxidant gene expression in immune cells.

The next steps

Building on the data collected, the researchers are currently exploring the effects of NR supplementation in mild-moderate psoriasis patients in an in vivo placebo-controlled clinical trial [6]. The findings from this study builds on a growing body of evidence suggesting that increasing NAD+ levels with NR supplementation not only defends against inflammation for healthy individuals, but also suggests a potential therapeutic application for individuals with autoimmune disorders, such as psoriasis, pending further research confirmation.

And finally…

The above research was enabled by the ChromaDex External Research Program (CERP), which earlier this year celebrated 10 years of providing independent researchers from some of the world’s top institutions with the ingredients necessary to advance the study of nicotinamide adenine dinucleotide (NAD+). 

Also enabled by CERP was a recent two year phase II clinical study that demonstrated that long-term supplementation with Niagen NR effectively increased whole blood NAD+ levels in Ataxia Telangiectasia (AT) patients. AT is a rare, inherited neurodegenerative disorder characterized by premature aging, cerebellar degeneration, immunodeficiency and cancer predisposition.

In the study, NAD+ levels increased up to fourfold, and improved coordination and enhanced eye movement were observed; importantly, biomarkers of stable liver and kidney function were maintained. The study, published in Movement Disorders, indicates that NR supplementation may be a potential therapeutic strategy for AT patients [7].

[1] https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(23)00310-5
[2] https://www.cell.com/cell-reports/fulltext/S2211-1247%2819%2930940-4
[3] https://www.sciencedirect.com/science/article/pii/S0002916522008103
[4] https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30940-4
[5] https://www.jci.org/articles/view/139828
[6] https://classic.clinicaltrials.gov/ct2/show/NCT04271735
[7] https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29645

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