A growing body of clinical research suggests that boosting levels of NAD (nicotinamide adenine dinucleotide) may play a meaningful role in reducing inflammation in humans. This topic recently came up in a podcast conversation between Dr. Rhonda Patrick and Dr. Charles Brenner.
Additionally, Patrick made a social media post talking about the research. She explains: “NAD depletion is a hallmark of chronic inflammatory states, from respiratory infections to metabolic disease to unhealthy aging. In many of these conditions, inflammation itself disrupts NAD metabolism, creating a vicious cycle where inflammation lowers NAD, and low NAD impairs the body’s ability to resolve stress and repair damage.”
Raising NAD levels reduces inflammation in humans.
At least 8 randomized controlled trials show that ~1 gram per day of nicotinamide riboside (NR) lowers key inflammatory cytokines, including IL-6 and TNF-α.
NAD depletion is a hallmark of chronic inflammatory states, from… pic.twitter.com/Hxg4lFlnVv
— Dr. Rhonda Patrick (@foundmyfitness) February 11, 2026
At least eight randomized controlled trials have now demonstrated that supplementation with nicotinamide riboside (NR), a precursor to NAD, reduces key inflammatory markers in people. The dosage used in these studies typically hovers around one gram daily, and the results have proven consistent across different populations.
“We’ve been able to show that in human beings and randomized control trials that nicotinamide riboside at like a gram a day type doses is anti-inflammatory,” explains Dr. Charles Brenner, a leading NAD researcher. “So that’s now a proven fact.”
The connection between NAD and inflammation appears to work both ways, creating what researchers describe as a destructive feedback loop. Inflammatory conditions deplete NAD levels, while low NAD impairs the body’s capacity to manage oxidative stress and conduct essential repair processes.
This relationship has been observed across a spectrum of health challenges, from respiratory infections to metabolic disorders to the gradual decline associated with aging.
The path to understanding NAD’s anti-inflammatory effects in humans took an unexpected turn. One of the first trials to document this relationship wasn’t initially designed to measure inflammation at all.
“The first trial that reported that NR is anti-inflammatory set out to determine whether NR could improve old men’s grip strength in like two or three weeks,” Brenner recounts.
The premise, he admits, was flawed from the start. “It’s kind of a dumb trial, Rhonda. Because if you want to get stronger, you have to exercise. Not take a pill.”
The trial enrolled older men, conducted muscle biopsies, and used a crossover design where participants received either NR or placebo in alternating phases. Predictably, grip strength showed no improvement.
But when researchers examined their secondary measurements, they discovered something unexpected: NR was dramatically lowering inflammatory markers including IL-6 and IL-10.
The anti-inflammatory response was so robust that it persisted even after participants switched from NR to placebo. “The people that had the NR first followed by placebo still had lower anti-inflammatory results after three weeks on placebo,” Brenner notes, though “the effect was strongest right after NR.”
For researchers accustomed to laboratory work, this discovery presented a methodological puzzle. “The thing that clinical researchers will tell you is that your pre-specified endpoint is the most valuable thing,” Brenner explains.
When a study measures multiple outcomes, statistically significant findings can emerge by chance, particularly in secondary measures that weren’t the trial’s original focus.
“For every 20 things that you measure, you might find one thing that achieves this statistical significance at P.05,” he points out. This statistical reality means researchers must approach secondary findings with appropriate caution.
However, the anti-inflammatory signal proved too strong and too consistent to dismiss as coincidence. Since that initial observation, multiple independent trials have replicated the finding. More recently, studies have been designed with inflammation as the primary target from the outset.
One recent trial enrolled patients with COPD, a respiratory condition characterized by persistent inflammation.
“The patient population all had COPD. So they’re all very inflammatory. They’re looking at inflammatory markers and sputum,” Brenner describes. “NR lowers those inflammatory markers. Placebo doesn’t.”
This study was particularly meaningful because it measured inflammation in the context of actual disease, in tissue directly relevant to the condition being studied.
Why does restoring NAD levels calm inflammation? The answer lies in NAD’s fundamental role in cellular function. This molecule serves as an essential cofactor for numerous biological processes: DNA repair machinery, mitochondrial energy generation, sirtuin signaling pathways, and cellular antioxidant defense systems all depend on adequate NAD availability.
When NAD levels drop, these protective and restorative systems become compromised. Brenner’s hypothesis centers on rebuilding depleted reserves: “What I think it’s doing is it’s rebuilding NAD in a system in which the NAD systems come under attack. Rebuilding those supplies so that free radical species can be detoxified and the anabolic processes and the repair processes can work better.”
The research has also revealed that inflammatory triggers themselves disrupt NAD metabolism. “We’ve shown that inflammatory stimuli like coronaviruses disturb the NAD system,” Brenner notes.
This bidirectional relationship creates a situation where inflammation depletes NAD, and NAD depletion hampers the body’s ability to resolve inflammation and conduct repairs.
While the evidence for NR’s anti-inflammatory properties in humans is now substantial, researchers emphasize that supplementation should complement, not replace, foundational health practices.
Brenner’s position is clear on this point: exercise, proper nutrition, quality rest, and maintaining a healthy weight remain primary interventions. In fact, he and his colleagues have published work arguing that physical activity should be considered standard care, with supplements like NR evaluated for their ability to provide additional benefits beyond that foundation.
