- Shelly Albaum
Can Nicotinamide Riboside Reduce Inflammation?
Updated: Dec 6, 2022
Studies show that raising NAD levels can help fight inflammation.
Chronic inflammation is characterized by increased levels of the enzyme CD38, which lowers NAD levels.
What Is Inflammation?
Inflammation starts out as your body attempting to heal itself. Inflammation comes from the innate immune system, which is different from the acquired immune system.
The acquired or adaptive immune system learns to recognize pathogens and develops antibodies to protect against them.
The innate immune system is what you are born with, and it does not learn new things. Its job is to recognize when something bad has happened, and then initiate a cascade of processes to deal with it. The innate immune system is why that watermelon seed you ingested won't grow into a watermelon -- foreign objects are recognized and attacked simply because they are foreign.
The innate immune system doesn't just respond to foreign objects, though -- another bad thing might be a compression injury, if you banged your finger, or maybe you got a burn. Pattern Recognition Receptors in the cell try to figure out what happened, and when they recognize a pattern -- for example, a pathogen-associated molecular pattern, or PAMP -- then they spring into action, and emit chemical signals.
Early in the drama the innate immune system will usually trigger inflammation, which summons help. Chemicals like histamines, bradykinins, and prostaglandins might sensitize pain receptors, dilate blood vessels, manage clotting, and attract phagocytes to eat bacteria and also attract neutrophils, which have several modes of attack. Cytokines like interleukens might invoke a fever or suppress your appetite.
Some of your cells might have been injured beyond repair. The innate immune system will supervise the dismantling, destruction, and replacement of those cells with new ones.
That's really good, even though it hurts when your pain receptors are sensitized -- but that pain keeps you from doing it again. Meanwhile your innate immune system is attacking the things that need to be attacked.
This is called acute inflammation, and it is a healthy response to all kinds of traumas, like inhaling pollen or falling on your face. It's all very beautiful, and it keeps you alive.
But you can have too much of a good thing. At some point the repair is complete, or as complete as it can be, and the emergency is over. Then the innate immune system needs to turn off the sirens, let the swelling go down, and allow things to return to normal.
But what if it doesn't turn off? What if the immune response just keeps going, long after the threat has been resolved? That's a real problem.
Persistent low-level inflammatory proteins can damage your body and lead to auto-immune diseases, as well as just about every other bad thing, like diseases of the kidney, liver, heart, brain, and cancer. It can cause anxiety and depression. One study concluded that chronic inflammation was a "highly significant risk factor for both morbidity and mortality in the elderly people, as most if not all age-related diseases share an inflammatory pathogenesis." Persistent low-level chronic inflammation is really dangerous. It is a hallmark of aging. And you might not even know that you have it.
How to Combat Chronic Inflammation
So what to do? First, don't be old.
But that's not an option for everyone. So next, exercise, eat right, avoid obesity, and don't smoke. Avoid stress, too. And don't drink too much.
I am not your doctor and this is not medical advice. But I would not be surprised if my physician told me that if I am sedentary, obese, smoking, stressed, with high alcohol consumption, and a poor diet, I would be a good candidate to develop chronic inflammation, and there is not much that any health supplement could do about it.
With that said, there is a growing body of evidence that NAD+ precursors can have anti-inflammatory effects:
There is a growing body of evidence that NAD+ precursors can have anti-inflammatory effects.
-- Cell Metabolism, March 6, 2018
One group of researchers noted that age, chronic inflammation, and CD38, which is an NAD-consuming enzyme, all go up together, and NAD levels go down. They discovered that it's no coincidence, that the causes are intertwined: Senescent cells that accumulate with aging secrete inflammatory cytokines that cause pro-inflammatory white blood cells from the innate immune system to multiply, and those white blood cells express CD38, which results in NAD decline during aging.
Or, as another group described it, the immune system generates CD38, and CD38 knocks down NAD:
Recent studies showed that inflammation increases CD38-mediated NAD+ degradation activity, which decreases NAD+. The increase in CD38 in metabolic tissues during aging is likely mediated by accumulation of pro-inflammatory M1-like macrophages that also express CD38
-- Frontiers in Molecular Biosciences, May 19, 2021
Mouse studies have noted decreased inflammation for mice taking NR:
We detected a general decline in inflammatory cytokines in the circulation of NR-treated old mice...The decline in inflammatory factors...overlapped with those reported (IL-6 and TNF-α) in a study of oral NR supplementation in humans.
-- Aging Cell, September 21, 2021
And NR reduces inflammation in humans, too: a literature review published earlier this year found five human clinical trials evaluating the effects of nicotinamide riboside on inflammation, concluding:
NR may improve some inflammatory measures, with potential for more robust effects among populations with compromised NAD + and higher inflammation status, e.g., elderly or diseased...
-- Current Developments in Nutrition, June 14, 2022
One of those studies did not see much effect overall from Nicotinamide Riboside supplementation after just three weeks, but one effect they did find after just three weeks was significant reduction in specific pro-inflammatory cytokines:
We show that NR suppresses specific circulating inflammatory cytokine levels...Overall, these studies support that oral NR is available to human skeletal muscle, and they reveal anti-inflammatory NR properties, both of which may be beneficial in the context of aging, muscle, or inflammatory disease groups.
-- Cell Reports, August 13, 2019
Acute, short-term inflammation is essential to the body's healing process. Chronic, long-term inflammation is actually harmful. Chronic inflammation is marked by increased levels of CD38, which knocks down NAD levels. Some human clinical studies show that replenishing NAD levels reduces inflammation. If that's correct, then for people worried about healthy aging, that effect would by itself be enough reason to consider an NAD booster.
Read More: Research involving inflammation and NAD...