A “helper molecule” in the body’s cells may play a greater role in cellular metabolism, inflammation, and disease progression than previously thought, according to scientific reports.
 
Scientists have long known about nicotinamide adenine dinucleotide, or NAD+, as a coenzyme that carries out various processes in the body. What first seemed like a “simple” molecule, is shaping up to be a “pivotal” player in healthy aging and supporting cellular defense.
 
This shift in perspective has “led to a new wave of scientific interest,” several scientists said in a recent paper published in Nature Metabolism. They discussed the current research and implications for the future.
 
Simply put, NAD+ is a “cofactor” that is central to cellular metabolism. A cofactor helps an enzyme or protein to function properly. In this case, NAD+ helps cells produce energy. As scientists have studied NAD+ more, they’ve also observed a link between declining NAD+ levels and age, lack of sleep and exercise, and infection. In a review published in the European Medical Journal, the authors highlighted the role of NAD-related enzymes in the disease progression of rheumatoid arthritis, suggesting that replenishing NAD+ pools may provide a therapeutic benefit in individuals that suffer from this condition. Furthermore, the potential anti-inflammatory effects of NAD+ are currently being studied in other autoimmune disorders such as lupus and psoriasis. Since autoimmune diseases are characterized by abnormal or overactive immune responses which often lead to swelling and inflammation, scientists have postulated improving or supporting energy metabolism could potentially make a difference. 
 
Multiple preclinical studies have demonstrated that NAD+ plays a role in neurological disorders, including age-related conditions such as Alzheimer’s disease and Parkinson’s disease. Scientists have called for translational research that will move the science forward to address whether augmenting NAD+ levels may impact the development or progression of these diseases. 
 
“There are still major gaps in applying laboratory science to design the most effective trials,” said a group of researchers in Norway. They discussed  the translational potential in March in Mechanisms of Ageing and Development.
 
“A consensus is emerging with respect to the design of clinical trials in order to measure meaningful parameters and ensure safety,” they wrote.
 
For the most part, B3 vitamins from whole and fortified foods provide the body with the precursors to produce NAD+ to help the body’s 37 trillion cells. However, NAD+ tends to decline as we age, which can lead to a wide variety of diseases. Just as overall metabolism falls over time, so does NAD+.
 
That’s why researchers have focused on understanding the different roles NAD+ plays in health. If there’s a way to boost NAD+ or prevent the levels from declining as we age, this may help to maintain health and function, and in turn, reduce the risk or progression of chronic diseases.
 
One of the ingredients that scientists have found that both safely and effectively increase NAD+ levels is nicotinamide riboside, or NR, which is an alternative form of vitamin B3. NR is known as an “NAD+ precursor” since the body converts the ingredient into NAD+ and increases the levels in our cells.
 
In recent years, researchers have studied both NAD+ and NR in various diseases and body systems. For instance, according to researchers from Massachusetts General Hospital and Harvard Medical School, preclinical models of acute kidney injury suggest NAD+ could potentially help with long-term chronic issues, systemic inflammation and toxic injury. Furthermore, there are ongoing clinical trials registered on clinicaltrials.gov looking at the effects of NAD+ supplementation on both acute and chronic kidney injury. 
 
“Further understanding … may lead to novel approaches for the prevention and treatment of kidney disease,” they wrote in Nature Reviews Nephrology in February. 
 
Recently published studies on NR have reported promising results as well. In a study published in Biochemical Pharmacology, researchers found that NR had an anti-inflammatory effect in human aortic endothelial cells (HAEC). In another study published in Molecular Systems Biology researchers found that NR, in combination with L‐serine, N‐acetyl‐L‐cysteine, and L‐carnitine, could potentially promote oxidation of liver fat in patients with non-alcoholic fatty liver disease (NAFLD).
 
In another study recently published in the journal Neurotoxicology, researchers investigated the effects of NR on brain bioenergetics and neuroinflammation in a Gulf War Illness (GWI) mouse model. The brains of NR treated GWI mice had lower pro-inflammatory cytokines, reduced inflammation, and decreased fatigue-type behavior in compared to untreated GWI mice. 
 
As the research continues to evolve, scientists hope to learn more about the links to disease progression and the major roles that NAD+ and NR can play in health. There’s still more to learn, which makes it an exciting area to watch. As scientists publish more studies and the updates move forward, we may learn even more about the ways that NAD+ and NR supplementation are essential for health promotion by supporting our cellular health and defense.