Nicotinamide Riboside (NR), a compound being broadly researched as a potential multi-use nutritional supplement and therapeutic intervention, has been found in both animal and human trials to raise levels of circulating NAD+, a vital molecule in many biological processes.

Last year, Scandinavian researchers conducting long-term human trials looking to see if NR could help muscle mitochondrial efficiency in 40 overweight men, found that NR reduced the abundance of nicotinamide phosphoribosyl-transferase, or (NAMPT) for short, a key enzyme in the transformation of NAD+ precursors like NR and nicotinamide mononucleotide (NMN) into NAD+.

As popularity demands answers to NR supplementation’s safety and efficacy, studies have shown that NAMPT is also found in high levels in various forms of cancer including colorectal, gastric, ovarian, breast, brain and prostate cancers.

There is no evidence that NAMPT increases incidences of cancer, but reporting from Scientific American cites a study that demonstrates blocking or inhibiting NAMPT in animals has shown promise both for outrightly killing cancer cells, as well as increasing the effectiveness of other cancer interventions.

“There’s a lot of buzz about taking NAD+ precursors for their anti-aging effects, which is based on a lot of great science,” said Albert Kim MD Ph.D. in a statement.

In 2016 Kim blocked NAMPT expression in tumor cells of a deadly brain cancer called glioblastoma, after they had been transplanted into mice. The mice with suppressed NAMPT had less tumor proliferation and increased survival.

“I don’t know if taking NAD+ precursors makes existing tumors grow faster, but one implication of our work is that we don’t yet fully understand all of the consequences of enhancing NAD+ levels”.

While the Scandinavian study found that even though NAMPT levels decreased by 14%, “steady‐state NAD+ levels as well as gene expression and protein abundance of other [enzymes that turn NAD+-precursors into NAD+] remained unchanged”.

Essentially while a fall in the cancer-marker NAMPT was observed, NAD+ levels, which one would have imagined might fall, were maintained.

This could be an important find, even though the study also concluded puzzlingly that NAD+ levels were not raised even though the supplemented dose was quite high — 1,000 milligrams twice per day for 12 weeks.

NR and Longevity

Other studies have shown that chronic NR supplementation is not dangerous, and it can raise blood level NAD+.

A study published merely months after the first, using the same supplementation protocol on a shorter, 6-week timeline, looking for better results for insulin sensitivity, mitochondrial function, and other metabolic health parameters in 13 healthy obese individuals, had better results to report.

Compared with placebo, the second study indeed found substantial increases in skeletal muscular NAD+ metabolite concentrations, but like the first study, limited effects on metabolic health.

When World at Large reported on NR supplementation last year, the genesis for much of the recent research looking at NR for metabolic health, especially in instances of obesity and diabetes, were rodent studies.

The variations in the similar tests could be how the effects were measured, as neither study used methods used in the other. A second reason could be that, because all tissues need NAD+, the NR was taken up in different ways in different places in some individuals, perhaps influenced by genetic factors.

Further still could be dosage, which experts admit is not yet established. Could it be that too much NR, 2,000 milligrams per day, was enough to create some kind of resistance in the same way the body creates resistance to insulin?

Without NAD+ our body would simply stop working, and it would happen in a matter of seconds. Quite remarkably, there is almost no NAD+ in any food source we eat, and our bodies evolved the NAD+ Salvage Pathway as a massive recycling apparatus to pull NAD+ out of, and convert it from, other molecules.

Falls in production of NAD+ are observed in aging animals, leading to the suggestion that increased NAD+ slows the aging process and improves its outcomes. A search on Google Scholar bares witness to all the different conditions scientists hypothesize could be improved with increased NAD+ levels, often resulting from supplementation of NR or NMN.

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