The latest study on nicotinamide riboside clinical trial is about the combination of NR and pterostilbene powder (NRPT). Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the world, affecting about 25% of the population. Over 90% of obese people, 60% of diabetics, and up to 20% of people with average body weight are at risk for developing this condition, which is more common in developed countries. In the United States and Europe, NAFLD is the primary cause of chronic liver disease and the second most frequent reason for liver transplantation. These facts claim the need for urgent prevention and treatment of this chronic disease.
The findings
NAFLD is a condition of excessive fat accumulation in the liver from an unknown cause, leading to chronic liver disease. The studies indicate that the combination of nicotinamide riboside (NR) and pterostilbene (PT), known as NRPT, may enhance liver function in healthy people. In addition, because the presence of liver enzymes in the blood are biomarkers for liver health, this combination can affect liver enzymes’ blood levels, thus protecting the liver and treating liver conditions.
A double-blind, placebo-controlled clinical trial is conducted to investigate the effects of this combination. In this study, 111 adults aged 18 to 70 were supplemented with NAFLD for 6 months. The recommended daily dose of NRPT was 2 capsules (250 mg NR capsule and 50 mg PT capsule). There was also a placebo and double dose of NRPT, e.g., 4 capsules per day (500 mg of NR and 100 mg PT).
After the study, the results showed that NRPT is safe, non-toxic, and well-tolerated among the participants. In the group where NARP 1X was given, a decrease in the liver enzymes alanine transferase (ALT) and gamma-glutamyltransferase (GGT) was seen versus placebo. The result was time-dependent. In addition, a significant decrease in the toxic lipid levels and ceramide 14:0 was observed in the NRPT 1X group when compared with the placebo group. This positive result was linked with the decrease in ALT levels in the participants in this group.
No effects and dose-dependent results were observed in the second group, where 2X NRPT was given.
NRPT increases NAD+ levels
The amount of NAD+ in our bodies affects how quickly we age. NAD+ levels are higher in tissues and cells in younger people. Younger individuals typically are more physically active and have better cognitive ability, cell repair, and regeneration capability. The amount of NAD+ in our bodies starts to decrease as we age. This manifests as a slower cognitive response, memory loss, and decreased agility.
Nicotinamide adenine dinucleotide (NAD+) is a possible target for preventing and treating NAFLD. A variety of enzymes, including sirtuins (SIRT), use NAD+ as a substrate since it is a crucial redox component for energy metabolism. Oral supplementation with NAD+ precursors such as Nicotinamide riboside (NR) enhances hepatic NAD+ levels and inhibits the buildup of hepatic lipids in pre-clinical models of NAFLD. In pre-clinical NAFLD models, NAD+ precursors enhance hepatic mitochondrial activity and lower oxidative stress. However, the first clinical trials were done on people with obesity.
Another Elysium’s study was conducted, where NAD+ levels were increased by 40% in adults taking the daily recommended dose of NRPT. In this trial, 120 healthy adults between the ages of 60 and 80 years participated and were given the recommended dose of NRPT (NRPT 1X), a double dose of NRPT (NRPT 2X), and a placebo. After 30 days, the results showed that NRPT recommended dose increased NAD+ levels by 40% from the baseline, and maintained that result after 60 days. In the double dose group, the NAD+ levels in the participants were increased by 90% after 30 days over the baseline, and 55% after 60 days.
NAD+ levels also increased the Sirtuins genes, which are involved in many biological processes such as DNA repair, cell metabolism, regulation of cellular homeostasis, and more. In addition, the sirtuins are NAD+-dependent, so increasing NAD+ levels is crucial.
The placebo group showed no changes at all. After the study, the doses given were safe with no side effects among individuals.
Dellinger RW, Santos SR, Morris M, Evans M, Alminana D, Guarente L, Marcotulli E. Repeat dose NRPT increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study. NPJ Aging Mech Dis. 2017 Nov 24;3:17. doi: 10.1038/s41514-017-0016-9.
(NAD+ levels were increased after 30 days with NRPT supplementation from the baseline in humans.)
In previous studies, the combination of NR and PT prevents acute kidney injury after heart injury. In 138 adults, the Basis was given 2 weeks before the surgery and 6 weeks after the heart surgery, compared to a placebo group. Because PT is similar to resveratrol, which is an activator of SIRT1, the results show positive effects of NR with PT against kidney damage, because SIRT 1 is a protective marker due to its antioxidative injury, thus high levels of NAD+ precursors can rise Sirtuins levels which can help in prevention from liver damage and contribute to healthy liver functions.
Limitations in the study
Although the NRPT combination is proven to be safe and well-tolerated in the participants, further findings are needed to observe the long-term effects in more participants. Furthermore, there is a question of why there was a decrease in liver enzymes in the first NRPT 1X group and no changes in the second NRPT 2X group. The scientists thought that excessive NR increases nicotinamide levels which may inhibit the effect of PT. The next explanation was that lower AST and ALT levels may mask the effects in NRPT 2X group.
To sum up
Higher levels of NAD+ activate the Sirtuins genes, which both are key points to lower liver inflammation and contribute to a healthy liver. In both studies, the combination of NR and PT is well-tolerated and safe without adverse effects, proving that it can be used as a possible treatment for NAFLD. The scientists also investigate if this combination can help NASH (nonalcoholic steatohepatitis), a type of NAFLD.
Reference:
- Dellinger, R. W., Holmes, H. E., Hu‐Seliger, T., Butt, R. W., Harrison, S. A., Mozaffarian, D., Chen, O., & Guarente, L. (2022). NRPT reduces markers of hepatic inflammation in non‐alcoholic fatty liver disease: a double‐blind, placebo‐controlled clinical trial. In Hepatology. Wiley. https://doi.org/10.1002/hep.32778
