Clinical Trials

Elysium Scientists Combine NAD+ Booster with Sirtuin Activator to Reduce Inflammation in Liver Disease

MIT professor Leonard Guarente leads a study showing nicotinamide riboside (NR) and pterostilbene reduce inflammatory markers in adults with non-alcoholic fatty liver disease (NAFLD).

By Bennett M. Sherman

Key Points:

  • Adults with NAFLD who took a nicotinamide riboside (NR) and pterostilbene cocktail (NRPT) exhibited diminished inflammatory liver enzyme levels.
  • NRPT facilitated reduced levels of a toxic lipid that contributes to liver disease called ceramide 14:0.
  • These findings only applied to the daily recommended dosage as taking twice the recommended dose didn’t confer these benefits.

Approximately 1 billion people worldwide have non-alcoholic fatty liver disease (NAFLD), characterized by fat accumulation and inflammation. Rodent studies have shown that combating this rampant condition entails activating pro-longevity proteins called sirtuins. Along with sirtuin activating compounds (STACs) like pterostilbene, increasing nicotinamide adenine dinucleotide (NAD+) levels with the supplements NR or nicotinamide mononucleotide (NMN) can activate sirtuins. Now, researchers have begun combining these two compounds to treat NAFLD.

Published in Hepatology, Guarente and colleagues of the supplement company Elysium Health find that a combination of NR and pterostilbene (NRPT) reduces the presence of markers for liver inflammation in the blood. Moreover, NRPT significantly diminishes the amount of toxic, bioactive fats (ceramide 14:0) known to contribute to liver disease. These results depend on the dosage of NRPT administered since adults taking double the recommended dose do not see the same benefits. Overall, the results suggest that NRPT may alleviate liver inflammation in patients with NAFLD.

NR and Pterostilbene Combination Lowers Liver Inflammatory Markers

Guarente and colleagues measured liver enzymes associated with inflammation from 111 NAFLD patients 90 and 180 days following NRPT treatment to find if the compound cocktail provides benefits. The researchers found significantly diminished alanine transaminase and gamma-glutamyltransferase enzyme levels, markers of inflammation, at day 180 when patients took the recommended daily dosage. These findings didn’t apply to those who took twice the recommended dose. While not all of the measured liver enzymes showed significantly reduced levels, these results suggest that the NRPT cocktail may alleviate liver inflammation.

liver enzymes
(Dellinger et al., 2022 | Hepatology) A combination of NR and pterostilbene lowers liver inflammatory markers. The NRPT combination recommended daily dosage lowers markers of liver inflammation alanine transaminase and gamma-glutamyltransferase in the blood

Guarente and colleagues then measured another liver disease indicator, ceramide 14:0, a deleterious, bioactive lipid that contributes to NAFLD. Following six months of NRPT supplementation, the group that took the recommended dosage displayed significantly reduced ceramide 14:0 levels, but the group that took twice this amount did not. These findings suggest that NRPT reduces the abundance of these toxic fats at its recommended daily dose but perhaps not at higher doses.

Only the Daily Recommended Dosage Confers Benefits

A big concern with the study’s findings was that NRPT provided benefits at the recommended daily dosage but not at twice this dosage. This may stem from the consumed NR breaking down to nicotinamide, which is known to inhibit pro-longevity sirtuin enzyme activity. NR is converted to NAD+, which is then used by sirutins as fuel. However, if too much NR is broken down to nicotinamide, the sirtuins could be shut off.  For this reason, too much NR may counteract the sirtuin-activating effects of NRPT. Too much nicotinamide could also override the activation of sirtuins by pterostilbene. Another possibility is that two times the recommended pterostilbene dosage exceeds its peak efficacy, rendering the sirtuin-activating compound ineffective

Significant results weren’t found for all of the measured inflammatory liver enzymes, such as alkaline phosphatase and aspartate transaminase. What’s more, NRPT supplementation didn’t significantly change liver fat content. These results call into question whether the reductions of inflammatory liver enzymes alanine transaminase and gamma-glutamyltransferase, along with the toxic fat ceramide 14:0 occurred by chance. To confirm NRPT’s anti-inflammatory effects in NAFLD, future studies should include more participants and extend over longer treatment periods.

Model and Dosage

Model: Adults with non-alcoholic fatty liver disease

Dosage: 250 mg nicotinamide riboside and 50 mg pterostilbene per day or 500 mg nicotinamide riboside and 100 mg pterostilbene per day

Source

Dellinger RW, Holmes HE, Hu-Seliger T, Butt RW, Harrison SA, Mozaffarian D, Chen O, Guarente L. NRPT reduces markers of hepatic inflammation in non-alcoholic fatty liver disease: a double-blind, placebo-controlled clinical trial. Hepatology. 2022 Sep 9. doi: 10.1002/hep.32778. Epub ahead of print. PMID: 36082508.

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