ChromaDex (Los Angeles, CA) has stopped taking new orders of pterostilbene, a popular antioxidant, effective July 31 because of new research1 that indicates the ingredient increases low-density lipoprotein (LDL) cholesterol. The firm is only fulfilling orders made prior to the July 31 date as a commitment to its clients.
The research was conducted by product marketer Elysium Health on its product called Basis and was published in Aging and Mechanisms of Disease. The supplement combines the ingredients nicotinamide riboside (NR) and pterostilbene. ChromaDex was originally the sole supplier to Elysium of both these ingredients prior to a legal dispute between the two companies that continues to be litigated.
The purpose of Elysium Health’s research was to study the product’s safety and ability to increase nicotinamide adenine dinucleotide (NAD+) levels. The researchers explain, “[Basis] is a combination of NR and pterostilbene (PT), a naturally occurring analog of the polyphenol resveratrol, which has been found to be a potent SIRT1 activator. Despite the reported physiological beneficial effect of resveratrol, its bioavailability in humans is poor. PT exhibits greater bioavailability due to the presence of two methoxy groups that allow it to have increased lipophilic and oral absorption, as well as a longer half-life due to reduced oxidation. Based on these considerations, the combination of NR and pterostilbene is predicted to synergistically support metabolic health through NR providing NAD+ to all seven sirtuins and pterostilbene providing additional activation of SIRT1.”
The sirtuin family of proteins are NAD+ dependent enzymes that are key regulators in aging. However, in a letter to the editor2 recently published in Clinical Nutrition and critical of Elysium’s study, written by Charles Brenner, PhD, head and chair of biochemistry at the University of Iowa, and Amy C. Boileau, vice president of research and development for ChromaDex, the authors contend that despite the researchers’ intentions, resveratrol does not depend on sirtuin 1 for its metabolic effects and that pterostilbene has not been shown to bind to sirtuin 1. If the ingredient were activating sirtuin 1, it would be expected to improve lipid management, they state; yet, the research showed a significant increase in LDL cholesterol.
In the Aging and Mechanisms of Disease study, the researchers did disclose that the ingredient increased cholesterol levels. “Total cholesterol and LDL-cholesterol showed within-group increases at day 30 (NRPT 2X) and day 60 (NRPT 1X [single dose] and NRPT 2X [double dose]) compared to baseline. The increase in total cholesterol in the NRPT 1X group compared to the placebo group was not significant at day 30 or day 60,” they wrote. “Larger increases in total cholesterol and LDL cholesterol were observed in the NRPT 2X group. However, there were significant across-group differences in total and LDL cholesterol at baseline mainly due to lower levels in the placebo group, confounding the interpretation of the study data.”
Researchers continued, “Thus, we stratified the three treatment groups by BMI and reanalyzed the data. Subjects in the NRPT 1X group with normal BMI (18–25) showed no significant increases in LDL cholesterol at day 30 or day 60. Subjects in the NRPT 2X group with normal BMI did show increases in LDL cholesterol at day 30 and day 60. Subjects in the overweight category (BMI 25-32) showed increases in LDL cholesterol at day 30 and day 60 in both the NRPT 1X and NRPT 2X groups. However, overweight subjects in the placebo group also showed a significant increase at day 60. Overall, these findings suggest a small but significant increase in cholesterol may occur at the normal dose of NRPT, at least for people with a higher than normal BMI.”
The researchers said they found this increase in LDL cholesterol to be significant, but minimal, and therefore called little attention to it in their study. By contrast, the Clinical Nutrition letter-to-the-editor authors Brenner and Boileau criticize the Elysium study researchers for minimizing the adverse results and not citing previous research3 that corroborates evidence that pterostilbene increased LDL cholesterol.
“The authors did not release their primary data for independent assessment of significance and did not disclose results previously reported for pterostilbene that are wholly consistent with the study’s finding of what is clearly a clinically meaningful increase in LDL-C,” they wrote. “While the authors cite this study to point out the earlier observation that pterostilbene reduced blood pressure, they neglected to cite clinically meaningful increases in LDL-C for treatment groups receiving 100 mg or 250 mg daily pterostilbene for 6-8 weeks as well as significantly decreased high-density lipoprotein cholesterol in subjects who were not taking statins.”
While ChromaDex was aware of this previous study that showed increases in LDL cholesterol from taking pterostilbene, it was this new research on Elysium’s product that pushed the company to decide to cease supplying the ingredient. “At that time, it was the only study of the ingredient, but the 2017 Elysium study reinforced this risk,” the company told Nutritional Outlook. “This caused us to take a careful review of the ingredient. After careful consideration of our obligations to our business partners, we made the decision to stop taking new orders. Our conversations were respectful and transparent.”
Elysium, in turn, defends its research and the safety of its product. “The American Heart Association states that LDL levels can normally fluctuate by as much as 9.5% daily,” the company told Nutritional Outlook. “In Elysium Health’s study, taking the recommended dose of Basis led to no significant increase in total cholesterol and an increase in LDL of about 3%, meaning that the change seen may be reflective of daily diet and other lifestyle factors,” adding, “For reasons unrelated to the study, the starting LDL levels of the groups taking Basis were already much higher than those in the placebo group.”
1. Dellinger RW et al. “Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study.” Aging and Mechanisms of Disease. Published online ahead of print November 24, 2017.
2. Brenner C and Boileau AC. “Pterostilbene raises low-density lipoprotein cholesterol in people.” Clinical Nutrition. Accepted for publication October 3, 2019.
3. Riche DM et al. “Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial.” Evidence-Based Complementary and Alternative Medicine. Published online ahead of print June 25, 2014.