Study investigated the safety and tolerability of NR trial of patients with heart failure, marking a milestone for future clinical research.
ChromaDex has announced promising findings from a clinical study, as reported in the peer-reviewed journal Journal of the American College of Cardiology (JACC): Basic to Translational Science.
Led by the University of Washington School of Medicine’s Dr Kevin O’Brien (Division of Cardiology, Department of Medicine) in collaboration with Dr Rong Tian (Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine), a team of scientists carried out the clinical study as part of the ChromaDex External Research Program (CERP); the team investigated the safety and tolerability of the company’s proprietary Niagen ingredient, patented nicotinamide riboside or NR, in Stage C heart failure patients with reduced ejection fraction (HFrEF), which occurs when the left ventricular ejection fraction (LVEF) is 40% or less .
Additionally, the effects of NR on white blood cells’ mitochondrial respiratory function, inflammation and whole blood nicotinamide adenine dinucleotide (NAD+) levels were assessed.
Longevity.Technology: The promising results from this study demonstrated that high-dose NR was safe and well-tolerated, almost doubling whole blood NAD+ levels, increasing white blood cell mitochondrial respiratory function and decreasing the expression of inflammatory markers. This study marks a major milestone as it is the first study to investigate the safety and tolerability of NR in a randomised, placebo-controlled trial of patients with heart failure – a crucial step that should pave the way for future clinical research.
“On behalf of CERP, we are thrilled with the results of this study as it builds on the pilot study by Zhou et al, 2020, which demonstrated oral supplementation of NR in Stage D heart failure patients increased whole blood NAD+ levels,” said Dr Andrew Shao, ChromaDex Senior Vice President of Global Scientific & Regulatory Affairs.
Heart failure is a clinical condition that is caused by structural and functional defects in the heart, which results in impaired filling or pumping of blood. There are four stages to heart disease, A, B, C and D, with Stage C patients having been diagnosed with heart failure and had or currently have symptoms of the condition. Recent research suggests that a decline in NAD+ levels may contribute to dysfunctional energy metabolism in conditions like heart failure, and increasing NAD+ levels through precursor supplementation may play a role in the progression of heart failure [3,4,5]. NR is an NAD+ precursor and further research is needed to understand its potential as a therapeutic option for heart failure patients.
“The study met its primary endpoint by confirming that NR was safe and well-tolerated in patients with clinically stable heart failure,” said Dr Kevin O’Brien. “In addition, we found that, in these patients, increasing blood NAD+ levels with NR improved the ability of white blood cell mitochondria to generate energy .”
“The anti-inflammatory effect of NR, although not a primary endpoint of the trial, is an exciting finding. It offers a new therapeutic opportunity in heart failure and other conditions associated with chronic inflammation,” said Dr Rong Tian .
This randomised, double-blinded, placebo-controlled clinical study analysed 30 Stage C heart failure patients over 12 weeks. The patients were supplemented with escalating doses of NR or placebo starting at 250mg twice per day, then increasing by 250mg twice per day each week resulting in a final dose of 2000mg/day at week 3 and beyond.
The results demonstrated that:
- NR was well-tolerated, with no adverse side effects and nearly doubled whole blood NAD+ levels.
- Increased NAD+ resulted in increased white blood cell mitochondrial respiration and decreased expression of inflammatory markers, such as NLRP3 (when there is extreme damage in the heart, the protein NLRP3 can induce excessive inflammation, leading to tissue damage, cardiac remodeling and impaired function). This suggests that boosting NAD+ helps reduce systemic inflammation.
These results are promising and suggest that NR supplementation may have therapeutic potential in patients with heart failure; this study sets the groundwork for future research to determine its use as a potential therapeutic strategy.