Nicotinamide riboside side effects
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Side Effects of Nicotinamide Riboside: A Comprehensive Review
Introduction to Nicotinamide Riboside
Nicotinamide riboside (NR) is a form of vitamin B3 and a precursor to nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular metabolism. NR has gained attention for its potential benefits in metabolic health, neuroprotection, and cardioprotection. However, understanding its side effects is essential for safe supplementation.
General Safety and Tolerability
Clinical Trials in Humans
Several clinical trials have assessed the safety of NR supplementation in humans. A study involving obese, insulin-resistant men found that 12 weeks of NR supplementation at a dose of 2000 mg/day did not result in any serious adverse events, and safety blood tests remained normal. Another trial with healthy overweight or obese individuals reported no significant adverse effects with a 6-week supplementation of 1000 mg/day of NR. Additionally, a safety study in patients with acute kidney injury (AKI) using NR combined with pterostilbene (NRPT) showed that doses up to 1000 mg/200 mg twice daily for 2 days were well tolerated, with only minor gastrointestinal side effects reported by a few patients.
Animal Studies
Animal studies have also contributed to the safety profile of NR. A 90-day toxicology study in rats showed that NR had a similar toxicity profile to nicotinamide, with the liver, kidney, ovaries, and testes identified as target organs of toxicity at high doses. The no observed adverse effect level (NOAEL) was determined to be 300 mg/kg/day.
Specific Side Effects and Concerns
Metabolic Health
While NR is generally considered safe, some studies have raised concerns about its effects on metabolic health. In mice fed a mildly obesogenic diet, high-dose NR supplementation (9000 mg/kg diet) led to glucose intolerance, white adipose tissue dysfunction, and systemic insulin resistance. These effects were associated with molecular changes in adipose tissue, including increased inflammation and impaired glucose signaling.
Cardiovascular Health
NR has shown potential cardioprotective effects, particularly in the context of doxorubicin-induced cardiomyopathy. Studies in animal models demonstrated that NR could reduce fibrous tissue formation and improve antioxidant system performance, suggesting a protective role against cardiotoxicity . However, the long-term cardiovascular effects of NR in humans remain to be fully elucidated.
Conclusion
Nicotinamide riboside appears to be safe for short-term use in humans at doses up to 2000 mg/day, with no serious adverse events reported in clinical trials. However, high doses may pose risks to metabolic health, as evidenced by animal studies. Further research is needed to fully understand the long-term safety and potential side effects of NR supplementation, particularly in different populations and at varying doses.
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