Vitamin B3, more commonly known as niacin, is a precursor of the coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) (Kevin Comerford, 2015). They serve a multitude of functions in the body, and are required in most metabolic redox processes in which substrates are oxidized and reduced (“Niacin: Fact Sheet for Health Professionals,” 2020). Numerous studies have explored the effects of niacin supplementation on cardiovascular disease (CVD). A 2018 systematic review explored dietary supplements in relation to CVD, myocardial infarction, and stroke. In 3 randomized control trials, niacin taken at pharmacological doses (1-3 g/day) was associated with increased all-cause mortality by 10% (p=0.05) when assessed against a background in which statins were taken in both test and control groups (Jenkins et al., 2018). The researchers postulated this was due to its adverse effects on glycemic response (Jenkins et al., 2018; Todd J. Anderson, 2014).
Another study compared escalating doses of immediate-release (IR) and sustained-release (SR) niacin for effectiveness in reducing LDL cholesterol and triglycerides while increasing HDL cholesterol. 46 adults (23 in each group) were given sequential doses of 500, 1,000, 1,500, 2,000, and 3,000 mg/day for 6 weeks. The SR niacin lowered LDL levels significantly more than IR niacin did at all dosage levels (James M. McKenney, 1994). The reduction in triglyceride levels was similar with IR and SR niacin. The study found the SR form of niacin to be hepatotoxic, whereas the IR form was preferred for the management of hypercholesteremia, although not without significant side effects (James M. McKenney, 1994). Adverse effects included skin flushing, itching, rash, eczema exacerbation, and gastrointestinal upset (James M. McKenney, 1994; Kevin Comerford, 2015).
Lastly, a 2019 systematic review looked at 119 clinical trials, 17 of which documented niacin’s effects on at least 1 CVD outcome. Cumulative evidence found no preventive association of niacin with CVD outcomes; conversely, stratified meta-analyses showed an association of niacin monotherapy with a reduction of some CVD events without statin treatment (D’Andrea, Hey, Ramirez, & Kesselheim, 2019). However, these results were derived from 2 studies in the 1970s and 1980s.
The current Recommended Dietary Allowance (RDA) for niacin has been established in mg of niacin equivalents (NE). For the general public recommendations include 16 mg NE and 14 mg NE for males and females over the age of 19, respectively (“Niacin: Fact Sheet for Health Professionals,” 2020). The upper limit, defined as the maximum daily intake unlikely to cause adverse health effects, is 35 mg for both males and females over the age of 19. As for niacin supplementation in the context of CVD, both the American College of Cardiology and the American Heart Association do not support non-statin therapies to provide atherosclerotic CVD benefits (“Niacin: Fact Sheet for Health Professionals,” 2020). However, for patients unable to tolerate statins, both societies suggest 500 mg/day of extended-release nicotinic acid supplements and increasing the dose to a maximum of 2,000 mg/day over 4 to 8 weeks. Patients also have the option to take 100 mg of immediate-release nicotinic acid 3x/day and increase the dose to 3,000 mg/day divided into 2 or 3 doses. It is imperative for those taking niacin supplements to be closely monitored for adverse effects and to consult with their healthcare professional.
D’Andrea, E., Hey, S. P., Ramirez, C. L., & Kesselheim, A. S. (2019). Assessment of the Role of Niacin in Managing Cardiovascular Disease Outcomes: A Systematic Review and Meta-analysis. JAMA Netw Open, 2(4), e192224. doi:10.1001/jamanetworkopen.2019.2224
James M. McKenney, P. J. D. P., MD; Scott Harris, PharmD; Vernon M. Chinchili, PhD. (1994). A Comparison of the Efficacy and Toxic Effects of Sustained- vs Immediate- Release Niacin in Hypercholesterolemic Patients. Journal of American Medical Association, 271(9).
Jenkins, D. J. A., Spence, J. D., Giovannucci, E. L., Kim, Y. I., Josse, R., Vieth, R., . . . Sievenpiper, J. L. (2018). Supplemental Vitamins and Minerals for CVD Prevention and Treatment. J Am Coll Cardiol, 71(22), 2570-2584. doi:10.1016/j.jacc.2018.04.020
Kevin Comerford, P. (2015). NUT 111AV: Water Soluble and and Fat Soluble Vitamins. Lecture Presentation. Department of Nutrition. University of California, Davis.
Niacin: Fact Sheet for Health Professionals. (2020, June 3, 2020). NIH Office of Dietary Supplements. Retrieved from https://ods.od.nih.gov/factsheets/Niacin-HealthProfessional/
Todd J. Anderson, M. D., William E. Boden, M.D., Patrice Desvigne-Nickens, M.D., Jerome L. Fleg, M.D., Moti L. Kashyap, M.D., Ruth McBride, Sc.B., Jeffrey L. Probstfield, M.D. (2014). Safety Profile of Extended-Release Niacin in the AIM-HIGH Trial. New England Journal of Medicine, 371(3), 288-290. doi:10.1056/NEJMc1406274
