This randomized placebo-controlled blinded trial of a single dose of immediate release niacin demonstrates the association between OTCs and important adverse effects (flushing, chills, and gastrointestinal side effects), severe enough in 9% of these young healthy volunteers to necessitate medical attention. The severity of the adverse effects and the relative frequency of them following a single dose of the product could not have been predicted from reviewing the product information available at the point of retail.
Our study used random allocation of participants and blinding to limit bias in the ascertainment of treatment effects, particularly since participants self-reported the adverse effects of treatment. We studied young healthy volunteers instead of older patients with comorbidities, a group more representative of those likely to use niacin to treat dyslipidemia. However, the development of intolerable side effects in 1 out of 5 young healthy volunteers likely underestimates the impact of adverse effects among older patients with comorbidities. Our study is of brief duration and only ascertained the effect of a single dose of niacin in a fasting state. Longer-term niacin use has been associated with liver disease, an outcome that we did not set out to investigate . Patients may be able to tolerate niacin's adverse effects with continued use, dose titration, switch to sustained-release preparations, pre-treatment with low-dose aspirin, or ingesting niacin with a meal. Given the findings of our study, clinicians considering niacin should begin with low-dose or time-released niacin to determine tolerability. However, while clinicians are generally aware of these strategies to limit the side effects of niacin, individuals buying immediate release niacin over-the-counter may not know how to prevent them.
We know of two other randomized trials specifically studying the adverse effects of 500 mg immediate-release niacin and testing the use of aspirin and ibuprofen to prevent them [12, 13]. None of those studies used controls not receiving niacin and, therefore, provide limited inferences as to the true relative risk of adverse effects with immediate release niacin. Furthermore, they did not set out to investigate the extent to which aspirin pre-treatment reduced the impact of gastrointestinal side effects, the most severe and distressing adverse effect in our study.
Clinicians should consider sharing information with their patients about the relative safety of OTCs. However, when clinicians turn to the literature to learn about the safety of OTCs they will find very little reliable evidence . The vast majority of information regarding adverse drug reactions is derived from case reports (30%) . Controlled trials investigating therapy often report adverse drug reactions yet are often underpowered to provide robust estimates of the risk for rare but severe adverse drug reactions . Additionally, not all clinical drug trials provide data on the frequency of adverse effects nor are likely to mention this in an abstract . Thus, searching databases for information on adverse drug reactions has many limitations [19, 20]. The post-marketing voluntary reporting process is haphazard and unreliable, particularly when physicians do not personally observe these reactions . In certain situations, consumers, clinicians, and policymakers could benefit from rigorous trials designed and powered to detect and characterize common and acute adverse effects of commonly used medications (or OTCs). However, in most situations (i.e., when products exhibit rare but severe adverse effects with long-term use), reliable and precise safety information will remain simply unattainable.
Our study highlights the trade-off involved in policy decisions to make health products available in retail stores without mediation of a health professional, such as a pharmacist. This study suggests potentially important economic considerations, not only from widespread unregulated consumption of these products, but also from resource utilization to treat their adverse effects. For instance, does the public know to consider safety issues when buying yet another vitamin? (Niacin is identified as a vitamin, vitamin B3) It may be possible to implement regulation, which ensure product labels contain detailed information regarding potential adverse effects. Further debate about the public health implications of expanding the pool of OTCs and keeping natural health products unregulated is long overdue.
While the adverse effects observed in this trial may be well known from clinical experiences, it is possible that niacin would have difficulties passing licensure from a regulatory body. This study additionally addresses the public perception that natural health products are natural, and thus safe. When considering the risk-benefit profile of common statins to niacin, the stains have evidence of safety and efficacy above niacin [22, 23].