We feel that Gray and colleagues' data [1] do not support their claim that controlled-release and immediate-release niacin have similar toxic effects when used in equipotent doses. Because their study did not include a control group, it did not provide a basis for evaluating differences between the controlled-release and immediate-release forms. The study design probably also resulted in an underestimation of the incidence of niacin-associated hepatotoxicity (the most serious niacin toxicity). Hepatotoxicity was identified by notations on the medical record or by evidence of elevated alkaline phosphatase or aminotransferase levels. However, the authors did not report the frequency of either clinic visits or laboratory monitoring. If visits or monitoring occurred infrequently, asymptomatic elevations of hepatic enzyme levels or hepatotoxicity presenting as a mild flu-like illness could have been missed.

In contrast, the clinical trial of McKenney and colleagues [2] was designed to evaluate differences between sustained-release and immediate-release niacin across varying doses. With sustained-release niacin, they found significant increases in aspartate aminotransferase and alanine aminotransferase levels at doses of 1500 mg/d or greater; with immediate-release niacin, no such increases were seen at doses as high as 3000 mg/d. Moreover, therapy had to be discontinued because of elevated liver enzyme levels in 12 of 23 patients receiving sustained-release niacin but in no patients receiving immediate-release niacin. Therapy with sustained-release niacin was discontinued at a dose of 1000 mg/d in one patient and at 1500 mg/d in two patients. These findings suggest that sustained-release niacin is more hepatotoxic than immediate-release niacin, even when administered at half the dosage, and argue against Gray and colleagues' claim of similar toxicity at equipotent doses.

The data of McKenney and associates [2] and numerous case reports [3, 4] continue to support the greater hepatotoxic potential of controlled-release niacin preparations and the use of immediate-release niacin as the preferred preparation.