No-Flush Niacin for the Treatment of Hyperlipidemia

Reza Taheri, PharmD

Disclosures

January 15, 2003

Question

I am looking for information on the use of inositol hexaniacinate ("no-flush niacin") in the treatment of hyperlipidemia. Most of the information I have been able to find is anecdotal. I understand that this product has been used in Europe for many years. Data on clinical studies, dose titration, side effects, and effectiveness would be appreciated.

Bob Kittams

Response from Reza Taheri, PharmD

Inositol hexaniacinate, otherwise known as inositol nicotinate or no-flush niacin, consists of 6 nicotinic acid molecules crossed-linked together with an inositol molecule. Inositol hexaniacinate appears to have vasodilatory, fibrinolytic, as well as lipid-lowering activities.[1] These properties lend themselves to the use of this product in the setting of peripheral vascular disorders such as intermittent claudication and Raynaud's disease,[2,3,4] as well as in the management of dyslipidemia.[5,6,7,8,9]

Studies of inositol nicotinate in the setting of dyslipidemia are sparse, involve small numbers of patients, and most have focused on the benefit of this product in combination with clofibrate. In a study of 20 dyslipidemic patients (10 type IIa, 7 type IV, and 3 type V), Hutt and colleagues[6] investigated the effect of inositol nicotinate combined with clofibrate. In this study, type IIa patients received clofibrate and inositol nicotinate in respective doses of 1500 mg and 2400 mg daily, while types IV and V patients received 1500 mg and 900 mg daily, respectively. In type IIa patients, total cholesterol decreased by 60 mg/dL and triglycerides by 27 mg/dL on average. In types IV and V patients, total cholesterol was not altered significantly while triglycerides dropped 30% and 76%, respectively. High-density lipoprotein cholesterol (HDL-C) increased by 24% in type IV patients and remained unchanged in types IIa and V patients. In another study, Wilke and colleagues[8] investigated the effect of combining clofibrate 250 mg and inositol nicotinate 180 mg daily (14 patients) vs clofibrate 500 mg daily (22 patients) on cholesterol over an 8-week period. Both groups had similar reductions in total cholesterol and triglycerides. When 1200 mg/day of inositol nicotinate was combined with 1500 mg/day of clofibrate, in a study by Schwartzkopff and colleagues,[7] the reduction in total cholesterol and triglycerides was similar to monotherapy with clofibrate. Even though inositol nicotinate has been around for many years, there are not any well-designed, large, prospective studies evaluating its efficacy and safety. The few studies available in the literature are limited by their small sample size, design flaws, and lack of comparative data with niacin. These limited studies suggest that lower daily doses (ie, 180 mg, 900 mg, or 1500 mg) may not be enough and daily doses of 2400 mg or higher may be needed to produce any meaningful changes in cholesterol parameters. The daily doses should be given in 2-3 divided doses to minimize the intensity of side effects.

In terms of adverse effects, inositol nicotinate potentially has types of reactions similar to those of niacin (eg, flushing, pruritis, gastrointestinal complaints, hepatotoxicity, hyperuricemia, and impaired glucose tolerance) because it is broken down to 6 niacin molecules. The intensity and severity of these adverse effects may be less than those of niacin, as the hydrolysis of inositol nicotinate into free nicotinic acid and inositol molecules takes place very slowly and peak serum levels of nicotinic acid are not achieved until about 10-12 hours after the dose.[1] However, this information is based mainly on the pharmacokinetics of the product, and actual clinical experience in the reported literature is not sufficient to justify this theoretical assumption.

In summary, the paucity of data as well as the limitations in the available data make it difficult to assess the true benefit of inositol hexaniacinate in the setting of dyslipidemia. The very limited data available suggest that inositol hexaniacinate may not be effective for the management of dyslipidemia at lower doses, and doses of > 2400 mg/day may be necessary to provide any added benefit for dyslipidemia management. Even at high doses the true value of inositol hexaniacinate is far from established. Finally, the safety profile of inositol hexaniacinate is not well understood for there are no reports in the literature systematically evaluating its adverse effect profile.

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