Effectiveness of low-dose crystalline nicotinic acid in men with low high-density lipoprotein cholesterol levels

Background: Hypoalphalipoproteinemia (low serum concentration of high-density lipoprotein cholesterol [HDL-C]) is a common pattern of dyslipidemia associated with coronary heart disease. High doses of nicotinic acid effectively raise HDL-C levels in this condition, but they are commonly accompanied by side effects. The efficacy of low doses of nicotinic acid that may produce fewer side effects has not been adequately studied. Objective: To determine the effects of low-dose nicotinic acid on HDL-C levels in patients with hypoalphalipoproteinemia. Methods: Forty-four men with low HDL-C levels (<1.03 mmol/L [<40 mg/dL]) entered the study. Twenty-four patients otherwise had normal lipid levels, and 20 were moderately hypertriglyceridemic (range of plasma triglyceride levels, 2.82 to 5.64 mmol/L [250 to 500 mg/dL). The trial consisted of 3 phases; each phase lasted 8 weeks. The first phase was diet only (30% fat diet); in the second phase, crystalline nicotinic acid was added at 1.5 g/d; and in the third phase, the dose was increased to 3 g/d. Results: Of the 44 patients who entered the study, 37 completed the low-dose phase (1.5 g/d); the remaining patients were withdrawn because of side effects to nicotinic acid. Four other patients who completed the low-dose phase were excluded from the higher dose phase because of side effects that developed when they were receiving the low dose. Ten other patients withdrew during the high-dose phase because of side effects. In both groups, responses to nicotinic acid therapy tended to be dose-dependent. For both groups, the higher dose generally produced a greater reduction in apolipoprotein B-containing lipoproteins and a greater rise in HDL-C levels. However, for both groups, the low dose of nicotinic acid gave an average 20% increase in HDL-C levels. Conclusions: A low dose (1.5 g/d) of crystalline nicotinic acid causes an average 20% increase in HDL-C levels and significantly lowers triglyceride levels in both normolipidemic and hyperlipidemic patients with low HDL-C levels. Although the changes induced by this dose are less than those that can be achieved by a higher dose, the lower dose is better tolerated. Nicotinic acid may be useful in combined drug therapy for secondary prevention of coronary heart disease, and if higher doses cannot be tolerated, use of a lower dose should still be useful for producing a moderate rise in HDL-C levels in patients with hypoalphalipoproteinemia.