Evaluation of Nicotinic Acid as an Hypocholesteremic and Anti-Atherogenic Substance *

Abstract

Despite the gaps existing in our contemporary understanding of the origin, the function, the mode of regulation and even the eventual fate of plasma cholesterol, various drugs have been introduced and applied to lower this particular lipid in the blood stream of man. It is perhaps suggestive of the clinical eagerness to accomplish this lowering that the precise modus operandi by which any of these substances effect their reduction of cholesterol in blood still remains to be determined.One of these substances is nicotinic acid. Its administration and subsequent cholesterol-lowering effect in clinical subjects was first reported by Altschul, Hoffer and Stephen ( 1), thereafter to be confirmed by Parsons and co-workers (2), and by Miller, Hamilton and Goldsmith (3). Administration of this substance to rats (4) and rabbits (5) also has been followed by a reduction in serum cholesterol. Thus there appears to be little doubt that the oral administration of nicotinic acid is capable of reducing the serum cholesterol of both the normo-and the hypercholesteremic subject and laboratory animal when no dietary control is exercised.Interested in the possible mechanism of this action, we performed various studies upon both the rat and the rabbit. The results, as we shall indicate below, suggest that the chief efficacy of the drug in regard to the cholesterol dynamics of the rat and rabbit appears to reside in its anoretic properties. METHODSA. Effect of nicotinic acid upon intestinal absorption of cholesterol and lipid by the rat. Ten rats (Long Evans strain) were maintained for 12 days on regular Purina Lab Chow® to which nicotinic acid (1 per cent) had been

Effect of Nicotinic Acid on Cholesterol Metabolism in Monkeys

“…cholesterol concentration in rabbits (Altschul, Hoffer & Stephen, 1955;Merrill & Lemley-Stone, 1957), but not in rats (Friedman & Byers, 1959;Duncan & Best, 1960) or dogs (Grande & Amatuzio, 1960). According to some reports, nicotinic acid inhibits cholesterol synthesis in rat liver (Garattini, Paoletti, Bizzi, Grossi & Vertua, 1961;Gamble & Wright, 1961); according to others (Merrill, 1958;Hardy, Gaylor & Baumann, 1960), it has a stimulatory effect.…”