The Mechanism of the Fructose Effect on the Ethanol Metabolism of the Human Liver*

Abstract

Ethanol is normally metabolized at a constant rate by the liver of man and animals. Attempts to change this rate have included treatment with metabolically active substances such as glucose, pyruvate, amino acids, dinitrophenol, insulin, and thyroid hormone. In some cases an increase has been observed, but usually only a very small one. The only exception so far discovered is the effect of fructose, first demonstrated by Stuhlfauth and Neumaier (1). This was confirmed by Pletscher, Bernstein, and Staub (2), who found an average increase in the elimination rate of ethanol of 80% in dogs receiving 1 to 2 g of fructose per kg per hour, and about 70% in human subjects who had fructose infused intravenously in comparable quantities (3). Oral ingestion of fructose in man gave the same result (4). Smaller or no effects have also been reported (5, 6), but in these cases the amount of fructose given was probably -insufficient.Several explanations of the phenomenon (which we shall refer to as the "fructose effect") have been offered, but since none of them were supported by direct experimental evidence, a detailed, quantitative investigation of the problem appeared desirable. Furthermore, it was of interest to study the circulatory and metabolic reactions of the liver during accelerated ethanol metabolism, as previous studies have shown that under normal con-

Splanchnic and renal exchange of infused fructose in insulin-deficient type 1 diabetic patients and healthy controls.

“…The remaining theoretically possible end products of hepatic fructose metabolism are glycerol and sorbitol. However, fructose-derived glycerol and/or sorbitol production by the liver was probably essentially absent in the present study since it appears to occur only when the redox state of the hepatocyte is disturbed by ethanol administration (8).…”

“…The major end products of hepatic fructose metabolism are glucose, lactate, and glycogen (7,8,12). In addition, fructose-derived oxidation and lipogenesis by the liver must be considered when the fate of hepatic fructose metabolism is discussed.…”

Sugars are complementary resources to ethanol in foods consumed by Egyptian fruit bats

“…During ethanol catabolism NAD is reduced to NADH, and the supply of NAD might limit ethanol oxidation. It has been proposed that during fructose metabolism NADH is transformed into NAD, and thus fructose increases ethanol oxidation (Scholz and Nohl, 1976;Thieden et al, 1972;Tygstrup et al, 1965). However, this idea is not fully accepted yet (Mascord et al, 1991).…”

Effects of intravenously administered fructose and glucose on splanchnic amino acid and carbohydrate metabolism in hypertriglyceridemic men.

“…Release into the hepatic vein of glucose, ['4C]C02, and lactate plus a small allowance for pyruvate (56) could account for about 80% of fructose removed in the splanchnic region during the intravenous administration of fructose (Table VII). Release of ['4C]CO2, lactate, and pyruvate (57) could account for only about 30% of glucose removed in the splanchnic region in subjects given glucose.…”

“…The remaining hexose would be available for conversion to glycogen (5) and/or triglycerides (58). Blood pyruvate levels are reported to rise during administration of either hexose (41,56,57).…”