Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women

Abstract

Background/objectives: The results of short-term studies in humans suggest that, compared with glucose, acute consumption of fructose leads to increased postprandial energy expenditure and carbohydrate oxidation and decreased postprandial fat oxidation. The objective of this study was to determine the potential effects of increased fructose consumption compared with isocaloric glucose consumption on substrate utilization and energy expenditure following sustained consumption and under energy-balanced conditions.

Subjects/methods: As part of a parallel arm study, overweight/obese male and female subjects, 40-72 years, consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and during the 10th week of intervention.

Results: Consumption of fructose, but not glucose, led to significant decreases of net postprandial fat oxidation and significant increases of net postprandial carbohydrate oxidation (P<0.0001 for both). Resting energy expenditure (REE) decreased significantly from baseline values in subjects consuming fructose (P=0.031) but not in those consuming glucose.

Conclusions: Increased consumption of fructose for 10 weeks leads to marked changes of postprandial substrate utilization including a significant reduction of net fat oxidation. In addition, we report that REE is reduced compared with baseline values in subjects consuming fructose-sweetened beverages for 10 weeks.

Figure 1

Net carbohydrate oxidation rate (g/min) profiles over 15 hours for subjects consuming glucose- and fructose-sweetened beverages. Subjects consumed meals at 09:00, 13:00, and 18:00 as indicated. The first 2 data points represent resting values and the remaining 14 data points represent postprandial values. Data points represent the mean of 10-min measurements ± SEM with n=31 (fructose group n=16; glucose group n=15) for resting values and n=30 (fructose group n=15; glucose group n=15) for postprandial values.

Figure 2

Net fat oxidation rate (g/min) profiles over 15 hours for subjects consuming glucose-and fructose sweetened beverages. Subjects consumed meals at 09:00, 13:00, and 18:00 as indicated. The first 2 data points represent resting values and the remaining 14 data points represent postprandial values. Data points represent the mean of 10-min measurements ± SEM. with n=31 (fructose group n=16; glucose group n=15) for resting values and n=30 (fructose group n=15; glucose group n=15) for postprandial values.

Figure 3

Proposed mechanisms contributing to observed changes of substrate utilization in subjects consuming fructose-sweetened beverages. In the liver fructose is phosphorylated by fructokinase (which is not regulated by cellular energy status) and largely bypasses phosphofructokinase (PFK), the enzyme catalyzing the rate-limiting step of glycolysis (which is subject to inhibition by ATP and citrate). Ultimately fructose enters the glycolytic pathway as glyceraldehyde-3-phosphate. Following a high-fructose meal, an unregulated flux of fructose (Frc) carbon upregulates carbohydrate metabolism in the liver (increased CHO-Ox), leading to an increased flux of acetyl CoA through the tricarboxylic acid (TCA) cycle and a concomitant increase in cellular energy status (increased ATP/ADP ratio and NADH/NAD⁺ ratio). A high NADH/NAD⁺ ratio in the mitochondria results in substrate inhibition of isocitrate dehydrogenase (ICD) in the TCA cycle, leading to increased export of citrate to the cytosol, activation of acetyl-CoA carboxylase (ACC), and increased production of malonyl-CoA, the precursor to fatty acid synthesis (DNL). Elevated cytosolic concentrations of malonyl-CoA inhibit the carnitine shuttle via carnitine palmitoyl transferase (CPT), leading to reduced entry of fatty acids (FAs) into the mitochondria, decreased fat oxidation. The elevation of cellular energy status following a high-fructose meal would also lead to reduced mitochondrial availability of the fixed pool of oxidized cofactors NAD⁺ and FAD, which are required substrates for β-oxidation, also resulting in reduced fat oxidation (Locke et al 2008, Mayes 1993, McGarry 1995, Williamson and Cooper 1980).