A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults

Abstract

Background: National Health and Nutrition Examination Survey data show an increased risk of cardiovascular disease (CVD) mortality with an increased intake of added sugar.

Objective: We determined the dose-response effects of consuming beverages sweetened with high-fructose corn syrup (HFCS) at zero, low, medium, and high proportions of energy requirements (Ereq) on circulating lipid/lipoprotein risk factors for CVD and uric acid in adults [age: 18-40 y; body mass index (in kg/m(2)): 18-35].

Design: We conducted a parallel-arm, nonrandomized, double-blinded intervention study in which adults participated in 3.5 inpatient days of baseline testing at the University of California Davis Clinical and Translational Science Center's Clinical Research Center. Participants then consumed beverages sweetened with HFCS at 0% (aspartame sweetened, n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) of Ereq during 13 outpatient days and during 3.5 inpatient days of intervention testing at the research center. We conducted 24-h serial blood collections during the baseline and intervention testing periods.

Results: Consuming beverages containing 10%, 17.5%, or 25% Ereq from HFCS produced significant linear dose-response increases of lipid/lipoprotein risk factors for CVD and uric acid: postprandial triglyceride (0%: 0 ± 4; 10%: 22 ± 8; 17.5%: 25 ± 5: 25%: 37 ± 5 mg/dL, mean of Δ ± SE, P < 0.0001 effect of HFCS-dose), fasting LDL cholesterol (0%: -1.0 ± 3.1; 10%: 7.4 ± 3.2; 17.5%: 8.2 ± 3.1; 25%: 15.9 ± 3.1 mg/dL, P < 0.0001), and 24-h mean uric acid concentrations (0%: -0.13 ± 0.07; 10%: 0.15 ± 0.06; 17.5%: 0.30 ± 0.07; 25%: 0.59 ± 0.09 mg/dL, P < 0.0001). Compared with beverages containing 0% HFCS, all 3 doses of HFCS-containing beverages increased concentrations of postprandial triglyceride, and the 2 higher doses increased fasting and/or postprandial concentrations of non-HDL cholesterol, LDL cholesterol, apolipoprotein B, apolipoprotein CIII, and uric acid.

Conclusions: Consuming beverages containing 10%, 17.5%, or 25% Ereq from HFCS produced dose-dependent increases in circulating lipid/lipoprotein risk factors for CVD and uric acid within 2 wk. These results provide mechanistic support for the epidemiologic evidence that the risk of cardiovascular mortality is positively associated with consumption of increasing amounts of added sugars. This trial was registered at clinicaltrials.gov as NCT01103921.

Keywords: apolipoprotein CIII; fructose; risk factors; sugar; uric acid.

© 2015 American Society for Nutrition.

Figures

FIGURE 1

Effects of consuming beverages containing 0%, 10%, 17.5%, and 25% Ereq-HFCS. The least squares means (adjusted for sex, BMI, and [outcome] at baseline) ± SEs of (A) Δbody weight; (B) ΔFST and PP plasma non–HDL cholesterol, LDL cholesterol, and apoB concentrations; (C) ΔFST and PP plasma apoCIII concentrations and ΔFST and 24-h mean plasma uric acid concentrations; and (D) ΔFST, 24-h mean, and PP plasma triglyceride concentrations in young men and women after consuming beverages providing 0% (n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) of Ereq from HFCS for 2 wk. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, effect of HFCS group; 2-factor (HFCS group, sex) ANCOVA of Δ with adjustment for BMI and [outcome] at baseline. aΔ different from bΔ or bcΔ and abΔ different from cΔ, Tukey’s multiple-comparisons test. +P < 0.05, ++P < 0.01, +++P < 0.001, ++++P < 0.0001, least squares mean different from zero. Significance notations in red indicate that difference did not retain significance after correction for multiple comparisons (P < 0.0031). apoB, apolipoprotein B; apoCIII, apolipoprotein CIII; Ereq, energy requirement; FST, fasting; HFCS, high-fructose corn syrup; PP, postprandial; Δ, absolute change.

FIGURE 2

The 24-h circulating uric acid concentrations during consumption of complex carbohydrate and during consumption of sweetened beverages containing 0%, 10%, 17.5%, and 25% of Ereq-HFCS. Circulating 24-h uric acid plasma concentrations during consumption of energy-balanced baseline diets containing 55% Ereq complex carbohydrate at 0 wk and during consumption of energy-balanced intervention diets containing isocaloric amounts of carbohydrate as complex carbohydrate and (A) 0% Ereq-HFCS (n = 23), (B) 10% Ereq-HFCS (n = 18), (C) 17.5% Ereq-HFCS (n = 15), or (D) 25% Ereq-HFCS (n = 28) at 2 wk. (E) The change in circulating 24-h uric acid plasma concentrations (2 wk – 0 wk) quantified for each group as Δ24-h uric acid AUC. ****P < 0.0001, effect of HFCS group; 2-factor (HFCS group, sex) ANCOVA of Δ with adjustment for BMI and [outcome] at baseline. aΔ different from bΔ, Tukey’s multiple-comparisons test. +P < 0.05, ++++P < 0.0001, least squares mean different from zero. Significance notations in red indicate that difference did not retain significance after correction for multiple comparisons (P < 0.0031). Data are means ± SEs. CHO, carbohydrate; Ereq, energy requirement; HFCS, high-fructose corn syrup; Δ, absolute change.

FIGURE 3

The 24-h circulating triglyceride concentrations during consumption of complex carbohydrate and during consumption of sweetened beverages containing 0%, 10%, 17.5%, and 25% of Ereq-HFCS. Circulating 24-h triglyceride plasma concentrations during consumption of energy-balanced baseline diets containing 55% Ereq complex carbohydrate at 0 wk and during consumption of energy-balanced intervention diets containing isocaloric amounts of carbohydrate as complex carbohydrate and (A) 0% Ereq-HFCS (n = 23), (B) 10% Ereq-HFCS (n = 18), (C) 17.5% Ereq-HFCS (n = 15), or (D) 25% Ereq-HFCS (n = 28) at 2 wk. (E) The change in circulating 24-h triglyceride plasma concentrations (2 wk – 0 wk) quantified for each group as Δ24-h uric acid AUC. *P < 0.05, effect of HFCS group; 2-factor (HFCS group, sex) ANCOVA of Δ with adjustment for BMI and [outcome] at baseline. aΔ different from bΔ, Tukey’s multiple-comparisons test. ++P < 0.01, least squares mean different from zero. Significance notations in red indicate that difference did not retain significance after correction for multiple comparisons (P < 0.0031). Data are means ± SEs. CHO, carbohydrate; Ereq, energy requirement; HFCS, high-fructose corn syrup; Δ, absolute change.