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. 2022 Apr 5;116(1):15–39. doi: 10.1093/ajcn/nqac084

TABLE 4.

Summary of clinical trials examining the effects of high SSB consumption on metabolic health1

Reference, year Subjects Study duration Intervention Main findings
Aeberli et al., 2011 (125) 29 healthy young males (mean ± SD age, 26.3 ± 6.6 y) Six 3-wk interventions separated by a minimum of a 4-wk washout period 600 mL SSBs per day containing 40 g fructose (medium fructose; 6.5% daily caloric intake) vs. 80 g fructose (high fructose; 13% daily caloric intake) vs. 40 g glucose (medium glucose) vs. 80 g glucose (high glucose) vs. 80 g sucrose (high sucrose) vs. dietary advice to consume low amounts of fructose Mean ± SD waist-to-hip ratio was significantly higher in all interventions containing fructose (0.92 ± 0.05 to 0.93 ± 0.05) compared to baseline (0.92 ± 0.06; P < 0.0083)LDL particle size was significantly smaller in high-fructose (mean ± SD, −0.51 ± 0.80) and high-sucrose interventions (mean ± SD, −0.43 ± 0.81) compared with baseline. There was a significant decrease in large LDL I subclasses in the medium-fructose, high-fructose, and high-sucrose groups (P < 0.0083)Fasting glucose and CRP rose significantly after all interventions (by 4%–9% and 60%–109% respectively; P < 0.05)
Bruun et al., 2015 (124) 47 overweight but otherwise healthy subjects (mean ± SEM age, 38.6 ± 1.1 y; 36.2% males) 6 mo 1 L of sugar-sweetened cola, aspartame sweetener cola, semi-skimmed milk, or still mineral water Only those in the sugar-sweetened cola group had an increase in serum uric acid level at the end of the intervention (15% increase; P = 0.02)
No significant change in body weight or total fat mass was observed in all groups, but the sugar-sweetened cola group had a significant increase in VAT of 30% (P = 0.02), and a more than 2-fold increase in hepatic fat (P = 0.01)
Ebbeling et al., 2006 (116) 103 adolescents aged between 13–18 y who were regular SSB consumers (mean ± SD ages, 16.0 ± 1.1 vs. 15.8 ± 1.1 for intervention and control groups, respectively; 44.3% males) 25 wk Weekly home deliveries of noncaloric beverages vs. control (consumption of SSB) Those who received weekly home deliveries of noncaloric beverages had a lower increase in BMI compared with controls, although the difference was statistically nonsignificantA subgroup analysis revealed a significant difference between the intervention and control groups only amongst those with baseline BMIs ≥ 25.6 kg/m2 (mean ± SEM changes in BMI, −0.63 ± 0.23 kg/m2 vs. +0.12 ± 0.26 kg/m2; P = 0.03)
Geidl-Flueck et al., 2021 (127) 94 healthy, young males aged 18–30 y 7 wk Beverages sweetened with 80 g/d of fructose, sucrose, or glucose vs. control (nonconsumption) Compared with the control group, consumption of beverages sweetened with fructose and sucrose led to a 2-fold increase in basal hepatic fractional secretion rates [median FSR percentages per day: sucrose, 20.8 (P = 0.0015); fructose, 19.7 (P = 0.013); control, 9.1], whereas glucose had no significant effect on FSR
Compared to the control, absolute secretion rates of newly synthesized VLDL palmitate was increased after consumption of fructose-sweetened beverages (P = 0.055) and sucrose-sweetened beverages (P = 0.008)
Hieronimus et al., 2020 (134) 145 healthy young adults aged 18–40 y (49.0% females) 2 wk Beverages sweetened with aspartame (noncaloric control) vs. 25% daily caloric intake from glucose vs. 17.5% or 25% kcal from fructose vs. 10%, 17.5% or 25% kcal from HFCS vs. 25% kcal from sucrose Compared with the control group, a 24-hour increase in TG level was highest after consuming beverages sweetened with 25% daily energy intake from fructose (6.66 mmol/L × 24 hours; 95% CI, 1.90–11.63; P = 0.0013), increase in levels of LDL cholesterol and apoB were highest after consuming beverages sweetened with 25 daily energy intake kcal from HFCS [0.46 mmol/L (95% CI, 0.16–0.77; P = 0.0002) and 0.108 g/L (95% CI, 0.032–0.184; P  = 0.001), respectively]
James et al., 2004 (117) 644 children aged 7–11 y (mean ± SD age, 8.7 ± 0.9 y; 49.7% girls) 1 school y School-based focused nutrition education program aimed at reducing SSB consumption vs. control (no intervention) The intervention results in a decrease in SSB consumption by 0.6 glasses, which correlates with a 0.2% point decrease in the proportion of overweight and obese children. This is in contrast to the increase in both measures in the control group
Johnston et al., 2013 (130) 31 overweight but otherwise healthy males aged 18–50 y 2-wk isocaloric period +6-wk washout period +2-wk hypercaloric period High fructose vs. glucose intake in the form of beverages (25% of daily calories) During the isocaloric period, both high-fructose and high-glucose intake led to stable body weight, liver TG, and concentrations of liver enzymes, including ALT and AST, and the intergroup difference was not significant
During the hypercaloric period, both interventions led to similar increases in body weight, liver TG, and concentrations of ALT and AST
Low et al., 2018 (118) 16 healthy adults (mean ± SEM ages, 42.8 ± 1.8 vs. 46.6 ± 0.9 for males and females, respectively; 50% males) 2 study d separated by a 4-wk washout period Low- fructose (20 g) vs. high-fructose (60 g) drinks Significantly higher contribution of DNL fatty acids to VLDL-TG after high fructose consumption (time × meal interaction P < 0.01). No significant difference was observed in males
Maersk et al., 2012 (119) 47 overweight but otherwise healthy subjects aged 20–50 y (63.8% females) 6 mo 1 L of sugar-sweetened cola, aspartame sweetener cola, semi-skimmed milk, or still mineral water Sugar-sweetened cola resulted in significantly higher liver fat, skeletal muscle fat, visceral fat, blood TG, and total cholesterol than the other beverages. However, no significant difference was observed for total fat mass
Pearson et al., 2021 (126) 8 young healthy males (22 ± 1.79 y) 1 d per diet separated by a 1-wk washout period (cross-over design) Mixed macronutrient meal with 20 oz of diet coke (artificially sweetened) or regular coke (HFCS sweetened) or control (water) Sugar-sweetened cola resulted in significantly lower fat oxidation and higher carbohydrate oxidation than artificially sweetened cola (P = 0.006 and 0.014, respectively) and water (P = 0.001 and 0.001, respectively)
Raben et al., 2002 (120) 41 overweight males and females (mean ± SEM ages, 33.3 ± 2.0 vs. 37.1 ± 2.2 in high- and low-sucrose groups, respectively; 14.6% males) 10 wk 152 vs. 0 g/d sucrose supplements (∼70% from beverages and ∼30% from solid foods) Sucrose supplements, mostly in the form of beverages, resulted in significant increases in energy intake (+1.6 MJ/d; Pdiet×time = 0.03), body weight (+1.6 kg; Pdiet×time < 0.0001), fat mass (+1.3 kg; Pdiet×time < 0.05), and systolic and diastolic blood pressure (+3.8 and 4.1 mmHg, respectively)
Sigala et al., 2020 (128) 131 adults aged 18–40 y (51.9% males) 2 wk Beverages sweetened with aspartame or 25% energy requirement as glucose, fructose, HFCS, or sucrose There was no significant difference in body weight change between groups.High-sucrose (+14%; P < 0.0015), high-fructose (+9%; P = 0.015), and HFCS (+8%; P = 0.017) intakes increased energy intake compared with the aspartame group (−4%; P = 0.0037).High-fructose intake decreased 24-hour leptin AUC (−13.6 ± 7.6 ng/ml × 24 hours; P = 0.0008) compared with sucrose
Stanhope et al., 2009 (122) 32 overweight and obese subjects (50% males) 10 wk 25% kcal daily kcal requirement from glucose- vs. fructose-sweetened beverages The fructose group but not the glucose group had a significant increase in VAT, despite similar weight gain in both groups
DNL and postprandial TG were both higher in the fructose group, which coincided with increases in markers of dyslipidemia, such as apoB and LDL, as well as insulin resistance
Stanhope et al., 2015 (121) 85 adults (aged 18–40 y; 49.4% males) 20 d Artificially sweetened beverages vs. SSBs providing 10 vs. 17.5 vs. 25% daily kcal requirement Compared with the artificially sweetened beverages, the HFCS-containing SSBs caused increases in postprandial TG, as well as increased fasting and postprandial LDL cholesterol, apoB and apoCII, and uric acid
Taskinen et al., 2017 (129) 71 abdominally obese men (mean ± SD age, 49.1 ± 10 y; range, 21–65 y) 12 wk Beverages sweetened with 75 g/d of fructose, no control group (pretest vs. post-test) Fructose consumption significantly increased the liver fat content (mean ± SD, +0.67 ± 2.2%; P = 0.008). There were also significant but minor increases in body weight (mean ± SD, +1.1 ± 1.7%; P < 0.0001) and waist circumference (mean ± SD, +0.67 ± 2.5%; P = 0.006)
1

ALT, alanine aminotransferase; AST, aspartate aminotransferase; CRP, C-reactive protein; DNL, de novo lipogenesis; FSR, fractional secretion rate; HFCS, high-fructose corn syrup; SSB, sugar-sweetened beverage; TG, triglyceride; VAT, visceral adipose tissue.