Way back for fructose and liver metabolism: Bench side to molecular insights

Table 1 Overview of fructose-related human studies

Authors	Subjects	Study characteristics	Sugar	Main results
Browning et al[11]	18 NAFLD (5 men, 13 women), BMI: 35 ± 7 kg/m2	Intervention study 2 wk dietary carbohydrate and calorie restriction		Reductions in body weight (-4.6 ± 1.5 kg vs -4.0 ± 1.5 kg) and hepatic triglycerides (-55% ± 14% vs -28% ± 23%) were significantly greater with dietary carbohydrate restriction than with calorie restriction
Maersk et al[12]	60 overweight/obese nondiabetic subjects	Randomized intervention study Ingestion of 4 different drinks (1 L/d, SSB, isocaloric semiskim milk, aspartame-sweetened and water) for 6 mo	S	Daily intake of SSB with sucrose increased ectopic fat accumulation (liver, skeletal muscle) and lipids (blood cholesterol and triglycerides) compared with the other beverages
Silbernagel et al[13]	Healthy male (12) and female (8) adults	Dietary intervention study 150 g/d for 4 wk	F and G	Visceral and liver fat content associated to cholesterol synthesis Cholesterol synthesis appeared to be dependent on fructose/glucose intake
Stanhope et al[14]	48 adults, BMI 18-35 kg/m2	Dietary intervention study Consumption of simple sugars at 25% of energy requirements for 2 wk	F and G	F consumption increased cardiovascular risk factors (AUC-Tg, fasting LDL and apo B) more than G
de Koning et al[15]	40 389 healthy men	Prospective cohort study 20 yr of follow-up of SSB and artificially sweetened beverages consumption	F, G and S SSB	After adjustment for several confounders, the hazard ratio for the association of SSB with incident type 2 diabetes was 1.24 for the comparison of the top with the bottom quartile of SSB intake
Silbernagel et al[16]	Healthy male (12) and female (8) adults	Dietary intervention study 150 g/d for 4 wk	F and G	Insulin sensitivity decreased in both intervention groups, while plasma triglycerides were increased in the F group
Cox et al[17]	Overweight/obese male (16) and female (15) adults	Intervention study 10 wk supplementation with SSB at 25% of energy requirements	F and G SSB	F-consuming subjects had a significant reduction in net postprandial fat oxidation and resting energy expenditure
Maier et al[18]	15 overweight/obese children (5-8 yr)	Dietary intervention study parental training to reduce dietary sugar content (–50% from baseline, 12 wk) and 12 wk of follow-up	F, G and S	Reductions in sugar intake were related to significant reductions in BMI and BMI standard deviation scores
Pollock et al[19]	559 adolescents (14-18 yr)	Association study of F intake and cardiometabolic risk factors	F	After adjustment, higher F consumption directly associated to BP, fasting glucose, HOMA-IR and C-reactive protein, and inversely to HDL-cholesterol and adiponectin. The introduction of visceral fat as a covariate attenuated these trends
Cox et al[21]	Overweight/obese male (16) and female (15) adults	Intervention study 10 wk supplementation with SSB at 25% of energy requirements	F and G SSB	Fasting concentrations of MCP-1, PAI-1 and E-selectin as well as postprandial concentrations of PAI-1 increased in subjects consuming F but not in those consuming G
Brown et al[22]	2696 people	Cross-sectional association study	F, G and S SSB	Direct and independent associations of SSB intake and BP
				Greater sugar-BP differences for persons with higher sodium excretion
Friberg et al[25]	61 226 women	Population-based cohort study 18.4 yr of follow-up of total sucrose, high-sugar-foods	F, G and S	Total sucrose intake and consumption of sweet buns and cookies was associated with increased risk of endometrial cancer
Ye et al[26]	737 non diabetic adults	Association study of sugar intake and cognitive function	F, G and S	Greater intakes of total sugars, added sugars and SSB beverages, but not of sugar sweetened solid foods, were significantly associated with lower MMSE scores, after adjusting for covariates

F: Fructose; G: Glucose; S: Sucrose; SSB: Sugar-sweetened beverages; BP: Blood pressure; NAFLD: Nonalcoholic fatty liver disease; BMI: Body mass index; MCP-1: Monocyte chemoattractant protein-1; PAI-1: Plasminogen activator inhibitor-1; HOMA-IR: Homeostasis model assessment-estimated insulin resistance; HDL: High-density lipoprotein; AUC-Tg: 24 h area under the curve for plasma triglycerides; LDL: Low-density lipoprotein; MMSE: Mini-mental state examination.