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Effect of fructose instead of glucose or sucrose on cardiometabolic markers: a systematic review and meta-analysis of isoenergetic intervention trials.
Fattore, E, Botta, F, Bosetti, C
Nutrition reviews. 2021;(2):209-226
Abstract
CONTEXT Free, or added, sugars are considered important determinants in the pandemics of obesity and associated chronic diseases, and fructose has emerged as the sugar of main concern. OBJECTIVE The aim of this review was to assess the evidence of the effects of isoenergetic replacement of fructose or high-fructose corn syrup (HFCS) for glucose or sucrose on cardiometabolic markers in controlled dietary intervention trials. DATA SOURCES The electronic databases PubMed/MEDLINE, the Cochrane Library, and Embase were searched from 1980 to May 5, 2020. STUDY SELECTION Studies were eligible if they measured at least one of the following outcomes: total cholesterol, low- and high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A1, apolipoprotein B, systolic blood pressure, diastolic blood pressure, fasting glucose, and body weight. DATA EXTRACTION For each outcome, the mean values and the corresponding measure of dispersion were extracted after the intervention or control diet. DATA ANALYSIS Fixed-effects and random-effects models were used to pool study-specific estimates. Between-study heterogeneity was assessed by the χ2 test and the I2 statistic and publication bias by the Egger test and funnel plots. RESULTS Twenty-five studies involving 1744 volunteers were identified. No significant effects were found when fructose or HFCS was substituted for glucose, except for a slight decrease in diastolic blood pressure when fructose was substituted for glucose. Similarly, no effects were found when fructose or HFCS was substituted for sucrose, except for a small increase, of uncertain clinical significance, of apolipoprotein B when HFCS was substituted for sucrose. CONCLUSIONS Isoenergetic substitution of fructose or HFCS for glucose or sucrose has no significant effect on most of the cardiometabolic markers investigated; however, some results were affected by residual between-study heterogeneity and studies with high or unclear risk of bias. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42016042930.
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Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.
Butler, AA, St-Onge, MP, Siebert, EA, Medici, V, Stanhope, KL, Havel, PJ
Scientific reports. 2015;:14691
Abstract
Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations.
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No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial.
Kuzma, JN, Cromer, G, Hagman, DK, Breymeyer, KL, Roth, CL, Foster-Schubert, KE, Holte, SE, Callahan, HS, Weigle, DS, Kratz, M
The American journal of clinical nutrition. 2015;(6):1373-80
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BACKGROUND Increased energy intake is consistently observed in individuals consuming sugar-sweetened beverages (SSBs), likely mainly because of an inadequate satiety response to liquid calories. However, SSBs have a high content of fructose, the consumption of which acutely fails to trigger responses in key signals involved in energy homeostasis. It is unclear whether the fructose content of SSBs contributes to the increased energy intake in individuals drinking SSBs. OBJECTIVE We investigated whether the relative amounts of fructose and glucose in SSBs modifies ad libitum energy intake over 8 d in healthy adults without fructose malabsorption. DESIGN We conducted 2 randomized, controlled, double-blind crossover studies to compare the effects of consuming 4 servings/d of a fructose-, glucose-, or aspartame-sweetened beverage (study A; n = 9) or a fructose-, glucose-, or high-fructose corn syrup (HFCS)-sweetened beverage (study B; n = 24) for 8 d on overall energy intake. SSBs were provided at 25% of estimated energy requirement, or an equivalent volume of the aspartame-sweetened beverage, and consumption was mandatory. All solid foods were provided at 125% of estimated energy requirements and were consumed ad libitum. RESULTS In study A, ad libitum energy intake was 120% ± 10%, 117% ± 12%, and 102% ± 15% of estimated energy requirements when subjects consumed the fructose-, glucose-, and aspartame-sweetened beverages. Energy intake was significantly higher in the fructose and glucose phases than in the aspartame phase (P < 0.003 for each), with no difference between the fructose and glucose phases (P = 0.462). In study B, total energy intake during the fructose, HFCS, and glucose phases was 116% ± 14%, 116% ± 16%, and 116% ± 16% of the subject's estimated total energy requirements (P = 0.880). CONCLUSIONS In healthy adults, total 8-d ad libitum energy intake was increased in individuals consuming SSBs compared with aspartame-sweetened beverages. The energy overconsumption observed in individuals consuming SSBs occurred independently of the relative amounts of fructose and glucose in the beverages. These trials were registered at clinicaltrials.gov as NCT00475475 and NCT01424306.
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Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation.
Jameel, F, Phang, M, Wood, LG, Garg, ML
Lipids in health and disease. 2014;:195
Abstract
BACKGROUND Recent studies have demonstrated a relationship between fructose consumption and risk of developing metabolic syndrome. Mechanisms by which dietary fructose mediates metabolic changes are poorly understood. This study compared the effects of fructose, glucose and sucrose consumption on post-postprandial lipemia and low grade inflammation measured as hs-CRP. METHODS This was a randomized, single blinded, cross-over trial involving healthy subjects (n=14). After an overnight fast, participants were given one of 3 different isocaloric drinks, containing 50 g of either fructose or glucose or sucrose dissolved in water. Blood samples were collected at baseline, 30, 60 and 120 minutes post intervention for the analysis of blood lipids, glucose, insulin and high sensitivity C-reactive protein (hs-CRP). RESULTS Glucose and sucrose supplementation initially resulted in a significant increase in glucose and insulin levels compared to fructose supplementation and returned to near baseline values within 2 hours. Change in plasma cholesterol, LDL and HDL-cholesterol (measured as area under curve, AUC) was significantly higher when participants consumed fructose compared with glucose or sucrose (P<0.05). AUC for plasma triglyceride levels however remained unchanged regardless of the dietary intervention. Change in AUC for hs-CRP was also significantly higher in subjects consuming fructose compared with those consuming glucose (P<0.05), but not sucrose (P=0.07). CONCLUSION This study demonstrates that fructose as a sole source of energy modulates plasma lipids and hsCRP levels in healthy individuals. The significance of increase in HDL-cholesterol with a concurrent increase in LDL-cholesterol and elevated hs-CRP levels remains to be delineated when considering health effects of feeding fructose-rich diets. REGISTRATION NUMBER FOR CLINICAL TRIALS ACTRN12614000431628.
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High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels.
Yu, Z, Lowndes, J, Rippe, J
Nutrition research (New York, N.Y.). 2013;(12):1043-52
Abstract
Intake of high-fructose corn syrup (HFCS) has been suggested to contribute to the increased prevalence of obesity, whereas a number of studies and organizations have reported metabolic equivalence between HFCS and sucrose. We hypothesized that HFCS and sucrose would have similar effects on energy-regulating hormones and metabolic substrates at normal levels of human consumption and that these values would not change over a 10-week, free-living period at these consumption levels. This was a randomized, prospective, double-blind, parallel group study in which 138 adult men and women consumed 10 weeks of low-fat milk sweetened with either HFCS or sucrose at levels of the 25th, 50th, and 90th percentile population consumption of fructose (the equivalent of 40, 90, or 150 g of sugar per day in a 2000-kcal diet). Before and after the 10-week intervention, 24-hour blood samples were collected. The area under the curve (AUC) for glucose, insulin, leptin, active ghrelin, triglyceride, and uric acid was measured. There were no group differences at baseline or posttesting for all outcomes (interaction, P > .05). The AUC response of glucose, active ghrelin, and uric acid did not change between baseline and posttesting (P > .05), whereas the AUC response of insulin (P < .05), leptin (P < .001), and triglyceride (P < .01) increased over the course of the intervention when the 6 groups were averaged. We conclude that there are no differences in the metabolic effects of HFCS and sucrose when compared at low, medium, and high levels of consumption.
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Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women.
Cox, CL, Stanhope, KL, Schwarz, JM, Graham, JL, Hatcher, B, Griffen, SC, Bremer, AA, Berglund, L, McGahan, JP, Havel, PJ, et al
European journal of clinical nutrition. 2012;(2):201-8
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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.
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A randomized, prospective, comparison study of a mixture of acacia fiber, psyllium fiber, and fructose vs polyethylene glycol 3350 with electrolytes for the treatment of chronic functional constipation in childhood.
Quitadamo, P, Coccorullo, P, Giannetti, E, Romano, C, Chiaro, A, Campanozzi, A, Poli, E, Cucchiara, S, Di Nardo, G, Staiano, A
The Journal of pediatrics. 2012;(4):710-5.e1
Abstract
OBJECTIVES To compare the effectiveness of a mixture of acacia fiber, psyllium fiber, and fructose (AFPFF) with polyethylene glycol 3350 combined with electrolytes (PEG+E) in the treatment of children with chronic functional constipation (CFC); and to evaluate the safety and effectiveness of AFPFF in the treatment of children with CFC. STUDY DESIGN This was a randomized, open label, prospective, controlled, parallel-group study involving 100 children (M/F: 38/62; mean age ± SD: 6.5 ± 2.7 years) who were diagnosed with CFC according to the Rome III Criteria. Children were randomly divided into 2 groups: 50 children received AFPFF (16.8 g daily) and 50 children received PEG+E (0.5 g/kg daily) for 8 weeks. Primary outcome measures were frequency of bowel movements, stool consistency, fecal incontinence, and improvement of other associated gastrointestinal symptoms. Safety was assessed with evaluation of clinical adverse effects and growth measurements. RESULTS Compliance rates were 72% for AFPFF and 96% for PEG+E. A significant improvement of constipation was seen in both groups. After 8 weeks, 77.8% of children treated with AFPFF and 83% of children treated with PEG+E had improved (P = .788). Neither PEG+E nor AFPFF caused any clinically significant side effects during the entire course of the study period. CONCLUSIONS In this randomized study, we did not find any significant difference between the efficacy of AFPFF and PEG+E in the treatment of children with CFC. Both medications were proved to be safe for CFC treatment, but PEG+E was better accepted by children.
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Effect of glycemic index and fructose content in lunch on substrate utilization during subsequent brisk walking.
Sun, FH, Wong, SH, Chen, YJ, Huang, YJ, Hsieh, SS
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2011;(6):985-95
Abstract
The purpose of the present study was to investigate the effect of glycemic index (GI) and fructose content in lunch on substrate utilization during subsequent brisk walking. Ten healthy young males completed 3 main trials in a counterbalanced crossover design. They completed 60 min of brisk walking at approximately 50% maximal oxygen consumption after consuming a standard breakfast and 1 of 3 lunch meals, i.e., a low GI meal without fructose (LGI), a low GI meal that included fructose beverage (LGIF), or a high GI meal (HGI). The 3 lunch meals were isocaloric and provided 1.0 g·kg⁻¹ carbohydrate. Substrate utilization was measured using indirect respiratory calorimetry method. Blood samples were collected at certain time points. During the 2-h postprandial period after lunch, the incremental area under the blood response curve values of glucose and insulin were higher (p < 0.05) in the HGI trial than those in the LGI and LGIF trials (HGI vs. LGI and LGIF glucose, 223.5 ± 24.4 vs. 92.5 ± 10.4 and 128.0 ± 17.7 mmol·min·L⁻¹; insulin, 3603 ± 593 vs. 1425 ± 289 and 1888 ± 114 mU·min·L⁻¹). During brisk walking, decreased carbohydrate oxidation was observed (p < 0.05) in the LGI trial than in the LGIF and HGI trials (LGI vs. LGIF and HGI: 60.8 ± 4.0 vs. 68.1 ± 6.0 and 74.4 ± 4.7 g). No difference was found in fat oxidation among the 3 trials (LGI vs. LGIF vs. HGI: 21.6 ± 2.3 vs. 19.2 ± 2.3 vs. 16.4 ± 2.2 g). It appeared that fructose content was an important influencing factor when considering the effect of different GI lunch meals on substrate utilization during subsequent moderate intensity exercise.
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Effects of a short-term overfeeding with fructose or glucose in healthy young males.
Ngo Sock, ET, Lê, KA, Ith, M, Kreis, R, Boesch, C, Tappy, L
The British journal of nutrition. 2010;(7):939-43
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Consumption of simple carbohydrates has markedly increased over the past decades, and may be involved in the increased prevalence in metabolic diseases. Whether an increased intake of fructose is specifically related to a dysregulation of glucose and lipid metabolism remains controversial. We therefore compared the effects of hypercaloric diets enriched with fructose (HFrD) or glucose (HGlcD) in healthy men. Eleven subjects were studied in a randomised order after 7 d of the following diets: (1) weight maintenance, control diet; (2) HFrD (3.5 g fructose/kg fat-free mass (ffm) per d, +35 % energy intake); (3) HGlcD (3.5 g glucose/kg ffm per d, +35 % energy intake). Fasting hepatic glucose output (HGO) was measured with 6,6-2H2-glucose. Intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) were measured by 1H magnetic resonance spectroscopy. Both fructose and glucose increased fasting VLDL-TAG (HFrD: +59 %, P < 0.05; HGlcD: +31 %, P = 0.11) and IHCL (HFrD: +52 %, P < 0.05; HGlcD: +58 %, P = 0.06). HGO increased after both diets (HFrD: +5 %, P < 0.05; HGlcD: +5 %, P = 0.05). No change was observed in fasting glycaemia, insulin and alanine aminotransferase concentrations. IMCL increased significantly only after the HGlcD (HFrD: +24 %, NS; HGlcD: +59 %, P < 0.05). IHCL and VLDL-TAG were not different between hypercaloric HFrD and HGlcD, but were increased compared to values observed with a weight maintenance diet. However, glucose led to a higher increase in IMCL than fructose.
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Effects of intravenous fructose on gastric emptying and antropyloroduodenal motility in healthy subjects.
Stevens, JE, Doran, S, Russo, A, O'Donovan, D, Feinle-Bisset, C, Rayner, CK, Horowitz, M, Jones, KL
American journal of physiology. Gastrointestinal and liver physiology. 2009;(6):G1274-80
Abstract
Gastric emptying (GE) of glucose is regulated closely, not only as a result of inhibitory feedback arising from the small intestine, but also because of the resulting hyperglycemia. Fructose is used widely in the diabetic diet and is known to empty from the stomach slightly faster than glucose but substantially slower than water. The aims of this study were to determine whether intravenous (iv) fructose affects GE and antropyloroduodenal motility and how any effects compare to those induced by iv glucose. Six healthy males (age: 26.7 +/- 3.8 yr) underwent concurrent measurements of GE of a solid meal (100 g ground beef labeled with 20 MBq (99m)Tc-sulfur colloid) and antropyloroduodenal motility on three separate days in randomized order during iv infusion of either fructose (0.5 g/kg), glucose (0.5 g/kg), or isotonic saline for 20 min. GE (scintigraphy), antropyloroduodenal motility (manometry), and blood glucose (glucometer) were measured for 120 min. There was a rise in blood glucose (P < 0.001) after iv glucose (peak 16.4 +/- 0.6 mmol/l) but not after fructose or saline. Intravenous glucose and fructose both slowed GE substantially (P < 0.005 for both), without any significant difference between them. Between t = 0 and 30 min, the number of antral pressure waves was less after both glucose and fructose (P < 0.002 for both) than saline, and there were more isolated pyloric pressure waves during iv glucose (P = 0.003) compared with fructose and saline (P = NS for both) infusions. In conclusion, iv fructose slows GE and modulates gastric motility in healthy subjects, and the magnitude of slowing of GE is comparable to that induced by iv glucose.