Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women - PubMed (original) (raw)
Clinical Trial
Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women
C L Cox et al. Eur J Clin Nutr. 2012 Feb.
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.
Conflict of interest statement
Conflict of interest
None of the authors had any financial or personal conflicts of interest.
Figures
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).
Similar articles
- Endocrine and metabolic effects of consuming beverages sweetened with fructose, glucose, sucrose, or high-fructose corn syrup.
Stanhope KL, Havel PJ. Stanhope KL, et al. Am J Clin Nutr. 2008 Dec;88(6):1733S-1737S. doi: 10.3945/ajcn.2008.25825D. Am J Clin Nutr. 2008. PMID: 19064538 Free PMC article. Review. - Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans.
Stanhope KL, Schwarz JM, Keim NL, Griffen SC, Bremer AA, Graham JL, Hatcher B, Cox CL, Dyachenko A, Zhang W, McGahan JP, Seibert A, Krauss RM, Chiu S, Schaefer EJ, Ai M, Otokozawa S, Nakajima K, Nakano T, Beysen C, Hellerstein MK, Berglund L, Havel PJ. Stanhope KL, et al. J Clin Invest. 2009 May;119(5):1322-34. doi: 10.1172/JCI37385. Epub 2009 Apr 20. J Clin Invest. 2009. PMID: 19381015 Free PMC article. - Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake.
Tey SL, Salleh NB, Henry J, Forde CG. Tey SL, et al. Int J Obes (Lond). 2017 Mar;41(3):450-457. doi: 10.1038/ijo.2016.225. Epub 2016 Dec 13. Int J Obes (Lond). 2017. PMID: 27956737 Clinical Trial. - Circulating concentrations of monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and soluble leukocyte adhesion molecule-1 in overweight/obese men and women consuming fructose- or glucose-sweetened beverages for 10 weeks.
Cox CL, Stanhope KL, Schwarz JM, Graham JL, Hatcher B, Griffen SC, Bremer AA, Berglund L, McGahan JP, Keim NL, Havel PJ. Cox CL, et al. J Clin Endocrinol Metab. 2011 Dec;96(12):E2034-8. doi: 10.1210/jc.2011-1050. Epub 2011 Sep 28. J Clin Endocrinol Metab. 2011. PMID: 21956423 Free PMC article. - The metabolic and endocrine response and health implications of consuming sugar-sweetened beverages: findings from recent randomized controlled trials.
Rippe JM. Rippe JM. Adv Nutr. 2013 Nov 6;4(6):677-86. doi: 10.3945/an.113.004580. eCollection 2013 Nov. Adv Nutr. 2013. PMID: 24228199 Free PMC article. Review.
Cited by
- The Intersection of Genetic Factors, Aberrant Nutrient Metabolism and Oxidative Stress in the Progression of Cardiometabolic Disease.
Butcko AJ, Putman AK, Mottillo EP. Butcko AJ, et al. Antioxidants (Basel). 2024 Jan 10;13(1):87. doi: 10.3390/antiox13010087. Antioxidants (Basel). 2024. PMID: 38247511 Free PMC article. Review. - Different dietary carbohydrate component intakes and long-term outcomes in patients with NAFLD: results of longitudinal analysis from the UK Biobank.
Liu Z, Huang H, Xie J, Hou L, Xu C. Liu Z, et al. Nutr J. 2023 Dec 8;22(1):67. doi: 10.1186/s12937-023-00897-y. Nutr J. 2023. PMID: 38062487 Free PMC article. - Sugar and Dyslipidemia: A Double-Hit, Perfect Storm.
Gugliucci A. Gugliucci A. J Clin Med. 2023 Aug 31;12(17):5660. doi: 10.3390/jcm12175660. J Clin Med. 2023. PMID: 37685728 Free PMC article. Review. - The fructose survival hypothesis for obesity.
Johnson RJ, Lanaspa MA, Sanchez-Lozada LG, Tolan D, Nakagawa T, Ishimoto T, Andres-Hernando A, Rodriguez-Iturbe B, Stenvinkel P. Johnson RJ, et al. Philos Trans R Soc Lond B Biol Sci. 2023 Sep 11;378(1885):20220230. doi: 10.1098/rstb.2022.0230. Epub 2023 Jul 24. Philos Trans R Soc Lond B Biol Sci. 2023. PMID: 37482773 Free PMC article. Review.
References
- Bezerra RM, Ueno M, Silva MS, Tavares DQ, Carvalho CR, Saad MJ. A high fructose diet affects the early steps of insulin action in muscle and liver of rats. J Nutr. 2000;130:1531–1535. - PubMed
- Bingham SA. Urine nitrogen as a biomarker for the validation of dietary protein intake. J Nutr. 2003;133(Suppl 3):921S–924S. - PubMed
- Bray GA, Nielsen SJ, Popkin BM. Consumption of high-fructose corn syrup in beverages may play a role in the epidemic of obesity. Am J Clin Nutr. 2004;79:537–543. - PubMed
- Chong MF, Fielding BA, Frayn KN. Mechanisms for the acute effect of fructose on postprandial lipemia. Am J Clin Nutr. 2007;85:1511–1520. - PubMed
- Couchepin C, Le KA, Bortolotti M, da Encarnacao JA, Oboni JB, Tran C, et al. Markedly blunted metabolic effects of fructose in healthy young female subjects compared with male subjects. Diabetes Care. 2008;31:1254–1256. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- R01HL-075675/HL/NHLBI NIH HHS/United States
- AT-002993/AT/NCCIH NIH HHS/United States
- R21 AT002599/AT/NCCIH NIH HHS/United States
- R01 HL075675-05/HL/NHLBI NIH HHS/United States
- AT-003545/AT/NCCIH NIH HHS/United States
- R21 AT002993/AT/NCCIH NIH HHS/United States
- UL1 RR024146/RR/NCRR NIH HHS/United States
- R01 HL075675/HL/NHLBI NIH HHS/United States
- R01 HL107256/HL/NHLBI NIH HHS/United States
- R01 HL091333/HL/NHLBI NIH HHS/United States
- AT-002599/AT/NCCIH NIH HHS/United States
- HL-091333/HL/NHLBI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Medical
Research Materials