Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women
Open accessAbstract
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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Fructose contained in sugar sweetened beverages is suggested to likely induce the onset of obesity by reducing resting energy expenditure and promoting leptin resistance.
“fructose contained in sugar sweetened beverages is suggested to likely induce the onset of obesity by reducing resting energy expenditure and promoting leptin resistance.102 103”
From Dietary sugar consumption and health: umbrella review (2023) · cites this paper as [102]
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Butler, A. A., St‐Onge, M., Siebert, E., Medici, V., Stanhope, K. L., & Havel, P. J. (2015) · Scientific Reports · doi:10.1038/srep14691 · Cited by 41 · see citing works
Self-citationRendeiro, C., Masnik, A. M., Mun, J. G.-H., Du, K., Clark, D. I., Dilger, R. N., Dilger, A. C., & Rhodes, J. S. (2015) · Scientific Reports · doi:10.1038/srep09589 · Cited by 41 · see citing works
Heidari, A. (2020) · Advanced Science Engineering and Medicine · doi:10.1166/asem.2020.2635 · Cited by 36 · see citing works
Refeeding and metabolic syndromes: two sides of the same coin
Obeid, O., Hachem, D. H., & Ayoub, J. J. (2014) · Nutrition and Diabetes · doi:10.1038/nutd.2014.21 · Cited by 34 · see citing works
Trovato, F. M., Catalano, D., Musumeci, G., & Trovato, G. M. (2014) · The EPMA Journal · doi:10.1186/1878-5085-5-21 · Cited by 34 · see citing works
Tappy, L., Egli, L., Lecoultre, V., & Schneider, P. (2013) · Nutrition & Metabolism · doi:10.1186/1743-7075-10-54 · Cited by 34 · see citing works
Hochuli, M., Herter‐Aeberli, I., Weiss, A., Hersberger, M., Troxler, H., Gerber, P. A., Spinas, G. A., & Berneis, K. K. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3856 · Cited by 34 · see citing works
French Recommendations for Sugar Intake in Adults: A Novel Approach Chosen by ANSES
Tappy, L., Morio, B., Azzout‐Marniche, D., Champ, M. M. J., Gerber, M., Houdart, S., Mas, E., Rizkalla, S. W., Slama, G., Mariotti, F., et al. (2018) · Nutrients · doi:10.3390/nu10080989 · Cited by 34 · see citing works
Akter, S., Akhter, H., Chaudhury, H. S., Rahman, M. H., Gorski, A., Hasan, M. N., Shin, Y., Rahman, M. A., Nguyen, M. N., Choi, T. G., et al. (2022) · BioFactors · doi:10.1002/biof.1886 · Cited by 33 · see citing works
Effects of chronic sugar consumption on lipid accumulation and autophagy in the skeletal muscle
Stefanis, D. D., Mastrocola, R., Nigro, D., Costelli, P., & Aragno, M. (2017) · European Journal of Nutrition · doi:10.1007/s00394-015-1086-8 · Cited by 27 · see citing works
Alesi, S., Habibi, N., Silva, T. R., Cheung, N., Torkel, S., Tay, C. T., Quinteros, A., Winter, H., Teede, H. J., Mousa, A., et al. (2023) · Human Reproduction Update · doi:10.1093/humupd/dmad018 · Cited by 30 · see citing works
“Excess sugar consumption, specifically fructose, directly precipitates cardiovascular disease by dysregulation of lipid, carbohydrate (Cox et al. , 2012; Stanhope et al. , 2015), and insulin (Meyers et al. , 2017) homeostasis independent of excess weight.”
BackgroundDiabetes and Kidney Disease in American Indians: Potential Role of Sugar-Sweetened Beverages
Yracheta, J., Lanaspa, M. A., Le, M. T., Abdelmalak, M. F., Alfonso, J., Sánchez‐Lozada, L. G., & Johnson, R. J. (2015) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2015.03.018 · Cited by 29 · see citing works
“Studies in humans have also shown that intake of sugar-sweetened beverages or fructose causes intrahepatic adenosine triphosphate depletion, uric acid generation, hepatic lipogenesis, hepatic insulin resistance, preferential visceral fat accumulation, and a reduction in energy expenditure.(96-102) Given these findings,”
Fructose and liver function – is this behind nonalcoholic liver disease?
Jin, R., & Vos, M. B. (2015) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000203 · Cited by 26 · see citing works
Hieronimus, B., Griffen, S. C., Keim, N. L., Bremer, A. A., Berglund, L., Nakajima, K., Havel, P. J., & Stanhope, K. L. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8070913 · Cited by 26 · see citing works
“Hepatic fructose overload leads to upregulated DNL [3,8–10], reduced fat oxidation [8,9,11], and increased liver fat content [8,9,12], which are associated with increased synthesis and secretion of TG-rich VLDL1 (very low density lipoprotein) [13].”
BackgroundSelf-citationLatulippe, M. E., Méheust, A., Augustin, L. S. A., Benton, D., Berčík, P., Birkett, A. M., Eldridge, A. L., Faintuch, J., Hoffmann, C., Jones, J. M., et al. (2013) · Food & Nutrition Research · doi:10.3402/fnr.v57i0.19214 · Cited by 24 · see citing works
“and reductions in energy expenditure (98).”
Clinical Research Strategies for Fructose Metabolism
Laughlin, M. R., Bantle, J. P., Havel, P. J., Parks, E. J., Klurfeld, D. M., Teff, K. L., & Maruvada, P. (2014) · Advances in Nutrition · doi:10.3945/an.113.005249 · Cited by 25 · see citing works
“Ten weeks of fructose ingestion at 25% of the total energy requirement established at study baseline reduced resting metabolic rate relative to a diet with the same glucose dose in obese, insulin-resistant middle-aged individuals, but a similar amount of fructose for 4 wk (18% of total energy requirements) did not alt…”
BackgroundSelf-citationJohnson, R. J., Wilson, W. L., Bland, S. T., & Lanaspa, M. A. (2020) · Evolution and Human Behavior · doi:10.1016/j.evolhumbehav.2020.09.006 · Cited by 27 · see citing works
Kloster, A., Hyer, M., Dyer, S., Salome-Sanchez, C., & Neigh, G. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2019.11.039 · Cited by 19 · see citing works
“Here, caloric efficiency was modified by diet in weeks 5 and 6 of the paradigm in female rats, indicating that alterations in energy utilization are a possible source of the observed increases in body mass beyond that of the control-fed female rats (Schwarz et al., 1992; Cox et al., 2012).”
Simopoulos, A. P. (2014) · Lifestyle Genomics · doi:10.1159/000375495 · Cited by 19 · see citing works
Dietary treatment of nonalcoholic steatohepatitis
Perito, E. R., Rodríguez, L. A., & Lustig, R. H. (2012) · Current Opinion in Gastroenterology · doi:10.1097/mog.0b013e32835ca11d · Cited by 19 · see citing works
“The largest decreases in postprandial fat oxidation rates were in individuals with metabolic syndrome.[59] In adults, high-fructose diets exacerbate dyslipidemia and insulin resistance more than isocaloric highglucose diets, with effects most pronounced on adults who already have metabolic syndrome.”
BackgroundChronic arsenic exposure impairs adaptive thermogenesis in male C57BL/6J mice
Castriota, F., Zushin, P. H., Sanchez, S. S., Phillips, R. V., Hubbard, A., Stahl, A., Smith, M. T., Wang, J.-C., & Merrill, M. A. L. (2020) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00282.2019 · Cited by 18 · see citing works
Sugar and Dyslipidemia: A Double-Hit, Perfect Storm
Gugliucci, A. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12175660 · Cited by 18 · see citing works
“The main solid ingredient in fruit juices is also free sugar, which can range in concentration from 100 to 120 g/L, depending on the type and quality of the fruit [20,41,48,49].”
BackgroundSigala, D. M., Hieronimus, B., Medici, V., Lee, V., Nuñez, M. V., Bremer, A. A., Cox, C. L., Price, C. A., Benyam, Y., Abdelhafez, Y. G., et al. (2022) · Nutrients · doi:10.3390/nu14081648 · Cited by 17 · see citing works
“Fructose and/or its metabolites induce expression of sterol regulatory element binding protein 1c (SREBP-1c) and carbohydrate response element binding protein (ChREBP) and lead to increased de novo lipogenesis (DNL) [37,38] and apolipoprotein CIII (apoCIII) production [38,39], and decreased fat oxidation [10,40].”
BackgroundSelf-citationQuintana‐Castro, R., Aguirre-Maldonado, I., Soto-Rodríguez, I., Lago, R. A. D., Gruber-Pagola, P., de Larrea, Y. K. U., Juárez-Rivera, V. E., Ramos-Manuel, L. E., & Alexander-Aguilera, A. (2019) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2019.106404 · Cited by 17 · see citing works
Eekelen, E. W.-V., Beulens, J. W. J., Geelen, A., Schrauwen‐Hinderling, V. B., Lamb, H. J., Roos, A., Rosendaal, F. R., & de Mutsert, R. (2018) · Journal of Nutrition · doi:10.1093/jn/nxy313 · Cited by 16 · see citing works
“Moreover, chronic fructose consumption has been shown to decrease resting energy expenditure in a 10-wk trial (59).”
BackgroundStookey, J. D., Hamer, J., Espinoza, G., Higa, A., Ng, V., Tinajero-Deck, L., Havel, P. J., & King, J. C. (2012) · Advances in Nutrition · doi:10.3945/an.112.001990 · Cited by 17 · see citing works
“The significantly lower fat oxidation 30 min after breakfast with orange juice in the adults may therefore reflect noninsulinmediated effects of fructose availability (50) or other factors such as gastric emptying, nutrient absorption, insulin sensitivity, glycogen stores, acid/base balance, cortisol, and hydration st…”
BackgroundSelf-citationImpact of dietary glycemic challenge on fuel partitioning
Bosy‐Westphal, A., Hägele, F. A., & Nas, A. (2016) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2016.230 · Cited by 15 · see citing works
Thompson, Z., Kolb, E. M., & Garland, T. (2017) · Behavioural Processes · doi:10.1016/j.beproc.2017.11.004 · Cited by 15 · see citing works
“Recent studies have shown that fructose can suppress home-cage activity in rodents (Rendeiro et al., 2015) and decrease energy expenditure in humans (Cox et al., 2012).”
Jurado‐Fasoli, L., Amaro‐Gahete, F. J., Merchán-Ramírez, E., Labayen, I., & Ruiz, J. R. (2020) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2020.11.021 · Cited by 15 · see citing works
Monar, G. V. F., Cruz, C. S., & Martinez, E. C. (2025) · Journal of Nutrition and Metabolism · doi:10.1155/jnme/5571686 · Cited by 14 · see citing works
Comparison of aspartame- and sugar-sweetened soft drinks on postprandial metabolism
Pearson, R. C., Green, E. S., Olenick, A. A., & Jenkins, N. T. (2023) · Nutrition and Health · doi:10.1177/02601060211057415 · Cited by 12 · see citing works
Butcko, A. J., Putman, A. K., & Mottillo, E. P. (2024) · Antioxidants · doi:10.3390/antiox13010087 · Cited by 12 · see citing works
“…through decreased expression of fatty acid oxidation genes (i.e., PPAR α ) as well as direct effects on modifying the mitochondrial proteome [64,65]. fructose reduces fa tt y acid oxidation through decreased expression of fa tt y acid oxidation genes (i.e., PPAR α ) as well as direct e ff…”
BackgroundFructose: metabolic signal and modern hazard
Johnson, R. J., Lanaspa, M. A., Tolan, D. R., Goncalves, M. D., Softic, S., Stanhope, K. L., Sánchez‐Lozada, L. G., Herman, M. A., & Rabinowitz, J. D. (2026) · Nature Metabolism · doi:10.1038/s42255-026-01506-y · Cited by 11 · see citing works
“The decrease in fatty acid oxidation following fructose ingestion is distinct from glucose and is greatest in the postprandial period 37,38 , and may be mediated, in part, by fructose’s ability to increase hepatocellular malonyl-CoA, which drives fatty acid synthesis and inhibits fat oxidation…”
InfluentialSelf-citationSmeraglio, A., Kennedy, E. K., Horgan, A., Purnell, J. Q., & Gillingham, M. B. (2013) · Nutrition Research · doi:10.1016/j.nutres.2013.03.007 · Cited by 11 · see citing works
“Recently, fructose consumption has also been shown to decrease fat oxidation in obese subjects fed a high fructose diet over a tenweek period [20].”
BackgroundLiu, Z., Huang, H., Xie, J., Hou, L., & Xu, C. (2023) · Nutrition Journal · doi:10.1186/s12937-023-00897-y · Cited by 10 · see citing works
“Studies in humans and animals have reported that fructose promotes de novo lipogenesis and inhibits 𝛽 -fatty acid oxidation in the liver [30–32].”
BackgroundWu, H., Li, S., Chen, L., Yang, X., & Tan, X. W. (2024) · Food & Function · doi:10.1039/d3fo04602h · Cited by 11 · see citing works
Gugliucci, A. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13175229 · Cited by 10 · see citing works
Precision nutrition for obesity management: A gut microbiota–centered weight-loss approach
Carvalho, L. M., da Mota, J. C. N. L., Ribeiro, A., Carvalho, B. G., Martínez, J. A., & Nicoletti, C. F. (2025) · Nutrition · doi:10.1016/j.nut.2025.112892 · Cited by 10 · see citing works
Ibrahim, M. A., Bonfiglio, S. M., Schlögl, M., Vinales, K. L., Piaggi, P., Venti, C. A., Walter, M. F., Krakoff, J. A., & Thearle, M. S. (2017) · Obesity · doi:10.1002/oby.22068 · Cited by 9 · see citing works
“Contrary to our findings, a study assessing EE responses to long-term consumption of glucose- versus fructose-sweetened beverages in subjects with overweight found that consuming fructose was associated with reductions in resting EE over a 10-week period (26), so it is possible that longer-term feeding with our diets…”
ResultChan, W., Smith, B. H., Stegall, M. D., & Borrows, R. (2018) · Transplantation · doi:10.1097/tp.0000000000002424 · Cited by 8 · see citing works
Macedo, R. C. O., Vieira, A., Moritz, C. E. J., & Reischak-Oliveira, Á. (2018) · British Journal Of Nutrition · doi:10.1017/s0007114518001538 · Cited by 8 · see citing works
“Moreover, it is associated with the reduction of liver sensitivity to insulin (49) , even at moderate doses (40g/d) (19) , and decrease of fat oxidation (50) .”
Understanding the Impact of Added Sugar Consumption on Risk for Type 2 Diabetes
Price, C. A., & Stanhope, K. L. (2016) · Journal of the California Dental Association · doi:10.1080/19424396.2016.12221068 · Cited by 8 · see citing works
Self-citationDietary Fructose: A Literature Review of Current Evidence and Implications on Metabolic Health
Agarwal, V., Das, S., Kapoor, N., Prusty, B., & Das, B. (2024) · Cureus · doi:10.7759/cureus.74143 · Cited by 9 · see citing works
Fructose and Nonalcoholic Fatty Liver Disease
Lustig, R. H. (2016) · Journal of the California Dental Association · doi:10.1080/19424396.2016.12221067 · Cited by 7 · see citing works
What should we advise MAFLD patients to eat and drink?
Machado, M. V. (2021) · Metabolism and Target Organ Damage · doi:10.20517/mtod.2021.11 · Cited by 7 · see citing works
Fructose-containing sugars and metabolic risk: a systematic review and meta-analysis
Prasetya, G., Astina, J., Palupi, E., Namkieat, P., Jiamjarasrangsi, W., & Sapwarobol, S. (2025) · Food & Nutrition Research · doi:10.29219/fnr.v69.11062 · Cited by 6 · see citing works
“These results are inconsistent with prior research suggesting that free fructose may pose a greater risk for metabolic syndrome components than sucrose (29).”
Cohen, C. C., Dabelea, D., Michelotti, G. A., Tang, L., Shankar, K., Goran, M. I., & Perng, W. (2022) · Metabolites · doi:10.3390/metabo12060559 · Cited by 6 · see citing works
“Fructose intake may also alter hepatic lipid metabolism by stimulating lipogenic gene expression via the activation of several transcriptional activator families, including carbohydrateresponsive element-binding protein (ChREBP), sterol regulatory element-binding protein (SREBP), and peroxisome proliferator-activated…”
BackgroundHyer, M. M., Dyer, S. K., Kovalchick, L. V., Targett, I. L., Burns, C. M., Kloster, A., Wegener, A. J., Salome-Sanchez, C., & Neigh, G. N. (2022) · Psychoneuroimmunology Journal · doi:10.32371/pnij/246142 · Cited by 6 · see citing works
Brown, M., & Matveyenko, A. V. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.842603 · Cited by 6 · see citing works
“Despite differing perspectives on the dietary etiology of T2DM, long-term ingestion of a diet rich in saturated fatty acids and/or refined sugars has been clearly demonstrated to lead to increased visceral adiposity (57, 58), reduced energy expenditure (59, 60), peripheral insulin resistance (61, 62), and pancreatic i…”
Background
- Authors
- Cox, C. L., Stanhope, K. L., Schwarz, J. M., Graham, J. L., Hatcher, B., Griffen, S. C., Bremer, A. A., Berglund, L., McGahan, J. P., Havel, P. J., & Keim, N. L.
- Affiliations
- University of California, Davis (US)
- Touro University California (US)
- Vanderbilt University (US)
- United States Department of Agriculture (US)
- Corresponding author
- Keim, N L
- Venue
- European Journal of Clinical Nutrition
- Published
- 2011-09-28
- Volume
- 66
- Issue
- 2
- Pages
- 201-208
- ISSN
- 0954-3007 (ISSN-L)
- 1476-5640
- PMC
- PMC3252467
- OpenAlex
- W2121517321
- Cited by
- 132
- References
- 30
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 11 · 2022: 13 · 2021: 5 · 2020: 9 · 2019: 12 · 2018: 11 · 2017: 7 · 2016: 6 · 2015: 14 · 2014: 10 · 2013: 11 · 2012: 6
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Clinical Nutrition (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- American Diabetes Association (UL1 RR024146)
- U.S. Department of Agriculture (5306‐51530‐019‐00D, UL1 RR024146, 5306‐51530‐019)
- National Institutes of Health (5r01hl075675-05, 5r01hl091333-02, HL‐091333, RR024146)
- University of California, Davis (RR024146, UL1 RR024146)
- Agricultural Research Service
- National Heart, Lung, and Blood Institute (R01 HL-075675, R01 HL-091333, HL-091333, R01HL107256)
- National Center for Research Resources (UL1RR024146)
- National Center for Complementary and Integrative Health (AT0-02993, AT0-03545, AT 002599, R21AT002993, R21AT002599)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- fructose, glucose, fat oxidation, energy expenditure, resting energy expenditure, substrate utilization, carbohydrate oxidation, overweight, obesity, energy balance, postprandial metabolism
- MeSH terms
- Aged, Basal Metabolism, Beverages, Energy Intake, Energy Metabolism, Female, Fructose, Glucose, Humans, Male, Middle Aged, Obesity, Oxidation-Reduction, Sweetening Agents, Dietary Sucrose, Carbohydrate Metabolism, Lipid Metabolism
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