Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss

Hyde, Parker N.; Sapper, Teryn N.; Crabtree, Christopher D.; LaFountain, Richard A.; Bowling, Madison L.; Buga, Alex; Fell, Brandon; McSwiney, Fionn T.; Dickerson, Ryan M.; Miller, Vincent J.; Scandling, Debbie; Simonetti, Orlando P.; Phinney, Stephen D.; Kraemer, William J.; King, Sarah A.; Krauss, Ronald M.; Volek, Jeff S.

doi:10.1172/jci.insight.128308

Cited by 210Diet and metabolism studiesDietary Effects on HealthDiet, Metabolism, and Disease

Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss

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Hyde, Parker N., Sapper, Teryn N., Crabtree, Christopher D., LaFountain, Richard A., Bowling, Madison L., Buga, Alex, Fell, Brandon, McSwiney, Fionn T. +9 more·2019·JCI Insight

DOI 10.1172/jci.insight.128308PMC PMC6629108

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Abstract

BACKGROUNDMetabolic syndrome (MetS) is highly correlated with obesity and cardiovascular risk, but the importance of dietary carbohydrate independent of weight loss in MetS treatment remains controversial. Here, we test the theory that dietary carbohydrate intolerance (i.e., the inability to process carbohydrate in a healthy manner) rather than obesity per se is a fundamental feature of MetS.METHODSIndividuals who were obese with a diagnosis of MetS were fed three 4-week weight-maintenance diets that were low, moderate, and high in carbohydrate. Protein was constant and fat was exchanged isocalorically for carbohydrate across all diets.RESULTSDespite maintaining body mass, low-carbohydrate (LC) intake enhanced fat oxidation and was more effective in reversing MetS, especially high triglycerides, low HDL-C, and the small LDL subclass phenotype. Carbohydrate restriction also improved abnormal fatty acid composition, an emerging MetS feature. Despite containing 2.5 times more saturated fat than the high-carbohydrate diet, an LC diet decreased plasma total saturated fat and palmitoleate and increased arachidonate.CONCLUSIONConsistent with the perspective that MetS is a pathologic state that manifests as dietary carbohydrate intolerance, these results show that compared with eucaloric high-carbohydrate intake, LC/high-fat diets benefit MetS independent of whole-body or fat mass.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT02918422.FUNDINGDairy Management Inc. and the Dutch Dairy Association.

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Precision Nutrition for Alzheimer’s Prevention in ApoE4 Carriers
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Dietary Saturated Fats and Health: Are the U.S. Guidelines Evidence-Based?
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Ethnicity and Metabolic Syndrome: Implications for Assessment, Management and Prevention
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Regulation of Macronutrients in Insulin Resistance and Glucose Homeostasis during Type 2 Diabetes Mellitus
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Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients with Type 2 Diabetes: A Novel Anti-Atherogenic Effect
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Are Dietary Proteins the Key to Successful Body Weight Management? A Systematic Review and Meta-Analysis of Studies Assessing Body Weight Outcomes after Interventions with Increased Dietary Protein
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“recently showed that substituting carbohydrate with fat in isoenergetic diets benefits metabolic syndrome risk factors independent of whole-body or fat mass [82].”
Background
A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health
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Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD
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Effect of low-carbohydrate diets on cardiometabolic risk, insulin resistance, and metabolic syndrome
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Dietary patterns and cardiometabolic health: Clinical evidence and mechanism
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Engineered butyrate-producing bacteria prevents high fat diet-induced obesity in mice
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Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes
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Ketogenic diets, not for everyone
Goldberg, I. J., Ibrahim, N., Bredefeld, C., Foo, S. T., Lim, V., Gutman, D. C., Huggins, L.-A., & Hegele, R. A. (2020) · Journal of clinical lipidology · doi:10.1016/j.jacl.2020.10.005 · Cited by 65 · see citing works
Elevated LDL Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a “Lean Mass Hyper-Responder” Phenotype
Norwitz, N. G., Feldman, D., Soto-Mota, A., Kalayjian, T., & Ludwig, D. S. (2021) · Current Developments in Nutrition · doi:10.1093/cdn/nzab144 · Cited by 62 · see citing works
Protection Strategies Against Palmitic Acid-Induced Lipotoxicity in Metabolic Syndrome and Related Diseases
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Alternative Dietary Patterns for Americans: Low-Carbohydrate Diets
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Nutrition as Metabolic Treatment for Anxiety
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Evaluating the beneficial effects of dietary restrictions: A framework for precision nutrigeroscience
Wilson, K. A., Chamoli, M., Hilsabeck, T. A. U., Pandey, M., Bansal, S., Chawla, G., & Kapahi, P. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.08.018 · Cited by 56 · see citing works
Low Carb and Ketogenic Diets Increase Quality of Life, Physical Performance, Body Composition, and Metabolic Health of Women with Breast Cancer
Kämmerer, U., Klement, R. J., Joos, F., Sütterlin, M., & Reuss-Borst, M. A. (2021) · Nutrients · doi:10.3390/nu13031029 · Cited by 55 · see citing works
Public health guidelines should recommend reducing saturated fat consumption as much as possible: NO
Krauss, R. M., & Kris‐Etherton, P. M. (2020) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqaa111 · Cited by 54 · see citing works
Comparison of Ketogenic Diets with and without Ketone Salts versus a Low-Fat Diet: Liver Fat Responses in Overweight Adults
Crabtree, C. D., Kackley, M. L., Buga, A., Fell, B., LaFountain, R. A., Hyde, P. N., Sapper, T. N., Kraemer, W. J., SCANDLING, D. M., Simonetti, O. P., et al. (2021) · Nutrients · doi:10.3390/nu13030966 · Cited by 53 · see citing works
The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review
Sethi, S., & Ford, J. M. (2022) · Journal of Psychiatry and Brain Science · doi:10.20900/jpbs.20220009 · Cited by 51 · see citing works
Prediction of Insulin Resistance by Modified Triglyceride Glucose Indices in Youth
Song, K., Park, G., Lee, H. S., Choi, Y., Oh, J. S., Choi, H. S., Suh, J., Kwon, A., Kim, H.-S., & Chae, H. W. (2021) · Life · doi:10.3390/life11040286 · Cited by 48 · see citing works
Measuring ketone bodies for the monitoring of pathologic and therapeutic ketosis
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Coconut oil intake and its effects on the cardiometabolic profile – A structured literature review
Santos, H. O., Howell, S. L., Earnest, C. P., & Teixeira, F. J. (2019) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2019.11.001 · Cited by 46 · see citing works
Increased low-density lipoprotein cholesterol on a low-carbohydrate diet in adults with normal but not high body weight: A meta-analysis
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Effect of low carbohydrate diets on insulin resistance and the metabolic syndrome
Foley, P. J. (2021) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000659 · Cited by 41 · see citing works
The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate-Restricted Diets
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Low and high carbohydrate isocaloric diets on performance, fat oxidation, glucose and cardiometabolic health in middle age males
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Lipid Traffic Analysis reveals the impact of high paternal carbohydrate intake on offsprings’ lipid metabolism
Furse, S., Watkins, A. J., Hojat, N., Smith, J., Williams, H. E. L., Chiarugi, D., & Koulman, A. (2021) · Communications Biology · doi:10.1038/s42003-021-01686-1 · Cited by 39 · see citing works
The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketone Salts, on Body Composition Responses
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Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance
Volek, J. S., Yancy, W. S., Gower, B. A., Phinney, S. D., Slavin, J. L., Koutnik, A. P., Hurn, M., Spinner, J. R., Cucuzzella, M. T., & Hecht, F. M. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1376098 · Cited by 37 · see citing works
Low-carbohydrate diets: Effects on metabolism and exercise – A comprehensive literature review
Macedo, R. C. O., Santos, H. O., Tinsley, G. M., & Reischak-Oliveira, Á. (2020) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2020.07.022 · Cited by 38 · see citing works
Type 2 Diabetes Prevention Focused on Normalization of Glycemia: A Two-Year Pilot Study
McKenzie, A. L., Athinarayanan, S. J., McCue, J. J., Adams, R. N., Keyes, M., McCarter, J. P., Volek, J. S., Phinney, S. D., & Hallberg, S. J. (2021) · Nutrients · doi:10.3390/nu13030749 · Cited by 37 · see citing works
Self-citation
Long-term fasting improves lipoprotein-associated atherogenic risk in humans
Grundler, F., Plonné, D., Mesnage, R., Müller, D., Sirtori, C. R., Ruscica, M., & de Toledo, F. W. (2021) · European Journal of Nutrition · doi:10.1007/s00394-021-02578-0 · Cited by 37 · see citing works
Innovations in Geroscience to enhance mobility in older adults
Anton, S. D., Cruz‐Almeida, Y., Singh, A., Alpert, J. M., Bensadon, B. A., Cabrera, M., Clark, D. J., Ebner, N. C., Esser, K. A., Fillingim, R. B., et al. (2020) · Experimental Gerontology · doi:10.1016/j.exger.2020.111123 · Cited by 37 · see citing works
Genetic variants for personalised management of very low carbohydrate ketogenic diets
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Dietary pattern and hepatic lipid metabolism
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Effects of Consuming Almonds on Insulin Sensitivity and Other Cardiometabolic Health Markers in Adults With Prediabetes
Palacios, O. M., Maki, K. C., Xiao, D., Wilcox, M. L., Dicklin, M. R., Kramer, M. W., Trivedi, R., Burton‐Freeman, B. M., & Edirisinghe, I. (2019) · Journal of the American College of Nutrition · doi:10.1080/07315724.2019.1660929 · Cited by 32 · see citing works
Nutritional Ketosis in Parkinson's Disease — a Review of Remaining Questions and Insights
Choi, A. H., Hallett, M., & Ehrlich, D. J. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01067-w · Cited by 31 · see citing works
Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified?
Diamond, D. M., O’Neill, B. J., & Volek, J. S. (2020) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000568 · Cited by 33 · see citing works
Benefits of low carbohydrate diets: a settled question or still controversial?
Landry, M. J., Crimarco, A., & Gardner, C. D. (2021) · Current Obesity Reports · doi:10.1007/s13679-021-00451-z · Cited by 31 · see citing works
Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: a systematic review and meta-analysis
Falkenhain, K., Roach, L. A., McCreary, S., McArthur, E., Weiss, E. J., François, M. E., & Little, J. P. (2021) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqab212 · Cited by 34 · see citing works
Feasibility and metabolic outcomes of a well-formulated ketogenic diet as an adjuvant therapeutic intervention for women with stage IV metastatic breast cancer: The Keto-CARE trial
Buga, A., Harper, D. G., Sapper, T. N., Hyde, P. N., Fell, B., Dickerson, R. M., Stoner, J. T., Kackley, M. L., Crabtree, C. D., Decker, D. D., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0296523 · Cited by 26 · see citing works
A systematic review and meta-analysis of randomized controlled trials: effects of mediterranean diet and low-fat diet on liver enzymes and liver fat content of NAFLD
Xiong, Y., Shi, X., Xiong, X., Li, S., Zhao, H., Song, H., Wang, J., Zhang, L., You, S., Ji, G., et al. (2024) · Food & Function · doi:10.1039/d4fo01461h · Cited by 25 · see citing works
Statin therapy is not warranted for a person with high LDL-cholesterol on a low-carbohydrate diet
Diamond, D. M., Bikman, B. T., & Mason, P. (2022) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000764 · Cited by 27 · see citing works
Dietary medium-chain triacylglycerols in metabolic regulation
Cao, Y., Kanta, J. M., Bishop, C. A., Kiens, B., Fritzen, A. M., & Kleinert, M. (2025) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2025.09.010 · Cited by 25 · see citing works
Effects of Microalgae on Metabolic Syndrome
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Beneficial Effects of the Ketogenic Diet on Nonalcoholic Fatty Liver Disease (NAFLD/MAFLD)
Dyńka, D., Rodzeń, Ł., Rodzeń, M., Łojko, D., Kraszewski, S., Ibrahim, A., Hussey, M., Deptuła, A., Grzywacz, Ż., Ternianov, A., et al. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13164857 · Cited by 23 · see citing works
Characterization of a high-resolution breath acetone meter for ketosis monitoring
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Consuming a ketogenic diet leads to altered hypoglycemic counter-regulation in mice
Morrison, C. D., Hill, C. M., DuVall, M. A., Coulter, C. E., Gosey, J. L., Herrera, M. J., Maisano, L. E., Sikaffy, H. X., & McDougal, D. H. (2020) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2020.107557 · Cited by 22 · see citing works
Restricting carbohydrates and calories in the treatment of type 2 diabetes: a systematic review of the effectiveness of ‘low-carbohydrate’ interventions with differing energy levels
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The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial
McCullough, D., Harrison, T., Boddy, L. M., Enright, K. J., Amirabdollahian, F., Schmidt, M., Doenges, K., Quinn, K. D., Reisdorph, N. A., Mazidi, M., et al. (2022) · Nutrients · doi:10.3390/nu14183691 · Cited by 22 · see citing works
Management of Hypertriglyceridemia: Common Questions and Answers.
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The effects of a 6-week controlled, hypocaloric ketogenic diet, with and without exogenous ketone salts, on cognitive performance and mood states in overweight and obese adults
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Very Low Calorie Ketogenic Diet: What Effects on Lipid Metabolism?
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The biochemistry of low-carbohydrate and ketogenic diets
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Dietary medium-chain fatty acids reduce hepatic fat accumulation via activation of a CREBH-FGF21 axis
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Pharmacological and physiological roles of adipokines and myokines in metabolic-related dementia
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Treating Diabetes Utilizing a Low Carbohydrate Ketogenic Diet and Intermittent Fasting Without Significant Weight Loss: A Case Report
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Effects of Hypocaloric Low-Fat, Ketogenic, and Ketogenic and Ketone Supplement Diets on Aldosterone and Renin
Belany, P. A., Kackley, M. L., Zhao, S., Kluwe, B., Buga, A., Crabtree, C. D., Nedungadi, D., Kline, D., Brock, G. N., Simonetti, O. P., et al. (2023) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgad009 · Cited by 18 · see citing works
Dietary protection against the visual and motor deficits induced by experimental autoimmune encephalomyelitis
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The Impact of the Mediterranean Diet and Lifestyle Intervention on Lipoprotein Subclass Profiles among Metabolic Syndrome Patients: Findings of a Randomized Controlled Trial
Candás‐Estébanez, B., Fernández‐Cidón, B., Corbella, E., Tebé, C., Fanlo‐Maresma, M., Esteve-Luque, V., Salas‐Salvadó, J., Fitó, M., Riera‐Mestre, A., Ros, E., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021338 · Cited by 18 · see citing works
The Molecular Effects of Dietary Acid Load on Metabolic Disease (The Cellular PasaDoble: The Fast-Paced Dance of pH Regulation)
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Metabolic Syndrome: An Overview on Its Genetic Associations and Gene–Diet Interactions
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Application of nutrient essentiality criteria to dietary carbohydrates
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The therapeutic properties of ketogenic diets, slow-wave sleep, and circadian synchrony
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The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained, Recreational Distance Runners: A Randomized, Cross-Over Trial
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The Effect of Exercise Intensity and Volume on Metabolic Phenotype in Patients with Metabolic Syndrome: A Randomized Controlled Trial
von Korn, P., Keating, S. E., Mueller, S., Haller, B., Kränkel, N., Dinges, S. M.-T., Duvinage, A., Scherr, J., Wisløff, U., Tjønna, A. E., et al. (2020) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2020.0105 · Cited by 17 · see citing works
Dietary Assessment Tools and Metabolic Syndrome: Is It Time to Change the Focus?
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Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts
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Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM
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Hiding unhealthy heart outcomes in a low-fat diet trial: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial finds that postmenopausal women with established coronary heart disease were at increased risk of an adverse outcome if they consumed a low-fat ‘heart-healthy’ diet
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Effectiveness of Technology-Enabled, Low Carbohydrate Dietary Interventions, in the Prevention or Treatment of Type 2 Diabetes Mellitus in Adults: A Systematic Literature Review of Randomised Controlled and Non-Randomised Trials
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Health at Every Size®-Based Interventions May Improve Cardiometabolic Risk and Quality of Life Even in the Absence of Weight Loss: An Ancillary, Exploratory Analysis of the Health and Wellness in Obesity Study
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Fish Oil Enriched n-3 Polyunsaturated Fatty Acids Improve Ketogenic Low-Carbohydrate/High-Fat Diet-Caused Dyslipidemia, Excessive Fat Accumulation, and Weight Control in Rats
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Low‐carbohydrate diet score is associated with improved blood pressure and cardio‐metabolic risk factors among obese adults
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A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and impacts systemic inflammation and experimental atherosclerosis
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Potential anti‐obesity effect of saponin metabolites from adzuki beans: A computational approach
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Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes
Alzahrani, A. H., Skytte, M. J., Samkani, A., Thomsen, M. N., Astrup, A. V., Ritz, C., Frystyk, J., Holst, J. J., Madsbad, S., Haugaard, S. B., et al. (2021) · Nutrients · doi:10.3390/nu13051694 · Cited by 12 · see citing works
The Effects of Concurrent Training Combined with Low-Carbohydrate High-Fat Ketogenic Diet on Body Composition and Aerobic Performance: A Systematic Review and Meta-Analysis
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Carbohydrate restriction uniquely benefits metabolic syndrome and saturated fat metabolism
Volek, J. S. (2012) · BMC Proceedings · doi:10.1186/1753-6561-6-s3-o27
Carbohydrate Restriction has a More Favorable Impact on the Metabolic Syndrome than a Low Fat Diet
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Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction
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Effects of a Moderately-Restricted Carbohydrate Diet on Cardiovascular Risk Factors among Women with Metabolic Syndrome
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Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome
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Authors: Hyde, P. N., Sapper, T. N., Crabtree, C. D., LaFountain, R. A., Bowling, M. L., Buga, A., Fell, B., McSwiney, F. T., Dickerson, R. M., Miller, V. J., Scandling, D., Simonetti, O. P., Phinney, S. D., Kraemer, W. J., King, S. A., Krauss, R. M., & Volek, J. S.
Affiliations: The Ohio State University (US)
Department of Human Sciences, The Ohio State University, Columbus, Ohio, USA.
Waterford Institute of Technology (IE)
The Ohio State University Wexner Medical Center (US)
Virta Health, San Francisco, California, USA.
Department of Atherosclerosis Research, Children’s Hospital Oakland Research Institute, Oakland, California, USA.
Corresponding author: Volek, Jeff S.
ORCID: Hyde, Parker N.
Sapper, Teryn N.
Crabtree, Christopher D.
LaFountain, Richard A.
Buga, Alex
McSwiney, Fionn T.
Dickerson, Ryan M.
Miller, Vincent J.
Simonetti, Orlando P.
Phinney, Stephen D.
Kraemer, William J.
Krauss, Ronald M.
Volek, Jeff S.
Venue: JCI Insight
Publisher: American Society for Clinical Investigation
Published: 2019-06-20
Volume: 4
Issue: 12
ISSN: 2379-3708 (ISSN-L)
DOI: 10.1172/jci.insight.128308
PMC: PMC6629108
OpenAlex: W2952929143
Cited by: 210
References: 54
Citations by year: 2026: 18 · 2025: 21 · 2024: 29 · 2023: 26 · 2022: 33 · 2021: 47 · 2020: 28 · 2019: 8
FWCI: 19.88
Type: journal article
Language: en
Open access: gold
doi.org
Locations: JCI Insight (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion)
Funders: Dairy Management Inc (GRT00036921)
Dutch Dairy Association (GRT00036921)
Topics: Health Sciences › Medicine › Physiology › Diet and metabolism studies
Health Sciences › Medicine › Physiology › Dietary Effects on Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords: metabolic syndrome, carbohydrate restriction, low-carbohydrate diet, weight-maintenance diet, obesity, fat oxidation, triglycerides, HDL cholesterol, fatty acid composition, saturated fat, palmitoleic acid, arachidonic acid, carbohydrate intolerance
MeSH terms: Adult, Aged, Diet, Dietary Carbohydrates, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Obesity, 8,11,14-Eicosatrienoic Acid, Weight Loss, Arachidonic Acid, Cross-Over Studies, Metabolic Syndrome

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Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss

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