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Metabolic Disorders

Obesity/Weight loss

Systematic Reviews, Meta-Analyses, and other reviews

  1. Akbari, M. et al. (2024) ‘Comparison of weight loss effects among overweight/obese adults: A network meta-analysis of mediterranean, low carbohydrate, and low-fat diets’, Clinical Nutrition ESPEN, 64, pp. 7–15. Available at: https://doi.org/10.1016/j.clnesp.2024.08.023.
  2. Liao, T. et al. (2024) ‘The impact of 3 different dietary interventions on overweight or obese adults: A network meta-analysis’, Medicine, 103(42), p. e39749. Available at: https://doi.org/10.1097/MD.0000000000039749.
  3. Muscogiuri G, El Ghoch M, Colao A, et al. European Guidelines for Obesity Management in Adults with a Very Low-Calorie Ketogenic Diet: A Systematic Review and Meta-Analysis. OFA. Published online April 21, 2021:1-24. doi:10.1159/000515381
  4. Darand, M. et al. (2023) ‘Comparison of the Effect of a Low-Carbohydrate Diet with a Low-Fat Diet on Anthropometric Indices and Body Fat Percentage: A Systematic Review and Meta-Analysis of Randomized Controlled Trials’, Journal of Nutrition and Food Security, 8(3), pp. 493–520. Available at: https://doi.org/10.18502/jnfs.v8i3.13297.
  5. Willems AEM, Sura–de Jong M, van Beek AP, Nederhof E, van Dijk G. Effects of macronutrient intake in obesity: a meta-analysis of low-carbohydrate and low-fat diets on markers of the metabolic syndrome. Nutr Rev. doi:10.1093/nutrit/nuaa044
  6. Lei, L. et al. (2022) ‘Effects of low-carbohydrate diets versus low-fat diets on metabolic risk factors in overweight and obese adults: A meta-analysis of randomized controlled trials’, Frontiers in Nutrition, 9, p. 935234. Available at: https://doi.org/10.3389/fnut.2022.935234.
  7. Sievert K, Hussain SM, Page MJ, et al. Effect of breakfast on weight and energy intake: systematic review and meta-analysis of randomised controlled trials. BMJ. 2019;364:l42. doi:10.1136/bmj.l42
  8. Choi YJ, Jeon S-M, Shin S. Impact of a Ketogenic Diet on Metabolic Parameters in Patients with Obesity or Overweight and with or without Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials. Nutrients. 2020;12(7):2005. doi:10.3390/nu12072005
  9. Mansoor N, Vinknes KJ, Veierød MB, Retterstøl K. Effects of low-carbohydrate diets v. low-fat diets on body weight and cardiovascular risk factors: a meta-analysis of randomised controlled trials. Br J Nutr. 2016;115(3):466-479. doi:10.1017/S0007114515004699
  10. Sackner-Bernstein J, Kanter D, Kaul S. Dietary Intervention for Overweight and Obese Adults: Comparison of Low-Carbohydrate and Low-Fat Diets. A Meta-Analysis. PLoS ONE. 2015;10(10):e0139817. doi:10.1371/journal.pone.0139817
  11. Bueno NB, de Melo ISV, de Oliveira SL, da Rocha Ataide T. Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br J Nutr. 2013;110(7):1178-1187. doi:10.1017/S0007114513000548
  12. Ludwig DS, Dickinson SL, Henschel B, Ebbeling CB, Allison DB. Do Lower-Carbohydrate Diets Increase Total Energy Expenditure? An Updated and Reanalyzed Meta-Analysis of 29 Controlled-Feeding Studies. J Nutr. doi:10.1093/jn/nxaa350
  13. Amini MR, Aminianfar A, Naghshi S, Larijani B, Esmaillzadeh A. The effect of ketogenic diet on body composition and anthropometric measures: A systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. Published online January 14, 2021:1-14. doi:10.1080/10408398.2020.1867957
  14. Lee HS, Lee J. Effects of Combined Exercise and Low Carbohydrate Ketogenic Diet Interventions on Waist Circumference and Triglycerides in Overweight and Obese Individuals: A Systematic Review and Meta-Analysis. International Journal of Environmental Research and Public Health. 2021;18(2):828. doi:10.3390/ijerph18020828
  15. Nicholas AP, Soto-Mota A, Lambert H, Collins AL. 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. Journal of Nutritional Science. 2021;10. doi:10.1017/jns.2021.67
  16. Ludwig DS, Aronne LJ, Astrup A, et al. The carbohydrate-insulin model: a physiological perspective on the obesity pandemic. The American Journal of Clinical Nutrition. 2021;(nqab270). doi:10.1093/ajcn/nqab270

Trials/Studies

  1. Sun, J. et al. (2023) ‘The effect of dietary carbohydrate and calorie restriction on weight and metabolic health in overweight/obese individuals: a multi-center randomized controlled trial’, BMC Medicine, 21, p. 192. Available at: https://doi.org/10.1186/s12916-023-02869-9.
  2. Saslow, L.R. et al. (2023) ‘Comparing Very Low-Carbohydrate vs DASH Diets for Overweight or Obese Adults With Hypertension and Prediabetes or Type 2 Diabetes: A Randomized Trial’, Annals of Family Medicine, 21(3), pp. 256–263. Available at: https://doi.org/10.1370/afm.2968.
  3. Ebbeling CB, Feldman HA, Klein GL, et al. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ. 2018;363:k4583. doi:10.1136/bmj.k4583
  4. Goss AM, Gower B, Soleymani T, et al. Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial. Nutrition & Metabolism. 2020;17(1):64. doi:10.1186/s12986-020-00481-9
  5. Röhling M, Martin K, Ellinger S, Schreiber M, Martin S, Kempf K. Weight Reduction by the Low-Insulin-Method—A Randomized Controlled Trial. Nutrients. 2020;12(10):3004. doi:10.3390/nu12103004
  6. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet. New England Journal of Medicine. 2008;359(3):229-241. doi:10.1056/NEJMoa0708681
  7. Aude YW, Agatston AS, Lopez-Jimenez F, et al. The national cholesterol education program diet vs a diet lower in carbohydrates and higher in protein and monounsaturated fat: a randomized trial. Arch Intern Med. 2004;164(19):2141-2146. doi:10.1001/archinte.164.19.2141
  8. Brinkworth GD, Noakes M, Buckley JD, Keogh JB, Clifton PM. Long-term effects of a very-low-carbohydrate weight loss diet compared with an isocaloric low-fat diet after 12 mo. Am J Clin Nutr. 2009;90(1):23-32. doi:10.3945/ajcn.2008.27326
  9. Follis, S. et al. (2024) ‘Effect of Low-Carbohydrate vs Low-Fat Diet Intervention on Visceral Fat in a 12-Month Randomized Controlled Trial’. Available at: https://doi.org/10.21203/rs.3.rs-4926524/v1. (preprint)
  10. Tricò D, Moriconi D, Berta R, et al. Effects of Low-Carbohydrate versus Mediterranean Diets on Weight Loss, Glucose Metabolism, Insulin Kinetics and β-Cell Function in Morbidly Obese Individuals. Nutrients. 2021;13(4):1345. doi:10.3390/nu13041345
  11. Volek J, Sharman M, Gómez A, et al. Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women. Nutrition & Metabolism. 2004;1(1):13. doi:10.1186/1743-7075-1-13
  12. Samaha FF, Iqbal N, Seshadri P, et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. N Engl J Med. 2003;348(21):2074-2081. doi:10.1056/NEJMoa022637
  13. Garr Barry V, Stewart M, Soleymani T, Desmond RA, Goss AM, Gower BA. Greater Loss of Central Adiposity from Low-Carbohydrate versus Low-Fat Diet in Middle-Aged Adults with Overweight and Obesity. Nutrients. 2021;13(2):475. doi:10.3390/nu13020475
  14. Wu, W., Zhou, Q., Yuan, P., Qiao, D., Deng, S., Cheng, H., Ren, Y., 2022. A Novel Multiphase Modified Ketogenic Diet: An Effective and Safe Tool for Weight Loss in Chinese Obese Patients. DMSO 15, 2521–2534. doi.org/10.2147/DMSO.S365192
  15. Falkenhain K, Locke SR, Lowe DA, et al. Keyto App and Device versus WW App on Weight Loss and Metabolic Risk in Adults with Overweight or Obesity: A Randomized Trial. Obesity. n/a(n/a). doi:10.1002/oby.23242    PDF
  16. Walker L, Smith N, Delon C. Weight loss, hypertension and mental well-being improvements during COVID-19 with a multicomponent health promotion programme on Zoom: a service evaluation in primary care. BMJ Nutrition, Prevention & Health. Published online February 13, 2021:bmjnph. doi:10.1136/bmjnph-2020-000219   PDF
  17. Al Aamri, K.S. et al. (2022) ‘The effect of low-carbohydrate ketogenic diet in the management of obesity compared with low caloric, low-fat diet’, Clinical nutrition ESPEN, 49, pp. 522–528. Available at: https://doi.org/10.1016/j.clnesp.2022.02.110.
  18. Paoli A, Bianco A, Grimaldi KA, Lodi A, Bosco G. Long term successful weight loss with a combination biphasic ketogenic Mediterranean diet and Mediterranean diet maintenance protocol. Nutrients. 2013;5(12):5205-5217. doi:10.3390/nu5125205
  19. Gomez-Arbelaez D, Crujeiras AB, Castro AI, et al. Resting metabolic rate of obese patients under very low calorie ketogenic diet. Nutr Metab (Lond). 2018;15. doi:10.1186/s12986-018-0249-z

  20. Ebbeling CB, Bielak L, Lakin PR, et al. Energy Requirement Is Higher During Weight-Loss Maintenance in Adults Consuming a Low- Compared with High-Carbohydrate Diet. J Nutr. 2020;150(8):2009-2015. doi:10.1093/jn/nxaa150

  21. Zhang S, Wu P, Tian Y, et al. Gut Microbiota Serves a Predictable Outcome of Short-Term Low-Carbohydrate Diet (LCD) Intervention for Patients with Obesity. Microbiology Spectrum. 0(0):e00223-21. doi:10.1128/Spectrum.00223-21 

Women

A recent paper by Cooper et al. (2023) comments on the long term effects of being in nutritional ketosis for women. They found sustained ketosis showed no adverse health effects and metabolic flexibility was preserved.

The second paper in this series (2024) looked at biomarkers associated with aging, with no adverse effects.

For weight loss and reproductive health, see ‘Female Reproductive Health’ further down in the listing.

  1. Michalczyk MM, Klonek G, Maszczyk A, Zajac A. The Effects of a Low Calorie Ketogenic Diet on Glycaemic Control Variables in Hyperinsulinemic Overweight/Obese Females. Nutrients. 2020;12(6):1854. doi:10.3390/nu12061854
  2. Kong Z, Sun S, Shi Q, Zhang H, Tong TK, Nie J. Short-Term Ketogenic Diet Improves Abdominal Obesity in Overweight/Obese Chinese Young Females. Front Physiol. 2020;11. doi:10.3389/fphys.2020.00856
  3. Maseroli, E. et al. (2023) ‘(055) Application of a Very Low Calorie Ketogenic Diet (VLCKD) Protocol in Women’s Endocrinology: Psychosexual Correlates of Weight Loss’, The Journal of Sexual Medicine, 20(Supplement_2), p. qdad061.051. Available at: https://doi.org/10.1093/jsxmed/qdad061.051.
  4. Hutchison AT, Liu B, Wood RE, et al. Effects of Intermittent Versus Continuous Energy Intakes on Insulin Sensitivity and Metabolic Risk in Women with Overweight. Obesity (Silver Spring). 2019;27(1):50-58. doi:10.1002/oby.22345 PDF
  5. Gardner CD, Kiazand A, Alhassan S, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007;297(9):969-977. doi:10.1001/jama.297.9.969 
  6. Brehm BJ, Spang SE, Lattin BL, Seeley RJ, Daniels SR, D’Alessio DA. The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets. J Clin Endocrinol Metab. 2005;90(3):1475-1482. doi:10.1210/jc.2004-1540
  7. Aronica L, Rigdon J, Offringa LC, Stefanick ML, Gardner CD. Examining differences between overweight women and men in 12-month weight loss study comparing healthy low-carbohydrate vs. low-fat diets. International Journal of Obesity. Published online November 14, 2020:1-10. doi:10.1038/s41366-020-00708-y
  8. Sun S, Kong Z, Shi Q, Zhang H, Lei O-K, Nie J. Carbohydrate Restriction with or without Exercise Training Improves Blood Pressure and Insulin Sensitivity in Overweight Women. Healthcare. 2021;9(6):637. doi:10.3390/healthcare9060637
  9. Nicolosi, A.E. et al. (2024) ‘P-641 A prospective observational case series on the effects of a very low-calorie ketogenic diet (VLCKD) in overweight and obese infertile women’, Human Reproduction, 39(Supplement_1), p. deae108.973. Available at: https://doi.org/10.1093/humrep/deae108.973.
  10. Arbour MW, Stec M, Walker KC, Wika JC. Clinical Implications for Women of a Low-Carbohydrate or Ketogenic Diet With Intermittent Fasting. Nursing for Women’s Health. 2021;25(2):139-151. doi:10.1016/j.nwh.2021.01.009 ABSTRACT
  11. Yılmaz SK, Eskici G, Mertoǧlu C, Ayaz A. Effect of different protein diets on weight loss, inflammatory markers, and cardiometabolic risk factors in obese women. J Res Med Sci. 2021;26:28. doi:10.4103/jrms.JRMS_611_20 
  12. Tavakoli A, Mirzababaei A, Mirzaei K. Association between low carbohydrate diet (LCD) and sleep quality by mediating role of inflammatory factors in women with overweight and obesity: A cross-sectional study. Food Science & Nutrition. n/a(n/a). doi:10.1002/fsn3.2584

  13. Ciaffi, J. et al. (2023) ‘Efficacy, safety and tolerability of very low-calorie ketogenic diet in obese women with fibromyalgia: a pilot interventional study’, Frontiers in Nutrition, 10. Available at: https://www.frontiersin.org/articles/10.3389/fnut.2023.1219321 .

  14. Al-jammaz, M.H. et al. (2023) ‘The modulation of carbohydrate intake and intermittent fasting in obese Saudi women: a pilot study’, Bulletin of the National Research Centre, 47(1), p. 146. Available at: https://doi.org/10.1186/s42269-023-01118-6.
  15. Martins, C. et al. (2025) ‘The impact of a low-carbohydrate (vs. low-fat) diet on fat mass loss in African American women is modulated by insulin sensitivity’, Obesity (Silver Spring, Md.) [Preprint]. Available at: https://doi.org/10.1002/oby.24201. ABSTRACT
  16. Domaszewski P, Konieczny M, Pakosz P, Bączkowicz D, Sadowska-Krępa E. Effect of a Six-Week Intermittent Fasting Intervention Program on the Composition of the Human Body in Women over 60 Years of Age. International Journal of Environmental Research and Public Health. 2020;17(11):4138. doi:10.3390/ijerph17114138
 

Fasting and weight loss

  1. Patikorn, C. et al. (2021) ‘Intermittent Fasting and Obesity-Related Health Outcomes: An Umbrella Review of Meta-analyses of Randomized Clinical Trials’, JAMA Network Open, 4(12), p. e2139558. doi:10.1001/jamanetworkopen.2021.39558.
  2. Yan S, Wang C, Zhao H, et al. Effects of fasting intervention regulating anthropometric and metabolic parameters in subjects with overweight or obesity: a systematic review and meta-analysis. Food Funct. Published online April 27, 2020. doi:10.1039/D0FO00287A
  3. Harris L, Hamilton S, Azevedo LB, et al. Intermittent fasting interventions for treatment of overweight and obesity in adults: a systematic review and meta-analysis. JBI Database System Rev Implement Rep. 2018;16(2):507-547. doi:10.11124/JBISRIR-2016-003248
  4. Cioffi I, Evangelista A, Ponzo V, et al. Intermittent versus continuous energy restriction on weight loss and cardiometabolic outcomes: a systematic review and meta-analysis of randomized controlled trials. Journal of Translational Medicine. 2018;16(1):371. doi:10.1186/s12967-018-1748-4
  5. Welton S, Minty R, O’Driscoll T, et al. Intermittent fasting and weight loss: Systematic review. Canadian Family Physician. 2020;66(2):117-125.
  6. Trepanowski JF, Kroeger CM, Barnosky A, et al. Effect of Alternate-Day Fasting on Weight Loss, Weight Maintenance, and Cardioprotection Among Metabolically Healthy Obese Adults: A Randomized Clinical Trial. JAMA Intern Med. 2017;177(7):930-938. doi:10.1001/jamainternmed.2017.0936 
  7. Aksungar FB, Sarıkaya M, Coskun A, Serteser M, Unsal I. Comparison of Intermittent Fasting Versus Caloric Restriction in Obese Subjects: A Two Year Follow-Up. J Nutr Health Aging. 2017;21(6):681-685. doi:10.1007/s12603-016-0786-y ABSTRACT  
  8. Catenacci VA, Pan Z, Ostendorf D, et al. A randomized pilot study comparing zero-calorie alternate-day fasting to daily caloric restriction in adults with obesity. Obesity (Silver Spring). 2016;24(9):1874-1883. doi:10.1002/oby.21581 PDF
  9. Varady KA, Bhutani S, Klempel MC, et al. Alternate day fasting for weight loss in normal weight and overweight subjects: a randomized controlled trial. Nutr J. 2013;12:146. doi:10.1186/1475-2891-12-146  
  10. Kalam F, Gabel K, Cienfuegos S, et al. Alternate day fasting combined with a low‐carbohydrate diet for weight loss, weight maintenance, and metabolic disease risk reduction. Obes Sci Pract. 2019;5(6):531-539. doi:10.1002/osp4.367
  11. Klempel MC, Bhutani S, Fitzgibbon M, Freels S, Varady KA. Dietary and physical activity adaptations to alternate day modified fasting: implications for optimal weight loss. Nutrition Journal. 2010;9(1):35. doi:10.1186/1475-2891-9-35  
  12. Li C, Ostermann T, Hardt M, et al. Metabolic and Psychological Response to 7-Day Fasting in Obese Patients with and without Metabolic Syndrome. CMR. 2013;20(6):413-420. doi:10.1159/000353672   
  13. Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutrition Journal. 2012;11(1):98. doi:10.1186/1475-2891-11-98   
  14. Rynders CA, Thomas EA, Zaman A, Pan Z, Catenacci VA, Melanson EL. Effectiveness of Intermittent Fasting and Time-Restricted Feeding Compared to Continuous Energy Restriction for Weight Loss. Nutrients. 2019;11(10):2442. doi:10.3390/nu11102442
  15. Liu, T. et al. (2023) ‘Efficacy and safety of modified fasting therapy for weight loss in 2054 hospitalized patients’, Obesity (Silver Spring, Md.), 31(6), pp. 1514–1529. Available at: https://doi.org/10.1002/oby.23756. ABSTRACT

Lymphoedema and Lipoedema

 
  1. Amato, A.C.M., Amato, J.L.S. and Benitti, D.A. (2024) ‘The Efficacy of Ketogenic Diets (Low Carbohydrate; High Fat) as a Potential Nutritional Intervention for Lipedema: A Systematic Review and Meta-Analysis’, Nutrients, 16(19), p. 3276. Available at: https://doi.org/10.3390/nu16193276.
  2. Lundanes, J., Storliløkken, G.E., et al. (2024) ‘Gastrointestinal hormones and subjective ratings of appetite after low-carbohydrate vs low-fat low-energy diets in females with lipedema – A randomized controlled trial’, Clinical nutrition ESPEN, 65, pp. 16–24. Available at: https://doi.org/10.1016/j.clnesp.2024.11.018.
  3. Lundanes, J., Gårseth, M., et al. (2024) ‘The effect of a low-carbohydrate diet on subcutaneous adipose tissue in females with lipedema’, Frontiers in Nutrition, 11. Available at: https://doi.org/10.3389/fnut.2024.1484612.
  4. Jeziorek, M. et al. (2023) ‘The Benefits of Low-Carbohydrate, High-Fat (LCHF) Diet on Body Composition, Leg Volume, and Pain in Women with Lipedema’, Journal of Obesity, 2023, p. e5826630. Available at: https://doi.org/10.1155/2023/5826630. 
  5. Lodewijckx, I. et al. (2024) ‘Potential therapeutic effect of a ketogenic diet for the treatment of lymphoedema: Results of an exploratory study’, Journal of Human Nutrition and Dietetics: The Official Journal of the British Dietetic Association [Preprint]. Available at: https://doi.org/10.1111/jhn.13330. 
  6. Lundanes, J. et al. (2024) ‘Effect of a low-carbohydrate diet on pain and quality of life in female patients with lipedema: a randomized controlled trial’, Obesity, n/a(n/a). Available at: https://doi.org/10.1002/oby.24026.
  7. Jeziorek, M. et al. (2023) ‘The Effect of a Low-Carbohydrate High-Fat Diet on Laboratory Parameters in Women with Lipedema in Comparison to Overweight/Obese Women’, Nutrients, 15(11), p. 2619. Available at: https://doi.org/10.3390/nu15112619
  8. Jeziorek, M., Szuba, A., Kujawa, K., Regulska-Ilow, B., 2022. The Effect of a Low-Carbohydrate, High-Fat Diet versus Moderate-Carbohydrate and Fat Diet on Body Composition in Patients with Lipedema. DMSO 15, 2545–2561. doi.org/10.2147/DMSO.S377720
  9. Keith L, Seo CA, Rowsemitt C, et al. Ketogenic Diet as a Potential Intervention for Lipedema. Medical Hypotheses. Published online November 27, 2020:110435. doi:10.1016/j.mehy.2020.110435
  10. Sørlie V, De Soysa AK, Hyldmo ÅA, Retterstøl K, Martins C, Nymo S. Effect of a ketogenic diet on pain and quality of life in patients with lipedema: The LIPODIET pilot study. Obesity Science & Practice. (2021). doi:10.1002/osp4.580  PDF
  11. Keith L, Rowsemitt C, Richards LG. Lifestyle Modification Group for Lymphedema and Obesity Results in Significant Health Outcomes. Am J Lifestyle Med. 2017;14(4):420-428. doi:10.1177/1559827617742108 ABSTRACT
  12. Di Renzo, L. et al. (2023) ‘Modified Mediterranean-Ketogenic Diet and Carboxytherapy as Personalized Therapeutic Strategies in Lipedema: A Pilot Study’, Nutrients, 15(16), p. 3654. Available at: https://doi.org/10.3390/nu15163654.
  13. Cannataro, R. et al. (2021) ‘Management of Lipedema with Ketogenic Diet: 22-Month Follow-Up’, Life, 11(12), p. 1402. doi:10.3390/life11121402.
  14. Verde, L. et al. (2023) ‘Ketogenic Diet: A Nutritional Therapeutic Tool for Lipedema?’, Current Obesity Reports [Preprint]. Available at: https://doi.org/10.1007/s13679-023-00536-x.
  15. García-Caballero M, Zecchin A, Souffreau J, et al. Role and therapeutic potential of dietary ketone bodies in lymph vessel growth. Nature Metabolism. 2019;1(7):666-675. doi:10.1038/s42255-019-0087-y   ABSTRACT  (Preclinical study)

Metabolic Syndrome/Pre-diabetes/Insulin Resistance

Systematic Reviews, Meta-analyses, and other reviews

  1. de Menezes EVA, Sampaio HA de C, Carioca AAF, et al. Influence of Paleolithic diet on anthropometric markers in chronic diseases: systematic review and meta-analysis. Nutrition Journal. 2019;18(1):41. doi:10.1186/s12937-019-0457-z
  2. Sohouli MH, Fatahi S, Lari A, et al. The effect of paleolithic diet on glucose metabolism and lipid profile among patients with metabolic disorders: a systematic review and meta-analysis of randomized controlled trials. Crit Rev Food Sci Nutr. Published online January 25, 2021:1-12. doi:10.1080/10408398.2021.1876625 ABSTRACT
  3. Manheimer EW, van Zuuren EJ, Fedorowicz Z, Pijl H. Paleolithic nutrition for metabolic syndrome: systematic review and meta-analysis. Am J Clin Nutr. 2015;102(4):922-932. doi:10.3945/ajcn.115.113613   
  4. Volek, J.S. et al. (2009) ‘Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet’, Lipids, 44(4), pp. 297–309. doi:10.1007/s11745-008-3274-2.
  5. Volek, J.S. and Feinman, R.D. (2005) ‘Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction’, Nutrition & Metabolism, 2, p. 31. doi:10.1186/1743-7075-2-31.
  6. Castro-Barquero S, Ruiz-León AM, Sierra-Pérez M, Estruch R, Casas R. Dietary Strategies for Metabolic Syndrome: A Comprehensive Review. Nutrients. 2020;12(10). doi:10.3390/nu12102983
  7. Hoyas I, Leon-Sanz M. Nutritional Challenges in Metabolic Syndrome. Journal of Clinical Medicine. 2019;8(9):1301. doi:10.3390/jcm8091301 
  8. Shemirani F, Golzarand M, Salari-Moghaddam A, Mahmoudi M. Effect of low-carbohydrate diet on adiponectin level in adults: a systematic review and dose-response meta-analysis of randomized controlled trials. Critical Reviews in Food Science and Nutrition. 2021;0(0):1-10. doi:10.1080/10408398.2021.1871588 ABSTRACT
  9. Foley PJ. Effect of low carbohydrate diets on insulin resistance and the metabolic syndrome. Current Opinion in Endocrinology, Diabetes, and Obesity. 2021;28(5):463. doi:10.1097/MED.0000000000000659
  10. Guarnotta, V. et al. (2022) ‘Very Low-Calorie Ketogenic Diet: A Potential Application in the Treatment of Hypercortisolism Comorbidities’, Nutrients, 14(12), p. 2388. Available at: https://doi.org/10.3390/nu14122388.

Trials/Studies

  1. Ismael SA. Effects of low carbohydrate diet compared to low fat diet on reversing the metabolic syndrome, using NCEP ATP III criteria: a randomized clinical trial. BMC Nutr. 2021;7(1):62. doi:10.1186/s40795-021-00466-8
  2. Dorans, K.S. et al. (2022) ‘Effects of a Low-Carbohydrate Dietary Intervention on Hemoglobin A 1c: A Randomized Clinical Trial’, JAMA Network Open, 5(10), p. e2238645. Available at: https://doi.org/10.1001/jamanetworkopen.2022.38645.
  3. Stentz FB, Brewer A, Wan J, et al. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial. BMJ Open Diabetes Res Care. 2016;4(1). doi:10.1136/bmjdrc-2016-000258
  4. Gardner, C.D. et al. (2022) ‘Effect of a Ketogenic Diet versus Mediterranean Diet on HbA1c in Individuals with Prediabetes and Type 2 Diabetes Mellitus: the Interventional Keto-Med Randomized Crossover Trial’, The American Journal of Clinical Nutrition, p. nqac154. doi:10.1093/ajcn/nqac154.
  5. McKenzie AL, Athinarayanan SJ, McCue JJ, et al. Type 2 Diabetes Prevention Focused on Normalization of Glycemia: A Two-Year Pilot Study. Nutrients. 2021;13(3):749. doi:10.3390/nu13030749
  6. Cummings, P.J. et al. (2022) ‘Lifestyle Therapy Targeting Hyperinsulinemia Normalizes Hyperglycemia and Surrogate Markers of Insulin Resistance in a Large, Free-Living Population’, AJPM Focus, 1(2). Available at: https://doi.org/10.1016/j.focus.2022.100034.
  7. McKenzie A, Athinarayanan S, Adams R, Hallberg S, Volek J, Phinney SD. Predictors of Normalization of Fasting Glucose in Patients With Prediabetes Using Remote Continuous Care Emphasizing Low Carbohydrate Intake. J Endocr Soc. 2021;5(Suppl 1):A323. doi:10.1210/jendso/bvab048.659
  8. Unwin DJ, Tobin SD, Murray SW, Delon C, Brady AJ. Substantial and Sustained Improvements in Blood Pressure, Weight and Lipid Profiles from a Carbohydrate Restricted Diet: An Observational Study of Insulin Resistant Patients in Primary Care. International Journal of Environmental Research and Public Health. 2019;16(15):2680. doi:10.3390/ijerph16152680  
  9. Hyde PN, Sapper TN, Crabtree CD, et al. Dietary carbohydrate restriction improves metabolic syndrome independent of weight loss. JCI Insight. 2019;4(12). doi:10.1172/jci.insight.128308  
  10.  Lustig RH, Mulligan K, Noworolski SM, et al. Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Obesity (Silver Spring). 2016;24(2):453-460. doi:10.1002/oby.21371
  11. Maekawa S, Kawahara T, Nomura R, et al. Retrospective study on the efficacy of a low-carbohydrate diet for impaired glucose tolerance. Diabetes Metab Syndr Obes. 2014;7:195-201. doi:10.2147/DMSO.S62681
  12. Pérez-Guisado J, Muñoz-Serrano A. A Pilot Study of the Spanish Ketogenic Mediterranean Diet: An Effective Therapy for the Metabolic Syndrome. Journal of Medicinal Food. 2011;14(7-8):681-687. doi:10.1089/jmf.2010.0137    PDF
  13. Griauzde DH, Saslow L, Patterson K, et al. Mixed methods pilot study of a low-carbohydrate diabetes prevention programme among adults with pre-diabetes in the USA. BMJ Open. 2020;10(1). doi:10.1136/bmjopen-2019-033397 
  14. Gershuni VM, Yan SL, Medici V. Nutritional Ketosis for Weight Management and Reversal of Metabolic Syndrome. Curr Nutr Rep. 2018;7(3):97-106. doi:10.1007/s13668-018-0235-0 
  15. Samaha FF, Iqbal N, Seshadri P, et al. A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity. N Engl J Med. 2003;348(21):2074-2081. doi:10.1056/NEJMoa022637
  16. Yost O, DeJonckheere M, Stonebraker S, et al. Continuous Glucose Monitoring With Low-Carbohydrate Diet Coaching in Adults With Prediabetes: Mixed Methods Pilot Study. JMIR Diabetes. 2020;5(4):e21551. doi:10.2196/21551
  17. Nakagata T, Tamura Y, Kaga H, et al. Ingestion of an Exogenous Ketone Monoester Improves the Glycemic Response during Oral Glucose Tolerance Test in Subjects with Impaired Glucose Tolerance: A Crossover Randomized Trial. Journal of Diabetes Investigation. n/a(n/a). doi:10.1111/jdi.13423 
  18. Cucuzzella MT, Tondt J, Dockter NE, Saslow L, Wood TR. A low-carbohydrate survey: Evidence for sustainable metabolic syndrome reversal. Journal of Insulin Resistance. 2017;2(1):25. doi:10.4102/jir.v2i1.30
  19. Bharmal SH, Cho J, C Alarcon Ramos G, Ko J, Cameron-Smith D, Petrov MS. Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial. The Journal of Nutrition. 2021;151(4):921-929. doi:10.1093/jn/nxaa417 ABSTRACT

Type 2 Diabetes

Systematic Reviews, Meta-analyses, and other reviews

There have now been a number of reviews on this topic. A recent (07/2021) narrative review paper from Wheatley et al is an excellent overview of the literature, the remaining areas of controversy, and practical recommendations. A recent review of meta-analyses and clinical trials from Dyńka et al contains useful summary tables of trials. In addition, this paper from Brown et al focuses on options for remission (08/2021).

  1. Li S, Ding L, Xiao X. Comparing the Efficacy and Safety of Low-Carbohydrate Diets with Low-Fat Diets for Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. International Journal of Endocrinology. 2021;2021:e8521756. doi:10.1155/2021/8521756
  2. Yuan X, Wang J, Yang S, et al. Effect of the ketogenic diet on glycemic control, insulin resistance, and lipid metabolism in patients with T2DM: a systematic review and meta-analysis. Nutrition & Diabetes. 2020;10(1):1-8. doi:10.1038/s41387-020-00142-z
  3. Ghasemi, P. et al. (2024) ‘Impact of very low carbohydrate ketogenic diets on cardiovascular risk factors among patients with type 2 diabetes; GRADE-assessed systematic review and meta-analysis of clinical trials’, Nutrition & Metabolism, 21(1), p. 50. Available at: https://doi.org/10.1186/s12986-024-00824-w.
  4. Meng Y, Bai H, Wang S, Li Z, Wang Q, Chen L. Efficacy of low carbohydrate diet for type 2 diabetes mellitus management: A systematic review and meta-analysis of randomized controlled trials. Diabetes Research and Clinical Practice. 2017;131:124-131. doi:10.1016/j.diabres.2017.07.006 ABSTRACT

  5.  Lan, J. et al. (2024) ‘Efficacy of different dietary carbohydrate intake for glycaemic control and insulin resistance in type 2 diabetes: A systematic review and dose-response meta-analysis’, Asia Pacific Journal of Clinical Nutrition [Preprint]. Available at: https://doi.org/10.6133/apjcn.202412/PP.0003.

  6. Tian, W. et al. (2025) ‘The effects of low-carbohydrate diet on glucose and lipid metabolism in overweight or obese patients with T2DM: a meta-analysis of randomized controlled trials’, Frontiers in Nutrition, 11. Available at: https://doi.org/10.3389/fnut.2024.1516086.

  7. Alarim RA, Alasmre FA, Alotaibi HA, Alshehri MA, Hussain SA. Effects of the Ketogenic Diet on Glycemic Control in Diabetic Patients: Meta-Analysis of Clinical Trials. Cureus. 12(10). doi:10.7759/cureus.10796
  8. Turton J, Brinkworth GD, Field R, Parker H, Rooney K. An evidence‐based approach to developing low‐carbohydrate diets for type 2 diabetes management: a systematic review of interventions and methods. Diabetes, Obesity and Metabolism. doi:10.1111/dom.13837
  9. Snorgaard O, Poulsen GM, Andersen HK, Astrup A. Systematic review and meta-analysis of dietary carbohydrate restriction in patients with type 2 diabetes. BMJ Open Diabetes Res Care. 2017;5(1):e000354. doi:10.1136/bmjdrc-2016-000354
  10. Ajala O, English P, Pinkney J. Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr. 2013;97(3):505-516. doi:10.3945/ajcn.112.042457
  11. Goldenberg JZ, Day A, Brinkworth GD, et al. Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data. BMJ. 2021;372:m4743. doi:10.1136/bmj.m4743
  12. Churuangsuk, C. et al. (2021) ‘Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission’, Diabetologia. doi:10.1007/s00125-021-05577-2
  13. Apekey, T.A. et al. (2022) ‘Comparison of the Effectiveness of Low Carbohydrate Versus Low Fat Diets, in Type 2 Diabetes: Systematic Review and Meta-Analysis of Randomized Controlled Trials’, Nutrients, 14(20), p. 4391. Available at: https://doi.org/10.3390/nu14204391.
  14. Kelly T, Unwin D, Finucane F. Low-Carbohydrate Diets in the Management of Obesity and Type 2 Diabetes: A Review from Clinicians Using the Approach in Practice. International Journal of Environmental Research and Public Health. 2020;17(7):2557. doi:10.3390/ijerph17072557
  15. Hallberg SJ, Gershuni VM, Hazbun TL, Athinarayanan SJ. Reversing Type 2 Diabetes: A Narrative Review of the Evidence. Nutrients. 2019;11(4):766. doi:10.3390/nu11040766
  16. Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition. 2015;31(1):1-13. doi:10.1016/j.nut.2014.06.011
  17. Taylor R, Ramachandran A, Yancy WS, Forouhi NG. Nutritional basis of type 2 diabetes remission. BMJ. 2021;374:n1449. doi:10.1136/bmj.n1449

Trials/Studies

  1. Tay J, Thompson CH, Luscombe-Marsh ND, et al. Effects of an energy-restricted low-carbohydrate, high unsaturated fat/low saturated fat diet versus a high-carbohydrate, low-fat diet in type 2 diabetes: A 2-year randomized clinical trial. Diabetes Obes Metab. 2018;20(4):858-871. doi:10.1111/dom.13164
  2. Saslow LR, Daubenmier JJ, Moskowitz JT, et al. Twelve-month outcomes of a randomized trial of a moderate-carbohydrate versus very low-carbohydrate diet in overweight adults with type 2 diabetes mellitus or prediabetes. Nutr Diabetes. 2017;7(12):304. doi:10.1038/s41387-017-0006-9
  3. Goday A, Bellido D, Sajoux I, et al. Short-term safety, tolerability and efficacy of a very low-calorie-ketogenic diet interventional weight loss program versus hypocaloric diet in patients with type 2 diabetes mellitus. Nutr Diabetes. 2016;6(9):e230. doi:10.1038/nutd.2016.36
  4. Tay J, Luscombe-Marsh ND, Thompson CH, et al. Comparison of low- and high-carbohydrate diets for type 2 diabetes management: a randomized trial. Am J Clin Nutr. 2015;102(4):780-790. doi:10.3945/ajcn.115.112581
  5. Tay J, Luscombe-Marsh ND, Thompson CH, et al. A very low-carbohydrate, low-saturated fat diet for type 2 diabetes management: a randomized trial. Diabetes Care. 2014;37(11):2909-2918. doi:10.2337/dc14-0845
  6. Chen C-Y, Huang W-S, Chen H-C, et al. Effect of a 90 g/day low-carbohydrate diet on glycaemic control, small, dense low-density lipoprotein and carotid intima-media thickness in type 2 diabetic patients: An 18-month randomised controlled trial. PLOS ONE. 2020;15(10):e0240158. doi:10.1371/journal.pone.0240158
  7. Durrer C, McKelvey S, Singer J, et al. A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes. Nat Commun. 2021;12(1):5367. doi:10.1038/s41467-021-25667-4
  8. Thomsen MN, Skytte MJ, Astrup A, et al. The clinical effects of a carbohydrate-reduced high-protein diet on glycaemic variability in metformin-treated patients with type 2 diabetes mellitus: A randomised controlled study. Clinical Nutrition ESPEN. Published online August 1, 2020. doi:10.1016/j.clnesp.2020.07.002 ABSTRACT
  9. Han, Y. et al. (2021) ‘A Low-Carbohydrate Diet Realizes Medication Withdrawal: A Possible Opportunity for Effective Glycemic Control’, Frontiers in Endocrinology, 12. doi:10.3389/fendo.2021.779636.
  10. Yamada Y, Uchida J, Izumi H, et al. A Non-calorie-restricted Low-carbohydrate Diet is Effective as an Alternative Therapy for Patients with Type 2 Diabetes. Internal Medicine. 2014;53(1):13-19. doi:10.2169/internalmedicine.53.0861
  11. Athinarayanan SJ, Adams RN, Hallberg SJ, et al. Long-Term Effects of a Novel Continuous Remote Care Intervention Including Nutritional Ketosis for the Management of Type 2 Diabetes: A 2-Year Non-randomized Clinical Trial. Front Endocrinol. 2019;10. doi:10.3389/fendo.2019.00348 
  12. McKenzie A, Athinarayanan S, Adams R, Volek J, Phinney S, Hallberg S. SUN-LB113 A Continuous Remote Care Intervention Utilizing Carbohydrate Restriction Including Nutritional Ketosis Improves Markers of Metabolic Risk and Reduces Diabetes Medication Use in Patients With Type 2 Diabetes Over 3.5 Years. J Endocr Soc. 2020;4(Supplement_1). doi:10.1210/jendso/bvaa046.2302        (5 Year Data https://doi.org/10.2337/db22-832-P )
  13. Guldbrand H, Lindström T, Dizdar B, et al. Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus. Diabetes Res Clin Pract. 2014;106(2):221-227. doi:10.1016/j.diabres.2014.08.032
  14. Unwin, D. et al. (2020) ‘Insights from a general practice service evaluation supporting a lower carbohydrate diet in patients with type 2 diabetes mellitus and prediabetes: a secondary analysis of routine clinic data including HbA1c, weight and prescribing over 6 years’, BMJ Nutrition, Prevention & Health, 3(2), pp. 285–294. Available at: https://doi.org/10.1136/bmjnph-2020-000072.
  15. Unwin, D. et al. (2023) ‘What predicts drug-free type 2 diabetes remission? Insights from an 8-year general practice service evaluation of a lower carbohydrate diet with weight loss’, BMJ Nutrition, Prevention & Health, p. e000544. Available at: https://doi.org/10.1136/bmjnph-2022-000544.
  16. Nielsen JV, Joensson EA. Low-carbohydrate diet in type 2 diabetes: stable improvement of bodyweight and glycemic control during 44 months follow-up. Nutrition & Metabolism. 2008;5(1):14. doi:10.1186/1743-7075-5-14
  17. Moriconi E, Camajani E, Fabbri A, Lenzi A, Caprio M. Very-Low-Calorie Ketogenic Diet as a Safe and Valuable Tool for Long-Term Glycemic Management in Patients with Obesity and Type 2 Diabetes. Nutrients. 2021;13(3):758. doi:10.3390/nu13030758
  18. Romano L, Marchetti M, Gualtieri P, et al. Effects of a Personalized VLCKD on Body Composition and Resting Energy Expenditure in the Reversal of Diabetes to Prevent Complications. Nutrients. 2019;11(7):1526. doi:10.3390/nu11071526
  19. Taylor PJ, Thompson CH, Luscombe-Marsh ND, Wycherley TP, Wittert G, Brinkworth GD. Efficacy of Real-Time Continuous Glucose Monitoring to Improve Effects of a Prescriptive Lifestyle Intervention in Type 2 Diabetes: A Pilot Study. Diabetes Ther. 2019;10(2):509-522. doi:10.1007/s13300-019-0572-z
  20. Ahmed SR, Bellamkonda S, Zilbermint M, Wang J, Kalyani RR. Effects of the low carbohydrate, high fat diet on glycemic control and body weight in patients with type 2 diabetes: experience from a community-based cohort. BMJ Open Diabetes Res Care. 2020;8(1). doi:10.1136/bmjdrc-2019-000980
  21. Lu, N. et al. (2024) ‘Impact of a ketogenic diet on intestinal microbiota, cardiometabolic, and glycemic control parameters in patients with Type 2 diabetes mellitus.’, Investigación Clínica, 65(3), pp. 358–368. Available at: https://doi.org/10.54817/ic.v65n3a08.
  22. Glandt, M. et al. (2024) ‘Use of a very low carbohydrate diet for prediabetes and type 2 diabetes: An audit’, Journal of Metabolic Health. 2023rd-12th–21st edn. Available at: https://journalofmetabolichealth.org/index.php/jmh/article/view/87
  23. Laza-Cagigas R, Chan S, Sumner D, Rampal T. Effects and feasibility of a prehabilitation programme incorporating a low-carbohydrate, high-fat dietary approach in patients with type 2 diabetes: A retrospective study. Diabetes Metab Syndr. 2020;14(3):257-263. doi:10.1016/j.dsx.2020.03.010
  24. Soto-Mota A, Norwitz NG, Evans R, Clarke K, Barber TM. Exogenous ketosis in patients with type 2 diabetes: Safety, tolerability and effect on glycaemic control. Endocrinology, Diabetes & Metabolism. n/a(n/a):e00264. doi:https://doi.org/10.1002/edm2.264

Case Reports

  1. Cummings, P.J. et al. (2023) ‘Rapid remission of chronic, progressive conditions and reducing polypharmacy by utilizing lifestyle therapy to target insulinemic lifestyle components’, AJPM Focus, p. 100118. Available at: https://doi.org/10.1016/j.focus.2023.100118.
  2. Iwasaki K. Low carbohydrate diet rescued severe type 2 diabetes patient from insulin injection, a case report. Journal of Family Medicine and Primary Care. 2021;10(1):550. doi:10.4103/jfmpc.jfmpc_1798_20 
  3. Nie L, Zhai Q, Wei Y, Wang T, Li P. Ketogenic Diets Potentially Reverse Type 2 Diabetes Via Continuous Remote Care Intervention: A Case Study in Central China. Current Developments in Nutrition. 2021;5(Supplement_2):437-437. doi:10.1093/cdn/nzab038_049
  4. Jones EC, Jardet CL. Functional Improvement in -Islet Cells and Hepatocytes with Decreasing Deuterium from Low Carbohydrate Intake in a Type-II Diabetic. Medical Research Archives. 2021;9(6). doi:10.18103/mra.v9i6.2475
  5. Gavidia K, Kalayjian T. Treating Diabetes Utilizing a Low Carbohydrate Ketogenic Diet and Intermittent Fasting Without Significant Weight Loss: A Case Report. Front Nutr. 2021;8. doi:10.3389/fnut.2021.687081

Fasting and Type 2 Diabetes

  1. Wang X, Li Q, Liu Y, Jiang H, Chen W. Intermittent fasting versus continuous energy-restricted diet for patients with type 2 diabetes mellitus and metabolic syndrome for glycemic control: A systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. Published online August 12, 2021:109003. doi:10.1016/j.diabres.2021.109003 ABSTRACT
  2. Borgundvaag E, Mak J, Kramer CK. Metabolic impact of intermittent fasting in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of interventional studies. J Clin Endocrinol Metab. Published online December 15, 2020. doi:10.1210/clinem/dgaa926
  3. Obermayer, A. et al. (2022) ‘Efficacy and Safety of Intermittent Fasting in People With Insulin-Treated Type 2 Diabetes (INTERFAST-2)-A Randomized Controlled Trial’, Diabetes Care, p. dc221622. Available at: https://doi.org/10.2337/dc22-1622.
  4.  Albosta M, Bakke J. Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians. Clinical Diabetes and Endocrinology. 2021;7(1):3. doi:10.1186/s40842-020-00116-1
  5. Furmli S, Elmasry R, Ramos M, Fung J. Therapeutic use of intermittent fasting for people with type 2 diabetes as an alternative to insulin. Case Reports. 2018;2018:bcr-2017-221854. doi:10.1136/bcr-2017-221854  
  6. Li C, Sadraie B, Steckhan N, et al. Effects of A One-week Fasting Therapy in Patients with Type-2 Diabetes Mellitus and Metabolic Syndrome – A Randomized Controlled Explorative Study. Exp Clin Endocrinol Diabetes. 2017;125(9):618-624. doi:10.1055/s-0043-101700 ABSTRACT
  7. Gabel K, Kroeger CM, Trepanowski JF, et al. Differential Effects of Alternate-Day Fasting Versus Daily Calorie Restriction on Insulin Resistance. Obesity. 0(0). doi:10.1002/oby.22564
  8. DiNicolantonio JJ, McCarty M. Autophagy-induced degradation of Notch1, achieved through intermittent fasting, may promote beta cell neogenesis: implications for reversal of type 2 diabetes. Open Heart. 2019;6(1):e001028. doi:10.1136/openhrt-2019-001028
  9. Zubrzycki A, Cierpka-Kmiec K, Kmiec Z, Wronska A. The role of low-calorie diets and intermittent fasting in the treatment of obesity and type-2 diabetes. J Physiol Pharmacol. 2018;69(5). doi:10.26402/jpp.2018.5.02 

Type 1 Diabetes

Trials/Studies

 For information on the implementation of therapeutic carbohydrate reduction for type 1 diabetes see this comprehensive resource from the IPTN: McNally, B. et al. (2024) ‘THERAPEUTIC CARBOHYDRATE REDUCTION IN TYPE 1 DIABETES: A GUIDE FOR DIETITIANS & NUTRITIONISTS’.
 
  1. Kalayjian, T. et al. (2024) ‘The SMHPTM position statement on therapeutic carbohydrate reduction for type 1 diabetes’, Journal of Metabolic Health, 7(1), p. 9. Available at: https://doi.org/10.4102/jmh.v7i1.100.
  2. Paul, J. et al. (2024) ‘Low carbohydrate diets, glycaemic control, enablers, and barriers in the management of type 1 diabetes: a mixed methods systematic review’, Diabetology & Metabolic Syndrome, 16, p. 261. Available at: https://doi.org/10.1186/s13098-024-01496-5.
  3. Stamati, A. et al. (2023) ‘Efficacy and safety of carbohydrate restriction in patients with type 1 diabetes: A systematic review and meta-analysis’, Diabetes, Obesity & Metabolism, 25(9), pp. 2770–2773. Available at: https://doi.org/10.1111/dom.15124.
  4. Neuman, V. et al. (2024) ‘Low-carbohydrate diet in children and young people with type 1 diabetes: A randomized controlled trial with cross-over design’, Diabetes Research and Clinical Practice, 217, p. 111844. Available at: https://doi.org/10.1016/j.diabres.2024.111844.
  5. Levran, N. et al. (2024) ‘Low-carbohydrate diet proved effective and safe for youths with type 1 diabetes: A randomised trial’, Acta Paediatrica (Oslo, Norway: 1992) [Preprint]. Available at: https://doi.org/10.1111/apa.17455.
  6. Mahmood, B.S. (2023) ‘Impact of low carbohydrate diet on patients with type 1 Diabetes’, E3S Web of Conferences, 391, p. 01132. Available at: https://doi.org/10.1051/e3sconf/202339101132.
  7. Isaksson, S.S. et al. (2023) ‘The effect of carbohydrate intake on glycaemic control in individuals with type 1 diabetes: a randomised, open-label, crossover trial’, The Lancet Regional Health – Europe, 0(0). Available at: https://doi.org/10.1016/j.lanepe.2023.100799.
  8. Schmidt S, Christensen MB, Serifovski N, et al. Low versus High Carbohydrate Diet in Type 1 Diabetes: A 12-week randomized open-label crossover study. Diabetes Obes Metab. March 2019. doi:10.1111/dom.13725
  9. Turton, J.L. et al. (2023) ‘Effects of a low-carbohydrate diet in adults with type 1 diabetes management: A single arm non-randomised clinical trial’, PLOS ONE, 18(7), p. e0288440. Available at: https://doi.org/10.1371/journal.pone.0288440.
  10. Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: critical review and evidence base. Nutrition. 2015;31(1):1-13. doi:10.1016/j.nut.2014.06.011
  11. Kleiner, A. et al. (2022) ‘Safety and Efficacy of Eucaloric Very Low-Carb Diet (EVLCD) in Type 1 Diabetes: A One-Year Real-Life Retrospective Experience’, Nutrients, 14(15), p. 3208. Available at: https://doi.org/10.3390/nu14153208.
  12. Krebs, J.D. et al. (2016) ‘A randomised trial of the feasibility of a low carbohydrate diet vs standard carbohydrate counting in adults with type 1 diabetes taking body weight into account’, Asia Pacific Journal of Clinical Nutrition, 25(1), pp. 78–84. Available at: https://doi.org/10.6133/apjcn.2016.25.1.11. ABSTRACT
  13. Lehmann, V. et al. (2020) ‘Lower Daily Carbohydrate Intake Is Associated With Improved Glycemic Control in Adults With Type 1 Diabetes Using a Hybrid Closed-Loop System’, Diabetes Care [Preprint]. Available at: https://doi.org/10.2337/dc20-1560
  14. Nielsen, J.V. et al. (2012) ‘Low carbohydrate diet in type 1 diabetes, long-term improvement and adherence: A clinical audit’, Diabetology & Metabolic Syndrome, 4(1), p. 23. Available at: https://doi.org/10.1186/1758-5996-4-23.
  15. Dimosthenopoulos C, Liatis S, Kourpas E, et al. The beneficial short-term effects of a high-protein/low-carbohydrate diet on glycemic control assessed by continuous glucose monitoring in patients with type 1 diabetes. Diabetes Obes Metab. Published online March 26, 2021. doi:10.1111/dom.14390 ABSTRACT
  16. Paul, J. et al. (2022) ‘Association between a low carbohydrate diet, glycemic control, and quality of life in Australian adults living with type 1 diabetes: a pilot study’, Endocrine Practice: Official Journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, pp. S1530-891X(22)00578-X. Available at: https://doi.org/10.1016/j.eprac.2022.08.003.
  17. Nielsen JV, Jönsson E, Ivarsson A. A low carbohydrate diet in type 1 diabetes: clinical experience–a brief report. Ups J Med Sci. 2005;110(3):267-273. doi:10.3109/2000-1967-074
  18. Herschede AM. Grit Pregnancies: How to Have a Healthy Pregnancy and Normal Blood Sugars with Type 1 Diabetes. Allison Herschede; 2021. ISBN-10 : 1737084309
  19. Lake I. Nutritional ketosis is well-tolerated, even in type 1 diabetes: the ZeroFive100 Project; a proof-of-concept study. Current Opinion in Endocrinology, Diabetes and Obesity. 2021;28(5):453-462. doi:10.1097/MED.0000000000000666
  20. Berger B, Jenetzky E, Köblös D, et al. Seven-day fasting as a multimodal complex intervention for adults with type 1 diabetes: Feasibility, benefit and safety in a controlled pilot study. Nutrition. 2021;86:111169. doi:10.1016/j.nut.2021.111169    PDF
  21. Ozoran, H. et al. (2023) ‘Type 1 diabetes and low carbohydrate diets—Defining the degree of nutritional ketosis’, Diabetic Medicine, 40(10), p. e15178. Available at: https://doi.org/10.1111/dme.15178.
  22. Kristensen, K.B. et al. (2023) ‘Effects of a low-carbohydrate-high-protein pre-exercise meal in type 1 diabetes – a randomised, crossover trial’, The Journal of Clinical Endocrinology and Metabolism, p. dgad427. Available at: https://doi.org/10.1210/clinem/dgad427. ABSTRACT

Case Reports

  1. Watso, J.C. et al. (2024) ‘Advanced Cardiovascular Physiology in an Individual with Type 1 Diabetes After 10-Year Ketogenic Diet’, American Journal of Physiology-Cell Physiology [Preprint]. Available at: https://doi.org/10.1152/ajpcell.00694.2023.
  2. Koutnik, A.P. et al. (2024) ‘Efficacy and Safety of Long-term Ketogenic Diet Therapy in a Patient With Type 1 Diabetes’, JCEM Case Reports, 2(7), p. luae102. Available at: https://doi.org/10.1210/jcemcr/luae102.
  3. Winje, E., Lake, I. and Dankel, S.N. (2024) ‘Case report: Ketogenic diet alleviated anxiety and depression associated with insulin-dependent diabetes management’, Frontiers in Nutrition, 11. Available at: https://doi.org/10.3389/fnut.2024.1404842.
  4. Ozoran, H. et al. (2024) ‘Prolonged remission followed by low insulin requirements in a patient with type 1 diabetes on a very low-carbohydrate diet’, Endocrinology, Diabetes & Metabolism Case Reports, 2024(1). Available at: https://doi.org/10.1530/EDM-23-0130.
  5. Wood, M., Ebe, K. and Bando, H. (2023) ‘Prolonged Honeymoon Period in Type I Diabetes (T1D) Patients on Low-Carbohydrate Diet (LCD)’, Asploro Journal of Biomedical and Clinical Case Reports, 6(3), pp. 248–253. Available at: https://doi.org/10.36502/2023/ASJBCCR.6324.
  6. Smee, S. et al. (2023) ‘A very-low-carbohydrate diet for minimising blood glucose excursions during ultra-endurance open-water swimming in type 1 diabetes: a case report’, Applied Physiology, Nutrition, and Metabolism [Preprint]. Available at: https://doi.org/10.1139/apnm-2023-0266.
  7. Gardemann, C., Knowles, S. and Marquardt, T. (2023) ‘Managing type 1 diabetes mellitus with a ketogenic diet’, Endocrinology, Diabetes & Metabolism Case Reports, 2023(3). Available at: https://doi.org/10.1530/EDM-23-0008.
  8. Eiswirth M, Clark E, Diamond M. Low carbohydrate diet and improved glycaemic control in a patient with type one diabetes. Endocrinol Diabetes Metab Case Rep. 2018;2018. doi:10.1530/EDM-18-0002 
  9. Buehler LA, Noe D, Knapp S, Isaacs D, Pantalone KM. Ketogenic diets in the management of type 1 diabetes: Safe or safety concern? CCJM. 2021;88(10):547-555. doi:10.3949/ccjm.88a.20121 (review & case report)
  10. Thewjitcharoen Y, Wanothayaroj E, Jaita H, et al. Prolonged Honeymoon Period in a Thai Patient with Adult-Onset Type 1 Diabetes Mellitus. Case Reports in Endocrinology. 2021;2021:e3511281. doi:10.1155/2021/3511281
  11. Tóth C, Clemens Z. Type 1 diabetes mellitus successfully managed with the paleolithic ketogenic diet. International Journal of Case Reports and Images. 2014;5. doi:10.5348/ijcri-2014124-CR-10435 
  12. Schönlaub A, Höller A, Hofer S, Haberlandt E, Karall D, Scholl-Bürgi S. Glut1 Deficiency Syndrome and Diabetes Mellitus Type 1: Review of the Literature and Presentation of a New Case. In: Neuropediatrics. Vol 52. Georg Thieme Verlag KG; 2021:FV1.32. doi:10.1055/s-0041-1739666
  13. Oyibo, S.O. (2022) ‘Partial Remission of Diabetes in a Young Adult While Testing Positive for Several Islet Cell Autoantibodies: A Case Report, Literature Review, and Patient Perspective’, Cureus, 14(6). Available at: https://doi.org/10.7759/cureus.25746.
  14. Bouillet B, Rouland A, Petit JM, Vergès B. A low-carbohydrate high-fat diet initiated promptly after diagnosis provides clinical remission in three patients with type 1 diabetes. Diabetes Metab. July 2019. doi:10.1016/j.diabet.2019.06.004 NO ABSTRACT

Media Links

  1. Dr Carrie Diulus- You Tube – Low Carb (Vegan Keto) Diet Results for Type 1 Diabetes. 2018
  2. Andrew Koutnik – You Tube – Low Carbohydrate Diet for Type-1 Diabetes? Patient and Research Perspective. 2019
  3. Dr. Andrew Koutnik, PhD – Rethinking Nutrition for Type 1 Diabetes. 2020. 
  4. Dr Olivia Rimington – You tube – Low Carb Nutrition for T1DM. 2019

LADA (Latent Autoimmune Diabetes in Adults)

  1. Frazier AR. Correct Diabetes Diagnosis and Treatment Allows Sailor to Remain on Active Duty. Mil Med. 2020;185(9-10):e1843-e1846. doi:10.1093/milmed/usaa012

Cardiovascular Disease Risk Factors

Systematic Reviews and Meta-Analyses

 

  1. Ghasemi, P. et al. (2024) ‘Impact of very low carbohydrate ketogenic diets on cardiovascular risk factors among patients with type 2 diabetes; GRADE-assessed systematic review and meta-analysis of clinical trials’, Nutrition & Metabolism, 21(1), p. 50. Available at: https://doi.org/10.1186/s12986-024-00824-w.
  2. Luo, W. et al. (2022) ‘Low carbohydrate ketogenic diets reduce cardiovascular risk factor levels in obese or overweight patients with T2DM: A meta-analysis of randomized controlled trials’, Frontiers in Nutrition, 9, p. 1092031. Available at: https://doi.org/10.3389/fnut.2022.1092031.
  3. Gjuladin-Hellon T, Davies IG, Penson P, Amiri Baghbadorani R. Effects of carbohydrate-restricted diets on low-density lipoprotein cholesterol levels in overweight and obese adults: a systematic review and meta-analysis. Nutr Rev. 2019;77(3):161-180. doi:10.1093/nutrit/nuy049
  4. Fechner E, Smeets ETHC, Schrauwen P, Mensink RP. The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans—A Systematic Review and Meta-Analysis. Nutrients. 2020;12(4):991. doi:10.3390/nu12040991
  5. Dong T, Guo M, Zhang P, Sun G, Chen B. The effects of low-carbohydrate diets on cardiovascular risk factors: A meta-analysis. PLoS ONE. 2020;15(1):e0225348. doi:10.1371/journal.pone.0225348
  6. Nordmann AJ, Nordmann A, Briel M, et al. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166(3):285-293. doi:10.1001/archinte.166.3.285
  7. Chawla S, Tessarolo Silva F, Amaral Medeiros S, Mekary RA, Radenkovic D. The Effect of Low-Fat and Low-Carbohydrate Diets on Weight Loss and Lipid Levels: A Systematic Review and Meta-Analysis. Nutrients. 2020;12(12):3774. doi:10.3390/nu12123774
  8. Zhu Y, Bo Y, Liu Y. Dietary total fat, fatty acids intake, and risk of cardiovascular disease: a dose-response meta-analysis of cohort studies. Lipids in Health and Disease. 2019;18(1):91. doi:10.1186/s12944-019-1035-2
  9. Harcombe Z, Baker JS, Cooper SM, et al. Evidence from randomised controlled trials did not support the introduction of dietary fat guidelines in 1977 and 1983: a systematic review and meta-analysis. Open Heart. 2015;2(1):e000196. doi:10.1136/openhrt-2014-000196 
  10. Santos FL, Esteves SS, da Costa Pereira A, Yancy WS, Nunes JPL. Systematic review and meta-analysis of clinical trials of the effects of low carbohydrate diets on cardiovascular risk factors. Obes Rev. 2012;13(11):1048-1066. doi:10.1111/j.1467-789X.2012.01021.x ABSTRACT 
  11. Yang Q, Lang X, Li W, Liang Y. The effects of low-fat, high-carbohydrate diets vs. low-carbohydrate, high-fat diets on weight, blood pressure, serum liquids and blood glucose: a systematic review and meta-analysis. Eur J Clin Nutr. Published online June 24, 2021. doi:10.1038/s41430-021-00927-0 ABSTRACT
  12. Ishak AI, Harikrishna AH, Chrysostomou SC, Karpettas NK. Should we really avoid fat in diet? The beneficial effects of low carbohydrate diet versus low fat diet on cardiovascular health: a systematic review and meta-analysis. European Heart Journal. 2021;42(Supplement_1). doi:10.1093/eurheartj/ehab724.2427

Other Reviews

  1. Dyńka, D. et al. (2023) ‘The Ketogenic Diet and Cardiovascular Diseases’, Nutrients, 15(15), p. 3368. Available at: https://doi.org/10.3390/nu15153368.
  2. Ravnskov U, de Lorgeril M, Diamond DM, et al. LDL-C does not cause cardiovascular disease: a comprehensive review of the current literature. Expert Rev Clin Pharmacol. 2018;11(10):959-970. doi:10.1080/17512433.2018.1519391
  3. Malhotra A, DiNicolantonio JJ, Capewell S. It is time to stop counting calories, and time instead to promote dietary changes that substantially and rapidly reduce cardiovascular morbidity and mortality. Open Heart. 2015;2(1). doi:10.1136/openhrt-2015-000273
  4. Ting, K.K.Y. (2024) ‘John Yudkin’s hypothesis: sugar is a major dietary culprit in the development of cardiovascular disease’, Frontiers in Nutrition, 11, p. 1407108. Available at: https://doi.org/10.3389/fnut.2024.1407108.
  5. Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Review of current evidence and clinical recommendations on the effects of low-carbohydrate and very-low-carbohydrate (including ketogenic) diets for the management of body weight and other cardiometabolic risk factors: A scientific statement from the National Lipid Association Nutrition and Lifestyle Task Force. Journal of Clinical Lipidology. September 2019. doi:10.1016/j.jacl.2019.08.003
  6. Zhang, W. et al. (2021) ‘Ketogenic Diets and Cardio-Metabolic Diseases’, Frontiers in Endocrinology, 12. doi:10.3389/fendo.2021.753039
  7. Butler T, Kerley CP, Altieri N, et al. Optimum nutritional strategies for cardiovascular disease prevention and rehabilitation (BACPR). Heart. Published online February 25, 2020. doi:10.1136/heartjnl-2019-315499 
  8. Diamond, D.M., Leaverton, P.E., Diamond, D.M. and Leaverton, P.E. (2023) ‘Historical Review of the Use of Relative Risk Statistics in the Portrayal of the Purported Hazards of High LDL Cholesterol and the Benefits of Lipid-Lowering Therapy’, Cureus, 15(5). Available at: https://doi.org/10.7759/cureus.38391
  9. Diamond DM, Alabdulgader AA, Lorgeril M de, et al. Dietary Recommendations for Familial Hypercholesterolaemia: an Evidence-Free Zone. BMJ Evidence-Based Medicine. Published online July 5, 2020. doi:10.1136/bmjebm-2020-111412
  10. Astrup A, Magkos F, Bier DM, et al. Saturated Fats and Health: A Reassessment and Proposal for Food-based Recommendations: JACC State-of -the-Art Review. Journal of the American College of Cardiology. Published online June 17, 2020. doi:10.1016/j.jacc.2020.05.077
  11. Nasser S, Vialichka V, Biesiekierska M, Balcerczyk A, Pirola L. Effects of ketogenic diet and ketone bodies on the cardiovascular system: Concentration matters. World Journal of Diabetes. 2020;11(12):584-595. doi:10.4239/wjd.v11.i12.584
  12. Aronica L, Volek J, Poff A, D’agostino DP. Genetic variants for personalised management of very low carbohydrate ketogenic diets. BMJNPH. Published online December 12, 2020:bmjnph-2020-000167. doi:10.1136/bmjnph-2020-000167
  13. Murray SW, McKelvey S, Heseltine TD, et al. The “discordant doppelganger dilemma”: SGLT2i mimics therapeutic carbohydrate restriction – food choice first over pharma? Journal of Human Hypertension. Published online February 9, 2021:1-8. doi:10.1038/s41371-021-00482-y

Trials/Studies

  1. Saslow, L.R. et al. (2023) ‘Comparing Very Low-Carbohydrate vs DASH Diets for Overweight or Obese Adults With Hypertension and Prediabetes or Type 2 Diabetes: A Randomized Trial’, The Annals of Family Medicine, 21(3), pp. 256–263. Available at: https://doi.org/10.1370/afm.2968.
  2. Mason AE, Saslow LR, Moran PJ, et al. Lipid findings from the Diabetes Education to Lower Insulin, Sugars, and Hunger (DELISH) Study. Nutr Metab (Lond). 2019;16(1):58. doi:10.1186/s12986-019-0383-2
  3. Harvey CJDC, Schofield GM, Zinn C, Thornley SJ, Crofts C, Merien FLR. Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: A randomised clinical trial. PeerJ. 2019;7:e6273. doi:10.7717/peerj.6273
  4. Petrisko M, Kloss R, Bradley P, et al. Biochemical, Anthropometric, and Physiological Responses to Carbohydrate-Restricted Diets Versus a Low-Fat Diet in Obese Adults: A Randomized Crossover Trial. J Med Food. Published online March 2, 2020. doi:10.1089/jmf.2019.0266
  5. Bhanpuri NH, Hallberg SJ, Williams PT, et al. Cardiovascular disease risk factor responses to a type 2 diabetes care model including nutritional ketosis induced by sustained carbohydrate restriction at 1 year: an open label, non-randomized, controlled study. Cardiovasc Diabetol. 2018;17(1):56. doi:10.1186/s12933-018-0698-8
  6. Athinarayanan SJ, Hallberg SJ, McKenzie AL, et al. Impact of a 2-year trial of nutritional ketosis on indices of cardiovascular disease risk in patients with type 2 diabetes. Cardiovascular Diabetology. 2020;19(1):208. doi:10.1186/s12933-020-01178-2        (5 Year Data   https://doi.org/10.2337/db22-212-OR )
  7. Yancy WS, Olsen MK, Guyton JR, Bakst RP, Westman EC. A Low-Carbohydrate, Ketogenic Diet versus a Low-Fat Diet To Treat Obesity and Hyperlipidemia: A Randomized, Controlled Trial. Annals of Internal Medicine. 2004;140(10):769. doi:10.7326/0003-4819-140-10-200405180-00006 
  8. Ebbeling CB, Knapp A, Johnson A, et al. Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia—a randomized controlled feeding trial. The American Journal of Clinical Nutrition. 2021;(nqab287). doi:10.1093/ajcn/nqab287 
  9. Sánchez, E. et al. (2022) ‘Randomized Clinical Trial to Evaluate the Morphological Changes in the Adventitial Vasa Vasorum Density and Biological Markers of Endothelial Dysfunction in Subjects with Moderate Obesity Undergoing a Very Low-Calorie Ketogenic Diet’, Nutrients, 14(1), p. 33. doi:10.3390/nu14010033.
  10. Vergara M, Hauser ME, Aronica L, et al. Associations of Changes in Blood Lipid Concentrations with Changes in Dietary Cholesterol Intake in the Context of a Healthy Low-Carbohydrate Weight Loss Diet: A Secondary Analysis of the DIETFITS Trial. Nutrients. 2021;13(6):1935. doi:10.3390/nu13061935
  11. Alzahrani AH, Skytte MJ, Samkani A, et al. Effects of a Self-Prepared Carbohydrate-Reduced High-Protein Diet on Cardiovascular Disease Risk Markers in Patients with Type 2 Diabetes. Nutrients. 2021;13(5):1694. doi:10.3390/nu13051694
  12. Gram-Kampmann, E.M. et al. (2022) ‘Effects of a six-month low-carbohydrate diet on glycemic control, body composition and cardiovascular risk factors in patients with type 2 diabetes: an open-label RCT’, Diabetes, Obesity & Metabolism [Preprint]. doi:10.1111/dom.14633.
  13. Volek JS, Sharman MJ. Cardiovascular and Hormonal Aspects of Very-Low-Carbohydrate Ketogenic Diets. Obesity Research. 2004;12(S11):115S-123S. doi:10.1038/oby.2004.276
  14. Forsythe CE, Phinney SD, Feinman RD, et al. Limited effect of dietary saturated fat on plasma saturated fat in the context of a low carbohydrate diet. Lipids. 2010;45(10):947-962. doi:10.1007/s11745-010-3467-3
  15. Dashti HM, Mathew TC, Hussein T, et al. Long-term effects of a ketogenic diet in obese patients. Exp Clin Cardiol. 2004;9(3):200-205. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/ 
  16. Ballard KD, Quann EE, Kupchak BR, et al. Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins. Nutr Res. 2013;33(11):905-912. doi:10.1016/j.nutres.2013.07.022 ABSTRACT
  17. Creighton BC, Hyde PN, Maresh CM, Kraemer WJ, Phinney SD, Volek JS. Paradox of hypercholesterolaemia in highly trained, keto-adapted athletes. BMJ Open Sport Exerc Med. 2018;4(1):e000429. doi:10.1136/bmjsem-2018-000429 
  18. Wood RJ, Volek JS, Davis SR, Dell’Ova C, Fernandez ML. Effects of a carbohydrate-restricted diet on emerging plasma markers for cardiovascular disease. Nutr Metab (Lond). 2006;3:19. doi:10.1186/1743-7075-3-19
  19. Pergola* GD, Zupo R, Lampignano L, et al. Effects of a Low Carb Diet and Whey Proteins on Anthropometric, Hematochemical, and Cardiovascular Parameters in Subjects with Obesity. Endocrine, Metabolic & Immune Disorders – Drug Targets. Published November 30, 2020. doi: 10.2174/1871530320666200610143724
  20. Waldman HS, Smith JW, Lamberth J, et al. A 28-Day Carbohydrate-Restricted Diet Improves Markers of Cardiovascular Disease in Professional Firefighters. The Journal of Strength & Conditioning Research. 2019;Publish Ahead of Print. doi:10.1519/JSC.0000000000003749
  21. Sharman MJ, Kraemer WJ, Love DM, et al. A Ketogenic Diet Favorably Affects Serum Biomarkers for Cardiovascular Disease in Normal-Weight Men. J Nutr. 2002;132(7):1879-1885. doi:10.1093/jn/132.7.1879
  22. Neudorf, H. et al. (2021) ‘A Low-Carbohydrate, High-Fat Ketogenic Diet Program Implemented by an Interdisciplinary Primary Care Team Improves Markers of Cardiometabolic Health in Adults With Type 2 Diabetes: A Retrospective Secondary Analysis’, Canadian Journal of Diabetes [Preprint]. doi:10.1016/j.jcjd.2021.09.001.
  23. Falkenhain K, Locke SR, Lowe DA, et al. Keyto App and Device versus WW App on Weight Loss and Metabolic Risk in Adults with Overweight or Obesity: A Randomized Trial. Obesity. n/a(n/a). doi:10.1002/oby.23242    PDF 

Lean Mass Hyper-Responder Phenotype and associated studies

  1. Norwitz, N.G. et al. (2022) ‘The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate-Restricted Diets’, Metabolites, 12(5), p. 460. doi:10.3390/metabo12050460. (LTEs – Mindrum; Moore et al., and Reply)
  2. Norwitz NG, Feldman D, Soto-Mota A, Kalayjian T, Ludwig DS. Elevated LDL-Cholesterol with a Carbohydrate-Restricted Diet: Evidence for a ‘Lean Mass Hyper-Responder’ Phenotype. Curr Dev Nutr. doi:10.1093/cdn/nzab144    
  3. Soto-Mota, A. et al. (2024b) ‘Increased LDL-cholesterol on a low-carbohydrate diet in adults with normal but not high body weight: a meta-analysis’, The American Journal of Clinical Nutrition [Preprint]. Available at: https://doi.org/10.1016/j.ajcnut.2024.01.009.
  4. Budoff, M. et al. (2024) ‘Carbohydrate Restriction-Induced Elevations in LDL-Cholesterol and Atherosclerosis’, JACC: Advances, 3(8), p. 101109. Available at: https://doi.org/10.1016/j.jacadv.2024.101109.
  5. Cooper, I.D. et al. (2023) ‘Thyroid markers and body composition predict LDL-cholesterol change in lean healthy women on a ketogenic diet: experimental support for the lipid energy model’, Frontiers in Endocrinology, 14. Available at: https://www.frontiersin.org/articles/10.3389/fendo.2023.1326768 .
  6. Diamond, D.M., Mason, P. and Bikman, B.T. (2024) ‘Opinion: Are mental health benefits of the ketogenic diet accompanied by an increased risk of cardiovascular disease?’, Frontiers in Nutrition, 11. Available at: https://doi.org/10.3389/fnut.2024.1394610.
  7. Norwitz, N.G. et al. (2022) ‘Case Report: Hypercholesterolemia “Lean Mass Hyper-Responder” Phenotype Presents in the Context of a Low Saturated Fat Carbohydrate-Restricted Diet’, Frontiers in Endocrinology, 13, p. 830325. doi:10.3389/fendo.2022.830325.
  8. Feldman, D., Huggins, S. and Norwitz, N.G. (2022) ‘Short-term hyper-caloric high-fat feeding on a ketogenic diet can lower low-density lipoprotein cholesterol: the cholesterol drop experiment’, Current Opinion in Endocrinology, Diabetes and Obesity, p. 10.1097/MED.0000000000000762. Available at: https://doi.org/10.1097/MED.0000000000000762.
  9. Norwitz NG, Mindrum MR, Giral P, et al. Elevated LDL-cholesterol levels among lean mass hyper-responders on low-carbohydrate ketogenic diets deserve urgent clinical attention and further research. Journal of Clinical Lipidology. Published online November 2, 2022. doi:10.1016/j.jacl.2022.10.010. ABSTRACT
  10. Das S, McCreary J, Shamim S, Kalayjian T. Reversal of severe hypertriglyceridemia with intermittent fasting and a very-low-carbohydrate ketogenic diet: a case series. Curr Opin Endocrinol Diabetes Obes. Published online July 27, 2020. doi:10.1097/MED.0000000000000566
  11. Norwitz NG, Loh V. A Standard Lipid Panel Is Insufficient for the Care of a Patient on a High-Fat, Low-Carbohydrate Ketogenic Diet. Front Med. 2020;7. doi:10.3389/fmed.2020.00097
  12. Surma, S. et al. (2023) ‘Low carbohydrate/ketogenic diet in the optimization of lipoprotein(a) levels: do we have sufficient evidence for any recommendation?’, European Heart Journal, p. ehad635. Available at: https://doi.org/10.1093/eurheartj/ehad635.
  13. Scholl JG. Does a ketogenic diet lower a very high Lp(a)? A striking experiment in a male physician. BMJ Nutrition, Prevention & Health. Published online November 20, 2020:bmjnph-2020-000189. doi:10.1136/bmjnph-2020-000189
  14. Diamond, D.M., Bikman, B.T., Mason, P., n.d. Statin therapy is not warranted for a person with high LDL-cholesterol on a low-carbohydrate diet. Current Opinion in Endocrinology, Diabetes and Obesity 10.1097/MED.0000000000000764. https://doi.org/10.1097/MED.0000000000000764
  15. Kendrick, M. (2022) ‘Assessing cardiovascular disease: looking beyond cholesterol’, Current Opinion in Endocrinology, Diabetes and Obesity, p. 10.1097/MED.0000000000000761. Available at: https://doi.org/10.1097/MED.0000000000000761.

Women

  1. Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003;88(4):1617-1623. doi:10.1210/jc.2002-021480
  2. Barrea, L. et al. (2023) ‘Very low-calorie ketogenic diet (VLCKD): an antihypertensive nutritional approach’, Journal of Translational Medicine, 21(1), p. 128. Available at: https://doi.org/10.1186/s12967-023-03956-4.
  3. Klonek, G. et al. (2024) ‘Effects of a 12 Week Ketogenic Diet Intervention on Obese and Overweight Females with Glucose and Lipid Metabolism Disturbance’, Nutrients, 16(23), p. 4218. Available at: https://doi.org/10.3390/nu16234218.
  4. Wekesa AL, Doyle LM, Fitzmaurice D, et al. Influence of a low-carbohydrate diet on endothelial microvesicles in overweight women. 2016. https://core.ac.uk/reader/74028323. 
  5. Volek JS, Sharman MJ, Gómez AL, Scheett TP, Kraemer WJ. An isoenergetic very low carbohydrate diet improves serum HDL cholesterol and triacylglycerol concentrations, the total cholesterol to HDL cholesterol ratio and postprandial pipemic responses compared with a low fat diet in normal weight, normolipidemic women. J Nutr. 2003;133(9):2756-2761. doi:10.1093/jn/133.9.2756 
  6. Hwang C-L, Ranieri C, Szczurek MR, et al. The Effect of Low-Carbohydrate Diet on Macrovascular and Microvascular Endothelial Function is Not Affected by the Provision of Caloric Restriction in Women with Obesity: A Randomized Study. Nutrients. 2020;12(6). doi:10.3390/nu12061649
  7. Hanners, A. et al. (2022) ‘Ketogenic diet, African American women, and cardiovascular health: A systematic review’, Worldviews on Evidence-Based Nursing [Preprint]. doi:10.1111/wvn.12561.
  8. Sun S, Kong Z, Shi Q, Zhang H, Lei O-K, Nie J. Carbohydrate Restriction with or without Exercise Training Improves Blood Pressure and Insulin Sensitivity in Overweight Women. Healthcare. 2021;9(6):637. doi:10.3390/healthcare9060637
  9. Halton TL, Willett WC, Liu S, et al. Low-Carbohydrate-Diet Score and the Risk of Coronary Heart Disease in Women. New England Journal of Medicine. 2006;355(19):1991-2002. doi:10.1056/NEJMoa055317  
  10. Mozaffarian D, Rimm EB, Herrington DM. Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr. 2004;80(5):1175-1184. doi:10.1093/ajcn/80.5.1175
  11. Jeppesen J, Schaaf P, Jones C, Zhou MY, Chen YD, Reaven GM. Effects of low-fat, high-carbohydrate diets on risk factors for ischemic heart disease in postmenopausal women. Am J Clin Nutr. 1997;65(4):1027-1033. doi:10.1093/ajcn/65.4.1027
  12. Shah S, MacDonald C-J, El Fatouhi D, et al. The associations of the Palaeolithic diet alone and in combination with lifestyle factors with type 2 diabetes and hypertension risks in women in the E3N prospective cohort. Eur J Nutr. Published online April 28, 2021. doi:10.1007/s00394-021-02565-5
  13. Noakes TD. 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. Open Heart. 2021;8(2):e001680. doi:10.1136/openhrt-2021-001680
  14. Yılmaz SK, Eskici G, Mertoǧlu C, Ayaz A. Effect of different protein diets on weight loss, inflammatory markers, and cardiometabolic risk factors in obese women. J Res Med Sci. 2021;26:28. doi:10.4103/jrms.JRMS_611_20 
  15. Ma Y, Sun Y, Sun L, et al. Effects of gut microbiota and fatty acid metabolism on dyslipidemia following weight-loss diets in women: Results from a randomized controlled trial. Clin Nutr. 2021;40(11):5511-5520. doi:10.1016/j.clnu.2021.09.021
  16. Tavakoli A, Mirzababaei A, Mirzaei K. Association between low carbohydrate diet (LCD) and sleep quality by mediating role of inflammatory factors in women with overweight and obesity: A cross-sectional study. Food Science & Nutrition. n/a(n/a). doi:10.1002/fsn3.2584
  17. Silveira, E.A. et al. (2021) ‘Which Diets Are Effective in Reducing Cardiovascular and Cancer Risk in Women with Obesity? An Integrative Review’, Nutrients, 13(10). doi:10.3390/nu13103504.
 

Hypertension

Systematic Reviews, Meta-Analyses and other reviews

  1. Evans CE, Greenwood DC, Threapleton DE, Gale CP, Cleghorn CL, Burley VJ. Glycemic index, glycemic load, and blood pressure: a systematic review and meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition. 2017;105(5):1176-1190. doi:10.3945/ajcn.116.143685
  2. Yu Z, Nan F, Wang LY, Jiang H, Chen W, Jiang Y. Effects of high-protein diet on glycemic control, insulin resistance and blood pressure in type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials. Clinical Nutrition. Published online August 15, 2019. doi:10.1016/j.clnu.2019.08.008 
  3. Rebholz CM, Friedman EE, Powers LJ, Arroyave WD, He J, Kelly TN. Dietary Protein Intake and Blood Pressure: A Meta-Analysis of Randomized Controlled Trials. American Journal of Epidemiology. 2012;176(suppl_7):S27-S43. doi:10.1093/aje/kws245
  4. Mente A, O’Donnell M, Yusuf S. Sodium Intake and Health: What Should We Recommend Based on the Current Evidence? Nutrients. 2021;13(9):3232. doi:10.3390/nu13093232

Trials/Studies

  1. Yancy WS, Westman EC, McDuffie JR, et al. A Randomized Trial of a Low-Carbohydrate Diet vs Orlistat Plus a Low-Fat Diet for Weight Loss. Arch Intern Med. 2010;170(2):136. doi:10.1001/archinternmed.2009.492 

  2. Chiu S, Bergeron N, Williams PT, Bray GA, Sutherland B, Krauss RM. Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet and a higher-fat DASH diet on blood pressure and lipids and lipoproteins: a randomized controlled trial1–3. The American Journal of Clinical Nutrition. 2016;103(2):341-347. doi:10.3945/ajcn.115.123281Unwin DJ, T

  3. Unwin DJ, Tobin SD, Murray SW, Delon C, Brady AJ. Substantial and Sustained Improvements in Blood Pressure, Weight and Lipid Profiles from a Carbohydrate Restricted Diet: An Observational Study of Insulin Resistant Patients in Primary Care. International Journal of Environmental Research and Public Health. 2019;16(15):2680. doi:10.3390/ijerph16152680

  4. Pérez-Guisado J, Muñoz-Serrano A. A Pilot Study of the Spanish Ketogenic Mediterranean Diet: An Effective Therapy for the Metabolic Syndrome. Journal of Medicinal Food. 2011;14(7-8):681-687. doi:10.1089/jmf.2010.0137
  5. Walker L, Smith N, Delon C. Weight loss, hypertension and mental well-being improvements during COVID-19 with a multicomponent health promotion programme on Zoom: a service evaluation in primary care. BMJ Nutrition, Prevention & Health. Published online February 13, 2021:bmjnph. doi:10.1136/bmjnph-2020-000219   PDF
  6. Barrea, L. et al. (2023) ‘Very low-calorie ketogenic diet (VLCKD): an antihypertensive nutritional approach’, Journal of Translational Medicine, 21(1), p. 128. Available at: https://doi.org/10.1186/s12967-023-03956-4.
  7. Sun S, Kong Z, Shi Q, Zhang H, Lei O-K, Nie J. Carbohydrate Restriction with or without Exercise Training Improves Blood Pressure and Insulin Sensitivity in Overweight Women. Healthcare. 2021;9(6):637. doi:10.3390/healthcare9060637
  8. Shah S, MacDonald C-J, El Fatouhi D, et al. The associations of the Palaeolithic diet alone and in combination with lifestyle factors with type 2 diabetes and hypertension risks in women in the E3N prospective cohort. Eur J Nutr. Published online April 28, 2021. doi:10.1007/s00394-021-02565-5
  9. Kim D, Roberts C, McKenzie A, George MP. Nutritional ketosis to treat pulmonary hypertension associated with obesity and metabolic syndrome: a case report. Pulm Circ. 2021;11(1):2045894021991426. doi:10.1177/2045894021991426 
  10. Ballard KD, Quann EE, Kupchak BR, et al. Dietary carbohydrate restriction improves insulin sensitivity, blood pressure, microvascular function, and cellular adhesion markers in individuals taking statins. Nutr Res. 2013;33(11):905-912. doi:10.1016/j.nutres.2013.07.022 ABSTRACT

Association Studies

  1. Peng W, Xie Y, Cao H, et al. Association study of fasting blood glucose and salt sensitivity of blood pressure in community population: the EpiSS study. Nutrition, Metabolism and Cardiovascular Diseases. 2021;0(0). doi:10.1016/j.numecd.2021.04.026    PDF
  2. He D, Sun N, Xiong S, Qiao Y, Ke C, Shen Y. Association between the proportions of carbohydrate and fat intake and hypertension risk: findings from the China Health and Nutrition Survey. Journal of Hypertension. 2021;Publish Ahead of Print. doi:10.1097/HJH.0000000000002803 ABSTRACT

Fasting

  1. Maifeld A, Bartolomaeus H, Löber U, et al. Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients. Nature Communications. 2021;12(1):1970. doi:10.1038/s41467-021-22097-0 
  2. Grundler F, Mesnage R, Michalsen A, Wilhelmi de Toledo F. Blood Pressure Changes in 1610 Subjects With and Without Antihypertensive Medication During Long‐Term Fasting. J Am Heart Assoc. 2020;9(23). doi:10.1161/JAHA.120.018649
  3. Luke K, Ferona NA, Putri HLAS, et al. THE EFFECT OF RAMADAN FASTING TO BLOOD PRESSURE IN HYPERTENSIVE PATIENTS: A META-ANALYSIS. Journal of Community Medicine and Public Health Research. 2021;2(2):53-59. doi:10.20473/jcmphr.v2i2.26821     PDF
  4. Touyz Rhian M. Gut Dysbiosis–Induced Hypertension Is Ameliorated by Intermittent Fasting. Circulation Research. 2021;128(9):1255-1257. doi:10.1161/CIRCRESAHA.121.319147 ABSTRACT – a commentary on the following pre-clinical study

Mechanisms

  1. Barrea, L. et al. (2023) ‘Effects of very low-calorie ketogenic diet on hypothalamic–pituitary–adrenal axis and renin–angiotensin–aldosterone system’, Journal of Endocrinological Investigation, 46(8), pp. 1509–1520. Available at: https://doi.org/10.1007/s40618-023-02068-6.
  2. da Silva AA, do Carmo JM, Li X, Wang Z, Mouton AJ, Hall JE. Role of Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic Syndrome Revisited. Can J Cardiol. 2020;36(5):671-682. doi:10.1016/j.cjca.2020.02.066 
  3. Yanai H, Tomono Y, Ito K, Furutani N, Yoshida H, Tada N. The underlying mechanisms for development of hypertension in the metabolic syndrome. Nutrition Journal. 2008;7(1):10. doi:10.1186/1475-2891-7-10
  4. Preuss HG, Kaats GR, Mrvichin N, Bagchi D. Analyzing Blood Pressure Ascent during Aging in Non-Diabetics: Focusing on Links to Insulin Resistance and Body Fat Mass. Journal of the American College of Nutrition. 2021;40(4):317-326. doi:10.1080/07315724.2021.1875339
  5. Senarathne, R. et al. (2021) ‘Metabolic syndrome in hypertensive and non-hypertensive subjects’, Health Science Reports, 4(4), p. e454. doi:10.1002/hsr2.454.

Heart Function

For more on heart function e.g., heart failure, cardiomyopathy, glycogen storage diseases, and the role of ketones in heart function, see the section under ‘metabolic component‘.

Liver Function/NAFLD

Reviews

  1. Watanabe M, Tozzi R, Risi R, et al. Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature. Obesity Reviews. n/a(n/a). doi:10.1111/obr.13024
  2. Worm N. Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD. Nutrients. 2020;12(5):1316. doi:10.3390/nu12051316
  3. Schugar RC, Crawford PA. Low-carbohydrate ketogenic diets, glucose homeostasis, and nonalcoholic fatty liver disease. Curr Opin Clin Nutr Metab Care. 2012;15(4):374-380. doi:10.1097/MCO.0b013e3283547157    PDF
  4. Gunaseelan L, Khan US, Khalid F, Hamid MA. Non-alcoholic Fatty Liver Disease and Carbohydrate Restricted Diets: A Case Report and Literature Review. Cureus. 2021;13(10). doi:10.7759/cureus.18641
  5. Parra-Vargas M, Rodriguez-Echevarria R, Jimenez-Chillaron JC. Nutritional Approaches for the Management of Nonalcoholic Fatty Liver Disease: An Evidence-Based Review. Nutrients. 2020;12(12):3860. doi:10.3390/nu12123860
  6. Pugliese N, Torres MCP, Petta S, Valenti L, Giannini EG, Aghemo A. Is there an “ideal” diet for patients with NAFLD? European Journal of Clinical Investigation. n/a(n/a):e13659. doi:10.1111/eci.13659
  7. Rosa SC da S, Nayak N, Caymo AM, Gordon JW. Mechanisms of muscle insulin resistance and the cross-talk with liver and adipose tissue. Physiological Reports. 2020;8(19):e14607. doi:10.14814/phy2.14607
  8. Chakravarthy MV, Neuschwander‐Tetri BA. The metabolic basis of nonalcoholic steatohepatitis. Endocrinol Diabetes Metab. 2020;3(4). doi:10.1002/edm2.112
  9. Różański, G. et al. (2022) ‘Effect of Different Types of Intermittent Fasting on Biochemical and Anthropometric Parameters among Patients with Metabolic-Associated Fatty Liver Disease (MAFLD)—A Systematic Review’, Nutrients, 14(1), p. 91. doi:10.3390/nu14010091.

Trials/Studies

  1. Holmer M, Lindqvist C, Petersson S, et al. Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet – a randomized controlled trial. JHEP Reports. Published online February 17, 2021:100256. doi:10.1016/j.jhepr.2021.100256
  2. Gepner Y, Shelef I, Komy O, et al. The Beneficial effects of Mediterranean diet over low-fat diet may be mediated by decreasing hepatic fat content. J Hepatol. May 2019. doi:10.1016/j.jhep.2019.04.013

  3. Chirapongsathorn, S. et al. (2025) ‘Effect of a Ketogenic Diet on Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) Progression: A Randomized Controlled Trial’, JGH Open: An Open Access Journal of Gastroenterology and Hepatology, 9(1), p. e70099. Available at: https://doi.org/10.1002/jgh3.70099.

  4. Vilar-Gomez E, Athinarayanan SJ, Adams RN, et al. Post hoc analyses of surrogate markers of non-alcoholic fatty liver disease (NAFLD) and liver fibrosis in patients with type 2 diabetes in a digitally supported continuous care intervention: an open-label, non-randomised controlled study. BMJ Open. 2019;9(2):e023597. doi:10.1136/bmjopen-2018-023597      (5 year data https://doi.org/10.2337/db22-212-OR. )
  5. Skytte MJ, Samkani A, Petersen AD, et al. A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial. Diabetologia. July 2019. doi:10.1007/s00125-019-4956-4 
  6. London, A. et al. (2024) ‘The Impact of Short-term Eucaloric Low-Carbohydrate and High-Carbohydrate Diet on Liver Triacylglycerol Content in Males with Overweight and Obesity; a Randomized Cross-Over Study’, The American Journal of Clinical Nutrition [Preprint]. Available at: https://doi.org/10.1016/j.ajcnut.2024.06.006. 
  7. Sila, A. et al. (2024) ‘Higher-Level Steatosis Is Associated with a Greater Decrease in Metabolic Dysfunction-Associated Steatoic Liver Disease after Eight Weeks of a Very Low-Calorie Ketogenic Diet (VLCKD) in Subjects Affected by Overweight and Obesity’, Nutrients, 16(6), p. 874. Available at: https://doi.org/10.3390/nu16060874.
  8. Kord-Varkaneh, H. et al. (2022) ‘Effects of time-restricted feeding (16/8) combined with a low-sugar diet on the management of non-alcoholic fatty liver disease: A randomized controlled trial’, Nutrition (Burbank, Los Angeles County, Calif.), 105, p. 111847. Available at: https://doi.org/10.1016/j.nut.2022.111847
  9. Rinaldi, R. et al. (2023) ‘The Effects of Eight Weeks’ Very Low-Calorie Ketogenic Diet (VLCKD) on Liver Health in Subjects Affected by Overweight and Obesity’, Nutrients, 15(4), p. 825. Available at: https://doi.org/10.3390/nu15040825.
  10.  Balestra, F. et al. (2024) ‘Extracellular Vesicles Modulate Liver Cells Viability and Reactive Oxygen Species in Patients Following a Very Low-Calorie Ketogenic Diet’, Nutrients, 16(15), p. 2386. Available at: https://doi.org/10.3390/nu16152386.
  11. Kwon, S., Jeyaratnam, R. and Kim, K.-H. (2024) ‘Targeting ketone body metabolism to treat fatty liver disease’, Journal of Pharmacy & Pharmaceutical Sciences, 27, p. 13375. Available at: https://doi.org/10.3389/jpps.2024.13375.
  12. Luukkonen PK, Dufour S, Lyu K, et al. Effect of a ketogenic diet on hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. Proc Natl Acad Sci U S A. 2020;117(13):7347-7354. doi:10.1073/pnas.1922344117
     
  13. De Nucci, S. et al. (2023) ‘Effects of an Eight Week Very Low-Calorie Ketogenic Diet (VLCKD) on White Blood Cell and Platelet Counts in Relation to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Subjects with Overweight and Obesity’, Nutrients, 15(20), p. 4468. Available at: https://doi.org/10.3390/nu15204468.
  14. Unwin D, Cuthbertson D, Feinman R, Sprung V. A pilot study to explore the role of a low-carbohydrate intervention to improve GGT levels and HbA 1 c. Diabesity in Practice Vol 4 No 3 2015.   PDF
  15. Mardinoglu A, Wu H, Bjornson E, et al. An Integrated Understanding of the Rapid Metabolic Benefits of a Carbohydrate-Restricted Diet on Hepatic Steatosis in Humans. Cell Metab. 2018;27(3):559-571.e5. doi:10.1016/j.cmet.2018.01.005 
  16. Khorunzha V, Samiilenko N, Bielokoz H, et al. Effects of a Low Carbohydrate Diet on Patients With Metabolic Syndrome Complicated by Non-alcoholic Fatty Liver Disease (NAFLD). Current Developments in Nutrition. 2021;5(Supplement_2):1221-1221. doi:10.1093/cdn/nzab055_031
  17. Thomsen, M.N. et al. (2022) ‘Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial’, Diabetologia [Preprint]. doi:10.1007/s00125-021-05628-8.
 

Women

  1. Chen J, Huang Y, Xie H, et al. Impact of a low-carbohydrate and high-fiber diet on nonalcoholic fatty liver disease. Asia Pacific Journal of Clinical Nutrition. 2020;29(3):483-490. doi:10.6133/apjcn.202009_29(3).0006
  2. D’Abbondanza M, Ministrini S, Pucci G, et al. Very Low-Carbohydrate Ketogenic Diet for the Treatment of Severe Obesity and Associated Non-Alcoholic Fatty Liver Disease: The Role of Sex Differences. Nutrients. 2020;12(9):2748. doi:10.3390/nu12092748

The Role of Sugar Sweetened Beverages (SSBs)

  1. Wijarnpreecha K, Thongprayoon C, Edmonds PJ, Cheungpasitporn W. Associations of sugar- and artificially sweetened soda with nonalcoholic fatty liver disease: a systematic review and meta-analysis. QJM: An International Journal of Medicine. 2016;109(7):461-466. doi:10.1093/qjmed/hcv172
  2. Chen H, Wang J, Li Z, et al. Consumption of Sugar-Sweetened Beverages Has a Dose-Dependent Effect on the Risk of Non-Alcoholic Fatty Liver Disease: An Updated Systematic Review and Dose-Response Meta-Analysis. Int J Environ Res Public Health. 2019;16(12). doi:10.3390/ijerph16122192
  3. Nier A, Brandt A, Conzelmann IB, Özel Y, Bergheim I. Non-Alcoholic Fatty Liver Disease in Overweight Children: Role of Fructose Intake and Dietary Pattern. Nutrients. 2018;10(9). doi:10.3390/nu10091329
  4. Ma J, Fox CS, Jacques PF, et al. Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts. J Hepatol. 2015;63(2):462-469. doi:10.1016/j.jhep.2015.03.032
  5. Abdelmalek MF, Day C. Sugar sweetened beverages and fatty liver disease: Rising concern and call to action. Journal of Hepatology. 2015;63(2):306-308. doi:10.1016/j.jhep.2015.05.021

Fasting and Liver Function

  1. Khalafi, M. et al. (2025) ‘Efficacy of intermittent fasting on improving liver function in individuals with metabolic disorders: a systematic review and meta-analysis’, Nutrition & Metabolism, 22(1), p. 1. Available at: https://doi.org/10.1186/s12986-024-00885-x.

  2. Wang, Y. et al. (2024) ‘Effect of 5:2 intermittent fasting diet versus daily calorie restriction eating on metabolic-associated fatty liver disease—a randomized controlled trial’, Frontiers in Nutrition, 11. Available at: https://doi.org/10.3389/fnut.2024.1439473.

  3. Drinda S, Grundler F, Neumann T, et al. Effects of Periodic Fasting on Fatty Liver Index—A Prospective Observational Study. Nutrients. 2019;11(11):2601. doi:10.3390/nu11112601

Kidney Function

Systematic Reviews, Meta-Analyses and other Reviews

  1. Oyabu C, Hashimoto Y, Fukuda T, et al. Impact of low-carbohydrate diet on renal function: a meta-analysis of over 1000 individuals from nine randomised controlled trials. Br J Nutr. 2016;116(4):632-638. doi:10.1017/S0007114516002178 

  2. Li, D., Dawson, J. and Gunton, J.E. (2025) ‘Therapeutic Potential of Ketogenic Interventions for Autosomal-Dominant Polycystic Kidney Disease: A Systematic Review’, Nutrients, 17(1), p. 145. Available at: https://doi.org/10.3390/nu17010145.

  3. Xiao, X. and Li, Z. (2025) ‘The Potential of Dietary Strategies: The Impact of Low-Carbohydrate Diet on Cardiovascular-Kidney-Metabolic Syndrome’. medRxiv, p. 2025.01.03.25319951. Available at: https://doi.org/10.1101/2025.01.03.25319951.  PDF

  4.  Pezzuoli, C., Biagini, G. and Magistroni, R. (2024) Ketogenic Interventions in Autosomal Dominant Polycystic Kidney Disease: A Comprehensive Review of Current Evidence. Available at: https://doi.org/10.20944/preprints202407.0919.v1. (preprint)

  5. Annunziata, G. et al. (2024) ‘Nutritional assessment and medical dietary therapy for management of obesity in patients with non-dialysis chronic kidney disease: a practical guide for endocrinologist, nutritionists and nephrologists. A consensus statement from [Italian groups]’, Journal of Endocrinological Investigation [Preprint]. Available at: https://doi.org/10.1007/s40618-024-02446-8.

  6. Suyoto PST. Effect of low-carbohydrate diet on markers of renal function in patients with type 2 diabetes: A meta-analysis. Diabetes Metab Res Rev. 2018;34(7):e3032. doi:10.1002/dmrr.3032 ABSTRACT
  7. Devries MC, Sithamparapillai A, Brimble KS, Banfield L, Morton RW, Phillips SM. Changes in Kidney Function Do Not Differ between Healthy Adults Consuming Higher- Compared with Lower- or Normal-Protein Diets: A Systematic Review and Meta-Analysis. The Journal of Nutrition. 2018;148(11):1760-1775. doi:10.1093/jn/nxy197
  8. Athinarayanan, S.J. et al. (2024) ‘The case for a ketogenic diet in the management of kidney disease’, BMJ Open Diabetes Research and Care, 12(2), p. e004101. Available at: https://doi.org/10.1136/bmjdrc-2024-004101
  9.  Messing, M. et al. (2024) ‘Trigger Warning: How Modern Diet, Lifestyle, and Environment Pull the Trigger on Autosomal Dominant Polycystic Kidney Disease Progression’, Nutrients, 16(19), p. 3281. Available at: https://doi.org/10.3390/nu16193281.
  10. Weimbs, T., Saville, J. and Kalantar-Zadeh, K. (2023) ‘Ketogenic metabolic therapy for chronic kidney disease – the pro part’, Clinical Kidney Journal, p. sfad273. Available at: https://doi.org/10.1093/ckj/sfad273. See Joshi et al. (2023) for: Risks of the ketogenic diet in CKD – the con part

Chronic Kidney Disease – Trials/Studies

  1. A, Golan R, Harman-Boehm I, et al. Renal function following three distinct weight loss dietary strategies during 2 years of a randomized controlled trial. Diabetes Care. 2013;36(8):2225-2232. doi:10.2337/dc12-1846 
  2. Zainordin NA, Warman NAE, Mohamad AF, et al. Safety and efficacy of very low carbohydrate diet in patients with diabetic kidney disease—A randomized controlled trial. PLOS ONE. 2021;16(10):e0258507. doi:10.1371/journal.pone.0258507
  3. Unwin D, Unwin J, Crocombe D, Delon C, Guess N, Wong C. Renal function in patients following a low carbohydrate diet for type 2 diabetes: a review of the literature and analysis of routine clinical data from a primary care service over 7 years. Current Opinion in Endocrinology, Diabetes and Obesity. Published online July 23, 2021. doi:10.1097/MED.0000000000000658
  4. ATHINARAYANAN, S.J. et al. (2023) ‘410-P: Two-Year (2y) eGFR Slope in People with Type 2 Diabetes (T2D) Receiving a Very Low Carbohydrate Diet (VLCD) Intervention’, Diabetes, 72(Supplement_1), pp. 410-P. Available at: https://doi.org/10.2337/db23-410-P.
  5. Bruci A, Tuccinardi D, Tozzi R, et al. Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients With Obesity and Mild Kidney Failure. Nutrients. 2020;12(2):333. doi:10.3390/nu12020333
  6. Mitchell NS, Batch BC, Tyson CC. Retrospective cohort study of changes in estimated glomerular filtration rate for patients prescribed a low carb diet. Curr Opin Endocrinol Diabetes Obes. Published online August 12, 2021. doi:10.1097/MED.0000000000000673
  7. Nielsen JV, Westerlund P, Bygren P. A low-carbohydrate diet may prevent end-stage renal failure in type 2 diabetes. A case report. Nutrition & Metabolism. 2006;3(1):23. doi:10.1186/1743-7075-3-23
  8. Friedman AN, Ogden LG, Foster GD, et al. Comparative effects of low-carbohydrate high-protein versus low-fat diets on the kidney. Clin J Am Soc Nephrol. 2012;7(7):1103-1111. doi:10.2215/CJN.11741111 
  9. Brinkworth GD, Buckley JD, Noakes M, Clifton PM. Renal Function Following Long-Term Weight Loss in Individuals with Abdominal Obesity on a Very-Low-Carbohydrate Diet vs High-Carbohydrate Diet. Journal of the American Dietetic Association. 2010;110(4):633-638. doi:10.1016/j.jada.2009.12.016 ABSTRACT 
  10. Tay J, Thompson CH, Luscombe-Marsh ND, et al. Long-Term Effects of a Very Low Carbohydrate Compared With a High Carbohydrate Diet on Renal Function in Individuals With Type 2 Diabetes: A Randomized Trial. Medicine (Baltimore). 2015;94(47):e2181. doi:10.1097/MD.0000000000002181 ABSTRACT
  11. Truche, A.-S. et al. (2022) ‘A Specific High-Protein Weight Loss Program Does Not Impair Renal Function in Patients Who Are Overweight/Obese’, Nutrients, 14(2), p. 384. doi:10.3390/nu14020384.
  12. ROBERTS, C.G.P. et al. (2022) ‘212-OR: Five-Year Follow-Up of Lipid, Inflammatory, Hepatic, and Renal Markers in People with T2 Diabetes on a Very-Low-Carbohydrate Intervention Including Nutritional Ketosis (VLCI) via Continuous Remote Care (CRC)’, Diabetes, 71(Supplement_1), pp. 212-OR. Available at: https://doi.org/10.2337/db22-212-OR.
  13. De Almeida, R.J.R. et al. (2023) ‘Effects of Ketogenic Diet Intervention on Metabolic Acidosis in Patients with Obesity and Chronic Kidney Disease’, Missouri Medicine, 120(6), pp. 451–458. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10743335/ .

  14. Trapanese, V. et al. (2024) ‘Impressive weight loss induced by a very low-calorie ketogenic diet in a morbidly complex obese patient with a recent episode of acute kidney injury and advanced chronic kidney disease: a case report’, Italian Journal of Medicine, 18(3). Available at: https://doi.org/10.4081/itjm.2024.1787.

Autosomal Dominant Polycystic Kidney Disease –Trials/Studies

  1. Cukoski, S. et al. (2023) ‘Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD—a randomized controlled trial’, Cell Reports Medicine, 0(0). Available at: https://doi.org/10.1016/j.xcrm.2023.101283.
  2. Cukoski, S. et al. (2024) ‘#2160 Ketosis moderates the effect on kidney volume in dietary interventions for ADPKD—more insights on the KETO ADPKD trial’, Nephrology Dialysis Transplantation, 39(Supplement_1), pp. gfae069-0738–2160. Available at: https://doi.org/10.1093/ndt/gfae069.738.
  3. Oehm, S. et al. (2022) ‘RESET-PKD: A pilot trial on short-term ketogenic interventions in autosomal dominant polycystic kidney disease’, Nephrology, Dialysis, Transplantation: Official Publication of the European Dialysis and Transplant Association – European Renal Association, p. gfac311. Available at: https://doi.org/10.1093/ndt/gfac311.

  4.  Muensterman, E.G. et al. (2024) ‘Real-Life Data from a Ketogenic Metabolic Therapy Program for Autosomal-Dominant Polycystic Kidney Disease Suggests Significant Benefits to Participants: TH-PO440’, Journal of the American Society of Nephrology, 35(10S), p. 10.1681/ASN.2024kqy7mws6. Available at: https://doi.org/10.1681/ASN.2024kqy7mws6.

  5. Knol, M.G.E. et al. (2023) ‘Higher beta-hydroxybutyrate ketone levels associated with a slower kidney function decline in ADPKD’, Nephrology Dialysis Transplantation, p. gfad239. Available at: https://doi.org/10.1093/ndt/gfad239.

  6. Torres, J.A. et al. (2024) ‘“β-Hydroxybutyrate Recapitulates the Beneficial Effects of Ketogenic Metabolic Therapy in Polycystic Kidney Disease”’, iScience, p. 110773. Available at: https://doi.org/10.1016/j.isci.2024.110773.

Media Links

  1. Diet Doctor Podcast with Dr Bret Scher, Dr Thomas Weimbs and registered dietitian and renal nutrition expert Jessianna Saville – #102 – Keto diets and kidney health (2022), Google Podcasts.
  2. Diet Doctor Podcast with Dr Bret Scher and Dr Keith Runyan – #103 – Keto, type 1 diabetes, and kidneys (2022). Google Podcasts.

Female Reproductive Health

General

  1. McGrice M, Porter J. The Effect of Low Carbohydrate Diets on Fertility Hormones and Outcomes in Overweight and Obese Women: A Systematic Review. Nutrients. 2017;9(3). doi:10.3390/nu9030204
  2. Camajani, E. et al. (2023) ‘Ketogenic Diet as a Possible Non-pharmacological Therapy in Main Endocrine Diseases of the Female Reproductive System: A Practical Guide for Nutritionists’, Current Obesity Reports [Preprint]. Available at: https://doi.org/10.1007/s13679-023-00516-1.
  3. Kackley, M.L. et al. (2024) ‘Self-reported menses physiology is positively modulated by a well-formulated, energy-controlled ketogenic diet vs. low fat diet in women of reproductive age with overweight/obesity’, PLOS ONE. Edited by L. Yanes Cardozo, 19(8), p. e0293670. Available at: https://doi.org/10.1371/journal.pone.0293670.
  4. Salcedo, A.C. et al. (2023) ‘Therapeutic Carbohydrate Restriction as a Metabolic Modality for the Prevention and Treatment of Abnormal Uterine Bleeding’, Nutrients, 15(17), p. 3760. Available at: https://doi.org/10.3390/nu15173760.

  5. Pasca, L. et al. (2023) ‘Ketonemia variability through menstrual cycle in patients undergoing classic ketogenic diet’, Frontiers in Nutrition, 10. Available at: https://www.frontiersin.org/articles/10.3389/fnut.2023.1188055.

  6. Maseroli, E. et al. (2023) ‘(055) Application of a Very Low Calorie Ketogenic Diet (VLCKD) Protocol in Women’s Endocrinology: Psychosexual Correlates of Weight Loss’, The Journal of Sexual Medicine, 20(Supplement_2), p. qdad061.051. Available at: https://doi.org/10.1093/jsxmed/qdad061.051.
  7. Hantoushzadeh, S. et al. (2023) ‘Glucose metabolism tests and recurrent pregnancy loss: evidence from a systematic review and meta-analysis’, Diabetology & Metabolic Syndrome, 15(1), p. 3. Available at: https://doi.org/10.1186/s13098-022-00973-z.
  8. Cai, W.-Y. et al. (2022) ‘Insulin resistance in women with recurrent miscarriage: a systematic review and meta-analysis’, BMC Pregnancy and Childbirth, 22(1), p. 916. Available at: https://doi.org/10.1186/s12884-022-05256-z.
  9. Alghamdi, A.A. and Alotaibi, A.S. (2023) ‘High Insulin Resistance in Saudi Women with Unexplained Recurrent Pregnancy Loss: A Case–control Study’, Saudi Journal of Medicine & Medical Sciences, 11(4), p. 314. Available at: https://doi.org/10.4103/sjmms.sjmms_82_23.
  10. Grieger JA, Grzeskowiak LE, Smithers LG, et al. Metabolic syndrome and time to pregnancy: a retrospective study of nulliparous women. BJOG: An International Journal of Obstetrics & Gynaecology. 2019;126(7):852-862. doi:10.1111/1471-0528.15647
  11. Hilali NG, Sak S, Incebiyik A, et al. Recurrent pregnancy loss and metabolic syndrome. Ginekologia Polska. 2020;91(6):320-323. doi:10.5603/GP.a2020.0063 PDF
  12. Shehata H, Berry A, Riba C, Salcedo AC. Insulin Resistance and Other Risk Factors of Cardiovascular Disease in Abnormal Uterine Bleeding. In Review; 2021. doi:10.21203/rs.3.rs-604656/v1 (concepts expanded and discussed by Dr Salcedo in this podcast – Protecting Your NEST with Dr. Tony Hampton – Dr. Andrea Salcedo & the Metabolic/Gynecologic Connection)
  13. Wang H, Zhang Y, Fang X, Kwak-Kim J, Wu L. Insulin Resistance Adversely Affect IVF Outcomes in Lean Women Without PCOS. Frontiers in Endocrinology. 2021;12. doi:10.3389/fendo.2021.734638
  14. Hooshiar, S.H., Yazdani, A. and Jafarnejad, S. (2024) ‘Does an alternate-day modified fasting diet improve premenstrual syndrome symptoms and health-related quality of life in obese or overweight women with premenstrual syndrome? A randomized, controlled trial’, Frontiers in Nutrition, 10. Available at: https://www.frontiersin.org/articles/10.3389/fnut.2023.1298831.

Polycystic Ovarian Syndrome (PCOS)

Systematic Reviews, Meta-analyses & Narrative Reviews

  1. Khalid, K. et al. (2023) ‘Effects of Ketogenic Diet on Reproductive Hormones in Women With Polycystic Ovary Syndrome’, Journal of the Endocrine Society, 7(10), p. bvad112. Available at: https://doi.org/10.1210/jendso/bvad112.
  2. Xing, N., Ren, F. and Yang, H. (2024) ‘Effects of ketogenic diet on weight loss parameters among obese or overweight patients with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trails’, Food & Nutrition Research [Preprint]. Available at: https://doi.org/10.29219/fnr.v68.9835.
  3. Zhang X, Zheng Y, Guo Y, Lai Z. The Effect of Low Carbohydrate Diet on Polycystic Ovary Syndrome: A Meta-Analysis of Randomized Controlled Trials. Int J Endocrinol. 2019;2019. doi:10.1155/2019/4386401 
  4. Shang Y, Zhou H, He R, Lu W. Dietary Modification for Reproductive Health in Women With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology. 2021;12:1408. doi:10.3389/fendo.2021.735954 
  5. Kackley, M.L. et al. (2024) ‘Self-reported menses physiology is positively modulated by a well-formulated, energy-controlled ketogenic diet vs. low fat diet in women of reproductive age with overweight/obesity’, PLOS ONE. Edited by L. Yanes Cardozo, 19(8), p. e0293670. Available at: https://doi.org/10.1371/journal.pone.0293670.
  6. Saadati, N. et al. (2021) ‘The effect of low glycemic index diet on the reproductive and clinical profile in women with polycystic ovarian syndrome: A systematic review and meta-analysis’, Heliyon, 7(11), p. e08338. doi:10.1016/j.heliyon.2021.e08338
  7. Porchia LM, Hernandez-Garcia SC, Gonzalez-Mejia ME, López-Bayghen E. Diets with lower carbohydrate concentrations improve insulin sensitivity in women with polycystic ovary syndrome: a meta-analysis. European Journal of Obstetrics & Gynecology and Reproductive Biology. Published online March 6, 2020. doi:10.1016/j.ejogrb.2020.03.010 ABSTRACT
  8. Ramírez-Martínez, L. et al. (2024) ‘The Potential for Ketogenic Diets to Control Glucotoxicity, Hyperinsulinemia, and Insulin Resistance to Improve Fertility in Women with Polycystic Ovary Syndrome’, Clinical and Experimental Obstetrics & Gynecology, 51(3), p. 57. Available at: https://doi.org/10.31083/j.ceog5103057.
  9. Pateguana NB, Janes A. The contribution of hyperinsulinemia to the hyperandrogenism of polycystic ovary syndrome. Journal of Insulin Resistance. 2019;4(1):3. doi:10.4102/jir.v4i1.50 

Trials/Studies

  1. Sharifi, M. et al. (2024) ‘The effects of portfolio moderate-carbohydrate and ketogenic diets on anthropometric indices, metabolic status, and hormonal levels in overweight or obese women with polycystic ovary syndrome: a randomized controlled trial’, Nutrition Journal, 23(1), p. 152. Available at: https://doi.org/10.1186/s12937-024-01056-7.
  2. Mei, S. et al. (2022) ‘Mediterranean Diet Combined With a Low-Carbohydrate Dietary Pattern in the Treatment of Overweight Polycystic Ovary Syndrome Patients’, Frontiers in Nutrition, 9, p. 876620. doi:10.3389/fnut.2022.876620.
  3. Pandurevic, S. et al. (2022) ‘Efficacy of very low calorie ketogenic diet in obese PCOS: a randomized controlled study’, in Endocrine Abstracts. ECE 2022, 24th European Congress of Endocrinology, Bioscientifica. doi:10.1530/endoabs.81.P193.
  4. Li J, Bai W-P, Jiang B, et al. Ketogenic diet in women with polycystic ovary syndrome and liver dysfunction who are obese: A randomized, open-label, parallel-group, controlled pilot trial. J Obstet Gynaecol Res. Published online January 18, 2021. doi:10.1111/jog.14650
  5. Palafox-Gómez, C. et al. (2023) ‘Adding a ketogenic dietary intervention to IVF treatment in patients with polycystic ovary syndrome improves implantation and pregnancy’, Reproductive Toxicology (Elmsford, N.Y.), 119, p. 108420. Available at: https://doi.org/10.1016/j.reprotox.2023.108420.
  6. Masood, I. et al. (2023) ‘Effect of ketogenic diet and hypocaloric Mediterranean diet on metabolic and endocrine parameter in women suffering from Polycystic Ovary Syndrome’, International Journal of Food Properties, 26(2), pp. 3187–3196. Available at: https://doi.org/10.1080/10942912.2023.2275528. 
  7. NAVEED, A. et al. (2024) ‘EFFECTS OF A KETOGENIC DIET IN OVERWEIGHT WOMEN WITH POLYCYSTIC OVARY SYNDROME’, Biological and Clinical Sciences Research Journal, 2024, p. 734. Available at: https://doi.org/10.54112/bcsrj.v2024i1.734.
  8. Paoli A, Mancin L, Giacona MC, Bianco A, Caprio M. Effects of a ketogenic diet in overweight women with polycystic ovary syndrome. Journal of Translational Medicine. 2020;18(1):104. doi:10.1186/s12967-020-02277-0
  9. Tsushima, Y. et al. (2024) ‘Ketogenic diet improves fertility in patients with polycystic ovary syndrome: a brief report’, Frontiers in Nutrition, 11, p. 1395977. Available at: https://doi.org/10.3389/fnut.2024.1395977.
  10. Pohlmeier AM, Phy JL, Watkins P, et al. Effect of a Low Starch/Low Dairy Diet on Fat Oxidation in Overweight and Obese Women with Polycystic Ovary Syndrome. Appl Physiol Nutr Metab. 2014;39(11):1237-1244. doi:10.1139/apnm-2014-0073
  11. Moran LJ, Noakes M, Clifton PM, Tomlinson L, Norman RJ. Dietary Composition in Restoring Reproductive and Metabolic Physiology in Overweight Women with Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2003;88(2):812-819. doi:10.1210/jc.2002-020815 
  12. Gower BA, Chandler-Laney PC, Ovalle F, et al. Favourable metabolic effects of a eucaloric lower-carbohydrate diet in women with PCOS. Clin Endocrinol (Oxf). 2013;79(4):550-557. doi:10.1111/cen.12175 
  13. Yang, M. et al. (2022) ‘Metabolic effects of a ketogenic diet in overweight/obese women with polycystic ovary syndrome with different uric acid levels: a prospective cohort study’, Reproductive BioMedicine Online [Preprint]. doi:10.1016/j.rbmo.2022.03.023.
  14. Mavropoulos JC, Yancy WS, Hepburn J, Westman EC. The effects of a low-carbohydrate, ketogenic diet on the polycystic ovary syndrome: a pilot study. Nutr Metab (Lond). 2005;2:35. doi:10.1186/1743-7075-2-35 
  15. Rossetti, R. et al. (2024) ‘A Ketogenic Diet Followed by Gradual Carbohydrate Reintroduction Restores Menstrual Cycles in Women with Polycystic Ovary Syndrome with Oligomenorrhea Independent of Body Weight Loss: Results from a Single-Center, One-Arm, Pilot Study’, Metabolites, 14(12), p. 691. Available at: https://doi.org/10.3390/metabo14120691.
  16.  

Pregnancy

  1. Moses RG, Luebcke M, Davis WS, et al. Effect of a low-glycemic-index diet during pregnancy on obstetric outcomes. Am J Clin Nutr. 2006;84(4):807-812. doi:10.1093/ajcn/84.4.807 
  2. Nina R W Geiker, Faidon Magkos, Helle Zingenberg, Jens Svare, Elizaveta Chabanova, Henrik S Thomsen, Christian Ritz, Arne Astrup (2021) ‘A high protein low glycemic index diet attenuates gestational weight gain in pregnant women with obesity: the APPROACH randomized controlled trial’. doi: 10.1093/ajcn/nqab405 
  3. Iii JFC. Maternal carbohydrate intake and pregnancy outcome. Proceedings of the Nutrition Society. 2002;61(1):45-50. doi:10.1079/PNS2001129 
  4. Herschede AM. Grit Pregnancies: How to Have a Healthy Pregnancy and Normal Blood Sugars with Type 1 Diabetes. Allison Herschede; 2021. ISBN-10 : 1737084309
  5. Lavie M, Lavie I, Maslovitz S. Paleolithic diet during pregnancy-A potential beneficial effect on metabolic indices and birth weight. Eur J Obstet Gynecol Reprod Biol. 2019;242:7-11. doi:10.1016/j.ejogrb.2019.08.013 ABSTRACT
  6. Yan W, Zhang Y, Wang L, et al. Maternal dietary glycaemic change during gestation influences insulin-related gene methylation in the placental tissue: a genome-wide methylation analysis. Genes Nutr. 2019;14. doi:10.1186/s12263-019-0634-x
  7. Zhao J, Hong X, Zhang H, et al. Pre-pregnancy maternal fasting plasma glucose levels in relation to time to pregnancy among the couples attempting first pregnancy. Hum Reprod. doi:10.1093/humrep/dez069
  8. Huang L, Shang L, Yang W, et al. High starchy food intake may increase the risk of adverse pregnancy outcomes: a nested case-control study in the Shaanxi province of Northwestern China. BMC Pregnancy and Childbirth. 2019;19(1):362. doi:10.1186/s12884-019-2524-z
  9. Casas R, Castro Barquero S, Estruch R. Impact of Sugary Food Consumption on Pregnancy: A Review. Nutrients. 2020;12(11):3574. doi:10.3390/nu12113574
  10. Ding M, He F, Li X, et al. Consistent Role of Insulin Resistance in Recurrent Pregnancy Loss and Recurrent Implantation Failure: A Case-control Study. Published online August 30, 2021. doi:10.21203/rs.3.rs-827067/v1
  11. Hilali NG, Sak S, Incebiyik A, et al. Recurrent pregnancy loss and metabolic syndrome. Ginekologia Polska. 2020;91(6):320-323. doi:10.5603/GP.a2020.0063 PDF
  12. Zhang X, Gong Y, Della Corte K, et al. Relevance of dietary glycemic index, glycemic load and fiber intake before and during pregnancy for the risk of gestational diabetes mellitus and maternal glucose homeostasis. Clinical Nutrition. Published online April 5, 2021. doi:10.1016/j.clnu.2021.03.041 
  13. Selen DJ, Edelson PK, James K, et al. Physiologic Subtypes of Gestational Glucose Intolerance and Risk of Adverse Pregnancy Outcomes. Am J Obstet Gynecol. Published online August 19, 2021:S0002-9378(21)00886-3. doi:10.1016/j.ajog.2021.08.01 ABSTRACT
  14. Aminianfar A, Soltani S, Hajianfar H, Azadbakht L, Shahshahan Z, Esmaillzadeh A. The association between dietary glycemic index and load and risk of gestational diabetes mellitus: a prospective study. Diabetes Research and Clinical Practice. 2020;0(0). doi:10.1016/j.diabres.2020.108469 ABSTRACT
  15. Chen Y, Qin Y, Zhang Z, et al. Association of the low-carbohydrate dietary pattern with postpartum weight retention in women. Food Funct. Published online October 5, 2021. doi:10.1039/d1fo00935d ABSTRACT
  16. Azizi R, Soltani-Zangbar MS, Sheikhansari G, et al. Metabolic syndrome mediates inflammatory and oxidative stress responses in patients with recurrent pregnancy loss. J Reprod Immunol. 2019;133:18-26. doi:10.1016/j.jri.2019.05.001 ABSTRACT
  17. Flanagan, E. Kebbe,M et al. (11.2021) ‘Assessment of Eating Behaviors and Perceptions of Time Restricted Eating During Pregnancy’. The Journal of Nutrition. doi: 10.1093/jn/nxab397
  18. Cortés-Albornoz MC, García-Guáqueta DP, Velez-van-Meerbeke A, Talero-Gutiérrez C. Maternal Nutrition and Neurodevelopment: A Scoping Review. Nutrients. 2021;13(10):3530. doi:10.3390/nu13103530
  19. North S, Crofts C, Thoma C, Zinn C. The role of maternal diet on offspring hyperinsulinaemia and adiposity after birth: a systematic review of randomised controlled trials. Journal of Developmental Origins of Health and Disease. Published online November 2, 2021:1-14. doi:10.1017/S2040174421000623
  20. Kramer J, Smith L. Ketogenic Diet in Glut 1 Deficiency Through the Life Cycle: Pregnancy to Neonate to Preschooler. Child Neurology Open. 2021;8:2329048X211034655. doi:10.1177/2329048X211034655
  21. Louw EJTM van der, Williams TJ, Henry-Barron BJ, et al. Ketogenic diet therapy for epilepsy during pregnancy: A case series. Seizure – European Journal of Epilepsy. 2017;45:198-201. doi:10.1016/j.seizure.2016.12.019

Lactation

Caution – there are several reports of lactation ketoacidosis occuring in the literature (see Possible Complications). For a prudent interpretation of the literature regarding breastfeeding, the link below to Dr. Andreas Eenfeldt – Diet Doctor, may be helpful – Breastfeeding on a low-carb diet – is it dangerous? Diet Doctor. 

  1. Dwyer, G.G., Akers, L.H. and Akers, J. (2023) ‘Experiences of Women Following a Low-Carbohydrate Diet While Breastfeeding’, Clinical Lactation, 14(2), pp. 72–84. Available at: https://doi.org/10.1891/CL-2022-0015.
  2. Alsharairi NA. The Role of Short-Chain Fatty Acids in Mediating Very Low-Calorie Ketogenic Diet-Infant Gut Microbiota Relationships and Its Therapeutic Potential in Obesity. Nutrients. 2021;13(11):3702. doi:10.3390/nu13113702
  3. Tan-Smith C, Little H, Fabe J, Dickson C, Shillito P. Increase of Human Milk Fat Inducing Nutritional Ketosis in Exclusively Breastfed Infant, Brought About by Treating the Mother With Ketogenic Dietary Therapy. J Hum Lact. Published online October 5, 2021:8903344211048422. doi:10.1177/08903344211048422 
  4. Kramer J, Smith L. Ketogenic Diet in Glut 1 Deficiency Through the Life Cycle: Pregnancy to Neonate to Preschooler. Child Neurology Open. 2021;8:2329048X211034655. doi:10.1177/2329048X211034655 

Media Links

  1. Dr. Tim O’Dowd – Reproduction Nutrition – YouTube
  2. Lily Nichols – Is Low Carb Safe During Pregnancy? – YouTube

Gestational Diabetes

  1. Viana LV, Gross JL, Azevedo MJ. Dietary Intervention in Patients With Gestational Diabetes Mellitus: A Systematic Review and Meta-analysis of Randomized Clinical Trials on Maternal and Newborn Outcomes. Diabetes Care. 2014;37(12):3345-3355. doi:10.2337/dc14-1530
  2. S, Hernandez TL. Low-Carbohydrate Diets for Gestational Diabetes. Nutrients. 2019;11(8):1737. doi:10.3390/nu11081737
  3. Trout, K.K., Compher, C.W., Dolin, C., Burns, C., Quinn, R., Durnwald, C., 2022. Increased Protein with Decreased Carbohydrate Intake Reduces Postprandial Blood Glucose Levels in Women with Gestational Diabetes: The iPRO Study. Women’s Health Reports 3, 728–739. doi.org/10.1089/whr.2022.0012
  4. Mulla WR. Carbohydrate Content in the GDM Diet: Two Views: View 2: Low-Carbohydrate Diets Should Remain the Initial Therapy for Gestational Diabetes. Diabetes Spectr. 2016;29(2):89-91. doi:10.2337/diaspect.29.2.89  
  5. Moreno-Castilla C, Hernandez M, Bergua M, et al. Low-Carbohydrate Diet for the Treatment of Gestational Diabetes Mellitus. Diabetes Care. 2013;36(8):2233-2238. doi:10.2337/dc12-2714
  6. Cypryk K, Kamińska P, Kosiński M, Lewiński MP-MA. A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes. Endokrynologia Polska. 2007;58(4):313-320. ISSN 2299-8306
  7. Cui, M. et al. (2022) ‘Effect of Carbohydrate-Restricted Dietary Pattern on Insulin Treatment Rate, Lipid Metabolism and Nutritional Status in Pregnant Women with Gestational Diabetes in Beijing, China’, Nutrients, 14(2), p. 359. doi:10.3390/nu14020359.
  8. Mierzyński R, Poniedziałek-Czajkowska E, Sotowski M, Szydełko-Gorzkowicz M. Nutrition as Prevention Factor of Gestational Diabetes Mellitus: A Narrative Review. Nutrients. 2021;13(11):3787. doi:10.3390/nu13113787
  9. Moses RG, Barker M, Winter M, Petocz P, Brand-Miller JC. Can a Low–Glycemic Index Diet Reduce the Need for Insulin in Gestational Diabetes Mellitus? Diabetes Care. 2009;32(6):996. doi:10.2337/dc09-0007 
  10. Filardi T, Panimolle F, Crescioli C, Lenzi A, Morano S. Gestational Diabetes Mellitus: The Impact of Carbohydrate Quality in Diet. Nutrients. 2019;11(7):1549. doi:10.3390/nu11071549
  11. Yu W, Wu N, Li L, OuYang H, Qian M, Shen H.A Review of Research Progress on Glycemic Variability and Gestational Diabetes. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. doi:10.2147/DMSO.S261486
  12. Ali AM, Kunugi H. Intermittent Fasting, Dietary Modifications, and Exercise for the Control of Gestational Diabetes and Maternal Mood Dysregulation: A Review and a Case Report. International Journal of Environmental Research and Public Health. 2020;17(24):9379. doi:10.3390/ijerph17249379
  13. Callahan ML, Schneider-Worthington CR, Martin SL, Gower BA, Catalano PM, Chandler-Laney P. Association of weight status and carbohydrate intake with gestational weight gain. Clin Obes. Published online April 9, 2021:e12455. doi:10.1111/cob.12455

Menopause

As oestrogen/progesterone are insulin sensitizing hormones, a reduction in these hormones can increase insulin resistance which may contribute to the metabolic dysregulation and symptoms of menopause. This section includes studies that support potential benefits of a TCR approach to help manage areas of common concern during menopause, primarily as a means of reducing glycaemic variability and insulin resistance.

Insulin resistance, weight gain and cardiovascular disease 

Therapeutic carbohydrate reduction is one way to combat insulin resistance, weight gain, and inflammation – risk factors for CVD. Insulin resistance also contributes to platelet dysfunction and clotting risk. 

  1. Mozaffarian D, Rimm EB, Herrington DM. Dietary fats, carbohydrate, and progression of coronary atherosclerosis in postmenopausal women. Am J Clin Nutr. 2004;80(5):1175-1184. doi:10.1093/ajcn/80.5.1175
  2. Grant, L. et al. (2024) ‘0019 Body Weight Reduction Following 8-weeks of Time-restricted Eating in Peri- and Postmenopausal Women with Obesity’, Sleep, 47(Supplement_1), p. A8. Available at: https://doi.org/10.1093/sleep/zsae067.0019.
  3. Blomquist C, Chorell E, Ryberg M, et al. Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet. Eur J Nutr. 2018;57(8):2877-2886. doi:10.1007/s00394-017-1558-0 
  4. McPhee JC, Zinn C, Smith M. Exploring the acceptability of, and adherence to a carbohydrate-restricted diet as self-reported by women aged 40-55 years. J Holistic Performance NutritionTM. doi: 10.26712/230120181  PDF 
  5. Segal-Isaacson C, Johnson S, Tomuta V, Cowell B, Stein DT. A Randomized Trial Comparing Low-Fat and Low-Carbohydrate Diets Matched for Energy and Protein. Obesity Research. 2004;12(S11):130S-140S. doi:10.1038/oby.2004.278 
  6. Nickols-Richardson, S.M. et al. (2005) ‘Perceived hunger is lower and weight loss is greater in overweight premenopausal women consuming a low-carbohydrate/high-protein vs high-carbohydrate/low-fat diet’, Journal of the American Dietetic Association, 105(9), pp. 1433–1437. doi:10.1016/j.jada.2005.06.025. 
  7. Simpson, S.J., Raubenheimer, D., Black, K.I., Conigrave, A.D., n.d. Weight gain during the menopause transition: Evidence for a mechanism dependent on protein leverage. BJOG: An International Journal of Obstetrics & Gynaecology n/a. doi.org/10.1111/1471-0528.17290

For more on this see CVD, obesity, and insulin resistance sections.

Glycaemic variability, insulin resistance and hot flashes 

In addition to reducing hyperinsulinaemia, a TCR approach reduces glycaemic variability – keeping blood sugars more stable and can successfully reduce abdominal adiposity. 

  1. Dormire SL. The Potential Role of Glucose Transport Changes in Hot Flash Physiology: A Hypothesis. Biol Res Nurs. 2009;10(3):241-247. doi:10.1177/1099800408324558
  2. Dormire S, Howharn C. The Effect of Dietary Intake on Hot Flashes in Menopausal Women. J Obstet Gynecol Neonatal Nurs. 2007;36(3):255-262. doi:10.1111/j.1552-6909.2007.00142.x
  3. Namgoung, S. et al. (2022) ‘Metabolically healthy and unhealthy obesity and risk of vasomotor symptoms in premenopausal women: cross-sectional and cohort studies’, BJOG: an international journal of obstetrics and gynaecology [Preprint]. doi:10.1111/1471-0528.17224.
  4. Huang W-Y, Chang C-C, Chen D-R, Kor C-T, Chen T-Y, Wu H-M. Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes. PLoS One. 2017;12(4). doi:10.1371/journal.pone.0176430
  5. Thurston RC, Sowers MR, Sutton-Tyrrell K, et al. Abdominal adiposity and hot flashes among midlife women. Menopause. 2008;15(3):429-434. doi:10.1097/gme.0b013e31815879cf

Sleep 

Sleep has a bidirectional effect on metabolic health.  Poor sleep patterns, such as shift work, can increase insulin resistance and increase the risk of developing metabolic syndrome. Increasing insulin resistance via other mechanisms, like changes in hormones, can reduce melatonin (inverse relationship) and affect sleep. 

  1. Kravitz HM, Kazlauskaite R, Joffe H. Sleep, Health, and Metabolism in Midlife Women and Menopause: Food for Thought. Obstet Gynecol Clin North Am. 2018;45(4):679-694. doi:10.1016/j.ogc.2018.07.008 
  2. Gangwisch JE, Hale L, St-Onge M-P, et al. High glycemic index and glycemic load diets as risk factors for insomnia: analyses from the Women’s Health Initiative. Am J Clin Nutr. 2020;111(2):429-439. doi:10.1093/ajcn/nqz275 
  3. Siegmann MJ, Athinarayanan SJ, Hallberg SJ, et al. Improvement in patient-reported sleep in type 2 diabetes and prediabetes participants receiving a continuous care intervention with nutritional ketosis. Sleep Medicine. 2019;55:92-99. doi:10.1016/j.sleep.2018.12.014
  4. Tavakoli A, Mirzababaei A, Mirzaei K. Association between low carbohydrate diet (LCD) and sleep quality by mediating role of inflammatory factors in women with overweight and obesity: A cross-sectional study. Food Science & Nutrition. n/a(n/a). doi:10.1002/fsn3.2584

For more on this, see section on sleep.

Brain glucose hypometabolism and cognitive decline

‘The peri-menopausal transition is a tipping point for female brain aging. From the metabolic perspective, the process begins with decline in glucose metabolism and increase in insulin resistance, followed by a compensatory mechanism to use fatty acids and ketone bodies as an auxiliary fuel source’ Wang et al

TCR reduces brain insulin resistance and inflammation. If carbohydrate intake is sufficiently reduced ketone bodies can provide an alternative fuel source for the brain, further supporting cognitive function. 

  1. Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov. 2020;19(9):609-633. doi:10.1038/s41573-020-0072-x 
  2. Yang H, Shan W, Zhu F, Wu J, Wang Q. Ketone Bodies in Neurological Diseases: Focus on Neuroprotection and Underlying Mechanisms. Front Neurol. 2019;10. doi:10.3389/fneur.2019.00585 
  3. Mishra, A. et al. (2021) ‘A Tale of Two Systems: Lessons Learned from Female Mid-Life Aging with Implications for Alzheimer’s Prevention & Treatment’, Ageing Research Reviews, p. 101542. doi:10.1016/j.arr.2021.101542.
  4. Phillips MCL, Deprez LM, Mortimer GMN, et al. Randomized crossover trial of a modified ketogenic diet in Alzheimer’s disease. Alzheimer’s Research & Therapy. 2021;13(1):51. doi:10.1186/s13195-021-00783-x
  5. Taylor MK, Sullivan DK, Mahnken JD, Burns JM, Swerdlow RH. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimers Dement (N Y). 2017;4:28-36. doi:10.1016/j.trci.2017.11.002 

For more on this, see section on Neurodegeneration.

Insulin resistance and mental health

This is an emerging area. See the section on Mental Health for the full collection.

  1. Jeremiah OJ, Cousins G, Boland F, Kirby BP, Ryan BK. Evaluation of the effect of insulin sensitivity-enhancing lifestyle- and dietary-related adjuncts on antidepressant treatment response: A systematic review and meta-analysis. Heliyon. 2020;6(9):e04845. doi:10.1016/j.heliyon.2020.e04845 
  2. Firth J, Gangwisch JE, Borisini A, Wootton RE, Mayer EA. Food and mood: how do diet and nutrition affect mental wellbeing? BMJ. 2020;369. doi:10.1136/bmj.m2382
  3. Setayesh L, Ebrahimi R, Pooyan S, Yarizadeh H, Rashidbeygi E, Badrooj N, et al. The possible mediatory role of adipokines in the association between low carbohydrate diet and depressive symptoms among overweight and obese women. PloS one. 2021;16(9). doi:10.1371/journal.pone.0257275

Insulin resistance and bone turnover  

Diet quality affects bone markers and metabolic syndrome is associated with reduced bone mineral density therefore addressing metabolic health through diet may have a valid role in protection from osteoporosis.

  1. Hu T, Yao L, Bazzano L. Effects of a 12-month Low-Carbohydrate Diet vs. a Low-Fat Diet on Bone Mineral Density: A Randomized Controlled Trial. The FASEB Journal. 2016;30(S1):678.12-678.12. doi:10.1096/fasebj.30.1_supplement.678.12
  2. Campillo-Sánchez F, Usategui-Martín R, Ruiz -de Temiño Á, et al. Relationship between Insulin Resistance (HOMA-IR), Trabecular Bone Score (TBS), and Three-Dimensional Dual-Energy X-ray Absorptiometry (3D-DXA) in Non-Diabetic Postmenopausal Women. Journal of Clinical Medicine. 2020;9(6):1732. doi:10.3390/jcm9061732 
  3. Sharma DK, Anderson PH, Morris HA, Clifton PM. Visceral Fat Is a Negative Determinant of Bone Health in Obese Postmenopausal Women. International Journal of Environmental Research and Public Health. 2020;17(11):3996. doi:10.3390/ijerph17113996 
  4. Cooper ID, Brookler KH, Crofts CAP. Rethinking Fragility Fractures in Type 2 Diabetes: The Link between Hyperinsulinaemia and Osteofragilitas. Biomedicines. 2021;9(9):1165. doi:10.3390/biomedicines9091165 
  5. Salas R, Tijerina A, Cardona M, et al. Association between Bone Mineral Density and Metabolic Syndrome among Reproductive, Menopausal Transition, and Postmenopausal Women. Journal of Clinical Medicine. 2021;10(21):4819. doi:10.3390/jcm1021481
  6. Hunt HB, Miller NA, Hemmerling KJ, et al. Bone tissue composition in post-menopausal women varies with glycemic control from normal glucose tolerance to type 2 diabetes mellitus. Journal of Bone and Mineral Research. 2020;n/a(n/a). doi:10.1002/jbmr.4186 ABSTRACT
  7. Crivelli M, Chain A, da Silva ITF, Waked AM, Bezerra FF. Association of Visceral and Subcutaneous Fat Mass With Bone Density and Vertebral Fractures in Women With Severe Obesity. Journal of Clinical Densitometry. Published online October 16, 2020. doi:10.1016/j.jocd.2020.10.005 ABSTRACT

For more on this, see section on bone health.

Breast Cancer and Insulin Resistance

Multiple factors contribute to increased risk of breast cancer – the presence of insulin resistance/metabolic syndrome is known to impact risk and prognosis. For more on this, see section on cancer.

  1. Dong S, Wang Z, Shen K, Chen X. Metabolic Syndrome and Breast Cancer: Prevalence, Treatment Response, and Prognosis. Front Oncol. 2021;11. doi:10.3389/fonc.2021.629666
  2. Kundaktepe BP, Durmus S, Cengiz M, et al. The Significance of Insulin Resistance in Nondiabetic Breast Cancer Patients. Journal of Endocrinology and Metabolism. 2021;11(2):42-48. doi:10.14740/jem.v11i2.729
  3. Maiello M, Cecere A, Ciccone MM, Palmiero P. Metabolic syndrome and breast cancer: a dangerous association for postmenopausal women. A postmenopausal women prevention study. Acta Bio Medica : Atenei Parmensis. 2021;92(4). doi:10.23750/abm.v92i4.11335 

Male Reproductive Health

Systematic Reviews, Meta-Analyses, and other reviews

  1. Maresch CC, Stute DC, Alves MG, Oliveira PF, de Kretser DM, Linn T. Diabetes-induced hyperglycemia impairs male reproductive function: a systematic review. Hum Reprod Update. 2018;24(1):86-105. doi:10.1093/humupd/dmx033
  2. Corona G, Rastrelli G, Monami M, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. European Journal of Endocrinology. 2013;168(6):829-843. doi:10.1530/EJE-12-0955 
  3. Furini, C., Spaggiari, G., Simoni, M., Greco, C., Santi, D., 2022. Ketogenic state improves testosterone serum levels—results from a systematic review and meta-analysis. Endocrine. https://doi.org/10.1007/s12020-022-03195-5
  4. Izzo, G. et al. (2023) ‘Male obesity secondary hypogonadism: effectiveness of ketogenic diet on testicular function’, Exploration of Foods and Foodomics, 1(4), pp. 178–191. Available at: https://doi.org/10.37349/eff.2023.00014.
  5. Katib, A. (2015) ‘Mechanisms linking obesity to male infertility’, Central European Journal of Urology, 68(1), pp. 79–85. doi:10.5173/ceju.2015.01.435 
  6. Russo, V., Chen, R. and Armamento-Villareal, R. (2021) ‘Hypogonadism, Type-2 Diabetes Mellitus, and Bone Health: A Narrative Review’, Frontiers in Endocrinology, 11. doi:10.3389/fendo.2020.607240
  7. Martins AD, Majzoub A, Agawal A. Metabolic Syndrome and Male Fertility. The World Journal of Men’s Health. 2019;37(2):113. doi:10.5534/wjmh.180055

Trials/Studies

  1. Moran LJ, Brinkworth GD, Martin S, et al. Long-Term Effects of a Randomised Controlled Trial Comparing High Protein or High Carbohydrate Weight Loss Diets on Testosterone, SHBG, Erectile and Urinary Function in Overweight and Obese Men. PLoS One. 2016;11(9). doi:10.1371/journal.pone.0161297
  2. Corsetti, V., Notari, T. and Montano, L. (2023) ‘Effects of the low-carb organic Mediterranean diet on testosterone levels and sperm DNA fragmentation’, Current Research in Food Science, 7, p. 100636. Available at: https://doi.org/10.1016/j.crfs.2023.100636.
  3. da Silva Schmitt, C., da Costa, C.M., Souto, J.C.S., Chiogna, L.M., de Albuquerque Santos, Z.E., Rhoden, E.L. and Neto, B.S. (2023) ‘The effects of a low carbohydrate diet on erectile function and serum testosterone levels in hypogonadal men with metabolic syndrome: a randomized clinical trial’, BMC Endocrine Disorders, 23(1), p. 30. Available at: https://doi.org/10.1186/s12902-023-01278-6.
  4. Cicolani, G. et al. (2024) ‘Poster: Impact of ketogenic diet on semen quality in obesepatients: Cytological and molecular aspects, a pilot study’, in. Available at: https://doi.org/10.1111/andr.13714. POSTER
  5. Cignarelli, A. et al. (2022) ‘Very low-calorie ketogenic diet rapidly augments testosterone levels in non-diabetic obese subjects’, Andrology [Preprint]. Available at: https://doi.org/10.1111/andr.13357.
  6. La Vignera S, Cannarella R, Galvano F, et al. The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study. Endocrine. Published online October 15, 2020. doi:10.1007/s12020-020-02518-8
  7. Mongioì LM, Cimino L, Condorelli RA, et al. Effectiveness of a Very Low Calorie Ketogenic Diet on Testicular Function in Overweight/Obese Men. Nutrients. 2020;12(10):2967. doi:10.3390/nu12102967
  8. Almsaid H, Muhsin H. The effect of Ketogenic diet on vitamin D3 and testosterone hormone in patients with diabetes mellitus type 2. Current Issues in Pharmacy and Medical Sciences. 2021;33:202-205. doi:10.2478/cipms-2020-0033 
  9. Cignarelli A, Conte E, Genchi VA, et al. Effects of a very low-calorie ketogenic diet on androgen levels in overweight/obese men: a single-arm uncontrolled study. In: Endocrine Abstracts. Vol 73. Bioscientifica; 2021. doi:10.1530/endoabs.73.PEP4.3 ABSTRACT
  10. Le MT, Nguyen HTT, Dang HNT, Nguyen TTT, Van Nguyen T, Nguyen QHV. Impact of metabolic syndrome on the viability of human spermatozoa: a cross-sectional descriptive study in men from infertile couples. Basic and Clinical Andrology. 2021;31(1):22. doi:10.1186/s12610-021-00142-8
  11. Esposito K, Ciotola M, Giugliano F, et al. Mediterranean diet improves erectile function in subjects with the metabolic syndrome. International Journal of Impotence Research. 2006;18(4):405-410. doi:10.1038/sj.ijir.3901447
  12. Letkiewicz S, Pilis K, Ślęzak A, et al. Eight Days of Water-Only Fasting Promotes Favorable Changes in the Functioning of the Urogenital System of Middle-Aged Healthy Men. Nutrients. 2021;13(1):113. doi:10.3390/nu13010113
  13. Russo GI, Cimino S, Fragalà E, et al. Insulin resistance is an independent predictor of severe lower urinary tract symptoms and of erectile dysfunction: results from a cross-sectional study. J Sex Med. 2014;11(8):2074-2082. doi:10.1111/jsm.12587 
  14. Renck A, Afonso TT, Risso PJ, Barbosa TE, Hallak J, Maria FCE. Semen quality improvement after weight loss by very low-calorie ketogenic dietary: A report of two cases. In: Endocrine Abstracts. Vol 70. Bioscientifica; 2020. doi:10.1530/endoabs.70.EP379

Adolescents and Children

This review from Calkins et al., 2024 is an important read that informs on reduced carbohydrate approaches in young people ‘Carbohydrate reduction for metabolic disease is distinct from the ketogenic diet for epilepsy’.

  1. Gow ML, Garnett SP, Baur LA, Lister NB. The Effectiveness of Different Diet Strategies to Reduce Type 2 Diabetes Risk in Youth. Nutrients. 2016;8(8). doi:10.3390/nu8080486
  2. Zinn, C. et al. (2022) ‘Assessing the Nutrient Status of Low Carbohydrate, High-Fat (LCHF) Meal Plans in Children: A Hypothetical Case Study Design’, Nutrients, 14(8), p. 1598. doi:10.3390/nu14081598.
  3. Stefan M, Sharp M, Gheith R, Lowery R, Wilson J. The Effect of Exogenous Beta-Hydroxybutyrate Salt Supplementation on Metrics of Safety and Health in Adolescents. Nutrients. 2021;13(3):854. doi:10.3390/nu13030854
  4. Lustig RH, Mulligan K, Noworolski SM, et al. Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Obesity (Silver Spring). 2016;24(2):453-460. doi:10.1002/oby.21371
  5. Stoica RA, Diaconu CC, Rizzo M, et al. Weight loss programmes using low carbohydrate diets to control the cardiovascular risk in adolescents (Review). Experimental and Therapeutic Medicine. 2021;21(1):1-1. doi:10.3892/etm.2020.9522 PDF
  6. Jebeile H, Grunseit AM, Thomas M, Kelly T, Garnett SP, Gow ML. Low-carbohydrate interventions for adolescent obesity: Nutritional adequacy and guidance for clinical practice. Clinical Obesity. 2020;10(4):e12370. doi:https://doi.org/10.1111/cob.12370 ABSTRACT
  7. Zeybek C, Celebi A, Aktuglu-Zeybek C, et al. The effect of low-carbohydrate diet on left ventricular diastolic function in obese children. Pediatr Int. 2010;52(2):218-223. doi:10.1111/j.1442-200X.2009.02940.x ABSTRACT

  8. Chakraborty, S. et al. (2025) ‘A very low carbohydrate diet improved metabolic profile in congenital generalized lipodystrophy type 4’. Available at: https://doi.org/10.1530/EDM-24-0063.

  9. Rodrigue C, Iceta S, Bégin C. Food Addiction and Cognitive Functioning: What Happens in Adolescents? Nutrients. 2020;12(12):3633. doi:10.3390/nu12123633 (added for completeness – for more on this complex and emerging area see Food Addiction and Binge Eating Disorder Spectrum)

Obesity/Weight Loss

  1.  Rohani, P. et al. (2024) ‘Effect of a carbohydrate-restricted diet on weight loss in overweight and obese pediatric population: a meta-analysis of randomized controlled trials’, Diabetology & Metabolic Syndrome, 16(1), p. 210. Available at: https://doi.org/10.1186/s13098-024-01458-x.

  2. Zhang, Y. et al. (2024) ‘Low-Carbohydrate Diet is More Helpful for Weight Loss Than Low-Fat Diet in Adolescents with Overweight and Obesity: A Systematic Review and Meta-Analysis’, Diabetes, Metabolic Syndrome and Obesity, Volume 17, pp. 2997–3007. Available at: https://doi.org/10.2147/DMSO.S467719.

  3. Cucuzzella, M. et al. (2024a) ‘Beyond Obesity and Overweight: The Clinical Assessment and Treatment of Excess Body Fat in Children : Part 1 – Insulin Resistance as the Root Cause of Pediatric Obesity’, Current Obesity Reports [Preprint]. Available at: https://doi.org/10.1007/s13679-024-00565-0. ABSTRACT
  4. Cucuzzella, M. et al. (2024b) ‘Beyond Obesity and Overweight: the Clinical Assessment and Treatment of Excess Body Fat In Children : Part 2 – the Prescription of Low-Carbohydrate Eating as the First Approach’, Current Obesity Reports [Preprint]. Available at: https://doi.org/10.1007/s13679-024-00564-1. ABSTRACT
  5. Kirk S, Brehm B, Saelens BE, et al. Role of Carbohydrate Modification in Weight Management among Obese Children: A Randomized Clinical Trial. The Journal of Pediatrics. 2012;161(2):320-327.e1. doi:10.1016/j.jpeds.2012.01.041 PDF
  6. Sondike SB, Copperman N, Jacobson MS. Effects of a low-carbohydrate diet on weight loss and cardiovascular risk factor in overweight adolescents. J Pediatr. 2003;142(3):253-258. doi:10.1067/mpd.2003.4   PDF
  7. Krebs NF, Gao D, Gralla J, Collins JS, Johnson SL. Efficacy and safety of a high protein, low carbohydrate diet for weight loss in severely obese adolescents. J Pediatr. 2010;157(2):252-258. doi:10.1016/j.jpeds.2010.02.010   PDF
  8. Pauley M, Mays C, Bailes JR, et al. Carbohydrate-Restricted Diet: A Successful Strategy for Short-Term Management in Youth with Severe Obesity—An Observational Study. Metabolic Syndrome and Related Disorders. Published online February 9, 2021. doi:10.1089/met.2020.0078
  9. Lustig RH, Mulligan K, Noworolski SM, et al. Isocaloric fructose restriction and metabolic improvement in children with obesity and metabolic syndrome. Obesity (Silver Spring). 2016;24(2):453-460. doi:10.1002/oby.21371
  10.  Stoica RA, Diaconu CC, Rizzo M, et al. Weight loss programmes using low carbohydrate diets to control the cardiovascular risk in adolescents (Review). Exp Ther Med. 2021;21(1). doi:10.3892/etm.2020.9522
  11. Cakmak HM, IlknurArslanoglu, Sungur MA, Bolu S. Clinical Picture at Attendance and Response to Flexible FamilyBased Low-Carb Life Style Change in Children With Obesity. IJCHN. 2021;10(1):9-16. doi:10.6000/1929-4247.2021.10.01.2     PDF
  12. Favret J, Wood CT, Maradiaga Panayotti GM. Ketogenic diet as an advanced option for the management of pediatric obesity. Curr Opin Endocrinol Diabetes Obes. Published online July 15, 2021. doi:10.1097/MED.0000000000000661
  13. Calcaterra V, Verduci E, Pascuzzi MC, et al. Metabolic Derangement in Pediatric Patient with Obesity: The Role of Ketogenic Diet as Therapeutic Tool. Nutrients. 2021;13(8):2805. doi:10.3390/nu13082805
  14. Chung, S.T. and Magge, S. (2021) ‘Abstract 9768: Relationship of Atherogenic Lipoproteins with Insulin Resistance and Carotid Intimal Thickness in Youth at Risk for Cardiovascular Disease’, Circulation, 144(Suppl_1), pp. A9768–A9768. doi:10.1161/circ.144.suppl_1.9768

Liver Function

  1. Katsagoni CN, Papachristou E, Sidossis A, Sidossis L. Effects of Dietary and Lifestyle Interventions on Liver, Clinical and Metabolic Parameters in Children and Adolescents with Non-Alcoholic Fatty Liver Disease: A Systematic Review. Nutrients. 2020;12(9):2864. doi:10.3390/nu12092864
  2. Schwimmer JB, Ugalde-Nicalo P, Welsh JA, et al. Effect of a Low Free Sugar Diet vs Usual Diet on Nonalcoholic Fatty Liver Disease in Adolescent Boys: A Randomized Clinical Trial. JAMA. 2019;321(3):256-265. doi:10.1001/jama.2018.20579 
  3. Mandala A, Janssen RC, Palle S, Short KR, Friedman JE. Pediatric Non-Alcoholic Fatty Liver Disease: Nutritional Origins and Potential Molecular Mechanisms. Nutrients. 2020;12(10):3166. doi:10.3390/nu12103166
  4. Schwarz J-M, Noworolski SM, Erkin-Cakmak A, et al. Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children with Obesity. Gastroenterology. 2017;153(3):743-752. doi:10.1053/j.gastro.2017.05.043
  5. Goss AM, Dowla S, Pendergrass M, et al. Effects of a carbohydrate-restricted diet on hepatic lipid content in adolescents with non-alcoholic fatty liver disease: A pilot, randomized trial. Pediatr Obes. Published online March 4, 2020:e12630. doi:10.1111/ijpo.12630 ABSTRACT

The Role of Sugar Sweetened Beverages (SSBs)

  1. Nier A, Brandt A, Conzelmann IB, Özel Y, Bergheim I. Non-Alcoholic Fatty Liver Disease in Overweight Children: Role of Fructose Intake and Dietary Pattern. Nutrients. 2018;10(9). doi:10.3390/nu10091329
  2. Abdelmalek MF, Day C. Sugar sweetened beverages and fatty liver disease: Rising concern and call to action. Journal of Hepatology. 2015;63(2):306-308. doi:10.1016/j.jhep.2015.05.021

Glycogen Storage Disease

  1. Reason, S. et al. (2017) ‘Can a Low-Carbohydrate Diet Improve Exercise Tolerance in Mcardle Disease?’, Journal of Rare Disorders: Diagnosis & Therapy, 03. Available at: https://doi.org/10.21767/2380-7245.100054.
  2. Mayorandan S, Meyer U, Hartmann H, Das AM. Glycogen storage disease type III: modified Atkins diet improves myopathy. 2014. https://core.ac.uk/reader/81156938. 
  3. Hoogeveen IJ, Boer F de, Boonstra WF, et al. Effects of acute nutritional ketosis during exercise in adults with glycogen storage disease type IIIa are phenotype-specific: An investigator-initiated, randomized, crossover study. Journal of Inherited Metabolic Disease. n/a(n/a). doi:https://doi.org/10.1002/jimd.12302
  4. Kalkan Uçar, S. et al. (2024) ‘Long-term personalized high-protein, high-fat diet in pediatric patients with glycogen storage disease type IIIa: Evaluation of myopathy, metabolic control, physical activity, growth, and dietary compliance’, Journal of Inherited Metabolic Disease, n/a(n/a). Available at: https://doi.org/10.1002/jimd.12741.
  5. Bhattacharya K, Pontin J, Thompson S. Dietary Management of the Ketogenic Glycogen Storage Diseases. Journal of Inborn Errors of Metabolism and Screening. 2016;4:2326409816661359. doi:10.1177/2326409816661359 
  6. Marusic T, Zerjav Tansek M, Sirca Campa A, et al. Normalization of obstructive cardiomyopathy and improvement of hepatopathy on ketogenic diet in patient with glycogen storage disease (GSD) type IIIa. Mol Genet Metab Rep. 2020;24. doi:10.1016/j.ymgmr.2020.100628
  7. Similä ME, Auranen M, Piirilä PL. Beneficial Effects of Ketogenic Diet on Phosphofructokinase Deficiency (Glycogen Storage Disease Type VII). Front Neurol. 2020;11. doi:10.3389/fneur.2020.00057
  8. Hettiarachchi D, Lakmal K, Dissanayake VHW. A Concise Review of Ketogenic Dietary Interventions in the Management of Rare Diseases. Journal of Nutrition and Metabolism. doi:https://doi.org/10.1155/2021/6685581

Prader-Willi Syndrome

  1. Irizarry KA, Mager DR, Triador L, Muehlbauer MJ, Haqq AM, Freemark M. Hormonal and metabolic effects of carbohydrate restriction in children with Prader-Willi syndrome. Clin Endocrinol (Oxf). 2019;90(4):553-561. doi:10.1111/cen.13933 PDF
  2. Teke Kısa, P. et al. (2023) ‘Positive effects of ketogenic diet on weight control in children with obesity due to Prader-Willi syndrome.’, Clinical endocrinology, 98(3). Available at: https://doi.org/10.1111/cen.14864.
  3. Felix G, Kossoff E, Barron B, Krekel C, Testa EG, Scheimann A. The modified Atkins diet in children with Prader-Willi syndrome. Orphanet Journal of Rare Diseases. 2020;15(1):135. doi:10.1186/s13023-020-01412-w
  4. Barrea, L., Vetrani, C., Fintini, D., de Alteriis, G., Panfili, F.M., Bocchini, S., Verde, L., Colao, A., Savastano, S., Muscogiuri, G., 2022. Prader–Willi Syndrome in Adults: An Update On Nutritional Treatment and Pharmacological Approach. Curr Obes Rep. doi.org/10.1007/s13679-022-00478-w
  5. Kweh, F.A. et al. (2023) ‘Hyperinsulinemia is a probable trigger for weight gain and hyperphagia in individuals with Prader‐Willi syndrome’, Obesity Science & Practice, p. osp4.663. Available at: https://doi.org/10.1002/osp4.663.

Type 1 Diabetes

  1. Neuman, V. et al. (2024) ‘Low-carbohydrate diet in children and young people with type 1 diabetes: A randomized controlled trial with cross-over design’, Diabetes Research and Clinical Practice, 217, p. 111844. Available at: https://doi.org/10.1016/j.diabres.2024.111844

  2. Levran, N. et al. (2024) ‘Low-carbohydrate diet proved effective and safe for youths with type 1 diabetes: A randomised trial’, Acta Paediatrica (Oslo, Norway: 1992) [Preprint]. Available at: https://doi.org/10.1111/apa.17455.

  3. Lennerz BS, Barton A, Bernstein RK, et al. Management of Type 1 Diabetes With a Very Low-Carbohydrate Diet. Pediatrics. 2018;141(6). doi:10.1542/peds.2017-3349 
  4. Neuman V, Plachy L, Pruhova S, et al. Low-Carbohydrate Diet among Children with Type 1 Diabetes: A Multi-Center Study. Nutrients. 2021;13(11):3903. doi:10.3390/nu13113903
  5. Harray, A.J. et al. (2023) ‘Experiences and Attitudes of Parents Reducing Carbohydrate Intake in the Management of Their Child’s Type 1 Diabetes: A Qualitative Study’, Nutrients, 15(7), p. 1666. Available at: https://doi.org/10.3390/nu15071666.
  6. Runge C, Lee JM. How Low Can You Go? Does Lower Carb Translate to Lower Glucose? Pediatrics. 2018;141(6). doi:10.1542/peds.2018-0957
  7. Öz NA, Arslanoglu I, Cangür S, Bolu S, Kocabay K. Low-carb Diet in Hospitalized Late Pubertal Type 1 Diabetic Girls: A Short-Term CGM Study. Indian J Endocrinol Metab. 2021;25(1):31-37. doi:10.4103/ijem.ijem_176_21
  8. Rydin AA, Spiegel G, Frohnert BI, et al. Medical Management of Children with Type 1 Diabetes on Low Carbohydrate or Ketogenic Diets. Pediatric Diabetes. n/a(n/a). doi:https://doi.org/10.1111/pedi.13179
  9. Tóth C, Clemens Z. A child with type 1 diabetes mellitus (T1DM) successfully treated with the Paleolithic ketogenic diet: A 19-month insulin-freedom. IJCRI. 2015;6(12):752. doi:10.5348/ijcri-2015121-CR-10582
  10. de Souza Bosco Paiva C, Lima MHM. Introducing a very low carbohydrate diet for a child with type 1 diabetes. Br J Nurs. 2019;28(15):1015-1019. doi:10.12968/bjon.2019.28.15.1015 ABSTRACT

Infants and very young children

See section on Epilepsy and Autism Spectrum Disorder

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