The long-term effect of therapeutic diets in obesity treatment is a challenge at present. The current study aimed to evaluate the long-term effect of a very low-calorie-ketogenic (VLCK) diet on excess adiposity. Especial focus was set on visceral fat mass, and the impact on the individual burden of disease. A group of obese patients (n = 45) were randomly allocated in two groups: either the very low-calorie-ketogenic diet group (n = 22), or a standard low-calorie diet group; (n = 23). Both groups received external support. Adiposity parameters and the cumulative number of months of successful weight loss (5 or 10 %) over a 24-month period were quantified. The very low-calorie-ketogenic diet induced less than 2 months of mild ketosis and significant effects on body weight at 6, 12, and 24 months. At 24 months, a trend to regress to baseline levels was observed; however, the very low-calorie-ketogenic diet induced a greater reduction in body weight (−12.5 kg), waist circumference (−11.6 cm), and body fat mass (−8.8 kg) than the low-calorie diet (−4.4 kg, −4.1 cm, and −3.8 kg, respectively; p < 0.001). Interestingly, a selective reduction in visceral fat measured by a specific software of dual-energy x-ray absorptiometry (DEXA)-scan (−600 g vs. −202 g; p < 0.001) was observed. Moreover, the very low-calorie-ketogenic diet group experienced a reduction in the individual burden of obesity because reduction in disease duration. Very low-calorie-ketogenic diet patients were 500 months with 5 % weight lost vs. the low-calorie diet group (350 months; p < 0.001). In conclusion, a very low-calorie-ketogenic diet was effective 24 months later, with a decrease in visceral adipose tissue and a reduction in the individual burden of disease.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
K.M. Flegal, M.D. Carroll, B.K. Kit, C.L. Ogden, Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. Jama. 307, 491–497 (2012)
J.L. Gutierrez-Fisac, P. Guallar-Castillon, L.M. Leon-Munoz, A. Graciani, J.R. Banegas, F. Rodriguez-Artalejo, Prevalence of general and abdominal obesity in the adult population of Spain, 2008-2010: the ENRICA study. Obes. Rev. 13, 388–392 (2010)
F.F. Casanueva, B. Moreno, R. Rodriguez-Azeredo, C. Massien, P. Conthe, X. Formiguera, V. Barrios, B. Balkau, Relationship of abdominal obesity with cardiovascular disease, diabetes and hyperlipidaemia in Spain. Clin. Endocrinol. 73, 35–40 (2010)
X. Pi-Sunyer, The medical risks of obesity. Postgrad. Med. 121, 21–33 (2009)
G. Fruhbeck, V. Yumuk. Obesity: a gateway disease with a rising prevalence. Obes. Facts 7 Suppl 2, 33–36 (2014)
E.A. Spieker, N. Pyzocha, Economic impact of obesity. Prim. Care. 43, 83–95 (2016)
J.E. Blundell, J. Hebebrand, J.M. Oppert, What is the value of obesity research? Obes. Facts 3, 279–282 (2010)
G.A. Bray, G. Fruhbeck, D.H. Ryan, J.P. Wilding Management of obesity. Lancet. (2016).
W.T. Cefalu, G.A. Bray, P.D. Home, W.T. Garvey, S. Klein, F.X. Pi-Sunyer, F.B. Hu, I. Raz, L. Van Gaal, B.M. Wolfe, D.H. Ryan, Advances in the science, treatment, and prevention of the disease of obesity: reflections from a diabetes care editors’ expert forum. Diabetes Care 38, 1567–1582 (2015)
G. Di Dalmazi, V. Vicennati, R. Pasquali, U. Pagotto, The unrelenting fall of the pharmacological treatment of obesity. Endocrine 44, 598–609 (2013)
J.P. Despres, A. Golay, L. Sjostrom, Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N. Engl. J. Med. 353, 2121–2134 (2005)
R.V. Dvorak, A.M. Sharma, A. Astrup, Anti-obesity drugs: to be or not to be? Obes. Rev. 11, 833–834 (2010)
M. Hopkins, N.A. King, J.E. Blundell, Acute and long-term effects of exercise on appetite control: is there any benefit for weight control? Curr. Opin. Clin. Nutr. Metab. Care. 13, 635–640 (2010)
L.F. Van Gaal, A.M. Rissanen, A.J. Scheen, O. Ziegler, S. Rossner, Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 365, 1389–1397 (2005)
G.A. Bray, L.A. Tartaglia, Medicinal strategies in the treatment of obesity. Nature 404, 672–677 (2000)
A. Astrup, T. Meinert Larsen, A. Harper, Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss? Lancet 364, 897–899 (2004)
A.B. Crujeiras, M.A. Zulet, I. Abete, M. Amil, M.C. Carreira, J.A. Martinez, F.F. Casanueva, Interplay of atherogenic factors, protein intake and betatrophin levels in obese-metabolic syndrome patients treated with hypocaloric diets. Int. J. Obes. 40, 403–410 (2015)
D. Paddon-Jones, E. Westman, R.D. Mattes, R.R. Wolfe, A. Astrup, M. Westerterp-Plantenga, Protein, weight management, and satiety. Am. J. Clin. Nutr. 87, 1558S–1561S (2008)
A. Paoli, Ketogenic diet for obesity: friend or foe? Int. J. Environ. Res. Public Health. 11, 2092–2107 (2014)
A. Al-Khalifa, T.C. Mathew, N.S. Al-Zaid, E. Mathew, H.M. Dashti, Therapeutic role of low-carbohydrate ketogenic diet in diabetes. Nutrition 25, 1177–1185 (2009)
H.M. Dashti, T.C. Mathew, M. Khadada, M. Al-Mousawi, H. Talib, S.K. Asfar, A.I. Behbahani, N.S. Al-Zaid, Beneficial effects of ketogenic diet in obese diabetic subjects. Mol. Cell. Biochem. 302, 249–256 (2007)
M.J. Sharman, W.J. Kraemer, D.M. Love, N.G. Avery, A.L. Gomez, T.P. Scheett, J.S. Volek, A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men. J. Nutr. 132, 1879–1885 (2002)
B.G. Allen, S.K. Bhatia, C.M. Anderson, J.M. Eichenberger-Gilmore, Z.A. Sibenaller, K.A. Mapuskar, J.D. Schoenfeld, J.M. Buatti, D.R. Spitz, M.A. Fath, Ketogenic diets as an adjuvant cancer therapy: history and potential mechanism. Redox. Biol. 2C, 963–970 (2014)
A.F. Branco, A. Ferreira, R.F. Simoes, S. Magalhaes-Novais, C. Zehowski, E. Cope, A.M. Silva, D. Pereira, V.A. Sardao, T. Cunha-Oliveira, Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur. J. Clin. Invest. 46, 285–298 (2016)
N.B. Bueno, I.S. de Melo, S.L. de Oliveira, T. da Rocha Ataide, Very-low-carbohydrate ketogenic diet v. low-fat diet for long-term weight loss: a meta-analysis of randomised controlled trials. Br. J. Nutr. 110, 1178–1187 (2013)
B. Moreno, D. Bellido, I. Sajoux, A. Goday, D. Saavedra, A.B. Crujeiras, F.F. Casanueva, Comparison of a very low-calorie-ketogenic diet with a standard low-calorie diet in the treatment of obesity. Endocrine 47, 793–805 (2014)
A. Astrup, S. Rossner, Lessons from obesity management programmes: greater initial weight loss improves long-term maintenance. Obes. Rev. 1, 17–19 (2000)
S.G. Camps, S.P. Verhoef, K.R. Westerterp, Weight loss, weight maintenance, and adaptive thermogenesis. Am. J. Clin. Nutr. 97, 990–994 (2013)
A.B. Crujeiras, E. Goyenechea, I. Abete, M. Lage, M.C. Carreira, J.A. Martinez, F.F. Casanueva, Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J. Clin. Endocrinol. Metab. 95, 5037–5044 (2010)
A.B. Crujeiras, M. Pardo, R.R. Arturo, S. Navas-Carretero, M.A. Zulet, J.A. Martinez, F.F. Casanueva, Longitudinal variation of circulating irisin after an energy restriction-induced weight loss and following weight regain in obese men and women. Am. J. Hum. Biol. 26, 198–207 (2014)
A.B. Crujeiras, M.A. Zulet, P. Lopez-Legarrea, R. de la Iglesia, M. Pardo, M.C. Carreira, J.A. Martinez, F.F. Casanueva, Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients. Metabolism 63, 520–531 (2014)
P.S. Maclean, A. Bergouignan, M.A. Cornier, M.R. Jackman, Biology’s response to dieting: the impetus for weight regain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 301, R581–600 (2011)
R.R. Wing, S. Phelan, Long-term weight loss maintenance. Am. J. Clin. Nutr. 82, 222S–225S (2005)
R.R. Wing, D.F. Tate, A.A. Gorin, H.A. Raynor, J.L. Fava, A self-regulation program for maintenance of weight loss. N. Engl. J. Med. 355, 1563–1571 (2006)
FAO/WHO/UNU. Energy and Protein requirements. Technical Report Series N° 724. World Health Organization, Geneva (1985)
M. Gargallo Fernandez, J.B. Marset, I.B. Lesmes, J.Q. Izquierdo, X.F. Sala, J. Salas-Salvado, [FESNAD-SEEDO consensus summary: evidence-based nutritional recommendations for the prevention and treatment of overweight and obesity in adults]. Endocrinol. Nutr. 59, 429–437 (2011)
SCOOP-VLCD task 7.3 Reports on tasks for scientific cooperation. Collection of data on products intended for use in very-low-calorie-diets. Report Brussels European Comission, September (2002)
S. Kaul, M.P. Rothney, D.M. Peters, W.K. Wacker, C.E. Davis, M.D. Shapiro, D.L. Ergun, Dual-energy X-ray absorptiometry for quantification of visceral fat. Obesity 20, 1313–1318 (2012)
L.K. Micklesfield, J.H. Goedecke, M. Punyanitya, K.E. Wilson, T.L. Kelly, Dual-energy X-ray performs as well as clinical computed tomography for the measurement of visceral fat. Obesity 20, 1109–1114 (2012)
Kelly TL, Wilson KE, Ruth CR Estimating visceral fat by dual-energy X-ray absorptiometry. US patent application number US2010-0234719 Hologic, Inc. (2010).
Kelly TL, Wilson KE, Ruth CR Visceral fat measurement. US patent application number US2011-0235881 Hologic, Inc. (2011).
I. Shai, D. Schwarzfuchs, Y. Henkin, D.R. Shahar, S. Witkow, I. Greenberg, R. Golan, D. Fraser, A. Bolotin, H. Vardi, O. Tangi-Rozental, R. Zuk-Ramot, B. Sarusi, D. Brickner, Z. Schwartz, E. Sheiner, R. Marko, E. Katorza, J. Thiery, G.M. Fiedler, M. Bluher, M. Stumvoll, M.J. Stampfer, Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N. Engl. J. Med. 359, 229–241 (2008)
B. Cabia, S. Andrade, M.C. Carreira, F.F. Casanueva, A.B. Crujeiras, A role for novel adipose tissue-secreted factors in obesity-related carcinogenesis. Obes. Rev. 17, 361–376 (2016)
M.C. Amato, G. Pizzolanti, V. Torregrossa, G. Misiano, S. Milano, C. Giordano, Visceral adiposity index (VAI) is predictive of an altered adipokine profile in patients with type 2 diabetes. PLoS One 9, e91969 (2014)
A.B. Crujeiras, B. Cabia, M.C. Carreira, M. Amil, J. Cueva, S. Andrade, L.M. Seoane, M. Pardo, A. Sueiro, J. Baltar, T. Morais, M.P. Monteiro, R. Lopez-Lopez, F.F. Casanueva, Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes. Int. J. Obes. 40, 514–523 (2015)
I.J. Neeland, C.R. Ayers, A.K. Rohatgi, A.T. Turer, J.D. Berry, S.R. Das, G.L. Vega, A. Khera, D.K. McGuire, S.M. Grundy, J.A. de Lemos, Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obesity 21, E439–447 (2013)
D. Vissers, W. Hens, J. Taeymans, J.P. Baeyens, J. Poortmans, L. Van Gaal, The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis. PLoS One 8, e56415 (2013)
I. Wolz, I. Hilker, R. Granero, S. Jimenez-Murcia, A.N. Gearhardt, C. Dieguez, F.F. Casanueva, A.B. Crujeiras, J.M. Menchon, F. Fernandez-Aranda, “Food Addiction” in Patients with Eating Disorders is Associated with Negative Urgency and Difficulties to Focus on Long-Term Goals. Front Psychol. 7, 61 (2016)
M.M. Ibrahim, Subcutaneous and visceral adipose tissue: structural and functional differences. Obes. Rev. 11, 11–18 (2010)
B.L. Wajchenberg, D. Giannella-Neto, M.E. da Silva, R.F. Santos, Depot-specific hormonal characteristics of subcutaneous and visceral adipose tissue and their relation to the metabolic syndrome. Horm. Metab. Res. 34, 616–621 (2002)
B. Bjorndal, L. Burri, V. Staalesen, J. Skorve, R.K. Berge, Different adipose depots: their role in the development of metabolic syndrome and mitochondrial response to hypolipidemic agents. J. Obes. 2011, 490650 (2011)
L. Webber, D. Divajeva, T. Marsh, K. McPherson, M. Brown, G. Galea, J. Breda, The future burden of obesity-related diseases in the 53 WHO European-Region countries and the impact of effective interventions: a modelling study. BMJ Open 4, e004787 (2014)
H.P. Booth, T.A. Prevost, A.J. Wright, M.C. Gulliford, Effectiveness of behavioural weight loss interventions delivered in a primary care setting: a systematic review and meta-analysis. Fam. Pract. 31, 643–653 (2014)
A. Abdullah, R. Wolfe, J.U. Stoelwinder, M. de Courten, C. Stevenson, H.L. Walls, A. Peeters, The number of years lived with obesity and the risk of all-cause and cause-specific mortality. Int. J. Epidemiol. 40, 985–996 (2011)
R.Z. Stolzenberg-Solomon, C. Schairer, S. Moore, A. Hollenbeck, D.T. Silverman, Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study cohort. Am. J. Clin. Nutr. 98, 1057–1065 (2013)
J.P. Reis, C.M. Loria, C.E. Lewis, T.M. Powell-Wiley, G.S. Wei, J.J. Carr, J.G. Terry, K. Liu, Association between duration of overall and abdominal obesity beginning in young adulthood and coronary artery calcification in middle age. Jama. 310, 280–288 (2013)
M. Arnold, N. Pandeya, G. Byrnes, A.G. Renehan, G.A. Stevens, M. Ezzati, J. Ferlay, J.J. Miranda, I. Romieu, R. Dikshit, D. Forman, I. Soerjomataram, Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol. 16, 36–46 (2015)
J.A. Nazare, J. Smith, A.L. Borel, P. Aschner, P. Barter, L. Van Gaal, C.E. Tan, H.U. Wittchen, Y. Matsuzawa, T. Kadowaki, R. Ross, C. Brulle-Wohlhueter, N. Almeras, S.M. Haffner, B. Balkau, J.P. Despres, Usefulness of measuring both body mass index and waist circumference for the estimation of visceral adiposity and related cardiometabolic risk profile (from the INSPIRE ME IAA study). Am. J. Cardiol. 115, 307–315 (2015)
We acknowledge the Pronokal Division of Protein Supplies SL Spain for providing free of charge the diet of the ketosis group.
Conflict of interest
BM, ABC, DB, AG, and FFC received advisory board fees and or research grants from Pronokal Protein Supplies Spain.
Basilio Moreno and Ana B Crujeiras authors equally contributed to this work.
About this article
Cite this article
Moreno, B., Crujeiras, A.B., Bellido, D. et al. Obesity treatment by very low-calorie-ketogenic diet at two years: reduction in visceral fat and on the burden of disease. Endocrine 54, 681–690 (2016). https://doi.org/10.1007/s12020-016-1050-2
- Waist Circumference
- Lean Mass
- Visceral Adipose Tissue
- Soft Tissue Mass
- Ketogenic Diet