Efficacy and safety of very low calorie ketogenic diet (VLCKD) in patients with overweight and obesity: A systematic review and meta-analysis

  • Marco Castellana
  • Eleonora Conte
  • Angelo Cignarelli
  • Sebastio Perrini
  • Andrea Giustina
  • Luca Giovanella
  • Francesco Giorgino
  • Pierpaolo TrimboliEmail author


Very low calorie ketogenic diet (VLCKD) has been proposed as a promising option to achieve a significant weight loss in a short time period. We conducted a systematic review and meta-analysis to evaluate its efficacy and safety in patients with overweight and obesity. Four databases were searched on May 2019. Studies reporting data on body weight, body mass index (BMI), waist circumference, body composition, blood pressure, HbA1c, lipids, and markers of liver and kidney function were selected. Discontinuation was also assessed. Twelve studies were included. VLCKD was associated with weight losses of −10.0 kg (I2 = 6%) and − 15.6 kg (I2 = 37%) in studies with a ketogenic phase up to and of at least four weeks, respectively. The weight lost during the ketogenic phase was stable in the subsequent follow-up up to two years (p = 0.12). Also, VLCKD was associated with reductions of BMI (−5.3 kg/m2), waist circumference (−12.6 cm), HbA1c (−0.7%), total cholesterol (−28 mg/dl), triglycerides (−30 mg/dl), AST (−7 U/l), ALT (−8 U/l), GGT (−8 U/l), systolic and diastolic blood pressure (−8 and − 7 mmHg, respectively). No changes in LDL cholesterol, HDL cholesterol, serum creatinine, serum uric acid and serum potassium were found. Serum sodium increased during VLCKD (+1.6 mEq/l). The overall prevalence of patients discontinuing VLCKD was 7.5% and this was similar to patients undergoing a low calorie diet (p = 0.83). The present review supports the use of VLCKD as an effective strategy for the management of overweight and obesity. Future guidelines should include a specific recommendation for this intervention.


Very low calorie ketogenic diet VLCKD Obesity Overweight Systematic review Meta-analysis 


Data accessibility

The datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

Author Contributions

MC and PT conceived the meta-analysis, developed the search strategy and provided statistical expertise. MC, EC, AC, and PT drafted the manuscript. All Authors contributed to the development of the selection criteria, the risk of bias assessment strategy and data extraction criteria. All Authors read, provided feedback, and approved the final manuscript.

Funding information

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Compliance with ethical standards

Ethical approval

These systematic review and meta-analysis were in accordance with the principles of the Declaration of Helsinki. Analyses were performed on data extracted from published papers.

Conflict of interest

MC, EC, AC, SP, AG, LG, FG, and PT declare that they have no conflict of interest.

Supplementary material

11154_2019_9514_MOESM1_ESM.pdf (411 kb)
ESM 1 (PDF 411 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Emergency and Organ TransplantationUniversity of Bari Aldo MoroBariItaly
  2. 2.IRCCS San Raffaele HospitalSan Raffaele Vita Salute UniversityMilanItaly
  3. 3.Clinic for Nuclear Medicine and Competence Center for Thyroid Diseases, Imaging Institute of Southern SwitzerlandEnte Ospedaliero CantonaleBellinzonaSwitzerland
  4. 4.Clinic for Nuclear MedicineUniversity Hospital and University of ZurichZurichSwitzerland

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