Adherence and Tolerability of Four Very Low-Calorie Ketogenic Diet Approaches in Adults With Obesity or Complicated Overweight (KOBE)

University of Bologna

Status: Completed

Conditions: Obesity & Overweight; Insulin Resistance; Type 2 Diabetes; MASLD/MASH (Metabolic Dysfunction-Associated Steatotic Liver Disease / Metabolic Dysfunction-Associated Steatohepatitis)

Study type: Observational

Funder types: Other

Identifiers

NCT07389122

650/2021/Oss/AOUBo

Details and patient eligibility

About

This study, called KOBE Study, looks at how well different very low-calorie ketogenic diets (VLCKD) are followed and tolerated by adults with obesity or complicated overweight in routine clinical practice.

Ketogenic diets are medical nutrition therapies that greatly reduce carbohydrates and calories to promote weight loss and improve metabolic health. Several VLCKD approaches are used in clinical care, but they differ in the type of protein sources used (natural foods versus meal replacements or supplements). At present, there is limited evidence comparing these approaches in terms of adherence, side effects, satisfaction, and dropout rates.

The KOBE Study is a single-center, prospective, observational study conducted during standard clinical care at a hospital nutrition clinic. Participants choose one of four VLCKD protocols based on personal preference:

• diets using only natural protein foods,
• natural proteins plus one protein supplement,
• natural proteins plus two meal replacements,
• or diets based entirely on meal replacements.

All participants follow the same structured program lasting about 26 weeks (longer for individuals with severe obesity), consisting of:

1. an initial ketogenic phase,
2. a gradual reintroduction of carbohydrates,
3. a maintenance phase based on a low-glycemic index Mediterranean-style diet. Throughout the study, patients undergo routine clinical visits and assessments, including measurements of body weight, body composition, blood tests, liver imaging, and questionnaires on hunger, bowel habits, quality of life, and satisfaction with the diet. No additional tests beyond standard care are required.

The main goal of the study is to compare the different ketogenic protocols in terms of:

• how well patients can follow them,
• how well they are tolerated,
• the occurrence of side effects,
• and overall satisfaction. Secondary objectives include evaluating changes in body composition, metabolic parameters, and liver health.

The results of this study aim to help patients and healthcare professionals make more informed, evidence-based decisions when choosing among different ketogenic diet options for weight management and metabolic disease.

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Obesity with or without comorbidities (BMI ≥ 30 kg/m²) OR
• Overweight with comorbidity of MASLD (BMI 25.0-29.9 kg/m²) PLUS
• Previous unsuccessful attempt at a prescribed hypocaloric diet

Exclusion criteria

• Age < 18 years
• Pregnancy
• Breastfeeding
• Moderate or severe kidney failure
• Cardiovascular diseases: heart failure (NYHA III-IV), unstable angina, acute coronary syndrome or stroke within the past 12 months, paroxysmal atrial fibrillation, any type of atrioventricular block, left bundle branch block
• Liver diseases: Child-Pugh C, elevated transaminases with AST or ALT ≥ 5 times the upper limit of normal, INR ≥ 1.5, total bilirubin ≥ 2 mg/dL
• Diabetes: type 1 diabetes mellitus, type 2 diabetes mellitus with insufficient pancreatic endocrine reserve (C-peptide < 0.8 ng/mL), type 2 diabetes mellitus on multiple daily insulin injections
• Last attempt of VLCKD outside the research protocol within the past 12 months
• Eating disorders: anorexia nervosa, bulimia nervosa, binge eating disorder
• Psychiatric comorbidities, alcohol or substance dependence
• Frail elderly patients

Trial design

110 participants in 4 patient groups

Arm A

Description:

In arm A, protein intake was derived exclusively from natural food sources, with three or four daily meals according to individual energy and protein requirements. Protein sources included lean white meats (chicken, rabbit, turkey), lean red meats (veal and pork), lean and defatted cured meats (bresaola, cured and cooked ham), fish (gilthead seabream, cod, hake, trout), and 0% fat Greek yogurt.

Arm B

Description:

In arm B, the same natural food sources were combined with one daily meal, corresponding to breakfast, based on whey protein supplementation.

Arm C

Description:

In arm C, one or two daily meals, according to individual energy and protein requirements, consisted of natural foods, whereas the remaining two meals were provided as commercial meal replacement products.

Arm D

Description:

In arm D, all daily meals consisted exclusively of commercial meal replacement products.