Effect of KETOgenic Diet on Metabolism, Inflammation, Nutrition Deficiencies and OXidative Stress in Women With Overweight

Study Overview
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Brief Summary
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In recent times, the prevalence of obesity increases, reaching an epidemic scale. Elevated body weight is a risk factor in the development of several diseases such as diabetes, hypertension and cancer. Therefore, obesity management solutions, such as diet therapy are needed. The key issue is to choose the most appropriate diet to obtain an efficient outcome in losing weight, without experiencing adverse effects and a decrease in general health. A ketogenic diet, an auxiliary therapy for epilepsy, is recently one of the options commonly used for losing weight by overweight individuals, tempted by the commercials and internet influencers. However, there is limited knowledge about the effect of this diet on human health. To date, the majority of studies were conducted with a very-low-calorie regime applied before the bariatric surgeries, which itself may affect the loss of body weight, and in most studies, the control diets were missing. Taking into consideration that a ketogenic diet is an extremely eliminating diet, there is a risk of nutritional deficiencies after following it. Therefore, there is a strong need for more in-depth and comprehensive elucidation of the safety and physiological effects of the ketogenic diet used for the weight loss in overweight and obese individuals. This Project aims to evaluate the effectiveness of the eight-week, isocaloric, energy-restricted, ketogenic diet as a weight management solution in women with overweight and obesity compared to the standard, balanced diet with the same calorie content.

Detailed Description
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In recent times, the prevalence of obesity increases, reaching an epidemic scale. A new factor supporting a weight gain is a current coronaviros (COVID-19) pandemic, associated with reduced physical activity, high stress and overeating, which resulted in 2-5 kg weight gain in 20 % of the American population within a few months 1. Elevated body weight is a risk factor in developing several diseases such as diabetes, hypertension and cancer. Therefore, obesity management solutions, such as diet therapy, are needed. The critical issue is to choose the most appropriate diet to obtain an efficient outcome in losing weight without experiencing adverse effects and a decrease in general health. A ketogenic diet, an auxiliary therapy for epilepsy, is recently one of the options commonly used for losing weight by individuals with overweight, tempted by the commercials and internet influencers. However, there is limited knowledge about the effect of this diet on human health. To date, the majority of studies were conducted with a very low-calorie regime applied before the bariatric surgeries, which itself may affect the loss of body weight. In most studies, the control diets were missing. Considering that a ketogenic diet is an extremely eliminating diet, there is a risk of nutritional deficiencies after following it. Therefore, there is a strong need for more in-depth and comprehensive elucidation of the safety and physiological effects of the energy-restricted ketogenic diet used for weight loss in individuals with overweight and obese. This Project aims to evaluate the effectiveness of the eight-week, isocaloric, energy-restricted, ketogenic diet as a weight management solution in women with overweight and obesity compared to the standard, balanced diet with the same calorie content.

Official Title
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KETO-MINOX: The Effect of Isocaloric, Energy-restrictive, KETOgenic Diet on Metabolism, Inflammation, Nutrition Deficiencies and OXidative Stress in Women With Overweight and Obesity

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Other: Ketogenic diet
* Other: Control diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: women age 18-45 overweight (BMI 27 - 35) motivation to lose weight and participate in the nutritional intervention trial Exclusion Criteria: overweight/obesity secondary to genetic syndromes endocrine diseases, acute systemic disease, autoimmune disorders pregnancy breastfeeding type 1 and 2 diabetes any other chronic diseases requiring pharmacotherapy (including topical steroids in allergy disorders supplement or medication use influencing appetite, weight or metabolism) participation in other clinical trials severe obesity (BMI > 35) > 3 kg weight loss 12 weeks before the initial test day extreme changes in exercise intensity 4 weeks prior any diagnosed psychiatric disorders

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ketogenic diet<br>40 women which will follow the ketogenic diet with 1700 kcal daily for 8 weeks | Other: Ketogenic diet<br>* 1700 kcal ketogenic diet (fat: protein: carbohydrate ratio of 70:20:10)<br>|
| Active Comparator: Control diet<br>40 women which will follow the standard diet with 1700 kcal daily for 8 weeks | Other: Control diet<br>* 1700 kcal standard diet (fat: protein: carbohydrate ratio of 20:30:50)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory markers (G-CSF, GM-CSF, INF-gamma, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, MCP-1, MIP-1b, TNF-a) | Analysis using Bio-Plex Pro™ Human Cytokine 17-plex Assay in serum. | 12 months | 
| Oxidative stress markers | analysis of malondialdehyde, superoxide dismutase, 8-isoprostane and 8-hydroxydeoxyguanosine (8-OHdG) using commercial ELISA kits in serum. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight and composition | Body weight in kg and composition in % will be measured using Body Composition Analyser | 12 months | 
| Waist circumference | The waist circumference in cm will be measured using a standard measurement tape. | 12 months | 
| Free amino acids | Analysis of free amino acids in serum using gas chromatography-mass spectrometry, expressed in nmol/mL | 12 months | 
| Fat-soluble vitamins | Fat-soluble vitamins in serum using commercial ELISA kits (vitamin D) and high-performance liquid chromatography (vitamin A,E & K) | 12 months | 
| Metabolites in breath | Volatile organic compounds in breath will be measured using dwo dimensional chromatography with time of flight mass spectrometry (GCxGC-ToFMS) | 12 months | 
| Obesity-related markers (C-peptide, ghrelin, gastric inhibitory peptide (GIP), glucagon-like peptide 1 (GLP-1), glucagon, insulin, leptin, plasminogen activation inhibitor-1 (PAI-1), resistin and visfatin, adipsin and adiponectin) | Analyses will be performed using Bio-Plex Assays | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diet, nutrition, ketogenic diet, inflammation, oxidative stress, overweight