Ketogenic Diet in Women With Lipedema

Effect of a Low-Carbohydrate, High-Fat (LCHF) Ketogenic Diet on Adipose Tissue Hormones, Oxidative Stress, Inflammation, Lymphatic and Angiogenic Factors, Metabolomics, Symptoms, and Quality of Life in Women With Lipedema

Lipedema is a chronic fat tissue disorder that usually affects the lower limbs, excluding the feet. Clinical symptoms of lipedema include a noticeable disproportion between the upper and lower body, a tendency to easy bruising, and pain in the fatty tissue. It is a common disorder that occurs almost exclusively in women, potentially affecting around 11% of the adult population worldwide. The disease, especially in its advanced stages, has negative psychosocial consequences, leading to social isolation or depression, among other issues. The etiology of the disease is unknown, but genetic, hormonal, and inflammatory factors are likely involved in its pathogenesis. This disorder is characterized by the presence of low-grade inflammation in the fat tissue. The use of reduction diets combined with physical activity or bariatric surgery does not constitute an effective therapeutic approach for lipedema. Recent interventional studies show that an anti-inflammatory ketogenic diet leads to a reduction in leg volume and lipedema symptoms, including pain in the extremities.

This study aims to evaluate clinical, metabolic, inflammatory, and vascular characteristics in women with lipedema and to assess potential changes associated with dietary intervention - 7 months of ketogenic diet (low carbohydrate, high fat).

Participants undergo clinical, laboratory, and patient-reported outcome assessments to evaluate anthropometric parameters, quality of life, and selected biomarkers. The findings are expected to improve understanding of the biological mechanisms underlying lipedema and to support the development of targeted therapeutic strategies.

Study Overview

• Status: Completed
• Conditions: Overweight and Obesity; Lipedema
• Intervention / Treatment: Behavioral: Low carbohydrate high fat (ketogenic) diet with anti-inflammatory properties

Detailed Description

A total of 121 women were invited to participate in the study. The study group consisted of patients from the Angiology Outpatient Clinic at Wroclaw Medical University in Poland with the diagnosis of lipedema made by an angiologist (n=66). The control volunteer group was composed of women with overweight or obesity (body mass index, BMI= 25 kg/m2) who were not affected by lipedema (n=55).

All participants recruited to the study underwent following procedures at the beginning and at the end of the study:

1. Measurement of anthropometric parameters:

   • height - A TANITA HR-001 growth meter (Tanita, Tokyo, Japan)
   • weight and body composition parameters (body fat, lean body mass, body water, visceral fat) - A TANITA MC-780MA (Tanita, Tokyo, Japan)
   • waist, hip and leg circumferences (at 4 cm intervals from the ankle to the groin on the side of the leg) - standard tape measure to the nearest 1 cm

2. Questionnaires:

   • assessment of pain level in the leg - visual analogue scale (VAS)

   • assessment of psychological status, symptoms and quality of life:

     • The World Health Organization Disability Assessment Schedule (WHO-DAS II)
     • Beck's Depression Inventory - II (BDI-II)
     • The Hospital Anxiety and Depression Scale (HADS)
     • symptoms of the lower extremities (LYMQOL)
     • distress symptoms (GHQ28)
     • quality of life (SF-36)
   • assessment of food consuming - Food Frequency Questionnaire (FFQ)

3. Blood samples collection:

   • collection of approximately 25 ml of peripheral blood for laboratory tests

   • adipose tissue hormones: adiponectin, leptin, resistin, visfatin, and vaspin
   • oxidative stress markers: lipid peroxidation (TBARS)TBARS, 8-iso-prostaglandin F2α concentration, protein carbonyl content, serum total antioxidant capacity (TAC), superoxide dismutase (SOD) activity, catalase (CAT) activity, serum antioxidant vitamins (C, A and E)
   • angiogenic and lymphangiogenic factors: VEGF-A, VEGF-C, VEGF-D, angiopoietin-2, sICAM-1, sVCAM-1, P-selectin
   • endothelial adhesion molecules: sVCAM-1, sICAM-1, P-selectin
   • inflammatory cytokines: TNF-α, IL-1β, IL-8, IL-10, IL-13, CRP
   • targeted metabolomics: selected eicosanoids, endocannabinoids, and nitric oxide metabolites

4. Fat samples collection from the subcutaneous fatty tissue • collection of a drop subcutaneous fat from the thigh for metabolomic tests:

   • angiogenic and lymphangiogenic factors: VEGF-A, VEGF-C, VEGF-D, angiopoietin-2, sICAM-1, sVCAM-1, P-selectin
   • endothelial adhesion molecules: sVCAM-1, sICAM-1, P-selectin
   • inflammatory cytokines: TNF-α, IL-1β, IL-8, IL-10, IL-13
   • targeted metabolomics: selected eicosanoids, endocannabinoids, and nitric oxide metabolites

Of the original study population, 48 patients completed the study (28 in the lipedema group and 24 with overweight/obesity).

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Lower Silesian Voivodeship
    • Wroclaw, Lower Silesian Voivodeship, Poland, 50-367
      • Wroclaw Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• consent to participate in the study
• diagnosis of lipedema proved by an angiologist
• overweight or obesity based on BMI>25 kg/m2

Exclusion Criteria:

• pregnancy and period of 6 months after pregnancy,
• breastfeeding,
• diagnosis of lymphedema,
• edema in the course of chronic vein insufficiency or heart failure,
• diabetes mellitus,
• kidney or liver failure,
• hormonally unbalanced thyroid disease,
• cancer
• implanted cardiac devices (cardiac pacemaker, implantable cardioverter-defibrillator, resynchronization therapy)
• metal implants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with lipedema (interventional group); Patients with diagnosis of lipedema who following the interventional (ketogenic) diet.	Behavioral: Low carbohydrate high fat (ketogenic) diet with anti-inflammatory properties; The interventional diet structure was similar to a typical ketogenic diet, with less than 50 g of carbohydrates per day. The diet was designed as a Mediterranean style with many food products with anti-inflammatory properties such as antioxidants, unsaturated fatty acids, herbs, spices, tea and coffee. The diet was reduced in saturated fatty acids and processed foods. All the involved participants received the personalized caloric-restricted low-carbohydrate high-fat (ketogenic) diet, based on the patient's preferences. The daily energy intake was divided into 3 meals, consisting of a source of protein, fat, and vegetable additives. They received individual 7-day meal plans to repeat for 7 months with recipes and a shopping list. The personalization of the dietary plans aimed to increase compliance with the diets. Additionally, each patient received detailed dietary recommendations that facilitated adherence to the dietary plan.
Experimental: Patients with overweight/obesity (control group); Patients with overweight/obesity (BMI > 25 kg/m2) without lipedema symptoms who following the interventional (ketogenic) diet.	Behavioral: Low carbohydrate high fat (ketogenic) diet with anti-inflammatory properties; The interventional diet structure was similar to a typical ketogenic diet, with less than 50 g of carbohydrates per day. The diet was designed as a Mediterranean style with many food products with anti-inflammatory properties such as antioxidants, unsaturated fatty acids, herbs, spices, tea and coffee. The diet was reduced in saturated fatty acids and processed foods. All the involved participants received the personalized caloric-restricted low-carbohydrate high-fat (ketogenic) diet, based on the patient's preferences. The daily energy intake was divided into 3 meals, consisting of a source of protein, fat, and vegetable additives. They received individual 7-day meal plans to repeat for 7 months with recipes and a shopping list. The personalization of the dietary plans aimed to increase compliance with the diets. Additionally, each patient received detailed dietary recommendations that facilitated adherence to the dietary plan.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in leg circumferences	Changes in leg circumferences between 2 timepoints (baseline and end of study)	Up to 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body weight	Change in body weight in kilograms measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).	Up to 7 months
Change in body fat	Change in body fat percentage (%) measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).	Up to 7 months
Change in lean body mass	Change in lean body mass in kilograms measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).	Up to 7 months
Change in body water	Change in body water in kilograms measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).	Up to 7 months
Change in visceral fat level	Change in visceral fat level measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study). Visceral fat level is measured on a scale from 1 (lowest level) to 20 (highest level).	Up to 7 months
Change in disability level	Change in disability level measured using the World Health Organization Disability Assessment Schedule II (WHO-DAS II) total score between 2 timepoints (baseline and end of study).	Up to 7 months
Change in depressive symptoms	Change in depressive symptoms measured using the Beck Depression Inventory-II (BDI-II) total score between 2 timepoints (baseline and end of study).	Up to 7 months
Change in anxiety and depression symptoms	Change in anxiety and depression symptoms measured using the Hospital Anxiety and Depression Scale (HADS) total score between 2 timepoints (baseline and end of study).	Up to 7 months
Change in lower extremity symptoms	Change in lower extremity symptoms measured using the Lymphedema Quality of Life Questionnaire (LYMQOL) total score between 2 timepoints (baseline and end of study).	Up to 7 months
Change in psychological distress	Change in psychological distress measured using the General Health Questionnaire (GHQ-28) total score between 2 timepoints (baseline and end of study).	Up to 7 months
Change in quality of life	Change in quality of life measured using the Short Form Health Survey (SF-36) total score between 2 timepoints (baseline and end of study).	Up to 7 months
Change in pain intensity in the legs	Change in pain intensity assessed using the Visual Analogue Scale (VAS) between 2 timepoints (baseline and end of study). Pain intensity is measured using the VAS, a 10-cm scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. Higher scores indicate greater pain intensity.	Up to 7 months
Change in leptin concentration	Change in serum leptin concentration [ng/ml] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in adiponectin concentration	Change in serum adiponectin concentration [ng/ml] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in resistin concentration	Change in serum resistin concentration [pg/ml] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in vaspin concentration	Change in serum vaspin concentration [pg/ml] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in visfatin concentration	Change in serum visfatin concentration [ng/ml] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in TNF-α concentration	Change in serum tumor necrosis factor-alpha (TNF-α) concentration measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in IL-1β concentration	Change in serum interleukin-1 beta (IL-1β) concentration measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in IL-8 concentration	Change in serum interleukin-8 (IL-8) concentration measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in IL-10 concentration	Change in serum interleukin-10 (IL-10) concentration measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in IL-13 concentration	Change in serum interleukin-13 (IL-13) concentration measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in CRP concentration	Change in serum C-reactive protein (CRP) concentration measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in TBARS concentration	Change in serum thiobarbituric acid reactive substances (TBARS) concentration [µmol/l] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in 8-iso-prostaglandin F2α concentration	Change in serum 8-iso-prostaglandin F2α concentration [pg/mL] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in protein carbonyl content	Change in serum protein carbonyl content [nmol/mg protein] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in total antioxidant capacity	Change in serum total antioxidant capacity (TAC) [mmol Trolox eqiv./l] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in SOD activity	Change in serum superoxide dismutase (SOD) [U/ml] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in CAT activity	Change in serum catalase (CAT) [U/ml] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in vitamin C concentration	Change in serum vitamin C concentration [µmol/l] measured between 2 timepoints (baseline and end of study).	Up to months
Change in vitamin A concentration	Change in serum vitamin A concentration [µmol/l] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in vitamin E concentration	Change in serum vitamin E concentration [µmol/l] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in VEGF-A concentration	Change in serum and subcutaneous tissue VEGF-A concentration [pg/mL] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in VEGF-C concentration	Change in serum and subcutaneous tissue VEGF-C concentration [pg/mL] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in VEGF-D concentration	Change in serum and subcutaneous tissue VEGF-D concentration [pg/mL] measured between 2 timepoints (baseline and end of study).	Up to months
Change in angiopoietin-2 concentration	Change in serum and subcutaneous tissue angiopoietin-2 concentration [pg/mL] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in sICAM-1 concentration	Change in serum and subcutaneous tissue soluble ICAM-1 (sICAM-1) concentration [ng/mL] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in sVCAM-1 concentration	Change in serum and subcutaneous tissue soluble VCAM-1 (sVCAM-1) concentration [ng/mL] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in P-selectin concentration	Change in serum and subcutaneous tissue p-selectin concentration [pg/mL] measured between 2 timepoints (baseline and end of study).	Up to 7 months
Change in eicosanoids concentrations	Change in serum/plasma concentrations of selected eicosanoids measured between 2 timepoints (baseline and end of study) using targeted metabolomics (ng/mL): 13,14-dihydro Prostaglandin E1 [ng/mL]; 15-deoxy-Δ12,14-Prostaglandin J2 [ng/mL]; Prostaglandin D2 [ng/mL]; Prostaglandin E2 [ng/mL]; 6-keto Prostaglandin F1α [ng/mL]; Prostaglandin F2α [ng/mL]; Leukotriene B4 [ng/mL]; Thromboxane B2 [ng/mL]	Up to 7 months
Change in endocannabinoids concentrations	Change in serum/plasma concentrations of selected endocannabinoids concentrations measured between 2 timepoints (baseline and end of study) using targeted metabolomics (ng/mL): Arachidonoyl ethanolamide (AEA) [ng/mL]; Oleoyl ethanolamide (OEA) [ng/mL]; Palmitoyl ethanolamide (PEA) [ng/mL]; 1-Arachidonoyl glycerol (1-AG) [ng/mL]; 2-Arachidonoyl glycerol (2-AG) [ng/mL]	Up to 7 months
Change in nitric oxide metabolites concentrations	Change in serum/plasma concentrations of selected nitric oxide metabolites concentrations measured between 2 timepoints (baseline and end of study) using targeted metabolomics (µmol/L): asymmetric dimethylargininine (ADMA); symmetric dimethylargininine (SDMA)	Up to 7 months

Collaborators and Investigators

• Sponsor: Wroclaw Medical University

Study record dates

Study Major Dates

• Study Start (Actual): February 20, 2020
• Primary Completion (Actual): December 22, 2022
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: March 30, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: inflammation; angiogenesis; ketogenic diet; personalized nutrition; metabolomics; lipedema; lymphatic function
• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Overnutrition; Body Weight; Connective Tissue Diseases; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Signs and Symptoms; Overweight; Obesity; Inflammation; Lipedema; Diet, Food, and Nutrition; Physiological Phenomena; Nutritional Physiological Phenomena; Diet
• Other Study ID Numbers: WroclawMJ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All data used to support the findings of this study are available from the corresponding author upon reasonable request due to the privacy of patients.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No