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NCT Number: NCT07530341

Ketogenic Diet 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.

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Key information

Conditions

Lipedema Body Weight Connective Tissue Diseases Inflammation Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Overweight and Obesity Pathologic Processes Pathological Conditions, Signs and Symptoms Signs and Symptoms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Wroclaw Medical University

Wroclaw, Lower Silesian Voivodeship, 50-367, Poland

About this study

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:

  • 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
  • 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)
  • 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
  • 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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Low carbohydrate high fat (ketogenic) diet with anti-inflammatory properties

Behavioral

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.

Primary outcomes

  1. Change in leg circumferences

    Time frame: Up to 7 months

    Changes in leg circumferences between 2 timepoints (baseline and end of study)

Secondary outcomes

  1. Change in body weight

    Time frame: Up to 7 months

    Change in body weight in kilograms measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).

  2. Change in body fat

    Time frame: Up to 7 months

    Change in body fat percentage (%) measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).

  3. Change in lean body mass

    Time frame: Up to 7 months

    Change in lean body mass in kilograms measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).

  4. Change in body water

    Time frame: Up to 7 months

    Change in body water in kilograms measured using bioelectrical impedance analysis between 2 timepoints (baseline and end of study).

  5. Change in visceral fat level

    Time frame: Up to 7 months

    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).

  6. Change in disability level

    Time frame: Up to 7 months

    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).

  7. Change in depressive symptoms

    Time frame: Up to 7 months

    Change in depressive symptoms measured using the Beck Depression Inventory-II (BDI-II) total score between 2 timepoints (baseline and end of study).

  8. Change in anxiety and depression symptoms

    Time frame: Up to 7 months

    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).

  9. Change in lower extremity symptoms

    Time frame: Up to 7 months

    Change in lower extremity symptoms measured using the Lymphedema Quality of Life Questionnaire (LYMQOL) total score between 2 timepoints (baseline and end of study).

  10. Change in psychological distress

    Time frame: Up to 7 months

    Change in psychological distress measured using the General Health Questionnaire (GHQ-28) total score between 2 timepoints (baseline and end of study).

  11. Change in quality of life

    Time frame: Up to 7 months

    Change in quality of life measured using the Short Form Health Survey (SF-36) total score between 2 timepoints (baseline and end of study).

  12. Change in pain intensity in the legs

    Time frame: Up to 7 months

    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.

  13. Change in leptin concentration

    Time frame: Up to 7 months

    Change in serum leptin concentration [ng/ml] measured between 2 timepoints (baseline and end of study).

  14. Change in adiponectin concentration

    Time frame: Up to 7 months

    Change in serum adiponectin concentration [ng/ml] measured between 2 timepoints (baseline and end of study).

  15. Change in resistin concentration

    Time frame: Up to 7 months

    Change in serum resistin concentration [pg/ml] measured between 2 timepoints (baseline and end of study).

  16. Change in vaspin concentration

    Time frame: Up to 7 months

    Change in serum vaspin concentration [pg/ml] measured between 2 timepoints (baseline and end of study).

  17. Change in visfatin concentration

    Time frame: Up to 7 months

    Change in serum visfatin concentration [ng/ml] measured between 2 timepoints (baseline and end of study).

  18. Change in TNF-α concentration

    Time frame: Up to 7 months

    Change in serum tumor necrosis factor-alpha (TNF-α) concentration measured between 2 timepoints (baseline and end of study).

  19. Change in IL-1β concentration

    Time frame: Up to 7 months

    Change in serum interleukin-1 beta (IL-1β) concentration measured between 2 timepoints (baseline and end of study).

  20. Change in IL-8 concentration

    Time frame: Up to 7 months

    Change in serum interleukin-8 (IL-8) concentration measured between 2 timepoints (baseline and end of study).

  21. Change in IL-10 concentration

    Time frame: Up to 7 months

    Change in serum interleukin-10 (IL-10) concentration measured between 2 timepoints (baseline and end of study).

  22. Change in IL-13 concentration

    Time frame: Up to 7 months

    Change in serum interleukin-13 (IL-13) concentration measured between 2 timepoints (baseline and end of study).

  23. Change in CRP concentration

    Time frame: Up to 7 months

    Change in serum C-reactive protein (CRP) concentration measured between 2 timepoints (baseline and end of study).

  24. Change in TBARS concentration

    Time frame: Up to 7 months

    Change in serum thiobarbituric acid reactive substances (TBARS) concentration [µmol/l] measured between 2 timepoints (baseline and end of study).

  25. Change in 8-iso-prostaglandin F2α concentration

    Time frame: Up to 7 months

    Change in serum 8-iso-prostaglandin F2α concentration [pg/mL] measured between 2 timepoints (baseline and end of study).

  26. Change in protein carbonyl content

    Time frame: Up to 7 months

    Change in serum protein carbonyl content [nmol/mg protein] measured between 2 timepoints (baseline and end of study).

  27. Change in total antioxidant capacity

    Time frame: Up to 7 months

    Change in serum total antioxidant capacity (TAC) [mmol Trolox eqiv./l] measured between 2 timepoints (baseline and end of study).

  28. Change in SOD activity

    Time frame: Up to 7 months

    Change in serum superoxide dismutase (SOD) [U/ml] measured between 2 timepoints (baseline and end of study).

  29. Change in CAT activity

    Time frame: Up to 7 months

    Change in serum catalase (CAT) [U/ml] measured between 2 timepoints (baseline and end of study).

  30. Change in vitamin C concentration

    Time frame: Up to months

    Change in serum vitamin C concentration [µmol/l] measured between 2 timepoints (baseline and end of study).

  31. Change in vitamin A concentration

    Time frame: Up to 7 months

    Change in serum vitamin A concentration [µmol/l] measured between 2 timepoints (baseline and end of study).

  32. Change in vitamin E concentration

    Time frame: Up to 7 months

    Change in serum vitamin E concentration [µmol/l] measured between 2 timepoints (baseline and end of study).

  33. Change in VEGF-A concentration

    Time frame: Up to 7 months

    Change in serum and subcutaneous tissue VEGF-A concentration [pg/mL] measured between 2 timepoints (baseline and end of study).

  34. Change in VEGF-C concentration

    Time frame: Up to 7 months

    Change in serum and subcutaneous tissue VEGF-C concentration [pg/mL] measured between 2 timepoints (baseline and end of study).

  35. Change in VEGF-D concentration

    Time frame: Up to months

    Change in serum and subcutaneous tissue VEGF-D concentration [pg/mL] measured between 2 timepoints (baseline and end of study).

  36. Change in angiopoietin-2 concentration

    Time frame: Up to 7 months

    Change in serum and subcutaneous tissue angiopoietin-2 concentration [pg/mL] measured between 2 timepoints (baseline and end of study).

  37. Change in sICAM-1 concentration

    Time frame: Up to 7 months

    Change in serum and subcutaneous tissue soluble ICAM-1 (sICAM-1) concentration [ng/mL] measured between 2 timepoints (baseline and end of study).

  38. Change in sVCAM-1 concentration

    Time frame: Up to 7 months

    Change in serum and subcutaneous tissue soluble VCAM-1 (sVCAM-1) concentration [ng/mL] measured between 2 timepoints (baseline and end of study).

  39. Change in P-selectin concentration

    Time frame: Up to 7 months

    Change in serum and subcutaneous tissue p-selectin concentration [pg/mL] measured between 2 timepoints (baseline and end of study).

  40. Change in eicosanoids concentrations

    Time frame: Up to 7 months

    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]

  41. Change in endocannabinoids concentrations

    Time frame: Up to 7 months

    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]

  42. Change in nitric oxide metabolites concentrations

    Time frame: Up to 7 months

    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)

Sponsors and collaborators

Lead sponsor

Wroclaw Medical University

Other

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2022
Study completion
2023
First posted
Apr 15, 2026
Registry last updated
Apr 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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