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.

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).

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