Changes in Cytokines and Fibrotic Growth Factors after Low-Carbohydrate or Low-Fat Low-Energy Diets in Females with Lipedema

Julianne Lundanes; Vilde Fiske Nes; Oda Aakervik; Liv Ryan; Patrik Hansson; Anne Mari Rokstad; Catia Martins; Siren Nymo

doi:10.1016/j.cdnut.2025.104571

Changes in Cytokines and Fibrotic Growth Factors after Low-Carbohydrate or Low-Fat Low-Energy Diets in Females with Lipedema

Curr Dev Nutr. 2025 Feb 20;9(3):104571. doi: 10.1016/j.cdnut.2025.104571. eCollection 2025 Mar.

Authors

Julianne Lundanes^{1

2}, Vilde Fiske Nes³, Oda Aakervik^{2

4}, Liv Ryan¹, Patrik Hansson^{3

5}, Anne Mari Rokstad¹, Catia Martins⁶, Siren Nymo^{2

7

8}

Affiliations

¹ Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
² Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway.
³ Clinical Nutrition Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
⁴ Centre for Nutrition, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
⁵ Department of Food and Nutrition and Sport Science, University of Gothenburg, Gothenburg, Sweden.
⁶ Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, United States.
⁷ Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
⁸ Centre for Obesity and Innovation, Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway.

Abstract

Background: Lipedema is considered an inflammation-related disease, and low-carbohydrate ketogenic diets may help reduce inflammation. However, no randomized controlled trials have investigated the effect of a low-carbohydrate ketogenic diet on inflammatory markers in females with lipedema.

Objectives: To compare changes in inflammatory and fibrosis-associated markers after a low-energy low-carbohydrate diet (LCD) compared with a low-fat diet in females with lipedema, and to explore potential associations between changes in pain and changes in inflammatory and fibrosis-associated markers.

Methods: Females with lipedema and obesity were randomly assigned to either an LCD or low-fat diet (both 1200 kcal/d) for 8 weeks. Body composition [fat mass (FM) and fat-free mass] and the plasma concentrations of high-sensitivity C-reactive protein (hsCRP), cytokines, and fibrosis-associated markers were measured pre- and postintervention.

Results: A total of 70 females were included (35/group) (mean age: 47.3 ± 10.9 y, BMI: 36.9 ± 4.9 kg/m²). Both groups lost weight and FM (kg and %), with a greater reduction in the LCD group. A reduction in macrophage inflammatory protein-1ß, tumor necrosis factor-α, and hsCRP was seen in the LCD group only, despite no significant differences between groups. No associations were found between changes in pain and changes in cytokines and fibrosis-associated markers.

Conclusions: Changes in cytokines and fibrosis-associated markers did not differ between low-energy LCD and low-fat diets in females with lipedema, despite a beneficial profile in the LCD group. Inflammation does not seem to be involved in pain reduction following LCD in this patient group.

Trial registration number: This trial was registered at clinicaltrials.gov as NCT04632810.

Keywords: CRP; TNF; inflammation; ketogenic diet; weight loss.

Associated data

ClinicalTrials.gov/NCT04632810