Changes in plasma fatty acid composition in females with lipedema following low-carbohydrate vs low-fat diets and associations with pain reduction

Journal article, 2026

Background Lipedema is a chronic female disease characterized by a painful accumulation of adipose tissue in the limbs. Plasma fatty acid (FA) composition has been proposed as a potential modulator of pain. However, the pathophysiology behind lipedema pain remains uncertain. The primary objective of this secondary analysis was to compare changes in plasma concentrations of FAs between low-energy diets either low in carbohydrates or low in fat, in females with lipedema and obesity. A secondary objective was to investigate potential associations between changes in pain and changes in the concentration of several FAs.

Methods Females with lipedema and obesity (BMI 30–45 kg/m2) were randomized to isocaloric low-energy diets, either low-carbohydrate diet (LCD) or low-fat diet for 8 weeks. Plasma concentrations of FAs were quantified using gas chromatography and subjective pain using the Brief Pain Inventory, before and after the intervention.

Results 70 females were included in the analyses, with a mean BMI of 37 ± 5 kg/m2 and mean age of 47 ± 11 years. Significant decreases in the concentration of the saturated FAs (SFAs) myristic, stearic, and behenic acids, and the polyunsaturated FAs (PUFA) gamma-linolenic (GLA), dihomo-gamma-linolenic (DGLA), alpha-linolenic (ALA), eicosapentaenoic (EPA), and docosapentaenoic acids (DPA) were seen in both groups. A reduction in the SFA arachidic acid, and the monounsaturated FAs (MUFA) palmitoleic and oleic acids was seen in the LCD group only, while an increase in the SFA lignoceric acid and a decrease in the PUFA linoleic acid was seen only the low-fat diet group. Changes in myristic and palmitic acids (SFAs) were positively associated with changes in pain.

Conclusion A reduction in most FAs was found after energy restricted LCD and low-fat diets in females with lipedema and obesity. Notably, reductions in SFAs seem to be associated with the reduction in pain seen in the LCD group, especially myristic acid. These findings suggest that FA composition may play a role in pain reduction in females with lipedema.

Trial registration NCT04632810, Effect of Ketosis on Pain and Quality of Life in Patients With Lipedema (Lipodiet).