Testing
Cutting dietary saturated fat raises Lp(a) levels and reshapes its lipid composition, not just its concentration, two DELTA feeding trials find (Nutrients 2025)
Original title: Lipoprotein(a) Lipidome: Responses to Reduced Dietary Saturated Fat Intake in Two Randomized Controlled Feeding Trials
This analysis combined two multicenter, randomized, controlled, crossover feeding trials, DELTA 1 (96 healthy individuals) and DELTA 2 (79 metabolically challenged individuals), both of which had previously shown that reducing dietary saturated fat significantly raises Lp(a) levels, to test whether this dietary shift also changes the Lp(a) particle's own composition, including its oxidised phospholipid (OxPL) cargo. No between-diet differences emerged for total Lp(a)-OxPL or four major OxPL subspecies in DELTA 1, but one subspecies, ALDOPC, decreased significantly in DELTA 2 when saturated fat was replaced with carbohydrates (P = 0.014). Of 440 lipid species profiled in the Lp(a) lipidome, 87 differed significantly between diets (P < 0.05, adjusted), with triacylglycerol species showing the most pronounced diet-driven changes, particularly those with more carbon atoms and double bonds increasing most with saturated fat reduction. Alongside the known rise in plasma Lp(a) concentration, saturated fat reduction also reshapes the particle's lipid composition, showing Lp(a) is more dynamic and diet-responsive than its genetic determination would suggest.
Original abstract
Background/Objectives: An elevated level of lipoprotein(a) [Lp(a)] is a genetically determined risk factor for cardiovascular disease. The atherogenic properties of Lp(a) include attribution to its role as a carrier of oxidized phospholipids (OxPL). Despite genetic control, Lp(a) levels increase with dietary saturated fat (SFA) reduction. However, little is known about the impact of dietary factors on Lp(a) risk properties. Methods: We assessed total Lp(a)-OxPL concentration, Lp(a)-OxPL subspecies abundance, and Lp(a) lipidomics in response to SFA reduction in two multicenter, randomized, controlled, crossover feeding trials, DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) 1 (96 healthy individuals) and 2 (79 metabolically challenged individuals). In both trials, significant increases in Lp(a) levels were reported previously. Results: While no between-diet differences in the concentrations of total Lp(a)-OxPL and four major OxPL subspecies (ALDOPC, POVPC, PAzPC, and PGPC) were observed in DELTA 1, ALDOPC decreased significantly in DELTA 2 when SFA was replaced with carbohydrates (p = 0.014). Of 440 individual lipid species annotated in an untargeted analysis of the Lp(a) lipidome, 87 lipids differed significantly (p < 0.05 adjusted for multiplicity) between diets, with triacylglycerol species showing the most pronounced changes in both trials. For all intervention diets, triacylglycerol species with a higher average number of carbon atoms and double bonds increased the most in abundance with SFA reduction. Conclusions: In parallel with an increase in plasma Lp(a) levels, significant changes in Lp(a) lipid composition occurred. The findings demonstrate the dynamic nature of intraindividual Lp(a) lipid composition in response to diet interventions.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.