Mechanisms
A low-fat, high-carbohydrate diet raises Lp(a) alongside oxidized phospholipids and smaller LDL particles, a crossover trial of 63 healthy adults (J Lipid Res 2010)
Original title: Changes in lipoprotein(a), oxidized phospholipids, and LDL subclasses with a low-fat high-carbohydrate diet
This randomised crossover trial fed 63 healthy subjects a high-fat low-carbohydrate (HFLC) diet and a low-fat high-carbohydrate (LFHC) diet for 4 weeks each, in random order, to test whether LFHC-induced Lp(a) increases relate to oxidized phospholipid (OxPL) and LDL subclass changes. Compared with the HFLC diet, the LFHC diet significantly raised Lp(a) (P<0.01), OxPL/apoB (P<0.005), and OxPL-apo(a) (P<0.05), while LDL peak particle size became significantly smaller (P<0.0001). Diet-induced Lp(a) changes strongly correlated with OxPL/apoB changes (P<0.0001), and Lp(a) increases also correlated with decreases in medium LDL particles (P<0.01) and increases in very small LDL particles (P<0.05). The findings show a low-fat, high-carbohydrate diet raises Lp(a) alongside increased oxidized phospholipids and a shift toward smaller, denser LDL particles, suggesting altered Lp(a) particle metabolism.
Original abstract
Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)], a preferential lipoprotein carrier of oxidized phospholipids (OxPLs) in plasma, as well as small dense LDL particles. We sought to determine whether increases in plasma Lp(a) induced by a low-fat high-carbohydrate (LFHC) diet are related to changes in OxPL and LDL subclasses. We studied 63 healthy subjects after 4 weeks of consuming, in random order, a high-fat low-carbohydrate (HFLC) diet and a LFHC diet. Plasma concentrations of Lp(a) (P < 0.01), OxPL/apolipoprotein (apo)B (P < 0.005), and OxPL-apo(a) (P < 0.05) were significantly higher on the LFHC diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller (P < 0.0001). Diet-induced changes in Lp(a) were strongly correlated with changes in OxPL/apoB (P < 0.0001). The increases in plasma Lp(a) levels after the LFHC diet were also correlated with decreases in medium LDL particles (P < 0.01) and increases in very small LDL particles (P < 0.05). These results demonstrate that induction of increased levels of Lp(a) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a) particles.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.