An Isocaloric High Saturated Fat Diet Increases Endogenous Cholesterol Production Which is Reversed by a Protein-Enriched Diet in Normal-Weight Humans

Lathosterol is a marker of endogenous cholesterol synthesis whereas plant sterols (e. g. campesterol) reflect cholesterol absorption. Obesity and type 2 diabetes mellitus are associated with increased endogenous cholesterol production and decreased cholesterol absorption. Only few studies evaluated cholesterol homeostasis under isocaloric nutritional conditions. This study investigated endogenous cholesterol production in healthy humans after consumption of isocaloric diets enriched with carbohydrates (KH) or saturated fat (HF) or protein (HP). 24 normal weight participants (women and men, age 18 - 70) were investigated for 18 weeks. An isocaloric diet rich in carbohydrates (55% carbohydrates, 30% fat, 15% protein, KH) was applied followed by an isocaloric diet rich in saturated fat (40% carbohydrates, 45% fat, 15% protein, HF) and finally followed by an isocaloric diet enriched with proteins (45% carbohydrates, 30% fat, 25% protein, HP); each for 6 weeks. Body weight (BW), serum total and LDL cholesterol and serum lathosterol and campesterol levels were analyzed after the KH period, after one week (HF1) and 6 weeks (HF6) of the HF and after the HP period. BW did not change during the study. Serum total and LDL cholesterol increased from 4.38±0.2 and 2.74±0.2 mmol/L, respectively at KH to 4.82±0.2 and 2.97±0.2 mmol/L, respectively at HF6 (both P<0.01) and were decreased back to KH levels at HP. Serum lathosterol levels increased 1.26-fold and 1.16-fold, respectively at HF1 and HF6 (P<0.05 compared to LF), however decreased by 10.1% at HP (compared to KH levels, P<0.05). Serum campesterol levels moderately decreased at HF1 and HF6 and were restored to KH levels at HP (P<0.01 compared to HF6). These data show that composition of macronutrients are responsible for diet induced elevation of serum cholesterol levels due to an increased endogenous cholesterol production in normal weight humans regardless of the energy content of the diet. Disclosure M.Kruse: None. S.Matysik: None. D.Hoffmann: None. T.Frahnow: None. A.F.Pfeiffer: Advisory Panel; Abbott Diabetes, Speaker's Bureau; Novo Nordisk, Sanofi-Aventis Deutschland GmbH. Funding German Federal Ministry of Education and Research (0315424)