Background: Lipid lowering response to weight loss in subjects with genetic hyperlipidemias and overweight or obesity and its effect on cholesterol metabolism has not been studied.

Objective: To explore the effects of weight loss on lipid values and cholesterol metabolism, by measuring circulating non-cholesterol sterols, in overweight or obese subjects with genetic hypercholesterolemias.

Design: The investigators conducted a 6-months weight loss intervention in subjects with the diagnosis of familial hypercholesterolemia (FH) or familial combined hyperlipidemia (FCHL), body mass index >25 kg/m2, steady weight (±3 kg in the last 3 months) and absence of lipid lowering drugs in the previous 5 weeks. They were advised to follow a hypocaloric diet with a deficit of 600 kcal (30% fat, 15% protein, and 55% carbohydrates) per day as calculated from the person's resting energy expenditure and activity level. Anthropometric data, biochemical analysis including lipids, apolipoproteins and non-cholesterol sterols were evaluated at baseline, 3 months and 6 months.

Inclusion Criteria:

• Age ≥18 years.

• Diagnosis of Familial Combined Hyperlipidemia* and Familial Hypercholesterolemia**.

• Body mass index > 25 kg/m2.

• Steady weight (±3 kg in the last 3 months).

• Absence of lipid lowering drugs including sterols supplements in the previous 5 weeks.

  • Familial Combined Hyperlipidemia diagnosis was based on the presence of primary combined hyperlipidaemia in untreated patients whose serum cholesterol and triglyceride concentrations were above the sex- and age-specific 90th percentiles for the Spanish population, serum total apolipoprotein B concentration ≥ 120 mg/dL and there was at least one first-degree relative with hyperlipidemia (total cholesterol and/or triglycerides >90th percentile) (Gómez-Gerique JA et al; 1999).

    • Familial Hypercholesterolemia was diagnosed in subjects with off-treatment LDL cholesterol concentrations above the age- and sex-specific 95th percentile of a Spanish reference population, triglyceride below 200 mg/dL and familial vertical transmission with at least one first-degree relative with LDL cholesterol above age- and sex-specific 95th percentiles (Gómez-Gerique JA et al; 1999).

Exclusion Criteria:

• Alcohol consumption >30 gr/day.
• Uncontrolled type-2 diabetes (HbA1c >8%).
• Any other disease that could interfere with the ability to comply with the study protocol were excluded
• Personal history of cardiovascular disease, very high risk as defined by the presence of ≥ 2 major risk factors, or total cholesterol ≥ 350 mg/dL since lipid-lowering drug were considered highly recommended.