Weight Loss May Suppress Cholesterol Synthesis

Nutrition Research Newsletter, Sept, 1999 by Marco di Buono, Judy S. Hannah, Leslie I. Katzel, Peter J. H. Jones

Both obesity and elevated cholesterol levels are major risk factors for cardiovascular disease. A 10% reduction in weight in men corresponds to a ~20% reduction in coronary heart disease incidence, which includes a reduction in circulating lipid levels. The mechanism through which weight loss decreases lipid levels remains unclear.

Besides outside dietary sources, the body cholesterol pools receive approximately 2/3 of their input from de novo cholesterol synthesis. However, this production of cholesterol within the body has been overlooked as a possible CVD risk factor in obese subjects. A recent Canadian study was designed to evaluate the effects of weight loss on in vivo circulating cholesterol concentrations and synthesis among middle-aged men with mildly elevated cholesterol levels.

Six subjects, 64-77 years old, were recruited for this nine-month, two-phase prospective trial. During the first three months, the subjects were expected to follow the American Heart Association Step I diet, with the target intakes being 55%, 15%, and 30% of calories from carbohydrate, protein, and fat, respectively. The men were educated on the diet by a registered dietitian, who also advocated that fat be consumed in the form of 8%, 10%, and 12% of calories from saturated, polyunsaturated, and monounsaturated fats, respectively. The subjects were to follow this diet with no change in regular energy intake and were asked not to exercise in activity that would expend greater than 400 calories per activity. Immediately following this first phase, the men were placed on a six-month energy-restricted AHA step I diet, which would achieve a weight loss of 8 kg over this time period. Plasma lipid levels were taken during each phase, while the incorporation rate of deuterium from body water was utilized as an index of cholesterol synthesis.

Weight loss was achieved during phase II, with losses ranging from 3-8 kg. BMI and body fat also decreased. Mean total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides all significantly decreased, while HDL cholesterol (HDL-C) did not change, as compared with lipid levels in phase I. Cholesterol fractional synthesis rate (FSR), which represents the fraction of the tree portion of the central cholesterol pool that is synthesized within 24 hours, and absolute synthesis rate (ASR) were also significantly reduced in all subjects after weight loss.

The findings of this study, which indicate improvement in lipid profiles after weight loss, were similar to other studies on this topic. However, the results also show that weight loss achieved through energy restriction alone results in lipid level reductions along with a substantial decrease in cholesterol synthesis. This new exciting information is consistent with sterol balance methods, which have shown that obese individuals synthesize almost twice as much cholesterol per kilogram body weight as do non-obese individuals. In addition, decreasing cholesterol de novo synthesis may offer other beneficial effects in the prevention of CVD. A depression in cholesterol synthesis ultimately leads to a decrease in smooth muscle cell migration and proliferation, which have been implicated in atherogenesis.

Marco di Buono, Judy S. Hannah, Leslie I. Katzel and Peter J. H. Jones, Weight Loss Due to Energy Restriction Suppresses Cholesterol Biosynthesis in Overweight, Mildly Hypercholesterolemic Men, J Nutr, 129: 1545-1548 (August 1999) [Correspondence: Peter J. H. Jones, School of Dietetics and Human Nutrition, Macdonald Campus of McGill University, Ste-Anne-de-Bellevue, Quebec, PQ H9X 3V9, Canada.]