An Update on Statin Alternatives and Adjuncts

Matthew J Sorrentino

Disclosures

Clin Lipidology. 2012;7(6):721-730. 

In This Article

Dietary Approach

A correlation between the intake of dietary fat and the incidence of coronary heart disease has been observed in multiple population studies.[11] Very low-fat diets have been advocated to lower serum cholesterol levels. A very low-fat diet is defined as a diet in which ≤15% of total calories are derived from fat. This would correlate to 33 g of fat for a 2000 calorie diet. Adhering to a very low-fat diet has been shown to reduce LDL-C by 10–20%.[12] The reduction in LDL-C is attributed to a decrease in saturated fat in the diet. Most very low-fat diets are vegetarian-type diets.

The Lifestyle Heart Trial combined a very low-fat diet (10% fat) with intensive lifestyle changes, including aerobic exercise, stress management, smoking cessation and group psychosocial support for 5 years, in selected individuals with coronary artery disease.[13] At 1 year, LDL-C decreased by 40%. In addition, the study documented more regression of coronary atherosclerosis and fewer clinical cardiovascular events in the very low-fat group compared with a control group of patients.

Adherence to a very low-fat diet can be difficult for most patients. The NCEP Adult Treatment Panel III has advocated a normal-fat diet (25–35% of total calories), but with reduced saturated fats of <7% of calories and of cholesterol <200 mg/day.[14] In addition, it was recommended to enhance LDL-C lowering by adding 2 g/day of plant stanols and sterols, and increasing soluble fiber to 10–25 g/day.

The Portfolio diet studies were designed to determine whether a diet containing all the recommended food components by the NCEP can significantly lower LDL-C. The Portfolio diet is a vegetarian-type diet. The initial study randomized 46 hyperlipidemic individuals to either a low-saturated fat diet (control), the same diet plus lovastatin 20 mg/day (statin) or a Portfolio diet – high in plant sterols (1 g/1000 kcal) soy protein (21.4 g/1000 kcal), soluble fiber (9.8 g/1000 kcal) and almonds (14 g/1000 kcal).[15] During the 4-week study period, the diets were provided to the participants. The control, statin and portfolio-diet groups had a mean LDL-C reduction of 8.0, 30.9 and 28.6%, respectively. This study suggested that adherence to the NCEP therapeutic lifestyle diet can achieve the same degree of LDL-C lowering as using a starting-dose statin medication.

Patients using a dietary approach to lipid lowering can have difficulty maintaining ongoing strict adherence to the diet. The Portfolio study group followed-up the original study with a 6-month dietary advice study of 351 participants instead of a protocol where the diet was given to the individuals.[16] The participants in the study received dietary advice regarding a low-saturated fat diet (control) or the portfolio diet, emphasizing the incorporation of plant sterols, soy protein, soluble fiber and nuts into the diet. LDL-C reductions were 13.8% for the portfolio diet compared with 3.0% for the control diet. More frequent dietary advice to a subset of participants did not achieve further LDL-C reduction. Although this study showed that dietary advice over a 6-month period can achieve a significant reduction in LDL-C, the degree of lipid lowering is less than can be expected with a statin medication.

Dietary therapy can be useful as adjunctive therapy to medication. The combination of a low-dose or an intermittent dosing statin, and strict adherence to a low-saturated fat diet, may allow patients to achieve their LDL-C goals, while limiting toxicity from the drug therapy. The combination of a very low-fat diet (Pritikin diet with <10% calories from total fat) with background statin therapy added an additional 19% total cholesterol reduction on top of the 20% reduction already achieved by the statin therapy.[17]

The portfolio diet added soy protein as the major protein source, replacing animal protein in the diet. A number of studies suggest that replacing animal protein with soy protein can reduce LDL-C and total cholesterol. A meta-analysis of 38 controlled clinical trials indicated that an average soy protein intake of 47 g/day lowered total cholesterol by approximately 9% and LDL-C 13%.[18]

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