Greater than 50% of Americans use some form of a dietary supplement, and a diagnosis of coronary artery disease is associated with higher supplement use. The objective of this study was to compare nutritional supplements (pectin, polyphenols, and phytosterols) to lovastatin to reduce serum cholesterol. Familial hypercholesterolemic (FH) swine received the same amount of basal diet (control) in addition to pectin (30 g/day), polyphenols (20 g/day), phytosterols (6 g/day), and all possible combinations in contrast to lovastatin (3 mg/kg of body weight). The experimental design consisted of 4 weeks of basal diet followed by 4 weeks of basal diet plus the supplement treatment. All of the supplements, except pectin, reduced total cholesterol by an average of 71 +/- 19 mg/dL in comparison to the control diet (53 +/- 20 mg/dL) and lovastatin (143 +/- 21 mg/dL) during the 5-8-week treatment period. Serum high-density lipoprotein-cholesterol remained unchanged, while serum triglycerides changed independent of diet. During the 5-8-week treatment period serum low-density lipoprotein (LDL)-cholesterol was reduced maximally 22%, 19%, 20%, 17%, 18%, and 17% by polyphenols, phytosterols, pectin + polyphenols, pectin + phytosterols, polyphenols + phytosterols, and pectin + polyphenols + phytosterols, respectively, compared to control (8%) and lovastatin (40%). Phytosterols was the most effective supplementation, while both phytosterol and polyphenol supplements enhanced the reduction in LDL-cholesterol of pectin-containing diets. Supplements effectively reduced cholesterol in FH swine by half compared to lovastatin. Results suggest that more research on the use of dietary supplements, alone or in combination with statins, to reduce LDL-cholesterol is justified.