The Dietary Reference Intakes for fiber are based on an association between a high-fiber diet and a reduced risk of cardiovascular disease. Only 5% of Americans consume the recommended levels of dietary fiber; most consume approximately half the recommended level. If a fiber supplement is used to achieve the recommended level, it is important that the isolated fiber has the requisite physical properties to reduce the risk of cardiovascular disease by lowering elevated serum low-density lipoprotein and total cholesterol. The current study was designed to directly assess the cholesterol-lowering effects of psyllium, a natural nonfermented viscous/gel-forming fiber, versus wheat dextrin, a semisynthetic, readily fermented nonviscous supplement. The study was a 3-month, randomized, parallel-group design (n = 20 enrolled) that assessed psyllium husk (3.4 g) and wheat dextrin (3.5 g) dosed 3 times a day before meals. The results showed that gel-forming psyllium significantly (P < .05) lowered both low-density lipoprotein cholesterol (−17%) and total cholesterol (−11%), without affecting high-density lipoprotein cholesterol, versus wheat dextrin. In conclusion, clinicians and consumers should be aware that the physical characteristics of a fiber supplement determine whether it will provide specific health benefits, and it is recommended to only take those fiber supplements with evidence of clinically meaningful health benefits from well-controlled clinical studies.