The typical small size of clinical nutrition studies has far-reaching effects. Because these studies are expensive and require great commitments of labor and space, it generally is very difficult for a single investigator funded by a traditional research grant to enroll, feed, and study more than 20 to 25 participants at one time. This imposes constraints on duration, design, and statistical power; consequently, many human nutrition studies lack sufficient power to detect biologically meaningful differences between groups or treatments. To avoid outside sources of variability that would further reduce study power, investigators usually make efforts to assemble a 'homogeneous' study population and minimize the number of factors that might impinge on the experimental design; thus, studies are most often conducted in young Caucasian males with average or even low plasma cholesterol levels. Not much is known, therefore, about how response to diet is affected by sex, age, race, co-morbid conditions (such as obesity), lipoprotein phenotype and other factors that would make the results more generalizable to the population at large. Furthermore, the mechanisms underlying the so-called 'hypo-responder' phenomenon, wherein individuals are presumed to be insensitive to the effects of diet on plasma lipid levels, cannot be elucidated unless individuals with a wide range of response are studied in adequate numbers.