The purpose of this study was to evaluate the differences that occur within the plasma compartment of normolipidemic men, classified on the basis of their response to prolonged consumption of additional dietary cholesterol. Using a crossover design, 40 men aged 18-57 y were randomly allocated to an egg (640 mg/d additional dietary cholesterol) or placebo group (0 mg/d additional dietary cholesterol), for two 30-d periods, which were separated by a 3-wk washout period. Subjects were classified as hypo- [increase in plasma total cholesterol (TC) of <0.05 mmol/L for each additional 100 mg of dietary cholesterol consumed] or hyperresponders (increase in TC of > or =0.06 mmol/L for each additional 100 mg of dietary cholesterol consumed) on the basis of their plasma reaction to the additional dietary cholesterol provided. Male hyporesponders did not experience an increase in LDL cholesterol (LDL-C) or HDL cholesterol (HDL-C) during the egg period, whereas both lipoproteins were significantly (P < 0.0001 and P < 0.05, respectively) elevated in hyperresponders. Although the LDL/HDL ratio was increased in male hyperresponders after the high cholesterol period, the mean increase experienced by this population was still within National Cholesterol Education Program guidelines. Furthermore, male hyperresponders had higher lecithin cholesterol acyltransferase (P < 0.05) and cholesteryl ester transfer protein (P < 0.05) activities during the egg period, which suggests an increase in reverse cholesterol transport. These data suggest that additional dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in healthy men, regardless of their response classification.

These data revealed that excess dietary cholesterol does not increase the risk of developing an atherogenic lipoprotein profile in pre-menopausal women, regardless of their response classification. Although the addition of 640 mg of cholesterol to the diet did result in an increase in plasma cholesterol in hyperresponders, the LDL/HDL ratio was maintained. This result, accompanied by increases in CETP activity, leads to the speculation that hyper-responders may process the excess cholesterol in the plasma compartment through an enhancement of the reverse cholesterol transport pathway. With this mechanism identified, further measurement of additional parameters is needed to verify this conclusion.

Despite being considered a good or excellent source of 11 nutrients (1), egg intake accounted for only 1.3% of the total energy consumed by the average American in 2000 (2). The perception of cholesterol-rich eggs as a "forbidden food" developed in response to the highly publicized 1970s recommendation by the American Heart Association (AHA) to restrict

Waist circumference (WC) has been postulated to have stronger associations with biomarkers of coronary heart disease (CHD) than BMI. In this study, we measured the level of activity by determining steps walked per day and select biomarkers for CHD risk in 80 overweight or obese (BMI = 25-37 kg/m(2)) premenopausal women to evaluate whether these biomarkers are associated with WC or BMI. The plasma biomarkers measured, using samples from women who had fasted for 12 h, were lipids, apolipoproteins (apo), LDL peak diameter, LDL susceptibility to oxidation, glucose, leptin, and insulin. We identified subjects with the metabolic syndrome (11%) and insulin resistance (30%) to further distinguish subjects at increased risk for CHD. Both BMI and WC were positively correlated with insulin (r = 0.376 and 0.384, respectively, P < 0.05) and leptin (r = 0.614 and 0.512, respectively, P < 0.01) and negatively correlated with the number of steps taken per day (r = -0.245 and -0.354, respectively, P < 0.05). In addition, WC had positive correlations with diastolic blood pressure (r = 0.250, P < 0.05), plasma triglycerides (TG) (r = 0.270, P < 0.05), and apo C-III (r = 0.240, P < 0.05). Women with BMI > or = 30 kg/m(2) or WC > 88 cm had significantly higher leptin concentrations than women having a BMI < 30 kg/m(2) or a WC < or = 88 cm; women with WC > 88 cm also had higher diastolic pressure (P < 0.05), and higher plasma TG (P < 0.05) and apo C-III (P < 0.05) concentrations than those with WC < or = 88. In addition, subjects with the higher WC walked an average of 1000 fewer steps per day (P < 0.01). These results suggest that WC is a stronger predictor of CHD risk than BMI and is more closely associated with the level of exercise in premenopausal women.

The ATP binding cassette G5 (ABCG5) polymorphisms have been postulated to play a role in the response to dietary cholesterol. The objective of this study was to examine the contribution of the ABCG5 polymorphism on the plasma response to consumption of cholesterol and carotenoids from eggs. For this purpose, genotyping was conducted for 40 men and 51 premenopausal women who were randomly assigned to consume an egg (EGG, 640 mg/d additional dietary cholesterol and 600 microg lutein+ zeaxanthin) or placebo (SUB, 0 mg/d cholesterol, 0 microg lutein + zeaxanthin) diet for 30 d. The two arms of the dietary intervention were separated by a 3-wk washout period. Plasma concentrations of total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol were determined. Because eggs are an excellent source of lutein and zeaxanthin, the plasma levels of these carotenoids were also measured in a subset of subjects to determine whether the response to carotenoid intake was similar to that seen for dietary cholesterol and to evaluate the contribution of ABCG5 polymorphism to both responses. Individuals possessing the C/C genotype experienced a greater increase in both LDL-C (P < 0.05) and a trend for lutein (P = 0.08) during the EGG period compared with those individuals with the C/G (heterozygote) or G/G genotypes (homozygotes). These results, although obtained from a small number of subjects, suggest that the ABCG5 polymorphism may play a role in the plasma response to dietary cholesterol and carotenoids.