Men with MetS consumed a pre-determined MedDiet under carefully controlled isoenergetic feeding conditions, after standardization of the participants’ diet on a control diet to minimize inter-individual variations in baseline apoA-I kinetics. We showed that 4–5 week short-term consumption of a MedDiet significantly reduced plasma apoA-I concentrations and pool size, but had no impact on average on plasma HDL-C concentrations. This is at odds with data from studies having shown that adherence to MedDiet principles was associated with improvements in HDL-C concentrations [15, 16]. However, adherence to MedDiet has also been associated with significantly lower body weight [15, 16], which is likely to have confounded the effect of the diet on HDL-C concentrations [17, 18]. Although consumption of the MedDiet had no impact on mean apoA-I FCR and plasma VLDL-TG concentrations, the individual HDL-C response to MedDiet in men with MetS appeared to be primarily determined by how apoA-I FCR and VLDL-TG concentrations were modified by the diet in each individual.
Consumption of the MedDiet vs. the control diet implied several changes in diet composition, including greater intakes of fibers, alcohol and MUFA and lower intakes of trans fatty acids (TFA) and SFA. Kinetic studies have shown that total dietary fat and/or SFA are associated with apoA-I PR (positively) and apoA-I FCR (negatively) [19, 20]. A high MUFA diet consumed ad libitum reduced apoA-I PS with no significant change in apoA-I PR and FCR . Consumption of trans fat has been shown to increase apoA-I FCR relative to a SFA rich diet in hypercholesterolemic women . Water-soluble fibers have been shown to reduce LDL-C without affecting HDL-C concentrations . Kinetic studies indicated that alcohol consumption increases plasma HDL-C and apoA-I concentrations mainly by increasing the PR of apoA-I [24, 25]. Thus, variations in apoA-I kinetics in response to MedDiet in the present study must be interpreted in light of all of these individual nutrient-specific effects combined together. We hypothesize that the apparent reduction in apoA-I PR is partly attributable to the reduced amount of dietary SFA (−6.3%) in MedDiet vs. the control diet. Indeed, restricting dietary total fat and SFA has been shown to reduce hepatic apoA-I mRNA expression in livers of Cebus monkeys [20, 26]. The significant reduction in LDL-C and apoB concentrations with MedDiet  may also have contributed to lowering apoA-I PR. Indeed, apoA-I PR has been positively correlated with plasma LDL-C and LDL-apoB concentrations , suggesting less need for reverse cholesterol transport when the plasma LDL-C pool is reduced. It appears that the impact of increasing alcohol intake as part of the MedDiet on raising apoA-I PR did not fully compensate for these effects.
Men with MetS in the present study were characterized by an elevated apoA-I FCR after the control diet (0.32 pool/day), and these figures are comparable with those from a previous kinetic study in which dyslipidemic subjects with MetS also had higher apoA-I FCR compared with controls (0.30 vs. 0.20 pool/day) . Two other groups have shown that low HDL-C and apoA-I concentrations in overweight/obese subjects with insulin resistance were mainly accounted for by an apoA-I hypercatabolism [29, 30]. Our results showed that the HDL-C response to MedDiet was highly heterogeneous. Participants among whom HDL-C increased with MedDiet showed greater reductions in apoA-I clearance rates and in plasma apoB and VLDL-TG concentrations than those among whom HDL-C concentrations were reduced with MedDiet. Moreover, correlation analysis showed that individual variations in the catabolism of apoA-I and in VLDL-TG concentrations were the strongest correlates of individual changes in HDL-C concentrations with MedDiet. Our data reaffirm that even in the context of significant dietary changes, the FCR of apoA-I remains the key determinant of the HDL-C and apoA-I response to MedDiet among men with MetS . Indeed, although plasma apoA-I concentrations may be partly determined by the PR of apoA-I, change in the PR of apoA-I with MedDiet was not a significant correlate of concurrent variations in plasma concentrations of HDL-C and apoA-I in our study.
Several previous studies have shown that TG concentrations correlate positively with the catabolism of apoA-I [31, 32]. Our data are consistent with that concept. Reduction in VLDL-TG decreases the hetero-exchange of neutral lipids by CETP leading to less TG-enriched HDL particles . TG-poor HDL have been shown to be more stable and consequently, cleared less rapidly from the circulation . We hypothesize that the increase in alcohol consumption with the MedDiet may be partly responsible for the heterogeneous TG response in these subjects with MetS. Indeed, a recent study has shown that heavy alcohol consumption can lead to either high or low concentrations of VLDL-TG . Finally, low-carbohydrate/high-fat diets have HDL-C raising and TG lowering effects compared with high-carbohydrate/low-fat diets . It is possible that the relatively high carbohydrate content of the MedDiet in our study may have attenuated its impact on plasma HDL-C concentrations. Indeed, a high fat MedDiet supplemented with nuts have been shown to reduce TG and increase HDL-C concentrations compared with a low fat diet .
To the best of our knowledge, this is the first study having documented the impact of the MedDiet on apoA-I kinetic in men with MetS. The carefully controlled feeding feature of the present study, the high compliance to the pre-determined diets and the relatively large number of participants considering a kinetic study are important strengths that need to be emphasized. Limitations of the current study pertain to the fact that there was no control group independent of the intervention and that participants were not randomized to the two experimental diets in this fixed sequence study. However, standardization of the baseline diet with a control North American diet prior to consuming the MedDiet allowed us to minimize inter-individual variations in baseline apoA-I kinetics and each participant acts as their own control. The sort-term duration of the study precludes any formal interpretation regarding longer term effects of MedDiet on HDL and apoA-I kinetics. Although MedDiet had no impact on HDL-C, some functions of HDL particles might still be beneficially altered by the diet, but this remained to be investigated.