Consumption of both low and moderate-fat PS enriched soy beverages reduced fasting total and LDL-C in comparison with 1% dairy milk. Although direct statistical comparison between the two clinical studies is not possible, the numerical plasma cholesterol responses between the two studies suggest that the fat content of the soymilk had little impact on vehicle performance as LDL-C reductions following consumption of the low and moderate-fat soymilk beverages were similar (13 and 15%, respectively). Direct comparisons of the clinical effectiveness of PS products between studies are often limited by differences in study design, as cholesterol reductions in response to PS consumption are modulated by multiple factors including background diet [18
], PS dose [19
] and form [20
], frequency of PS consumption [21
], level and type of fat in food vehicle [6
], and baseline LDL-C concentration of study subjects [18
]. As the background diet and factors pertaining to the dose, form and frequency of PS consumption were identical between our two studies, the comparable cholesterol-lowering response between the soymilk beverages may help clarify confusion that exists surrounding the effectiveness of PS enriched beverages with differing fat content. The only minor difference between our study protocols was the lower LDL-C baseline concentrations of the low-fat soy beverage group compared with the moderate-fat soymilk study subjects. It has been suggested that subjects with higher LDL-C may respond more favourably, and with further cholesterol reductions, than individuals with lower LDL-C concentrations [19
]. However, when the analysis was conducted in hypercholesterolemic subjects with entry LDL-C concentrations above 3.4 mmol/L, TC and LDL-C reductions following PS-enriched low-fat soymilk consumption were similar to those reported for the entire study population. Therefore, our results suggest that patients with lower LDL-C concentrations may also benefit from the consumption of PS enriched soymilk.
Consumption of the moderate-fat PS enriched soymilk was associated with a 9% reduction in circulating triglycerides. Although PS consumption is not traditionally associated with modulation of triglyceride metabolism, Plat et al. recently observed a reduction in circulating TAG by 27.5% in metabolic syndrome patients with hypertriglyceridemia following the consumption of a PS yogurt drink [22
]. Furthermore, this report follows a recent meta-analysis suggesting a PS-induced modulation of plasma triglycerides [23
], although previous meta-analyses have failed to establish this relationship [6
]. This PS-induced reduction in plasma triglycerides was only observed in subjects from study 2 who had elevated triglyceride concentrations compared to study 1 subjects, giving merit to Plat's speculation that modulation of triglycerides in response to PS consumption may be more readily detected in study populations with high baseline triglycerides.
It is increasingly clear that some individuals respond with major shifts in lipid profiles to PS consumption whereas others are much less sensitive to PS challenges. This variability of responsiveness is likely associated with single nuclear polymorphisms (SNPs) in Niemann-Pick C1-like 1 (NPC1L1) and ATP binding cassette proteins G5 (ABCG5) and G8 (ABCG8), genes that regulate intestinal sterol absorption and efflux [24
]. Although the two soymilk beverages were associated with similar LDL-C reductions, it is clear that the low-fat soymilk study population included more non-responders that subjects in the moderate-fat soymilk study (Figure ). While consumption of the moderate-fat soy beverage was associated with an LDL-C lowering ranging from from 2 to 38%, LDL-C reductions following the low-fat soy beverage ranged from -33 to +37%, with 9 subjects displaying increased LDL-C following the low-fat soy treatment.
Individual % changes in LDL-C from baseline in response to the consumption of a low and moderate-fat PS-enriched soy beverage.
Cholesterol absorption was reduced by 27% following consumption of the moderate-fat PS fortified soy beverage. The cholesterol-lowering effects of PS are related to modulation of intestinal cholesterol absorption through several distinct mechanisms including interference with the micellular cholesterol incorporation [26
], competition with dietary and biliary cholesterol for uptake through the brush border NPC1L1 [27
], and reduction in cholesterol esterification and chylomicron assembly within the intestinal enterocyte [28
]. Surprisingly, although previous investigations typically report compensatory increases in cholesterol synthesis in response to PS consumption [29
], no difference was observed in cholesterol synthesis between the moderate-fat PS fortified soy beverage and control group in the current study. The hepatic expression of genes that regulate cholesterol synthesis and plasma LDL-C trafficking, including 3-hydroxy-3-methyl-glutaryl-CoA reductase, sterol-regulatory element binding protein 2, and LDL-receptor, have been shown to be transcriptionally regulated by individual protein and/or isoflavone components of soy [31
]. Therefore, it can be speculated that specific bioactive components inherent in the soy beverage may have suppressed the increase in cholesterol synthesis typically observed following PS consumption. Alternatively, consumption of isolated soy protein has been reported to increase cholesterol FSR by 7.6% in hypercholesterolemic human subjects compared with animal protein consumption [33
]. However, the effects of whole soymilk consumption on cholesterol synthesis has not been previously investigated.