4. Discussion
metabolic endotoxemia, obesity, Metabolic endotoxemia, MetS-associated complications, MEB, MetS, cardiometabolic disorders, LBP
OBESITY, INSULIN RESISTANCE, INFLAMMATORY RESPONSES, INSULIN SENSITIVITY
This rigorously controlled, randomized crossover trial demonstrated, contrary to our hypothesis, that two-week consumption of an MFGM-enriched full-fat milk beverage does not affect intestinal-level or circulating biomarkers of cardiometabolic health in MetS persons. Metabolic endotoxemia, based on complementary assessments of serum endotoxin and LBP:sCD14 at fasting or postprandially following a meal challenge, was unaffected by MEB compared with COMP. Corroborating findings also show that MEB did not affect expression of TLR4/NFκB inflammatory responses. MEB also had no effect on insulin resistance (HOMA-IR) or insulin sensitivity (Matsuda index), nor did it influence gut incretins. Lastly, despite compelling evidence from rodent models [Whether dairy foods, regardless of their fat content, impact cardiometabolic health has been long debated [The present RCT had rigorous dietary control to limit heterogeneity of the basal diet within and between participants and to promote weight stability to evaluate the independent effects of MEB. High compliance to the prescribed diet was evidenced based on no between-trial differences in energy or macronutrients, that 97–98% of total energy intakes were from administered foods, and that between-trial dietary patterns did not differ based on HEI-2015 scores. While a small but significant 0.75 kg decrease in body mass occurred in both study arms, this is unlikely to be confounding consistent with the lack of within-trial (time)-dependent effects on blood pressure and fasting concentrations of glucose, insulin, triglyceride, and total cholesterol. Scientific rigor was also enhanced by complementary assessments of compliance to test beverage consumption. We achieved 95% compliance based on returned beverage bottles and objectively confirmed ingestion by measures of spot urine PABA, which was added to all test beverages. On average, urinary PABA increased substantially, and 82–86% of all spot urines met the pre-established concentration threshold to achieve compliance. The small discrepancy between bottle counts and spot urines may reflect inflated compliance when bottle counts are used or could reflect a delay between when the test beverage was consumed relative to when the spot urine was collected; PABA has a rapid rate of elimination [The primary outcome of this RCT was an expected decrease in serum endotoxin in response to MEB. We focused on endotoxin because metabolic endotoxemia is implicated as a cause of obesity and insulin resistance [First, because metabolic endotoxemia results from enhanced translocation of gut-derived endotoxins to the systemic circulation, we considered that MFGM-enriched MEB would decrease intestinal permeability. Indeed, MFGM supplementation promotes development of the intestinal epithelium and improves tight junction protein patterns, at least in neonatal rat pups [Second, we considered that the reported benefits of MFGM and/or full-fat dairy milk on glycemic control [The present study was designed, in part, to establish efficacy and mechanistic insight of MEB to protect against MetS-associated complications, consistent with epidemiological studies indicating that higher intakes of full-fat dairy milk protect against cardiometabolic disorders [Although our RCT was supported by strong rationale [