4. Discussion
diet-induced obesity
OBESE, IMPAIRED GLUCOSE TOLERANCE, INSULIN SENSITIVITY, COMPLICATIONS
The objective of this study was to test 100% elderberry juice for effects on indirect calorimetry and glucose tolerance/insulin sensitivity. To strengthen the study design, the EBJ was compared to a custom-made sugar- and flavor-matched PL to allow for participant blinding to treatment, and to test EBJ for potential bioactive effects attributable to plant metabolites while accounting for its energy and macronutrient content. Testing was performed in a randomized, crossover design with a three-week washout period to ensure carryover effects were minimized. This project was informed by previous work in which insulin sensitivity and fat oxidation increased in overweight or obese men following a 7 day, 100% controlled, 40% fat diet with either 600 g of blackberries or an energy-matched control food per day [There is promising evidence in the rodent literature from several independent research groups that report the effectiveness of anthocyanins from berries against diet-induced obesity and resultant complications with glucose homeostasis (8–16). The proposed mechanisms of action of anthocyanins are broad and include inhibition of intestinal nutrient absorption, modulation of the gut microbiome, pan peroxisome proliferator-activated receptor (PPAR) activation, and modulation of adenosine monophosphate-kinase (AMPK), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1-alpha) molecular pathways related to energy balance and thermogenesis [Despite no effect of EBJ on serum glucose and insulin following a meal challenge, it caused a significant increase in average CHO oxidation, which was detectable by a metabolic cart measuring respiratory gasses in parallel to the MTT. Interestingly, increased average CHO oxidation was balanced by a significant decrease in average fat oxidation, while EE was unchanged between treatments. Similar directionality was maintained during a 30 min bout of low-intensity exercise, but without reaching significance. The increased CHO oxidation with the EBJ treatment contrasts the findings from our earlier work with blackberries, where a meal challenge with blackberries caused a significant reduction in insulin response and an increase in fat oxidation compared to placebo [The difference in substrate oxidation between treatments without detectable change in serum glucose and insulin response to the MTT are noteworthy, but there is precedent in other interventions. For instance, 1 month of carnitine supplementation increased CHO oxidation and decreased fat oxidation following an MTT in 11 impaired glucose tolerance volunteers, but without change in concurrent plasma glucose, insulin, or free fatty acids (FFA) [Anthocyanin bioavailability has often been reported as limited [Major strengths of this study include a robust crossover design, which was informed by earlier work, to incorporate an adequately spaced washout period and work with a food sciences research institute to prepare a flavor and sugar-matched placebo beverage. The 3-week washout period was informed by earlier work that suggested carryover effects on insulin sensitivity were possible with a shorter 1-week washout period; none of our linear models detected a significant sequence effect in this project. The decision to work closely with a food science institute to prepare a placebo was to account for participant bias and potential placebo effects by blinding treatment, which is a major challenge of nutritional interventions. Major weaknesses of this pilot study include a small sample size, and a lack of controlled feeding prior to test days. The limited sample size was driven primarily by the challenges surrounding the COVID-19 pandemic, and because this was a pilot study with limited resources, controlled feeding was not possible. To our knowledge, this is the first study to perform meal tolerance and calorimetry testing of high-anthocyanin 100% elderberry juice. This unique and nascent commodity [