Obesity is a costly and ongoing health complication in the United States and globally. Bioactive-rich foods, especially those providing polyphenols, represent an emerging and attractive strategy to address this issue. Berry-derived anthocyanins and their metabolites are of particular interest for their bioactive effects, including weight maintenance and protection from metabolic aberrations. Earlier findings from small clinical trials suggest modulation of substrate oxidation and glucose tolerance with mediation of prospective benefits attributable to the gut microbiota, but mixed results suggest appropriate anthocyanin dosing poses a challenge. The objective of this randomized, placebo-controlled study was to determine if anthocyanin-dense elderberry juice (EBJ) reproduces glucoregulatory and substrate oxidation effects observed with other berries and if this is mediated by the gut microbiota. Overweight or obese adults (BMI > 25 kg/m²) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. Each treatment period included 4 days of controlled feeding with a 40% fat diet to allow for comparison of measurements in fecal microbiota, meal tolerance testing (MTT), and indirect calorimetry between test beverages. Eighteen study volunteers completed the study. At the phylum level, EBJ significantly increased Firmicutes and Actinobacteria, and decreased Bacteroidetes. At the genus level, EBJ increased Faecalibacterium, Ruminococcaceae, and Bifidobacterium and decreased Bacteroides and lactic acid-producing bacteria, indicating a positive response to EBJ. Supporting the changes to the microbiota, the EBJ treatment significantly reduced blood glucose following the MTT. Fat oxidation also increased significantly both during the MTT and 30 min of moderate physical activity with the EBJ treatment. Our findings confirm the bioactivity of EBJ-sourced anthocyanins on outcomes related to gut health and obesity. Follow-up investigation is needed to confirm our findings and to test for longer durations.

Background/Objectives: Elderberry juice (EBJ) consumption prevents weight gain in mice fed a high-fat diet and increases fat oxidation in response to a meal challenge in overweight humans. Thyroid hormones influence metabolism and substrate oxidation, and the impact of EBJ consumption on thyroid homeostasis remains unexplored. Thus, the primary objective of this analysis was to investigate whether elderberry consumption in mice and humans affects serum thyroid biomarkers. Methods: Serum samples from a previous trial incorporating an EBJ intervention were analyzed for thyroxine (T4), thyroid stimulating hormone (TSH), and thyroglobulin (Tg). The samples are from a meal-tolerance test in 18 humans who followed a 7-day diet-controlled crossover design. Samples from 33 male mice were collected after 13 weeks following a high-fat diet with or without EBJ powder, and with or without free wheel running. Results: Short-term EBJ consumption in humans resulted in significant increases in T4 (PL: 42.3 ± 3.2 vs. EBJ: 49.3 ± 4.1 ng/mL, p < 0.05), and TSH (PL: 0.094 ± 0.012 vs. EBJ: 0.104 ± 0.011 ng/mL, p < 0.05), with no change in Tg (p > 0.05). Whereas supplementation with EBJ powder in rodents resulted in a non-significant reduction in T4 (p = 0.07). Conclusions: These findings suggest that elderberry juice consumption may influence thyroid metabolism, contributing to the observed metabolic benefits, such as improved fat oxidation, body composition, and protection against high-fat diet-induced weight gain. The increased T4 and TSH in humans align with enhanced metabolic rate, while the reduction in T4 in rodents indicates potential long-term adaptations requiring further exploration.

Background: Metabolic flexibility, the ability to efficiently switch between fuel sources in response to changing nutrient availability and energy demands, is recognized as a key determinant of metabolic health. In a recent randomized controlled human feeding trial, overweight individuals receiving American black elderberry juice (EBJ) demonstrated improvements in multiple clinical indices of metabolic flexibility, but the mechanisms of action were unexplored. The objective of this study was to utilize RNA sequencing to examine how EBJ modulates the transcriptional response to fasting and feeding, focusing on pathways related to metabolic flexibility. Methods: Overweight or obese adults (BMI > 25 kg/m²) without chronic illnesses were randomized to a 5-week crossover study protocol with two 1-week periods of twice-daily EBJ or placebo (PL) separated by a washout period. RNA sequencing was performed on peripheral blood mononuclear cells from 10 participants to assess transcriptomic responses collected at fasting (pre-meal) and postprandial (120 min post-meal) states during a meal-challenge test. Results: The fasted-to-fed transition for EBJ showed 234 differentially expressed genes following EBJ consumption compared to 59 genes following PL, with 44 genes shared between interventions. EBJ supplementation showed significantly higher enrichment of several metabolic pathways including insulin, FoxO, and PI3K–Akt signaling. KEGG pathway analysis showed 27 significant pathways related to metabolic flexibility compared to 7 for PL. Conclusions: Our findings indicate that short-term elderberry juice consumption may promote metabolic flexibility in overweight adults.