3. Discussion
obesity, metabolic syndrome, diabetes
OBESITY, DISEASE, INSULIN RESISTANCE, METABOLIC SYNDROME, DIABETES
In our clinical trial of dietary strawberry supplementation in adults with features of metabolic syndrome and insulin resistance, several targeted and untargeted serum metabolites were shown to be modulated. When analyzed by treatment phases, the serum valine and leucine were significantly lower following the high-dose (2.5 servings/day) strawberry phase when compared with the low-dose and control phases. Untargeted metabolites revealed a significant group of compounds that were predictive of strawberry intake when compared with the baseline; elevated levels of hydroxyphenyl propionic acid indicated colonic degradation of strawberry phytochemicals, as well as an increase in propionic acid that has been associated with improved insulin resistance and metabolism. Elevated serum phosphate, as a primary metabolite, indicates the role of strawberry supplementation in improving energy-related pathways in tissue metabolism.Branched-chain amino acids (BCAAs) have been correlated with energy and glucose metabolism, and the circulating levels of leucine, isoleucine, and valine have been shown to be elevated in obesity and predict insulin resistance and diabetes [To our knowledge, no previous study has reported the effects of strawberry or other berry supplementation on serum metabolomics associated with the energy metabolism and lipid metabolism pathways in adults with features of metabolic syndrome. Our findings show that whole strawberries can lower selected BCAAs that can improve insulin resistance and the energy/lipid metabolism pathways, and lower diabetes risk [Among the untargeted metabolites, several compounds were shown to be modulated following the strawberry-supplementation phase. The serum levels of phosphate-containing metabolites, such as glycerol phosphate and phosphate, as well as cholesterol, were significantly predictive of strawberry supplementation, thereby showing the role of strawberry polyphenols in upregulating glycolysis-related lipids and energy metabolism pathways. While serum LDL-cholesterol has been shown to be lowered by berry and/or polyphenol supplementation in adults in previous studies [Overall, our study provides unique mechanistic data underlying the effects of strawberry consumption on serum metabolic profiles that have not been previously reported. We also examined differences in habitual macronutrient and flavonoid intakes after each study phase, and in the absence of any significant differences in habitual diet, the observed differences could be attributed to strawberry supplementation. Some limitations of our study include the inclusion of adults with obesity and features of metabolic syndrome and those not taking medications for lowering glucose, lipids, and/or blood pressure, which reduces generalizability to adults on multiple medications and disease risks. We did not analyze serum metabolites according to the features of metabolic syndrome in each patient, which would require a larger sample size and thus must be examined in future studies. Additionally, we did not measure gut microbiome profiles separately in this study; thus, the serum profiles may not distinguish between metabolites derived from strawberries vs. those derived from the microbial metabolism of these compounds. Thus, future studies in adults with metabolic syndrome must examine these differences to determine how strawberries may modulate pathogenic metabolites contributing to this condition. Finally, our study cohort was predominately women; thus, these data may not be applicable to men. However, excluding the two male participants from the analysis did not affect the significant study findings.