Investigators are proposing to leverage ongoing research funded by USDA to study in greater depth the effect of strawberry intake on chronic low grade inflammation and its relation to endothelial function and insulin sensitivity (InsS). Investigators' rationale is based on facts that inflammation is a key feature in the development of atherosclerotic cardiovascular disease and diabetes, and strawberry intake has been shown to modulate biomarkers of inflammation, but with inconsistencies deserving follow up and better understanding. Of note, meal-induced inflammatory responses seem to be counteracted better with lower amounts of strawberry intake \[\~1 cup fresh weight equivalent (FWeq) vs 3 cups FWeq\]. In contrast, markers of inflammation in the fasting state in humans have been relatively unremarkable showing no or limited change with daily strawberry intake. However, many of these investigations used higher intake levels (\~2-3 cup FWeq) to test hypotheses on alternative endpoints (ie., lipids) and in groups with varied health risks. To better understand the effects of strawberry intake on systemic inflammation, investigators propose to study mechanisms (ie., NF-kB/Nrf-2 mediated signaling) within a sub population of immune cells (ie., monocytes) that result in plasma markers of inflammation. Investigators propose to do this by harvesting monocytes from subjects and study the activation of these signaling pathways after 4-week strawberry intake compared to a control condition. To address dose-response dynamics, investigators propose to study two strawberry intake levels (1 cup FWeq and 3 cup FWeq vs Control). Investigators are also interested in expanding recently completed vascular work in our lab showing improved vasodilation (by flow mediated vasodilation) 1 h after strawberry intake and after 4-week strawberry intake (3 cup FWeq) daily in individuals with modestly elevated cholesterol levels. Because chronic inflammation and oxidative stress impair endothelial function, investigators hypothesize that intake levels of strawberry that have the greatest benefit in reducing inflammation and oxidative stress will align with lower markers of endothelial inflammation and enhanced endothelial function (ie., vasodilation). Dietary patterns and components of the diet that preserve or improve endothelial function have an important risk lowering impact on cardiovascular disease development.

And finally, investigators aim to explore more deeply the relationship of strawberry intake, inflammation and InsS using the Liquid Meal Tolerance (LMTT) if intravenous glucose tolerance test (IVGTT) method cannot be used due to supply chain issues of sterile Dextrose. Investigators' previous work with strawberries is suggestive of improved peripheral InsS in a meal-challenge paradigm in overweight individuals with 1 cup FWeq and in abdominally obese individuals and impaired InsS with 3 cup FWeq. Changes in fasting insulin concentrations after intake of strawberries with 1-3 cup FWeq have been neutral.

However, fasting insulin concentrations give insight about liver InsS and less about peripheral InsS, which is relevant in post-meal glucose tolerance. In normal physiology, a major function of insulin in post meal state is to suppress hepatic gluconeogenesis while stimulating glucose uptake into muscle and fat. As impaired InsS is a major risk for developing pre-diabetes and type 2 diabetes, intervening early and strategically with diet, and with specific foods as science supports to restore InsS, is prudent. The proposed research can help characterize the role of strawberries in improving InsS and its relation to inflammation status.

Glucoregulation will be assessed by placing a Continuous Glucose monitoring (CGM) machine (Dexcom-6) which monitors interstitial glucose levels every 5 minutes for 10 days. This will be placed to participants at the beginning of the study for 7-10 days and similarly at the end of the study for 7-10 days of period. The study is focused on three areas important to public health and consumers: inflammation, vascular, and metabolic health. The project will provide new, deeper knowledge in these areas elucidating pathways by which strawberries reduce inflammation and risk for atherosclerotic vascular disease and diabetes. The data can contribute to health claim petitions. The new knowledge can be used to inform/educate a number of stakeholders, including the strawberry industry, consumers, health professionals, the scientific, medical and regulatory communities/agencies, and contribute to the evidence-base for establishing intake recommendations of polyphenolic rich fruits, like strawberries, in the USA, to promote health and reduce chronic disease risk.