Understanding Dose Related Effects of Strawberry — STRW  

Inflammation Clinical Trial

Official title: Understanding Dose Related Effects of Strawberry Intake on Chronic Inflammation, Oxidative Stress, and Their Relationship With Endothelial Function and Insulin Sensitivity

Status Recruiting

Clinical Trial Summary

The proposed research is designed to extend previous research findings building on the knowledge of strawberries as fruits that support a healthy immune and vascular system. The proposed research leverages a recently funded proposal by the USDA to study in greater depth inflammation, glucoregulation and oxidative stress defense and their relation to improving endothelial function and insulin sensitivity.

Before and after strawberry intake, blood samples will be collected for monocyte (immune cells and source of inflammatory cytokines) isolation and activation via changes in cellular NF-κB and Nrf-2 (key transcription factors of inflammation/oxidative stress defense) status along with products of their activation (ie., plasma cytokines). Because inflammation and oxidative stress impairs endothelial function and insulin sensitivity, acutely and chronically, investigators will also study changes in vascular and insulin sensitivity status, assessing changes in vascular adhesion molecules, endothelial responsiveness through flow mediated vasodilation (ie., FMD) and insulin sensitivity using the Liquid Meal Tolerance (LMTT) if intravenous glucose tolerance test (IVGTT) method cannot be used due to supply chain issues of sterile Dextrose. Glucoregulation will be assessed by placing a Continuous Glucose monitoring (CGM) machine (Dexcom-6) to participants for 10 days at the beginning and at the end of the study period of intervention. The study will be a randomized, double-blinded, 3-arm parallel, 4-week, dose-response study. Individuals with chronic low grade inflammation will be sought to test the anti-inflammation - vaso-relaxing - insulin sensitivity effects of strawberry.

Clinical Trial Description

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. ;

Related Conditions & MeSH terms

• Hypersensitivity
• Inflammation
• Insulin Resistance
• Insulin Sensitivity
• Pre-diabetes
• Prediabetic State

• NCT number: NCT06173765
• Study type: Interventional
• Source: Clinical Nutrition Research Center, Illinois Institute of Technology
• Contact: Indika Edirisinghe, PhD
• Phone: 708-308-0178
• Email: iedirisi@iit.edu
• Status: Recruiting
• Phase: N/A
• Start date: August 31, 2022
• Completion date: February 28, 2024