Clinical trial NCT02949115: Effects of Red Beetroot Juice on High-Fat Meal-Induced Endothelial Dysfunction and Cardiometabolic Disturbances
Official title: Acute and Chronic Effects of Red Beetroot Juice on High-Fat Meal-Induced Endothelial Dysfunction and Cardiometabolic Disturbances
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Overweight
Obesity
Aging
Menopause
Keywords: Red beetroot
Dietary Nitrate
Polyphenols
Endothelial Function
High-Fat Meal
Overweight
Obesity
Aging
Cardiometabolic
Lead sponsor: Colorado State University
Sponsor class: OTHER
Collaborators: name: United States Department of Agriculture (USDA)
First posted: 2016-10-31
Enrollment: 15
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: Aside from aging, numerous factors increase the risk for developing cardiovascular disease (CVD) including diet and nutrition. High-fat meal consumption induces postprandial vascular endothelial dysfunction and other cardiometabolic disturbances (e.g. dyslipidemia and hyperglycemia) in normal weight individuals and is exacerbated in overweight/obese individuals. These postprandial responses are likely largely due to activation of pro-inflammatory and pro-oxidant pathways. Given that much of the day is spent in the postprandial state, this may further impair cardiovascular health in aging overweight/obese individuals. Interventions that attenuate these responses are needed. Red beetroot (Beta vulgaris L.) is an excellent source of bioactive compounds including nitrate, flavonoids, phenolic acids, betalains, carotenoids, and ascorbic acid. These bioactive compounds and their metabolites have been shown to have antioxidative, anti-inflammatory, and cardiovascular-protective effects. These effects, particularly the cardiovascular-protective effects, have been primarily attributed to its high content of nitrate since it is converted to nitric oxide independent of the vascular endothelium via the enterosalivary nitrate-nitrite-nitric oxide pathway. However, red beetroot juice contains a number of other potentially beneficial bioactive compounds and few studies have aimed to determine whether these compounds work independently, additively, or synergistically in exerting these effects. Given the findings of previously conducted research in the broad area of red beetroot juice consumption and human health, it can be suggested that: 1) acute red beetroot juice consumption may prevent or attenuate the adverse postprandial responses to consuming a high-fat meal in individuals with exaggerated responses; and 2) chronic consumption of red beetroot may improve underlying factors contributing to these exaggerated responses. Accordingly, this project aims to: 1) investigate the efficacy of acute and chronic whole red beetroot juice consumption compared with its bioactive components in attenuating postprandial vascular endothelial dysfunction and adverse cardiometabolic responses to a high-fat meal; and 2) to gain insight into the underlying mechanisms responsible.

Detailed description: This is a randomized, double-blind, placebo-controlled, 4-period, 4-week crossover pilot clinical trial consisting of 2 postprandial tests for each period. Overweight or obese postmenopausal women and men aged 40 to 65 will be recruited from the greater Fort Collins, CO area. After telephone prescreening, participants will report to the study site for their first visit (Screening) where they will receive verbal and written explanation of the project, provide informed consent, followed by screening assessments. Qualified participants will be scheduled for a baseline visit and randomly assigned to their respective treatments. On the second visit (Baseline) following an overnight fast, anthropometrics and blood pressure will be measured and diet and physical activity records will be collected. Subjects will ingest their respective treatment 10 min prior to consuming the high-fat test meal. Various assessments will be performed and samples collected prior to and up to 4 hours post-meal consumption. At the third visit (Final), all assessments and sample collections will be repeated at the same time points but 24 hours after consuming the last dose of their respective treatments to test chronic rather than acute effects. Subjects will undergo a 4-week washout period before crossing over to the next treatment period. This will be repeated for all 4 treatments.

Eligibility criteria: Inclusion Criteria:

* Postmenopausal women and men
* BMI between 25 and 40 kg/m2

Exclusion Criteria:

* Hypertension, cardiovascular disease, diabetes, cancer, or kidney, liver, or pancreatic disease
* Individuals taking gastroesophageal reflux, antihypertensive, hypoglycemic, lipid-lowering, hormone replacement, erectile dysfunction medications or nitrates
* Participating in a weight loss program or actively trying to lose weight
* Smokers
* Heavy drinkers (\> 3 drinks on any given occasion and/or \> 7 drinks/week for women, or \> 4 drinks on any given occasion and/or \> 14 drinks/week for men)
* Allergy to meals/treatments
* Consuming \> 2 servings red beetroot or beetroot juice/wk

Primary outcomes:
measure: Vascular endothelial function
timeFrame: 0 and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
Secondary outcomes:
measure: Blood glucose, insulin, and indices of insulin sensitivity and resistance
timeFrame: 0 and 1, 2, and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
measure: Blood triglycerides
timeFrame: 0 and 1, 2, and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
measure: Blood pressure
timeFrame: 0 and 1, 2, and 4 hours post-meal consumption at baseline and 1 month for each treatment period
measure: Heart rate
timeFrame: 0 and 1, 2, and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
measure: Arterial stiffness
timeFrame: Pre-meal consumption at baseline and 1 month for each treatment period.
measure: Nitric oxide biomarkers
timeFrame: 0 and 1, 2, and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
measure: Oxidative stress biomarkers
timeFrame: 0 and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
measure: Pro-inflammatory biomarkers
timeFrame: 0 and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
Other outcomes:
measure: Blood polyphenols and polyphenol metabolites
timeFrame: 0, 1, 2 and 4 hours post-meal consumption at baseline and 1 month for each treatment period.
measure: Urinary polyphenols and polyphenol metabolites
timeFrame: 0 and 24 hours post-meal consumption at baseline and 1 month for each treatment period.
measure: Oral and gut microbiome
timeFrame: Pre-meal consumption at baseline and 1 month for each treatment period.
Locations:
city: Fort Collins
country: United States
facility: Department of Food Science and Human Nutrition, Colorado State University
state: Colorado
Study officials:
References:
citation: Litwin NS, Van Ark HJ, Hartley SC, Michell KA, Vazquez AR, Fischer EK, Melby CL, Weir TL, Wei Y, Rao S, Hildreth KL, Seals DR, Pagliassotti MJ, Johnson SA. Impact of Red Beetroot Juice on Vascular Endothelial Function and Cardiometabolic Responses to a High-Fat Meal in Middle-Aged/Older Adults with Overweight and Obesity: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. Curr Dev Nutr. 2019 Oct 17;3(11):nzz113. doi: 10.1093/cdn/nzz113. eCollection 2019 Nov.