Vasoprotective Activities of Low-Fat Milk in Individuals With Metabolic Syndrome

The purpose of this study is to define whether the acute consumption of low-fat milk protects against postprandial vascular endothelial dysfunction by reducing oxidative stress responses that limit nitric oxide bioavailability to the vascular endothelium. The investigators hypothesis is that the consumption of low-fat milk will improve postprandial vascular endothelial function in an oxidative stress-dependent manner that allows greater nitric oxide (NO) bioavailability. The objectives of this study are to 1) examine improvements in postprandial vascular endothelial function in response to low-fat milk ingestion, 2) define low-fat milk-mediated improvements in circulating biomarkers of redox status, and 3) define the mechanism by which low-fat milk improves NO bioavailability. Collectively, the successful completion of these studies is expected to define NO mediated activities of low-fat milk that protect against vascular endothelial dysfunction in individuals at high risk for developing CVD.

Study Overview

• Status: Completed
• Conditions: Obesity; Cardiovascular Disease; Metabolic Syndrome
• Intervention / Treatment: Other: Low-Fat Milk; Other: Rice Milk

Detailed Description

Cardiovascular disease (CVD) is the leading cause of death in the United States, accounting for ~830,000 deaths annually. Oxidative stress and inflammatory responses are fundamental mechanisms leading to vascular endothelial dysfunction because of their role in reducing nitric oxide (NO) bioavailability. Greater intakes of dairy foods have been associated with a lower incidence of CVD-related morbidity. Although the mechanisms by which dairy protects against CVD remain unclear, epidemiological and experimental evidence suggest that the concerted actions of bioactive milk-derived peptides and micronutrients may protect against hypertension and future CVD risk by improving vascular endothelial function. Therefore, the objective of this study is to define the mechanisms by which the acute consumption of low-fat milk protects against postprandial vascular endothelial dysfunction by reducing oxidative stress responses that limit NO bioavailability to the vascular endothelium. In this study, participants having the metabolic syndrome will ingest low-fat milk or rice milk on a single occasion. Then, vascular function and biomarkers of oxidative stress and NO metabolism will be monitored at 30 min intervals throughout a 180 min postprandial period. Collectively, these studies will help identify how postprandial vascular function is regulated in individuals at high-risk for CVD, and whether low-fat dairy consumption can be used as a strategy to better improve vascular function.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Storrs, Connecticut, United States, 06269
      • University of Connecticut

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• specific criteria of the metabolic syndrome (waist circumference (102-137 or 88-123 cm for men and women, respectively), fasting triglycerides 150-300 mg/dL, and fasting glucose (110-180 mg/dL)
• BMI: >30 kg/m2,
• non-dietary supplement users for >2-mo
• no use of any prescription or over-the-counter medications known to affect vasodilatory responses
• no known history of vascular disease
• nonsmokers
• resting blood pressure <140 mmHg
• not taking any medications that control hypertension

Exclusion Criteria:

• lactose-intolerant
• excessive alcohol consumption (>3 drinks/d or >10 drinks/wk)
• >7 h/wk of aerobic activity
• use of medications known to affect carbohydrate or lipid/lipoprotein metabolism
• regular use of any anti-inflammatory medications (e.g. aspirin, non-steroidal anti-inflammatory drugs) or over-the-counter aids (e.g. fish oils)
• women who are pregnant, lactating, and have initiated or changed birth control in the past 3-mo

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-Fat Dairy; Participants will ingest 2 cups of low-fat milk on 1 occasion prior to measure postprandial changes in vascular function	Other: Low-Fat Milk; Participants will ingest 2 cups of low-fat milk on 1 occasion.
Active Comparator: Rice Milk; Participants will ingest 2 cups of rice milk on 1 ocassion prior to measuring postprandial vascular function	Other: Rice Milk; Participants will ingest 2 cups of rice milk on 1 occasion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
endothelial function	Brachial artery flow-mediated dilation will be assessed at 30 min intervals during a 3 hour postprandial period	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarkers of oxidative stress and nitric oxide metabolism	At 30 min intervals throughout a 3 hour postprandial period, biomarkers of oxidative stress (glutathione, malondialdehyde, nitrotyrosine, and antioxidants) as well as nitric oxide metabolism (arginine, asymmetric dimethylarginine, and nitric oxide metabolites) will be evaluated.	3 hours

Collaborators and Investigators

• Sponsor: University of Connecticut
• Investigators: Principal Investigator: Richard S Bruno, PhD, RD, University of Connecticut

Publications and helpful links

General Publications

• Ballard KD, Mah E, Guo Y, Pei R, Volek JS, Bruno RS. Low-fat milk ingestion prevents postprandial hyperglycemia-mediated impairments in vascular endothelial function in obese individuals with metabolic syndrome. J Nutr. 2013 Oct;143(10):1602-10. doi: 10.3945/jn.113.179465. Epub 2013 Aug 21.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: August 4, 2011
• First Submitted That Met QC Criteria: August 5, 2011
• First Posted (Estimate): August 8, 2011

Study Record Updates

• Last Update Posted (Estimate): January 6, 2014
• Last Update Submitted That Met QC Criteria: January 3, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: obesity; cardiovascular disease; oxidative stress; metabolic syndrome; endothelial function; dairy consumption
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Cardiovascular Diseases; Syndrome; Metabolic Syndrome
• Other Study ID Numbers: H11-124