Dairy Fat as a Mediator of Vitamin E Adequacy in Individuals With Metabolic Syndrome

This study is conducted to investigate if vitamin E status in healthy individuals and individuals with metabolic syndrome can be improved by dairy fat. The investigators hypothesize that full-fat dairy will substantially increase the bioavailability of alpha-tocopherol, a form of vitamin E. The results of this study will contribute to the application of dairy fat as a simple and effective strategy for improving vitamin E status, which is partly due to poor vitamin E intake. By completing this study, the investigators anticipate developing new dietary recommendations to achieve adequate vitamin E status through the regular consumption of dairy fat paired with foods containing vitamin E.

Study Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Non-alcoholic Fatty Liver
• Intervention / Treatment: Other: Fat-Free Milk; Other: Low-Fat Milk; Other: Full-Fat Milk; Other: Soy Milk

Detailed Description

Nonalcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome and affects >70 million Americans. Weight loss and vitamin E supplementation are leading strategies for preventing and/or treating NASH. However, the long-term success of weight loss is limited and >92% of Americans fail to meet dietary recommendations for vitamin E. Thus, the objective is to define the extent to which dairy fat facilitates adequate vitamin E status in individuals with metabolic syndrome, a population at high-risk for NASH, by improving α-tocopherol bioavailability. The central hypothesis is that full-fat dairy will substantially increase alpha-tocopherol (a-T) bioavailability to the extent needed to facilitate production of alpha-carboxyethyl-hydroxy-chromanol (a-CEHC), a metabolite of a-T that predict a-T status. The will therefore complete the following specific aims: 1) define milk fat-mediated improvements in a-T bioavailability, and 2) define dairy fat-mediated improvements in a-T status. This study involves a randomized crossover study design where healthy adults and those with metabolic syndrome (n = 10/group) will ingest deuterium-labeled a-T (15 mg) with 1 cup of either fat-free milk, low-fat milk, whole milk, or soy milk. Urine and blood samples will be collected at timed intervals prior to and following milk consumption. Blood will be collected at timed intervals over 72 h, and plasma will be analyzed by liquid chromatography with mass spectrometry to determine pharmacokinetic parameters by measuring labeled and unlabeled a-T and a-CEHC. Risk to participants is expected to be minimal and will be outlined in the informed consent form in clear and simple terms. Upon successful completion of this study, it is expected to show that a-T bioavailability increases in a milk fat-dependent manner and that dairy milk compared with soy milk significantly improves a-T bioavailability. The results are expected to provide timely evidence demonstrating the amount and type of fat needed to achieve optimal vitamin E status specifically in a population of significant public health concern. Overall, these studies will fill a substantial knowledge gap regarding the importance of dairy fat in contributing to optimal health and provide a simple dietary approach to ameliorate poor vitamin E status among a significant proportion of Americans.

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

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• specific criteria of the metabolic syndrome: large waist circumference (>102 or >89 cm for men and women, respectively), high fasting triglycerides (150-300 mg/dL), low fasting HDL (<40 and <50 mg/dL for men and women, respectively), high blood pressure (>130/85 mm Hg) and high fasting glucose (110-180 mg/dL)
• BMI: >30 kg/m2,
• non-dietary supplement users for >2-mo
• no use of medications known to affect lipid metabolism
• no history of gastrointestinal disorders
• resting blood pressure <140 mm Hg
• not taking any medications that control hypertension

Exclusion Criteria:

• lactose-intolerance
• excessive alcohol consumption (>3 drinks/d)
• >5 h/wk of aerobic activity
• women who are pregnant, lactating, or have initiated or changed birth control in the past 3-mo
• plasma alpha-tocopherol >20 μmol/L.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acute Fat-Free Milk Ingestion; Participants will ingest 1 cup of fat-free milk with 15 mg deuterium-labeled alpha-tocopherol.	Other: Fat-Free Milk; Fat-free milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.
Experimental: Acute Low-Fat Milk Ingestion; Participants will ingest 1 cup of low-fat milk with 15 mg deuterium-labeled alpha-tocopherol.	Other: Low-Fat Milk; Low-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.
Experimental: Acute Full-Fat Milk Ingestion; Participants will ingest 1 cup of full-fat milk with 15 mg deuterium-labeled alpha-tocopherol.	Other: Full-Fat Milk; Full-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.
Experimental: Acute Soy Milk Ingestion; Participants will ingest 1 cup of soy milk with 15 mg deuterium-labeled alpha-tocopherol.	Other: Soy Milk; Soy milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve 0-72 h (Deuterium Labeled Alpha-tocopherol)		0, 3, 6, 9, 12, 24, 36, 48, and 72 h post test meal
Cmax	Maximal plasma concentration of deuterium labelled alpha-tocopherol	0-72 h post-meal
Tmax	Time to maximal plasma concentration of deuterium labelled alpha-tocopherol	0-72 h post-meal
Elimination Rate	Rate of plasma elimination of deuterium labelled alpha-tocopherol	0-72 h post-meal
Estimated Absorption (% Dose)	Absorption of deuterium labelled alpha-tocopherol	0-72 h post-meal

Collaborators and Investigators

• Sponsor: Ohio State University

Publications and helpful links

General Publications

• Mah E, Sapper TN, Chitchumroonchokchai C, Failla ML, Schill KE, Clinton SK, Bobe G, Traber MG, Bruno RS. alpha-Tocopherol bioavailability is lower in adults with metabolic syndrome regardless of dairy fat co-ingestion: a randomized, double-blind, crossover trial. Am J Clin Nutr. 2015 Nov;102(5):1070-80. doi: 10.3945/ajcn.115.118570. Epub 2015 Oct 7.
• Traber MG, Mah E, Leonard SW, Bobe G, Bruno RS. Metabolic syndrome increases dietary alpha-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial. Am J Clin Nutr. 2017 Mar;105(3):571-579. doi: 10.3945/ajcn.116.138495. Epub 2017 Jan 11.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: February 6, 2013
• First Submitted That Met QC Criteria: February 6, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Estimate): November 22, 2016
• Last Update Submitted That Met QC Criteria: September 30, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Metabolic syndrome; Vitamin E; Fatty liver; Liver disease; Non-alcoholic liver steatohepatitis; Dairy consumption
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Liver Diseases; Insulin Resistance; Hyperinsulinism; Syndrome; Fatty Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 2012H0344

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data will be shared when it becomes available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No