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

Primary Purpose

Non-alcoholic Fatty Liver, Metabolic Syndrome

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Fat-Free Milk
Low-Fat Milk
Full-Fat Milk
Soy Milk
Sponsored by
Ohio State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Non-alcoholic Fatty Liver focused on measuring Vitamin E, Metabolic syndrome, Liver disease, Non-alcoholic liver steatohepatitis, Fatty liver, Dairy consumption

Eligibility Criteria

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Ohio State University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Acute Fat-Free Milk Ingestion

Acute Low-Fat Milk Ingestion

Acute Full-Fat Milk Ingestion

Acute Soy Milk Ingestion

Arm Description

Participants will ingest 1 cup of fat-free milk with 15 mg deuterium-labeled alpha-tocopherol.

Participants will ingest 1 cup of low-fat milk with 15 mg deuterium-labeled alpha-tocopherol.

Participants will ingest 1 cup of full-fat milk with 15 mg deuterium-labeled alpha-tocopherol.

Participants will ingest 1 cup of soy milk with 15 mg deuterium-labeled alpha-tocopherol.

Outcomes

Primary Outcome Measures

Area Under the Curve 0-72 h (Deuterium Labeled Alpha-tocopherol)
Cmax
Maximal plasma concentration of deuterium labelled alpha-tocopherol
Tmax
Time to maximal plasma concentration of deuterium labelled alpha-tocopherol
Elimination Rate
Rate of plasma elimination of deuterium labelled alpha-tocopherol
Estimated Absorption (% Dose)
Absorption of deuterium labelled alpha-tocopherol

Secondary Outcome Measures

Full Information

First Posted
February 6, 2013
Last Updated
September 30, 2016
Sponsor
Ohio State University
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1. Study Identification

Unique Protocol Identification Number
NCT01787591
Brief Title
Dairy Fat as a Mediator of Vitamin E Adequacy in Individuals With Metabolic Syndrome
Official Title
Dairy Fat as a Mediator of Vitamin E Adequacy in Individuals With Metabolic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver, Metabolic Syndrome
Keywords
Vitamin E, Metabolic syndrome, Liver disease, Non-alcoholic liver steatohepatitis, Fatty liver, Dairy consumption

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Acute Fat-Free Milk Ingestion
Arm Type
Experimental
Arm Description
Participants will ingest 1 cup of fat-free milk with 15 mg deuterium-labeled alpha-tocopherol.
Arm Title
Acute Low-Fat Milk Ingestion
Arm Type
Experimental
Arm Description
Participants will ingest 1 cup of low-fat milk with 15 mg deuterium-labeled alpha-tocopherol.
Arm Title
Acute Full-Fat Milk Ingestion
Arm Type
Experimental
Arm Description
Participants will ingest 1 cup of full-fat milk with 15 mg deuterium-labeled alpha-tocopherol.
Arm Title
Acute Soy Milk Ingestion
Arm Type
Experimental
Arm Description
Participants will ingest 1 cup of soy milk with 15 mg deuterium-labeled alpha-tocopherol.
Intervention Type
Other
Intervention Name(s)
Fat-Free Milk
Intervention Description
Fat-free milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.
Intervention Type
Other
Intervention Name(s)
Low-Fat Milk
Intervention Description
Low-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.
Intervention Type
Other
Intervention Name(s)
Full-Fat Milk
Intervention Description
Full-fat milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.
Intervention Type
Other
Intervention Name(s)
Soy Milk
Intervention Description
Soy milk ingestion with 15 mg deuterium-labeled alpha-tocopherol.
Primary Outcome Measure Information:
Title
Area Under the Curve 0-72 h (Deuterium Labeled Alpha-tocopherol)
Time Frame
0, 3, 6, 9, 12, 24, 36, 48, and 72 h post test meal
Title
Cmax
Description
Maximal plasma concentration of deuterium labelled alpha-tocopherol
Time Frame
0-72 h post-meal
Title
Tmax
Description
Time to maximal plasma concentration of deuterium labelled alpha-tocopherol
Time Frame
0-72 h post-meal
Title
Elimination Rate
Description
Rate of plasma elimination of deuterium labelled alpha-tocopherol
Time Frame
0-72 h post-meal
Title
Estimated Absorption (% Dose)
Description
Absorption of deuterium labelled alpha-tocopherol
Time Frame
0-72 h post-meal

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard Bruno, PhD, RD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Data will be shared when it becomes available
Citations:
PubMed Identifier
26447154
Citation
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.
Results Reference
result
PubMed Identifier
28077381
Citation
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.
Results Reference
derived

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

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