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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Non-alcoholic Fatty Liver, Metabolic Syndrome

Intervention / Treatment
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* Other: Fat-Free Milk
* Other: Low-Fat Milk
* Other: Full-Fat Milk
* Other: Soy Milk


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin E, Metabolic syndrome, Liver disease, Non-alcoholic liver steatohepatitis, Fatty liver, Dairy consumption