Clinical trial NCT01787591: 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
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver
Metabolic Syndrome
Keywords: Vitamin E
Metabolic syndrome
Liver disease
Non-alcoholic liver steatohepatitis
Fatty liver
Dairy consumption
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2013-02-08
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Area Under the Curve 0-72 h (Deuterium Labeled Alpha-tocopherol)
timeFrame: 0, 3, 6, 9, 12, 24, 36, 48, and 72 h post test meal
measure: Cmax
timeFrame: 0-72 h post-meal
measure: Tmax
timeFrame: 0-72 h post-meal
measure: Elimination Rate
timeFrame: 0-72 h post-meal
measure: Estimated Absorption (% Dose)
timeFrame: 0-72 h post-meal
Secondary outcomes:
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
Study officials:
affiliation: Ohio State University
name: Richard Bruno, PhD, RD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.