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

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 investigators' 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 investigators' 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 investigators 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 with 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 collection will be performed using single needle sticks or
cannula (for frequent blood collections) by skilled personnel. Plasma samples will be
analyzed by liquid chromatography with mass spectrometry to determine pharmacokinetic
parameters and vitamin E adequacy 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, the investigators expect
to demonstrate that whole milk, compared to low-fat and fat-free milk, increases a-T
bioavailability in a milk fat-dependent manner and that low-fat milk compared to soy milk
(both beverages contain identical amounts of total fat, but differ in fatty acid profile),
significantly improves a-T bioavailability. The investigators' results will 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.

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.