Identification of dietary and biological factors influencing vitamin K metabolism
Harshman, Stephanie.
2017
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Abstract: Vitamin K is an essential vitamin required for multiple
physiological functions. There are two known forms of vitamin K: (1) phylloquinone, the
predominant dietary source found in green leafy vegetables and vegetable oils; and (2)
menaquinones, which vary in length and saturation of the side chain and are found in animal
byproducts and fermented foods. Of the menaquinones, menaquinon... read moree-4 is unique in that it is
endogenously produced from dietary phylloquinone. In establishing recommendations for the
U.S. population, it is important to capture trends in dietary patterns and changes in
consumption that may influence dietary intake. However, the large inter-individual
variability in vitamin K status is not entirely explained by dietary intakes. Non-dietary
factors, including age and sex, need to be addressed in order to better define current
recommendations. Endogenous menaquinone-4 production is linked to cholesterol metabolism.
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also known as
statins, are potent inhibitors of endogenous cholesterol synthesis and could potentially
limit the conversion of phylloquinone to menaquinone-4 in tissues. The overall objective of
this thesis project was to characterize the dietary and non-dietary factors influencing
vitamin K status and metabolism, with a focus on the conversion of phylloquinone to
menaquinone-4. In order to meet this objective, we examined the National Health and
Nutrition Examination Survey 2011-2012, a large publically-available data set to examine
usual dietary intakes of phylloquinone in U.S. adults. The usual phylloquinone intakes of
adults in the U.S. were consistent with the previous report of NHANES data from 1988-1994,
and vegetables continue to be the primary dietary contributors to phylloquinone intake.
However, we found that the food sources of phylloquinone appear to be shifting because
mixed dishes, such as macaroni and cheese, sandwiches, and pizza are the second highest
contributor to phylloquinone intake. We then utilized a C57Bl6 mouse model to determine the
effects of diet manipulation, sex, age, and statin treatment on vitamin K status and
metabolism. Female mice had higher tissue concentrations of both phylloquinone and
menaquinone-4 in response to adequate dietary phylloquinone concentrations compared to
their male counterparts. Older mice had higher concentrations of phylloquinone in the
liver, compared to young mice. Menaquinone-4 formation in kidney was reduced in response to
atorvastatin treatment, which may be indicative of tissue-specific function. Statin
treatment did not affect menaquinone-4 formation in intestine or brain. Collectively, the
findings of this thesis work indicate that dietary source, sex, age, and statins influence
vitamin K status and metabolism. Characterizing factors that influence vitamin K metabolism
will help identify additional functions of vitamin K, and ultimately help guide
recommendations and establish potential therapeutic uses and targets of vitamin
K.
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Biochemical and Molecular Nutrition.
Advisor: Sarah Booth.
Committee: Stefania Lamon-Fava, Andrew Greenberg, and Athan Kuliopulos.
Keyword: Nutrition.read less - ID:
- 3j333d38v
- Component ID:
- tufts:22239
- To Cite:
- DCA Citation Guide EndNote
