Identification of dietary and biological factors influencing vitamin K metabolism
Harshman, Stephanie G.
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, menaquinone-4 ... read moreis 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
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