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Title: Plasma response to deuterium-labeled vitamin K intake varies by TG response, but not age or vitamin K status, in older and younger adults

Author
item ELLIS, JESSICA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item AL RAJABI, ALA - Alberta Health Services
item Grusak, Michael
item SHEARER, MARTIN - Guy'S And St Thomas National Health Service Foundation
item NAUMOVA, ELENA - Tufts University
item SALTZMAN, EDWARD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BARGER, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/7/2018
Publication Date: 12/22/2018
Citation: Ellis, J.L., Fu, X., Al Rajabi, A., Grusak, M.A., Shearer, M., Naumova, E., Saltzman, E., Barger, K., Booth, S.L. 2018. Plasma response to deuterium-labeled vitamin K intake varies by TG response, but not age or vitamin K status, in older and younger adults. Journal of Nutrition. 149(1):18-25. https://doi.org/10.1093/jn/nxy216.
DOI: https://doi.org/10.1093/jn/nxy216

Interpretive Summary: Phylloquinone is the primary form of vitamin K in the diet and circulation. There is large variation in circulating phylloquinone when compared among individuals, which has been attributed in part to age. However, little is known about the factors, such as age, that influence phylloquinone metabolism. The purpose of this study was to compare the efficiency of phylloquinone absorption in older and younger adults following dietary phylloquinone depletion and repletion. Forty-two older and younger adults were maintained on sequential phylloquinone depletion and phylloquinone repletion diets. During each diet phase, participants were fed phylloquinone-rich collard greens that were labeled with heavy water. Labeled phylloquinone that originated from the collard greens was then measured in plasma over a 72 hour period. Participants absorbed phylloquinone from collard greens as efficiently when they were in low vitamin K status as when they were in adequate vitamin K status. Older adults appeared to have greater absorption efficiency compared to younger adults. However, when plasma levels were adjusted for blood lipids, which are elevated in older adults, the age effect in phylloquinone absorption efficiency was no longer significant. In summary, the variation in absorption of phylloquinone from collard greens among individuals is partially explained by higher blood lipids in older adults.

Technical Abstract: Background: Phylloquinone is the primary form of vitamin K in the diet and circulation. There are large intra- and inter-individual variances in circulating phylloquinone, which have been attributed in part to age. However, little is known about the dietary and non-dietary factors that influence phylloquinone absorption and excretion. Objective: The purpose of this study was to compare absorption efficiency of phylloquinone and urinary excretion of menadione, a phylloquinone metabolite, in older and younger adults following dietary phylloquinone depletion and repletion. Design: Forty-two older (55-80 y; n=21) and younger (18-40 y; n=21) adults were maintained on sequential 28-d phylloquinone depletion (~10 mcg phylloquinone/day) and 28-d phylloquinone repletion (~500 mcg phylloquinone/day) diets. On the 23rd day of each diet phase, participants were fed deuterated phylloquinone-rich collard greens (2H-phylloquinone), and sampled over 72 hours. Liquid chromatography-mass spectrometry (LC-MS) was used to measure deuterium (2H)-labeled and unlabeled phylloquinone in plasma and triglyceride-rich lipoprotein (TRL) fractions. High-performance liquid chromatography (HPLC) and LC-MS were used to measure total and percent enrichment of menadione, respectively. Results: Absorption efficiency of 2H-phylloquinone did not differ in response to phylloquinone depletion or repletion, but was significantly higher in older adults than in younger adults (p=0.02). Absorption efficiency of 2H-phylloquinone was highly correlated with the triglyceride AUC (r^2=0.45). After adjustment for triglycerides, the age effect in absorption efficiency was no longer significant. Excretion of 2H-menadione did not differ by age, sex, or between dietary depletion and repletion. Conclusions: Absorption efficiency of 2H-phylloquinone did not differ between phylloquinone depletion and repletion. The age effect observed was driven by triglyceride response and was completely attenuated after adjustment. Absorption of phylloquinone, therefore, seems to be a predominantly lipid-driven effect and not dependent on existing vitamin K status or non-dietary factors, such as age, sex, BMI, or percent body fat.