Plasma Response to Deuterium-Labeled Vitamin K Intake Varies by TG Response, but Not Age or Vitamin K Status, in Older and Younger Adults

Abstract

Background: Phylloquinone is the primary form of vitamin K in the diet and circulation. Large intra- and interindividual variances in circulating phylloquinone have been partially attributed to age. However, little is known about the nondietary factors that influence phylloquinone absorption and metabolism. Similarly, it is not known if phylloquinone absorption is altered by the individual's existing vitamin K status.

Objective: The purpose of this secondary substudy was to compare plasma response with deuterium-labeled phylloquinone intake in older and younger adults after dietary phylloquinone depletion and repletion.

Methods: Forty-two older [mean ± SD age: 67.2 ± 8.0 y; body mass index (BMI; in kg/m2): 25.4 ± 4.6; n = 12 men, 9 women] and younger (mean ± SEM age: 31.8 ± 6.6 y; BMI: 25.5 ± 3.3; n = 9 men, 12 women) adults were maintained on sequential 28-d phylloquinone depletion (∼10 µg phylloquinone/d) and 28-d phylloquinone repletion (∼500 µg phylloquinone/d) diets. On the 23rd d of each diet phase, participants consumed deuterated phylloquinone-rich collard greens (2H-phylloquinone). Plasma and urinary outcome measures over 72 h were compared by age group, sex, and dietary phase via 2-factor repeated-measures ANOVA.

Results: The plasma 2H-phylloquinone area under the curve (AUC) did not differ in response to phylloquinone depletion or repletion, but was 34% higher in older than in younger adults (P = 0.02). However, plasma 2H-phylloquinone AUC was highly correlated with the serum triglyceride (TG) AUC (r2 = 0.45). After adjustment for serum TG response, the age effect on the plasma 2H-phylloquinone AUC was no longer significant.

Conclusions: Plasma 2H-phylloquinone response did not differ between phylloquinone depletion and repletion in older and younger adults. The age effect observed was explained by the serum TG response and was completely attenuated after adjustment. Plasma response to phylloquinone intake, therefore, seems to be a predominantly lipid-driven effect and not dependent on existing vitamin K status. More research is required to differentiate the effect of endogenous compared with exogenous lipids on phylloquinone absorption. This trial was registered at clinicaltrials.gov as NCT00336232.

Figures

FIGURE 1

Concentration of total phylloquinone (A) and 2H-phylloquinone (B) in plasma over time by phase. Sexes within age groups are combined (n = 21 older, n = 21 younger). Points indicate arithmetic means and bars indicate 1 SEM.

FIGURE 2

Box and whisker plot of plasma 2H-phylloquinone AUC by dietary phase and age group (A); scatterplot and corresponding histograms of 2H-phylloquinone AUC and TG AUC (B). (A) Plasma 2H-phylloquinone AUC was not significantly different by dietary phase, but was significantly higher in older adults during both the depletion phase (r2 = 0.12, P = 0.02) and repletion phase (r2 = 0.15, P = 0.01). Bold central lines represent the median for each age group; lower and upper hinges represent the first and third quartiles, respectively. Whiskers extend to the furthest point within 1.5 × IQR, and dots represent data points beyond 1.5 × IQR. Sexes within age groups are combined (n = 21 older, n = 21 younger). *P ≤ 0.02. (B) Fitted line indicates ordinary least squares regression slope (r2 = 0.45, P < 0.001, n = 42, all participants combined). *ln-transformed for normality.

FIGURE 3

Box and whisker plot of total 2H-menadione excretion (nmol/72 h) by dietary phase and age group. Excretion of 2H-menadione in urine was not significantly different by phase or age group. Bold central lines represent the median for each age group; lower and upper hinges represent the first and third quartiles, respectively. Whiskers extend to the furthest point within 1.5 × IQR, and dots represent data points beyond 1.5 × IQR. Sexes within age groups are combined (depletion phase: n = 19 older, n = 21 younger; repletion phase: n = 20 older, n = 21 younger).