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. 2023 Feb 18;152(4):981–993. doi: 10.1093/jn/nxab332

TABLE 3.

Vitamin K concentrations of tissues from mice fed a diet containing 2.2 μmol/kg unlabeled PK (control), 2H7PK, 13C11MK4, 2H7MK7, or 2H7MK9 for 1 week (stable isotope study)1

Males Females
Group Group 2-way ANOVA P values
Tissue VK form2 Control, unlabeled PK, n = 7 2H7PK, n = 7 13C11MK4, n = 7 2H7MK7,n = 7 2H7MK9, n = 7 Control, unlabeled PK, n = 6 2H7PK, n = 7 13C11MK4, n = 7 2H7MK7, n = 7 2H7MK9, n = 7 Sex Group Sex × Group
Duodenum Unlabeled MK4 12.9a ± 2.13 5.96b ± 0.731 NDc 4.93b ± 0.789 4.99b ± 0.880 30.3a ± 4.44 9.47b ± 1.93 18.2a,b ± 2.39 12.9b ± 2.58 10.6b ± 1.64 <0.001
Administered VK form 13.9a ± 2.02 10.4a ± 1.69 10.7a ± 2.58 5.01b ± 0.810 8.64a,b ± 2.58 16.0a ± 2.38 22.6a ± 3.85 13.6a ± 2.76 9.60b ± 1.22 14.1a,b ± 1.45 <0.001 <0.001 0.35
Labeled MK4 NDc 10.3a ± 1.02 4.80b ± 1.04 8.24a ± 0.773 8.94a ± 1.28 NDb 30.0a ± 4.39 26.5a ± 2.22 29.4a ± 3.72 23.1a ± 2.83 0.03
Total VK 28.3a ± 1.86 27.7a ± 1.88 18.6a ± 3.06 18.8a ± 1.68 23.6a ± 3.73 46.9a ± 6.02 64.5a ± 7.38 60.5a ± 3.30 53.0a ± 6.26 49.0a ± 4.02 0.037
% Labeled MK4 (of total VK) 0%c 37.1%a,b ± 3.05% 25.8%b ± 3.44% 43.9%a ± 2.86% 37.9%a,b ± 4.06% 0%c 46.5%a,b ± 3.03% 43.8%b ± 2.77% 55.6%a ± 1.06% 47.3a,b ± 2.40% 0.026
Jejunum Unlabeled MK4 8.29a ± 0.467 4.57b ± 1.09 4.98b ± 0.887 3.90b ± 0.940 5.09b ± 1.46 23.2a ± 6.95 9.12b ± 3.70 8.11b ± 0.959 4.65b ± 2.63 4.36b ± 1.66 0.006 <0.001 0.135
Administered VK form 8.05a ± 1.32 3.33b ± 0.913 7.61a ± 1.53 NDb NDb 16.3a ± 2.64 13.1a ± 5.12 15.1a ± 2.64 9.71a ± 1.08 2.93b ± 0.729 0.002
Labeled MK4 NDb 5.10a ± 0.511 5.05a ± 0.883 6.22a ± 0.536 7.57a ± 0.927 NDc 21.8a ± 3.14 13.4b ± 1.16 17.9a,b ± 2.52 15.5a,b ± 1.45 <0.001
Total VK 16.9a ± 1.43 13.8a,b ± 1.65 18.6a ± 2.31 10.4a,b ± 1.33 12.9b ± 2.26 40.1a ± 9.21 45.9a,b ± 11.4 37.3a ± 4.18 33.9a,b ± 4.91 23.4b ± 3.91 <0.001 0.006 0.099
% Labeled MK4 (of total VK) 0%c 36.9%b ± 4.84% 27.2%b ± 2.72% 60.0%a ± 4.29% 58.7%a ± 3.82% 0%d 47.5%b ± 2.90% 36.0%c ± 1.43% 52.8%b ± 3.02% 66.3%a ± 3.42% 0.033
Ileum Unlabeled MK4 10.1a ± 1.40 4.87b ± 0.902 2.80b ± 0.429 2.81b ± 0.442 3.27b ± 0.752 41.7a ± 4.98 16.5b ± 3.56 16.9b ± 2.59 16.5b ± 4.33 13.2b ± 2.62 <0.001 <0.001 0.437
Administered VK form 7.67a ± 0.647 2.89c ± 0.629 4.54b ± 0.382 3.08c ± 0.500 2.89b,c ± 0.643 11.6a ± 1.68 3.62c ± 0.758 7.96b ± 0.871 3.97c ± 1.34 6.60b,c ± 1.63 <0.001 <0.001 0.343
Labeled MK4 NDc 10.4a ± 0.653 6.69b ± 0.708 10.9a ± 0.635 11.0a ± 1.03 NDc 33.8a ± 1.64 17.1b ± 3.18 36.1a ± 2.19 32.2a ± 2.46 <0.001
Total VK 18.1a,b ± 1.67 18.8a ± 1.18 14.2b ± 1.22 17.0a,b ± 1.23 17.8a,b ± 1.09 53.7a,b ± 6.22 55.5a ± 4.78 44.8b ± 5.19 59.0a,b ± 4.77 54.8a,b ± 4.74 <0.001 0.028 0.886
% Labeled MK4 (of total VK) 0%c 55.4%a ± 3.77% 47.2%b ± 2.45% 64.3%a ± 2.57% 61.6%a ± 4.06% 0%c 60.9%a ± 3.34% 38.2%b ± 5.87% 61.3%a ± 3.79% 58.8%a ± 5.04% 0.454 <0.001 0.553
Colon Unlabeled MK4 11.9a ± 1.42 4.20b ± 0.796 4.41b ± 0.886 3.45b ± 0.965 3.11b ± 0.539 38.8a ± 6.67 18.3b ± 1.99 21.9b ± 2.68 19.2b ± 5.03 17.4b ± 3.41 <0.001 <0.001 0.463
Administered VK form NDa NDa 4.91a ± 0.417 3.70a ± 5.24 5.96a ± 9.22 13.2a ± 1.11 5.97b,c ± 0.881 11.0a,b ± 1.96 3.13c ± 1.37 3.17c ± 1.54 <0.001
Labeled MK4 NDb 8.58a ± 0.989 7.04a ± 0.609 8.91a ± 0.622 8.03a ± 0.702 NDb 37.8a ± 3.04 25.0a ± 1.32 36.6a ± 5.83 27.9a ± 4.96 <0.001
Total VK 11.9 ± 1.42 13.5 ± 0.850 16.9 ± 1.18 17.8 ± 5.84 22.5 ± 8.47 53.2 ± 6.40 63.0 ± 4.02 59.2 ± 3.37 59.9 ± 10.9 50.2 ± 7.22 <0.001 0.279 0.080
% Labeled MK4 (of total VK) 0%c 63.7%a ± 6.00% 41.7%b ± 3.02% 50.0%a,b ± 7.03% 35.7%a,b ± 9.45% 0%c 60.0%a ± 1.48% 42.3%b ± 1.66% 61.2%a,b ± 1.14% 55.6%a,b ± 3.52% 0.163 <0.001 0.336
Liver Unlabeled MK4 ND ND ND ND ND 8.51a ± 2.20 2.80b ± 0.429 NDb NDb 2.76b ± 0.357 <0.001
Administered VK form 20.4a ± 4.68 20.9a ± 4.13 10.5a,b ± 0.628 6.27b ± 2.02 17.5a ± 2.84 48.6b ± 10.2 63.2a,b ± 10.5 18.1c ± 1.92 81.3a,b ± 7.57 104a ± 23.2 <0.001
Labeled MK4 NDb 3.88a ± 0.519 4.55a ± 0.672 4.08a ± 1.00 4.90a ± 1.58 NDb 16.9a ± 1.55 13.7a ± 0.656 16.4a ± 1.44 15.8a ± 0.773 <0.001
Total VK 20.4a,b ± 4.68 25.3a ± 4.10 15.1a,b ± 1.18 11.1b ± 2.62 23.5a ± 2.88 57.3b ± 12.3 82.7a,b ± 9.89 32.0c ± 2.30 98.5a,b ± 7.66 122a ± 23.0 <0.001
% Labeled MK4 (of total VK) 0%c 15.3%b ± 2.92% 30.1%a ± 2.29% 36.9%a ± 6.94% 20.9%a,b ± 5.34% 0%c 20.5%b ± 2.83% 42.7%a ± 2.30% 16.7%b ± 2.02% 12.9%b ± 2.53% <0.001
Brain Unlabeled MK4 21.1a ± 1.50 10.9b ± 1.08 8.01b ± 0.632 7.46b ± 0.755 8.97b ± 0.499 112a ± 19.9 61.0b ± 4.84 60.2b ± 6.24 57.6b ± 5.89 51.7b ± 4.76 <0.001 <0.001 0.20
Administered VK form ND ND ND ND ND ND ND ND ND ND
Labeled MK4 NDc 18.2a ± 1.70 11.7b ± 0.84 13.3b ± 0.935 15.9b ± 0.506 NDd 93.0a ± 7.42 62.2c ± 5.37 85.8a,b ± 8.35 72.6a,b ± 6.64 <0.001
Total VK 21.1 ± 1.50 29.1 ± 2.75 19.7 ± 1.41 20.9 ± 1.56 24.9 ± 0.944 112 ± 19.9 154 ± 12.0 122 ± 11.5 143 ± 14.2 124 ± 11.3 <0.001 0.144 0.447
% Labeled MK4 (of total VK) 0%c 62.5%a,b ± 0.844% 59.1%b ± 1.34% 63.9%a ± 1.67% 63.9%a ± 0.900% 0%c 60.4%a ± 0.737% 50.8%b ± 0.838% 59.8%a ± 0.509% 58.4%a ± 0.510% <0.001
Pancreas Unlabeled MK4 92.1a ± 6.07 50.5b ± 2.75 42.2b,c ± 3.11 43.7b,c ± 3.15 39.7c ± 2.28 359a ± 23.0 159b ± 4.96 154b,c ± 2.05 139b,c ± 5.63 143c ± 8.84 <0.001 <0.001 0.268
Administered VK form NDa NDa 2.18a ± 0.332 NDa NDa NDb NDb 5.49a ± 0.553 NDb NDb <0.001
Labeled MK4 NDc 76.6a ± 2.41 55.4b ± 3.88 71.0a ± 4.19 63.3a,b ± 3.58 NDc 276a ± 8.27 188b ± 6.85 242a ± 11.4 231a ± 18.4 <0.001
Total VK 92.1b ± 6.07 127a ± 4.94 99.9b ± 6.94 115a,b ± 6.57 103b ± 5.29 359b ± 23.0 435a ± 11.8 348b ± 6.67 382a,b ± 14.4 374b ± 26.3 <0.001 <0.001 0.637
% Labeled MK4 (of total VK) 0%c 60.2%a ± 0.777% 55.5%b ± 0.772% 61.7%a ± 1.53% 61.3%a ± 1.15% 0%c 63.5%a ± 0.673% 54.0%b ± 1.07% 63.4%a ± 1.17% 61.7%a ± 1.02% 0.249 <0.001 0.154
1

Values are geometric mean ± SEM; data are shown as pmol/g tissue (except % labeled MK4 rows). Superscript letters indicate pairwise comparisons by diet group across a row, where a > b > c > d for males and females separately, and geometric means sharing a common superscript are not significantly different from each other (Tukey's Honestly Significant Difference; P < 0.05). If analyses were not stratified on sex (i.e., the interaction term was nonsignificant), the effect of diet group was averaged over sex, and thus superscripts for males and females are parallel. All vitamin K concentrations were measured using C30 LC-MS assay with the following LLODs: 5 pmol/g for unlabeled PK, unlabeled MK4, 2H7MK7, and 2H7MK9 and 2.5 pmol/g for 2H7PK, 2H7MK4, 13C11MK4, and 13C6MK4. Abbreviations: LLOD, lower limit of detection; MK4, menaquinone-4; MK7, menaquinone-7; MK9, menaquinone-9; ND, nondetectable; PK, phylloquinone; VK, vitamin K.

2

“Administered VK form” refers to the VK form supplemented within that group (PK in the control group, 2H7PK in the 2H7PK group, and so on). “Labeled MK4” for the 13C11MK4 group refers to the generated 13C6MK4 only, not a sum of administered 13C11MK4 and generated 13C6MK4.