Deuterium-labeled phylloquinone fed to α-tocopherol-injected rats demonstrates sensitivity of low phylloquinone-containing tissues to menaquinone-4 depletion
Article first published online: 14 JUL 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Vitamin K Conundrums
Volume 58, Issue 8, pages 1610–1619, August 2014
How to Cite
Farley, S. M., Leonard, S. W., Stevens, J. F. and Traber, M. G. (2014), Deuterium-labeled phylloquinone fed to α-tocopherol-injected rats demonstrates sensitivity of low phylloquinone-containing tissues to menaquinone-4 depletion. Mol. Nutr. Food Res., 58: 1610–1619. doi: 10.1002/mnfr.201300659
- Issue published online: 4 AUG 2014
- Article first published online: 14 JUL 2014
- Manuscript Accepted: 23 MAY 2014
- Manuscript Revised: 19 APR 2014
- Manuscript Received: 9 SEP 2013
- National Research Initiative. Grant Number: 2009-35200-05031
- USDA National Institute for Food and Agriculture (MGT)
- National Institutes of Health. Grant Numbers: S10RR027878, P30ES000210
- 5C- and 7C-aglycones;
The influence of excess α-tocopherol (α-T) on tissue depletion of phylloquinone (PK) and menaquinone-4 (MK-4) was evaluated.
Methods and results
Rats (n = 5 per group) were fed deuterium-labeled PK (2 μmol/kg diet) for 17 days, thereby labeling the conversion from deuterium-labeled PK to d4-MK-4. Then they were injected subcutaneously daily for the last 7 days with saline, vehicle, or α-T (100 mg/kg body weight). α-T injections (i) increased α-T concentrations by tenfold in liver, doubled them in plasma and most tissues, but they were unchanged in brain; (ii) increased the α-T metabolite, carboxyethyl hydroxychromanol (α-CEHC) concentrations: >25-fold in liver and kidney, tenfold in plasma and lung, and 50-fold in heart; brain contained detectable α-CEHC (0.26 ± 0.03 nmol/g) only in α-T-injected animals; and (iii) depleted most tissues’ vitamin K. Compared with vehicle-injected rats, brains from α-T rats contained half the total vitamin K (10.3 ± 0.5 versus 21 ± 2 pmol/g, p = 0.0002) and one-third the d4-MK-4 (5.8 ± 0.5 versus 14.6 ± 1.7 pmol/g, p = 0.0002). Tissues with high PK concentrations (liver, 21–30 pmol/g and heart, 28–50 pmol/g) were resistant to K depletion.
We propose that α-T-dependent vitamin K depletion is likely mediated at an intermediate step in MK-4 production; thus, tissues with high PK are unaffected.