Vitamin K2

Vitamin K exists as K1 (phylloquinone) from green leaves, which the liver preferentially uses for clotting factors, and K2 (menaquinones) from fermented foods and animal products, which reaches extrahepatic tissues including bone and arterial wall. That tissue distribution is the entire case for supplementing K2 separately: a diet rich in kale can leave bone and vascular vitamin K-dependent proteins undercarboxylated even while clotting is perfectly adequate.

The mechanism is elegant and specific. Vitamin K is the cofactor for gamma-glutamyl carboxylase, which carboxylates glutamate residues on a family of Gla proteins. Osteocalcin, once carboxylated, binds calcium into the bone hydroxyapatite matrix. Matrix Gla protein, once carboxylated, is the body's most potent inhibitor of vascular calcification. Undercarboxylated forms of both circulate in a large fraction of adults and predict fracture risk and arterial stiffness respectively — this is the so-called calcium paradox, where calcium ends up in the wrong tissue.

Human trials support the bone side reasonably well: three years of MK-7 at 180 mcg/day in postmenopausal women reduced bone loss at the lumbar spine and femoral neck and decreased vertebral height loss. Japanese trials of high-dose MK-4 at 45 mg/day show fracture reduction, though those results have not replicated well outside Japan. The vascular data are promising but less settled, with the Rotterdam cohort linking higher K2 intake to lower coronary calcification and a three-year MK-7 trial showing reduced arterial stiffness in the stiffest subjects.

Practically, MK-7 has a three-day half-life versus MK-4's few hours, so 100-200 mcg once daily works where MK-4 requires large divided doses. Take it with fat and with vitamin D, since D increases production of the very Gla proteins that K2 must activate. The single serious caution is warfarin, whose entire mechanism is vitamin K antagonism.