Tests for Vitamin K Status: A Closer Look
Vitamin K travels through the blood almost entirely as a means of being delivered to our other tissues, so blood levels of vitamin K only reflect recent intake rather than long-term nutritional status. Red blood cells lack the organelles in which vitamin K function is important (the endoplasmic reticulum, mitochondria, and nucleus). Lymphocyte vitamin K concentrations could, perhaps, reflect long-term vitamin K status, but practically nothing is known about what vitamin K does in lymphocytes in the context of human nutrition, and such tests have never been validated to show anything important.
The appropriate way to test vitamin K status is to look at the carboxylation status of vitamin K-dependent proteins. These tests can be validated by showing that they respond to vitamin K depletion or supplementation and that they correlate with known health outcomes that respond in the same way. For example, the ability of the blood to clot reflects vitamin K status in the liver, where clotting factors are made; the carboxylation status of osteocalcin reflects vitamin K status in bone, where osteocalcin is made; and the carboxylation status of matrix Gla protein (MGP) reflects vitamin K status in blood vessels, where MGP is made.
Clotting disorders are life threatening and we have known about the role of vitamin K in this process for almost a century. As a result, a whole battery of tests for the different vitamin K-dependent clotting factors are readily available (for example, Ohishi, 2014). Vitamin K1 is perfectly good at supporting the production of clotting factors, and since hemorrhage can be life-threatening, clotting factors will always get priority over a limited pool of vitamin K. Thus, most people consume enough vitamin K for their clotting factors to be fully carboxylated and these tests are not useful measures of whether vitamin K status is adequate to support its other functions in other tissues.
The most common marker of vitamin K status in research studies is the carboxylation status of osteocalcin, which reflects vitamin K status in bone. This test is only useful if the proportion of osteocalcin in the carboxylated and undercarboxylated forms can be measured. Unfortunately, this is not available outside of research studies. Quest offers total osteocalcin, but doesn’t measure its carboxylation status; Genova offers undercarboxylated osteocalcin, but doesn’t measure the total. One could “hack” its carboxylation status by getting both, but this would require each “half” of the correct marker to be measured from separate blood samples analyzed by separate laboratories, making the interpretation highly questionable. Were it available, we would still have to interpret it with caution, because, independent of vitamin K status, bone resorption decarboxylates osteocalcin and releases the undercarboxylated form into the bloodstream where it has beneficial hormonal roles, so it isn’t a black-and-white marker of vitamin K status.
The most promising marker of vitamin K status on the horizon is desphospho-uncarboxylated matrix Gla protein (dc-ucMGP), which reflects vitamin K status in blood vessels and the risk of soft tissue calcification. It’s just a matter of time before it becomes available.