Special Vitamin K?

Many people think that vitamin K is used by the body only to clot blood after getting a cut.  That’s true, but this nutrient is much more complicated than that.  Because it’s fat-soluble, it requires fat to be absorbed, but unlike some other fat-soluble vitamins, it doesn’t get stored anywhere in large amounts.  Its name came from the German word koagulation in 1929, immediately after its newly discovered function.

Vitamin K is not a single substance, but a group of structurally similar vitamins that are necessary for the regulation of several proteins involved in metabolic pathways other than blood clotting, including bone and coronary health.  If all it did was to clot blood, vitamin K would be one of the more boring substances related to body function.  There are two natural forms of vitamin K—K1, also known as phylloquinone, and K2, also called menaquinone.   The former is made by plants; the latter, by animals, including humans.

The main dietary source of vitamin K as phylloquinone is plants, the bioavailability of which is questionable and lower than generally assumed.  The absorption of phylloquinone from plants is about one and a half times slower than the vitamin K from a supplement.  (Gijsbers, et al. 1996)  The liver absorbs it quickly and maintains the highest concentration, though significant amounts may be found in the heart.  Whether it is secreted by the liver and transported to other tissue is not known.  (Davidson. 1998)  Green leafy vegetables are rich in K1, and contribute almost half of the total dietary intake.

Vitamin K2, or menaquinone, is a collection of a few vitaminers, the most publicized of which are MK-4 and MK-7, although there are several other MK forms.  Found in egg yolks, butter, liver, certain cheeses and fermented soy products, K2 is also produced by bacteria that live in the gut.  The amount contributed by intestinal microflora is unclear, but dietary contribution of K2 is considerably less than that of K1.  The MK numeration refers to the number of side units that are attached to the main ring-like body of the molecule— MK-4 has four units; MK-7 has seven.  They range from one to ten.  These side chains are called isoprenoids, and are made from two or more hydrocarbons, each containing five carbon atoms.  MK-4 is not produced in significant amounts by bacteria, but appears to be made from phylloquinone.  There are at least three synthetic forms of vitamin K: K3, K4, and K5.  Vitamin K3, known as menadione and metabolized to vitamin K2, has demonstrated moderate toxicity, although it is being used in pet food.  Concentrations of menaquinones in tissue are higher than the phylloquinones, especially menaquinone-4 (MK-4), which is the major tissue-bound form.   Despite the difference, the origin of MK-4 is somewhat elusive.  Investigators in Japan determined that MK-4 is converted from phylloquinone by a metabolic removal of a side chain.  (Okano. 2008)

Deficiencies of vitamin K are uncommon, but are more likely to happen as a result of drug therapy or some diseases.  The most significant instances of deficiency manifest in newborns as an acquired disease, the hemorrhagic activity of which is quelled by oral and intramuscular administration of vitamin K at birth.  Efficiency of vitamin K absorption covers a wide range, from 10% to 80%.  The recommended allowances for this nutrient are set to forestall deficiency diseases, which concern themselves with blood clotting and little else.  The optimal amounts needed to address skeletal and arterial needs have been ignored.

The most studied subtypes of vitamin K2 are MK-4 and MK-7.  MK-4 comes from K1, where its conversion may occur in the testes, pancreas, and arterial walls.  Because scientists have seen the conversion in germ-free mice (having no intestinal microflora), they concluded that bacterial activity is not necessary to make MK-4.  (Ronden. 1998)

Antibiotics are generally non-selective, and will kill the intestinal microflora upon which we depend to manufacture vitamin K from plants.  This can reduce vitamin K (menaquinone) production by more than 70% when compared to those who are not taking antibiotics.  (Conly. 1994)

Vitamin K helps to regulate calcium in both bone and the arteries, working by way of an amino acid called “Gla,” which stands for gamma-carboxyglutamic acid, or gamma-carboxyglutamyl.  Gla responds to changes in dietary intake, an age-dependent process, but several days are needed to observe any alterations.  (Ferland. 1993)   Vitamin K has a modulating effect on several proteins, where it performs an action called carboxylation.  This gives the proteins a kind of claw-like function that enables them to hold on to calcium and move it around.  Without enough vitamin K, the proteins lack their claws.  If this happens, calcium migrates away from bones and teeth, and degradation becomes an issue.  Of all the Gla proteins, osteocalcin (OC) is best known.  It’s synthesized by osteoblasts, the bone-forming cells.  Although everything about osteocalcin is not known, it is believed to be related to bone mineralization.  Osteocalcin that is under-carboxylated, labeled ucOC, is a marker for vitamin K status. High levels of ucOC are indicative of reduced bone mineral density (BMD) and increased risk for fractures.  Vitamin K intake of the general population may not be sufficient to guarantee the carboxylation needed to maintain osteocalcin activity.  (Bach. 1996)  The player in the background of all this activity is vitamin D, which regulates osteocalcin transcription.

(Lian.  1989)  Lian and his team found a large region of nucleotides directly upstream from the transcription start area that supports a ten-fold stimulation of transcription of the OC gene by 1,25-dihydroxy vitamin D.

The vitaminer MK-4 has demonstrated the capacity to reduce bone fracture risks, and even to reverse bone loss.  The synergy of vitamins K and D was recognized in studies performed by the University of California, where MK-4 received the nod as the leader of the pack.  (Kidd. 2010)  Japanese researchers who preceded that study reported that a dose of 45 mg a day of vitamin K, accompanied by calcium supplementation, would increase BMD and lead to the prevention of nonvertebral fractures. (Sato. 2005)  Additionally, K2 was found to reduce the incidence of vertebral fractures without having a substantial effect on BMD.  (Iwamoto. 2006)

Not to be outdone by its analog MK-4, MK-7, sourced from fermented soy, has been found to stimulate osteoblastic bone formation while inhibiting osteoclastic bone resorption, all the while limiting calcium depletion by modulating prostaglandin E2. (Yamaguchi. 2006)   (Tsukamoto. 2004)

Some individuals with osteoporosis are likely to have an excess of calcium in their arteries.  Vascular calcification might even be viewed as vascular ossification—the formation of bone inside an artery.  The appearance of atherosclerotic plaques in arterial walls is a hallmark of cardiovascular disease (CVD).  The plaques cause decreased elasticity of the affected vessel and increased risk of clot formation.  In Dutch studies it was discovered that women with atherosclerotic calcifications have a lower bone mass, which, of course, puts them at greater risk for fractures.  Deficiency of vitamin K causes an increase of ucOC, leading to deposition of calcium in arteries, an activity that would be halted by carboxylated OC.  Menaquinone, including MK-4, but probably not phylloquinone, is associated with reduced coronary calcification.  (Beulens. 2009)  (Geleijnse. 2004)  These studies show that those who ingested the greatest amounts of vitamin K2 experienced a 57% reduction in cardiac fatalities.  No such relationship was found for K1.  In these studies, though, MK-4 and MK-7 were not separately analyzed, but were grouped together.  But in earlier studies it was learned that MK-4 has a distinct effect on plaque prevention in warfarin treatment, where MK-4 was three times more efficiently utilized in the aorta than vitamin K1, mostly by virtue of its bioavailability and use in carboxylation.  (Spronk. 2003)

Warfarin and other anticoagulants interfere with the activity of vitamin K.  Unfortunately, warfarin has the capacity to cause arterial calcification in the long run.  (Price. 1998)  (Danziger. 2008)   Generally, there are enough data to suggest that a constant dietary intake of 65-80 mcg of vitamin K a day during warfarin therapy is an acceptable practice, while avoiding fluctuations in vitamin K intake that would interfere with the activity of the drug.  (Booth. 1999)  It is strongly recommended that such patients work closely with their physicians to monitor prothrombin time, perhaps better known as INR.  It is accepted that vitamin K replacement is an important part of warfarin therapy. (Patriquin. 2011)  In some instances, aspirin may be the better choice.  (Chimowitz. 2005)

The activities of the special K vitamin extend beyond the scope of this newsletter.  Maybe that can be addressed another time.

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