Sunday 12 May 2013

The Vitamin You May Have Never Heard Of… Vitamin K!

by Chris “the Kiwi” Ashenden, and Liana Ashenden, PhD

Hey Mate,
I hope this finds you ROCKING!
Last week, my big sis and I outlined a vitamin D action plan and explained why getting sunshine on your skin is so important to your health .
If you missed it, or my speech on why the sunscreen industry approach is SO WRONG (and hurting your health) then get reading.
Vitamin D Action Plan
Why Your Doctor is WRONG About Sunscreen
Today let’s chat about a wonderful friend of ours, whom you should have over to dinner frequently.
A friend most people have never heard of, the all important Vitamin K.
Vitamin K is VITAL to the blood clotting process that stops you bleeding to death from injury. It helps to prevent fractures and has been linked to protective effects against coronary heart disease and some types of cancer. It may have a role to play in the brain and cognitive health.
Keep reading if you care about
  • Not bleeding to death
  • Preventing fractures
  • Protecting against heart disease
  • Brain health
  • Looking good naked
Vitamin K shares a number of similarities with vitamin D. Both substances are fat-soluble. Like vitamin D, vitamin K is important for bone health. Also like vitamin D, vitamin K has been studied for almost a century in relation to one particular area of health (blood clotting), while recent studies have suggested a much wider role in the body.
Some people confuse vitamin K with potassium, because the chemical symbol for potassium on the periodic table is K. These are NOT the same substances and have very different effects in the body.
I will show you why your mother was right about eating greens – they really are good for you – and why eating the whole animal makes sense from both a vitamin K perspective and evolutionary perspective…. Organ meats, anyone? Yummy.
The detailed version starts below, if you are in a hurry, you can skip all the science stuff if you want and go straight to the recommendations part, which will be marked like this
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BUT that would be boring and you won’t learn much.
For those sticking with me, let’s get to it.
First, some science background.

What is Vitamin K

Vitamin K is best known for its crucial role in blood clotting. Its name actually comes from the German ‘Koagulationsvitamin’, or ‘coagulation vitamin’, although vitamin K plays a role in anticoagulation and many other physiological functions as well.
Figure 1 Historically vitamin K is known for its role in blood clotting, but it may have a much wider role in the body (photo credit: Sansculotte)

Vitamin K is a fat-soluble vitamin, along with vitamins A, D, and E. Vitamin K is not one substance but rather a group of compounds with a similar chemical structure. The two naturally occurring forms identified so far are vitamin K1 and K2 and both are biologically active in animals and humans.
Vitamin K1 is found in green plants, where it plays a role in photosynthesis.
  • The richest dietary sources of vitamin K1 (400-700 mcg/100g) are the dark green leaves of kale, spinach, collards, Swiss chard, broccoli, Brussels sprouts, parsley, cabbage, mustard greens, and turnip greens.
  • Vitamin K1 can also be found in soybean, olive and rapeseed oils (50-200 mcg/100g).
Figure 2 Kale and other green leafy vegetables are a good source of Vitamin K1. (Photo credit: Evan-Amos)
Vitamin K2 is primarily made by bacteria.
  • Bacteria in the human gut produce long-chain subtypes of vitamin K2, but it remains unclear how much of this we absorb.
  • The vitamin K2 subtype menaquinone-7 (MK7) is found in foods produced by bacterial fermentation like natto (fermented soybeans) and cheese.
  • Human and animal tissues such as the brain and arterial walls convert vitamin K1 into a different subtype of vitamin K2, menaquinone-4 (MK4).
  • Dietary sources of MK4 include egg yolks, liver and other organs, and (to a lesser extent) meat.
Figure 3 Natto (made from fermented soybeans) is rich in vitamin K2, but doesn’t appeal to everyone as a delicacy! (Photo credit: Gleam)
Synthetic forms such as vitamin K3 are toxic and to be avoided.
Babies derive vitamin K1 and K2 from their mothers’ milk (or from formula if you are unlucky).
Geek box:
  • Vitamin K compounds all have a methylated naphthoquinone ring structure.
  • In photosynthesis, vitamin K1 (phylloquinone) acts as an electron acceptor during the electron transport chain in Photosystem I.
  • In bacterial anaerobic respiration, vitamin K2 (menaquinone) transfers electrons between enzyme complexes in the electron transport chain.
  • Cruciferous vegetables belonging to the Brassica genus contain particularly high levels of vitamin K1.
  • Vitamin K1 is called phylloquinone, phytonadione or phytomenadione.
  • Vitamin K2 is called menaquinone or menatetrenone.
  • Vitamin K3 is called menaphthone or menadione.
Completely random side-note.
Whenever I hear the word K2 I can’t help but envisage the MOUNTAIN of the same name in the Himalayas.
Famous for being the second highest mountain in the world and also the second deadliest taker of lives (as big mountains go), this thing is a beast and is considered one of the world’s most difficult summits to climb. Two movies about it I remember are K2 and Vertical Limit, but I digress.
Sorry.
The MOUNTAIN K2 – A beast, but this is not what we are talking about here. (photo credit: Svy123)

Health

Vitamin K1 and K2 are necessary for an important chemical process called carboxylation that allows certain important proteins to function properly. Without vitamin K, these Gla proteins, also known as vitamin K-dependent proteins, would not be able to bind calcium and interact with cell membranes.
Frequently referred to with a traffic light analogy, after speaking about it with my sister, we decided that perhaps the best analogy was your local postal system.
Figure 3: Think of the postal system (photo credit: kladcat)
Think of the postal system. Without stamps (calcium), chances are the envelopes and parcels (Gla proteins) in the mail won’t reach their destinations (tissues throughout the body). When mail doesn’t get delivered, especially crucial mail, life can suck.
The good folks at the Postal Service put the correct stamps in the correct place at the correct time in the correct amount on your mail, ensuring that the system works well (this is the role of vitamin K and associated enzymes).
Vitamin K-dependent proteins play important roles in tissues throughout the body.
Their function is still being understood and is a growth area in science – my bet: vitamin K1 and K2 will have many surprises in store for us yet as the science evolves.
Geek box:
  • Vitamin K compounds all have a methylated naphthoquinone ring structure.
  • Vitamin K is a cofactor for the enzyme gamma-glutamyl carboxylase.
  • This enzyme converts the glutamate (Glu) units or residues of vitamin K-dependent proteins into gamma-carboxyglutamate (Gla) residues that are able to bind calcium.
  • The binding of calcium ions is essential to the Gla proteins’ structure and function, facilitating interaction with phospholipids such as cell membranes.
Figure 4 3D image of a Gla protein (photo credit: proteinboxbot)
(note: I am pretty sure I drew this as a three year old)

Blood

Hemostasis is the first stage in wound healing and causes bleeding to stop via the blood clotting cascade. Vitamin K (especially K1) is essential to this process.
Drugs prescribed to prevent thrombosis such as warfarin act by blocking the action of vitamin K in all in forms. Warfarin decreases the concentration of vitamin K in body tissues and results in clotting factors with inadequate Gla. People taking warfarin or other vitamin K antagonists need to be especially careful and consistent with their vitamin K intake – please consult your doctor if you are on these medications.
Figure 5 Without the blood clotting cascade you would bleed to death from even a small injury. (photo credit: crystal)
A severe vitamin K deficiency results in bruising and bleeding. It is very rare in adults, but can sometimes occur in newborn babies. This is because vitamin K1 and K2 are not easily transported across the placenta and the baby’s intestines have not yet been colonized with vitamin K2 -synthesizing bacteria. Some pediatricians recommend supplementation with vitamin K for newborns, either orally or through an intramuscular injection. However this is a controversial practice because some studies suggested a correlation between newborn vitamin K supplementation and childhood cancers such as leukemia, although a causal link has not been substantiated.
Geek box: the vitamin K-dependent blood clotting cascade proteins carboxylated in the liver are coagulation factors II (prothrombin), VII, IX, and X, and anticoagulant proteins C, S, and Z.

Bone

Studies show that vitamin K has a protective effect against bone fractures and that osteoporosis is associated with low levels of vitamin K.
Figure 6 X-ray showing osteoporosis in the hand and wrist (photo credit: Nevit Dilmen)
Vitamin K2 may be more important than vitamin K1 in this regard, although some studies show also a beneficial effect of vitamin K1 on bone health:
  • A number of clinical trials showed that supplementation with vitamin K2 (but not vitamin K1) protects against fractures in the elderly, especially in post-menopausal women.
  • In Japan the vitamin K2 subtype MK4 is recommended as a treatment for osteoporosis.
  • Japanese people derive the vitamin K2 subtype MK7 through their dietary consumption of natto.
There is inconsistent evidence on vitamin K’s effect on bone mineral density. Some scientists suggest that vitamin K mediates its skeletal effects through other mechanisms, perhaps through collagen metabolism.
Some of you have asked me about the interaction between vitamin K and vitamin D.
Both are important for bone health. For example, vitamin D’s active form, calcitriol, regulates the synthesis of a protein called osteocalcin, but vitamin K activates this protein into a form that can bind calcium. The two vitamins also appear to have a synergistic effect. A clinical study showed that healthy women who took combined vitamin K1, vitamin D and calcium supplements showed greater increases in wrist bone mineral density than the women who took vitamin K1 only or vitamin D and calcium without vitamin K1.
Want good bones, you don’t just need good Vitamin D status, you need to get some Vitamin K action.
Some nutritionists suggest that potential toxic effects of very high vitamin D consumption are in fact only due to vitamin K deficiency, and therefore they advocate co-supplementation as a way to increase total vitamin D intake to higher levels. There is no rigorous evidence to support the safety of this approach.
Geek box:
  • Vitamin K-dependent proteins involved in bone metabolism include osteocalcin, matrix Gla protein and periostin.
  • Vitamin K-dependent protein S is made by osteoblasts (bone-forming cells).
  • Osteocalcin plays a role in bone mineralization and osteoblast and osteoclast activity, and is used as a marker of bone formation.
  • The vitamin K2 subtype MK7 induces more complete carboxylation of osteocalcin than vitamin K1.

Cardiovascular System

A build-up of calcium (calcification) in the arterial walls decreases their elasticity and increases the risk of clot formation. In atherosclerosis (hardening of the arteries), calcification of the atherosclerotic plaque occurs at a late stage of the disease.
Figure 7 Atherosclerosis in the internal carotid artery (photo credit: Patho)
Vitamin K helps to prevent a build-up of calcium in the arteries. A number of large, prospective cohort studies have shown that intake of K2 (but not K1) is associated with reduced risk of coronary heart disease and a protective effect against calcification of the coronary and aortic arteries. Vascular calcification is a potential side effect of taking vitamin K-antagonists such as warfarin.
Geek box:
  • The mechanism for vitamin K2’s action is likely to be through two vitamin K-dependent proteins that are carboxylated within the blood vessels (rather than in the liver).
  • Matrix Gla protein is not only found in bone and cartilage, but also in blood vessel walls and other soft tissues. In the arterial wall, it is expressed in vascular smooth muscle cells and is a potent inhibitor of arterial calcification.
  • Gas6 affects vascular smooth muscle cell apoptosis (cell death) and movement.

Cell Growth

Vitamin K may have an effect on cell growth through the vitamin K-dependent growth specific gene 6 protein, or Gas6, which promotes cell survival and inhibits cell death. Gas6 protein binds and activates receptor tyrosine kinases, enzymes that can stimulate cell replication and transformation.
In cancer cell lines in vitro, vitamin K has the opposite effect and inhibits cell growth. Prospective studies in humans suggest that dietary intake of K2 (but not K1) is associated with a reduced risk of prostate and lung cancer. However, rigorous clinical trials are needed to explore the potential effects of vitamin K2 on cancer.

Central Nervous System

It is possible that vitamin K in all its forms affects cognitive health via the carboxylation of proteins involved in the brain and nervous system. Vitamin K is involved in the biosynthesis of sphingolipids. These complex lipids are a structural component of cell membranes throughout the body and also play a role in cell signalling. They are present in high concentrations in neuronal and glial cell membranes in the brain. Two other vitamin K-dependent proteins are relevant here. Gas6 protein is involved in cell signalling in both the central and peripheral nervous systems and the anticoagulation protein S is expressed in the brain.
Figure 7: Sphingolipids, Gas6 protein, and protein S are found in the brain – These are all related to Vitamin K (Wiki Commons)

Gut Health

Studies in rats suggest that vitamin K1 and K2 may trigger gene expression of alkaline phosphatase in gut epithelial cells.

Biochemistry

By now you should have figured out that vitamin K1 and K2 can be obtained from the diet, and that our own bodies can make K2 from K1. The bacteria living in our gut can also provide us with K2 (as shown by vitamin K deficiency in people taking antibiotics). Both forms of vitamin K are transported around the blood by lipoproteins.
Vitamin K in both forms can be reused in the body because it undergoes a cycle of oxidation and reduction (the vitamin K cycle). However, it is also extensively metabolized in the liver and excreted in the urine and in feces (in bile), which means that vitamin K levels need to be continually replenished. Vitamin K1 is the major circulating form of vitamin K and vitamin K2 is the major form stored in the human liver. Vitamin K2 has a longer half life.
As outlined above, the two forms of vitamin K appear to have different physiological actions. Vitamin K1 is preferentially used up by the liver in the synthesis of active blood clotting factors, which may explain its low stores in the liver. Vitamin K2 is linked with skeletal and cardiovascular health.

Deficiency

Symptoms of deficiency include bleeding (including the gums and gut), heavy menstruation, and bruising. Severe deficiency results in low levels of carboxylated blood clotting factors and can lead to uncontrolled bleeding (hemorrhage).
If you’re worried, have a blood test. High serum levels of under-carboxylated prothrombin (coagulation factor II) can indicate sub-clinical vitamin K deficiency. Remember the postal analogy? This is like finding lots of mail without stamps.
Severe deficiency is very rare. People with the following conditions may be at risk of a sub-clinical vitamin K deficiency:
  • Fat mal-absorption syndromes
  • Inflammatory bowel disease
  • Liver disease
  • Pancreatic insufficiency
  • Cystic fibrosis
  • Anorexia and/or bulimia
  • Chronic alcoholism
Newborn infants have a higher risk of vitamin K deficiency.
Drugs can affect vitamin K1 and K2 levels in your body. For example, taking antibiotics is associated with low levels. Conversely, large, sudden increases or decreases in vitamin K1 or K2 intake can alter the effectiveness of warfarin and other anti-thrombotics.
If you have any of these medical conditions or are on medication, PLEASE seek your doctor’s advice before taking vitamin K supplements or increasing your dietary intake.
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Kiwi, I GET IT. Vitamin K IS Important – But what should I DO?

Clearly, vitamin K is important for the health of our blood, artery walls, and bones.
And vitamin K is likely to have a host of other physiological effects not yet elucidated by science.
No question, food is first, and food is best. I advocate consuming vitamin K in both of its forms through your DIET wherever possible.
Tip: remember that the bio-availability of vitamin K is improved by eating fats and by adequate bile synthesis and fat absorption in the gut. Take down some olive oil with that salad.
Strategically optimize your dietary intake of both K1 and K2 as they appear to have different effects in the body:
For vitamin K1 and blood health:
  • Eat plenty of dark green vegetables, such as kale, spinach, collards, Brussels sprouts, parsley and broccoli. When I’m eating out I often order an extra side dish (or two) of spinach.
  • Eat them alongside good fats and oils to increase bioavailability of the fat-soluble vitamins in the gut.
Figure 8 Mmm broccoli – a great source of Vitamin K1  (photo credit: David Monniaux)
Figure 9. DOUBLE MMMMMM Chicken livers fried with onions – organ meats are a great source of Vitamin K2  (photo credit: Ludovic Peron)
For vitamin K2 and bone and arterial health:
Figure 10 Egg yolks are a good source of vitamin K2, and also choline, another one of my favorite nutrients (photo credit: Paul Goyette)

What Dose Is Best, Kiwi?

In 2001, the non-governmental organization the Institute of Medicine published Adequate Intake (AI) recommendations for vitamin K of 120 mcg/day for men and 90 mcg/day for women.
You can safely consume more than this in the diet if you want to, because no cases of vitamin K toxicity have ever been reported, to my knowledge. Please note that I’m talking here about the naturally occurring forms vitamin K1 and K2. Do NOT take synthetic vitamin K3 as it can harm you.
As shown by the complementary effects of vitamin D and K on bone, the fat-soluble vitamins can often act synergistic-ally. I recommend that you optimize your intake of vitamins A, D, and K.
The dietary sources for the fat-soluble vitamins tend to overlap, which is helpful. You can get your vitamin A from the same leafy green vegetables and liver that you’re going to eat for vitamin K1 and K2 intake, respectively.
Get your vitamin D from exposing your skin to sunshine, eating oily fish or taking D3 supplements. For more information on vitamin D see my previous post.
Alrighty then mate?
Of course, the good folks at team Athletic Greens were nice enough to put Vitamin K2 in the formula, but as always I want you to start with food. Athletic Greens is there for the supercharge component.
So get eat your delicious dark green vegetables, eggs and organ meats to ensure your vitamin K and A intake, and while you’re at it, get outside for some sunshine and vitamin D.

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