Insufficient Vitamin K–Key Factor in the Development
of Varicose Veins

One of vitamin K's primary actions in the body is the carboxylation (activation) of matrix GLA protein (MGP). Critical to maintaining the health of the entire cardiovascular system, MGP is known to prevent calcification in the arteries. Now, new research shows vitamin K-activated MGP is also needed to prevent the excessive proliferation and mineralization of muscle cells in the walls of the veins that causes varicose veins. (Cario-Toumaniantz C, Boularan C, Schurgers L, et al. J Vasc Res. 2007)

Researchers compared healthy veins from 36 male patients (ranging in age from 30 to 83) with varicose veins from 50 male patients (age range 40 to 81). High levels of uncarboxylated (inactive) MGP and increased calcification were seen only in the varicose veins. When vitamin K was added to cultures of small muscle cells from the varicose veins, MGP was activated, stopping the mineralization process.

There are two main forms of vitamin K: phylloquinone (vitamin K1) which is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90% of the vitamin K in a typical Western diet; and the menaquinones (vitamins K2), which make up about 10% of Western vitamin K consumption. The K2 forms can be synthesized from K1 by microflora in the gut and are also found in the diet in meat and fermented food products like cheese and natto, an especially rich source.

Cario-Toumaniantz C, Boularan C, Schurgers LJ, Heymann MF, Le Cunff M, Léger J, Loirand G, Pacaud P. Identification of Differentially Expressed Genes in Human Varicose Veins: Involvement of Matrix Gla Protein in Extracellular Matrix Remodeling. J Vasc Res. 2007 Jul 20;44(6):444-459 [Epub ahead of print]
Abstract

Vitamin K Promotes Insulin Sensitivity

Intriguing new animal research shows that vitamin K is involved in regulating energy metabolism. Vitamin K-activates osteocalcin, a protein secreted by osteoblasts, the cells responsible for building bone. It turns out that osteocalcin is also directly involved in the proliferation of pancreatic β-cells (the cells that produce insulin), thus improving glucose tolerance and insulin sensitivity.

Mice genetically engineered to lack the genes expressed in osteoblasts that enable osteocalcin secretion are unable to produce normal levels of pancreatic β-cells, and become glucose intolerant and insulin resistant. In addition to stimulating the production of insulin by β-cells, vitamin K-activated osteocalcin also increases production of adiponectin, an insulin-sensitizing hormone produced by fat cells (adipocytes), further improving insulin sensitivity and glucose tolerance. (Lee NK, Sowa H, et al. Cell 2007)

Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007 Aug 10;130(3):456-69.
Abstract

Vitamin K's Anti-Wrinkle Actions

Vitamin K plays a key role in protecting skin elasticity and could soon be the latest nutraceutical appearing in savvy high-end cosmetic lines. The research is just coming out that people who cannot metabolize vitamin K end up with severe premature skin wrinkling. (Gheduzzi D, Boraldi F, et al. Lab Invest. 2007 Oct;87(10):998-1008.)

One of the principal researchers involved is Leon Schurgers, a vitamin K icon whose name appears on numerous landmark studies involving the nutrient. Schurgers thinks vitamin K deficiency is also highly likely to be linked to wrinkling in healthy "normal" populations because vitamin K2 (menaquinone) is necessary for the activation of Matrix γ-carboxyglutamic acid protein (MGP), which inhibits calcium from depositing in elastin fibers.

In the same way that vitamin K2 (via MGP) prevents calcification in the cardiovascular system, (a.k.a.,atherosclerosis or hardening of the arteries), vitamin K2 prevents calcification of our skin's elastin, the protein that gives skin the ability to spring back, smoothing out lines and wrinkles.

Could those unrelenting smile lines be a sign you're lacking optimal levels of vitamin K2? A few facts to consider:

• Even a diet quite rich in leafy greens supplies less than half the vitamin K needed for this nutrient's calcium-regulating activities. (Cranenburg EC, Schurgers LJ.  Thromb Haemost. 2007 Jul;98(1):120-5.)

• Unlike the other fat-soluble nutrients (vitamins A, D and E), vitamin K is not stored in the body, so must be provided daily. Despite vitamin K2's production by healthy intestinal bacteria, humans can develop a deficiency of the vitamin in as few as 7 days on a vitamin K-deficient diet. (Israels LG, Israels ED, et al, Semin Perinatol. 1997 Feb;21(1):90-6.)

• Absorption of vitamin K, like that of other fat-soluble nutrients (A, D and E), depends on healthy liver, gallbladder and digestive function. Deficiency is more likely in people with digestive problems like celiac disease, irritable bowel disease, or who have had intestinal bypass surgery, since all increase likelihood of fat malabsorption.

• Canola and soybean oils are a primary source of vitamin K in the American diet. However, hydrogenation changes the vitamin K in these oils into a form no longer capable of activating osteocalcin, MGP and other vitamin-K dependent proteins. If you eat a fair amount of processed or fast foods that contain hydrogenated oils, your risk of functional vitamin K deficiency is greatly increased. (Booth SL, Lichtenstein AH, et al. Am J Clin Nutr. 2001 Dec;74(6):783-90)

• Studies of healthy adults have found high levels of uncarboxylated (not activated) osteocalcin and matrix Gla-protein (MGP) in all subjects tested. K2 activates both proteins, so high levels of their inactive forms indicate a lack of sufficient K2 to do the job. (Cranenburg EC, Schurgers LJ.  Thromb Haemost. 2007 Jul;98(1):120-5.)

• Vitamin K needs increase with age. Older individuals (>70) require higher levels of vitamin K to keep levels of uncarboxylated (inactivated) vitamin-K dependent protein low. (Tsugawa N, Shiraki M, et al. Am J Clin Nutr. 2006 Feb;83(2):380-6.)

K2: Beauty from Within

By helping to keep our skin as well as our arteries supple, vitamin K2 gives new meaning to the old adage, "Beauty comes from within." While it's possible that vitamin K may soon appear in high-end cosmetics, no research has yet been done on topical application of the vitamin. Taking a daily K2 supplement, however, both for its demonstrated ability to get calcium into bone and keep it out of arteries, as well as it potential anti-wrinkle actions, seems like a wise move right now.

Gheduzzi D, Boraldi F, Annovi G, DeVincenzi CP, Schurgers LJ, Vermeer C, Quaglino D, Ronchetti IP. Matrix Gla protein is involved in elastic fiber calcification in the dermis of pseudoxanthoma elasticum patients. Lab Invest. 2007 Oct;87(10):998-1008.
Abstract

Cranenburg EC, Schurgers LJ, Vermeer C. Vitamin K: The coagulation vitamin that became omnipotent. Thromb Haemost. 2007 Jul;98(1):120-5.
Abstract

Israels LG, Israels ED, Saxena SP. The riddle of vitamin K1 deficit in the newborn. Semin Perinatol. 1997 Feb;21(1):90-6.
Abstract

Booth SL, Lichtenstein AH, O'Brien-Morse M, et al. Effects of a hydrogenated form of vitamin K on bone formation and resorption. Am J Clin Nutr. 2001 Dec;74(6):783-90
Abstract

Tsugawa N, Shiraki M, Suhara Y, et al. Vitamin K status of healthy Japanese women: age-related vitamin K requirement for gamma-carboxylation of osteocalcin. Am J Clin Nutr. 2006 Feb;83(2):380-6.
Abstract

Trans Fat Prevents Vitamin K Activity

Unfortunately, in the U.S. where the typical diet is low in green leafy vegetables and high in processed foods that contain partially hydrogentated fat (trans fat), the most consumed form of vitamin K is an unnatural form produced when oils containing vitamin K1 (phylloquinone) are hydrogenated. Called dihydrophylloquinone, this unnatural form of vitamin K is unable to carboxylate (activate) MGP.

In other new research, those individuals consuming higher amounts of dihydrophylloquinone were found to have lower bone mineral density at the neck, hip and spine. Given the importance of vitamin K to vascular health, it would be reasonable to assume that insufficient intake of natural vitamin K (phylloquinone) and/or a high intake of dihydrophylloquinone would also increase susceptibility to varicose veins and atherosclerosis. (Troy LM, Jacques PF, et al. Am J Clin Nutr. 2007)

Troy LM, Jacques PF, Hannan MT, Kiel DP, Lichtenstein AH, Kennedy ET, Booth SL. Dihydrophylloquinone intake is associated with low bone mineral density in men and women. Am J Clin Nutr. 2007 Aug;86(2):504-8.
Abstract

Increased Risk of Heart Attack Outweighs Decreased
Risk of Fracture in Women Taking Calcium to Prevent Osteoporosis–Insufficient Vitamin K Explains Why

To prevent osteoporosis and bone fractures, calcium supplementation has become standard practice for women during and after menopause, but research published in the February 2008 issue of the British Medical Journal indicates that just taking calcium, or even calcium plus vitamin D, can result in a highly unacceptable trade off: a 12% decrease in risk of fracture for a 212% increase in risk of cardiovascular disease!

The research, a randomized controlled trial involving 1,471 postmenopausal women, revealed that women taking calcium supplements increased their risk of heart attack an average of 149%, stroke 142%, and sudden death 137%. (Bolland MJ, Barber PA, et al. BMJ. 2008 Feb 2;336(7638):262-6.)

Why? Calcium supplements have generally been thought to be safe, and much has been made recently of the role played by vitamin D in our ability to absorb calcium. But what hasn't been considered is the equally essential role of vitamin K, which ensures that all that calcium we're absorbing ends up where we need it—in bone—and not where we don't—in blood vessels.

In an accompanying editorial titled, "Cardiovascular risks of calcium supplements in women," and subtitled, "Increased risk of myocardial infarction outweighs the reduction in fractures," the authors note:

"Under certain stimuli, vascular smooth muscle cells may undergo a phenotypic switch to bone-like cells, and in the presence of high amounts of calcium these may be capable of producing vascular calcification." (Jones G, Winzenberg T. BMJ. 2008 Feb 2;336(7638):226-7.)

In plain English, what this says is that certain stimuli – i.e., lack of sufficient vitamin K2, as the footnote attached to this sentence in the editorial makes clear, but the editorial fails to spell out – can cause the cells lining blood vessel walls to act like bone cells, i.e., absorb calcium. (Wallin R, Wajih N, et al. Med Res Rev. 2001 Jul;21(4):274-301.)

If you are taking calcium to protect your bones, especially if you are also taking vitamin D, which will, among it numerous other benefits, improve your absorption of calcium, you should also be eating lots of vitamin K-rich leafy greens and taking vitamin K2 to ensure that calcium ends up where you want it. These nutrients interact, and we ignore this fact at our peril.

Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised controlled trial. BMJ. 2008 Feb 2;336(7638):262-6.
Abstract

Jones G, Winzenberg T. Cardiovascular risks of calcium supplements in women. BMJ. 2008 Feb 2;336(7638):226-7.
Abstract

Wallin R, Wajih N, Greenwood GT, et al. Arterial calcification: a review of mechanisms, animal models, and the prospects for therapy. Med Res Rev. 2001 Jul;21(4):274-301.
Abstract

---