November 6, 2009
Vitamin K walks to a different beat. For starters, those who discovered the vitamin didnt follow the established nomenclature. The first vitamin named in 1912, vitamin A, started the alphabetical trend through vitamin H, until 1935, when Danish scientist Henrik Dam named vitamin K after the German word for clotting vitamin, Koagulationsvitamin.
Dam discovered when chickens were depleted of this fat-soluble vitamin, they developed hemorrhages and uncontrolled bleeding. Dam, along with Edward Adelbert Doisy of Saint Louis University, won the 1943 Nobel Prize for the discovery of the structure and chemical nature of vitamin K.
Their work lead to a greater understanding of how vitamin K works in aiding blood clotting. Vitamin K plays an essential role in adding a carboxyglutamyl group to proteins which regulate blood coagulation and bleeding, said Michael McBurney, Ph.D., FACN, head of scientific affairs, DSM Nutritional Products Inc.
Another extraordinary aspect of vitamin K is where humans source it. While one form of naturally occurring vitamin K, phylloquinone (K1) comes from foods, such as green, leafy vegetables and green tea, the other form, menaquinone (K2), comes from bacteria in the gut. This trade of human-made vitamins is only shared with vitamin D. Bacteria in the gut produce a range of vitamin K2 forms, each with side chains composed of a variable number of unsaturated isoprenoids, or chemical compounds; generally they are designated as MK-n, where n specifies the number of isoprenoids. Menaquinones can also be found in food that contains bacteria, such as cheese and natto, or in animals that also produce the vitamin via their gut bacteria.
However, its usually not the name or where its made that gets consumers thinking about vitamin K. Interest in vitamin K has been generated by the publicity that studies receive, especially when they relate to direct human benefits such as stronger bones, said Yi Wu, Ph.D., chief innovation director for The Wright Group. Others having an interest include a subgroup of the population known as hemophiliacs, whose blood is missing the clotting factor that is so dependent on vitamin K.
Frank Reilly, vice president, innovative products, The E.T. Horn Co., said interest in vitamin K follows the movement of healthier living. There is a greater trend toward proactive healthexercising, eating right and taking supplementsand away from reactive health or the tradition of only seeing a doctor and thinking about health when faced with an ailment, he said. Because of this trend, there has been a greater focus in the industry on the science behind the supplements. Recently, letter vitamins, like K, have had a resurgence through research, and new information about the roles they play in our health has prompted mainstream attention.
The reference dietary intakes (RDIs) for vitamin K vary by age and gender. For men, it ranges from 75 to 120 mg and for women, the range is 75 to 90 mg, depending on age.
These microgram-sized requirements may cause a trial to formulators. Because the requirement for K is in the microgram quantities, homogeneous mixing with other nutrients and excipients poses a challenge, said Dinesh Venkateswaran, technical marketing manager, DSM Nutritional Products Inc. For this reason, the vitamin product form must maximize the number of particles per gram to ensure homogeneity throughout the intended blend. Diane Hnat, senior technical marketing manager, DSM Nutritional Products Inc., added, Because the requirements are in the microgram quantities, it does become also challenging to conduct the retention studies. Many samples will generally have to be analyzed.
The natural products industry offers many ways for consumers to get their daily vitamin K requirements. Delivery innovations have dramatically evolved from the standard tablet or capsule, though they still rank amongst the most commonly used, said John Pham, sales manager, Anderson Global Group. But the new rise of functional bars and beverages has taken advantage of this, revealing itself in nearly every functional health category (digestive health, joint, weight loss, etc.).
Reilly agreed tablets are the most common form of vitamin K supplementation, but added, Softgels made with K2 oil are also popular. New delivery forms for beverages (i.e. stick paks) and fortified foods are also gaining momentum.
With new and old delivery forms, Reilly pointed out E.T. Horn had challenges in making its vitamin K ingredient Nutri-K stable. Vitamin K is light sensitive, which is one of the main challenges for production and packaging, he said. Temperature can also be a concern. Nutri-K utilizes a proprietary process which creates a heat stable product and also minimizes microbial levels.
Stable vitamin K ingredients added to tablets, foods or beverages can offer myriad health benefits. Not only does it help chickens, but vitamin K helps blood clotting in humans.1 This anti-clotting effect can be dangerous for people who are treating heart disease with blood thinners, such as Dicumarol or Warfarin.2 High vitamin K consumption can reverse the anticoagulation effect of the blood thinner, rendering the medication useless.
However, for those not on anticoagulants, vitamin K has shown heart-health benefits. A 2009 Netherlands study found a high intake of menoquinones, especially MK-7, MK-8 and MK-9, could protect against cardiovascular disease (CVD) in healthy women.3 Using data from food frequency questionnaires of 16,057 women, enrolled between 1993 and 1997 and aged 49 to 70 years, who were free of CVD at baseline, researchers determined vitamin K and other nutrient intakes. After eight years of follow-up, they observed an inverse association between menoquinones and risk of CVD. Every 10 mg increase in menoquinones consumed equaled a 9 percent reduction in the disease. Phylloquinone intake was not significantly related to CVD.
While vitamin K offers heart-health benefits, it is better known for its bone-heath properties. Vitamin K assists calcium retention, which helps prevent osteoporosis.4 In children, high vitamin K intake is related to heather bone mass,5 and children with juvenile idiopathic arthritis and who had high vitamin K states had higher bone properties.6 In healthy, prepubescent children, modest supplementation with MK-7 increased circulating concentrations of MK-7 and increased osteocalcin carboxylation.7
In postmenopausal women, menoquinones helped maintain bone strength in the neck and hip, whereas the women taking a placebo experienced a weakening of their bones,8 and 5 mg of vitamin K1 supplementation for two to four years may protect against fractures and cancers in postmenopausal women with osteopenia, a condition where bone mineral density (BMD) is lower than normal.9
Two studies done on VitamK7, which is the European version of E.T. Horns Nutri-K ingredient, show its bone-building behavior. In the first of the two unpublished trials, 90 mg of VitamK7 increased osteocalcin (Gal-OC), a vitamin-K dependent calcium-building protein, by 19 percent; and decreased undercarboxylated osteocalcin (Glu-OC), a biomarker of vitamin K status inversely associated with vitamin K intake, by 20 percent after one week in 12 healthy volunteers. The second study showed VitamK7 inhibited the production of prostaglandin E-2 (PGE-2), which stimulates bone resorption. Both studies were conducted by G. Littarru, Ph.D., of the University of Marche in Italy.
Vitamin K has also shown to protect against prostate and liver cancer. A 2008 German study found a dietary intake of menaquinones, but not phylloquinone, lead to a 35-percent reduction in prostate cancer risk in more than 11,000 men.10 In a follow up study, the same German researchers found similar results with improved status of vitamin K being linked to a lower risk of both advanced-stage prostate cancer and high-grade prostate cancer.11
Forty women diagnosed as having viral liver cirrhosis either received 45 mg/d of menaquinones or a placebo between 1996 and 1998 in a Japanese study.12 Liver cancer was detected in two of the 21 women given menaquinones and nine of the 19 women in the control group, making menaquinone intake associated with a 20-percent reduction in the risk of liver cancer.
One sweeping study on vitamin K published in October the 2009 issue of the American Journal of Clinical Nutrition found it may help prevent age-related conditions such as bone fragility, arterial and kidney calcification, CVD and, possibly, cancer. Researchers from the Children's Hospital Oakland Research Institute analyzed data from hundreds of published articles dating back to the 1970s and found an inverse relationship between vitamin K intake and age-related diseases.13
Also related to age, vitamin K supplementation may have a beneficial effect in preventing or treating Alzheimers disease.14 That same study found vitamin K may also reduce neuronal damage associated with CVD.
With health benefits ranging from cognition to bone health to heart health, this unique vitamin may be showing up in more supplements, functional foods and marketing campaigns. As Pham puts it, For vitamin K (and K2), I believe it to only be a matter of time before it is considered a standard in all multi-vitamin formulations.
With more promotion and studies, this anticoagulant just may get consumers and natural products manufactures blood pumping for more vitamin K products.
References on the next page
1. Cranenburg EC, Schurgers LJ, Vermeer C., Cranenburg EC, Schurgers LJ, Vermeer C. Thromb Haemost. 2007 Jul;98(1):120-5.
2. Kamien M. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust. 2005 Apr 4;182(7):366-7;
3. Gast GC, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009 Sep;19(7):504-10.
4. Brett, N.D., Jennifer. "How Vitamin K Works." 21 December 2006. HowStuffWorks.com. <http://www.howstuffworks.com/vitamin-k.htm> 28 September 2009.
5. van Summeren MJ, et al Vitamin K status is associated with childhood bone mineral content. Br J Nutr. 2008 Oct;100(4):852-8. Epub 2008 Feb 18.
6. van Summeren MJ, et al. Extremes in vitamin K status of bone are related to bone ultrasound properties in children with juvenile idiopathic arthritis. Clin Exp Rheumatol. 2008 May-Jun;26(3):484-91.
7. van Summeren MJ , et al. The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children. Br J Nutr. 2009 May 19:1-8.
8. Knapen MH, Schurgers LJ, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007 Jul;18(7):963-72.
9. Cheung AM, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008 Oct 14;5(10):e196.
10. Nimptsch K, et al. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2008 Apr;87(4):985-92.
11. Nimptsch K,et al. Serum undercarboxylated osteocalcin as biomarker of vitamin K intake and risk of prostate cancer: a nested case-control study in the Heidelberg cohort of the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2009 Jan;18(1):49-56.
12. Habu D, et al. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004 Jul 21;292(3):358-61.
13. McCann JC, Ames BN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am J Clin Nutr. 2009 Oct;90(4):889-907.
14. Allison AC. The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease. Med Hypotheses. 2001 Aug;57(2):151-5.
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