Animal & Veterinary
Vitamin K Substances and Animal Feed
FDA Veterinarian Newsletter 2008 Volume XXIII, No V
by Padmakumar B. Pillai, B.V.Sc.&A.H., M.V.Sc., Ph.D., Biologist, Division of Animal Feeds; Michaela G. Alewynse, Ph.D., Leader, Nutrition and Labeling Team, Division of Animal Feeds; and Sharon A. Benz , Ph.D., Director, Division of Animal Feeds, Center for Veterinary Medicine’s Office of Surveillance and Compliance
Editor’s Note:Although vitamin K is an important nutrient for animals and several sources are available, not all of those sources can or should be used in animal feed. Many have not been approved for use in the United States. Here’s an overview of appropriate use of vitamin K ingredients in the United States.
In his experiments to determine whether cholesterol was a dietary essential, Henrik Dam discovered a new substance, which he named vitamin K. In 1929, he observed a hemorrhagic syndrome in chicks fed a diet from which the sterols were extracted. Eventually, an active, anti-hemorrhagic factor was isolated from alfalfa and was identified as a vitamin K substance. The characterization of this anti-hemorrhagic factor was done by Edward Doisy of St. Louis University. Dam and Doisy shared the Nobel Prize in 1943 for the discovery of vitamin K and its chemical nature.
Green leafy vegetables are good source of vitamin K. Vitamin K is also found in liver, meat, milk, and egg yolk. The major clinical sign of vitamin K deficiency noticed in all species is the impairment of blood coagulation. Clinical signs include, but are not limited to, increased clotting time and hemorrhage. Acute cases of vitamin K deficiency might cause subcutaneous and internal hemorrhages. Vitamin K deficiency can also lead to impaired bone mineralization due to inadequate levels of osteocalcin, a protein involved in bone mineralization.
Deficiencies may result from inadequate vitamin K in the diet, disruption of microbial synthesis within the gut, inadequate absorption from the intestine, ingestion of vitamin K antagonists (substances that counteract the effect of vitamin K), or the inability of the liver to utilize available vitamin K.
Vitamin K can exist in three forms, two of them are naturally occurring and one is a synthetic analogue.
- Vitamin K1, also known as phytonadione or phylloquinone, is the form of vitamin K that occurs naturally in plants.
- Vitamin K2, or menaquinone, also naturally occurring, is the fat soluble form of vitamin K synthesized by the bacteria in the intestinal tract. Bacteria synthesize a range of related forms of this vitamin. These vitamin K analogues are collectively known as K2.
- Vitamin K3, also known as menadione, is the synthetic, water soluble analogue of vitamin K that can be converted to K2 in the intestine. Enzymes in mammalian and avian tissues are also capable of converting menadione to the active forms of vitamin K.
Ever since its initial discovery, vitamin K has been known to be important in the clotting process of blood, because of its involvement in the synthesis of four plasma clotting proteins. These proteins are factor II (prothrombin) and factors VII, IX, and X. More recent studies have shown that vitamin K also plays a role in calcium metabolism. According to the National Research Council’s (NRC’s) publication, Vitamin Tolerances of Animals (1987), the dietary adequacy of vitamin K is often defined as the amount of the vitamin needed to maintain normal levels of plasma vitamin-K-dependent clotting factors.
Poultry, such as broiler chickens and turkeys, are more likely to develop signs of vitamin K deficiency than other species of animals, which can be attributed to their short digestive tract and the fast rate of food passage. Ruminant animals such as cattle and sheep do not appear to need a dietary source of vitamin K due to the microbial synthesis of this vitamin that occurs in rumen, one of the compartments of the stomach of these animals. Since horses are herbivores, their vitamin K requirements may be met from sources present in plants and from microbial synthesis in the lower gut.
Different sources of vitamin K, including those that are listed in the Association of American Feed Control Officials’ Official Publication as accepted for use in animal feed, are broadly denoted as vitamin K active substances. There are two vitamin K active substances that are prior sanctioned for use in poultry feed. (Prior sanction means that these vitamin K active substances were used in poultry feeds prior to 1958, so they have a history of safe use, and they are the subject of a formal FDA sanction of the ingredient for a particular use; the sanction is generally in the form of a letter from FDA stating that the use is acceptable.) These prior sanctioned substances are menadione and menadione sodium bisulfite complex. These two compounds are also widely used in other types of animal feeds, including pet foods, as animal nutritionists often formulate diets with vitamin K active substances in order to prevent vitamin K deficiencies.
Menadione dimethylpyrimidinol bisulfite and menadione nicotinamide bisulfite are vitamin K active substances that are regulated as food additives for use in animal feed. Federal regulation 21 CFR 573.620 lays out how menadione dimethylpyrimidinol bisulfite must be used in feed. Menadione dimethylpyrimidinol bisulfite is a nutritional supplement for the prevention of vitamin K deficiency in chicken and turkey feeds at a level not to exceed 2 g per ton of complete feed, and in the feed of growing and finishing swine at a level not to exceed 10 g per ton of complete feed.
Menadione nicotinamide bisulfite is also used as a nutritional supplement for both the prevention of vitamin K deficiency and as a source of supplemental niacin in poultry and swine. Federal regulation 21 CFR 573.625 states that this substance can be added to chicken and turkey feeds at a level not to exceed 2 g per ton of complete feed, and to growing and finishing swine feeds at a level not to exceed 10 g per ton of complete feed.
Before either menadione dimethylpyrimidinol bisulfite or menadione nicotinamide bisulfite could be used in a manner different from that specified in the appropriate regulation, a new food additive petition would need to be submitted and approved by the Food and Drug Administration.
Substances with vitamin K activity are often added to animal diets to ensure that animals do not develop vitamin K deficiencies. Even though vegetable sources contain fairly high amounts of vitamin K, very little is known about the actual bioavailability of the vitamin from these sources. According to NRC’s publication, Vitamin Tolerances of Animals (1987), based on the limited amount of available information, vitamin K did not result in toxicity when high amounts of phylloquinone, the natural form of vitamin K, are consumed. It is also noted that menadione, the synthetic vitamin K usually used in animal feed, can be added up to levels as high as 1,000 times the dietary requirement without seeing any adverse effects in animals, except in horses. Administration of these compounds by injection has produced adverse effects in horses, and it is not clear if these effects would also occur when vitamin K active substances are added to the diet. Vitamin K and the vitamin K active substances serve important roles in providing an essential nutrient in animal diets.
Vitamin K is an important nutrient for all animals, but not all sources are safe for the animal, and some may raise food safety concerns. Therefore, feed formulators and livestock producers should be aware of what sources of vitamin K are appropriate for the animals they are feeding and choose ingredients accordingly.
Friedrich, W. 1988. Vitamins. Walter de Gruyter, Inc. McDowell, L. R. Vitamins in Animal and Human Nutrition. 2000. 2nd Ed. Iowa State Univ. Press, Ames.
National Research Council. Vitamin Tolerance of Animals. 1987. National Academy Press. Washington, DC.
Shearer, M. J. Vitamin K. Lancet. 1995. 345(8944):229-234