**4. Companion animals**

The species and breeds within species that have become companion animals have expanded considerably. Rabbits, rats and various exotic animals are increasingly being kept as domestic pets. In this section, we focus on cats and dogs as they dominate the sector.

#### **4.1. Canine vitamin K requirements**

The dog has been domesticated for possibly even longer than agricultural animals [101–103]. The possible breeding matrix that has led to the huge array of current domestic dogs is known to carry several genetic defects [104], and while there are several well‐described coagulopathies in the dog, vitamin K‐specific deficiency is not a widely reported genetic mutation. One case study [105], considered that a black Labrador retriever admitted for a ovariohysterectomy later presented clinically with a vitamin K deficiency coagulopathy. After ruling out several other options, including fat malabsorption problems, ingested coumarin‐based rodenticide, other xenobiotics, liver disease, and noting that the problem was resolved and managed by vitamin K administration, the authors suggested this was a possible case of vitamin K deficiency. This type of disease, therefore, remains a rare disease in the dog.

Conversely, scavenging for food has caused numerous cases of accidental coumarin‐based anticoagulation poisonings in the dog that carry through all geographical regions and is repeatedly reported over time [106–108]. The problem has probably become exacerbated with the introduction of more persistent anticoagulant rodenticides.

Some early studies [109, 110] found that the vitamin K1 supplemented dog stored most of the administered tritiated vitamer in the liver. It was also noted that a proportion was converted into menaquinones, particularly menaquinone‐4. In the light of the recent studies on UBIAD1 [38], this may have an explainable origin.

Incomplete gamma‐carboxylation of vitamin K‐dependent proteins has been implicated in human joint diseases [111, 112]. Some dog breeds have a predisposition to clinically significant arthritic diseases; however, studies on the potential to alter the course of arthritic disease in dogs with vitamin K have not been undertaken.

The commercial dog food manufacturers have an open policy on nutritional information in their products. Many do not explicitly refer to vitamin K content of their products. One major supplier notes that in their dry food product, vitamin K 'activity' is supplied as vitamin K3.

#### **4.2. Feline vitamin K requirements**

Cats are scavengers, they hunt birds and small animals including rodents, these activities bring them into contact with rodenticides [113], and therefore, it is not surprising that the principle reason for veterinary use of vitamin K clinically is as a rescue medication due to accidental rodenticide intoxication. As with the dog, the problem has probably been exacerbated by the increasing use of the more persistent anticoagulants used as rodenticides that have replaced warfarin in order to overcome rodent warfarin resistance.

Using menadione in fish feed is, however, not without problems; too high a dosage, in particular MSB, has proven to cause reduced growth [91, 100]. Nevertheless, it remains one of

The species and breeds within species that have become companion animals have expanded considerably. Rabbits, rats and various exotic animals are increasingly being kept as domestic

The dog has been domesticated for possibly even longer than agricultural animals [101–103]. The possible breeding matrix that has led to the huge array of current domestic dogs is known to carry several genetic defects [104], and while there are several well‐described coagulopathies in the dog, vitamin K‐specific deficiency is not a widely reported genetic mutation. One case study [105], considered that a black Labrador retriever admitted for a ovariohysterectomy later presented clinically with a vitamin K deficiency coagulopathy. After ruling out several other options, including fat malabsorption problems, ingested coumarin‐based rodenticide, other xenobiotics, liver disease, and noting that the problem was resolved and managed by vitamin K administration, the authors suggested this was a possible case of vitamin K deficiency. This

Conversely, scavenging for food has caused numerous cases of accidental coumarin‐based anticoagulation poisonings in the dog that carry through all geographical regions and is repeatedly reported over time [106–108]. The problem has probably become exacerbated with

Some early studies [109, 110] found that the vitamin K1 supplemented dog stored most of the administered tritiated vitamer in the liver. It was also noted that a proportion was converted into menaquinones, particularly menaquinone‐4. In the light of the recent studies on UBIAD1

Incomplete gamma‐carboxylation of vitamin K‐dependent proteins has been implicated in human joint diseases [111, 112]. Some dog breeds have a predisposition to clinically significant arthritic diseases; however, studies on the potential to alter the course of arthritic disease in

The commercial dog food manufacturers have an open policy on nutritional information in their products. Many do not explicitly refer to vitamin K content of their products. One major supplier notes that in their dry food product, vitamin K 'activity' is supplied as vitamin K3.

Cats are scavengers, they hunt birds and small animals including rodents, these activities bring them into contact with rodenticides [113], and therefore, it is not surprising that the principle

pets. In this section, we focus on cats and dogs as they dominate the sector.

the most common vitamin K supplements in fish feed.

type of disease, therefore, remains a rare disease in the dog.

the introduction of more persistent anticoagulant rodenticides.

[38], this may have an explainable origin.

**4.2. Feline vitamin K requirements**

dogs with vitamin K have not been undertaken.

**4. Companion animals**

224 Vitamin K2 - Vital for Health and Wellbeing

**4.1. Canine vitamin K requirements**

Starting in the 1950s in South West UK, a breed of Rex cat was developed out of some accidental breeding with feral tom cats, which led to some reverse mating into their own genetic line with the intent to maintain the Rex breed. One of these lines of development led to the Devon Rex cat. In 1990, three Devon Rex cats were described with a vitamin K deficiency character [114], after exclusion of other factors such as accidental anticoagulant ingestion, liver disease, intestinal malabsorption problems and treatment with vitamin K to correct their deficiency. The nature of the defect in the Devon Rex was investigated in the Netherlands, and this cat was found to have a decreased ability to gamma‐carboxylate vitamin K‐dependent clotting factors due to a decrease binding of reduced vitamin K and the clotting factors to the carbox‐ ylase enzyme [115].

With increasing age, cats also develop diseases that cause vitamin K deficiency coagulopathies, such as liver disease, inflammatory bowel disease and secondary malabsorption syndrome [116–118].

It is possible to induce a vitamin K deficiency through diet, presumably as the cat is not particularly associated with coprophagic behavior. In an early study of queens and their kittens fed either a commercial tuna‐ or a salmon‐based fish diet, there was a notable increase in blood clotting times [119]. Where the information is available, current commercial cat diets provide vitamin K 'activity' in the form of vitamin K3, principally in the dry food products.

The cat is also prone to present clinically with chronic kidney disease (CKD) [120], and the reported prevalence is high, particularly in aged cats. It is interesting that the pathophysiology of feline CKD has been proposed to be sufficiently similar to human disease that the cat could provide a natural model to investigate human CKD [121]. In human CKD, there are several reports of an association with low vitamin K status [122] and a recent multi‐ethnic study demonstrated an inverse association between estimated glomerular filtration rate and a functional marker of vitamin K deficiency, namely de‐phospho‐undercarboxylated matrix Gla protein [123].

Our pilot studies looking at circulating vitamin K in the healthy aged cats found that mena‐ quinone‐4 was the dominating form of vitamin K. This observation would suggest that the vitamin K3 in cat diet is converted through UBIAD1 to menaquinone‐4, although this has not been specifically demonstrated. There is a line of thought that vitamin K may also be provided to the cat through colonic bacterial supply. The absence of long‐chain menaquinones in our study suggest that this is unlikely and evidence supporting colonic absorption of fat‐soluble vitamins K in general is limited [124].

Systemic inflammation is widely accepted as a dominant driver in the aetiology of CKD, and this is an active area of therapeutic interest [125]. The re‐emerging observation of direct anti‐ inflammatory activity for vitamins K1 and K2 and in particular their common 7‐carbon carboxylic acid catabolite [126–128] suggests that a low vitamin K status in CKD may also translate to a weakened anti‐inflammatory potential in the CKD patient and the CKD cat. The role of vitamin K in the homeostatic physiology of the kidney and the pathophysiology of feline CKD has not been the subject of focused study.

**Author details**

Stephen J. Hodges1,3\*

, Bethany Scarrott1

\*Address all correspondence to: shodges@rvc.ac.uk

2 Nofima AS, Muninbakken, Breivika, Tromsø, Norway

and UIT‐The Arctic University of Norway, Tromsø, Norway

of the Red Sea. J Bacteriol. 2008;190(10):3580–7.

pathway. FEBS Lett. 2005;579(17):3493–6.

in germfree mice. Int J Vitam Nutr Res. 1988;58(1):55–9.

, Ragnhild Aven Svalheim2

1 Department of Comparative Biomedical Sciences, The Royal Veterinary College, London, UK

3 Anesthesia and Critical Care Research Group, The University Hospital of North Norway

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[2] Antunes A, Rainey FA, Wanner G, Taborda M, Pätzold J, Nobre MF, da Costa MS, Huber R. A new lineage of halophilic, wall‐less, contractile bacteria from a brine‐filled deep

[3] Srinivas TN, Anil Kumar P, Madhu S, Sunil B, Sharma TV, Shivaji S. Cesiribacter andamanensis gen. nov., sp. nov., isolated from a soil sample from a mud volcano. Int J Syst Evol Microbiol. 2011;61(7):1521–7. [Erratum: Int J Syst Evol Microbiol. 2011;61(10):

[4] Mimuro M, Tsuchiya T, Inoue H, Sakuragi Y, Itoh Y, Gotoh T, Miyashita H, Bryant DA, Kobayashi M. The secondary electron acceptor of photosystem I in Gloeobacter violaceus PCC 7421 is menaquinone‐4 that is synthesized by a unique but unknown

[5] Taggart WV, Matschiner JT. Metabolism of menadione‐6,7‐3H in the rat. Biochemistry.

[6] Dialameh GH, Taggart WV, Matschiner JT, Olson RE. Isolation and characterization of menaquinone‐4 as a product of menadione metabolism in chicks and rats. Int J Vitam

[7] Komai M, Shirakawa H, Kimura S. Newly developed model for vitamin K deficiency

[8] Thijssen HH, Drittij‐Reijnders MJ. Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone‐4. Br J Nutr. 1994;72(3):415–25.

cytochrome and menaquinone levels. FEMS Microbiol Lett. 1996;138(1):59–64.

, Jonathan Elliott1

and

Vitamin K2 in Animal Health: An Overview http://dx.doi.org/10.5772/63901 227

Jayde O'Neil1

**References**

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As with the ageing dog, cats are also likely to present with degenerative joint diseases [129] and the high co‐morbidity relationship with CKD suggests that vitamin K deficiency in the ageing cat is possible [130]. The function of vitamin K in the aetiology of feline degenerative joint diseases remains to be investigated.
