VITAMIN KQ® – "FUEL" FOR BONES AND JOINTS
Vitamin KQ® is a water-soluble, UV-stable, bioavailable form of Vitamin K1, which in turn activates the body's natural production of Vitamin K2. Overlooked for a long time, science has gained remarkable new insights into Vitamin K in recent years.
Vitamins K1 and K2 are involved in many physiological processes, such as blood clot regulation, bone metabolism, energy metabolism, as well as apoptosis and immunity-related metabolic processes. Another primary function of Vitamin K lies in regulating calcium metabolism. The enzyme carboxylates a range of VK-dependent proteins responsible for a wide spectrum of biological functions.
These processes are all related to the incorporation (into bones) or breakdown (in blood vessels) of calcium. Without Vitamin K, calcium cannot enter the bones. For example, Osteocalcin becomes metabolically active with the help of Vitamin K, which is necessary for the incorporation and binding of calcium in bones.
In the case of a Vitamin K deficiency, these corresponding proteins remain inactive, leading to lower bone density and an increased risk of bone diseases. The publication of the 2014 study in Australia and the 2015 study in the USA, "Vitamin K Absorption in Horses: Intestinal Absorption of Different K Vitamins," shows that Vitamin KQ® achieves significantly higher bioavailability compared to fat-soluble Vitamin K.
This study proves that the water-soluble form of Vitamin KQ® is the most effectively absorbed. This high efficacy of Vitamin KQ® is the basis of our BoneKare® products.
1: McCann and Ames, 2009
2: Skinner, Cawdell-Smith, Regtop, Talbot, Biffin, Bryden, University of Queensland, Australia, Agricure Pty. Ltd.
Vitamin KQ Equine Trial Example 1
Biffin JR, Regtop HL and Talbot AM. (2008) Proceedings of the Australian Equine Science Symposium 2:54
The primary source of VK in the food chain is phylloquinone (K1), a transient instantaneous product of photosynthesis in live green leaves but is destroyed in cut leaves of various grasses by light (Biffin et al., 2008b). VK levels were measured in this study in fresh-cut ryegrass, ryegrass hay after 2 days sun-drying, in hay 2 weeks after shedding, and in ryegrass haylage 2 weeks after packing in sealed bag. Levels were 8.9, 2.3, 1.9 and 7.8 mg/kg DM, respectively. Moreover, VK is poorly absorbed (c. 10%) from the GIT of animals, as it is tightly bound within chloroplasts, and being fat soluble is poorly transported in the gut.
VITAMIN KQ® EQUINE TRIAL EXAMPLE 2
Biffin JR, Regtop HL and Talbot AM. (2008) Proceedings of the Australian Equine Science Symposium 2:54
It has been shown (Biffin et al., 2008a) that to achieve 90% carboxylation of osteocalcin, 7 mg VK/ day was required by a 500 kg horse in a bioavailable soluable form (Vitamin KQ®,QAQ). In a subsequent double-blind trial, bone density development was assessed in 26, 2 year-old Thoroughbred racehorses in the same stable. The treatment group received 7 mg QAQ/day and the control group, a blank powder. Density was assessed as radiographic bone aluminium equivalence (RBAE) on digital Xray images of the third metacarpal bone. The trial continued for 8 months and during that period there was greater increase in bone density in the treatment when compared to the control group.
Change in bone density of 2year-old Thoroughbreds given a bioactive form of Vitamin K1
Marked decrease in the incidence of Shinsoreness (DMD).
Biffin JR, Regtop HL and Talbot AM. (2008) Proceedings of the Australian Equine Science Symposium 2:54
A total of 38 two year olds were divided into two groups of 19 (treatment and control) and monitored for clinical signs of DMD (dorsal metacarpal disease, "shinsoreness") from commencement of training in September 2008 to May 2009. The treated group received 7mg Vitamin K daily, control group an equal amount of blank powder daily. There were two incidences (10.5%) of DMD in the treated group and seven cases (36.8%) in the untreated group.
Both of the cases in the treated group were mild. The horses didn't have to spell and have since won races.
Bone mineral density can be correlated with visual radiographic lesions.
Biffin JR, Regtop HL and Talbot AM. (2008) Proceedings of the Australian Equine Science Symposium 2:54
This example shows that high bone mineral density (DMD) in horses can be correlated with reduced incidence of both dorsal metacarpal disease in young racehorses and visible radiographic lesions (VRL) in yearlings.
Radiographic Bone Aluminium Equivalence (RBAE) was measured on lateral view of the 3rd metacarpal of sixty-nine thoroughbred yearlings.
Vitamin K levels in Serum (ng/ml) in 14 yearlings grazing fresh green pasture.
Biffin JR, Regtop HL and Talbot AM. (2008) Proceedings of the Australian Equine Science Symposium 2:54
Fourteen thoroughbred yearlings were provided with a supplement to normal pasture grazing. Four yearlings were supplemented with a blank paste as placebo. Five were supplemented with Vitamin K in oil and five were supplemented with water-the soluble Vitamin K composition (Quinaquanone®). Serum Vitamin K was then determined. Then Carboxylation levels were determined on those provided with soluble Vitamin K and compared with those on placebo after 60 days.
It can be seen that administration of Vitamin K improved Vitamin K serum levels. Supplementation with a stabilised, water-soluble Vitamin K significantly changed serum levels in the horses, and significantly raised carboxylation in horses during this 60 day trial. This graph shows the range of each group.
Radiographs before and after supplementration with „KQ®"
Biffin JR, Regtop HL and Talbot AM. (2008) Proceedings of the Australian Equine Science Symposium 2:54
In this trial, 8 yearlings with servere OCD lesions on x-ray were supplemented with 14mg Vitamin K (KQ®) per day for 3-7 months and then re-examined. The table shows that Vitamin K supplementation was associated with a significant reversal in the severity of lesion score.
OCD CASE 1. 2.5 MONTHS WITH SUPPLEMENT
OCD CASE 2. 3 MONTHS WITH SUPPLEMENT
OCD CASE 3. 4 MONTHS WITH SUPPLEMENT
OCD CASE 4. 4 MONTHS WITH SUPPLEMENT
OCD CASE 5. 4 MONTHS WITH SUPPLEMENT
OCD CASE 6. 6.5 MONTHS WITH SUPPLEMENT
|
Case Nr. |
Initial Xray |
Re-Xray |
|
1 |
3 |
2 |
|
2 |
4 |
2 |
|
3 |
4 |
1 |
|
4 |
4 |
2 |
|
5 |
4 |
2 |
|
6 |
4 |
2 |
|
7 |
4 |
3 |
|
8 |
4 |
4 |
OCD lesion score of 8 thoroughbred yearlings from group 1-4
1= no significant visible lesions, 4= likely to be career-threatening
Intestinal absorption of different vitamin K compounds in the horse
J.E. Skinner*1, A.J. Cawdell-Smith 1, J.R. Biffen 2, A.M. Talbot 2, H.L. Regtop 2, and W.L. Bryden 1. 1 Equine Research Unit, The University of Queensland, Gatton, Queensland, Australia; 2 Agricure Pty Ltd., Braemar, New SouthWales, Australia
Twelve mature geldings were paired and allocated to 6 groups in a random crossover design. Sampling was undertaken over 6 experimental periods. There were 6 treatments consisting of a control, K1, K2 (in the form of MK-4), K3 and KQ (QAQ; a soluble form of K1 and K2 (10:1). These were administered as a 200 mg oral bolus to each horse. Blood sampling was undertaken for 480 min. In the last treatment K1 (200mg) was administered intravenously and blood samples collected at designated intervals for 2 h.
Plasma samples were analyzed by HPLC for K1, MK-4 and K3 concentrations. Plasma K1 concentrations differed significantly across time and between treatments (P < 0.001) with the highest plasma K1 concentrations occurring with the KQ treatment compared with the other treatments (P < 0.0001), with K1 peaking second highest. Both KQ and K1 showed no detectable conversion to K3 or MK4 in plasma. Moreover, the administration of K3 showed that plasma K3 was well absorbed, but there was no detectable conversion to MK4 in plasma. Pharmacokinetic parameters [area under the curve (AUC), time to maximum (tmax) and maximum concentration (Cmax)] were derived for each treatment and bioavailability calculated for oral treatments relative to K1 administered intravenously (100%). The bioavailability was 0.45% for QAQ and 0.14% for K1. The results of this study demonstrate that the horse appears to almost exclusively have K1 in plasma in contrast other species. This suggests that there is no specific conversion of K1 to K3 or K3 to MK-4 in the horse, contrary to what occurs in some other mammals. The soluble form of the vitamin, KQ was the most efficiently absorbed and should be evaluated in further studies that examine metabolism of vitamin K in the horse, especially bone metabolism.
Extent of vitamin K absorption from the equine hindgut
J.E. Skinner*1, A.J. Cawdell-Smith 1, J.R. Biffen 2, H.L. Regtop 2, A.M. Talbot 2, and W.L. Bryden 1. 1 Equine Research Unit, The University of Queensland, Gatton, Queensland, Australia; 2 Agricure Pty Ltd., Braemar, New SouthWales, Australia
Vitamin K consists of a group of structurally related compounds: phylloquinone (K1), that is synthesized by plants; the menaquinones (MKs also known as K2) synthesized by bacteria and menadione (K3), a synthetic vitamer that does not have a side-chain. There is increasing evidence that vitamin K has a significant role in bone metabolism, energy metabolism, spermatogenesis, apoptosis and innate immunity, in addition to blood coagulation. The lack of a side chain restricts the activity of K3 to a role in blood clotting. The consensus is that animals meet their vitamin K requirements from plant and bacterial sources. Bacterial synthesis and subsequent absorption of K2 is generally considered to be an important source of vitamin K and yet there are no published reports of the extent and efficiency of these processes. The aim of this study was to determine if vitamin K is absorbed from the hindgut of the horse. Vitamin K1 was coated with calcium alginate to prevent absorption in the small intestine thus allowing it to pass into the hindgut. Four mature geldings were dosed with a 200 mg oral of either (1) KQ [QAQ, Quinaquanone a soluble form of K1 and K2 (10:1)]; (2) KQ coated with 1.5% calcium alginate; or (3) K1 oil. Blood sampling was undertaken for 12 h and plasma samples were analyzed by HPLC for K1, MK-4 and K3 concentrations. In vitro studies with enzymes (amylase, protease, lipase, and cellulase) showed minimal release of K1 and breakdown of the alginate capsule over a period of 10 h. In contrast, when incubated with a concentrated microbial fraction of horse feces, breakdown of the alginate capsule was complete within 30 min.
Plasma K1 concentrations differed significantly between treatments (P < 0.05). Plasma K1 concentrations were 3-fold higher in the KQ treatment compared with K1 oil and K1 oil was higher than the encapsulated KQ; peak plasma values occurred for all 3 treatments at 4 h. The results of this study questions the absorption of vitamin K from the hindgut of the horse. It shows that the intestines are partly responsible for the breakdown of the capsule with encapsulated KQ reaching a Cmax of 1.5 ng/mL as opposed to 3.75 ng/mL for KQ at 4 h. There was no further uptake of K1 from the spheres in the hind gut, suggesting that the hindgut does not facilitate vitamin K absorption in the horse. Studies in rats and humans have also demonstrated extremely poor absorption of vitamin K from the hindgut suggesting that bacterially synthesized vitamin K does not contribute substantially to vitamin K status.
Maternal transfer of vitamin K to the foetus and neonatal foal
T.J. Fischera, A.J. Cawdell-Smitha, A.M. Talbotb, H.L. Regtopb, J.R. Biffinb, and W.L. Brydena
a) The University of Queensland, Equine Research Unit, School of Agriculture and Food Sciences, Gatton, 4343 ab) Agricure Pty Ltd, Braemar NSW, 2575
The role of vitamin K in blood coagulation has been known for many decades, but in recent years it has been shown to be a factor in many other physiological processes. Studies in humans and rodents have highlighted the role of vitamin K, and its dependent proteins, in bone metabolism, energy utilisation and immunity. Placental transfer of vitamin K is limited in the human, and there has been no research conducted on horses on this aspect of vitamin K metabolism or transfer of the vitamin into milk. The objective of this study was to determine if vitamin K crosses the equine placenta, and if the concentration of the vitamin in mare’s milk can be modulated by dietary supplementation.
Eighteen late gestation mares were allocated to three treatment groups. These treatments consisted of a control (no vitamin K administration), Vitamin K3 (menadione) and vitamin KQ (QAQ a soluble form of K1 and K2 (10:1)). The vitamin treatments were administered as a 4mg oral bolus paste to each horse, 3 times per week (Monday, Wednesday and Friday), until parturition. Administration of the paste commenced 28 days before the due foaling date. Blood sampling of the mares was undertaken weekly up to foaling, at parturition and 7 days later. Blood sampling of the foals and milk collection from the mares were performed simultaneously prior to first suckle by the mare, 12hrs, 24hrs and 7 days post birth. Plasma samples for each treatment along with milk samples were analysed by HPLC for vitamin K concentrations.
No differences in circulating concentrations of vitamin K were found in mares irrespective of supplementation group. However, milk concentrations at parturition reflected supplementation with KQ mares having a significantly (p<0.05) higher value than the other two groups. Values for both supplemented groups returned to control levels within 7 days of cessation of supplementation. The failure to detect differences in circulating levels in mares prior to foaling may reflect the time of sample collection as previous studies found that the half-life of vitamin K is rapid. Plasma K1 concentrations in umbilical cord plasma and foal plasma at birth (pre-suckle) were below the detection limit of the analysis (<0.01ng/mL); demonstrating that vitamin K does not cross the placenta in the mare. However, in the week following birth, foal plasma levels reflected milk levels. Plasma K1 concentrations in umbilical cord plasma and foal plasma at birth (pre-suckle) were below the detection limit of the analysis (<0.01ng/mL); demonstrating that vitamin K does not cross the placenta in the mare. However, in the week following birth, foal plasma levels reflected milk levels.
The results of this study clearly demonstrate that in the mare, as in women, vitamin K is not transported across the placenta. The study also demonstrates that milk can be enriched by supplementation of the mare with vitamin K.
This weanling was started on BoneKare® after the identification of a stifle OCD lesion. Follow up RADS demonstrated remarkable healing of the OCD lesion after 5.5 months. Clinical impressions suggest that BoneKare® has real effect on bone remodeling and development.
June, 03 – November, 24
Credit: Timothy R. Ober, DVM, MRCVS
FOAL AGE 2 ½ MONTHS
FOAL AGE 4 ½ MONTHS
NOTE: Coffin bone fractures are known to heal by fibrous union leaving a wide radiolucent fracture line that is evidence of an incomplete healing. There is a narrowing of the fracture line after 60 days, with continued treatment, complete healing will occur.
Credit: Daniel V. Flynn, VMD – Equine Veterinarian
3 MONTHS WITH SUPPLEMENT
DR CHRISTOPH ROWOLD
3 ½ MONTHS WITH SUPPLEMENT
DR CHRISTOPH ROWOLD
3 ½ MONTHS WITH SUPPLEMENT
DR CHRISTOPH ROWOLD
3 ½ MONTHS WITH SUPPLEMENT
DR CHRISTOPH ROWOLD
3 MONTHS WITH SUPPLEMENT
