Use of collagen supplementation in dogs with osteoarthritis: Difference between hydrolysed collagen peptides in SPECIFIC CJD Joint Support and UC-II in Flexadin Advance
Background
At the dog relaunch in December 2019, SPECIFIC CJD Joint Support has been optimised by the addition of Petagile® (hydrolysed collagen peptides), beta-1,3/1,6-glucans and an increased level of chondroitin sulphate (replacing glucosamine). Already existing dietary characteristics as a moderate energy density, high levels of EPA & DHA, added GLA, and increased levels of antioxidants and manganese remained unchanged. Flexadin Advanced (Vetoquinol) is a dietary supplement for support of dogs with osteoarthritis (OA), which contains UC-II (undenatured type 2 collagen), omega-3 fatty acids, Boswellia Serrata and vitamin E. Although SPECIFIC CJD and Flexadin both contain collagen, the collagen components and their working mechanism in both products are different.
Collagen
Collagen is a fibrous protein which is present in connective tissue, skin, bone etc, providing strength and firmness to tissues. Collagen has a complex structure of long peptide chains composed of primarily glycine, proline and hydroxyproline. There are different types of collagen with differences in the composition of the peptide chains. Collagen type I is the most prevalent type of collagen in mammals, which is present in skin, tendons, ligaments and bones. Type 2 is the most prevalent type of collagen in cartilage.
Collagen peptides (PETAGILE®) in SPECIFIC CJD Joint Support
SPECIFIC CJD Joint Supports contains 1.8% PETAGILE®. PETAGILE® is a mixture of specific bioactive collagen peptides of predominantly type I collagen with an average molecule weight of approximately 6000 Dalton for support of osteoarthritis. These collagen peptides are highly digestible, can be absorbed as amino acids, di-peptides and to some extend in molecular intact form and accumulate in cartilage tissue (Oesser et al. 1999). In in-vitro studies with porcine, bovine or canine chondrocytes, PETAGILE® collagen peptides increased biosynthesis of cartilage matrix and reduced inflammatory cytokines, activity of proteases and cartilage degradation (Oesser & Seifert 2003, Schunck et al 2009, Schunck et al. 2017). In a study with inbred mice (STR/ort), which spontaneously develop osteoarthritic lesions, PETAGILE® collagen peptides were able to slow down or even halt cartilage destruction (Oesser et al. 2007). In clinical trials with dogs with osteoarthritis, hydrolysed collage peptides reduced lameness and improved mobility (Weide 2004, Beynen et al. 2010, Schunck et al. 2017). The observed reduction in lameness and increased mobility of the dogs receiving collagen peptides was associated with significantly decreased plasma levels of MMP-3 (matrix metalloprotease-3; a biomarker for cartilage degradation) and increased levels of TIMP-1 (tissue inhibitor of metalloprotease-1; inhibits with high affinity MMP-3) (Weide 2004).
Undenatured type II collagen (UC-II) in Flexadin Advanced
The collagen in Flexadin Advanced is type 2 collagen, which has not been treated with high temperatures or chemicals, and thereby kept its original structure. It has been demonstrated that undenaturated type-II (UC-II) improved function and reduced deterioration of articular cartilage in a rat model of OA (Bagi et al. 2017), improved symptoms in human knee OA (Lugo et al. 2016) and reduced inflammation and pain (D’Atilio et al 2007, Gupta et al. 2011) and mobility ( Stabile et al. 2019) in dogs with OA. During OA, collagen in cartilage will get damaged and will be regarded as ‘foreign protein’, which will be attacked by the body’s immune system. It has been hypothesized that UC-II functions through oral tolerance, which takes place in the small intestine where food is being absorbed. After intake of a small amount of UC-II, a T-cell response in activated at the level of the Gut-Associated-Lymphoid-Tissue (GALT), in the Peyer’s patches. After this stimulation, regulatory T helper 2 and 3 (TH2 and TH3) cells migrate from the GALT through the lymphatic system into the peripheral circulation and, when they match the type 2 collagen as antigen (as in the arthritic joints), they secrete cytokines (such as TGF-b, IL-4, IL-10) that results in the downregulation of the TH1 cells (which are involved in producing the inflammation and destruction of collagen in OA) (Gupta et al. 2011, Stabile et al. 2019).
PETAGILE® in SPECIFIC CJD Joint Support vs (UC-II) in Flexadin Advanced
Not only the type of collagen in CJD and Flexadin is different, also the amount required for a beneficial effect on OA is different. Studies on PETAGILE® in dogs with OA have shown that improvement of mobility were obtained at an intake of about 1 gram PETAGILE® per 5 kg body weight. SPECIFIC CJD Joint supports contains 1.8% PETAGILE® in order to supply 1 gram of PETAGILE® per 5 kg body weight. Studies on UC-II in dogs with arthritis used 40 mg UC-II, which contains 10 mg undenatured UC-II, per day (Gupta et al. 2011, Stabile et al. 2019). The dose of denatured UC-II in Flexidin Advanced is similar to this amount. Although the daily intakes of the collagen components through CJD or Flexadin are very different, it can be concluded that both for CJD as Flexadin the product supplies the required amount of the specific collagen component which proved to be effective in clinical studies in dogs with OA.
Besides the collagen components SPECIFIC CJD and Flexadin Advanced contain also other components to support OA in dogs:
SPECIFIC CJD Joint Support contains per 100 g: 0.76 g EPA, 0.74 g DHA, 0.1 g GLA, 0.12 g beta-1,3/1,6-glucans, 0.23 g chondroitin sulphate, 82 mg vit E, 2.6 mg manganese, 16.8 mg vit C
Flexadin contains per chew: 95 g total n-3 fatty acids, 9.3 mg EPA, 21 mg vit E, Boswellia Serrata (dose unknown; no controlled studies on efficacy in dogs with OA)
In Table 1, a comparison of the daily intake of relevant components for support of OA in SPECIFIC CJD and Flexadin Advanced is shown. The products provide different types of collagen, but each at a proven effective dose for the specific type of collagen component. The amount of total omega-3 fatty acids, EPA and vitamin E in Flexadin Advanced is almost negligible compared to the levels provided through SPECIFIC CJD. Especially for EPA, studies have shown that EPA improves mobility in dogs with OA (Miller et al. 1992, Roush 2010, Fritsch et al. 2010) by reducing the activity of cartilage degrading enzymes and reduction of inflammatory mediators. In contrast to Flexadin Advanced, SPECIFIC CJD Joint Support also contains beta-glucans and chondroitin sulphate that can improve mobility in dogs with OA and manganese and vitamin C, which are important for the synthesis of cartilage.
Table 1. Comparison of relevant components for support of OA in dogs in SPECIFIC CJD Joint Support and Flexadin Advanced (daily intake for an average adult dog of 20 kg*)
Component
|
SPECIFIC CJD Joint Support
|
Flexadin Advanced
|
PETAGILE® , type 1 bioactive collagen peptides, mg |
5100 |
|
UC-II, type 2 undenaturated collagen type II, mg |
|
10
|
Total n-3, mg |
4845 |
95
|
EPA, mg |
2166 |
9.3
|
Vit E, mg |
234 |
21
|
Boswellia |
|
+ |
GLA, mg |
285 |
|
Beta1-3/1,6-glucans, mg |
340 |
|
Chondroitin sulphate, mg |
655 |
|
Vit C, mg |
48 |
|
Manganese, mg |
7.4 |
|
SPECIFIC Joint Support: 285 g/day; Flexadin Advanced: 1 chew/day