Stimulates joint cartilage renewal in dogs and high anti-inflammatory activity
(*) The sooner the joint condition is taken care of, the faster and the better the results will be.
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Daily serving: 5 gr (for 45 lbs dog) / Servings per container: 30
Calbrex-i™ shares the same core content of active substances with Calbrex™ but it has an added mix of components that provides a more powerful anti-inflammatory response. It makes Calbrex-i™ a more suitable option in the initial support phase of a joint condition that is severe or when the dog suffers from acute pain.
Boswellia Serrata (30% AKBA)
Controlling a major inflammation pathway (the 5-LOX route)
Boswellia is a gum-resin extracted from the trunk of a tree that grows in India. It has been used for centuries in ayuverdic medicine for its potent anti-inflammatory properties. It contains several phytoactive components and 4 boswellic acids that are responsible for its effectiveness without any side effects. Out of these four boswellic acids, the AKBA (acetyl11ketoβ) is the most powerful inhibitor of 5-lipoxygenase, an enzyme responsible for one of the most important inflammation pathways.
Calbrex-i™ contains a standardized extract of Bowellia with a 30% concentration in AKBA boswellic acid, while the basic AKBA fraction is only around 2% or 3%. This confers Calbrex-i™ a significant effectiveness as a 5-LOX inhibitor, an enzyme that is involved in the biosynthesis of pro-inflammatory leukotrienes.
Other studies also indicate that Boswellla 30% AKBA has an ability to significantly inhibit matrix metalloproteinase enzymes (MMP-3) that break down cartilage, collagen and connective tissues.
Calbrex-i™ with AKBA 30% Boswellic acid can enhance joint function within 7 days - Full effectiveness is reached at 90 days with a 50% average mobility improvement.
Bromelain is a combination of protein-digesting enzymes extracted from the stems of pineapple. It facilitates digestion, inhibits platelet aggregation and possesses notable anti-cancer properties. But It is mostly famous for its analgesic and anti-inflammatory activities. It can downregulate prostaglandin synthesis and is able to lower pro-inflammatory mediator serum and tissue levels of bradkynin, slowing down the cascade of cytokine release.(1)
Fibrin polymer formation is used for the foundation of the blod clot at a wound site and is essential to the coagulation process. However excessive synthesis of fibrin or fibrin deposition within damaged tissue is a critical contributing factor of inflammation in arthritic joints. Bromelain enhances the serum fibrinolytic activity, it inhibits the fibrinogen synthesis and it also directly degrades fibrin and fibrinogen. (2)
The proteolytic enzymes of Bromelain helps in post-operative surgery by limiting bruising and swelling. It improves the healing process and shortens the recovery time(3).
Celery Seed Extract
Standardized to 85% of 3nB (3-n-butylphthalide)
Celery seeds contain a remarkable substance that explains why it has been used as natural therapy for acute and chronic inflammatory conditions . This substance is called 3nB (3-n-butylphthalide) and the Celery Seed Extract (CSE) rich in 3nB has shown to be at least as effective as aspirin, ibuprofen, and naproxen in suppressing arthritis in a model of polyarthritis (1).
A human study on patients that suffered from osteoarthritis, osteoporosis or gout for more than 10 years to the point that they couldn't carry on regular daily activities showed great results. After 3 weeks of treatement with CSE 85% 3nB there was an average of 68% reduction in pain with no side effects (2).
An other study with 70 patients was made and the subjects received 75 mg of the CSE twice daily for three weeks. Subjects reported excellent results with clnically significant reductions in pain scores, mobility and quality of life. And again, no side effects were noted. CSE is also particularly helpful for sufferers of gout, as 3nB appears inhhibit the enzyme that causes the production of the uric acid that causes gout (3).
Bioactive Collagen HP-BCP Special Pets
The most effective form of collagen for joints adapted to dogs digestive system
Collagen HP-BCP is the best known form of collagen for joint health and it has been extensively studied in different clinical trials. Because dogs digestive system differs from humans, specific adjustments were made to ensure a high rate of absorption at the gut level. HP-BCP Pets is proven to enhance the joint renewal metabolism and stimulate the growth of new cartilage tissue in dogs. HP-BCP Pets is well absorbed and it concentrates in the joints where it has a significant impact on specific cells within the cartilage that are responsible for regularly producing new cartilage components. These cells, called chondrocytes, will increase their synthesis of collagen and proteoglycans, which together represent 95% of the cartilage structure.
Knee Cartilage Histological Section
A study by the Collagen Research Institute in Kiel, Germany, showed that HP-BCP accumulates in joint tissue and stimulates cell biosynthesis to produce collagen and proteoglycans. After 3 months of therapy, a significant change in formerly degraded cartilage is visible. Compared to joint cartilage with no treatment (left side), the joint cartilage appears supple, smooth and full in appearance.
(Orally administered collagen hydrolysate halts the progression of osteoarthritis in STR/ort MICE. Oesser S et al.(2007) Osteoarthritis Cartilage 15:C61-C62,94)
Magnetic Resonance Imaging
The study conducted at Tufts Medical Center and Harvard Medical School and presented at the OARSI congress (Osteoarthritis Research Society International) showed that oral intake of HP-BCP provides clear improvement in human cartilage, for the first time measured using MRI (Magnetic Resonance Imaging) technology.
(Change in knee osteoarthritis cartilage detected by delayed gadolinium enhanced magnetic resonance imaging following treatment with collagen hydrolysate: a pilot randomized controlled trial. McAlindon and Al. (2011) Osteoarthritis and Cartilage Volume 19, Issue 4, April 2011, Pages 399-405)
Hyaluronic Acid Complex HJ
Restoring and maintaining quality synovial fluid
To perform well, joints need lubrication and this is why there is a thick viscoelastic substance called the synovial fluid inside the joint capsule. What confers this fluid its remarkable properties is Hyaluronic Acid (HA), a molecule that has the ability to hold up 1000 times its weight in water. HA forms large viscoelastic gels that reduce friction between cartilage surfaces and protects them.
Arthritic joints have a much lower concentration of HA than normal joints and restoring adequate HA levels is an important part of joint health. The Hyaluronic Complex HJ is a unique patented natural ingredient with a high content of sodium hyaluronate as a mix of High/Very High molecular weight Hyaluronic Acid. HA is the chief component of synovial fluid and its usefulness has been proven in numerous clinical trials.
Low Molecular Weight Hyaluronic Acid (LMW-HA) is sometimes touted as a better HA because it allows for a better intestinal absorption. But scientific evidence shows that HA is only safe and beneficial in its High Molecular Weight form (HMW-HA). Research has revealed that LMW-HA can be harmful as it promotes inflammation and has other negative side effects. On the other hand HMW-HA is much more effective at retaining water and its rate of absorption is significant enough to accumulate in the joint cavity.
The uptake of high quality HA in the joints improves lubrication, reduces inflammation and slows down the degradation process. The cartilage is also better nourished, it helps the cartilage nenewal and it can significantly improve joint flexibility.
Research has observed that the sulfur content of cartilage decreases with age, and that this decrease parallels degeneration in the joints. A study has clearly shown that arthritic joints have sulfur levels three times lower than healthy ones. Sulfur is necessary for making collagen, the primary constituent of cartilage and connective tissue.
MSM is a bioavailable natural form of organic sulfur found in all living organisms. It is exceptionally well tolerated and it is rated as one of the safest substances in biology. Sulfur is the third most abundant mineral in humans and mamalians, after calcium and phosphorous. There is a general assumption that sulfur requirement is met with adequate protein intake which provides the amino acids methionine and cysteine, but disfunctions in methionine metabolism could induce sulfur deficiencies.
MSM is very helpful for joint metabolism. Even severe cases of joint alteration can benefit from MSM supplementation as it is able to significantly improve chronic pain without any side effects. Aside from its anti-inflammatory action MSM can also stimulate the the immune system and improve the internal production of Glutathione, the body's major own antioxidant.
Eggshell Membrane NEM®
Eggshell Membrane NEM®is a food-sourced ingredient derived from the membrane of an eggshell. It supplies essential nutrients needed to support joint mobility and the healthy production of cartilage and connective tissue. It is a unique biological matrix proven bioavailable and effective.Double-blind, placebo-controlled and open-label trials have all showcased an increase in joint comfort, flexibility, and increased range of motion. Published human studies have shown beneficial results in 7-10 days.
Harpagophytum procumbens, known as Devil's Claw is traditionnally used for its benefits on the joints and concerns about rheumatic ailments. It relieves pain and inflammation and Its effectiveness is commonly attributed to its identified special active constituents, the "harpagosides". Several clinical trials have shown effectiveness in alleviating pain and it appears to prevent the production of pro-inflammatory cytokines. This result seems derived from its harpagosides content but also from the interaction of several substances contained in its root (1).
Devil's Claw appears to be effective for chronic pain with a notable improvement of symptoms that reaches peak efficacy after a period that ranges from 6 to 8 weeks (2) (3) (4), though some scientific sources cite a 4 months duration to reach maximal efficacy (5).
Organic Silica (Orthosilicic acid)
Silicon is an essential trace mineral that is naturally present in the human body. It play a major role in bone strength, healthy skin and nails and cartilage formation. Studies have shown that a silicon deficient diet produces aberrant metabolism of the bone and connective tissue leading to structural abnormalities of the articular cartilage with small and poorly formed joints. It was later discovered that silicon deprivation decreases collagen formation in wound healing as well as bone formation.*
Silicon is widely available and abundant in nature but its bioavailability is very poor. It is an extremely unstable compound that crystalizes very quickly forming an insoluble inert substance. Its absorption is drastically low and it can’t be utilized by the human organism.
Calbrex-i™n contains a stable high absorption form of dietary silicon. It is an ortho-silicic acid molecule stabilized in maltodextrin. It is stabilized by a proprietary method that inhibits the polymerization of ortho-silicic acid, keeping the molecule stable and increasing its bioavailability in the body.
The ongoing studies conducted on the miracle spice from India keep confirming its usefulness for an ever wider range of health concerns. And Turmeric is also helpful for arthritis and other joint problems through its modulation of inflammatory signals in several different ways. Its active component, Curcumin, is able to prevent pro-inflammatory messaging, it can reduce the activity of pro-inflammatory enzymes and it can also downregulate the immune system over-reactivity on inflammation areas.
Clinical research on orally administrated curcumin has shown that it is equally or more potent than synthetic anti-inflammatory drugs when taken for several weeks and up to several months. The level of relief demonstrated is in the range of 40 - 60% reduction of symptoms of knee osteoarthritis on threadmill testing.
- M. Z. Siddiqui et al. Boswellia Serrata, A Potential Antiinflammatory Agent: An Overview. Indian J Pharm Sci. 2011 May-Jun; 73(3): 255–261.
- Roy S, et al. Regulation of vascular responses to inflammation: inducible matrix metalloproteinase-3 expression in human microvascular endothelial cells is sensitive to antiinflammatory Boswellia . Antioxid Redox Signal. (2006)
- Gupta I, et al. Effects of Boswellia serrata gum resin in patients with ulcerative colitis . Eur J Med Res. (1997)
- Sailer ER, et al. Acetyl-11-keto-beta-boswellic acid (AKBA): structure requirements for binding and 5-lipoxygenase inhibitory activity . Br J Pharmacol. (1996)
- Safayhi H, et al. Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase . J Pharmacol Exp Ther. (1992)
- 1. Effect of Bromelain or kaolin-induced inflammation in rats. Kumakura S, Yamashita M, Tsurufuji S. Eur J Pharmacol. 1988;150:295–301.
- 2. Targeting the coagulation factor fibrinogen for arthritis therapy. Raghu H1, Flick MJ. Curr Pharm Biotechnol. 2011 Sep;12(9):1497-506.
- 3. Therapeutic uses of pineapple-extracted bromelain in surgical care - A review. Muhammad ZA, Ahmad T. J Pak Med Assoc. 2017 Jan;67(1):121-125.
- 1. Powanda and al. - Novel Natural Products: Therapeutic Effects in Pain, Arthritis and Gastro-intestinal Diseases pp 133-153 (Celery Seed and Related Extracts with Antiarthritic, Antiulcer, and Antimicrobial Activities) 07/31/2015
- 2. Soundararajan S and Daunter B: Ajvine: Pilot biomedical study for pain relief in rheumatic pain. School of Medicine,The University of Queensland, Brisbane, Queensland, Australia, 1991-92.
- 3. Venkat S and al. Use of Ayurvedic medicine in the treatment of rheumatic illness. Department of Orthopaedics, Kovai Medical Center and Hospitals, Coimbatore, India, 1995.
- Oesser, S.; Adam, M., Babel, W. and Seifert, J. (1999). "Oral administration of 14C labelled gelatine hydrolysate leads to an accumulation of radioactivity in cartilage of mice (C57/BL)". Journal of nutrition 129 (10): 1891–1895. PMID 10498764
- Oesser, S.; Seifert, J. (2003). "Stimulation of type II collagen biosynthesis and secretion in bovine chondrocytes cultured with degraded collagen". Cell tissue research 311 (3): 393–399. doi:10.1007/s00441-003-0702-8. PMID 12658447
- In-Vivo: A Randomized Double Blind Placebo Clinical Trial Evaluating the Efficacy and Safety of Hyal-Joint® Compared to Placebo for the Improvement of Quality of Life in Adults with Osteoarthritis of the Knee. Kalman et al (2008) Nutrition Journal. 7(3) (http://www.nutritionj.com/content/7/1/3)
- Comparison of different experimental designs to evaluate of an intervention in osteoarthritis patients. D. Martinez-Puig, C. Chetrit, I. Möller. Osteoarthritis and Cartilage, Volume 19, Supplement 1, September 2011, Page S147
- Motohashi et al. Concentration and degradation of hyaluronic acid in knee synovial fluid from carrageenin-induced rabbit arthritis. Chem Pharm Bull (Tokyo). 1990 Jul;38(7):1953-6.
- Balogh et al. Absorption, uptake and tissue affinity of high-molecular-weight hyaluronan after oral administration in rats and dogs. J Agric Food Chem. 2008 Nov 26;56(22):10582-93.
- Bellamy et al. Viscosupplementation for the treatment of osteoarthritis of the knee. Database Syst Rev. 2006 Apr 19;(2):CD005321.
- Ruff and al. Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies. Clin Interv Aging. 2009; 4: 235–240.
- Wedekind et al. Beneficial effects of natural eggshell membrane (NEM) on multiple indices of arthritis in collagen-induced arthritic rats. Modern Rheumatology Volume 27, 2017 - Issue 5 p 838-848
- Benson et al. Effects of Natural Eggshell Membrane (NEM) on Cytokine Production in Cultures of Peripheral Blood Mononuclear Cells: Increased Suppression of Tumor Necrosis Factor- α Levels After In Vitro Digestion. Journal of medicinal food 15(4):360-8 · December 2011
- E. M. Carlisle, In vivo requirement for silicon in articular cartilage and connective tissue formation in the chick,J. Nutr. 106, 478–484 (1976).
- E. M. Carlisle, A silicon requirement for normal skull formation in chicks,J. Nutr. 110, 352–359 (1980). https://www.ncbi.nlm.nih.gov/pubmed/1255267?dopt=Abstract
- Formation in Wounds and Bone, and Ornithine Transaminase Enzyme Activity in Liver C. D. Seaborn and F. H. Nielsen March 1, 2002 https://link.springer.com/article/10.1385/BTER:89:3:251
- 1. Anauate and al. Effect of isolated fractions of Harpagophytum procumbens D.C. (devil's claw) on COX-1, COX-2 activity and nitric oxide production on whole-blood assay. Phytother Res. 2010 Sep;24(9):1365-9. doi: 10.1002/ptr.3124.
- 2. Chrubasik S, et al. Comparison of outcome measures during treatment with the proprietary Harpagophytum extract doloteffin in patients with pain in the lower back, knee or hip. Phytomedicine. (2002)
- 3. Chrubasik S, et al. A randomized double-blind pilot study comparing Doloteffin and Vioxx in the treatment of low back pain. Rheumatology (Oxford). (2003)
- 4. Chrubasik S, et al. A 1-year follow-up after a pilot study with Doloteffin for low back pain. Phytomedicine. (2005)
- 5. Thanner J, et al. Retrospective evaluation of biopsychosocial determinants and treatment response in patients receiving devil's claw extract (doloteffin). Phytother Res. (2009)
- Jackson JK, et al. The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis. Inflamm Res. (2006)
- Ramadan G, Al-Kahtani MA, El-Sayed WM. Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis. Inflammation. (2011)
- Belcaro G, et al. Efficacy and safety of Meriva®, a curcumin-phosphatidylcholine complex, during extended administration in osteoarthritis patients. Altern Med Rev. (2010)
Celery Seed Extract:
Eggshell Membrane NEM®
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