International Journal of Veterinary Health Science & Research (IJVHSR) / IJVHSR-2332-2748-08-101

Therapeutic Efficacy and Safety Evaluation if Flex Choicetm in Moderately Osteoarthritic Dogs*

Rachael E. Webber1, Ramesh C. Gupta1*, Robin B. Doss1, Jean Miller1, Terry D. Canerdy1, Laura K. Hoffman1, Ajay Srivastava2, Rajiv Lall2

1 Murray State University, Breathitt Veterinary Center, Murray/Hopkinsville, KY, USA.
2 Vets Plus Inc., Menomonie, WI, USA.

*Corresponding Author

Ramesh C. Gupta, DVM, MVSc, PhD, DABT, FACT, FACN, FATS,
Professor and Head, Toxicology Department, Murray State University,,br/> Breathitt Veterinary Center, 101 MSU Drive, Hopkinsville, KY 42240, USA.
Tel: (270) 886-3959
Fax: (270) 886-4295
E-mail: rgupta@murraystate.edu

Received: November 25, 2019; Accepted: January 07, 2020; Published: January 10, 2020

Citation: Rachael E. Webber, Ramesh C. Gupta, Robin B. Doss, Jean Miller, Terry D. Canerdy, Laura K. Hoffman, et al., Therapeutic Efficacy and Safety Evaluation if Flex Choicetm in Moderately Osteoarthritic Dogs*. Int J Vet Health Sci Res. 2020;8(1):242-251. dx.doi.org/10.19070/2332-2748-2000047

Copyright: Ramesh C. Gupta© 2020. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

Abstract

Osteoarthritis (OA) is a chronic inflammatory degenerative joint disease that affects humans and animals alike. Currently, >20% of the adult and 80% of the geriatric dog population in the US (>90 million) suffer from OA. The pathophysiology of OA is very complex as it involves multiple mechanisms and molecular pathways. Currently, there are several choices to manage OA, but many veterinarians choose nutraceuticals because of lesser or no side effects compared to pharmaceuticals. The present investigation was undertaken to assess anti-arthritic efficacy and safety of Flex ChoiceTM chews (Clinics Choice, LLC) in dogs with moderate OA. Flex ChoiceTM chews are composed of krill oil, hyaluronic acid, astaxanthin, Boswellia serrata extract, greenlipped mussel, and iron transport tocopheryl polyethylene glycol succinate (ITPGS). Dogs with OA received Flex ChoiceTM chews b.i.d. for 150 days. Each month, dogs were given a full exam and were evaluated for arthritic pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using the Glasgow scoring system, CBC, and serum biomarkers of liver (bilirubin, ALT, and AST), kidney (BUN and creatinine), and heart and skeletal muscle (CK) functions. Dogs receiving Flex ChoiceTM showed marked reductions in overall pain (52%), pain upon limb manipulation (35%), and pain after physical exertion (40%). The active ingredients in Flex ChoiceTM exert antioxidative, anti-inflammatory, immunomodulatory, analgesic, cartilage repair and anti-osteoarthritic effects. ITPGS, in addition to being a bioenhancer, exerts its effects such as antioxidative and anti-inflammatory. No significant (P>0.01) change occurred in physical parameters, CBC, and serum biomarkers of liver, kidney, and heart functions. Findings revealed that Flex ChoiceTM significantly ameliorated OA-associated pain, and it was well tolerated by dogs with moderate OA.

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1.Keywords
2.Abbreviations
3.Introduction
4.Materials and Methods
    4.1 Animals and their Treatment with Flex ChoiceTM
    4.2 Physical Examination
    4.3 Blood/Serum Analysis
    4.4 Pain Measurement
    4.5 Radiographic Evaluation
    4.6 Statistical Analysis
5.Results
6.Discussion
7.Conclusions
8.References

Keywords

Osteoarthritis; Canine; Flex Choice; Krill Oil; Hyaluronic Acid; Astaxanthin; Boswellia Serrata Extract; Green-Lipped Mussel; ITPGS.

Abbreviations

ACLT: Anterior Cruciate Ligament Transection; ADAMTS-4: A Disintegrin And Metalloproteinase Thrombospondin Motifs 4; ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; ATX: Astaxanthin; BSE; Boswellia Serrata Extract; BUN; Blood Urea Nitrogen; CBC; Complete Blood Count; CK: Creatine Kinase; COX: Cyclooxygenase; CT scan: Computed Tomography Scan; DBIL: Direct Bilirubin; DHA: Docosahexaenoic Acid; ECM: Extra Cellular Matrix; EDTA: Ethylene Diamine Tetra Acetic Acid; EPA: Eicosapentaenoic Acid; ESR: Erythrocyte Sedimentation Rate; ETA: Eicosatetraenoic Acid; GAG: Glycosaminoglycans; GLM: Green-Lipped Mussel; HA: Hyaluronic Acid; HCT: Hematocrit; HGB: Hemoglobin; IACUC: Institutional Animal Care and Use Committee; IL-1α: Interleukin-1α; IL-1β, iNOS: Inducible Nitric Oxide Synthase; interleukin-1β; ITPGS: Iron Transport Tocopheryl Polyethylene Glycol Succinate; LPO: Lipoxygenase; MDR: Multidrug Resistance; MMP: Matrix Metalloproteinase; MRI: Magnetic Resonance Imaging; mTOR: Mammalian Targets Of Rapamycin; NSAIDs: Non-Steroidal Anti-Inflammatory Drugs; OA: Osteoarthritis; PGE: Prostaglandin E; P-gp: P-Glycoprotein; PUFA: Polyunsaturated Fatty Acids; RA: Rheumatoid Arthritis; RBC: Red Blood Cell; RNS: Reactive Nitrogen Species; ROS: Reactive Oxygen Species; TBIL: Total Bilirubin; TNF-α: Tumor Necrosis Factor-Α; WBC: White Blood Cell.

Introduction

Currently, the world’s canine population is more than 900 million, of which 93 million reside in the US. In the US, the majority of dogs are companions while some others are used for service or special needs. Every fifth adult dog suffers from some form of arthritis. The two most common types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). OA occurs with greater frequency than RA, and large breed dogs are prone to develop OA (>45%) as compared to smaller breeds [34, 35]. OA is an inflammatory joint disease characterized by chronic and progressive cartilage degeneration, osteophyte formation, subchondral sclerosis, bone marrow lesions, hypertrophy of bone at the margin, and changes in the synovial membrane. OA not only affects cartilage, but the entire joint including bones, ligaments, nerves and surrounding muscles [58, 89]. Common clinical signs and symptoms associated with OA in dogs include limping, immobility, stiffness of joints, crepitus, periarticular swelling, palpable effusion, pain upon manipulation of the joint, and lameness [33, 81, 49, 29, 20, 67, 35, 41].

The pathophysiology of OA is very complex [80, 58, 22, 32, 61, 107, 34, 35] due to the involvement of multiple etiologies (aging, injury, excessive or lack of exercise, nutritional deficiency, obesity, genetic predisposition, infection, etc.) in this disease [60, 103, 54, 34, 35], and as a result, treatment isalso complicated [32-35]. Degradation of articular cartilage is a hallmark of OA, which occurs in two phases: an anabolic phase, in which chondrocytes attempt to repair the damaged extra cellular matrix (ECM); and a catabolic phase, in which enzymes produced by different cells (including chondrocytes) digest the ECM [101]. This catabolic phase also includes inhibition of matrix synthesis, thereby ensuing accelerated erosion of the cartilage [15, 44]. In OA cartilage, a decrease in the number of chondrocytes and in their ability to regenerate the ECM in response to stress has been described [75]. Cell death of chondrocytes is a combination between apoptosis and autophagy during the pathogenesis of OA [2]. During cartilage degeneration, the inflammatory processes cause excess production of ROS, RNS, oxygen, and PGE2 levels, and as a result, their increased levels can be found within the joint [8, 109, 18]. Activity of pro-inflammatory cytokine IL-1β can be detected in synovial fluid of OA joints where it induces gene expression of matrix-degrading enzymes in the chondrocytes. In addition to oxidative/nitrosative stress and inflammation, multiple molecular pathways are involved in structural and functional damage to cartilage, progression of OA, and OA associated pain [51, 83, 32, 110, 44, 34, 35].

In clinical veterinary settings, diagnosis of OA is based on observational [33, 49, 29, 67, 34, 35] and radiographic findings [67, 78]. Even today, CT scan and/or MRI findings reveal changes of the joint and cartilage degeneration, which are consistent with OA, but are limited to humans and experimental studies [74, 46, 27]. In recent years, a large number of biomarkers of OA have been recognized that play key roles in diagnosis, prognosis and therapeutic intervention [10, 31, 34, 35].

Since there is no cure for OA, management of OA in canines is usually aimed at minimizing joint pain by reducing inflammation, slowing the progression of cartilage degeneration and improving cartilage repair, thereby increasing the joint’s flexibility and quality of life for the animal. In the past, among various choices (such as NSAIDS, therapeutic drugs, physiotherapy, surgery, acupuncture, and lifestyle changes), veterinarians have used NSAIDs [26, 40, 48, 108, 71, 52, 25]. However, due to severe side effects such as gastrointestinal bleeding, cardiac, hepatic, and renal dysfunction, reduced appetite, vomiting, and inhibition of bone healing, many veterinarians are currently using nutraceuticals [63, 12, 66, 93, 76, 42, 87, 20, 1, 34, 35].

In a series of clinical trials, we have evaluated several nutraceuticals singly or in combination for their efficacy and safety in moderately OA dogs [24, 23, 72, 33, 49, 29, 67]. Some of these nutraceuticals provided remarkable reduction in pain and osteophyte formation and enhanced cartilage repair associated with OA in dogs. The present investigation was undertaken to evaluate the efficacy and safety of Flex ChoiceTM in moderately OA dogs. Flex ChoiceTM chews are composed of krill oil, hyaluronic acid, astaxanthin, Boswellia serrata extract, green-lipped mussel, and iron transport tocopheryl polyethylene glycol succinate (ITPGS). By having several ingredients, a novel nutraceutical product Flex ChoiceTM exerted an anti-arthritic effect via multiple mechanisms exerting antioxidative, anti-inflammatory, immunomodulatory, and analgesic effects.

Materials and Methods

Animals and their Treatment with Flex ChoiceTM

Five client-owned moderately osteoarthritic dogs, weighting between 35-65 pounds each, were used in this investigation. A brief description of each dog is provided below in Table 1.