Since 2008, Epiitalis® – our patented active ingredient, has undergone rigorous assessments in both laboratory and clinical trials to test its satety and etticacy across a variety of species including humans, horses dogs and cats.

Many of these studies have been peer reviewed and published in leading journals with Epiitalis® consistently demonstrating significant and clinically relevant modification of the symptoms of osteoarthritis. In addition, we have evidence from both labratory and an equine model of osteoarthtis that Epiitalis® may have disease-modifying activity in the setting of osteoarthritis.

Below, you’ll find a selection of our scientific highlights from a growingbody of evidence that supports the efficacy of Epiitalis® in the management of osteoarthritis.

*Note: The excerpts below have been highly summarised, please click on the links to read the full papers

  • Epiitalis® in Humans Studies

    Dr. Peter Mitchell

    BSc, Ph.D. Research Consultant - Interpath

    Dr. Peter Mitchell has a BSc. Honors degree in biochemistry, a Ph.D. in analytical chemistry. He additionally completed postdoctoral research at both Vanderbilt University and the Medical College of Wisconsin. He has authored more than 60 peer-reviewed publications and 50 abstracts.

    Dr. Peter Mitchell has a BSc. Honors degree in biochemistry, a Ph.D. in analytical chemistry. He additionally completed postdoctoral research at both Vanderbilt University and the Medical College of Wisconsin. He has authored more than 60 peer-reviewed publications and 50 abstracts. Dr. Mitchell has over 30 years’ experience in pharmaceutical and biotechnology R&D, working for two major multinational pharmaceutical companies in the USA,first as a drug discovery researcher focused on pain and disease modification in osteoarthritis, and then later in management working on early clinical development and translational medicine covering osteoarthritis and other chronic diseases. After many years of working with synthetic pharmaceuticals and of observing the many failures with respect to improving the lives of patients with OA.

    Dr. Mitchell oversaw the design and execution of our recent human clinical trial.
    Epiitalis® is efficacious at reducing the symptoms of knee osteoarthritis: a pilot, multi site, dose ranging, randomized, blinded, placebo controlled trial. Peter G. Mitchell, Corina A. Bright, Daniel R. Bright, Shalini N. Srivastava, Sonal S. Raote, & Santosh Kumar. Infammopharmacology, 2022

    “I’m excited to be working with Interpath to help bring a nutraceutical product to the market that has strong human efficacy data for treating osteoarthritis.”

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    Epiitalis® is effective at treating symptoms of x-ray diagnosed knee-osteoarthritis

    The study

    Epiitalis® is efficacious at reducing the symptoms of knee osteoarthritis: a pilot, multi site, dose ranging, randomized, blinded, placebo controlled trial.
    Peter G. Mitchell, Corina A. Bright, Daniel R. Bright, Shalini N. Srivastava, Sonal S. Raote, & Santosh Kumar.
    Infammopharmacology 2022 https://doi.org/10.1007/s10787-022-01013-y

         The study design:

    56 day, 6 site, 4 time point (Baseline, 14, 28 & 56 day) randomized, double blind, placebo- controlled trial of 3 doses of Epiitalis® vs. placebo in patients with X-ray verified KL-I and KL-II knee OA

    • Three Epiitalis® groups: high dose (HD,320 mg bi-daily), mid-dose (MD,320 mg once-daily), low dose (LD,160 mg once-daily)
    • Placebo: medium chain triglyceride oil matched for consistency & colour
    • 235 participants, N ≈ 50/group

    Primary Endpoints:
    Change in pain (100-point visual analogue scale, VAS*) from baseline to 56 Days.
    p values for paired comparison (Epiitalis® doses vs. placebo) calculated using ANOVA with Bonferroni adjustment.

    Exploratory Endpoints:
    mWOMAC, SF-36 Quality of Life questionnaire and OMERACT-OARSI responder index.
    Nominal p values for paired comparisons (Epiitalis® doses vs. placebo) calculated using ANOVA (mWOMAC and SF-36). Chi-square test was utilized to assess for differences between the distribution of OMERACT-OARSI responders in the hBO groups vs. the placebo group.

    Safety Endpoints:
    Number of adverse events/serious adverse events, blood pressure, pulse, kidney function (serumcreatinine) and liver function (serum AST & ALT)
    No SAEs, no IP-related AEs and no changes in safety measures outside of the normal limits.

     Figure 1: Change in VAS Pain (100-point scale; Day 0 – Day 56) Epiitalis® groups (High dose, Mid dose and, Low dose) vs Placebo     Summary of results:
    • Epiitalis® Intervention resulted in a 47% (mean of the three Epiitalis® groups) decrease in pain vs a 12.5% decrease in the placebo group
    • The kinetics of efficacy onset were similar in all Epiitalis® groups with maximal efficacy achieved at study end (Day 56)
    • Changes in VAS pain met accepted criteria for exceeding an established threshold for providing a minimal clinically important improvement (MCII)
    • At study end, the effect size for Epiitalis® vs. VAS pain for was similar to, or improved vs. that historically reported for NSAIDs/COX-2 inhibitors

    *The pain VAS is a unidimensional measure of pain intensity, used to record patients’ pain progression, or compare pain severity between patients with similar conditions

     Figure 2: Total SF-36 scores for the Epiitalis® groups (High dose, Mid dose and, Low dose)) vs placebo group, Baseline (Day 0) to Day 56 (study end).     Summary of results:

    Quality of life scores of patients taking a daily dose of Epiitalis® improved by ~83% (mean of the three Epiitalis® groups) compared to just 4% in patients taking a placebo.

    The SF-36 incorporates scores for 8 separate domains relating to a patients : physical functioning, role physical, bodily pain, general health, itality, social functioning, role emotional, and mental health.

     Figure 3: Total WOMAC score change), normalised to 100-point scale, Baseline to Day 56 for Epiitalis® groups (High dose, Mid dose and, Low dose) vs Placebo, Baseline (Day 0) to Day 56 (study end).     Summary of results:

    All Epiitalis® doses were similarly highly efficacious at decreasing the total WOMAC total score (pain/stiffness/function).

    mWOMAC: the Western Ontario and McMaster Universities Osteoarthritis Index, modified for use in India Total score that includes 3 subdomains: pain, stiffness and physical function

     Figure 4: Percentage of participants whose symptoms significantly responded to intervention with Epiitalis® (High dose; Mid dose and, Low dose) vs Placebo, measured using the OMERACT-OARSI Responder Index, Baseline (Day 0) to Day 56 (study end).     Summary of results:

    On day 56, the distribution of clinical responders in each Epiitalis® group was significantly different vs. the distribution in the placebo group (all p < 0.0001).

    OMERACT–OARSI responder index was developed by clinical researchers to distinguish between an efficacious active treatment and a placebo

     Figure 5: Kinetics for onset of clinical efficacy induced by Epiitalis® Mid dose (hBo-MD) vs Placebo, depicted by change in pain on a 100-VAS scale, from Baseline to Day 56. Error bars are +/- one standard deviation.     Summary of results:

    At the primary endpoint there was a clear differentiation in efficacy for decreasing VAS-pain between the placebo and each Epiitalis® group.

         Interpretation:

    In contrast to the rapid onset and plateau of efficacy observed in trials of NSAIDs, the efficacy of Epiitalis® continued to increase with time over the 56 day study period of our trial, with maximal efficacy observed at study end (56 days). It is unclear whether further increases in clinical efficacy might be observed with even longer dosing time periods.

         Conclusion:

    Results from our human clinical study with Epiitalis® demonstrate a robust and clinically meaningful reduction in the primary outcome of the trial i.e. knee pain. In addition quantitatively similar clinical benefits were observed in the trial exploratory outcomes and are supportive of Epiitalis® providing clinical efficacy vs. knee function and stiffness. Importantly, these improvements in clinical symptomatic measurements were accompanied by profound changes in measures of patient quality of life suggesting
    that not only are patients symptoms improving but they are returning to a more normal and full life. The outcomes of this trial provide confidence that Epiitalis® has the potential to provide meaningful clinical and quality of life benefits for patients suffering from knee osteoarthritis.

         Hypothesis:

    We hypothesise that in addition to it’s profound benefits vs. the clinical symptoms of osteoarthritis (e.g. pain, function, stiffness), Epiitalis® may also have beneficial effects on the underlying disease processes that occur in joint tissues (bone, cartilage, synovial membrane). In osteoarthritis clinical research, a drug intervention that modifies the structural progression of the disease is termed a Disease Modifying Osteoarthritis Drug or DMOAD. Our Epiitalis® DMOAD hypothesis is based on the following three observations from our Epiitalis® R&D: (1) In vitro research consistently  demonstrating that Epiitalis® and fractions of Epiitalis® increase the numbers of chondrocytes (cells that make up the articular cartilage) in both cartilage explants and chondrocyte monolayers; (2) data from a preclinical equine model of osteoarthritis (insert reference here) demonstrating profound inhibition of pathological bone changes observed after treatment with Epiitalis®, and (3) the relatively slow onset of clinical efficacy that hasnow been observed in both dogs (reference here) and in our human study. This relatively slow onset of clinical efficacy is inconsistent with a mechanism based on e.g. acute inhibition of a cyclooxygenase enzyme (as per NSAIDs and COX-2s), but is consistent with an accrual of clinical benefit due to Epiitalis® changing the underlying disease processes in one or more of the joint tissues. Although our R&D provides support for a DMOAD mechanism, additional studies would be required to formally demonstrate this in humans

  • Epiitalis® in Horses Studies

    C. Wayne McIlwraith

    BVSc (Dist), (DVM), PhD, DSc, FRCVS, Diplomate ACVS, Diplomate ACVSMR
    University Distinguished Professor Emeritus
    Barbara Cox Anthony University Chair in Orthopaedics Emeritus
    Founding Director of Orthopaedic Research Center Emeritus

    “Our placebo-controlled study at the CSU Orthopaedic Research Center showed that this is definitely a disease modifying osteoarthritis product. We have never seen the dramatic reduction of radiographic scores in any other study using this model. It was impressive”

    Dr. McIlwraith, a University Distinguished Professor Emeritus, is a Past-President of the American College of Veterinary Surgeons and the American Association of Equine Practitioners, and a recognized leader in the field of equine orthopaedic research and surgery.

    His research interests focus on equine orthopaedic surgery, joint disease research as well as osteoarthritis therapy (including gene therapy and stem cell therapies), articular cartilage repair, and early diagnosis in osteoarthritis and pre-fracture disease using imaging and fluid biomarkers.

    In addition to his roles at the Colorado State University, he had a private equine referral practice in Southern California for 40 years from 1983 – 2023 and is a consultant equine orthopaedic surgeon for clients in the US, Ireland, England, France and New Zealand.  Dr. McIlwraith has over 400 refereed publications, and has authored or  co-authored seven textbooks (with multiple additions) and has given over 700 presentations and workshops both nationally and internationally to equine practitioners, veterinary speciality groups and human orthopaedic meetings.

    Professor McIlwraith and his colleagues at the Orthopaedic Research Center at CSU lead groundbreaking equine research for Interpath.
    Examining the effects of the oral supplement Biota orientalis in the osteochondral fragment-exercise model of osteoarthritis in the horse. Kathryn A. Seabaugh, Myra F. Barrett, C. Wayne McIlwraith, David D. Frisbie. Frontiers in Veterinary Science, 2022; 9:858391

    “Our placebo-controlled study at the CSU Orthopaedic Research Center showed that this is definitely a disease modifying osteoarthritis product. We have never seen the dramatic reduction of radiographic scores in any other study using this model. It was impressive”

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    In an equine model of osteoarthritis, Epiitalis® decreased synovial fluid inflammation and pathological bone changes in the joint.

    The study

    Examining the effects of the oral supplement Biota orientalis in the osteochondral fragment-exercise model of osteoarthritis in the horse.
    Kathryn A. Seabaugh, Myra F. Barrett, C. Wayne McIlwraith, David D. Frisbie.
    Frontiers in Veterinary Science 2022 – https://doi.org/10.3389/fvets.2022.858391

         The study design:

    The study investigated the efficacy of Epiitalis® in horses with a surgically induced model of osteoarthritis previously developed at Colorado State University. The study utilized 16 healthy, 2–5-year-old horses with 8 in the Epiitalis® group and 8 in the placebo group.

    • Osteochondral fragment surgery, Day 0
    • Daily oral Epiitalis® gel: 2.2 ml Epiitalis® + 0.3 ml excipients
    • Daily oral placebo – 2.5 mL of gel containing excipients only
    • Daily treadmill exercise: Day 14 – Day 56

    Endpoints: synovial fluid markers of inflammation, joint tissue histology, clinical lameness, serum biochemical markers, and imaging (MRI and X-Ray).

     Epiitalis® significantly reduced pathological radiographic bone changes. Figure 1: Dorsolatero-palmaromedial oblique radiographs of a placebo-treated horse (A) and an Epiitalis® treated horse (B) on Day 70

    Osteochondral fragment visible in both horses. Sclerosis of third carpal bone and radiocarpal bone are visible in placebo-treated treated horse as well as enthesopathy of the joint capsule, and osteophytosis. Soft tissue swelling representing middle carpal joint effusion is the only common abnormality between the two horses.

     Figure 2. Mean differences in PGE2 values for placebo and Epiitalis treated horses. Measurements are in terms of changes from baseline.     Summary of results:

    Epiitalis® intervention produced significant changes in both synovial fluid inflammatory markers (PGE2 and white blood cell count), and in X-ray measured pathological bone scores. These results are highlighted below.

    Figure 1. When comparing the difference from baseline at 2 and 10 weeks, the total radiographic score was significantly lower (p = 0.001) in the Epiitalis® group vs. the placebo group. At the study endpoint, the total radiographic score of Epiitalis® treated horses was 63% lower than that of placebo treated horses. Of significant relevance to osteoarthritis, the osteophyte component of the overall total radiographic score was highly significantly reduced in the Epiitalis® group (p < 0.001).

    Figure 2. Over the time course of the study, there was a significant effect of Epiitalis® on reducing PGE2 concentrations in the synovial fluid compared to the placebo. Similarly, there was a significant effect of Epiitalis® on reducing synovial flud white blood cell count over the time course of the study.

    Although this work was a small pilot study with insufficient statistical power to detect changes in some endpoints (e.g. clinical lameness),

         Conclusion:

    The most significant effects of Epiitalis® in this surgically induced model of equine osteoarthritis were observed on reducing synovial fluid inflammation (PGE2 and white blood cell count), and in blocking pathological bone changes. PGE2 is a known mediator of inflammation and pain and reducing its concentration in the synovial fluid would likely contribute to the Epiitalis® induced reduction of clinical symptoms of joint disease as has been observed in other species, including dogs and humans. A surprising outcome from this equine study was the profound effects that Epiitalis® had on reducing the changes in bone pathology induced in this equine OA model. Changes in joint bone architecture, including bone shape and the growth of osteophytes at the joint margin, are observed across multiple species including man, as joint degenerative processes progress. In several human studies, the severity of clinical symptoms of osteoarthritis has been correlated with osteophyte presence and/or size. As noted by the authors of this equine study: “These improvements in radiographic outcome parameters are some of the most compelling seen in numerous iterations of this model and represent a noteworthy benefit of this treatment in the authors’ opinion. This finding is strongly supportive of a disease modifying effect with Epiitalis® treatment.”

    Improvement in equine arthritic symptoms after just one week using 4CYTE™ Epiitalis® Forte Horse

    The study

    To assess the efficacy of the clinical dose of Epiitalis® Forte in horses with symptomatic joint arthritis Dr Frederick W. Benker et al, Equine Medical Centre of Ocala (Internal, non-peer reviewed data)

         Figures 1 and 2: Changes in lameness and range of movement respectively in horses undergoing treatment with 4CYTE Epiitalis® Forte over 42 days The study design:

    Ten otherwise healthy horses showing signs of arthritis or joint effusion were selected for the 42-day trial. The ten horses were randomly allocated to two treatment groups (5 horses in each group). One group received 8g 4CYTE™ Epiitalis® Forte orally from day 1-14, then 4g from day 15-42. The second group received 8g 4CYTE™ Epiitalis® Forte orally from day 1-28 then 4g from day 29-42.

    Trial Endpoints
    Veterinary Lameness Score: scored as absent, difficult to observe, subtle limp or consistent lameness

    Range of Movement: scored as full range, slight reduction, significant reduction or extreme reduction

    Heat and Swelling: scored as absent, minimal, significant or extreme

    NB: joint circumference measurements were made but results are not reported as none of the trial animals had significant joint effusion at study initiation.

         Summary of results:

    Veterinary Scored Lameness: 7 of the 10 horses had consistent lameness at day 0. By Day 14, 8 of the 10 horses had lameness reported as either absent or as difficult to observe (See Figure 1). Only 1 horse still had a subtle limp after 42 days, and this horse exhibited adhesions in the digital tendon sheath of his right hind leg.

    Heat and Swelling: 6 of the 10 horses had significant heat and swelling at Day 0. By Day 14, 8 of the 10 horses were only showing nominal to absent levels of heat and swelling. On Day 42, 9 of 10 animals exhibited heat and swelling that was either absent or minimal.

    Range of Movement: 8 of 10 horses had a significant reduction in range of movement/mobility at Day 0. By day 14, 8 horses were displaying either full range of motion or only a slight reduction in range of movement/mobility. On Day 42, 9 of the 10 horses exhibited full range of movement mobility (see Figure 2).

         Conclusion:

    Within two weeks of beginning treatment with 4CYTE™ Epiitalis® Forte, 8 of the 10 trial animals already had clinical scores that were reported as either absent or minimal. At the conclusion of the trial (Day 42) 9 of the original 10 animals reported either the absence of clinical symptoms, or only minimal clinical symptoms.

    The results from this study provide support for 4CYTE™ Epiitalis® Forte providing relatively fast and, in most cases, near complete relief of symptoms in horses with clinical joint arthritis. This relief of clinical symptoms was accompanied by return to near normal functional mobility for most animals. As reported by one owner: “Went from retirement back to being able to compete in Barrel racing “

    The data from the two groups are reported together, as the trial was small and there were no clear differences between clinical outcomes for the two dose groups. It is possible that a higher loading dose may provide faster relief in those animals with more severe disease.

  • Epiitalis® in Dogs Studies

    A new leash on life: 4CYTE™ Epiitalis® Forte effectively treats the symptoms of osteoarthritis in dogs with established joint disease.

    The study

    A pilot study of 4CYTE™ Epiitalis® Forte for Dogs, a novel nutraceutical, in the management of naturally occurring osteoarthritis in dogs
    T Beths,* R Munn, SH Bauquier, P Mitchell and T Whittem
    Australian Veterinary Journal 2020 https://doi.org/10.1111/avj.13024

    93.5% of dogs who used 4CYTE™ showed improvement in their quality of life* 94% of dogs who used 4CYTE™ showed an improvement in movement and also showed an improvement in quality of life.* 74% of dogs who used 4CYTE™ showed improvement in movement* 71% of dogs using prescription OA medications showed further improvement when 4CYTE™ was added to their treatment regime*     The study design:

    In a peer reviewed and published clinical trial conducted at Melbourne University in 2020, 4CYTE™ Epiitalis® Forte was assessed in a 28-day pilot study involving 46 dogs with naturally occurring osteoarthritis.

    Two data collection tools were used, one that was objective (i.e. measured) and one that was subjective (i.e. based on owner observation). The objective measurement utilized gait analysis using a walkway system (GaitRite) that assessed paw strike (Pressure Index) as the dogs walked over a 5m mat with incorporated pressure sensors. The most symptomatic leg, defined as the limb exerting the least pressure at study initiation, was identified as the study limb. At each study timepoint, dogs completed 3 passes across the mat with the output data averaged from the 3 passes. Improvement was defined as a numerical increase in the Pressure Index value of the worse limb between Days 0 and 28.

    The subjective endpoint was the Helsinki Chronic Pain Index (HCPI), a clinically validated quality of life questionnaire. On Days 0 and 28, each owner completed an HCPI assessment of their dog. Clinical improvement in the quality of life was defined as a decrease of 5% or more in HCPI score between Days 0 and 28.

    Study dogs were assessed on Day 0 and then sent home with 4CYTE™ Epiitalis® Forte for daily dosing. Dogs returned 28 days later to complete their 2nd assessment.

         Summary of results:

    At day 28:

    1. 74% of dogs improved the pressure placed on their most symptomatic limb (Total Pressure Index), demonstrating an improvement in weight bearing and supporting a reduction in pain in this limb.
    2. 93.5% of dogs improved their “Quality of Life” (QOL) score from the HCPI assessment, demonstrating that the intervention improved the owner perception of the overall well-being of their dog.
    3. 79% of dogs who improved on QOL score, also improved on their Total Pressure Index
    4. At study entry, many dogs were already on some kind of pharmaceutical treatment for their joint disease. These dogs had their medication continued throughout the study, with 4CYTE™ Epiitalis® Forte added to their existing regimen. 71% of the dogs that were in this category demonstrated improvements in both the objective (Total Pressure Index) and subjective (HCPI) study endpoints.
         Conclusion

    This trial demonstrated that 4CYTE™ Epiitalis® Forte successfully both objective and subjective clinical symptoms in dogs with pre-existing symptomatic joint disease, irrespective of their current medication.

    4CYTETM with Epiitalis® is Non-Inferior to the Nonsteroidal Anti-inflammatory Drug, Carprofen, in Canines with Clinical Osteoarthritis

    The study

    A randomised controlled masked clinical trial of two treatments for osteoarthritis in dogs.
    T Whittem, L Richards, J Alexander, C Beck, C Knight, M Milne, M Rockman, R Saunders, D Tyrrell
    Australian Veterinary Journal 2021 https://doi.org/10.1111/avj.13066

         The study design:
    • 28 day randomised, masked, parallel group trial in dogs with naturally occurring osteoarthritis
    • Daily 4CYTE™ Canine, containing 3.6mg/kg ; carprofen, 2–4 mg/kg daily
    • Primary outcome: improvement in Owner Lameness Score at Day 28 compared with Day 0
    • Exploratory endpoints: Veterinary Lameness Scores and Owner Mobility Scores
     The percentage of dogs that showed no improvement (grey) or improvement (green) in their Owner Lameness Score after 28 days, with daily oral treatment of either 4CYTE™ Canine or carprofen.     Summary of results:
    • At study end, 4CYTE™ Canine was non-inferior to Carprofen vs. the primary outcome, Owner Lameness score
    • At study end in the 4CYTE™ Canine group, there were similar improvements and non-inferiority to Carprofen vs. exploratory endpoints: Veterinary Lameness Scores and Owner Mobility Scores
    • In contrast to Carprofen, the efficacy of 4CYTE™ Canine improved with duration of dosing
         Conclusion:

    4CYTE™ Canine containing Epiitalis® was non-inferior to Carprofen with respect to improving functional outcomes in canines with clinical osteoarthritis.

  • Epiitalis® in Cells Studies

    In Vitro Cell Research

    Epiitalis® has demonstrated two consistent properties in in vitro research utilizing cartilage explants and/or chondrocyte monolayers:

    1. Inhibition of IL-1 induced prostaglandin E2 (PGE2)
    2. Stimulation of chondrocyte number

    The study

    A preparation of Biota orientalis, treated to simulate the gastric digestion process in a whole animal, reduced PGE2 production from cartilage explants.
    Pearson W, Orth MW, Karrow NA, and Lindinger MI.
    Am J Vet Res 2008 https://doi.org/10.2460/ajvr.69.12.1560)

         The study design:

    Examples: In vitro Stimulation of Chondrocyte Number

    1. Extracts of Biota orientalis seeds added to monolayers of primary chondrocyte cultures and after 48 hrs, relative chondrocyte numbers in control and treated conditions ere assessed utilizing an MTT assay. The MTT assay, or 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction assay, is a colorimetric method that measures relative cell number
    2. Biota orientalis seed extract incubated with chondrocyte cells for 48 hours before assaying for cell number utilising an MTT assay.
         Summary of results:

    Stimulation of chondrocyte monolayers with Epiitalis® resulted in proliferation (increase) in cartilage cell numbers.

  • Epiitalis® Publication List

    1. Mitchell PG, Bright CA, Bright DR, Yadav SS, Raote S. (2022). A double-blind, double-dummy, dose-response, randomized, placebo-controlled study to assess the efficacy of Epiitalis® on knee pain in patients suffering from knee osteoarthritis. Inflammopharmaclogy Journal. doi.org/10.1007/s10787-022-01013-y
    2. Seabaugh KA, Barrett MF, McIlwraith W, Frisbi DD. (2022). Examining the Symptom-modifying and Disease-modifying Effects of the Oral Supplement Biota Orientalis in the Osteochondral Fragment-exercise Model of Osteoarthritis. Vet Sci J. 9:858391
    3. Beths, Munn R, Bauquier SH, Mitchell PG. and Whittem T. (2020). A pilot study of 4CYTE™ Epiitalis® Forte, a novel nutraceutical, in the management of naturally occurring Osteoarthritis in dogs. Aust Vet J. 2021 Jan;99(1-2):59. doi: 10.1111/avj.13046.
    4. Whittem et al. A Randomised Controlled Masked Clinical Trial of Two Treatments for Osteoarthritis in Dogs. Australian Veterinary Journal; Published Online, April 21, 2021
    5. Bailey SR, University of Melbourne. (2011). Anti-inflammatory, cell proliferative and chondroprotective effects of Constituent 4 (EPIITALIS®) Fractions and/or Sub-fractions in a cartilage explant model of inflammation. Internal Interpath Research Report
    6. Pearson W, Orth MW, and Lindinger MI. (2009). Evaluation of inflammatory responses induced via intra-articular injection of interleukin-1 in horses receiving a dietary nutraceutical and assessment of the clinical effects of long-term nutraceutical administration. Am J Vet Res;70:848-861.
    7. Pearson W, Orth MW, Karrow NA, and Lindinger MI. (2008). Effects of simulated digests of Biota Orientalis and a dietary nutraceutical on interleukin-1- induced inflammatory responses in cartilage explants. Am J Vet Res; 69:1560-1568