I have written extensively about various supplements and herbal treatments for arthritis. For the most part the evidence seems weak for all of these products, though there are a couple of suggestive studies that might lead to demonstrably effective treatments someday. I have also talked about the need for application of rigorous, explicit evidence-based medicine techniques (EBM) in veterinary medicine. A recent paper in the Journal of Veterinary Internal Medicine does an excellent job of illustrating EBM methods, and its subject is the use of nutraceutical for treatment of osteoarthritis in animals.
J.-M. Vandeweerd, C. Coisnon, P. Clegg, C. Cambier, A. Pierson, F. Hontoir, C. Saegerman, P. Gustin, S. Buczinski. Systematic Review of Efficacy of Nutraceuticals to Alleviate Clinical Signs of Osteoarthritis. Journal of Veterinary Internal Medicine. 2012. Epub ahead of Print.
The authors adapted the CONSORT statement and recommendations from the Centre for Evidence-Based Medicine at Oxford to design an explicit and detailed scoring sheet for research trials involving nutraceuticals for osteoarthritis. This sort of transparency, and establishing criteria for grading evidence in advance, are important aspects to an evidence-based review, which help to minimize the potential impact of personal bias on the results.
The authors then conducted a thorough literature search for articles in English and French that concerned the use of common nutraceuticals in arthritis treatment. A total of 67 articles were found, of which 22 met the inclusion criteria of the review (controlled clinical trials evaluating clinical signs of pain or locomotion). The literature search terms are presented in the report in a way that makes replicating the search straightforward.
An exhaustive evaluation of these 22 studies was then conducted, with a grading of the quality of evidence for the following nutraceuticals:
Chondroitin Sulfate (various forms)
Undenatured Type II Collagen
Avocado and Soybean
Omega-3 Fatty Acids (aka fish oil)
Green-Lipped Mussel Powder
Special Milk Protein Concentrate
Indian and Javanese Turmeric
Various combinations of these ingredients and such as manganese, vitamins, amino acids, chromium, and more
The conclusions were quite straightforward:
The strength of evidence was low for all nutraceuticals except for omega-3 fatty acid in dogs…The evidence of efficacy of nutraceuticals is poor, with the exception of diets supplemented with omega-3 fatty acids in dogs.
The authors also touched on many of the limitations of the available literature, not only the small numbers of studies and subjects, but the lack of replication, the tendency for all the research on a single subject to come from one researcher or research group, the lack of motivation for studies given the lack of effective regulation of dietary supplements and many others.
This is an excellent example of the application of EBM methods to veterinary questions. While the available evidence is often limited in quantity and quality, we need to critically appraise what there is in order to make the best clinical decisions. I think the methodology used in this paper is a model for how such reviews can be conducted and how they can be useful to general practitioners.
My only quibble was with the conclusion the authors reached concerning fish oils. I have previously reviewed three of the four studies they evaluated (here and here), and while I agree that they are generally good quality studies, I think the results are less convincing than the authors claim or than this review suggests. It can be difficult to balance an objective, checklist-based evaluation of the evidence, which reduces the influence of reviewer bias, with the need for a judicious assessment of the details of the evidence, and I think the authors of this review generally do a good job. But I think they reach the wrong conclusion with regard to the fish oil question.
Below is a detailed evaluation of the findings of each study, which I think illustrates why the few positive data reported provide only weak evidence of a benefit for fish oils in treatment of arthritis.
A. Dose-titration effects of fish oil in osteoarthritis dogs.
1. Semi-objective measure (veterinarian clinical assessment)
Of five measures assessed at four time points, all measures improved for all groups. Without a no-treatment arm, it is impossible to know how much of this apparent improvement is an artifact of study participation.
Only two measures improved significantly more for highest dose diet compared with the lowest dose diet (with no differences between the medium and lowest dose diets). These improvements were small and of dubious clinical significance: from 1.68 to 1.40 (~17% improvement) and from 2.00 to 1.64 (~18% improvement) on a scale where 1-no signs, 2-mild signs, 3-moderate signs, 4-severe signs).
2. Subjective measure (veterinarian estimate of overall change based on exam and owner input)
Veterinarians were asked, based on their own assessment and owner input, how much over the 90 days of the study they thought the diets had slowed or accelerated the dogs’ arthritis, or if they had no effect. All diets were believed to have slowed the progression of the disease, with the highest dose diet scoring 2.32 and the lowest dose diet 1.99 on a scale of 1-significantly slowed, 2-slightly slowed, 3-no effect.
Veterinarians were then asked, based on their own assessment and owner input, how much over the 90 days of the study they thought the dogs’ arthritis had changed. All dogs were believed to have improved, with those on the highest dose diet scoring 2.55 and those on the lowest dose diet scoring 3.15 on a scale of 1-extreme improvement, 2-moderate improvement, 3-slight improvement, 4-no effect.
- A multicenter study of the effects of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis.
Reduction of the carprofen dose was the stated goal of the study, and the dose decreased for both groups. The control diet group dose decreased over 12 weeks by an average of 0.59mg/kg/day (from 4.14 to 3.58mg/kg/day, ~14%). The test diet group dose decreased by an average 1.13mg/kg/day (from 4.39m to 3.26 mg/kg/day, ~26%). The final dose differed between the two groups by 0.32mg/kg/day.
C. Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs
1. Semi-objective measure (veterinarian clinical evaluation)
Out of five clinical measures over three time periods, there were no significant differences between control and test diet groups.
2. Subjective measure (owner survey)
Out of thirteen measures over three time periods, there were two measures that differed significantly between groups at the first evaluation and one other measure that differed significantly at the second and third time period. No express statistical controls for making multiple comparisons were described despite p-values being reported for fifty-four different comparisons.
D. Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis.
1. Objective Measure (force plate analysis)
Two measurements for each group were compared at two points in time and then a comparison was made of the percentage change in these measurements for both groups over the intervening period. Of the total of eight comparisons, one was significantly different between groups.
2. Semi-objective measure (veterinarian clinical evaluation)
Of five measures compared between groups at two points in time and in terms of change over time, the test group improved more than the control group in terms of two measures. This was the same measure of effect as used in Study 10, in which no such difference was seen.
3. Subjective measure (owner survey)
Of thirteen measures evaluated at two points in time, there were no significant differences between groups. This was the same measure of effect used in Study 10, in which three of the measures did differ at some of the time points.
1. Fritsch D, Allen TA, Dodd CE, et al. Dose-titration effects of fish oil in osteoarthritis dogs. J Vet Intern Med 2010;24:1020–1026.
2. Fritsch DA, Allen TA, Dodd CE, et al. A multicenter study of the effects of dietary supplementation with fish oil omega-3 fatty acids on carprofen dosage in dogs with osteoarthritis. J Am Vet Med Assoc 2010;236:535–539.
3. Roush JK, Dodd CE, Fritsch DA, et al. Multicenter veterinary practice assessment of the effects of omega-3 fatty acids on osteoarthritis in dogs. J Am Vet Med Assoc 2010;236:59–66.
4. Roush JK, Cross AR, Renberg WC, et al. Evaluation of the effects of dietary supplementation with fish oil omega-3 fatty acids on weight bearing in dogs with osteoarthritis. J Am Vet Med Assoc 2010;236:67–73.