This randomized double blind placebo-controlled clinical trial of Phytalgic®
, a composition marketed as a food supplement, showed that after three months patients randomized to Phytalgic®
used fewer concomitant analgesics and NSAIDs than patients randomized to placebo, and had better WOMAC scores. This effect increased regularly over the whole study period. There were no adverse reactions attributed to the drug other than digestive (flatulence and diarrhoea, fish-smelling eructations). The prespecified endpoints were reached and the study can be seen as a first demonstration of an effect of this product, confirming anecdotal reports of patient improvement and decreased use of NSAIDs, and the validity of some recommendations [22
Even though this is the first known trial of this specific combination, so that we really did not know what to expect, the magnitude of the effect we found, which is homogeneous over the different metrics used, was greater than we expected. The study had been powered to detect a 20% difference in the use of NSAIDs and analgesics over the study period. What we found was a greater than 50% reduction in the use of analgesics and NSAIDs.
We attempted to avoid the more common biases: Treatment allocation was random, and conformed to the usual methodology of clinical trials; the study was double-blinded, placebo and active treatments were identical in all respects. Though two patients on active treatment did complain of fish-smelling burping that might compromise blinding in these patients, removing them from the statistical analysis did not change the results of the study. Of course, this being a single-centre study should not be considered as definitive proof. Further, large scale studies will be needed to confirm these results, and possibly clarify optimal dosing and duration of treatment, maybe identify responders and non-responders, and so on.
We included run-of-the-mill patients with diverse manifestations of OA: unilateral or bilateral osteoarthritis of the knee and/or hip, which is an advantage and a drawback: an advantage because it can be seen as a real-life population, increasing generalisability of the results, a drawback because the patients were heterogeneous. Even though there did not appear to be any difference in response between patients with knee of hip OA, the numbers in each group were not sufficient for subgroup analysis. Any differential response between hip and knee OA would need to be explored in further studies.
The composition tested here, Phytalgic®
, was devised empirically, from products used traditionally to treat osteoarthritis. It has been used commercially for several years, and the present study was initiated following patient reports of activity. The exact mechanism of action of the composition remains unknown, as are its possibly active components. Most of the components of Phytalgic®
are commonly used in practice [21
], but clinical trials are few and often of low methodological quality. This specific combination has never to our knowledge been tested before in a randomized double-blind clinical trial, though individual components may have been: Fish oils and oils rich in omega-3 and/or omega-6 fatty acids are thought to have a possible effect on rheumatoid arthritis [27
] and osteoarthritis [18
], with experimental support [28
]. A clinical trial of cod oil in osteoarthritis however found no clear effect [29
], but the oils in the present composition come from cold-water fish rich in omega-3 and fatty acids (mackerel, herring, from the southern Pacific). Zinc is one of the essential elements for chondrocyte function, and has been associated with decreased inflammation [30
] and interleukin production [31
], but this would affect patients with rheumatoid arthritis more than those with OA. Nettles (Urtica dioica
) are commonly used to treat osteoarthritis [26
]. They may have an analgesic effect [33
], and have also been found to reduce the use of NSAIDs in patients with osteoarthritis [34
]. Selenium (from Urtica dioica
) alone or associated with vitamins A, C, E has been thought to modify the symptoms or the evolution of OA [35
], but recent clinical trials and meta-analyses are rather negative in this regard [36
Despite these mixed results and the calls for more clinical trials such as this one [21
], there seems to be an agreement that fish-oil and essential minerals are appropriate to use in patients with OA, and in this respect the preparation tested here appears to correspond with recommendations [22
The effect of the present combination may be related to any one of the individual components, or more probably to the association of these compounds, since none of the compounds used alone seem to have demonstrated effects of the magnitude found here.
Osteoarthritis is a debilitating disease that is not usually by itself life-threatening, but is painful and crippling, and severely degrades quality of life. Its treatment is mainly symptomatic, using analgesics and non-steroidal anti-inflammatory drugs, whose adverse effects (mostly digestive or renal, but also possibly vascular) are such that they may in fact be one of the main life-threatening risks of the disease. Because of these risks inherent in the analgesic and anti-inflammatory drugs, decreasing drug use, especially of NSAIDs, could be a relevant treatment endpoint. However, reduced use of analgesics should not be associated with increased pain or reduced quality of life, but should indicate in fact less need of the drugs. This is clearly the case here: there is in our study an improvement of WOMAC scores, in all three areas covered by the scores. This symptomatic improvement was regular and increased over time, and in parallel the use of analgesics and NSAIDs decreased substantially.
WOMAC scores did not change much over the course of the study in the placebo group, though the use of analgesics and NSAIDs decreased by 20-30%. Though an improvement in OA scores with placebo is common, this is usually found in trials of single treatments, when a new treatment is given as a replacement of previous treatment or as new-onset treatment. In our patients, usual treatment was pursued. The fact that our patients were treated with analgesics and NSAIDs at baseline may also explain the relative modesty of the baseline WOMAC scores: These baseline scores are not raw untreated OA scores, but those obtained under usual, recognized effective treatment.