Our results, examining fasting plasma levels of n-6 and n-3 PUFAs and OA, suggest subjects in MOST with high levels of total n-3 PUFAs (in the fourth quartile), specifically DHA, had lower patellofemoral cartilage loss. In contrast, MOST subjects with higher levels of AA tended to have higher synovitis severity.
We are unaware of other studies that have looked in vivo at the relation of n-6 and n-3 PUFA levels with knee structures in OA. There have been studies on the association of fatty acids with OA in general or elements related to disease. For example, in a study looking at fat in OA bone, levels of n-6 PUFAs, especially AA was almost double that seen in a comparator osteoporotic bone (29
). Also, in patients undergoing joint replacement surgery for OA, those taking fish oils (rich in n-3 PUFAs) before surgery had a near doubling of long chain fatty acids in synovial fluid and bone marrow compared to before supplementation (30
). AA has been shown to be increased in cartilage, serum, and synovial fluid in OA patients compared to non OA (31
We found an effect of both total n-3 PUFAs and of DHA on patellofemoral cartilage loss. These two analytes are not synonymous, with DHA representing only a small fraction of total n-3 PUFAS but representing one of the biologically active fractions. Our results are not unique in that others examining n-3 PUFA relations with disease have also reported an association uniquely with DHA (32
Why would there be an effect of relevant fatty acids on patellofemoral but not tibiofemoral cartilage? We are not sure but note that Ayral et al (4
) in a longitudinal arthrosopy study reported that cartilage loss occurred only adjacent to active synovitis and not distant from it. Synovitis predominates in the parapatellar area (33
). In our study subset, all subjects with moderate to severe synovitis had this inflammation in the parapatellar region. Therefore, it is possible that the patellar cartilage loss we saw was due to this adjacent synovits and that synovitis did not invest the tibiofemoral compartment.
We acknowledge that our findings are not consistent across n-6 and n-3 PUFAs or their components and some of our results are null. The inconsistent and null findings may partially be explained by the observational nature of the study. The levels of n-3 PUFAs did not attain levels reached in clinical trials where subjects are supplemented with n-3 PUFAs. As mentioned earlier, the Western diet is much higher in n-6 than n-3 PUFAs thereby reducing the potential antiflammatory benefits of n-3 PUFAs. In some trials the intake of n-6 PUFAS was restricted in conjunction with n-3 supplementation, and in these trials an enhanced benefit for n-3 PUFAs was seen (34
We interpret our findings as indicating a potential positive effect on synovitits and cartilage loss of n-3 PUFAs and negative effect of n-6 PUFAs, specifically AA. As the first descriptive observational study of these fatty acids and their relation to relevant structural abnormalities, we hope that these results generate further investigations that may clarify our findings.
There are several limitations when interpreting our data. We were only able to obtain one measurement of fatty acid intake at baseline. The measurement will be affected by current fatty acid intake and there is the potential for misclassification. We cannot make causal inferences because we have not manipulated the diet and we do not have longitudinal data. And, an observational association of health behaviors, such as dietary fatty acid intake, with disease may only indicate an indirect connection (ie. those with a healthy diet also exhibit other behaviors that are beneficial to their joints).
In conclusion, this observational study suggests that future studies manipulating the systemic levels of n-6 and n-3 PUFAs, which are influenced by diet, may be warranted to determine the effects of these fatty acids on synovitis and cartilage loss in knees with or at risk of OA.