Purpose: It is increasingly understood that neutraceuticals are potential candidates for Osteoarthritis (OA) management as treatment adjuvant. ω-3 poly-unsaturated fatty acids (PUFAs) are well-known for their anti-inflammatory potential through various mechanisms. A strong linkage of inflammation with OA pathology is now more and more recognized. The anti-inflammatory nature of ω-3 is thought to have a corrective impact on catabolic pathway and ultimately on the disease progression. However, its molecular mechanism is not much learnt. The present study was planned to investigate action of ω-3 on synoviocytes and its clinical relevance in OA patients with carefully selected biomarkers representing multiple pathologies associated with OA like, metalloproteinase-1 (MMP1) and MMP13 are pro-inflammatory, vascular endothelial growth factors (VEGF) expresses angiogenesis while SOX9 is associated with chondrogenesis.
Methods: Study I: rabbit synoviocytes cell line (HIG-82) was challenged with interleukin-1β for 72h and further treated with eicosapentaenoic acid (EPA) and docosahexaenoic acid(DHA) with the dose of 5, 25 and 50μM for 24, 48 and 72h and modulation of MMP1, MMP-13, SOX-9 and VEGF1 genes was recorded using real time PCR .
Study II: A pilot study of flax oil supplementation was conducted in 30 knee OA patients for a period of 21 days (with different disease severity, confirmed by radiographic Kellgren-Lawrence score) (Tab. Alvel 1gm - dose - 2 tabs/day; Alfa Linolenic Acid concentration - 50mg per tab). No dietary/physical/medicine restriction was applied. Compliance was confirmed by serum fatty acid analysis by Gas Chromatography and efficacy of supplementation was evaluated using Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) questionnaire (pre and post supplementation).
Study III: Study III was planned to nullify the placebo effect due to shorter duration in study II. Six respondents from study II were randomly enrolled for 90 days supplementation with a gap of 30 days. The supplementation was conducted as described earlier and WOMAC score was obtained every month (T0, T30, T60 and T90).
Results: Study I - EPA showed a significant down regulation of SOX9 and VEGF when treated for 72h with a dose of 50 μM; however remained ineffective for MMP1 and MMP13. On the other hand, a noteworthy reduction was noted in MMP13, SOX9 and VEGF when synoviocytes were treated with DHA for 72 h (50 μM). Initial increase was noted in MMP1 and MMP13 in first 48h when treated with 5 μM of EPA and DHA.
Study II - out of total 30 patients, two dropped out (for non clinical reasons); while seven remained non-respondent. Pre and post WOMAC score were analysed for 21 respondents using Wilcoxon’s Sign Rank Test to calculate supplementation efficacy. WOMAC sub-score ‘pain’ and ‘function’ revealed a dramatic improvement after 21 days (p=0.0012, p=0.0008 respectively); however, ‘stiffness’ remained unaltered (p=0.1266). Post-supplementation total WOMAC score showed a statistical significance at 1% level (p=0.0003).
Study III - out of six, 2 patients showed gradual reductions in WOMAC score over 90 days while two patients’ monthly WOMAC was static throughout the supplementation period; the remaining two were non-responsive for treatment.
Conclusions: ω-3 can target multiple pathways, which is ideal way to deal with a complex disease like OA. It has a good anti-inflammatory potential which effectively alleviates OA associated synovitis. Affected patients recorded a substantial reduction in WOMAC-pain and improved WOMAC function score endorsing the same. However, joint stiffness is secondary to chronic synovitis and hypertrophy which will take longer to resolve than treatment period. Long term follow-up studies are also needed to evaluate chondro-protective action of ω-3. To conclude, ω-3 fatty acid supplementation is safer alternative for managing OA associated pain and other linked pathologies.
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