Background/Purpose: Fish oil is widely used for the symptomatic treatment of osteoarthritis.  However, its effect on cartilage volume has not previously been investigated in an RCT. The objective of this study was to determine whether high dose fish oil is superior to low dose fish oil in retarding structural progression of symptomatic knee osteoarthritis.

Methods: Investigator initiated, government funded, randomized, double-blind, multicenter 24 month trial. Patients older than 40 years, with knee OA as defined by the ACR clinical criteria, suffering from regular knee pain were randomized 1:1 to (1) high dose fish oil liquid (EPA 18% and DHA 12%) 15mL/day or (2) low dose fish oil (blend of fish oil and sunola oil in a ratio of 1:9) 15mL/day. Each oil was also flavored with citrus to provide a comparable taste and ensure masking. Prior to randomization, a 4- week run in period with a similar oil was performed to exclude patients who were intolerant to liquid fish oil. Baseline knee radiographs were scored according to OARSI atlas. The co-primary end point was change in cartilage volume (medial tibial, lateral tibial, patellotibial) from baseline to 24 months. The co-primary endpoint of WOMAC pain score has previously been reported. Analysis of paired MRI data was performed, according to intention-to-treat and per-protocol analysis.

Results: Participants (N=202) were 49% female, mean age 60.9 yrs (SE 0.7), mean BMI 29.0 (SE 4.7).  There was significantly greater and earlier dropout in the high dose group (34.6%, median 3 months), compared to the low dose group (19.8%, median 7.5 months). Participants from one site were excluded (n=51) due to technical MRI issue with baseline MRI data and a further 35 participants were excluded due to lack of paired MRI data. There was similar baseline characteristics in each group, except for gender (low dose group 38% female, high dose 58% female, p=0.025). The OARSI joint space narrowing and osteophyte scores were not different between groups. In intention to treat analysis (n=116), both groups demonstrated preservation or a slight increase in cartilage volume in each compartment over time with no significant difference seen between the two groups (Table 1). Similarly, per protocol analysis (n=99) demonstrated no decrease over time or difference between groups. There was no difference in results when males and females were analyzed separately.

Table 1.

MRI	Group	CHANGE FROM BASELINE (ITT)			Delta-Delta1
		mean	sd	p-valchange	mean	sd	p-valueH vs L change
Lateral tibial	Low Dose	0.015	0.027	0.58	0.000	0.038	1.00
	High Dose	0.015	0.026	0.57
Medial tibial	Low Dose	0.015	0.029	0.60	0.020	0.040	0.63
	High Dose	0.035	0.028	0.63
Patellotibial	Low Dose	0.027	0.040	0.50	0.030	0.055	0.59
	High Dose	0.003	0.039	0.94

Conclusion: High dose fish oil supplementation for 2 years was not significantly different in its effect on cartilage volume in patients with symptomatic knee OA, when compared to low dose fish oil. The lack of a decrease in both groups is unexpected and may imply that both therapies have chondroprotective properties.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-fish-oil-on-structural-progression-in-knee-osteoarthritis-a-two-year-randomized-double-blind-clinical-trial-comparing-high-dose-with-low-dose/