Abstract: We included 29 RCTs; nine of them provided outcome data (3339 participants). Only one study included participants in the acute phase of stroke (haemorrhagic). Doses of marine-derived n-3 PUFAs ranged from 400 mg/day to 3300 mg/day. Risk of bias was generally low or unclear in most trials, with a higher risk of bias in smaller studies. We assessed results separately for short (up to three months) and longer (more than three months) follow-up studies. Short follow-up (up to three months) Functional outcome was reported in only one pilot study as poor clinical outcome assessed with GOSE (risk ratio (RR) 0.78, 95% confidence interval (CI) 0.36 to 1.68; 40 participants; very low quality evidence). Mood (assessed with GHQ-30, lower score better), was reported by only one study and favoured control (mean difference (MD) 1.41, 95% CI 0.07 to 2.75; 102 participants; low-quality evidence). We found no evidence of an effect of the intervention for the remainder of the secondary outcomes: vascular-related death (two studies, not pooled due to differences in population, RR 0.33, 95% CI 0.01 to 8.00, and RR 0.33, 95% CI 0.01 to 7.72; 142 participants; low-quality evidence); recurrent events (RR 0.41, 95% CI 0.02 to 8.84; 18 participants; very low quality evidence); incidence of other type of stroke (two studies, not pooled due to different type of index stroke, RR 6.11, 95% CI 0.33 to 111.71, and RR 0.63, 95% CI 0.25 to 1.58; 58 participants; very low quality evidence); and quality of life (physical component mean difference (MD) −2.31, 95% CI −4.81 to 0.19, and mental component MD −2.16, 95% CI −5.91 to 1.59; one study; 102 participants; low-quality evidence). Adverse events were reported by two studies (57 participants; very low quality evidence), one trial reporting extracranial haemorrhage (RR 0.25, 95% CI 0.04 to 1.73) and the other one reporting bleeding complications (RR 0.32, 95% CI 0.01 to 7.35). Longer follow-up (more than three months) One small trial assessed functional outcome with both Barthel Index (MD 7.09, 95% CI −5.16 to 19.34) for activities of daily living, and Rivermead Mobility Index (MD 1.30, 95% CI −1.31 to 3.91) for mobility (52 participants; very low quality evidence). We carried out meta-analysis for vascular-related death (RR 1.02, 95% CI 0.78 to 1.35; five studies; 2237 participants; low-quality evidence) and fatal recurrent events (RR 0.69, 95% CI 0.31 to 1.55; three studies; 1819 participants; low-quality evidence). We found no evidence of an effect of the intervention for mood (MD 1.00, 95% CI −2.07 to 4.07; one study; 14 participants; low-quality evidence). Incidence of other type of stroke and quality of life were not reported. Adverse events (all combined) were reported by only one study (RR 0.94, 95% CI 0.56 to 1.58; 1455 participants; low-quality evidence). We are very uncertain of the effect of marine-derived n-3 PUFAs therapy on functional outcomes and dependence after stroke as there is insufficient high-quality evidence. More well-designed RCTs are needed, specifically in acute stroke, to determine the efficacy and safety of the intervention. Studies assessing functionality might consider starting the intervention as early as possible after the event, as well as using standardised clinically-relevant measures for functional outcomes, such as the modified Rankin Scale. Optimal doses remain to be determined; delivery forms (type of lipid carriers) and mode of administration (ingestion or injection) also need further consideration.

Plain-language summary: We identified 29 studies that included participants with stroke or TIA and we found relevant information in nine of them (3339 participants in total). Three had a short follow-up (up to three months) and six had a longer follow-up. Three studies compared marine-derived omega-3 fatty acids to normal care and the remainder used a placebo (dummy). Not all the studies assessed all outcomes. Effects of marine-derived omega-3 fatty acids are unclear for stroke recovery. Only two very small studies reported it, without finding significant differences. One study found less improvement in mood with marine-derived omega-3 fatty acids but the evidence was of low quality. The effect of marine-derived omega-3 fatty acids on vascular-related death, recurrence of stroke, adverse events, and quality of life after having a stroke or TIA is unclear, due to the small number of studies that have assessed them. In the short follow-up, we considered the quality of the evidence very low for recovery, recurrence, frequency of other type of stroke (bleeding or blockage), and adverse events, and low for vascular-related death, quality of life, and mood. For the longer follow-up, the evidence was of very low quality for recovery from stroke, and low quality for vascular-related death, recurrence, adverse events, and mood. Frequency of other type of stroke and quality of life were not reported in the long follow-up.