BACKGROUND: Peripheral artery disease (PAD) is a progressive disorder characterised by stenosis or occlusion of arteries, or both, due to arteriosclerosis. Intermittent claudication (IC) and diminished walking ability are often present as the main symptoms of PAD. Omega-3 fatty acids have been used in the treatment and prevention of coronary artery disease, although current evidence suggests they may be of limited benefit. Peripheral arterial disease and coronary artery disease share a similar pathogenesis. It is uncertain whether omega-3 fatty acids benefit people with IC. This is an update of the review first published in 2004 and updated in 2013.
OBJECTIVES: To evaluate the benefits and harms of omega-3 fatty acid supplementation in people with intermittent claudication.
SEARCH METHODS: We used standard, extensive Cochrane search methods, and searched the Cochrane Vascular Specialised Register via the Cochrane Register of Studies, CENTRAL, MEDLINE Ovid, Embase Ovid, and two trials registers on 19 April 2024.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) of omega-3 fatty acids versus placebo or non-omega-3 fatty acids in people with intermittent claudication.
DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were quality of life, pain-free walking distance, and maximal walking distance. Secondary outcomes were ankle-brachial index, revascularisation procedures in the lower limb, amputation rate/frequency, lipid levels, blood pressure, all-cause and vascular mortality, non-fatal vascular events, and adverse effects of therapy. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS: We included 15 RCTs (1830 participants) comparing omega-3 fatty acid supplementation with placebo or alternative therapies. The follow-up was four weeks to six years. The majority of the studies had unclear risk of bias, and many could not be included in our meta-analysis, so were reported narratively. The evidence is very uncertain about the effect of omega-3 fatty acids on quality of life. One study measured quality of life but did not present any data. The study authors reported there was no improvement in any of the eight self-reported quality-of-life parameters in the SF-36 questionnaire between entry and 16 weeks for the intervention group. No results were presented for the control group (very low-certainty evidence). Omega-3 fatty acids may result in little to no effect on pain-free walking distance (mean difference (MD) 1.01 metre (m), 95% confidence interval (CI) -34.23 to 36.24; 3 studies, 147 participants; very low-certainty evidence), or maximal walking distance (MD -4.18 m, 95% CI -37.10 to 28.74; 3 studies, 164 participants; very low-certainty evidence). Omega-3 compared with a control may have little to no effect on ankle-brachial index (MD -0.02, 95% CI -0.08 to 0.04; 3 studies, 168 participants; very low-certainty evidence). One study assessed the incidence of revascularisation procedures (lower limb angioplasty/bypass surgery) and rate of amputation (progression of critical limb ischaemia/amputation) in the lower limb. Results showed that omega-3 may have little to no effect on either outcome (very low-certainty evidence). Seven studies reported adverse events. Details of reporting varied amongst studies, and we were unable to combine the results. A total of 47 adverse effects were reported in the intervention groups compared to 33 events in the control groups (7 studies, 488 participants; low-certainty evidence). The evidence suggests that omega-3 results in little to no difference in adverse events. Meta-analyses showed no differences between intervention and placebo groups for cholesterol, triglycerides, or blood pressure. Two studies assessed mortality. All-cause mortality and vascular mortality were reported by one study, and vascular mortality by another. We were unable to pool the studies, but both studies individually reported there were no differences between the omega-3 and the control groups. There was no difference between the intervention and placebo groups for the incidence of non-fatal coronary events (odds ratio (OR) 0.59, 95% CI 0.13 to 2.60; 2 studies, 141 participants), or the incidence of non-fatal stroke/transient ischaemic attack (OR 0.95, 95% CI 0.13 to 6.77; 2 studies, 110 participants).
AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effect of omega-3 fatty acids in people with intermittent claudication on quality of life, walking distance (pain-free or maximal), ankle-brachial index, and the incidence of revascularisation procedures or frequency of amputation in the lower limb. The evidence suggests that omega-3 results in little to no difference in adverse events. Further high-quality research is needed to fully evaluate short- and long-term effects of omega-3 fatty acids on the most clinically relevant outcomes in people with intermittent claudication.