Key messages
We are very uncertain whether taking omega-3 fatty acid supplements has any effect on the quality of life, walking distance, or blood flow to the legs of people with intermittent claudication.
We are very uncertain whether taking omega-3 fatty acid supplements has any effect on blood pressure, or blood levels of different types of cholesterol or triglycerides (build-up of fatty material).
Taking omega-3 may not influence fatal or non-fatal circulation problems or other side effects, but we are very uncertain about the results.
More, well-designed studies with more people are required to help understand whether omega-3 supplements carry any benefits or risks.
What is intermittent claudication?
Intermittent claudication is pain in the calf of the leg due to a lack of blood needed to supply those muscles with oxygen during exercise or movement, which causes a person to slow or stop moving. It is the most common symptom reported by people with long-standing lower limb arterial disease, which results when the arteries that supply blood to the lower limbs are narrowed. This narrowing most commonly occurs with atherosclerosis, a result of the accumulation of fatty materials, such as cholesterol and triglycerides.
How is intermittent claudication treated?
People with lower limb arterial disease are advised to stop smoking, control their blood glucose, participate in structured exercise treatment, take special medicines, and undergo more complex treatments, such as angioplasty (unblocking of a blood vessel) or surgical repair.
What did we want to find out?
We wanted to find out if omega-3 fatty acid supplements were better than dummy treatments (that do not contain any omega-3) or alternative treatments to improve:
· Quality of life
· Walking distance
· Blood flow in the legs
· Cholesterol and triglyceride levels
· Blood pressure
· Number of angioplasties (opening blocked or narrowed arteries) or surgical repairs
We also wanted to find out if omega -3 was associated with any unwanted side effects.
What did we do?
We searched for studies that examined omega-3 fatty acids compared with dummy treatments or alternative therapies in people with intermittent claudication. We wanted to find out if omega-3 supplements were better than dummy treatments or alternative therapies to improve the outcomes.
We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors, such as study methods and sizes.
What did we find?
We found 15 studies involving 1830 people with symptoms of intermittent claudication, lower limb arterial disease, or both. There were 971 people in the largest study and 18 in the smallest. Study locations included the United Kingdom, Australia, the Netherlands, Switzerland, the United States, and Spain. The average age of people who participated was between 62 and 69 years. Four studies only recruited men.
Omega-3 fish oil supplements were used in 11 studies, and foods containing omega-3 were used in the other four studies. Different dosages were used. Studies lasted between four weeks and approximately six years. All except one used a dummy treatment for comparison. Some were funded by the manufacturers of omega-3 supplements and food.
Main results
Compared with no omega-3 supplements:
Omega-3 supplements may have little to no effect on quality of life, walking distance, blood flow in the leg, or the amount of angioplasty, surgical repair, or amputation, but we are very uncertain about the results.
Omega-3 may have little to no effect on cholesterol or triglyceride blood levels, or blood pressure.
There did not appear to be any difference in fatal or non-fatal circulation-related problems between people taking omega-3 and those not taking omega-3, but we are very uncertain about the results.
Only 7 studies reported whether people experienced unwanted side effects, such as an upset stomach or headache. The evidence suggests there is little to no difference between those who took omega-3 and those who did not take omega-3 for side events.
What are the limitations of the evidence?
Our confidence in the evidence for each of the most important outcomes was very low to low. This was because of the way the studies were designed, the small numbers of people involved, and the differences in results between studies. Many studies also reported their results in a way that meant we could not include them in our statistical analyses.
How up-to-date is this evidence?
The evidence is up-to-date to 19 April 2024.
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.
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.
To evaluate the benefits and harms of omega-3 fatty acid supplementation in people with intermittent claudication.
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.
We included randomised controlled trials (RCTs) of omega-3 fatty acids versus placebo or non-omega-3 fatty acids in people with intermittent claudication.
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.
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).