Fish 'may cut' stroke risk – supplements don’t

‘Eating two portions of oily fish a week could help ward off a stroke’ the Daily Mail reports. The headline is based on the findings of a well-conducted review into oily fish consumption and stroke risk.

Past studies have suggested that omega-3 fatty acids have a protective effect against heart diesease. The researchers were interested if a similar effect could apply to strokes.

To investigate this they combined all available evidence looking at the association between fish consumption, fish oil supplements and stroke risk.

No clinical trials had investigated the effect of dietary fish consumption on risk of stroke, though a large number of observational studies had. Generally these studies found that higher self-reported fish intake was associated with slightly lower risk: compared to eating one or fewer servings a week, eating two to four servings of fish a week reduced stroke risk by 6%.

The problem is that, as this evidence has come from observational studies, it is difficult to exclude the possibility that confounding factors are having an influence. For example, people who choose to eat more fish a week may also be following a generally healthy lifestyle – and it could be this that is causing the slight reduction in stroke risk, and not fish directly.

Sadly, for those of us who are not fish fans, a similar protective effect was not found with fish oil supplements – neither in observational studies nor in clinical trials.

Overall, this review supports the general message that fish can form part of a healthy balanced diet, but does not provide any firm evidence that eating fish will directly benefit your health.

Where did the story come from?

The study was carried out by researchers from the University of Cambridge and other academic institutions in the UK, U.S. and Netherlands.

Individual authors were in receipt of funding from a Gates Cambridge scholarship, the Medical Research Council and a grant from Pfizer Nutrition (part of Pfizer Inc – a leading pharmaceutical multinational) – though there were no financial relationships between any of the researchers and Pfizer Inc.

The study was published in the peer-reviewed British Medical Journal.

The media’s coverage of this paper is generally representative, though it did not discuss the inherent limitations of the findings. Namely the fact that the main results come from observational studies, so other factors, aside from fish consumption, may also be influencing the results.

Also, The Independent’s headline of 'Fish oil supplements won't keep the doctor away', may suggest that this review is relevant to health in general, when it has only looked at one specific aspect of health – stroke risk. Other possible effects of fish or omega-3 fatty acids upon health have not been examined.

What kind of research was this?

This was a systematic review and meta-analysis which aimed to combine the findings of published literature that had investigated whether there was any association between consumption of fish or long chain omega-3 fatty acids (fish oils) and the risk of stroke.

The reasearchers were interested in looking at the effect of these substances on both:

primary prevention of strokes – that is, in a person who has never had a stroke
secondary prevention – that is, prevention of another stroke in a person who has already had one

A systematic review is the best way of identifying all relevant literature that has examined an association between the exposure and the outcome of interest.

However, the results of systematic reviews are often influenced by the variable methods of the individual studies, which may have included:

different populations
different doses/frequencies of food items or supplements over a variable period of time
measured disease outcomes differently

This systematic review included both observational studies and randomised controlled trials (RCTs).

RCTs are the more reliable study design for this question, as the randomisation process should balance out other (confounding) factors between the fish/fish oils groups and no fish/fish oils groups which may be having an influence.

For example, with the observational studies, a person who chooses to eat oily fish or take fish oil supplements may have generally healthier lifestyle habits, such as taking regular exercise, not smoking, and eating a healthy balanced diet – and it may be these things that are influencing their risk of stroke, rather than the fish or fish oils.

In other words, it is difficult to prove causation (a direct cause and effect association) from an observational study.

What did the research involve?

The researchers carried out an electronic search of literature databases to identify any studies that had reported associations between fish (or seafood) or omega-3 fatty acids consumption and risk of stroke, which was defined using three categories of stroke:

fatal or non-fatal ischaemic stroke – where the stroke is due to a blood clot
haemorrhagic stroke – where the stroke is due to bleeding inside the brain
transient ischaemic attack – a so-called mini stroke, where there is a tempoary disruption in the blood supply to part of the brain

Observational studies were included as long as they had at least one year of follow-up and looked at either general non-diseased populations, or those at high risk of cardiovascular disease. These observational studies were of the prospective cohort study design, people are followed over time to assess whether particular factors have an impact on health outcomes.

RCTs were included if they assessed dietary fish consumption or omega-3 fatty acid supplements and followed participants for at least one year looking at stroke outcomes.

When looking at risk associations in the studies, they looked at the calculations that had adjusted for the greatest number of potential confounding factors.

Where studies had used a common unit of comparison (for example, looking at the risk associated with two servings of fish per week) they pooled these results in meta-analysis.

What were the basic results?

The researchers identified 26 prospective cohort studies and 12 randomised controlled trials which included 794,000 people who experienced 34,817 stroke events.

Observational studies

Information on fish consumption was available for 21 cohort studies. The pooled findings of these studies found that people who ate two to four servings of fish a week had a 6% reduced risk of stroke compared to those who ate one or fewer servings a week (relative risk 0.94, 95% confidence interval [CI] 0.90 to 0.98).

People who ate five or more servings a week had a 12% reduced risk compared to those who ate one serving a week (RR 0.88, 95% CI 0.81 to 0.96).

There were 14 cohort studies which looked at fish oil supplements, 10 of which looked at dietary intake of omega-3 fatty acids, while four looked at circulating blood levels of omega-3.

These studies found no significant association between omega-3 fatty acids and risk of stroke.

Randomised controlled trials

No trials were identified that had examined the effect of dietary fish intake. Twelve RCTs had looked at the effect of omega-3 fatty acids supplementation on risk of stroke. These trials found no significant effect of supplementation upon stroke risk, either when taken for primary prevention of stroke (RR 0.98, 95% CI 0.89 to 1.08), or for secondary prevention of another stroke (RR 1.17, 95% CI 0.99 to 1.38). There was no evidence of heterogeneity between these trials, meaning that all individual trials found broadly similar results.

How did the researchers interpret the results?

The researchers conclude that available observational studies indicate a moderate reduced risk of stroke with increased fish consumption.

However, long chain omega-3 fatty acids supplements did not have an effect on risk of stroke, either in observational studies or clinical trials.

The researchers consider that the beneficial effect of fish intake on stroke risk is ‘likely mediated through the interplay of a wide range of nutrients abundant in fish’. For example, as the study notes, ‘fish are also a good source of vitamins D and B’.

Conclusion

This is a well conducted review that has combined all available observational studies and clinical trials looking at the association between fish consumption or omega-3 fatty acid (fish oil) supplements and risk of stroke. However, it finds no evidence that fish oil supplements will reduce your risk of stroke; and finds limited evidence that eating fish will reduce your risk of stroke.

Neither observational studies nor clinical trials found any significant effect of omega-3 fatty acids (fish oil) supplements on risk of stroke.
No clinical trials had investigated the effect of dietary fish consumption on risk of stroke. A large number of prospective cohort studies had, however, looked at self-reported fish intake and risk of stroke and found the main significant findings of this review: eating two to four servings of fish a week reduced risk of stroke by 6% compared to eating one or fewer servings a week, and eating five or more reduced risk by 12%. However, as these are observational studies and people are choosing their diet, it is difficult to exclude the possibility that other confounding factors are having an influence, such as the fact that people eating oily fish may tend to have a healthier lifestyle (for example, exercising regularly and not smoking) and it could be these other behaviours that are having a combined or individual effect on stroke risk..
A final point worth noting is that, while The Independent headline seems to refer to health in general, saying supplements ‘won’t keep the doctor away’, this review has only looked at one specific aspect of health – stroke risk. Other possible effects of fish or omega-3 fatty acids upon health have not been examined.