Diet, dosage and disease: Why some studies haven't reported omega-3's heart health benefits

Professor Trevor Mori, a research fellow at the university, was speaking at the recently concluded inaugural NutraIngredients Omega-3 Summit, which took place in Singapore from 20 to 22 February.

Referring specifically to EPA and DHA, he presented some key results from RCTs and meta-analyses surrounding omega-3’s heart health benefits within the last two decades.

Earlier evidence

"There are a number of studies that have looked at the benefits or potential benefits of omega-3 fatty acids on various aspects of cardiovascular disease," ​Mori said.

"A study published in 2004 showed that two to four fish meals per week conferred about a 23% reduction in coronary heart disease mortality. Another study showed that in patients with heart failure, increasing fish consumption from less than one meal per month to up to three meals per week also increased survival.​

"In a meta-analysis of over 170,000 patients with over 5,000 incident cases, there was about a 15% relative risk reduction with fish intake, and about 14% with omega-3 fatty acid intake.​

He further mentioned the JELIS trial in Japan: 18,645 men and women, hypercholesterolaemic at entry, were randomised to receiving either statin or a combination of statin and EPA; the intervention group showed a marked reduction in cardiovascular events of about 19%.

Considerations to the contrary

Despite these generally positive results, however, Mori said there was a need to also consider trials that had produced less favourable outcomes.

"We need to look at a balanced argument here — not all RCTs have shown benefits of omega-3 fatty acids on cardiovascular disease."​

He referred to a number of recent meta-analyses, one of which was published in late 2018 in the journal JAMA Cardiology​. The researchers had assessed 10 trials involving 77,917 individuals who were on average 64 years old, each receiving 226mg to 1.8g of omega-3 a day; the study reported no significant association between omega-3 supplementation and coronary heart disease death.

Pointing out a likely flaw in these studies, Mori said that of the 10 trials, seven were using low doses of omega-3 fatty acids.

He then said: "We have to ask ourselves why some of these studies, especially the more recent ones within the last 15 years, have failed to show any effect of omega-3 on heart disease.​

"There have been a number of theories proposed — amongst these, it'd been suggested that maybe, omega-3 fatty acids provide the greatest benefit to patients who are recent survivors of myocardial infarction, or who have heart failure.​

"Although some of these trials have been large in number, they were not necessarily powered to look at a reduction in sudden deaths. I think that's something that needs to be kept in mind.​

"What I think we also need to keep in mind is that a number of studies probably recruited patients with a number of comorbidities, who may have been on medication."​

Diet and dosage

Still, he added that there were likelier reasons for the disparities between some of the earlier results and those from within the last 10 to 15 years, one of which was dosage.

He elaborated that many of these studies had used doses he thought were too low to show any benefit, and that the effect of the 'background diet' should also be taken into account.

"When I talk about the 'background diet', I'm referring in particular to the omega-3 fatty acid intake. A number of studies may have included patients or participants who already had a high dietary omega-3 intake.​

"I know from my experience with our own clinical trials in Perth that it is difficult to recruit participants who aren't already taking omega-3 fatty acids — and in sufficiently high doses.​

"I also think we can't discount the fact that over the last 20 years, there have been substantial improvements in patient clinical care. It's really difficult to expect that omega-3 fatty acids can provide the same sort of benefits — over and above the clinical care patients are getting — compared to perhaps 20 to 25 years ago."​

Interventional improvements

However, Mori said there was still "some light at the end of the tunnel"​.

Referring to two recent high-profile studies, REDUCE-IT and VITAL, he said the data from the trials supported the benefits of omega-3 supplementation against coronary heart disease, stroke, anti-arrhythmic effects and heart failure.

In addition, other recent trials had also taken more factors into consideration, such as the impact of weight loss, and diuretics used by hypertension patients on omega-3's blood pressure-lowering potential, and DHA's effectiveness over EPA's in lowering ambulatory blood pressure and heart rate in human subjects.

Other cardiovascular benefits of omega-3 included the reduction of triglycerides, along with antithrombotic, anti-inflammatory and anti-oxidative actions.

Mori added: "4,000mg to 5,000mg per day of EPA and DHA can benefit patients with hypertriglyceridaemia, and omega-3 fatty acids can complement lifestyle changes and drug therapy in at-risk populations.​

"Magnitude benefits can be substantial when omega-3 fatty acids are incorporated into a broader dietary change, including increased fruit and vegetable intake, and moderation of salt intake."​