Eating fish associated with significant health benefits — Pooled analysis

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There is a significant protective benefit of fish consumption in people with cardiovascular disease, as well as with significant improvements in multiple other health outcomes.

An umbrella review of meta-analyses found that increased fish consumption also improved rates of cardiovascular and all-cause mortality. However, fish consumption had no significant effects on rates of hypertension, atrial fibrillation, or type 2 diabetes.

Although not directly reflected in the findings, modest fish consumption also appears to be was associated with significant improvements in multiple health outcomes, including the risks for myocardial infarction, stroke, and heart failure to have cardiac benefits, according to a JAMA commentary.

Medscape Medical News reports that researchers Jayedi and Shab-Bidar examined 34 meta-analyses of prospective observational studies, which featured a total of 40 different outcomes. Greater fish consumption of 100 g/day was associated with significant improvements in multiple health outcomes, including the risks for myocardial infarction, stroke, and heart failure.

Medscape Medical News comments that there is a lack of large studies that have differentiated the effects of fish consumption among adults with and without a history of cardiovascular disease (CVD). The current study addresses this gap.

People with CVD who regularly ate fish had significantly fewer major CVD events and there were fewer total deaths compared with similar individuals who did not eat fish, but there was no beneficial link from eating fish among the general population in prospective data collected from more than 191,000 people from 58 countries.

Despite the neutral finding among people without CVD, the finding that eating fish was associated with significant benefit for those with CVD or who were at high risk for CVD confirms the public health importance of regular fish or fish oil consumption, says one expert.

A little more than a quarter of those included in the new study had a history of CVD or were at high risk for CVD. In this subgroup of more than 51,000 people, those who consumed on average at least 2 servings of fish weekly (at least 175 g, or about 6.2 ounces per week) had a significant 16% lower rate of major CVD events during a median follow-up of about 7.5 years.

The rate of all-cause death was a significant 18% lower among people who ate 2 or more fish portions weekly compared with those who did not, say Dr Deepa Mohan, and associates. The researchers saw no additional benefit when people regularly ate greater amounts of fish.

“There is a significant protective benefit of fish consumption in people with cardiovascular disease,” summed up Dr Andrew Mente, a senior investigator on the study and an epidemiologist at McMaster University in Hamilton, Canada. “This study has important implications for guidelines on fish intake globally. It indicates that increasing fish consumption and particularly oily fish in vascular patients may produce a modest cardiovascular benefit,” he said in a statement released by McMaster.

The neutral finding of no significant benefit (as well as no harm) regarding either CVD events or total mortality among people without CVD “does not alter the large body of prior observational evidence supporting the cardiac benefits of fish intake in general populations,” notes Dr Dariush Mozaffarian, in a commentary that accompanies the report.

Although the new analysis failed to show a significant association between regular fish consumption and fewer CVD events for people without established CVD or CVD risk, “based on the cumulative evidence from prospective observational studies, randomised clinical trials, and mechanistic and experimental studies, modest fish consumption appears to have some cardiac benefits,” he adds.

“Adults should aim to consume about 2 servings of fish per week, and larger benefits may accrue from nonfried oily (dark meat) fish,” writes Mozaffarian, a professor of medicine and nutrition at Tufts University School of Medicine, Boston, Massachusetts. Oily, dark fishes include salmon, tuna steak, mackerel, herring, and sardines. Species such as these contain the highest levels of long-chain omega 3 fatty acids, eicosapentanoic acid, and docosapentanoic acid; these nutrients likely underlie the CVD benefits from fish, Mozaffarian says.

“Fish oil lowers heart rate, blood pressure, and triglycerides (at high dosages), increases adiponectin, improves endothelial function, and in some studies improves oxygen consumption in myocardium. If there is benefit from fish it’s from the omega 3s, and all in all the evidence supports this,” but because the evidence is primarily observational, it can only show linkage and cannot prove causation, he explains.

Given the potential benefit and limited risk: “I think everyone should aim to eat 2 servings of fish each week, preferentially oily fish. That’s very solid,” says Mozaffarian, who is also a cardiologist and dean of the Gerald J and Dorothy R Friedman School of Nutrition Science and Policy, Boston, Massachusetts.

The investigators did not have adequate data to compare the associations between outcomes and a diet with oily fish vs less oily fish.

For people who either can’t consume 2 fish meals a week or want to ensure their omega 3 intake is adequate, “it’s very reasonable for the average person to take 1 [over-the-counter] fish oil capsule a day,” Mozaffarian adds.

He acknowledges that several studies of fish oil supplements failed to show benefit, but several others have. “It’s a confusing field, but the evidence supports benefit from omega 3s,” he concludes.

He discounts the new finding that only people with established CVD or who are at high-risk benefit. “I’m not sure we should make too much of this, because many prior studies showed a lower CVD risk in fish-eating people without prevalent CVD,” he said. The new study “provides important information given its worldwide breadth,” he added.

The new report used data regarding 191,558 people enrolled prospectively in any of 4 studies. The average age of the participants was 54 years, and 52% were women.
During follow-up, death from any cause occurred in 6% of those without CVD or CVD risk and in 13% of those with these factors.

Major CVD events occurred in 5% and 17% of these 2 subgroups, respectively. To calculate the relative risks between those who ate fish and those who did not, the investigators used standard multivariate adjustment for potential confounders and adjusted for several dietary variables, Mente says.

 

Study details
Associations of Fish Consumption With Risk of Cardiovascular Disease and Mortality Among Individuals With or Without Vascular Disease From 58 Countries

Deepa Mohan; Andrew Mente; Mahshid Dehghan; Sumathy Rangarajan; Martin O’Donnell; Weihong Hu; Gilles Dagenais; Andreas Wielgosz; Scott Lear; Li Wei; Rafael Diaz; Alvaro Avezum; Patricio Lopez-Jaramillo; Fernando Lanas; Sumathi Swaminathan; Manmeet Kaur; K. Vijayakumar; Viswanathan Mohan; Rajeev Gupta; Andrzej Szuba; Romaina Iqbal; Rita Yusuf; Noushin Mohammadifard; Rasha Khatib; Khalid Yusoff; Sadi Gulec; Annika Rosengren; Afzalhussein Yusufali; Edelweiss Wentzel-Viljoen; Jephat Chifamba; Antonio Dans; Khalid F. Alhabib ; Karen Yeates; Koon Teo; Hertzel C Gerstein; Salim Yusuf; for the PURE, ONTARGET, TRANSCEND, and ORIGIN investigators

Published in JAMA Internal Medicine on 8 March 2021

Abstract
Importance
Cohort studies report inconsistent associations between fish consumption, a major source of long-chain ω-3 fatty acids, and risk of cardiovascular disease (CVD) and mortality. Whether the associations vary between those with and those without vascular disease is unknown.
Objective
To examine whether the associations of fish consumption with risk of CVD or of mortality differ between individuals with and individuals without vascular disease.
Design, Setting, and Participants
This pooled analysis of individual participant data involved 191 558 individuals from 4 cohort studies—147 645 individuals (139 827 without CVD and 7818 with CVD) from 21 countries in the Prospective Urban Rural Epidemiology (PURE) study and 43 413 patients with vascular disease in 3 prospective studies from 40 countries. Adjusted hazard ratios (HRs) were calculated by multilevel Cox regression separately within each study and then pooled using random-effects meta-analysis. This analysis was conducted from January to June 2020.
Exposures
Fish consumption was recorded using validated food frequency questionnaires. In 1 of the cohorts with vascular disease, a separate qualitative food frequency questionnaire was used to assess intake of individual types of fish.
Main Outcomes and Measures
Mortality and major CVD events (including myocardial infarction, stroke, congestive heart failure, or sudden death).
Results
Overall, 191 558 participants with a mean (SD) age of 54.1 (8.0) years (91 666 [47.9%] male) were included in the present analysis. During 9.1 years of follow-up in PURE, compared with little or no fish intake (≤50 g/mo), an intake of 350 g/wk or more was not associated with risk of major CVD (HR, 0.95; 95% CI, 0.86-1.04) or total mortality (HR, 0.96; 0.88-1.05). By contrast, in the 3 cohorts of patients with vascular disease, the HR for risk of major CVD (HR, 0.84; 95% CI, 0.73-0.96) and total mortality (HR, 0.82; 95% CI, 0.74-0.91) was lowest with intakes of at least 175 g/wk (or approximately 2 servings/wk) compared with 50 g/mo or lower, with no further apparent decrease in HR with consumption of 350 g/wk or higher. Fish with higher amounts of ω-3 fatty acids were strongly associated with a lower risk of CVD (HR, 0.94; 95% CI, 0.92-0.97 per 5-g increment of intake), whereas other fish were neutral (collected in 1 cohort of patients with vascular disease). The association between fish intake and each outcome varied by CVD status, with a lower risk found among patients with vascular disease but not in general populations (for major CVD, I2 = 82.6 [P = .02]; for death, I2 = 90.8 [P = .001]).
Conclusions and Relevance
Findings of this pooled analysis of 4 cohort studies indicated that a minimal fish intake of 175 g (approximately 2 servings) weekly is associated with lower risk of major CVD and mortality among patients with prior CVD but not in general populations. The consumption of fish (especially oily fish) should be evaluated in randomized trials of clinical outcomes among people with vascular disease.

 

Full Medscape Medical News report (Restricted access)

JAMA Internal Medicine study (Restricted access)

JAMA Internal Medicine commentary (Open access)

 

See also MedicalBrief archives:

Mixed results from trials on cardiovascular benefits of fish oil

Data stacking up against fish oils

Omega-3 intake link to reduced heart risk — Clinical trial meta-analysis


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