Benefits of Fish Oil, but Do They Hold Up Water?

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Regular consumption of fish oil is associated with a lower risk of all-cause mortality and cardiovascular disease (CVD), as well as CVD events, including stroke and myocardial infarction (MI), results from a large observational study suggest. However, at least one expert is “skeptical that the results are real”.

The researchers found that habitual fish oil supplementation was associated with a 13% lower risk of all-cause mortality, a 16% lower risk of cardiovascular mortality, and a 7% lower risk of cardiovascular events in the general population.

“Although, given the price and convenience, taking fish oil supplements can cause minor side effects such as bad breath, heartburn, nausea and gastrointestinal discomfort,” taking a daily over-the-counter fish oil supplement is “inexpensive, quick and safe”. Way for patients who want to be sure they are getting enough omega-3s, “Senior Researcher Prof Chen Mao, Department of Epidemiology, School of Public Health, Southern Medical University, Guangdong, China, told Medscape Medical News .

The study was published online in the BMJ on March 4.

Real-world study

As reported by Medscape Medical News, the recent Vitamin D and Omega-3 Trial (VITAL) linked omega-3 fatty acid supplementation with a significantly lower risk of MI, but found no association between fish oil consumption and one lower risk of CVD events.

Other previous research, including a meta-analysis of 13 randomized controlled trials, supports an association between omega-3 fatty acid intake, including fish oil intake, and the prevention of cardiovascular disease.

However, current researchers note that these studies were conducted under “ideal and controlled circumstances”.

To investigate the potential effects of fish oil supplementation in a real-life setting, Mao and his team conducted a population-based, prospective cohort study of 427,678 adults who participated in the UK Biobank Study between 2006 and 2010.

The researchers compared the results among the 31% of study participants who reported taking fish oil supplements regularly with results for those who reported no use of fish oil supplements. They used death certificates and hospital records to track the results through 2018.

A total of 12,928 people died from whatever reason during the study period. These included 3,282 CVD deaths, 1,423 from MI and 664 deaths from stroke.

There were 18,297 cardiovascular events including 7754 MIs and 4009 strokes.

The intake of fish oil was significantly associated with a lower risk of all-cause mortality (p <.05) after adjustment for age and gender. Regular use was also associated with a lower incidence of cardiovascular events and related deaths, MI, and strokes (all P <0.05).

Adjusted hazard rates associated with the use of fish oil were 0.87 (95% confidence interval.) [95% CI], 0.83-0.90) for all-cause mortality; 0.84 (95% CI, 0.78-0.91) for CVD mortality; and 0.80 (95% CI, 0.70-0.91) for MI mortality in a multivariable analysis.

The adjusted HRs for adverse events were 0.93 (95% CI, 0.90-0.96) for CVD; 0.92 (95% CI, 0.88-0.96) for MI; and 0.90 (95% CI, 0.84-0.97) for stroke.

In contrast, the researchers found no significant association between the consumption of fish oil and death from stroke (HR 0.87; 95% CI 0.73-1.04; P = 0.14).

Gender differences

Interestingly, the association between fish oil consumption and lower all-cause mortality was stronger in men than women (HRs, 0.81 vs. 0.95) and among current smokers than nonsmokers (HRs, 0.77 vs. 0.90).

“Our results seem at first glance to contradict those of the VITAL study, which did not show that fish oil reduced serious cardiovascular events or new cancer diagnoses in men and women who were cancer and cardiovascular disease-free at baseline “said Mao.

However, the point estimates for a reduction in CVD events for VITAL (HR, 0.92) and the current study (HR, 0.93) were similar. In addition, the confidence interval (0.90-0.96) in Mao’s study suggests that omega-3s “have a significant association with CVD events,” he added

In addition, a 2019 meta-analysis showed that supplement use was associated with a lower risk of MI, total coronary artery disease, death from coronary artery disease or CVD, and total CVD, Mao said.

The results held steady when researchers ruled out REDUCE-IT – a study that showed significant benefits of a prescription omega-3 fatty acid formulation for patients with high triglyceride levels, he added.

“Therefore, our results are reasonable and suggest that habitual fish oil use is associated with marginal benefit for CVD events in the general population,” Mao said.

Possible limitations of the study are the lack of information on dose, formulation and duration of fish oil consumption. Also, because the study was an observational study, “it is difficult to separate the effects of a healthy lifestyle from habitual use of fish oil supplements,” the researchers note.

“It might take more definitive testing in the future to crush our results and make them absolute, and both randomized and observational studies play a role,” Mao said.

“We can do studies to see what dose is needed to have a clinically meaningful effect,” he added. He and colleagues can also evaluate omega-3 fatty acid supplementation for primary prevention in high-risk patients.

Healthy skepticism?

Commenting on the results for Medscape Medical News, Deepak Bhatt, MD, MPH, principal investigator of the REDUCE-IT study, noted that “related randomized trials of these types of supplements have shown no significant benefit.

“So I’m skeptical about the real results,” said Bhatt, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital in Boston, Massachusetts.

Additionally, residual mix-ups could have affected results, as healthy individuals who are concerned about their health tend to consume supplements and vitamins and therefore appear to have better health outcomes than those who don’t, he said. In addition, healthy behavior could have contributed to the observed benefits.

“In addition, there is data showing that fish oil supplements vary from batch to batch in their exact omega-3 fatty acid content and that they contain other saturated fats as well,” added Bhatt.

Eric Rimm, ScD, also commented for Medscape Medical News that the results were “fascinating” and that the study enriched the literature. He found that the study included nearly half a million participants from the general population, in contrast to cohorts from clinical trials.

The researchers found some benefits of omega-3 supplementation, added Rimm, professor of epidemiology and nutrition, director of the cardiovascular epidemiology program at Harvard TH Chan School of Public Health, and professor of medicine at Harvard Medical School in Boston.

However, they found no difference between those who reported low fish consumption and those who reported a high value, “which is generally not the case in other studies”.

Although the researchers took multiple factors into account, “the part that worried me was that they didn’t pay attention to how much red meat or fiber people were getting in their diet … so I can’t say it really is that Omega-3 supplements are “that lend themselves the benefit,” he added.

The study was supported by the Pearl River Scholar Funded Scheme of Guangdong Province Universities and Colleges, the Construction of High-level University of Guangdong, the US National Institutes of Health / National Institute on Aging, and the National Natural Science Foundation of China. Mao and Rimm have not disclosed any relevant financial relationships. Bhatt was REDUCE-IT’s lead researcher, and Brigham and Women’s Hospital received research funding from Amarin Corp. for the study.

BMJ. Published online on March 4, 2020. Full text

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