Benefits of Fish Oil Surface, but Do They Hold 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). This is evident from the results of a large observational study. 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 CVD mortality, and a 7% lower risk of CVD 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 non-prescription fish oil supplement daily is the” inexpensive, quick, and safe way for patients to be safe. ” want them to get enough omega-3s, “lead 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 on March 4 in the BMJ.

Real-world study

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

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

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

To investigate the possible effects of a fish oil supplement in practice, Mao and his team conducted a population-based prospective cohort study of 427,678 adults who had participated in the UK Biobank Study between 2006 and 2010.

The researchers compared the results among the 31% of study participants who reported regular consumption of fish oil supplements with the 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 <0.05) after adjustment for age and gender. Regular use was also associated with a lower incidence of cardiovascular events and related deaths, MI, and stroke (all P <0.05).

The adjusted risk rates in connection with fish oil consumption 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 fish oil use and death from stroke (HR 0.87; 95% CI 0.73-1.04; P = 0.14).

Gender differences

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

“At first glance, our results seem to contradict those of the VITAL study, which failed to demonstrate that fish oil reduced major cardiovascular events or new cancer diagnoses in men and women who were cancer and cardiovascular free at baseline – There are diseases, “said Mao.

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

Additionally, a 2019 meta-analysis showed that supplement use was linked to lower risk of MI, total coronary artery disease, death from coronary artery disease or CVD, and total CVD, Mao said.

The results obtained 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, suggesting that habitual fish oil use is associated with minor 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. In addition, 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 cut and dry our results and make them absolute, and both randomized and observational studies play a role,” Mao said.

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

Healthy skepticism?

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

“So I’m skeptical that the results will be real,” said Bhatt, executive director for Interventional Cardiovascular Programs at Brigham and Women’s Hospital in Boston, Massachusetts.

Additionally, remaining confusion could have affected results, as healthy individuals who are concerned about their health tend to take supplements and vitamins and therefore seem 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 on Medscape Medical News, saying the results were “fascinating” and the study adds to 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 people with low fish consumption and those with high fish consumption, “which is generally not the case in other studies”.

Although the researchers tuned into multiple factors, “the part that worried me was that they didn’t study how much red meat or fiber people included in their diet … so I can’t say it really was the omega-3 supplements are “which they give the benefit,” he added.

The study was funded by the Pearl River Scholar Funded Scheme of the Universities and Colleges of Guangdong Province, the Construction of the High-Level University of Guangdong, the US National Institutes of Health / the National Institute on Aging, and the National Natural Science Foundation of China supported. 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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