In an analysis of more than 1,600 men from Sweden and Finland, researchers found that men with high levels of mercury in the body had an increased risk of heart attacks, while those with a high concentration of omega-3s had a lower risk.
Fish are considered part of a healthy diet, but the balance between potential risks and benefits from the two compounds is not clear.
While the study can't tease out cause and effect, researcher Maria Wennberg said there are ways to get fish oil naturally without getting a lot of mercury, too.
"Fish consumption two to three times per week, with at least one meal of fatty, non-predatory fish (such as salmon) and an intake of predatory fish not exceeding once a week can be recommended," Wennberg, of Umeå University in Sweden, told Reuters Health by email.
Predatory fish such as shark, swordfish, king mackerel and tilefish are at the top of the marine food chain and so concentrate mercury from the environment in their tissues.
The heavy metal is known to be toxic to the nervous system, especially in foetuses and children, and the US Environmental Protection Agency warns women of childbearing age and children against eating predatory fish.
The men in the new study, published in the American Journal of Clinical Nutrition, submitted hair and blood samples to measure their mercury and omega-3 levels, as well as information on their health and lifestyle.
The average mercury level among the Swedish men was 0.57 micrograms per gram of hair, whereas it was more than twice as high in their Finnish peers. Swedes, however, had higher levels of omega-3s than did Finns.
The researchers found that men with at least 3 micrograms of mercury per gram of hair had a somewhat increased risk of heart attacks compared with men with 1 microgram per gram, although they didn't calculate the exact risk.
But this only held true if the men also had low levels of omega-3 fats. For men with more of the fats, it took higher levels of mercury to see an increased heart attack risk - suggesting the two compounds might have opposite effects on the ticker.
The results don't prove that the high mercury levels were responsible for the increased risk of heart attack, but merely that the two are linked.
Dr. Dariush Mozaffarian of the Harvard School of Public Health in Boston said other factors, such as low education levels among those with high mercury levels, could also be at work.
Previous studies by Mozaffarian, who was not involved in the new work, did not show a link between mercury and heart attacks. But that research involved mercury levels much lower than in the current study.
He said the new results probably don't apply to most Americans, who have lower mercury levels than the men studied by Wennberg and her colleagues. And few people have high mercury levels and low omega-3s, because mercury from fish often comes with the healthy fats.
According to Mozaffarian, it's likely that the Finnish men with high mercury levels and low omega-3 levels ate contaminated whitefish from lakes in northern parts of the country.
Wennberg said her findings highlight the need to consider omega-3s when studying the link between mercury and disease.