Pittsburgh, PA and Shiga, Japan - The low rate of atherosclerosis and heart disease in Japanese people may be related to their very high levels of marine-derived omega-3 fatty acids rather than genetic factors, a new study suggests [1].

The study, published in the August 5, 2008 issue of the Journal of the American College of Cardiology (available online July 28), was conducted by a group led by Dr Akira Sekikawa (University of Pittsburgh, PA, and Shiga University of Medical Science, Japan).

They found that compared with white or Japanese American men living in the US, Japanese men living in Japan had twice the blood levels of omega-3 fatty acids—a finding that was independently linked to low levels of atherosclerosis.
 
"The death rate from coronary heart disease in Japan has always been puzzlingly low. Our study suggests that the very low rates of coronary heart disease among Japanese living in Japan may be due to their lifelong high consumption of fish," Sekikawa said.

The researchers note that CHD mortality in Japan has been decreasing since the 1970s, despite the changes in lifestyle toward Westernization that have brought a continuous increase in dietary fat intake and serum cholesterol. They point out that recent studies in Japan, where fish intake is one of the highest in the world, showed that additional supplementation or intake of marine-derived omega-3 fatty acids is significantly associated with a reduced risk of nonfatal coronary events. They thus conducted the current study to investigate whether greater levels of serum marine-derived omega-3 fatty acids in Japanese men vs white men are associated with lower levels of atherosclerosis.

The study, known as Electron-Beam Tomography, Risk Factor Assessment Among Japanese and US Men in the Post-World War II Birth Cohort (ERA JUMP) included 868 randomly selected men aged 40 to 49. Of these, 281 were Japanese men living in Japan; 306 were white men living in the US, and 281 were third- or fourth-generation Japanese American men from Hawaii. All study participants had a physical examination, completed a lifestyle questionnaire, and had blood tests to measure cholesterol levels and levels of omega-3 fatty acids. Atherosclerosis was assessed by measuring carotid intima-medial thickness (IMT) and coronary artery calcification (CAC).

Results showed that the Japanese men had the lowest levels of atherosclerosis, whereas whites and Japanese Americans had similar higher levels. The Japanese men also had twofold higher levels of marine-derived omega-3 fatty acids than white and Japanese Americans.

In addition, the significant differences between Japanese and American men in multivariable-adjusted IMT and CAC prevalence became nonsignificant after adjustment further for marine-derived omega-3 fatty acids.

The researchers say: "Our results suggest that marine-derived omega-3 fatty acids have antiatherogenic effects, especially at the high levels observed in Japanese men," a hypothesis they note is supported by two recent Japanese studies. The JELIS randomized trial showed a reduced CHD rate with eicosapentaenoic acid (EPA), and the JPHC study, a 10-year prospective cohort study of 41 578 middle-aged Japanese subjects, showed significant inverse associations between dietary intake of marine-derived omega-3 fatty acids and nonfatal coronary events.

They point out that in the current study, Japanese American men had similar or greater levels of atherosclerosis compared with US white men, a finding that they say was unexpected and was still apparent after they excluded those with diabetes, those with hypertension, and those taking lipid-lowering medications, indicating that the low atherosclerosis in Japanese men is unlikely to be primarily a result of genetic factors.

"Our findings indicate that the antiatherogenic effect of marine-derived omega-3 fatty acids is likely to be present only in populations with fish intake well above those of most Western populations. It thus appears unlikely that short-term supplementation in a low-fish-intake population would show such a relationship," Sekikawa et al comment.

They conclude: "If the high intake of marine-derived omega-3 fatty acids in Japanese men is the primary reason for their extremely low CHD mortality in the face of high traditional cardiovascular risk factors, dietary interventions to increase marine-derived omega-3 fatty acids in the US and other countries where fish intake is not as high as in Japan could have a very substantial impact on CHD."

In an accompanying editorial [2], Dr William Harris (Sanford Research/USD, Metabolism and Nutrition Research Center, Sioux Falls, South Dakota) notes that with the adoption of a more Western lifestyle, Japanese men have been found to have similar lifetime cholesterol and blood-pressure levels as white men in the US, along with a greater rate of smoking and prevalence of diabetes, but CHD rates in Japan remain less than one-half of those in the US. "This unexpected finding has stimulated the search for a factor or factors in the Japanese diet or lifestyle that have the power to withstand the onslaught of advancing risk factors," Harris comments, adding that the results of the current study add weight to the idea that omega-3 fatty acids could be that factor.

Harris reports that the Japanese consume between eight and 15 times more EPA and docosahexaenoic acid (DHA) than typical Westerners, but omega-3 intakes in Japan are only one-quarter of those in Eskimos, the population that birthed the omega-3 hypothesis, with studies conducted 30 years ago showing unusually low cholesterol and triglyceride levels and MI rates in Greenland Inuit despite a diet very low in fruits, vegetables, and complex carbohydrates and high in fat.

But he points out that more recent evidence from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study indicates that carotid atherosclerosis is not only unrelated to omega-3 fatty-acid intakes in this cohort, but its prevalence is now greater than that in US white populations. At least part of the problem in Alaska appears to be not a lack of omega-3 but the introduction of massive amounts of saturated fats into their Westernizing diet, Harris suggests, noting that a similar situation is also being seen in Norway. "The Japanese experience, when contrasted to that of the Inuit and the Norwegians, suggests that the cardioprotective punch of the long-chain omega-3 fatty acids may be no match for diets high in fat, particularly saturated fat," he comments.

Harris notes that while relatively short-term studies of high-dose omega-3 fatty acids have shown no effect on atherosclerosis progression, observational studies have shown slower progression of coronary artery disease in individuals with higher levels of DHA. "These findings suggest the not-unreasonable hypothesis that decades of a moderately high omega-3 dietary intake may be the best way to slow atherosclerosis. The observations of Sekikawa et al harmonize with this view and strongly suggest that the 'Japanese factor' is likely to be omega-3 fatty acids," he concludes.