Omega-3 and cancer: Lower EPA to arachidonic acid ratio linked to higher risk of death

By Gary Scattergood

- Last updated on GMT

The findings support the hypothesis that the balance between EPA and AA is important in relation to cancer risk. ©iStock
The findings support the hypothesis that the balance between EPA and AA is important in relation to cancer risk. ©iStock

Related tags Cancer

A Japanese population study suggests that lower levels of serum eicosapentaenoic acid to arachidonic acid (EPA:AA) is associated with an increased risk of cancer death.

Furthermore, this association remained robust even after adjustment for other confounding risk factors.

In particular, the risk of death from liver cancer significantly increased with lower levels of the serum EPA:AA ratio.

In contrast, the researchers found no clear evidence of an association between the serum docosahexaenoic acid to arachidonic acid (DHA:AA) ratio and cancer death.

Writing in the Journal of Epidemiology​, the investigators wrote: "To the best of our knowledge, this is the first report to show that decreased serum EPA:AA levels are an independent risk factor for cancer death.

"These findings suggest that the regular intake of EPA-rich foods may be effective for reducing the risk of cancer in the general Japanese population."

They pointed out that there had previously been conflicting results in studies looking at the association between omega-3 PUFAs intake and cancer risk.

Limited evidence

In several longitudinal observational studies, inverse associations were found between dietary intake of fish or omega-3 PUFAs and risk of some site-specific cancers, such as colon, breast, lung, and liver cancers, while some systematic reviews have provided limited evidence of a possible role of dietary omega-3 PUFAs in preventing colon cancer, but failed to reveal any conclusive evidence.

This latetst paper involved the The Hisayama Study, an ongoing, population-based epidemiological study in the town of Hisayama, which is located in a suburb of the Fukuoka metropolitan area on Kyushu Island, Japan.

The population of Hisayama is around 8,400 and has been stable for 50 years, and the age and occupational distributions of the town population are almost identical to those of Japan as a whole.

In 2002 and 2003, a screening examination involving 3,328 residents was performed in the town.

The subjects were followed up on prospectively for an average of 9.6 years, from the date of the screening examination to November 2012.

During the follow-up period, 121 subjects (73 men and 48 women) died of cancer.

"All cancer deaths were adjudicated on the basis of physical examination; a review of all clinical data, including medical records; and autopsy findings by a panel of the study members, who remained blind to the information on each subject's serum fatty acids levels," ​wrote the researchers.

Potential mechanisms

They found that age- and sex-adjusted cancer mortality increased with lower serum EPA:AA ratio levels (P​ trend<0.05).

In the multivariable-adjusted analysis, the subjects in the first quartile of the serum EPA:AA ratio had a 1.93-fold (95% confidence interval, 1.15–3.22) greater risk of cancer death than those in the fourth quartile. 

They wrote that several mechanisms may account for the potential preventive effects of elevated serum EPA:AA ratio levels against carcinogenesis and cancer proliferation.

The paper noted that EPA plays an important role in suppression of the inflammatory responses by competing with AA.

"In addition, AA-derived eicosanoids themselves promote cancer cell growth and progression via several biological processes…whereas EPA exerts other anti-carcinogenic effects through a reduction in the production of free radicals and reactive oxygen species, an increment of insulin sensitivity, and an alteration of oestrogen metabolism," ​they wrote.

"These findings support the hypothesis that the balance between EPA and AA is important for regulating the production of mediators and subsequent carcinogenesis and cancer proliferation.

"Moreover, EPA may be of importance for cancer development, because EPA, but not AA, tended to be associated with cancer risk."

The paper concluded that the analysis showed that lower levels of serum EPA:AA ratio, but not serum DHA:AA ratio, were significantly associated with a greater risk of cancer death.

"Notably, the serum EPA:AA ratio may relate to the risk of death from liver cancer,"​ they added.

"These findings imply that the regular intake of EPA-rich foods may be effective for reducing the risk of cancer. Further large-scale prospective cohort studies will be needed."

Source: Journal of Epidemiology

J Epidemiol​. 2017 Dec; 27(12): 578–583.

"The ratio of serum eicosapentaenoic acid to arachidonic acid and risk of cancer death in a Japanese community: The Hisayama Study"

Authors: ​Masaharu Nagata,  et al.

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