In vitro study: fish oil is anti-estrogenic

High doses of the fish fatty acid DHA may help protect the body from the impact of the female sex hormone estradiol. This is suggested by research done at the National Taiwan University, in which molecular scientists exposed human breast cancer cells to the fatty acid in test tubes. The experiment showed that DHA encourages cells to break down estradiol receptors.

The Taiwanese performed experiments because they were looking for an extra way to fight estradiol-sensitive cancers. Long-term treatment with the anti-estrogen tamoxifen makes some cells resistant. While the medicine does kick the estradiol-alpha receptors out of the cell’s nucleus, they manage to keep going outside. Because DHA – full name docosahexaenoic acid – inhibits cancer in many experiments, the researchers hoped that the fish fatty acid might possibly also play role. It might sound a little strange, but you never know your luck.

And lo and behold.

The figure below shows how the fish fatty acid reduced the number of estradiol-alpha receptors outside the cell nucleus.


The longer the exposure, the more estradiol-alpha receptors were destroyed in the cell nucleus.

Adding the omega-6 fatty acid arachidonic acid to DHA enhanced the reduction of the number of estradiol receptors.

When the researchers repeated their experiment with the proteasome inhibitor (MG132) they detected no effect. See below.


The proteasome is a molecular shredder that cuts up wrong bits of proteins into small pieces. If you give the cells enough DHA, it appears they also clear up estradiol-alpha receptors.

Bodybuilders who experiment with high doses of fish fatty acids report that they become drier. This could have something to do with the effect the Taiwanese came across.

Fish fatty acids are interesting to bodybuilders for other reasons too. A diet that is rich in fish fatty acids raises the concentration of IGF-1 in the body, enhances fat burning and inhibits the growth of fat reserves. These effects have been shown in animal studies, test tube studies, experiments and human trials. Animal studies also suggest that fish-oil in the diet helps muscles to recover more quickly after training.

Docosahexaenoic acid induces proteasome-dependent degradation of estrogen receptor alpha and inhibits the downstream signaling target in MCF-7 breast cancer cells.


About two thirds of breast cancers in women are hormone-dependent and require estrogen for growth, its effects being mainly mediated through estrogen receptor alpha (ERalpha). Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) have opposite effects on carcinogenesis, with DHA suppressing and AA promoting tumor growth both in vitro and in vivo. However, the mechanism is not clear. Here, we examined whether the effect is mediated through changes in ERalpha distribution. MCF-7 cells, an ERalpha-positive human breast cancer cell line, was cultured in estrogen-free medium containing 0, 10 or 60 microM DHA or AA, then were stimulated with estradiol. DHA supplementation resulted in down-regulation of ERalpha expression (particularly in the extranuclear fraction), a reduction in phosphorylated MAPK, a decrease in cyclin D1 levels and an inhibition in cell viability. In contrast, AA had no such effects. The DHA-induced decrease in ERalpha expression resulted from proteasome-dependent degradation and not from decreased ERalpha mRNA expression. We propose that breast cancer cell proliferation is inhibited by DHA through proteasome-dependent degradation of ERalpha, reduced cyclin D1 expression and inhibition of MAPK signaling.

PMID: 19369047 [PubMed – indexed for MEDLINE]