Is (±)-Equol Carcinogenic?

In early in vitro studies, the mechanism of action of equol was found to indicate that the compound may be associated with cancer risk. However, as research progresses, some people also believe that (±)-Equol has potential anti-cancer effects. These conflicting results have been shown to be concentration-dependent. Studies have found that high concentrations of equol can reduce the growth and proliferation of non-metastatic breast cancer cells and reduce breast cancer risk. However, we found that at lower physiological dietary concentrations, equol can promote cell proliferation, tumor growth and metastasis in a metastatic breast cancer cell model. In addition, equol can increase the expression of eukaryotic initiation factor 4G (eIF4G), thereby increasing cap-independent protein synthesis of cancer-promoting molecules. This may be related to the differential expression of key equol targets involved in the regulation of breast cancer metastasis, but the relationship between equol and cancer is still unclear.

Equol was first discovered in the urine of a pregnant horse in 1932. In 1980, equol was unexpectedly found in large amounts in rat urine and in mammalian lignans, enterolactones and enterodiols. It is also found in sheep, hens and dogs. Equol is a nonpolar molecule with a chiral center, so it exists in two enantiomeric forms: R-equol and S-equol. The substance is insoluble in solution and is highly susceptible to acid.

S-equol is a natural diastereomer produced by intestinal metabolism. Studies have found that adults who consume a lot of soy foods have higher concentrations of equol in their urine. Equol has a lower plasma clearance rate (6.85 l/h) compared to soy flavonoids (17.5 l/h). In addition to its potential role in fighting cancer, equol has also attracted attention for its health benefits. Studies have shown that equol can significantly reduce hot flashes in menopausal women, prevent bone density loss in middle-aged women, may help reduce the incidence of prostate cancer, and prevent the occurrence of breast cancer.

In rodent studies using racemic equol or daidzein, conducted in animals that produce equol, results showed that equol exposure did not stimulate breast tumor growth, but there was little evidence of a protective effect. Racemic equol has been shown to inhibit skin carcinogenesis in hairless mice. Epidemiological studies on the association between urinary or plasma isoflavone concentrations and breast cancer risk in women reported that higher equol levels were not associated with or increased breast cancer risk in populations with low soy intake, but in Asian populations, breast cancer risk tended to decrease with increasing equol intake. To date, there are few animal studies using daidzein or racemic equol, especially studies on S-(-)-equol. The number of epidemiological studies on human equol exposure and cancer risk is also limited, and the results are difficult to interpret. Therefore, whether (±)-Equol is carcinogenic requires further verification.

References:

[1] LAMPE J W. Emerging Research on Equol and Cancer, 2,[J]. Journal of Nutrition, 2010, 140 7: Pages 1369S-1372S. DOI:10.3945/jn.109.118323.

[2] AILED M CRUZ-COLLAZO. Protein Synthesis Regulation by Soy Isoflavones Metabolite Equol in Metastatic Breast Cancer Cells[J]. FASEB Journal, 2017. DOI:10.1096/fasebj.31.1\_supplement.600.4.