The rise in estrogen-dependent cancers in the U.S., and our limited success with their prevention and treatment, has spurred growing interest in the dietary habits of the Japanese who have one of the lowest rates of breast, endometrial and ovarian cancers in the world. Studies show that Japanese women have longer menstrual cycles and lower serum estradiol levels than their Western counterparts, factors that may contribute to their low risk of estrogen-dependent cancers. These dietary differences have been mainly attributed to higher soy intakes among Asians. Another less explored component but main staple of the Japanese diet is seaweed, which accounts for approximately 10-25% of their food intake. Studies from our laboratory suggest that the anti-estrogenic effects of dietary kelp seaweed may also contribute to these reduced cancer rates. As a follow-up to previous findings of endocrine modulation related to kelp ingestion in a pilot study of pre-menopausal women (Skibola CF, BMC Complement Altern Med., 2004), the endocrine modulating effects of kelp (Fucus vesiculosus) in female rats and human luteinized granulosa cells (hLGC) was investigated. Kelp administration significantly lengthened the rat estrous cycle from 4.3 ± 0.96 to 5.4±1.7 days at 175 mg kg-1 body weight day-1 and to 5.9 ± 1.9 days at 350mg kg-1 day-1 (P = 0.002), and also led to a 100% increase in the length of diestrus (P=0.02). Following 175 mg kg-1 day-1 treatment for 2 weeks, serum 17β-estradiol levels were reduced from 48.9 ± 4.5 pg/mL to 40.2 ± 3.2 pg/mL (P =0.13). After 4 weeks, 17β-estradiol levels were reduced to 36.7 ± 2.2 pg/mL (P =0.02). In hLGC, 25, 50 and 75 μmol/L treatment reduced 17β-estradiol levels from 4732 ± 591 to 3632 ± 758, 3313 ± 373, and 3060 ± 538 pg/mL, respectively. Kelp treatment also led to modest elevations in hLGC culture progesterone levels. The kelp extract inhibited the binding of estradiol to estrogen receptor α and β, and progesterone to the progesterone receptor, with IC50 values of 42.4, 31.8, and 40.7 μmol/L, respectively. These data show endocrine modulating effects of kelp at relevant doses and suggest that dietary kelp may contribute to the lower incidence of hormone-dependent cancers among the Japanese. Further, the anti-estrogenic effects of kelp may provide a simple means of dietary modification to reduce risk of estrogen-dependent cancers in the general population. Attempts to identify the anti-estrogenic components in Fucus vesiculosus may lead to the discovery of novel selective estrogen receptor modulators that may be useful in the treatment and/or prevention of estrogen-dependent cancers.
[Proc Amer Assoc Cancer Res, Volume 46, 2005]