Epidemiological studies show that incidence rates of estrogen-dependent diseases such as cancers of the breast, endometrium and ovary are among the highest in Western, industrialized countries, while rates are much lower in China and Japan [1
]. These disparities may be attributable, in part, to differences in dietary and environmental exposures associated with affluent and modern lifestyles that promote estrogenic stimulation and hormone imbalances [3
]. Although the mechanisms are not fully understood, epidemiological and experimental data suggest that exposure to estrogens, through endogenous production and exogenous exposures resulting in an imbalance in the estrogen/progesterone ratio, may be the most critical determinants in disease risk [6
]. In estrogen-sensitive tissues, estrogen triggers cell proliferation, and through prolonged stimulation, hyperplasia [9
] and possibly neoplasia can occur. Reproductive factors associated with increased exposure to menstruation resulting in persistent and sustained estrogenic stimulation, such as shorter menstrual cycles, reduced parity, early menarche, and late menopause, are known to increase risk of endometriosis and estrogen-dependent cancers [10
], while post-menopausal obesity, hormone replacement therapy and alcohol consumption may be associated with increased breast cancer risk [12
]. Therefore, limiting exposure to estrogens and reducing the overall number of menstrual cycles in one's lifetime through dietary and lifestyle changes may be the simplest means to reduce disease risk. In particular, the identification of dietary compounds that have estrogen- reducing effects holds great promise in developing chemopreventive strategies to abrogate risk of these diseases.
Studies show that Japanese women have longer menstrual cycle lengths (greater than the 28 day average) and lower circulating estrogen levels compared to Western populations [15
], which until now has been at least partly attributed to the increased intake of soy protein among Asian populations [18
]. Another less explored component but main staple of the Japanese diet is seaweed, which accounts for approximately 10–25% of their food intake [21
]. Other reported estimated daily intakes are as high as 3–13 g/day [23
]. A major source of dietary seaweed among Japanese populations is the edible brown kelp, wakame (Undaria pinnatifida
) and kombu (Laminaria japonica
). These species and the Atlantic brown kelp, bladderwrack (Fucus vesiculosus)
, have been shown to exert powerful anti-hypertensive activity related to angiotensin-I-converting enzyme inhibition [24
], to possess antibacterial and antioxidant properties related to their high polyphenolic content [25
], and to prevent dioxin absorption and accelerate dioxin excretion in rats [26
]. Other chemopreventive properties such as antiviral activity [27
], immunostimulatory effects [29
], anti-proliferative effects on 7,12-dimethylbenz(a)-anthracene-induced rat mammary tumors [30
], and anti-tumor and anti-metastatic activities in xenograft mouse models [32
], have been associated with the high level of sulfated polysaccharides, also known as fucoidans, found in brown seaweed.
Intake of bladderwrack, as well as other brown kelp species, also has been shown to alter cholesterol metabolism and to significantly lower plasma cholesterol levels [33
]. A possible mechanism of action involves competitive inhibition by fucosterols found in kelp. Since cholesterol is the precursor involved in steroid hormone biosynthesis, a reduction in cholesterol bioavailability could lower circulating plasma 17β-estradiol levels that may lead to alterations in menstrual cycling patterns in pre-menopausal women. Until now, no studies have been performed in humans to determine the effects of brown kelp on menstrual cycling patterns and sex hormone status in pre-menopausal women, particularly in women with or at risk for estrogen-dependent diseases. To explore the hypothesis that kelp consumption could reduce circulating17β-estradiol levels and attenuate menstrual cycle irregularities, bladderwrack was administered to three pre-menopausal women with abnormal menstrual cycling patterns and/or menstrual-related disease histories.