Can rye intake decrease risk of human breast cancer?

Background: Rye contains more fibre and bioactive compounds than other cereals used for bread production. The fibre and compounds of the fibre complex could provide protection against breast cancer (BC). Objective: To review the evidence and theoretical background for a role of rye and some of its components in the prevention of BC. Design: A short review based to a great extent on the work by scientists in the Nordic countries. Results: Some of the possible mechanisms by which the fibre complex could reduce BC risk are presented. The fibre through its effect on fermentation increases esterification of bile acids reducing toxicity of the free bile acids and is involved in the production of butyrate with potential anticancer effects including BC. The fibre reduces the enterohepatic circulation of the oestrogens leading to lower plasma oestrogen concentrations. The fibre complex contains bioactive compounds such as lignans and alkylresorcinols that are antioxidative and potentially anticarcinogenic. In addition, vitamins, minerals, and phytic acid in rye may provide protection against BC. Conclusion: Rye products made from wholegrain rye flour are likely to contribute to reduced BC risk

The phenolic complex in flaxseed

Flaxseed is the richest plant source of the lignan secoisolariciresinol diglucoside (SDG). In flaxseed, SDG exists in an oligomeric structure with 3-hydroxy-3-methyl glutaric acid (HMGA) forming a phenolic complex together with p-coumaric acid and ferulic acid glucosides and herbacetin diglucoside (HDG). Epidemiological and animal studies indicate protective effects of flaxseed and SDG towards hormone-dependent cancers and cardiovascular diseases, and reducing effect toward cholesterol levels in blood. Knowledge about the structural features and properties of the phenolic complex are required to further understand bioavailability, bioconversion and bioactivity of flaxseed lignans in humans and animals, the biosynthesis in flaxseed, as well as if it may affect technology and quality of food products containing flaxseed or the phenolic complex. A new fast and simple high-performance liquid chromatographic (HPLC) method was developed for analysing secoisolariciresinol diglucoside (SDG), p-coumaric acid glucoside and ferulic acid glucoside, based on direct hydrolysis of defatted flaxseed flour using alkali. Variations in SDG, p-coumaric acid glucoside and ferulic acid glucoside content were reported in flaxseed samples and bread products containing flaxseed. The composition and properties of flaxseed phenolic complex were studied by reversed-phase liquid chromatography and gel filtration fractionation. Results indicate that the phenolic glucosides exist in oligomers with variable molecular sizes. A complicated linkage pattern and/or possibly interactions with other components may contribute to the observed complexity. SDG and the phenolic complex showed similar hydrogen-donating abilities to ferulic acid but higher than α-tocopherol in the DPPH inhibition metod, suggesting that SDG was the only active antioxidant in the phenolic complex. Contradicting results were obtained on the effect of SDG on levels of Vitamin E and cholesterol in two rat studies

Phytoestrogens

Collectively, plants contain several different families of natural products among which are compounds with weak estrogenic or antiestrogenic activity toward mammals. These compounds, termed phytoestrogens, include certain isoflavonoids, flavonoids, stilbenes, and lignans. The best-studied dietary phytoestrogens are the soy isoflavones and the flaxseed lignans. Their perceived health beneficial properties extend beyond hormone-dependent breast and prostate cancers and osteoporosis to include cognitive function, cardiovascular disease, immunity and inflammation, and reproduction and fertility. In the future, metabolic engineering of plants could generate novel and exquisitely controlled dietary sources with which to better assess the potential health beneficial effects of phytoestrogens

Alkylresorcinols in cereal grains

Alkylresorcinols are phenolic lipids present at levels of up to 0.15% of whole grain wheat and rye, but little is known about their presence in food, absorption in animals and humans, and their in vivo biological effects. Because alkylresorcinols are present in the human diet in significant amounts only in products containing whole grain wheat or rye, they have potential to be biomarkers of whole grain wheat and rye intake. This thesis describes some of the research undertaken to investigate whether alkylresorcinols could be biomarkers of whole grain wheat and rye intake. A rapid gas chromatographic method was developed to analyse alkylresorcinols in whole cereal grains. This method was then applied to detect the presence and amount of alkylresorcinols in several cereal grains. Wheat, rye and triticale all contain moderate to high amounts of alkylresorcinols (300-1500 µg/g), while barley contains low amounts (~50 µg/g). In these cereals, alkylresorcinols are present in the bran fraction. All other cereals analysed (rice, oats, maize, sorghum and millet) did not contain any detectable amounts of alkylresorcinols. Previous studies have suggested that alkylresorcinols are destroyed by the baking process. However, an extraction method using hot propanol:water was able to recover all alkylresorcinols from experimental breads, indicating that alkylresorcinols are not destroyed during baking. The absorption of alkylresorcinols in rats, pigs and humans was determined, with values for absorption ranging from 34–79%, depending on the model and the amount of alkylresorcinols consumed. Alkylresorcinols in the plasma of pigs fed a single meal of rye, peaked at 3-4 hours, and remained elevated compared to the baseline levels after 16 hours. Preliminary studies to find alkylresorcinol metabolites in humans suggest that they have their alkyl chains shortened by β-oxidation. The effect of purified rye alkylresorcinols on lipid parameters (tocopherols, cholesterol and fatty acids) was tested on a rat model. Alkylresorcinols did not appear to affect rat performance, but in high amounts they could decrease liver cholesterol, and moderately elevate γ-tocopherol levels. Overall, the results suggest that alkylresorcinols do not have a large effect on lipid absorption/metabolism in rats

Higher usual dietary intake of phytoestrogens is associated with lower aortic stiffness in postmenopausal women

Objective¿ Phytoestrogens have been postulated to protect against cardiovascular diseases, but few studies have focused on the effect of Western dietary phytoestrogen intake. Methods and Results¿ Four hundred three women with natural menopause either between 1987 and 1989 or between 1969 and 1979 were selected from the baseline data of the PROSPECT study (n=17 395). Isoflavone and lignan intake was calculated from a food-frequency questionnaire. Aortic stiffness was noninvasively assessed by pulse-wave velocity measurement of the aorta. Linear regression analysis was used. After adjustment for age, body mass index, smoking, physical activity, mean arterial pressure, follow-up time, energy intake, dietary fiber intake, glucose, and high density lipoprotein cholesterol, increasing dietary isoflavone intake was associated with decreased aortic stiffness: -0.51 m/s (95% CI -1.00 to -0.03, fourth versus first quartile, P for trend=0.07). Increasing dietary intake of lignans was also associated with decreased aortic pulse-wave velocity: -0.42 m/s (95% CI -0.93 to 0.11, fourth versus first quartile, P for trend=0.06). Results were most pronounced in older women: for isoflavones, -0.94 m/s (95% CI -1.65 to -0.22, P for trend=0.02), and for lignans, -0.80 m/s (95% CI -1.85 to -0.05), fourth versus first quartile. Conclusions¿ The results of our study support the view that phytoestrogens have a protective effect on the risk of atherosclerosis and arterial degeneration through an effect on arterial walls, especially among older wome

The Association Between Urinary Genistein Levels and Mortality Among Adults in the United States

BackgroundCurrent research on the relationship between phytoestrogens and mortality has been inconclusive. We explored the relationship between genistein, a phytoestrogen, and mortality in a large cohort representative of the United States population.Methods: Data were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999–2010. Normalized urinary genistein (nUG) was analyzed as a log-transformed continuous variable and in quartiles. Mortality data were obtained from the National Death Index and matched to the NHANES participants. Survival analyses were conducted using the Kaplan-Meier analysis. Cox proportional hazard models were constructed for all-cause and cause-specific mortality without and with adjustment for potential confounding variables.Results: Of 11,497 participants, 944 died during the 64,443 person-years follow-up. The all-cause mortality rate was significantly lower in the lowest quartile compared to the highest quartile (incidence rate ratio = 2.14, 95%CI = 1.76 to 2.60). Compared to the lowest quartile, the highest quartile had significantly higher adjusted all-cause (HR = 1.57, 95%CI = 1.23 to 2.00), cardiovascular (HR = 1.67, 95%CI = 1.04 to 2.68), and other-cause (HR = 1.85, 95%CI = 1.33 to 2.57) mortality.Conclusion: We found that high urinary genistein levels were associated with increased risk of all-cause, cardiovascular, and other-cause mortality. This is contrary to popular opinion on the health benefits of genistein and needs further research

Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer.

Genistein is an isoflavone found in soy, and its chemo-preventive and -therapeutic effects have been well established from in vitro studies. Recently, however, its therapeutic actions in vivo have been questioned due to contradictory reports from animal studies, which rely on rodent models or implantation of cell lines into animals. To clarify in vivo effects of genistein in advanced prostate cancer patients, we developed a patient-derived prostate cancer xenograft model, in which a clinical prostatectomy sample was grafted into immune deficient mice. Our results showed an increased lymph node (LN) and secondary organ metastases in genistein-treated mice compared to untreated controls. Interestingly, invasive malignant cells aggregated to form islands/micrometastasis only in the secondary organs of the genistein-treated groups, not in the untreated control group. To understand the underlying mechanism for metastatic progression, we examined cell proliferation and apoptosis on paraffin-sections. Immunohistological data show that tumors of genistein-treated groups have more proliferating and fewer apoptotic cancer cells than those of the untreated group. Our immunoblotting data suggest that increased proliferation and metastasis are linked to enhanced activities of tyrosine kinases, EGFR and its downstream Src, in genistein-treated groups. Despite the chemopreventive effects proposed by earlier in vitro studies, the cancer promoting effect of genistein observed here suggests the need for careful selection of patients and safer planning of clinical trials