Wien Klin Wochenschr. 2006 Oct;118(19-20):580-93

Strohle A, Waldmann A, Wolters M, Hahn A.

Today vegetarian nutrition is more accepted and widespread in Europe than in former years. For a long time scientific research on vegetarian diets has focused mostly on malnutrition, whereas nowadays research centers increasingly on the preventive potential of plant-based diets. We followed a nutritive and a metabolic-epidemiological approach to obtain dietary recommendations. A MEDLINE research was performed for all plant food groups relevant for a vegetarian diet (key words: all relevant food groups, "vegetarian diet", "chronic disease", "cancer", "cardiovascular disease", "diabetes mellitus", "osteoporosis"). All relevant food groups were characterized regarding their nutrient content and rated with respect to the available metabolic-epidemiological evidence. Based on the evidence criteria of the WHO/FAO, cancer risk reduction by a high intake of vegetables and fruits is assessed as probable or possible, while a lowered risk of cardiovascular disease is convincing and a lowered risk of osteoporosis is probable. The evidence of a risk reducing effect of whole grain relating to colorectal cancer is assessed as possible, whereas it is probable relating to cardiovascular disease and diabetes mellitus type 2. There is an insufficient risk-reducing effect of legumes like soja relating to epithelial tumours and cardiovascular disease. The evidence of a risk-reducing effect of nuts to cardiovascular disease is assessed as probable, and in relation to cholelithiasis and diabetes mellitus type 2 as possible and insufficient, respectively. In conclusion, high consumption of fruits, vegetables, whole grains and nuts can lower the risk for several chronic diseases.

Clin Transl Oncol. 2006 Nov;8(11):812-20

Menendez JA, Vazquez-Martin A, Ropero S, Colomer R, Lupu R.

Background. Data derived from epidemiological and experimental studies suggest that alphalinolenic acid (ALA; 18:3n-3), the main omega-3 polyunsaturated fatty acid (PUFA) present in the Western diet, may have protective effects in breast cancer risk and metastatic progression. A recent pilot clinical trial assessing the effects of ALA-rich dietary flaxseed on tumor biological markers in postmenopausal patients with primary breast cancer demonstrated significant reductions in tumor growth and in HER2 (erbB-2) oncogene expression. Hypothesis. The molecular mechanism by which ALA inhibits breast cancer cell growth and metastasis formation may involve a direct regulation of HER2, a well-characterized oncogene playing a key role in the etiology, progression and response to some chemo- and endocrine therapies in approximately 20% of breast carcinomas. Methods. Using HER2-specific ELISA, flow cytometry, immunofluorescence microscopy, Western blotting, RT-PCR and HER2 promoter-reporter analyses, we characterized the effects of exogenous supplementation with ALA on the expression of HER2 oncogene, a master key player in the onset and metastasis formation of breast cancer disease. Metabolic status (MTT) assays were performed to evaluate the nature of the cytotoxic interaction between ALA and the humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin(R)). To study these issues we used BT-474 and SKBr-3 breast cancer cells, which naturally exhibit amplification of the HER2 oncogene. Results. ALA treatment dramatically suppressed the expression of HER2-coded p185(Her-2/neu) oncoprotein as determined by ELISA, flow cytometry, immunofluorescence microscopy and immunoblotting techniques. Interestingly, ALA-induced down-regulation of p185(Her-2/neu) correlated with a transcriptional response as no HER2 mRNA signal could be detected by RT-PCR upon treatment with optimal concentrations of ALA (up to 20 muM). Consistent with these findings, ALA exposure was found to dramatically repress the activity of a Luciferase reporter gene driven by the HER2 promoter. Moreover, the nature of the cytotoxic interaction between ALA and trastuzumab (Herceptin(R)) revealed a significant synergism as assessed by MTT-based cell viability assays. Conclusions. i) These findings reveal that the omega-3 PUFA ALA suppresses overexpression of HER2 oncogene at the transcriptional level, which, in turn, interacts synergistically with anti-HER2 trastuzumab- based immunotherapy. ii) Our results molecularly support a recent randomized double-blind placebo-controlled clinical trial suggesting that ALA may be a potential dietary alternative or adjunct to currently used drugs in the management of HER2-positive breast carcinomas. iii) Considering our previous findings demonstrating the <<HER2 upregulatory actions>> of the omega-6 PUFA linolenic acid (LA; 18:2n-6) and the <<HER2 down-regulatory actions >> of the omega-3 PUFA docosahexaenoic acid (DHA; 22:6n-3) and of the omega-9 monounsaturated fatty acid oleic acid (OA; 18:1n-9), it is reasonable to suggest that a low omega-6/omega-3 PUFA ratio and elevated MUFA levels, the two prominent <<fat features>> of the <<Mediterranean diet>>, should be extremely efficient at blocking HER2 expression in breast cancer cells.

J Nutr. 2006 May;136(5):1270-5

Wu WH, Kang YP, Wang NH, Jou HJ, Wang TA.

Sesame ingestion has been shown to improve blood lipids in humans and antioxidative ability in animals. Sesamin, a sesame lignan, was recently reported to be converted by intestinal microflora to enterolactone, a compound with estrogenic activity and also an enterometabolite of flaxseed lignans, which are known to be phytoestrogens. Whether sesame can be a source of phytoestrogens is unknown. This study was designed to investigate the effect of sesame ingestion on blood sex hormones, lipids, tocopherol, and ex vivo LDL oxidation in postmenopausal women. Twenty-six healthy subjects attended, and 24 completed, this randomized, placebo-controlled, crossover study. Half of them consumed 50 g sesame seed powder daily for 5 wk, followed by a 3-wk washout period, then a 5-wk 50-g rice powder placebo period. The other half received the 2 supplements in reverse order. After sesame treatment, plasma total cholesterol (TC), LDL-C, the ratio of LDL-C to HDL-C, thiobarbituric acid reactive substances in oxidized LDL, and serum dehydroepiandrosterone sulfate decreased significantly by 5, 10, 6, 23, and 18%, respectively. The ratio of alpha- and gamma-tocopherol to TC increased significantly by 18 and 73%, respectively. All of these variables differed significantly between the 2 treatments. Serum sex hormone-binding globulin and urinary 2-hydroxyestrone (n = 8) increased significantly by 15 and 72%, respectively, after sesame treatment, and these concentrations tended to differ (P = 0.065 and P = 0.090, respectively) from those after the placebo treatment. These results suggest that sesame ingestion benefits postmenopausal women by improving blood lipids, antioxidant status, and possibly sex hormone status.

Osteoporos Int. 2006 May 9; [Epub ahead of print]

Rejnmark L, Vestergaard P, Charles P, Hermann AP, Brot C, Eiken P, Mosekilde L.

INTRODUCTION: Vitamin K functions as a co-factor in the post-translational carboxylation of several bone proteins, including osteocalcin. AIM: The aim of this study was to investigate the relationship between vitamin K(1) intake and bone mineral density (BMD) and fracture risk in a perimenopausal Danish population. DESIGN: The study was performed within the Danish Osteoporosis Prevention Study (DOPS), including a population-based cohort of 2,016 perimenopausal women. During the study approximately 50% of the women received hormone replacement therapy (HRT). Associations between vitamin K(1) intake and BMD were assessed at baseline and after 5-years of follow-up (cross-sectional design). Moreover, associations between vitamin K(1) intake and 5-year and 10-year changes in BMD were studied (follow-up design). Finally, fracture risk was assessed in relation to vitamin K(1) intake (nested case-control design). RESULTS: In our cohort, dietary vitamin K(1) intake (60 mug/day) was close to the daily intake recommended by the Food and Agriculture Organization (FAO). Cross-sectional and longitudinal analyses showed no associations between intake of vitamin K(1) and BMD of the femoral neck or lumbar spine. Neither did BMD differ between those 5% that had the highest vitamin K(1) intake and those 5% that had the lowest. During the 10-years of follow-up, 360 subjects sustained a fracture (cases). In a comparison between the cases and 1,440 controls, logistic regression analyses revealed no difference in vitamin K(1) intake between cases and controls. CONCLUSION: In a group of perimenopausal and early postmenopausal women, vitamin K(1) intake was not associated with effects on BMD or fracture risk.

Biometals. 2006 May 11; [Epub ahead of print]

Liu G, Men P, Kenner GH, Miller SC.

Iron accumulation in tissues is believed to be a characteristic of aged humans and a risk factor for some chronic diseases. However, it is not known whether age-associated iron accumulation is part of the pathogenesis of postmenopausal osteoporosis that affects approximately one out three women worldwide. Here, we confirmed that this accumulation of iron was associated with osteopenia in ovariectomized (OVX) rats (a model of peri- and postmenopausal osteoporosis due to estrogen deficiency). To further investigate whether the increased iron level plays a causal role in the onset of bone loss, we treated OVX rats with an orally active and bone targeted chelator that prevented iron accumulation in their skeletal tissues. The results showed that this treatment mitigated the loss of bone mass and the deterioration of bone micro-architecture. We also found that one possible mechanism of the protective action of iron chelation was to significantly reduce bone resorption. Thus, these findings provide a novel target and a potentially useful therapeutic strategy for the prevention and treatment of postmenopausal osteoporosis and perhaps other age-related diseases.