query: prolactin

positive: Effect of a low-fat high-carbohydrate diet on symptoms of cyclical mastopathy. 21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.

positive: Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. OBJECTIVE: To test the hypothesis that a low-fat, vegetarian diet reduces dysmenorrhea and premenstrual symptoms by its effect on serum sex-hormone binding globulin concentration and estrogen activity. METHODS: In a crossover design, 33 women followed a low-fat, vegetarian diet for two menstrual cycles. For two additional cycles, they followed their customary diet while taking a supplement placebo pill. Dietary intake, serum sex-hormone binding globulin concentration, body weight, pain duration and intensity, and premenstrual symptoms were assessed during each study phase. RESULTS: Mean (+/- standard deviation [SD]) serum sex-hormone binding globulin concentration was higher during the diet phase (46.7 +/- 23.6 nmol/L) than during the supplement phase (39.3 +/- 19.8 nmol/L, P < .001). Mean (+/- SD) body weight was lower during the diet (66.1 +/- 11.3 kg) compared with the supplement phase (67.9 +/- 12.1 kg, P < .001). Mean dysmenorrhea duration fell significantly from baseline (3.9 +/- 1.7 days) to diet phase (2.7 +/- 1.9 days) compared with change from baseline to supplement phase (3.6 +/- 1.7 days, P < .01). Pain intensity fell significantly during the diet phase, compared with baseline, for the worst, second-worst, and third-worst days, and mean durations of premenstrual concentration, behavioral change, and water retention symptoms were reduced significantly, compared with the supplement phase. CONCLUSION: A low-fat vegetarian diet was associated with increased serum sex-hormone binding globulin concentration and reductions in body weight, dysmenorrhea duration and intensity, and premenstrual symptom duration. The symptom effects might be mediated by dietary influences on estrogen activity.

positive: Is there a role for surgery in the treatment of mastalgia? Breast pain is a common condition affecting most women at some stage in their reproductive life. Mastalgia is resistant to treatment in 6% of cyclical and 26% non-cyclical patients. Surgery is not widely used to treat this condition and only considered in patients with severe mastalgia resistant to medication. The aims of this study were to audit the efficacy of surgery in severe treatment resistant mastalgia and to assess patient satisfaction following surgery. This is a retrospective review of the medical records of all patients seen in mastalgia clinic in the University Hospital of Wales, Cardiff since 1973. A postal questionnaire was distributed to all patients who had undergone surgery. Results showed that of the 1054 patients seen in mastalgia clinic, 12 (1.2%) had undergone surgery. Surgery included 8 subcutaneous mastectomies with implants (3 bilateral, 5 unilateral), 1 bilateral simple mastectomy and 3 quadrantectomies (1 having a further simple mastectomy). The median duration of symptoms was 6.5 years (range 2-16 years). Five patients (50%) were pain free following surgery, 3 developed capsular contractures and 2 wound infections with dehiscence. Pain persisted in both patients undergoing quadrantectomy. We conclude that surgery for mastalgia should only be considered in a minority of patients. Patients should be informed of possible complications inherent of reconstructive surgery and warned that in 50% cases their pain will not be improved.

positive: Recommendations for the prevention of chronic disease: the application for breast disease. Experimental and epidemiological evidence suggest that a diet with dietary fat as low as 20% of kcal may be necessary to reduce the risk of breast cancer. Two groups of women, postmenopausal women treated for breast cancer and premenopausal women with cystic breast disease accompanied by cyclical mastaligia, participated in an intervention program to determine the feasibility of such a low-fat diet. After 3 mo of intervention both groups were consuming a low-fat diet; in the premenopausal groups serum estrogen levels decreased in response to the fat reduction. Other nutrition-education programs in research institutions, restaurants, and schools are attempting to influence the public's knowledge and behavior regarding the importance of dietary fat reduction.

positive: Serum prolactin and oestradiol levels in women with cyclical mastalgia. Basal serum prolactin and serum oestradiol-17-beta concentrations were measured four times during one menstrual cycle in 20 women with severe cyclical mastalgia and normal to slightly fibroadenotic breasts. A group of 10 normal women who had never experienced mastalgia served as controls. Basal serum prolactin was significantly elevated in patients compared to normals, although within the normal range. Serum oestradiol concentrations did not differ in the two groups and were also within the normal range. A significant positive correlation between oestradiol and prolactin was found in patients and normals, but with larger prolactin levels in patients. The results point towards a prolactin secretory hypersensitivity for oestradiol in patients with cyclical mastalgia. Prolactin is considered a central factor in the eliciting of cyclical mastalgia.

positive: Global study of women's experiences of premenstrual symptoms and their effects on daily life. OBJECTIVES: To determine cross-cultural and other effects on women's experiences of premenstrual symptoms and their impact on activities of daily life (ADL). STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49 recruited by random sampling with approximately 400 each from France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating, cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains. Severity of symptoms was directly proportional to duration (number of affected cycles) (R = 0.78). A linear model found that symptom prevalence (duration × severity) was associated with age (linear and quadratic effects), parity, current smoking and country. Premenstrual physical and mental symptom domains had similar negative effects on ADL. Impact on ADL was affected by education and exercise participation. Women's knowledge of the terms premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age, education and country. CONCLUSIONS: Four of the five most prevalent premenstrual symptoms were physical. There was a great deal of similarities of women's experiences of these symptoms across countries and regions. Women's knowledge of PMS terms is highly dependent on the country in which they live.

positive: Mastalgia: a review of management. Mastalgia affects up to two-thirds of women at some time during their reproductive lives. It is usually benign, but thefear of underlying breast cancer is why many women present for evaluation. Mastalgia can be associated with premenstrual syndrome, fibrocystic breast disease, psychologic disturbance and, rarely, breast cancer. Occasionally, extramammary conditions, like Tietzie syndrome, present as mastalgia. A thorough clinical evaluation is required to assess the cause. The majority of women can be reassured after a clinical evaluation. Approximately 15% require pain-relieving therapy. Mechanical breast support; a low-fat, high-carbohydrate diet; and topical nonsteroidal antiinflammatory agents are reasonable first-line treatments. Hormonal agents, such as bromocriptine, tamoxifen and danazol, have all demonstrated efficacy in the treatment of mastalgia. Side effects, however, limit their extensive use. Danazol is the only FDA-approved hormonal treatment and is best used in cyclic form to limit the adverse effects. Lisuride maleate is a new agent recently studied for the treatment of mastalgia. Initial data on this medication are encouraging. Sixty percent of cyclic mastalgia recurs after treatment. Noncyclic mastalgia responds poorly to treatment but resolves spontaneously in up to 50% of cases.

positive: Effect of flax seed ingestion on the menstrual cycle. Lignans are a group of phytochemicals shown to have weakly estrogenic and antiestrogenic properties. Two specific lignans, enterodiol and enterolactone, are absorbed after formation in the intestinal tract from plant precursors particularly abundant in fiber-rich food and are excreted in the urine. We evaluated the effect of the ingestion of flax seed powder, known to produce high concentrations of urinary lignans, on the menstrual cycle in 18 normally cycling women, using a balanced randomized cross-over design. Each subject consumed her usual omnivorous, low fiber (control) diet for 3 cycles and her usual diet supplemented with flax seed for another 3 cycles. The second and third flax cycles were compared to the second and third control cycles. Three anovulatory cycles occurred during the 36 control cycles, compared to none during the 36 flax seed cycles. Compared to the ovulatory control cycles, the ovulatory flax cycles were consistently associated with longer luteal phase (LP) lengths (mean +/- SEM, 12.6 +/- 0.4 vs. 11.4 +/- 0.4 days; P = 0.002). There were no significant differences between flax and control cycles for concentrations of either estradiol or estrone during the early follicular phase, midfollicular phase, or LP. Although flax seed ingestion had no significant effect on LP progesterone concentrations, the LP progesterone/estradiol ratios were significantly higher during the flax cycles. Midfollicular phase testosterone concentrations were slightly higher during flax cycles. Flax seed ingestion had no effect on early follicular phase concentrations of DHEA-S, PRL, or sex hormone-binding globulin. Our data suggest a significant specific role for lignans in the relationship between diet and sex steroid action, and possibly between diet and the risk of breast and other hormonally dependent cancers.

positive: A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease. A double blind crossover trial of the prolactin inhibitor bromocriptine in painful benign breast disease is reported. Twenty-nine women with cyclical mastalgia and 11 with non-cyclical pain were treated with bromocriptine, 5 mg daily, and placebo over six menstrual cycels. Assessment of response to treatment was made by a linear analogue system and clinical examination together with plasma prolactin estimations. Bromocriptine produced a significant improvement in breast symptoms and a significant fall in prolactin levels in the cyclical pain group, but had no effect in the non-cyclical group. These results suggest that bromocriptine offers a new and effective approach in the management of cyclical breast pain.

positive: Influence of dietary fat on self-reported menstrual symptoms. The Moos Menstrual Distress Questionnaire (MMDQ) was completed by thirty healthy premenopausal women randomized into one of two sets of weight-maintaining diets, those with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of 1.0 and those with a P/S ratio of 0.3. After a baseline interval of one menstrual cycle, both groups were fed a high fat diet (40% energy from fat) for four menstrual cycles per subject, followed by a similar interval on a low fat diet (20% energy from fat). There were no significant differences in self-reported menstrual symptoms between the two P/S groups. During both menses and the premenstrual week of the low fat dietary period there were significant decreases in self-reported symptoms associated with water retention. A decrease in symptoms in the group labelled "arousal" during the rest of the menstrual cycle was also reported.

positive: Low-fat dietary pattern and risk of benign proliferative breast disease: a randomized, controlled dietary modification trial Modifiable factors, including diet, might alter breast cancer risk. We used the WHI Dietary Modification (DM) trial to test the effect of the intervention on risk of benign proliferative breast disease, a condition associated with increased risk of and considered to be on the pathway to invasive breast cancer. The WHI DM trial was a randomized, controlled, primary prevention trial conducted in 40 US clinical centers from 1993–2005. 48,835 postmenopausal women, aged 50–79 years, without prior breast cancer, were enrolled. Participants were randomly assigned to the DM intervention group or to the comparison group. The intervention was designed to reduce total dietary fat intake to 20% of total energy intake, and to increase fruit and vegetable intake to ≥5 servings/day and intake of grain products to ≥6 servings/day, but resulted in smaller, albeit significant changes in practice. Participants had biennial mammograms and regular clinical breast exams. We identified women who reported breast biopsies free of cancer, obtained the histologic sections, and subjected them to standardized central review. During follow-up (average, 7.7 years), 570 incident cases of benign proliferative breast disease were ascertained in the intervention group and 793 in the comparison group. The hazard ratio for the association between DM and benign proliferative breast disease was 1.09 (95%CI, 0.98–1.23). Risk varied by levels of baseline total vitamin D intake but it varied little by levels of other baseline variables. These results suggest that a modest reduction in fat intake and increase in fruit, vegetable, and grain intake does not alter the risk of benign proliferative breast disease.

positive: Mastalgia. OBJECTIVE: To review the current management of women with breast pain. OPTIONS: The effect of various treatment modes and health practices, including medications, was considered for the management of both cyclical and noncyclical breast pain. OUTCOMES: Effective and timely management of the woman with breast pain and improved quality of life. EVIDENCE: A literature search was performed to identify reports published in English between 1975 and July 2003 using MEDLINE and Cochrane Database of Systematic Reviews. VALUES: Levels of evidence, as outlined, have been determined using the criteria outlined by the Canadian Task Force on the Periodic Health Examination. Participants were the principal authors: a clinical dietitian, a surgeon oncologist, and a nurse. BENEFITS, HARMS, AND COSTS: Utilizing the information will increase knowledge, enabling a consistent approach, which will reduce the number of ineffective interventions and ensure appropriate use medications. VALIDATION: Comparison has been made with management protocols in the literature, but no clinical guidelines have been located. No formal clinical testing has taken place. SPONSOR: The Society of Obstetricians and Gynaecologists of Canada (SOGC). Work on these guidelines was initiated by team members to fill a need for practice guidelines at Winnipeg Regional Health Authority Breast Health Centre, Winnipeg, MB. RECOMMENDATIONS: 1. Education and reassurance is an integral part of the management of mastalgia and should be the first-line treatment. (II-1 A) 2. The use of a well-fitting bra that provides good support should be considered for the relief of cyclical and noncyclical mastalgia. (II-3 B) 3. A change in dose, formulation, or scheduling should be considered for women on HRT. HRT may be discontinued if appropriate. (III C) 4. Women with breast pain should not be advised to reduce caffeine intake. (1 E) 5. Vitamin E should not be considered for the treatment of mastalgia. (1 E) 6. There is presently insufficient evidence to recommend the use of evening primrose oil (EPO) in the treatment of breast pain. (II-2 C) 7. Flaxseed should be considered as a first-line treatment for cyclical mastalgia. (I A) 8. Topical non-steroidal anti-inflammatory gel, such as diclofenac 2% in pluronic lethicin organogel, should be considered for pain control for localized treatment of mastalgia. (I A) 9. Tamoxifen 10 mg daily or danazol 200 mg daily should be considered when first-line treatments are ineffective. (I A) 10. Mastectomy or partial mastectomy should not be considered an effective treatment for mastalgia. (III E).

negative: Evidence for acne-promoting effects of milk and other insulinotropic dairy products. Acne vulgaris, the most common skin disease of western civilization, has evolved to an epidemic affecting more than 85% of adolescents. Acne can be regarded as an indicator disease of exaggerated insulinotropic western nutrition. Especially milk and whey protein-based products contribute to elevations of postprandial insulin and basal insulin-like growth factor-I (IGF-I) plasma levels. It is the evolutional principle of mammalian milk to promote growth and support anabolic conditions for the neonate during the nursing period. Whey proteins are most potent inducers of glucose-dependent insulinotropic polypeptide secreted by enteroendocrine K cells which in concert with hydrolyzed whey protein-derived essential amino acids stimulate insulin secretion of pancreatic β-cells. Increased insulin/IGF-I signaling activates the phosphoinositide-3 kinase/Akt pathway, thereby reducing the nuclear content of the transcription factor FoxO1, the key nutrigenomic regulator of acne target genes. Nuclear FoxO1 deficiency has been linked to all major factors of acne pathogenesis, i.e. androgen receptor transactivation, comedogenesis, increased sebaceous lipogenesis, and follicular inflammation. The elimination of the whey protein-based insulinotropic mechanisms of milk will be the most important future challenge for nutrition research. Both, restriction of milk consumption or generation of less insulinotropic milk will have an enormous impact on the prevention of epidemic western diseases like obesity, diabetes mellitus, cancer, neurodegenerative diseases and acne. Copyright © 2011 S. Karger AG, Basel.

negative: High-dose ascorbic acid increases intercourse frequency and improves mood: a randomized controlled clinical trial. BACKGROUND: Ascorbic acid (AA) modulates catecholaminergic activity, decreases stress reactivity, approach anxiety and prolactin release, improves vascular function, and increases oxytocin release. These processes are relevant to sexual behavior and mood. METHODS: In this randomized double-blind, placebo-controlled 14 day trial of sustained-release AA (42 healthy young adults; 3000 mg/day Cetebe) and placebo (39 healthy young adults), subjects with partners recorded penile-vaginal intercourse (FSI), noncoital partner sex, and masturbation in daily diaries, and also completed the Beck Depression Inventory before and after the trial. RESULTS: The AA group reported greater FSI (but, as hypothesized, not other sexual behavior) frequency, an effect most prominent in subjects not cohabiting with their sexual partner, and in women. The AA but not placebo group also experienced a decrease in Beck Depression scores. CONCLUSIONS: AA appears to increase FSI, and the differential benefit to noncohabitants suggests that a central activation or disinhibition, rather than peripheral mechanism may be responsible.

negative: Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.

negative: Body fat and animal protein intakes are associated with adrenal androgen secretion in children. BACKGROUND: Adrenarche is the increase in adrenal androgen (AA) production starting in childhood. Until now, it has been unknown whether or not nutritional factors modulate adrenarche. OBJECTIVE: The objective was to examine whether body composition and certain dietary intakes are associated with AA production in children after accounting for urinary indicators of major adrenarche-related steroidogenic enzymes. DESIGN: Androgen and glucocorticoid metabolites were profiled by gas chromatography-mass spectrometry in 24-h urine samples of 137 healthy prepubertal children aged 3-12 y, for whom birth characteristics, growth velocity data, and 3-d weighed-diet record information were available. Associations of the sum of C19 metabolites (reflecting daily AA secretion) with nutritional factors [fat mass (FM), fat-free mass (FFM), nutrient intakes, glycemic index, and glycemic load] and AA-relevant estimates of steroidogenic enzyme were examined in stepwise multiple regression models adjusted for age, sex, urine volume, and total energy intake. Enzyme activity estimates were calculated by using specific urinary steroid metabolite ratios. RESULTS: Of the nutrition-relevant predictors, FM (P < 0.0001) explained most of the variation of AA secretion (R(2) = 5%). Animal protein intake was also positively associated with AA secretion (P < 0.05), which explained 1% of its variation. FFM (P = 0.1) and total protein intake (P = 0.05) showed positive trends. The difference in daily AA secretion between the lowest and highest quartile of FM was comparable to that between the lowest and highest estimated activity of one of the major steroidogenic enzymes. CONCLUSIONS: Body fat mass may relevantly influence prepubertal adrenarchal androgen status. In addition, animal protein intake may also make a small contribution to AA secretion in children.

negative: A diet high in meat protein and potential renal acid load increases fractional calcium absorption and urinary calcium excretion without affecting m... Our objective in this study was to determine the effects of a high-protein and high-potential renal acid load (PRAL) diet on calcium (Ca) absorption and retention and markers of bone metabolism. In a randomized crossover design, 16 postmenopausal women consumed 2 diets: 1 with low protein and low PRAL (LPLP; total protein: 61 g/d; PRAL: -48 mEq/d) and 1 with high protein and high PRAL (HPHP; total protein: 118 g/d; PRAL: 33 mEq/d) for 7 wk each separated by a 1-wk break. Ca absorption was measured by whole body scintillation counting of radio-labeled (47)Ca. Compared with the LPLP diet, the HPHP diet increased participants' serum IGF-I concentrations (P < 0.0001), decreased serum intact PTH concentrations (P < 0.001), and increased fractional (47)Ca absorption (mean ± pooled SD: 22.3 vs. 26.5 ± 5.4%; P < 0.05) and urinary Ca excretion (156 vs. 203 ± 63 mg/d; P = 0.005). The net difference between the amount of Ca absorbed and excreted in urine did not differ between 2 diet periods (55 vs. 28 ± 51 mg/d). The dietary treatments did not affect other markers of bone metabolism. In summary, a diet high in protein and PRAL increases the fractional absorption of dietary Ca, which partially compensates for increased urinary Ca, in postmenopausal women. The increased IGF-I and decreased PTH concentrations in serum, with no change in biomarkers of bone resorption or formation, indicate a high-protein diet has no adverse effects on bone health.

negative: Is milk responsible for male reproductive disorders? The role of environmental compounds with estrogenic activity in the development of male reproductive disorders has been a source of great concern. Among the routes of human exposure to estrogens, we are particularly concerned about cows' milk, which contains considerable amounts of estrogens. The major sources of animal-derived estrogens in the human diet are milk and dairy products, which account for 60-70% of the estrogens consumed. Humans consume milk obtained from heifers in the latter half of pregnancy, when the estrogen levels in cows are markedly elevated. The milk that we now consume may be quite unlike that consumed 100 years ago. Modern genetically-improved dairy cows, such as the Holstein, are usually fed a combination of grass and concentrates (grain/protein mixes and various by-products), allowing them to lactate during the latter half of pregnancy, even at 220 days of gestation. We hypothesize that milk is responsible, at least in part, for some male reproductive disorders. Copyright 2001 Harcourt Publishers Ltd.

negative: Phytoestrogen consumption and association with breast, prostate and colorectal cancer in EPIC Norfolk. Phytoestrogens are polyphenolic secondary plant metabolites that have structural and functional similarities to 17beta-oestradiol and have been associated with a protective effect against hormone-related cancers. Most foods in the UK only contain small amounts of phytoestrogens (median content 21 microg/100 g) and the highest content is found in soya and soya-containing foods. The highest phytoestrogen content in commonly consumed foods is found in breads (average content 450 microg/100 g), the main source of isoflavones in the UK diet. The phytoestrogen consumption in cases and controls was considerably lower than in Asian countries. No significant associations between phytoestrogen intake and breast cancer risk in a nested case-control study in EPIC Norfolk were found. Conversely, colorectal cancer risk was inversely associated with enterolignan intake in women but not in men. Prostate cancer risk was positively associated with enterolignan intake, however this association became non-significant when adjusting for dairy intake, suggesting that enterolignans can act as a surrogate marker for dairy or calcium intake. 2010 Elsevier Inc. All rights reserved.

negative: Effect of mammalian lignans on the growth of prostate cancer cell lines. BACKGROUND: Mammalian lignans, enterolactone (EL) and enterodiol (ED), have been shown to inhibit breast and colon carcinoma. To date, there have been no reports of the effect of lignans on prostatic carcinoma. We investigated the effects of ED and EL on three human prostate cancer cell lines (PC-3, DU-145 and LNCaP). MATERIALS AND METHODS: Cells were treated with either 0.1% (v/v) DMSO (vehicle) or 10-100 microM of EL, ED or genistein (positive control) for 72 hours. Cell viability was measured by the propidium iodide nuclei staining fluorometric assay with each assay performed in triplicate. RESULTS: At 10-100 microM, EL significantly inhibited the growth of all cell lines, whereas ED only inhibited PC-3 and LNCaP cells. While EL was a more potent growth inhibitor than ED, both were less potent than genistein. The dose for 50% growth inhibition of LNCaP cells (IC50) by EL was 57 microM, whereas IC50 was 100 microM for ED, (the observed IC50 for genistein was 25 microM). CONCLUSION: ED and EL suppress the growth of prostate cancer cells, and may do so via hormonally-dependent and independent mechanisms.

negative: Dietary patterns, supplement use, and the risk of benign prostatic hyperplasia. It has long been appreciated that a healthy lifestyle plays a critical role in cardiovascular health. It is now apparent that the same is true in the development of benign prostatic hyperplasia (BPH). Prospective cohort data originating from recently published randomized trials on the medical treatment of BPH and prevention of prostate cancer have been invaluable. A growing body of evidence suggests that exercise and the intake of specific macronutrients and micronutrients through regular diet play a beneficial role. Most strikingly, the magnitude of these effects is similar to medical therapies using alpha-blockers and 5-alpha-reductase inhibitors. The use of supplements for prostate disease is a multibillion dollar business in the United States, and supplements are more commonly prescribed than medical therapy in many countries. In contrast to consumption of micronutrients through regular diet, supplemental intake of micronutrients and phytotherapies currently lack evidence to support their efficacy.

negative: Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics. I hypothesize here that the ability of probiotics to synthesize neuroactive compounds provides a unifying microbial endocrinology-based mechanism to explain the hitherto incompletely understood action of commensal microbiota that affect the host's gastrointestinal and psychological health. Once ingested, probiotics enter an interactive environment encompassing microbiological, immunological, and neurophysiological components. By utilizing a trans-disciplinary framework known as microbial endocrinology, mechanisms that would otherwise not be considered become apparent since any candidate would need to be shared among all three components. The range of neurochemicals produced by probiotics includes neurochemicals for which receptor-based targets on immune and neuronal elements (intestinal and extra-intestinal) have been well characterized. Production of neurochemicals by probiotics therefore allows for their consideration as delivery vehicles for neuroactive compounds. This unifying microbial endocrinology-based hypothesis, which may facilitate the selection and design of probiotics for clinical use, also highlights the largely unrecognized role of neuroscience in understanding how microbes may influence health. Copyright © 2011 WILEY Periodicals, Inc.

negative: Role of dietary lignans in the reduction of breast cancer risk. Lignans are a large group of fiber-associated phenolic compounds widely distributed in edible plants. Some of the ingested plant lignans are converted by intestinal microbiota to enterolignans, enterodiol (END) and enterolactone (ENL), the latter of which has been thought to be the major biologically active lignan, and suggested to be associated with low risk of breast cancer. In line with this, administration of plant lignans which are further metabolized to ENL, or ENL as such, have been shown to inhibit or delay the growth of experimental mammary cancer. The mechanism of anticarcinogenic action of ENL is not yet fully understood, but there is intriguing evidence for ENL as a modulator of estrogen signaling. These findings have generated interest in the use of lignans as components of breast cancer risk reducing functional foods. Identification of target groups, who would benefit most, is of pivotal importance. Therefore, further identification and validation of relevant biomarkers, which can be used as indicators of lignan or ENL action and breast cancer risk reduction at different stages of the disease, are of importance.

negative: The influence of μ-opioid receptor agonist and antagonist peptides on peripheral blood mononuclear cells (PBMCs). Milk is one of the main source of biologically-active peptides that may function as regulatory substances called food hormones. After passing the gut-blood barrier, the μ-opioid receptor agonist and antagonist peptides may become the new factors influencing various functions of the human organism. The aim of the conducted research was to determine the influence of μ-opioid receptor agonist peptides: human and bovine β-casomorphin-7 (h/bBCM-7) and antagonistic peptides: casoxin-6 and- D (CXN-6/D) on proliferation and cytokine secretion of human peripheral blood mononuclear cells (PBMCs). The PBMCs proliferation was measured by the use of the BrdU test, which assesses the DNA synthesis activity and the WST-1 test which assesses the activity of mitochondrial dehydrogenase enzymes. The influence of all the investigated peptides on secretion of IL-4, IL-8, IL-13 and IFN-γ was determined by the use of the ELISA tests. Incubating the cells with the peptides has not caused any changes to their enzymatic activity, which has been proved by a WST-1 test. When using a BrdU test, however, it has been observed that there appear changes to proliferation of PBMCs correlated to amounts of bromodeoxyuridine incorporated into the cellular DNA. Moreover, changes to secretion of IL-4 and IL-13 by the cells under the influence of agonists were detected, as well as changes to secretion of IFN-gamma under the influence of all the examined substances. The obtained results provide information on immunomodulatory effects of food-derived opioid peptides, which may be of clinical significance especially in the case of allergic diseases in newborns. Copyright © 2010 Elsevier Inc. All rights reserved.

negative: Bisphenol A (BPA) in U.S. food. Bisphenol A (BPA) is a chemical used for lining metal cans and in polycarbonate plastics, such as baby bottles. In rodents, BPA is associated with early sexual maturation, altered behavior, and effects on prostate and mammary glands. In humans, BPA is associated with cardiovascular disease, diabetes, and male sexual dysfunction in exposed workers. Food is a major exposure source. We know of no studies reporting BPA in U.S. fresh food, canned food, and food in plastic packaging in peer reviewed journals. We measured BPA levels in 105 fresh and canned foods, foods sold in plastic packaging, and in cat and dog foods in cans and plastic packaging. We detected BPA in 63 of 105 samples, including fresh turkey, canned green beans, and canned infant formula. Ninety-three of these samples were triplicates which had similar detected levels. Detected levels ranged from 0.23 to 65.0 ng/g ww and were not associated with type of food or packaging but did vary with pH. BPA levels were higher for foods of pH 5 compared to more acidic and alkaline foods. Detected levels were comparable to those found by others. Further research is indicated to determine BPA levels in U.S. food in larger, representative sampling.

negative: Beta-casomorphins-7 in infants on different type of feeding and different levels of psychomotor development. Casomorphins are the most important during the first year of life, when postnatal formation is most active and milk is the main source of both nutritive and biologically active material for infants. This study was conducted on a total of 90 infants, of which 37 were fed with breast milk and 53 were fed with formula containing cow milk. The study has firstly indicated substances with immunoreactivity of human (irHCM) and bovine (irBCM) beta-casomorphins-7 in blood plasma of naturally and artificially fed infants, respectively. irHCM and irBCM were detected both in the morning before feeding (basal level), and 3h after feeding. Elevation of irHCM and irBCM levels after feeding was detected mainly in infants in the first 3 months of life. Chromatographic characterization of the material with irBCM has demonstrated that it has the same molecular mass and polarity as synthetic bovine beta-casomorphin-7. The highest basal irHCM was observed in breast-fed infants with normal psychomotor development and muscle tone. In contrast, elevated basal irBCM was found in formula-fed infants showing delay in psychomotor development and heightened muscle tone. Among formula-fed infants with normal development, the rate of this parameter directly correlated to basal irBCM. The data indicate that breast feeding has an advantage over artificial feeding for infants' development during the first year of life and support the hypothesis for deterioration of bovine casomorphin elimination as a risk factor for delay in psychomotor development and other diseases such as autism.

negative: Identification of peptide hormones of the amphipathic helix class using the helical hydrophobic moment algorithm. Eisenberg's helical hydrophobic moment (less than mu H greater than) algorithm was applied to the analysis of the primary structure of amphipathic alpha-helical peptide hormones and an optimal method for identifying other peptides of this class determined. We quantitate and compare known amphipathic helical peptide hormones with a second group of peptides with proven nonamphipathic properties and determine the best method of distinguishing between them. The respective means of the maximum 11 residue less than mu H greater than for the amphipathic helical and control peptides were 0.46 (+/-/-0.07) and 0.33 (0.07) (P + 0.004). To better reflect the amphipathic potential of the entire peptide, the percent of 11 residue segments in each peptide above a particular less than mu H greater than was plotted vs less than mu H greater than. The resulting curves are referred to as HM-C. The mean HM-C (of the two groups) was highly significantly different such that the HM-C method was superior to others in its ability to distinguish amphipathic from nonamphipathic peptides. Several potential new members of this structural class were identified using this approach. Molecular modeling of a portion of one of these, prolactin inhibitory factor, reveals a strongly amphipathic alpha helix at residues 4-21. This computer-based method may enable rapid identification of peptides of the amphipathic alpha-helix class.

negative: Sub-clinical neurobehavioral abnormalities associated with low level of mercury exposure through fish consumption. In order to assess early neurotoxic effects associated with relatively low levels of mercury absorbed through fish eating, two groups of 22 adult male subjects, habitual consumers of tuna fish, and 22 controls were examined using a cross-sectional field study. The assessment included neurobehavioral tests of vigilance and psychomotor function, hand tremor measurements and serum prolactin assessment. Mercury in urine (U-Hg) and serum prolactin (sPRL) were measured in all exposed subjects and controls, whereas measurements of the organic component of mercury in blood (O-Hg) were available for only 10 exposed and six controls. U-Hg was significant higher among exposed subjects (median 6.5 microg/g of creatinine, range 1.8-21.5) than controls (median 1.5 microg/g of creatinine, range 0.5-5.3). The median values of O-Hg were 41.5 microg/l among the tuna fish eaters and 2.6 microg/l in the control group. Both U-Hg and O-Hg were significantly correlated with the quantity of fish consumed per week. Significant differences in sPRL were found between exposed (12.6 ng/ml) and controls (9.1 ng/ml). Individual sPRL were significantly correlated with both U-Hg and O-Hg levels. The neurobehavioral performance of subjects who consumed tuna fish regularly was significantly worse on color word reaction time, digit symbol reaction time and finger tapping speed (FT). After considering the education level and other covariates, the multiple stepwise regression analysis indicated that O-Hg concentration was most significantly associated with individual performance on these tests, accounting for about 65% of the variance in test scores.

negative: Excretion, isolation and structure of a new phenolic constituent of female urine. The regular occurrence of a peak due to an unidentified substance (X) in the gas chromatographic traces obtained from phenolic extracts of urine from human pregnant and non-pregnant females has been reported. The biphasic excretion of X with maxima in the luteal phase of the ovulatory cycle and relatively high levels in the first trimester of pregnancy were noteworthy and suggested that the substance may have a biological significance. Close similarities between the excretory pattern, the chemical and chromatographic properties of X and of those of the known phenolic steroids suggested initially that this compound was steroidal in nature. The same, or a similar, substance seems to be excreted in the vervet monkey (Cercopithecus aethiops pygerythrus). We now report the excretory pattern of X in more detail, the isolation of the pure compound from pooled pregnancy urine and the chemical structure. The structure determined by mass spectrometry, IR spectroscopy and NMR spectrometry is: trans-(+/-)-3,4-bis[(3-hydroxyphenyl)methyl]dihydro-2-(3H)-furanone (HPMF) and was confirmed by synthesis.

negative: Upregulation of lymphocyte apoptosis as a strategy for preventing and treating autoimmune disorders: a role for whole-food vegan diets, fish oil an... Induced apoptosis of autoreactive T-lymphocyte precursors in the thymus is crucial for the prevention of autoimmune disorders. IGF-I and prolactin, which are lymphocyte growth factors, may have the potential to suppress apoptosis in thymocytes and thus encourage autoimmunity; conversely, dietary fish oil rich in omega-3 fats appears to upregulate apoptosis in lymphocytes. Since whole-food vegan diets may downregulate systemic IGF-I activity, it is proposed that such a diet, in conjunction with fish oil supplementation and treatment with dopamine agonists capable of suppressing prolactin secretion, may have utility for treating and preventing autoimmune disorders. This prediction is consistent with the extreme rarity of autoimmune disorders among sub-Saharan black Africans as long as they followed their traditional quasi-vegan lifestyles, and with recent ecologic studies correlating risks for IDDM and for multiple sclerosis mortality with animal product and/or saturated fat consumption. Moreover, there is evidence that vegan or quasi-vegan diets are useful in the management of rheumatoid arthritis, multiple sclerosis, and possibly SLE. The dopamine agonist bromocryptine exerts anti-inflammatory effects in rodent models of autoimmunity, and there is preliminary evidence that this drug may be clinically useful in several human autoimmune diseases; better tolerated D2-specific agonists such as cabergoline may prove to be more practical for use in therapy. The moderate clinical utility of supplemental fish oil in rheumatoid arthritis and certain other autoimmune disorders is documented. It is not unlikely that extra-thymic anti-inflammatory effects contribute importantly to the clinical utility of vegan diets, bromocryptine, and fish oil in autoimmunity. The favorable impact of low latitude or high altitude on autoimmune risk may be mediated by superior vitamin D status, which is associated with decreased secretion of parathyroid hormone; there are theoretical grounds for suspecting that parathyroid hormone may inhibit apoptosis in thymocytes. Androgens appear to up-regulate thymocyte apoptosis, may be largely responsible for the relative protection from autoimmunity enjoyed by men, and merit further evaluation for the management of autoimmunity in women. It will probably prove more practical to prevent autoimmune disorders than to reverse them once established; a whole-food vegan diet, coupled with fish oil and vitamin D supplementation, may represent a practical strategy for achieving this prevention, while concurrently lowering risk for many other life-threatening 'Western' diseases. Copyright 2001 Harcourt Publishers Ltd.

negative: Estradiol, tamoxifen, and flaxseed alter IL-1β and IL-1Ra levels in normal human breast tissue in vivo. INTRODUCTION: Sex steroid exposure increases the risk of breast cancer by unclear mechanisms. Diet modifications may be one breast cancer prevention strategy. The proinflammatory cytokine family of IL-1 is implicated in cancer progression. IL-1Ra is an endogenous inhibitor of the proinflammatory IL-1α and IL-1β. OBJECTIVE: The objective of this study was to elucidate whether estrogen, tamoxifen, and/or diet modification altered IL-1 levels in normal human breast tissue. DESIGN AND METHODS: Microdialysis was performed in healthy women under various hormone exposures, tamoxifen therapy, and diet modifications and in breast cancers of women before surgery. Breast tissue biopsies from reduction mammoplasties were cultured. RESULTS: We show a significant positive correlation between estradiol and in vivo levels of IL-1β in breast tissue and abdominal sc fat, whereas IL-1Ra exhibited a significant negative correlation with estradiol in breast tissue. Tamoxifen or a dietary addition of 25 g flaxseed per day resulted in significantly increased levels of IL-1Ra in the breast. These results were confirmed in ex vivo culture of breast biopsies. Immunohistochemistry of the biopsies did not reveal any changes in cellular content of the IL-1s, suggesting that mainly the secreted levels were affected. In breast cancer patients, intratumoral levels of IL-1β were significantly higher compared with normal adjacent breast tissue. CONCLUSION: IL-1 may be under the control of estrogen in vivo and may be attenuated by antiestrogen therapy and diet modifications. The increased IL-1β in breast cancers of women strongly suggests IL-1 as a potential therapeutic target in breast cancer treatment and prevention.

negative: Mechanisms of twinning: VII. Effect of diet and heredity on the human twinning rate. OBJECTIVE: To evaluate the possible biochemical effect of diet and heredity on the rates of monozygotic and dizygotic twinning. STUDY DESIGN: In that insulin-like growth factor (IGF) has been found to be elevated in cows selected for their demonstrated increased twinning rate, the effect of agents that influence the level of IGF in women was examined. This was correlated with their prior history of singleton versus twin birthing. In particular, the effect of diets consisting of or excluding animal products that have elevated IGF content (e.g., milk) was considered. RESULTS: Vegan women, who exclude dairy products from their diets, have a twinning rate which is one-fifth that of vegetarians and omnivores. CONCLUSION: The results reported here support the proposed IGF model of dizygotic twinning. Genotypes favoring elevated IGF and diets including dairy products, especially in areas where growth hormone is given to cattle, appear to enhance the chances of multiple pregnancies due to ovarian stimulation.

negative: The DietCompLyf study: a prospective cohort study of breast cancer survival and phytoestrogen consumption. DietCompLyf is a multi-centre prospective study designed to investigate associations between phytoestrogens - naturally occurring plant compounds with oestrogenic properties - and other diet and lifestyle factors with breast cancer recurrence and survival. 3159 women with grades I-III breast cancer were recruited 9-15 months post-diagnosis from 56 UK hospitals. Detailed information on clinico-pathological, diet, lifestyle and quality of life is collected annually up to 5 years. Biological samples have also been collected as a resource for subsequent evaluation. The characteristics of the patients and associations between pre-diagnosis intake of phytoestrogens (isoflavones and lignans; assessed using the EPIC-Norfolk UK 130 question food frequency questionnaire) and breast cancer (i) risk factors and (ii) prognostic factors are described for 1797 women who had complete data for all covariates and phytoestrogens of interest. Isoflavone intakes were higher in the patients who were younger at diagnosis, in the non-smokers, those who had breast-fed and those who took supplements. Lignan intakes were higher in patients with a higher age at diagnosis, in ex-smokers, those who had breast-fed, who took supplements, had a lower BMI at diagnosis, lower age at menarche and were nulliparous. No significant associations between pre-diagnosis phytoestrogen intake and factors associated with improved breast cancer prognosis were observed. The potential for further exploration of the relationship between phytoestrogens and breast cancer recurrence and survival, and for the establishment of evidence to improve dietary and lifestyle advice offered to patients following breast cancer diagnosis using DietCompLyf data is discussed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

negative: Higher Levels of IGF-I and Adrenal Androgens at Age 8 Years Are Associated with Earlier Age at Menarche in Girls Context: Earlier age at menarche is associated with rapid infancy weight gain and childhood obesity. The role of hormone levels in mediating these associations is unclear. Objective: The aim of this study was to identify childhood hormone levels at age 8 yr that are associated with early menarche, independent of body size. Design, Settings, and Subjects: A total of 329 girls from a prospective United Kingdom birth cohort study provided blood samples at mean age 8.1 yr (range, 8.0–8.5) for hormone measurements and were followed longitudinally to establish age at menarche. Main Outcome Measures: Fasting plasma levels of IGF-I, androstenedione, dehydroepiandrosterone sulfate (DHEAS), leptin, insulin, IGF binding protein-1, and SHBG were measured. Age at menarche was reported by questionnaire and categorized as before 12.0, 12.0–13.0, or later than 13 yr. Results: Earlier menarche was associated with greater body weight, height, and body mass index at age 8 yr (all P-trend <0.001). Before adjustment for body size, earlier menarche was associated with higher levels of IGF-I, androstenedione, DHEAS, leptin, and fasting insulin, and with lower levels of IGF binding protein-1 and SHBG at age 8 yr (all P < 0.01). After adjustment for body mass index and height at age 8 yr, only IGF-I (P = 0.004), androstenedione (P = 0.01), and DHEAS (P = 0.01) remained associated with earlier menarche. Conclusions: Associations between higher levels of IGF-I and adrenal androgens at age 8 yr with earlier menarche, independent of body size, support functional roles of these hormones in regulating puberty timing in girls. Higher levels of these hormones reported in children who exhibited rapid weight gain during infancy may indicate their role in developmental pathways leading to earlier sexual maturation.

negative: Body fat composition and distribution in women with polycystic ovary syndrome. OBJECTIVES: The aims of the present study were to compare the distribution and accumulation of body fat in women with polycystic ovary syndrome (PCOS) and healthy controls matched for age and body mass index (BMI), and to investigate the association between androgen levels, insulin resistance and fat distribution. MATERIALS AND METHODS: Thirty-one PCOS women and 29 age- and BMI-matched healthy control women were evaluated in terms of subcutaneous adipose tissue thickness determined with a skinfold caliper and body composition analyzed by bioelectrical impedance analysis. Blood samples were obtained for determination of follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, 17-hydroxyprogesterone, basal prolactin, testosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG), androstenedione, insulin and glucose levels. Insulin sensitivity was estimated by fasting glucose/insulin ratio and free androgen index (FAI) was calculated as 100 x testosterone/SHBG. Differences between means were analyzed by Student's t test or the Mann-Whitney U test according to distribution of the data. Correlation analysis was performed between the body fat distribution and parameters concerning insulin resistance and androgens. RESULTS: FAI was significantly higher in patients with PCOS compared with the control group (p = 0.001). Fasting insulin was significantly higher and fasting glucose/insulin ratio was significantly lower in the PCOS group vs. controls (p = 0.03 and 0.001, respectively). There was significantly less subcutaneous adipose tissue in the controls than the PCOS women at the triceps (p = 0.04) and subscapular region (p = 0.04). Waist-to-hip ratio of PCOS women was significantly higher than that of control subjects (p = 0.04). CONCLUSION: Upper-half type body fat distribution is linked with PCOS, high free testosterone levels and insulin resistance.

negative: From milk to malignancy: the role of mammary stem cells in development, pregnancy and breast cancer Adult stem cells of the mammary gland (MaSCs) are a highly dynamic population of cells that are responsible for the generation of the gland during puberty and its expansion during pregnancy. In recent years significant advances have been made in understanding how these cells are regulated during these developmentally important processes both in humans and in mice. Understanding how MaSCs are regulated is becoming a particularly important area of research, given that they may be particularly susceptible targets for transformation in breast cancer. Here, we summarize the identification of MaSCs, how they are regulated and the evidence for their serving as the origins of breast cancer. In particular, we focus on how changes in MaSC populations may explain both the increased risk of developing aggressive ER/PR(−) breast cancer shortly after pregnancy and the long-term decreased risk of developing ER/PR(+) tumors.

negative: Reducing bioavailable sex hormones through a comprehensive change in diet: the diet and androgens (DIANA) randomized trial. High serum levels of testosterone and estradiol, the bioavailability of which may be increased by Western dietary habits, seem to be important risk factors for postmenopausal breast cancer. We hypothesized that an ad libitum diet low in animal fat and refined carbohydrates and rich in low-glycemic-index foods, monounsaturated and n-3 polyunsaturated fatty acids, and phytoestrogens, might favorably modify the hormonal profile of postmenopausal women. One hundred and four postmenopausal women selected from 312 healthy volunteers on the basis of high serum testosterone levels were randomized to dietary intervention or control. The intervention included intensive dietary counseling and specially prepared group meals twice a week over 4.5 months. Changes in serum levels of testosterone, estradiol, and sex hormone-binding globulin were the main outcome measures. In the intervention group, sex hormone-binding globulin increased significantly (from 36.0 to 45.1 nmol/liter) compared with the control group (25 versus 4%,; P < 0.0001) and serum testosterone decreased (from 0.41 to 0.33 ng/ml; -20 versus -7% in control group; P = 0.0038). Serum estradiol also decreased, but the change was not significant. The dietary intervention group also significantly decreased body weight (4.06 kg versus 0.54 kg in the control group), waist:hip ratio, total cholesterol, fasting glucose level, and area under insulin curve after oral glucose tolerance test. A radical modification in diet designed to reduce insulin resistance and also involving increased phytoestrogen intake decreases the bioavailability of serum sex hormones in hyperandrogenic postmenopausal women. Additional studies are needed to determine whether such effects can reduce the risk of developing breast cancer.

negative: A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome Chronic fatigue syndrome (CFS) is complex illness of unknown etiology. Among the broad range of symptoms, many patients report disturbances in the emotional realm, the most frequent of which is anxiety. Research shows that patients with CFS and other so-called functional somatic disorders have alterations in the intestinal microbial flora. Emerging studies have suggested that pathogenic and non-pathogenic gut bacteria might influence mood-related symptoms and even behavior in animals and humans. In this pilot study, 39 CFS patients were randomized to receive either 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) or a placebo daily for two months. Patients provided stool samples and completed the Beck Depression and Beck Anxiety Inventories before and after the intervention. We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those taking the probiotic vs controls (p = 0.01). These results lend further support to the presence of a gut-brain interface, one that may be mediated by microbes that reside or pass through the intestinal tract.

negative: Quantitative measurement of endogenous estrogen metabolites, risk-factors for development of breast cancer, in commercial milk products by LC-MS/MS. Increased levels of estrogen metabolites (EM) are associated with cancers of the reproductive system. One potential dietary source of EM is milk. In this study, the absolute quantities of unconjugated (free) and unconjugated plus conjugated (total) EM were measured in a variety of commercial milks (whole, 2%, skim, and buttermilk). The results show that the milk products tested contain considerable levels of EM; however, the levels of unconjugated EM in skim milk were substantially lower than that observed in whole milk, 2% milk, and buttermilk. Whole milk contained the lowest overall levels of EM while buttermilk contained the highest. As anticipated, soy milk did not contain the mammalian EM measured using this method. The relatively high levels of catechol estrogens detected in milk products support the theory that milk consumption is a source of EM and their ingestion may have a dietary influence on cancer risk.

negative: Milk stimulates growth of prostate cancer cells in culture. Concern has been expressed about the fact that cows' milk contains estrogens and could stimulate the growth of hormone-sensitive tumors. In this study, organic cows' milk and two commercial substitutes were digested in vitro and tested for their effects on the growth of cultures of prostate and breast cancer cells. Cows' milk stimulated the growth of LNCaP prostate cancer cells in each of 14 separate experiments, producing an average increase in growth rate of over 30%. In contrast, almond milk suppressed the growth of these cells by over 30%. Neither cows' milk nor almond milk affected the growth of MCF-7 breast cancer cells or AsPC-1 pancreatic cancer cells significantly. Soy milk increased the growth rate of the breast cancer cells. These data indicate that prostate and breast cancer patients should be cautioned about the possible promotional effects of commercial dairy products and their substitutes.

negative: Serum enterolactone levels and mortality outcome in women with early breast cancer: a retrospective cohort study. We previously demonstrated that high serum enterolactone levels are associated with a reduced incidence of breast cancer in healthy women. The present study was aimed at investigating whether a similar association might be found between serum enterolactone levels and the mortality of women with early breast cancer. The levels of enterolactone in cryopreserved serum aliquots obtained from 300 patients, operated on for breast cancer, were measured using a time-resolved fluoro-immunoassay. Levels were analyzed in respect to the risk of mortality following surgery. Cox proportional hazard regression models were used to check for prognostic features, to estimate hazard ratios for group comparisons and to test for the interaction on mortality hazards between the variables and enterolactone concentrations. The Fine and Gray competing risk proportional hazard regression model was used to predict the probabilities of breast cancer-related and breast cancer-unrelated mortalities. At a median follow-up time of 23 years (range 0.6-26.1), 180 patients died, 112 of whom died due to breast cancer-related events. An association between a decreased mortality risk and enterolactone levels ≥ 10 nmol/l was found in respect to both all-cause and breast cancer-specific mortality. The difference in mortality hazards was statistically significant, but it appeared to decrease and to lose significance after the first 10 years, though competing risk analysis showed that breast cancer-related mortality risk remained constantly lower in those patients with higher enterolactone levels. Our findings are consistent with those of most recent literature and provide further evidence that mammalian lignans might play an important role in reducing all-cause and cancer-specific mortality of the patients operated on for breast cancer.

negative: Declines in breast cancer after the WHI: apparent impact of hormone therapy. Large numbers of US women stopped taking hormone therapies (HT), especially estrogen/progestin (EP) formulations, after the Women's Health Initiative trial detected elevated risks of breast cancer in EP users and was halted in July 2002. Recent reports have indicated substantial and significant declines in population-based breast cancer incidence, particularly hormone-sensitive forms, for 2003 and 2004. Are these events linked? This commentary considers the available evidence linking the mass cessation of HT in 2002 to the breast cancer incidence declines of 2003/2004 and quantifies the potential impact of the cessation on the overall burden of breast cancer in the US.

negative: Milk consumption is a risk factor for prostate cancer in Western countries: evidence from cohort studies. We have previously found a positive association between milk consumption and prostate cancer risk using meta-analysis to analyze published case-control studies. In the present study, further meta-analysis was conducted to estimate the summary relative risk (RR) between the consumption of milk and dairy products and prostate cancer from cohort studies published between 1966- 2006. We found 18 relevant articles and 13 independent studies were available for our analysis. The summary RR was 1.13 (95% confidence interval = 1.02-1.24) when comparing the highest with the lowest quantile of consumption. The summary RRs by study stratification showed a positive association. A dose-response relationship was identified when combining the studies that partitioned the consumption by quintiles. We also evaluated the effects of some limitations, such as dairy classification, prostate cancer stages and publication bias, in the present study. These findings, together with the previous study, suggest that the consumption of milk and dairy products increases the risk of prostate cancer. This is biologically plausible since milk contains considerable amounts of fat, hormones, and calcium that are associated with prostate cancer risk.

negative: Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001. OBJECTIVE: To determine the effects of the probiotic lactic acid bacterium, Lactobacillus rhamnosus HN001, on natural cellular immunity when delivered orally in normal low-fat milk (LFM) or lactose-hydrolyzed low-fat milk (LFM-LH). DESIGN: A three stage, pre-post intervention trial, spanning nine weeks. SETTING: Taipei Medical College Hospital, Taipei, Taiwan. SUBJECTS: Fifty-two healthy middle-aged and elderly volunteers (17 males, 35 females; median age 63.5, range 44-80). INTERVENTIONS: Stage 1 (run-in diet): 25 g/200 mL reconstituted LFM powder, twice daily for 3 weeks. Stage 2 (probiotic intervention): LFM or LFM-LH, supplemented with 10(9) CFUs/g L. rhamnosus HN001 in each case, for 3 weeks. Stage 3 (wash-out): LFM for 3 weeks. MEASURES OF OUTCOME: In vitro phagocytic capacity of peripheral blood polymorphonuclear (PMN) leukocytes; in vitro tumoricidal activity of natural killer (NK) leukocytes. RESULTS: Immunological responses were unaffected by the run-in diet of LFM alone. In contrast, the relative proportion of PMN cells showing phagocytic activity increased by 19% and 15%, respectively, following consumption of HN001 in either LFM or LFM-LH; the relative level of NK cell tumor killing activity increased by 71% and 147%. In most cases these levels declined following cessation, but remained above baseline. CONCLUSIONS: Dietary consumption of L. rhamnosus HN001, in a base of low-fat milk or lactose-hydrolyzed low-fat milk, appears to enhance systemic cellular immune responses and may be useful as a dietary supplement to boost natural immunity.


query: whiting

positive: Reduction of faecal coliform, coliform and heterotrophic plate count bacteria in the household kitchen and bathroom by disinfection with hypochlori... Fourteen sites evenly divided between the household kitchen and bathroom were monitored on a weekly basis for numbers of faecal coliforms, total coliforms and heterotrophic plate count bacteria. The first 10 weeks comprised the control period, hypochlorite cleaning products were introduced into the household during the second 10 weeks, and a strict cleaning regimen using hypochlorite products was implemented during the last 10 weeks. The kitchen was more heavily contaminated than the bathroom, with the toilet seat being the least contaminated site. The highest concentrations of all three classes of bacteria were found on sites that were moist environments and/or were frequently touched; these included the sponge/dishcloth, the kitchen sink drain area, the bath sink drain area, and the kitchen faucet handle(s). The implementation of a cleaning regimen with common household hypochlorite products resulted in the significant reduction of all three classes of bacteria at these four sites and other household sites.

positive: Microbiological quality of sushi from sushi bars and retailers. Sushi is a traditional Japanese food, mostly consisting of rice and raw fish. Fish is considered a healthy food, but as with other animal products, consumption of raw muscle incurs potential health risks such as ingestion of pathogenic bacteria or parasites. In this study, 250 sushi samples were analyzed for their microbiological status and the prevalence of pathogenic bacteria. A comparison was made between frozen sushi from supermarkets and fresh sushi from sushi bars. Aerobic mesophilic bacteria counts differed for sushi from these two sources, with means of 2.7 log CFU/g for frozen sushi and 6.3 log CFU/g for fresh sushi. The prevalence of Escherichia coli and Staphylococcus aureus was higher in the fresh samples. Salmonella was found in four (1.6%) of the sushi samples, and Listeria monocytogenes was found in three (1.2%) of the samples. These results indicate that the microbiological quality of industrially processed sushi is higher than that of freshly prepared sushi. The quality of freshly prepared sushi strongly depends on the skills and habits of the preparation cooks, which may vary.

negative: The prevalence of celiac disease in the United States. OBJECTIVES: The prevalence of celiac disease (CD) in the United States is unknown. We sought to estimate CD prevalence nationwide by using a nationally representative sample. METHODS: This study included 7,798 persons aged 6 years or older who participated in the National Health and Nutrition Examination Survey 2009-2010. Serum samples from all participants were tested for immunoglobulin A (IgA) tissue transglutaminase antibodies and, if findings were abnormal, also for IgA endomysial antibodies. Information about prior diagnosis of CD and use of a gluten-free diet (GFD) was obtained by direct interview. CD was defined as having either double-positive serology (serologically diagnosed CD) or a reported diagnosis of CD by a doctor or other health-care professional and being on a GFD (reported clinical diagnosis of CD). RESULTS: CD was found in 35 participants, 29 of whom were unaware of their diagnosis. Median age was 45 years (interquartile range, 23-66 years); 20 were women and 29 were non-Hispanic white. The prevalence of CD in the United States was 0.71% (95% confidence interval (CI), 0.58-0.86%), with 1.01% (95% CI, 0.78-1.31%) among non-Hispanic whites. In all, 55 participants reported following a GFD, which corresponded to a prevalence of 0.63% (95% CI, 0.36-1.07%). CONCLUSIONS: The prevalence of CD in the United States was 0.71% (1 in 141), similar to that found in several European countries. However, most cases were undiagnosed. CD was rare among minority groups but affected 1% of non-Hispanic whites. Most persons who were following a GFD did not have a diagnosis of CD.

negative: Stevia (Stevia rebaudiana) a bio-sweetener: a review. Studies revealed that Stevia has been used throughout the world since ancient times for various purposes; for example, as a sweetener and a medicine. We conducted a systematic literature review to summarize and quantify the past and current evidence for Stevia. We searched relevant papers up to 2007 in various databases. As we know that the leaves of Stevia plants have functional and sensory properties superior to those of many other high-potency sweeteners, Stevia is likely to become a major source of high-potency sweetener for the growing natural food market in the future. Although Stevia can be helpful to anyone, there are certain groups who are more likely to benefit from its remarkable sweetening potential. These include diabetic patients, those interested in decreasing caloric intake, and children. Stevia is a small perennial shrub that has been used for centuries as a bio-sweetener and for other medicinal uses such as to lower blood sugar. Its white crystalline compound (stevioside) is the natural herbal sweetener with no calories and is over 100-300 times sweeter than table sugar.

negative: The color red reduces snack food and soft drink intake. Based on evidence that the color red elicits avoidance motivation across contexts (Mehta & Zhu, 2009), two studies investigated the effect of the color red on snack food and soft drink consumption. In line with our hypothesis, participants drank less from a red labeled cup than from a blue labeled cup (Study 1), and ate less snack food from a red plate than from a blue or white plate (Study 2). The results suggest that red functions as a subtle stop signal that works outside of focused awareness and thereby reduces incidental food and drink intake. Copyright Â© 2012 Elsevier Ltd. All rights reserved.

negative: Curcumin and obesity. Turmeric has been long recognized for its anti-inflammatory and health-promoting properties. Curcumin is one of the principal anti-inflammatory and healthful components of turmeric comprising 2-8% of most turmeric preparations. Experimental evidence supports the activity of curcumin in promoting weight loss and reducing the incidence of obesity-related diseases. With the discovery that obesity is characterized by chronic low-grade metabolic inflammation, phytochemicals like curcumin which have anti-inflammatory activity are being intensely investigated. Recent scientific research reveals that curcumin directly interacts with white adipose tissue to suppress chronic inflammation. In adipose tissue, curcumin inhibits macrophage infiltration and nuclear factor κB (NF-κB) activation induced by inflammatory agents. Curcumin reduces the expression of the potent proinflammatory adipokines tumor necrosis factor-α (TNFα), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor type-1 (PAI-1), and it induces the expression of adiponectin, the principal anti-inflammatory agent secreted by adipocytes. Curcumin also has effects to inhibit adipocyte differentiation and to promote antioxidant activities. Through these diverse mechanisms curcumin reduces obesity and curtails the adverse health effects of obesity. Copyright © 2013 International Union of Biochemistry and Molecular Biology, Inc.

negative: Ten years of life: Is it a matter of choice? BACKGROUND: Relative risk estimates suggest that effective implementation of behaviors commonly advocated in preventive medicine should increase life expectancy, although there is little direct evidence. OBJECTIVE: To test the hypothesis that choices regarding diet, exercise, and smoking influence life expectancy. METHODS: A total of 34 192 California Seventh-Day Adventists (75% of those eligible) were enrolled in a cohort and followed up from 1976 to 1988. A mailed questionnaire provided dietary and other exposure information at study baseline. Mortality for all subjects was ascertained by matching to state death tapes and the National Death Index. RESULTS: California Adventists have higher life expectancies at the age of 30 years than other white Californians by 7.28 years (95% confidence interval, 6.59-7.97 years) in men and by 4.42 years (95% confidence interval, 3.96-4.88 years) in women, giving them perhaps the highest life expectancy of any formally described population. Commonly observed combinations of diet, exercise, body mass index, past smoking habits, and hormone replacement therapy (in women) can account for differences of up to 10 years of life expectancy among Adventists. A comparison of life expectancy when these factors take high-risk compared with low-risk values shows independent effects that vary between 1.06 and 2.74 years for different variables. The effect of each variable is assessed with all others at either medium- or high-risk levels. CONCLUSIONS: Choices regarding diet, exercise, cigarette smoking, body weight, and hormone replacement therapy, in combination, appear to change life expectancy by many years. The longevity experience of Adventists probably demonstrates the beneficial effects of more optimal behaviors.

negative: Adherence to healthy lifestyle habits in US adults, 1988-2006. BACKGROUND: Lifestyle choices are associated with cardiovascular disease and mortality. The purpose of this study was to compare adherence to healthy lifestyle habits in adults between 1988 and 2006. METHODS: Analysis of adherence to 5 healthy lifestyle trends (>or=5 fruits and vegetables/day, regular exercise >12 times/month, maintaining healthy weight [body mass index 18.5-29.9 kg/m(2)], moderate alcohol consumption [up to 1 drink/day for women, 2/day for men] and not smoking) in the National Health and Nutrition Examination Survey 1988-1994 were compared with results from the National Health and Nutrition Examination Survey 2001-2006 among adults aged 40-74 years. RESULTS: Over the last 18 years, the percent of adults aged 40-74 years with a body mass index >or=30 kg/m(2) has increased from 28% to 36% (P <.05); physical activity 12 times a month or more has decreased from 53% to 43% (P <.05); smoking rates have not changed (26.9% to 26.1%); eating 5 or more fruits and vegetables a day has decreased from 42% to 26% (P <.05), and moderate alcohol use has increased from 40% to 51% (P <.05). Adherence to all 5 healthy habits has gone from 15% to 8% (P <.05). Although adherence to a healthy lifestyle was lower among minorities, adherence decreased more among non-Hispanic Whites over the period. Individuals with a history of hypertension/diabetes/cardiovascular disease were no more likely to be adherent to a healthy lifestyle than people without these conditions. CONCLUSIONS: Generally, adherence to a healthy lifestyle pattern has decreased during the last 18 years, with decreases documented in 3 of 5 healthy lifestyle habits. These findings have broad implications for the future risk of cardiovascular disease in adults.

negative: Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists. Epidemiologic studies of diet and pancreas cancer are few, and include ecologic comparisons and a limited number of prospective and case-control studies. Foods and/or nutrients that have been suggested to be associated with increased risk of this cancer include total fat intake, eggs, animal protein, sugar, meat, coffee and butter. Consumption of raw fruits and vegetables has been consistently associated with decreased risk. Dietary habits and medical history variables were evaluated in a prospective study of fatal pancreas cancer among 34,000 California Seventh-day Adventists between 1976 and 1983. Forty deaths from pancreas cancer occurred during the follow-up period. Compared to all US whites, Adventists experienced decreased risk from pancreas cancer death (standardized mortality ratio [SMR] = 72 for men; 90 for women), which was not statistically significant. Although there was a suggestive relationship between increasing meat, egg, and coffee consumption and increased pancreatic cancer risk, these variables were not significantly related to risk after controlling for cigarette smoking. However, increasing consumption of vegetarian protein products, beans, lentils, and peas as well as dried fruit was associated with highly significant protective relationships to pancreas cancer risk. A prior history of diabetes was associated with increased risk of subsequent fatal pancreas cancer, as was a history of surgery for peptic or duodenal ulcer. A history of tonsillectomy was associated with a slight, nonsignificant protective relationship as was history of various allergic reactions. These findings suggest that the protective relationships associated with frequent consumption of vegetables and fruits high in protease-inhibitor content are more important than any increase in pancreas cancer risk attendant on frequent consumption of meat or other animal products. Furthermore, the previously reported positive associations between diabetes and abdominal surgery and pancreas cancer risk are supported in these data.

negative: Sedentary time and cardio-metabolic biomarkers in US adults: NHANES 2003–06 Aims Prolonged sedentary time is ubiquitous in developed economies and is associated with an adverse cardio-metabolic risk profile and premature mortality. This study examined the associations of objectively assessed sedentary time and breaks (interruptions) in sedentary time with continuous cardio-metabolic and inflammatory risk biomarkers, and whether these associations varied by sex, age, and/or race/ethnicity. Methods and results Cross-sectional analyses with 4757 participants (≥20 years) from the 2003/04 and 2005/06 US National Health and Nutrition Examination Survey (NHANES). An Actigraph accelerometer was used to derive sedentary time [<100 counts per minute (cpm)] and breaks in sedentary time. Independent of potential confounders, including moderate-to-vigorous exercise, detrimental linear associations (P for trends <0.05) of sedentary time with waist circumference, HDL-cholesterol, C-reactive protein, triglycerides, insulin, HOMA-%B, and HOMA-%S were observed. Independent of potential confounders and sedentary time, breaks were beneficially associated with waist circumference and C-reactive protein (P for trends <0.05). There was limited evidence of meaningful differences in associations with biomarkers by age, sex, or race/ethnicity. Notable exceptions were sex-differences in the associations of sedentary time and breaks with HDL-cholesterol, and race/ethnicity differences in the association of sedentary time with waist circumference with associations detrimental in non-Hispanic whites, null in Mexican Americans, and beneficial in non-Hispanic blacks. Conclusion These are the first population-representative findings on the deleterious associations of prolonged sedentary time with cardio-metabolic and inflammatory biomarkers. The findings suggest that clinical communications and preventive health messages on reducing and breaking up sedentary time may be beneficial for cardiovascular disease risk.

negative: Prevalence of Kidney Stones in the United States Background The last nationally representative assessment of kidney stone prevalence in the United States occurred in 1994. After a 13-yr hiatus, the National Health and Nutrition Examination Survey (NHANES) reinitiated data collection regarding kidney stone history. Objective Describe the current prevalence of stone disease in the United States, and identify factors associated with a history of kidney stones. Design, setting, and participants A cross-sectional analysis of responses to the 2007–2010 NHANES (n = 12 110). Outcome measurements and statistical analysis Self-reported history of kidney stones. Percent prevalence was calculated and multivariable models were used to identify factors associated with a history of kidney stones. Results and limitations The prevalence of kidney stones was 8.8% (95% confidence interval [CI], 8.1–9.5). Among men, the prevalence of stones was 10.6% (95% CI, 9.4–11.9), compared with 7.1% (95% CI, 6.4–7.8) among women. Kidney stones were more common among obese than normal-weight individuals (11.2% [95% CI, 10.0–12.3] compared with 6.1% [95% CI, 4.8–7.4], respectively; p < 0.001). Black, non-Hispanic and Hispanic individuals were less likely to report a history of stone disease than were white, non-Hispanic individuals (black, non-Hispanic: odds ratio [OR]: 0.37 [95% CI, 0.28–0.49], p < 0.001; Hispanic: OR: 0.60 [95% CI, 0.49–0.73], p < 0.001). Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones. Conclusions Kidney stones affect approximately 1 in 11 people in the United States. These data represent a marked increase in stone disease compared with the NHANES III cohort, particularly in black, non-Hispanic and Hispanic individuals. Diet and lifestyle factors likely play an important role in the changing epidemiology of kidney stones.

negative: New metrics of affordable nutrition: which vegetables provide most nutrients for least cost? Measuring food prices per gram, rather than per calorie, is one way to make healthful vegetables appear less expensive. However, a better measure of affordability would take the nutrient content of vegetables into account. This study, based on analyses of US Department of Agriculture datasets, aimed to identify which vegetables, including juices and soups, provided the most nutrients per unit cost. Nutrient density was measured using the Nutrient Rich Foods (NRF) index, based on nine nutrients to encourage: protein; fiber; vitamins A, C, and E; calcium; iron; magnesium; and potassium; and on three nutrients to limit: saturated fat, added sugar, and sodium. Food cost in dollars was calculated per 100 g, per 100 kcal, per serving, and per nutrient content. One-way analyses of variance with post hoc tests were used to determine statistical significance. Results showed that tomato juices and tomato soups, dark green leafy and nonleafy vegetables, and deep yellow vegetables, including sweet potatoes, had the highest NRF scores overall. Highest NRF scores per dollar were obtained for sweet potatoes, white potatoes, tomato juices and tomato soups, carrots, and broccoli. Tomato sauces, raw tomatoes, and potato chips were eaten more frequently than were many other vegetables that were both more affordable and more nutrient-rich. These new measures of affordable nutrition can help foodservice and health professionals identify those vegetables that provide the highest nutrient density per unit cost. Processed vegetables, including soups and juices, can contribute to the quality and the affordability of the diet. Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

negative: Cadmium blood concentrations in relation to nutrition. Cadmium is a toxic element ubiquitous in the environment, which damages biological systems in various ways. The major source of cadmium exposure is food. High cadmium content in the soil leads to high cadmium concentrations in certain plants such as grains (above all surface layers and germs), oil or non-oil seeds, fruit and vegetables. These food commodities are the crucial components of a vegetarian nutrition. Blood cadmium concentrations were measured in two non-smoking population groups: the vegetarian group (n = 80) and the non-vegetarian (control) group of general population on traditional mixed diet (n = 84). The significantly higher blood cadmium content (1.78 +/- 0.22 vs. 0.45 +/- 0.04 microg/l) was measured in vegetarian group. Healthy risk values > 5 microg/l were found in 6 vegetarians vs. no non-vegetarian. The highest cadmium concentration (3.15 +/- 0.77 microg/l) was measured in vegan subgroup (plant food only, n = 10) and that value decreased with increasing animal food consumption (1.75 +/- 0.36 microg/l, lactovegetarian and lactoovovegetarian subgroup/added dairy products and eggs, n = 41/, 1.34 +/- 0.21 microg/I, semivegetarian subgroup /as a previous subgroup and added white meat, n = 291). Risk vegetarians vs. non-risk vegetarians consume significantly higher amounts of whole grain products, grain sprouts and oil seeds. Blood cadmium content is directly influenced by age (r = 0.32, p < 0.001), by whole grain product intake (r = 0.66, p < 0.001) and by duration of vegetarianism (r = 0.5, p < 0.001). Oxidative stress plays a major role in chronic cadmium induced hepatic and renal toxicity as well as in other consequences of cadmium injuries. Vegetarians have significantly higher plasma concentrations of natural antioxidants. The sufficient antioxidative protection against cadmium induced free radical formation in vegetarians may inhibit the harmful effects of greater cadmium intake from plant food.