Behavioral changes and hyperglycemia in NODEF mice following bisphenol S exposure are affected by diets.

Bisphenol S (BPS), an analogue of the controversial bisphenol A (BPA) that is found in epoxy resins and plastics, is a potential endocrine-disrupting chemical that can mimic endogenous hormone signaling. However, little is known about the behavioral or immunologic effects of BPS. The purpose of this study was to examine the impact of diets in BPS-treated mice in relation to hyperglycemia, development of type 1 diabetes, immunomodulation, and behavioral changes. Adult male and female nonobese diabetic excluded flora (NODEF) mice were exposed to environmentally relevant doses of BPS (VH, 30, or 300 µg/kg BW) and fed either a soy-based diet, a phytoestrogen-free diet, or a Western diet. NODEF male mice fed a soy-based diet exhibited a decreased curiosity/desire to explore, and possibly increased anxiety-like behavior and decreased short-term memory when exposed to BPS (300 µg/kg BW). In addition, these mice had significant increases in non-fasting blood glucose levels along with increased insulin sensitivity, impaired glucose tolerance, resistance to fasting and proinflammation. Although BPS had little effect on the glucose parameters in NODEF male mice fed a Western diet, there were decreases in %CD24+CD5+ and %B220+CD40L-cell populations and increases in distance traveled during the novel object test, suggesting hyperactivity. NODEF females fed a phytoestrogen-free diet exhibited slight decreases in time spent immobile during the tail suspension test in both the 30 and 300 µg/kg BW dose groups along with increases in %CD4+CD8+ and %Mac3+CD45R+ cell populations, signifying increased hyperactivity and anxiety-like behavior. In conclusion, BPS-exposed NODEF mice exhibited sex and diet-related changes in hyperglycemia, behaviors and immune endpoints.

Tolerance of soya lecithin in children with non-immunoglobulin E-mediated soya allergy: a randomised, double-blind, cross-over trial.

BACKGROUND: Soya lecithin is present in a wide variety of foods regularly consumed by children, in the form of an emulsifier or stabiliser. Children with non-immunoglobulin (Ig)E-mediated allergies who commonly have to avoid milk and soya will have a significantly restrictive diet with reduced alternative foods if soya lecithin also has to be eliminated. The present study aimed to establish whether children with non-IgE-mediated gastrointestinal soya allergy react to soya lecithin in food products. METHODS: A double-blind, cross-over study was performed in soya-allergic children aged between 8 months and 5 years. Eligible children had their soya allergy status confirmed with a home challenge. Children were randomly assigned to either placebo or challenge dose of soya lecithin (1.5 g per day) in a custom-made biscuit. This was followed by a 1-week washout period and cross-over to another 1 week of challenge or placebo dose. Symptoms were recorded prior to commencing the study and at the end of each week's challenge. RESULTS: Twenty-two children, 16 boys, with a median age of 44 months (range 21-58 months) were recruited, although only 20 completed the full study. The median number of foods avoided in addition to soya was 3. Over the challenge period, the parents reported reactions in six cases: five cases (23%) to the placebo and one case (5%) to the challenge dose. There was no statistical difference (P = 0.025) between the groups. CONCLUSIONS: One child with a non-IgE-mediated gastrointestinal allergy had a slight reaction to soya lecithin. Although single cases may react to soya lecithin, we suggest that soya lecithin should be included in children with this delayed allergy, unless they have a confirmed reaction to traces of soya within this emulsifier.

Dietary factors and risk of gout and hyperuricemia: a meta-analysis and systematic review.

BACKGROUND AND OBJECTIVES: To evaluate the associations of dietary factors and the risk of gout and hyperuricemia. METHODS AND STUDY DESIGN: PubMed and Embase databases were searched from inception to June 2017 for eligible studies. Nineteen prospective cohort or cross-sectional studies with adequate sample sizes are included, all involving red meat, seafoods, alcohol, fructose, dairy products, soy foods, high-purine vegetables and coffee. RESULTS: Meta-analysis revealed several dietary associations with gout risk: red meat: OR 1.29 (95% CI 1.16-1.44); seafoods: OR 1.31 (95% CI 1.01-1.68); alcohol: OR 2.58 (95% CI 1.81-3.66); fructose: OR 2.14 (95% CI 1.65- 2.78); dairy products: OR 0.56 (95% CI 0.44-0.70); soy foods: OR 0.85 (95% CI 0.76-0.96); high-purine vegetables: OR 0.86 (95% CI 0.75-0.98); coffee: OR 0.47 (95% CI 0.37-0.59).Dietary association with hyperuricemia risk (red meat: OR 1.24 (95% CI 1.04-1.48); seafoods: OR 1.47 (95% CI 1.16-1.86); alcohol: OR 2.06 (95% CI 1.60-2.67); fructose: OR 1.85 (95% CI 1.66-2.07); dairy products: OR 0.50 (95% CI 0.37-0.66); soy foods: OR 0.70 (95% CI 0.56-0.88); high-purine vegetables ingestion: OR 1.10 (95% CI 0.88-1.39), P=0.39; coffee:OR0.76 in men (95% CI 0.55-1.06), OR 1.58 in women (95% CI 1.16-2.16). CONCLUSION: The risk of hyperuricemia and gout is positively correlated with the intake of red meat, seafoods, alcohol or fructose, and negatively with dairy products or soy foods. High-purine vegetables showed no association with hyperuricemia, but negative association with gout. Coffee intake is negatively associated with gout risk, whereas it may be associated with increased hyperuricemia risk in women but decreased risk in men.

Surfing as a risk factor for sensitization to poly(γ-glutamic acid) in fermented soybeans, natto, allergy.

BACKGROUND: Poly(γ-glutamic acid) (PGA) is an allergen in natto, fermented soybeans, which causes late-onset anaphylaxis. We hypothesized that jellyfish stings sensitize adults to PGA because a surfer had allergies to both natto and jellyfish, whose sting contains PGA. The aim of the study was to identify behavioral factors, such as marine sports, associated with PGA sensitization. METHODS: Outpatients diagnosed with food allergies based on relevant clinical history, positive skin test and/or food challenge test answered a questionnaire during a regular visit in 2016. RESULTS: Questionnaire data from 140 outpatients were analyzed. These patients were divided into two groups: natto allergy group (13 patients, M:F = 10:3, mean age 40.6 years) and non-natto allergy group (127 patients, M:F = 46:81, mean age 44.5 years). All patients with natto allergy had positive results in skin prick test and basophil activation test with PGA. Of these, 92.3% had a marine sport hobby, especially surfing (84.6%). PGA sensitization was independently associated with marine sports (odds ratio, 278.0, 95 percent confidence interval, 36.9-6315.9, p < 0.001) adjusted for male sex and sea bathing, but not with male sex or sea bathing. In addition, although there was no significant difference in the experience of marine sports between natto and non-natto allergy groups, the natto allergy group participated significantly more frequently in marine sports than the non-natto allergy group (p < 0.001). There was no significant difference between natto consumption amount and PGA sensitization. CONCLUSIONS: Surfing is a risk factor for PGA sensitization in those with allergy to natto.

Nutrition research in cognitive impairment/dementia, with a focus on soya and folate.

Observational studies and treatment trials investigating nutrition and cognitive function, with a focus on folate and soya and dementia, were reviewed. Data suggested that effects of folic acid based interventions may only be shown before cognitive decline is evident and/or if people are folate deficient. In older people in Indonesia, Hawai'i and China, tofu, which can contain high levels of phytoestrogens, was found to increase dementia risk. This association was not mediated by a vegetarian diet, socioeconomic status, formaldehyde, thyroid function, or loss of teeth. On the other hand, human observational and animal treatment studies suggested that tempe, a fermented soya product containing phytoestrogens and folate, reduced dementia risk and improved memory. High oestrogen levels were found to increase dementia risk in older women. However, in women with adequate serum folate, high oestrogen levels did not confer additional dementia risk and may protect ageing neurons. In conclusion, reviews seem to suggest that folic acid interventions are only effective on cognitive outcomes in people who are folate deficient and do not have cognitive impairment. Frequent consumption of tofu may have detrimental effects on memory and increase dementia risk in older East Asian people, while tempe may reduce these risks. Possibly folate in tempe offsets the potential negative effects of oestrogenic compounds on ageing neurons.

Lifetime Genistein Intake Increases the Response of Mammary Tumors to Tamoxifen in Rats.

PURPOSE: Whether it is safe for estrogen receptor-positive (ER+) patients with breast cancer to consume soy isoflavone genistein remains controversial. We compared the effects of genistein intake mimicking either Asian (lifetime) or Caucasian (adulthood) intake patterns to that of starting its intake during tamoxifen therapy using a preclinical model. EXPERIMENTAL DESIGN: Female Sprague-Dawley rats were fed an AIN93G diet supplemented with 0 (control diet) or 500 ppm genistein from postnatal day 15 onward (lifetime genistein). Mammary tumors were induced with 7,12-dimethylbenz(a)anthracene (DMBA), after which a group of control diet-fed rats were switched to genistein diet (adult genistein). When the first tumor in a rat reached 1.4 cm in diameter, tamoxifen was added to the diet and a subset of previously only control diet-fed rats also started genistein intake (post-diagnosis genistein). RESULTS: Lifetime genistein intake reduced de novo resistance to tamoxifen, compared with post-diagnosis genistein groups. Risk of recurrence was lower both in the lifetime and in the adult genistein groups than in the post-diagnosis genistein group. We observed downregulation of unfolded protein response (UPR) and autophagy-related genes (GRP78, IRE1α, ATF4, and Beclin-1) and genes linked to immunosuppression (TGFß and Foxp3) and upregulation of cytotoxic T-cell marker CD8a in the tumors of the lifetime genistein group, compared with controls, post-diagnosis, and/or adult genistein groups. CONCLUSIONS: Genistein intake mimicking Asian consumption patterns improved response of mammary tumors to tamoxifen therapy, and this effect was linked to reduced activity of UPR and prosurvival autophagy signaling and increased antitumor immunity. Clin Cancer Res; 23(3); 814-24. ©2017 AACR.

Prenatal supplementation with Corn Soya Blend Plus reduces the risk of maternal anemia in late gestation and lowers the rate of preterm birth but does not significantly improve maternal weight gain and birth anthropometric measurements in rural Cambodian women: a randomized trial.

BACKGROUND: Corn Soya Blend (CSB) Plus is a fortified dietary supplement used to help Cambodian women meet their nutritional requirements in pregnancy, although little is known about its ability to improve pregnancy outcomes. OBJECTIVE: This study assessed the effect of prenatal CSB Plus supplementation on birth weight and secondary outcomes of low birth weight (<2500 g), small for gestational age, birth length and head circumference, preterm birth (<37 wk), maternal weight gain, and anemia at 24-28 wk, 30-32 wk, and 36-38 wk of gestation among rural Cambodian women. DESIGN: A cluster-randomized trial was conducted in 75 villages in Kampong Chhnang Province, in which 547 women received CSB Plus (treatment) during the first trimester until delivery or continued their normal diet (control) based on their village residence. All women received routine daily iron folic acid tablets and were treated with additional iron folic acid if they were anemic (hemoglobin <11 g/dL). Cluster-adjusted linear mixed-effect and logistic regression models were used to examine group differences. RESULTS: There was no significant difference in birth weight between the CSB Plus and control group (46 g; 95% CI: -31, 123 g; P = 0.24). Significant reductions were observed in preterm birth (OR = 0.33; 95% CI: 0.12, 0.89) and anemia at 36-38 wk (OR = 0.51; 95% CI: 0.34, 0.77). There were no significant differences in low birth weight, small for gestational age, birth length, head circumference, or maternal weight gain. A higher rate of fetal loss was observed in the treatment group (10.2% compared with 3.7%; P < 0.01). CONCLUSIONS: In Cambodian women, CSB Plus consumed during pregnancy did not significantly increase maternal weight gain or improve birth size but did reduce maternal anemia in late gestation and preterm birth in comparison with women consuming a normal diet. The unexpectedly higher rate of fetal loss in the treatment group is concerning and warrants further investigation. This trial was registered at clinicaltrials.gov as NCT01413776.

[A Systematic Review of the Acceptable Intake Level of Vitamin K among Warfarin Users].

The interaction of warfarin and vitamin K is a clinically significant issue. This study investigated the acceptable intake level of vitamin K among warfarin users by means of a systematic review. We searched two databases (PubMed and "Igaku chuo zasshi")for articles about adverse events arising from interaction of warfarin and vitamin K, published until October 2014. Of 1,310 citations retrieved, 16 studies met the selection criteria for examination of the upper limit, and 6 studies dealt with amounts below the limit. The intake of vitamin K in warfarin patients was acceptable in the range of 25-325 µg/day, with a maximum daily variation of 292 µg, and a value of 150 µg/day seemed optimum. When these results were applied to usual foods, except for dietary supplements or health foods, the only prohibited foods were fermented soybean (natto) and foods containing it, while green leafy vegetables could be acceptable if their intake is limited.

Effect of NaFeEDTA-fortified soy sauce on zinc absorption in children.

NaFeEDTA has been applied in many foods as an iron fortificant and is used to prevent iron deficiency in Fe-depleted populations. In China, soy sauce is fortified with NaFeEDTA to control iron deficiency. However, it is unclear whether Fe-fortified soy sauce affects zinc absorption. To investigate whether NaFeEDTA-fortified soy sauce affects zinc absorption in children, sixty children were enrolled in this study and randomly assigned to three groups (10 male children and 10 female children in each group). All children received daily 3 mg of (67)Zn and 1.2 mg of dysprosium orally, while the children in the three groups were supplemented with NaFeEDTA-fortified soy sauce (6 mg Fe, NaFeEDTA group), FeSO4-fortified soy sauce (6 mg Fe, FeSO4 group), and no iron-fortified soy sauce (control group), respectively. Fecal samples were collected during the experimental period and analyzed for the Zn content, (67)Zn isotope ratio and dysprosium content. The Fe intake from NaFeEDTA-fortified and FeSO4-fortified groups was significantly higher than that in the control group (P < 0.0001). The daily total Zn intake was not significantly different among the three groups. There were no significant differences in fractional Zn absorption (FZA) (P = 0.3895), dysprosium recovery (P = 0.7498) and Zn absorption (P = 0.5940) among the three groups. Therefore, NaFeEDTA-fortified soy sauce does not affect Zn bioavailability in children.

Can soy intake affect serum uric acid level? Pooled analysis from two 6-month randomized controlled trials among Chinese postmenopausal women with prediabetes or prehypertension.

PURPOSE: Hyperuricemia is a recognized risk factor for cardiovascular diseases. Soy foods contain a moderate amount of purine and may predispose to raised serum uric acid (UA). However, no study has examined the long-term effect of soy intake on UA levels. We examined whether consumption of soy foods and isoflavone extracts for 6 months altered serum UA. METHODS: The analysis included two randomized controlled trials (soy protein trial and whole soy trial) among total 450 postmenopausal women with either prehypertension or prediabetes. We conducted a pooled analysis by combining participants from both the soy flour and soy protein groups (combined soy foods group), participants from both the isoflavone and daidzein groups (combined isoflavone group) and participants from both milk placebo groups. Fasting venous samples were obtained at baseline and the end of the trial for serum UA analysis. RESULTS: In the pooled data, 417 subjects completed the study according to protocol. The baseline serum UA levels were comparable among the three combined groups. There was a lower decrease in UA levels among women in the combined soy foods group compared with women in the other two groups (p = 0.028 and 0.026). The net decrease and % decrease in UA were 14.5 µmol/L (95 % CI 1.93-25.6, p = 0.023) or 4.9 % (95 % CI 1.3-8.5 %, p = 0.023) between the combined soy foods group and placebo group. CONCLUSIONS: Among Chinese postmenopausal women with either prehypertension or prediabetes, soy intake did not increase urate levels.

Soy food and isoflavone intake and endometrial cancer risk: the Japan Public Health Center-based prospective study.

OBJECTIVE: Compared with western populations, the consumption of soy foods among Japanese is very high and the incidence of endometrial cancer very low. We evaluated the association of soy food and isoflavone intake with endometrial cancer risk in Japanese women. DESIGN: Prospective cohort study. SETTING: Ten public health centre areas in Japan. POPULATION: Forty nine thousand one hundred and twenty-one women of age 45-74 years who responded to a 5-year follow-up survey questionnaire. METHODS: Intakes of soy foods as well as other covariates were assessed in 1995-1998 by a self-administered food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). MAIN OUTCOME MEASURE: Incidence of endometrial cancer. RESULTS: During an average of 12.1 years of follow up, 112 newly diagnosed endometrial cancer cases were identified. Energy-adjusted intakes of soy food and isoflavone were not associated with the risk of endometrial cancer. The multivariate-adjusted HR per 25 g/day increase in the intake of soy food was 1.02 (95% CI 0.94-1.10), and the corresponding value for isoflavone intake per 15 mg/day was 1.01 (95% CI 0.84-1.22). CONCLUSION: In this population-based prospective cohort study of Japanese women, we observed no evidence of a protective association between soy food or isoflavone intake and endometrial cancer risk.

Soy and phytoestrogens: possible side effects.

Phytoestrogens are present in certain edible plants being most abundant in soy; they are structurally and functionally analogous to the estrogens. Phytoestrogens have been applied for compensation of hormone deficiency in the menopause. At the same time, soy products are used in infant food and other foodstuffs. Furthermore, soy is applied as animal fodder, so that residual phytoestrogens and their active metabolites such as equol can remain in meat and influence the hormonal balance of the consumers. There have been only singular reports on modified gender-related behavior or feminization in humans in consequence of soy consumption. In animals, the intake of phytoestrogens was reported to impact fertility, sexual development and behavior. Feminizing effects in humans can be subtle and identifiable only statistically in large populations.

Gluten contamination of naturally gluten-free flours and starches used by Canadians with celiac disease.

A large national investigation into the extent of gluten cross-contamination of naturally gluten-free ingredients (flours and starches) sold in Canada was performed. Samples (n = 640) were purchased from eight Canadian cities and via the internet during the period 2010-2012 and analysed for gluten contamination. The results showed that 61 of the 640 (9.5%) samples were contaminated above the Codex-recommended maximum level for gluten-free products (20 mg kg⁻¹) with a range of 5-7995 mg kg⁻¹. For the ingredients that were labelled gluten-free the contamination range (5-141 mg kg⁻¹) and number of samples were lower (3 of 268). This picture was consistent over time, with approximately the same percentage of samples above 20 mg kg⁻¹ in both the initial set and the subsequent lot. Looking at the total mean (composite) contamination for specific ingredients the largest and most consistent contaminations come from higher fibre ingredients such as soy (902 mg kg⁻¹), millet (272 mg kg⁻¹) and buckwheat (153 mg kg⁻¹). Of the naturally gluten-free flours and starches tested that do not contain a gluten-free label, the higher fibre ingredients would constitute the greatest probability of being contaminated with gluten above 20 mg kg⁻¹.

Hypoallergenicity of various miso pastes manufactured in Japan.

Miso paste (miso), a fermented soybean food, is popular in Japan and other Asian countries. However, the soybean is known to induce an allergenic response in some individuals. In the present study, we evaluated the allergenicity of various kinds of miso available in Japan. Total proteins were extracted from Amakuti-kome miso, Karakuti-kome miso, Mugi-miso and Mame-miso, and the protein profiles were analyzed. The major protein bands detected in the intact soybean extract were not present in any of the miso samples, which instead showed various low molecular weight protein bands of approximately 10-25 kDa. The existence levels of six major soybean allergens were determined by Western blotting using specific antibodies. We found that the allergen levels varied among miso and allergen types; however, allergen levels were consistently lower in miso than in the soybean extract. We obtained similar results for IgE-ELISA experiments using serum IgE from soybean allergy patients. Taken together, these results indicate that compared to soybean extract, various types of miso contain small quantities of intact soybean allergens. Additionally, several lines of evidence indicated that the allergen levels were exceptionally low in the dark-colored Karakuti-kome miso and Mame-miso, which are produced with relatively long fermentation periods, suggesting that the duration of fermentation might be a key factor in the hypoallergenicity of miso.

[Postmenopausal bleeding and dietary supplements: a possible causal relationship with hop- and soy-containing preparations]. / Postmenopauzaal bloedverlies en voedingssupplementen: mogelijk causaal verband met hop- en sojabevattende preparaten.

BACKGROUND: Many women suffering from menopausal symptoms choose to use dietary supplements made from plants for the relief of their symptoms. These herbal preparations can have phyto-oestrogenic properties. Although probably regarded as 'safe', such preparations can cause adverse drug reactions. CASE DESCRIPTION: We describe four patient reports to the Netherlands Pharmacovigilance Centre Lareb. All of these patients suffered from postmenopausal bleeding and used hop- and soy-containing dietary supplements. The reports were all from the same gynaecologist. CONCLUSION: Postmenopausal bleeding has many possible causes. The use of dietary supplements containing ingredients with phyto-oestrogenic properties, such as hop and soy, may give rise to proliferation of the endometrium. The four reports to Lareb illustrate the association between the use of these supplements and postmenopausal bleeding. Such products are available as over-the-counter preparations and consumers often mistakenly believe that they do not cause adverse drug reactions. During the diagnostic phase, it is important to be aware that the use of a dietary supplement or an herbal drug having phyto-oestrogenic properties may be a possible cause of postmenopausal bleeding.

[Soy isoflavones and human health: breast cancer and puberty timing]. / Isoflavonas de soya y salud humana: cáncer de mama y sincronización de la pubertad.

BACKGROUND: Accumulated exposure to high levels of estrogen is associated with an increased incidence of breast cancer. Thus, factors such as early puberty, late menopause and hormone replacement therapy are considered to be risk factors, whereas early childbirth, breastfeeding and puberty at a later age are known to consistently decrease the lifetime breast cancer risk. Epidemiological studies suggest that consumption of isoflavones correlates with a lower incidence of breast cancer. Data from human intervention studies show that the effects of isoflavones on early breast cancer markers differ between pre- and post-menopausal women. The reports from experimental animals (rats and mice) on mammary tumors are variable. These results taken together with heterogeneous outcomes of human interventions, have led to a controversy surrounding the intake of isoflavones to reduce breast cancer risk. This review summarizes recent studies and analyzes factors that could explain the variability of results. In mammary tissue, from the cellular endocrine viewpoint, we analyze the effect of isoflavones on the estrogen receptor and their capacity to act as agonists or antagonists. On the issue of puberty timing, we analyze the mechanisms by which girls, but not boys, with higher prepuberal isoflavone intakes appear to enter puberty at a later age.

Early life exposure to genistein and daidzein disrupts structural development of reproductive organs in female mice.

In mice, exposure to isoflavones (ISO), abundant in soy infant formula, during the first 5 d of life alters structural and functional development of reproductive organs. Effects of longer exposures are unknown. The study objective was to evaluate whether exposure to a combination of daidzein and genistein in the first 10 compared to 5 d of life results in greater adverse effects on ovarian and uterine structure in adult mice. Thirteen litters of 8-12 pups were cross-fostered and randomized to corn oil or ISO (2 mg daidzein + 5 mg genistein/kg body weight/d) for the first 5 or 10 d of life. The 10-d protocol mimicked the period when infants are fed soy protein formula (SPF) but avoids the time when suckling pups can consume mother's diet. Body and organ weights, and histology of ovaries and uteri were analyzed. There were no differences in the ovary or uterus weight, number of ovarian follicles, number of multiple oocyte follicles, or percent of ovarian cysts with 5 or 10 d ISO intervention compared to respective controls. The 10-d ISO group had higher body weights from 6 d to 4 mo of age and a higher percent of hyperplasia in the oviduct than the respective control. Lower number of ovarian corpus lutea and a higher incidence of abnormal changes were reported in the uteri of both ISO groups compared to their respective controls. Five and 10-d exposure to ISO had similar long-lasting adverse effects on the structure of ovaries and uterus in adult mice. Only the 10-d ISO exposure resulted in greater body weight gain at adulthood.