Effect of soy in men with type 2 diabetes mellitus and subclinical hypogonadism: a randomised controlled study

Context: Isoflavones found in soy products have a chemical structure similar to estrogen, leading to concerns of an adverse estrogenic effect in men, particularly in those with type 2 diabetes mellitus (T2DM) who have low testosterone levels due to hypogonadism. Objective: The primary outcome was change in total testosterone levels. The secondary outcomes were the changes in glycaemia and cardiovascular risk markers. Design: Randomised double blind parallel study. Setting: Secondary care setting in UK. Participants: 200 men with T2DM with a total testosterone level≤12nmol/L Intervention: 15g soy protein with 66mg of isoflavones (SPI) or 15g soy protein alone without isoflavones (SP) daily as snack bars for three months. Results: There was no change in either total testosterone or in absolute free testosterone levels with either SPI or SP. There was an increase in TSH and reduction in fT4 (p<0.01) after SPI supplementation. Glycaemic control improved with a significant reduction in HbA1c (-4.19(7.29)mmol/mol,p<0.01) and HOMA-IR after SPI. Cardiovascular risk improved with a reduction in triglycerides, CRP and diastolic BP (p<0.05) with SPI versus SP supplementation. There was 6% improvement in 10-year coronary heart disease risk after three months of SPI supplementation. Endothelial function improved with both SPI and SP supplementation (p<0.01) with an increased reactive hyperemia index that was greater for the SPI group (p<0.05). Conclusions: Testosterone levels were unchanged and there was a significant improvement in glycaemia and cardiovascular risk markers with SPI compared to SP alone over three months. There was significant increase in TSH and a reduction in fT4

The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: A randomized, double-blind, crossover study

Context: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism. Objective: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism. Design and Setting: We conducted a randomized, double-blind, crossover study in a tertiary care setting. Participants: Sixty patients with subclinical hypothyroidism participated in the study. Intervention: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2 mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16 mg phytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period. Main Outcome Measures: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP). Results: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2 mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged. Conclusion: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients. Copyright © 2011 by The Endocrine Society

Association of endocrine active environmental compounds with body mass index and weight loss following bariatric surgery

IntroductionThe objective of this study was to study associations of a wide range of halogenated biphenyls, dibenzo‐p‐dioxins, dibenzofurans, and diphenylethers with body mass index (BMI) and evaluate changes in their concentration following bariatric surgery.MethodsSubcutaneous fat, visceral fat, and liver tissue samples were collected from 106 patients undergoing Roux‐en‐Y gastric bypass surgery for weight loss or patients who were undergoing abdominal surgery for non‐bariatric reasons. We measured concentrations of an extensive panel of chlorinated and brominated biphenyls, dioxins, and furans, and brominated diphenylethers in the samples. We conducted linear regression to examine associations with BMI, adjusting for age and gender. Changes in concentration for indicator chemicals were evaluated in samples collected following bariatric surgery in a small sub‐population.ResultsAfter adjustments for age and gender and correction for multiple testing, seven ortho‐chlorinated biphenyls, one non‐ortho‐chlorinated biphenyl, four PCDD/F’s and one ortho‐brominated biphenyl were associated with BMI. The strongest associations between BMI and lipid‐adjusted concentrations were seen with PCB‐105 in subcutaneous fat (beta=16.838 P‐val=1.45E‐06) PCB‐126 in visceral fat (beta=15.067 P‐val=7.72E‐06) and PCB‐118 (beta=14.101 P‐val=2.66E‐05) in liver. The concentrations of sum PCBs, chlorinated toxic equivalent quantity (TEQ's) and brominated compounds increased significantly with weight loss in subcutaneous fat in a group of ten individuals resampled up to five years after bariatric surgery and substantial weight loss.ConclusionWe show that selected polychlorinated biphenyls PCBs and structurally related polychlorinated dibenzo‐p‐dioxins dibenzofurans (PCDD/Fs) were associated with BMI. Concentrations of these lipophilic compounds in subcutaneous fat increased following bariatric surgery

Soy isoflavones improve cardiovascular disease risk markers in women during 1 the early menopause 2 1

BackgroundHormone replacement therapy may be beneficial for cardiovascular disease risk (CVR) in post-menopausal women. Soy isoflavones may act as selective estrogen receptor modulators. The aim of this study was to evaluate whether soy isoflavones had an effect on CVR markers.MethodsThe expected 10-year risk of cardiovascular disease and mortality were calculated as a secondary endpoint from a double blind randomised parallel study involving 200 women (mean age 55 years, Caucasian, Hull, UK, 2012) in the early menopause who were randomised to 15 g soy protein with 66 mg isoflavone (SPI) or 15 g soy protein alone (depleted of all isoflavones; SP) given as a snack bar between meals daily for 6 months. Age, diabetes, smoking, blood pressure and lipid profiles were used to calculate CVR using the Framingham CVR engine.ResultsSPI treatment resulted in a significant reduction in the metabolic parameters and systolic blood pressure compared to SP (p < 0.01). There were no changes in fasting lipid profile and diastolic blood pressure with either treatment. At 6 months, changes in these parameters with SPI treatment were reflected in a calculated 27% (p < 0.01) reduction in 10 year coronary heart disease risk, a 37% (p < 0.01) reduction in myocardial infarction risk, a 24% (p < 0.04) reduction in cardiovascular disease and 42% (p < 0.02) reduction in cardiovascular disease death risk.ConclusionsSupplementation with soy protein with isoflavones for 6 months significantly improved CVR markers and calculated CVR at 6 months during early menopause compared to soy protein without isoflavones

Aspartame sensitivity? : a double blind randomised crossover study

Background Aspartame is a commonly used intense artificial sweetener, being approximately 200 times sweeter than sucrose. There have been concerns over aspartame since approval in the 1980s including a large anecdotal database reporting severe symptoms. The objective of this study was to compare the acute symptom effects of aspartame to a control preparation. Methods This was a double-blind randomized cross over study conducted in a clinical research unit in United Kingdom. Forty-eight individual who has self reported sensitivity to aspartame were compared to 48 age and gender matched aspartame non-sensitive individuals. They were given aspartame (100mg)-containing or control snack bars randomly at least 7 days apart. The main outcome measures were acute effects of aspartame measured using repeated ratings of 14 symptoms, biochemistry and metabonomics. Results Aspartame sensitive and non-sensitive participants differed psychologically at baseline in handling feelings and perceived stress. Sensitive participants had higher triglycerides (2.05 ± 1.44 vs. 1.26 ± 0.84mmol/L; p value 0.008) and lower HDL-C (1.16 ± 0.34 vs. 1.35 ± 0.54 mmol/L; p value 0.04), reflected in 1H NMR serum analysis that showed differences in the baseline lipid content between the two groups. Urine metabonomic studies showed no significant differences. None of the rated symptoms differed between aspartame and control bars, or between sensitive and control participants. However, aspartame sensitive participants rated more symptoms particularly in the first test session, whether this was placebo or control. Aspartame and control bars affected GLP-1, GIP, tyrosine and phenylalanine levels equally in both aspartame sensitive and non-sensitive subjects. Conclusion Using a comprehensive battery of psychological tests, biochemistry and state of the art metabonomics there was no evidence of any acute adverse responses to aspartame. This independent study gives reassurance to both regulatory bodies and the public that acute ingestion of aspartame does not have any detectable psychological or metabolic effects in humans

The effect of phytoestrogen on thyroid in subclinical hypothyroidism: Randomized, double blind, crossover study

Objective: Soy phytoestrogens are suggested to impair thyroid function but the effects of pharmacological doses of soy phytoestrogens are unknown; therefore, this study was performed to determine the effect of high dose soy phytoestrogens (66 mg) on thyroid function in subclinical hypothyroidism. Design and setting: Randomized, double-blind, crossover study. Participants: Forty four patients with subclinical hypothyroidism. Intervention: Participants were randomly allocated to either 66 mg phytoestrogen with 30 g soy protein (active) or 0 mg phytoestrogen with 30 g soy protein (placebo) supplementation for 8 weeks, washed out for 8 weeks and then crossed over for another 8 week period. Main outcome measures: The primary outcome was progression to overt hypothyroidism with the secondary outcome measures were changes in thyroid function tests. Results: Two patients in this trial progressed into overt hypothyroidism after high dose phytoestrogen supplementation. TSH, free thyroxine and triiodothyronine did not differ between groups. Conclusion: A pharmacological dose of 66 mg of soy phytoestrogens did not increase the overt thyroid failure rate or alter thyroid function tests in patients with subclinical hypothyroidism

Deoxynivalenol biomarkers in the urine of UK vegetarians

Deoxynivalenol (DON) is produced by Fusarium graminearum and is one of the most commonly occurring trichothecenes. Vegetarians are alleged to be a high-risk group for DON exposure due to high intakes of cereals susceptible to the growth of the mycotoxin. This study provides the levels of DON and de-epoxi Deoxynivalenol (DOM-1) in urine analysed by liquid chromatography-mass spectrometry (LC-MS) in UK vegetarians. Over two consecutive days, morning urine samples were collected from 32 vegetarians and 31 UK adult volunteers, and associated food consumption 24 h prior to the sample was recorded. Statistically significant differences between the weight of the UK adults and vegetarians (t = 3.15. df = 61, p ≤ 0.005 two-tailed) were observed. The mean levels of DON in urine for adults on day 1 was 3.05 ng free DON/mg creatinine, and on day 2 was 2.98 ng free DON/mg creatinine. Even though high mean levels were observed, most adults were within the tolerable daily intake. However, for vegetarians, the mean level of urinary DON on day 1 was 6.69 ng free DON/mg creatinine, and on day 2 was 3.42 ng free DON/mg creatinine. These levels equate to up to 32% of vegetarians exceeding recommended tolerable daily intakes (TDI) of exposure (1 µg/kg b.w./day). View Full-Tex