Neither soy nor isoflavone intake affects male reproductive hormones: An expanded and updated meta-analysis of clinical studies

Concerns that the phytoestrogens (isoflavones) in soy may feminize men continue to be raised. Several studies and case-reports describing feminizing effects including lowering testosterone levels and raising estrogen levels in men have been published. For this reason, the clinical data were meta-analyzed to determine whether soy or isoflavone intake affects total testosterone (TT), free testosterone (FT), estradiol (E₂), estrone (E₁), and sex hormone binding globulin (SHBG). PubMed and CAB Abstracts databases were searched between 2010 and April 2020, with use of controlled vocabulary specific to the databases. Peer-reviewed studies published in English were selected if (1) adult men consumed soyfoods, soy protein, or isoflavone extracts (from soy or red clover) and [2] circulating TT, FT, SHBG, E2 or E1 was assessed. Data were extracted by two independent reviewers. With one exception, studies included in a 2010 meta-analysis were included in the current analysis. A total of 41 studies were included in the analyses. TT and FT levels were measured in 1753 and 752 men, respectively; E₂ and E₁ levels were measured in 1000 and 239 men, respectively and SHBG was measured in 967 men. Regardless of the statistical model, no significant effects of soy protein or isoflavone intake on any of the outcomes measured were found. Sub-analysis of the data according to isoflavone dose and study duration also showed no effect. This updated and expanded meta-analysis indicates that regardless of dose and study duration, neither soy protein nor isoflavone exposure affects TT, FT, E₂ or E₁ levels in men

Seaweed and Soy: Companion Foods in Asian Cuisine and Their Effects on Thyroid Function in American Women

Seaweeds and soy are two commonly eaten foods in Asia. Both have been reported to affect thyroid function, seaweed because of its iodine content and soy because of its goitrogenic effect. Twenty-five healthy postmenopausal women (mean age 58 years) completed a double-blinded randomized crossover study. Ten capsules (5 g/day) of placebo or seaweed (Alaria exculenta), providing 475 ug of iodine/day, were consumed daily for 7 weeks. A powdered soy protein isolate (Solae Co., St. Louis, MO) providing 2 mg of isoflavones/kg of body weight, was given daily during the last week of each treatment arm. On average, this provided 141.3 mg of isoflavones/day and 67.5 g of protein/day. Blood samples and 48-hour urine samples were collected before and after each intervention period, and urinary I/C (ug of iodine/g of creatinine) and serum thyroxine, free thyroxine index, total triiodothyronine, and thyroidstimulating hormone (TSH) were measured. Seaweed ingestion increased I/C concentrations (P \u3c .0001) and serum TSH (P \u3c .0001) (1.69 +/- 0.22 vs. 2.19 +/- 0.22 uU/mL, mean +/- SE). Soy supplementation did not affect thyroid end points. Seven weeks of 5 g/day seaweed supplementation was associated with a small but statistically significant increase in TSH. Soy protein isolate supplementation was not associated with changes in serum thyroid hormone concentrations

Open tension free repair of inguinal hernias; the Lichtenstein technique

BACKGROUND: Recurrences have been a significant problem following hernia repair. Prosthetic materials have been increasingly used in hernia repair to prevent recurrences. Their use has been associated with several advantages, such as less postoperative pain, rapid recovery, low recurrence rates. METHODS: In this retrospective study, 540 tension-free inguinal hernia repairs were performed between August 1994 and December 1999 in 510 patients, using a polypropylene mesh (Lichtenstein technique). The main outcome measure was early and late morbidity and especially recurrence. RESULTS: Inguinal hernia was indirect in 55 % of cases (297 patients), direct in 30 % (162 patients) and of the pantaloon (mixed) type in 15 % (81 patients). Mean patient age was 53.7 years (range, 18 – 85). Follow-up was completed in 407 patients (80 %) by clinical examination or phone call. The median follow-up period was 3.8 years (range, 1 – 6 years). Seroma and hematoma formation requiring drainage was observed in 6 and 2 patients, respectively, while transient testicular swelling occurred in 5 patients. We have not observed acute infection or abscess formation related to the presence of the foreign body (mesh). In two patients, however, a delayed rejection of the mesh occurred 10 months and 4 years following surgery. There was one recurrence of the hernia (in one of these patients with late mesh rejection) (recurrence rate = 0.2 %). Postoperative neuralgia was observed in 5 patients (1 %). CONCLUSION: Lichtenstein tension-free mesh inguinal hernia repair is a simple, safe, comfortable, effective method, with extremely low early and late morbidity and remarkably low recurrence rate and therefore it is our preferred method for hernia repair since 1994

Isoflavone metabolism in domestic cats (Felis catus): comparison of plasma metabolites detected after ingestion of two different dietary forms of genistein and daidzein

Some felid diets contain isoflavones but the metabolic capacity of cats toward isoflavones is relatively unknown, despite the understanding that isoflavones have divergent biological potential according to their metabolite end products. The objective of this study was to determine the plasma metabolites detectable in domestic cats after exposure to 2 different dietary forms of isoflavones, either as a soy extract tablet ( n = 6) or as part of a dietary matrix ( n = 4). Serial blood samples were collected after isoflavone exposure to identify the plasma metabolites of each cat. Genistein was detected in its unconjugated form or as a monosulfate. Daidzein was detected as both a mono- and disulfate as well as in its unconjugated form. Other daidzein metabolites detected included equol mono- and disulfate, dihydrodaidzein, and O -desmethylangolensin. No β -glucuronide metabolites of either isoflavone were detected. Equol was produced in markedly fewer cats after ingestion of a soy extract tablet as a single oral bolus compared with cats consuming an isoflavone-containing diet. The detectable metabolites of the isoflavones, genistein and daidzein, in domestic cat plasma after dietary ingestion has been described in the present study for the first time. The metabolic capacity for isoflavones by domestic cats appears to be efficient, with only minimal proportions of the ingested amount detected in their unconjugated forms. This has implications for the potential of isoflavones to exert physiological activity in the domestic cat when consumed at concentrations representative of typical dietary intake

Analysis of jak2 catalytic function by peptide microarrays: The role of the JH2 domain and V617F mutation

Janus kinase 2 (JAK2) initiates signaling from several cytokine receptors and is required for biological responses such as erythropoiesis. JAK2 activity is controlled by regulatory proteins such as Suppressor of Cytokine Signaling (SOCS) proteins and protein tyrosine phosphatases. JAK2 activity is also intrinsically controlled by regulatory domains, where the pseudokinase (JAK homology 2, JH2) domain has been shown to play an essential role. The physiological role of the JH2 domain in the regulation of JAK2 activity was highlighted by the discovery of the acquired missense point mutation V617F in myeloproliferative neoplasms (MPN). Hence, determining the precise role of this domain is critical for understanding disease pathogenesis and design of new treatment modalities. Here, we have evaluated the effect of inter-domain interactions in kinase activity and substrate specificity. By using for the first time purified recombinant JAK2 proteins and a novel peptide micro-array platform, we have determined initial phosphorylation rates and peptide substrate preference for the recombinant kinase domain (JH1) of JAK2, and two constructs comprising both the kinase and pseudokinase domains (JH1-JH2) of JAK2. The data demonstrate that (i) JH2 drastically decreases the activity of the JAK2 JH1 domain, (ii) JH2 increased the Kmfor ATP (iii) JH2 modulates the peptide preference of JAK2 (iv) the V617F mutation partially releases this inhibitory mechanism but does not significantly affect substrate preference or Kmfor ATP. These results provide the biochemical basis for understanding the interaction between the kinase and the pseudokinase domain of JAK2 and identify a novel regulatory role for the JAK2 pseudokinase domain. Additionally, this method can be used to identify new regulatory mechanisms for protein kinases that provide a better platform for designing specific strategies for therapeutic approaches

The Janus kinases (Jaks)

The Janus kinase (Jak) family is one of ten recognized families of non-receptor tyrosine kinases. Mammals have four members of this family, Jak1, Jak2, Jak3 and Tyrosine kinase 2 (Tyk2). Birds, fish and insects also have Jaks. Each protein has a kinase domain and a catalytically inactive pseudo-kinase domain, and they each bind cytokine receptors through amino-terminal FERM (Band-4.1, ezrin, radixin, moesin) domains. Upon binding of cytokines to their receptors, Jaks are activated and phosphorylate the receptors, creating docking sites for signaling molecules, especially members of the signal transducer and activator of transcription (Stat) family. Mutations of the Drosophila Jak (Hopscotch) have revealed developmental defects, and constitutive activation of Jaks in flies and humans is associated with leukemia-like syndromes. Through the generation of Jak-deficient cell lines and gene-targeted mice, the essential, nonredundant functions of Jaks in cytokine signaling have been established. Importantly, deficiency of Jak3 is the basis of human autosomal recessive severe combined immunodeficiency (SCID); accordingly, a selective Jak3 inhibitor has been developed, forming a new class of immunosuppressive drugs

Consumption of a soy drink has no effect on cognitive function but may alleviate vasomotor symptoms in post-menopausal women; a randomised trial

Purpose: Cognitive decline is commonly reported during the menopausal transition, with memory and attention being particularly affected. The aim of this study was to investigate the effects of a commercially available soy drink on cognitive function and menopausal symptoms in post-menopausal women. Methods: 101 post-menopausal women, aged 44–63 years, were randomly assigned to consume a volume of soy drink providing a low (10 mg/day; control group), medium (35 mg/day), or high (60 mg/day) dose of isoflavones for 12 weeks. Cognitive function (spatial working memory, spatial span, pattern recognition memory, 5-choice reaction time, and match to sample visual search) was assessed using CANTAB pre- and post-the 12 week intervention. Menopausal symptoms were assessed using Greene’s Climacteric Scale. Results: No significant differences were observed between the groups for any of the cognitive function outcomes measured. Soy drink consumption had no effect on menopausal symptoms overall; however, when women were stratified according to the severity of vasomotor symptoms (VMS) at baseline, women with more severe symptoms at baseline in the medium group had a significant reduction (P = 0.001) in VMS post-intervention (mean change from baseline score: − 2.15 ± 1.73) in comparison to those with less severe VMS (mean change from baseline score: 0.06 ± 1.21). Conclusions: Soy drink consumption had no effect on cognitive function in post-menopausal women. Consumption of ~ 350 ml/day (35 mg IFs) for 12 weeks significantly reduced VMS in those with more severe symptoms at baseline. This finding is clinically relevant as soy drinks may provide an alternative, natural, treatment for alleviating VMS, highly prevalent among western women

Guidance from an NIH Workshop on Designing, Implementing, and Reporting Clinical Studies of Soy Interventions1–4

The NIH sponsored a scientific workshop, “Soy Protein/Isoflavone Research: Challenges in Designing and Evaluating Intervention Studies,” July 28–29, 2009. The workshop goal was to provide guidance for the next generation of soy protein/isoflavone human research. Session topics included population exposure to soy; the variability of the human response to soy; product composition; methods, tools, and resources available to estimate exposure and protocol adherence; and analytical methods to assess soy in foods and supplements and analytes in biologic fluids and other tissues. The intent of the workshop was to address the quality of soy studies, not the efficacy or safety of soy. Prior NIH workshops and an evidence-based review questioned the quality of data from human soy studies. If clinical studies are pursued, investigators need to ensure that the experimental designs are optimal and the studies properly executed. The workshop participants identified methodological issues that may confound study results and interpretation. Scientifically sound and useful options for dealing with these issues were discussed. The resulting guidance is presented in this document with a brief rationale. The guidance is specific to soy clinical research and does not address nonsoy-related factors that should also be considered in designing and reporting clinical studies. This guidance may be used by investigators, journal editors, study sponsors, and protocol reviewers for a variety of purposes, including designing and implementing trials, reporting results, and interpreting published epidemiological and clinical studies