Ketogenic nutritional therapy (KeNuT)-a multi-step dietary model with meal replacements for the management of obesity and its related metabolic disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-diet therapies in endocrinology and metabolism.

PURPOSE: The ketogenic nutritional therapy (KeNuT) is an effective dietary treatment for patients with obesity and obesity-related comorbidities, including type 2 diabetes, dyslipidaemia, hypertension, coronary artery disease, and some type of cancers. However, to date an official document on the correct prescription of the ketogenic diet, validated by authoritative societies in nutrition or endocrine sciences, is missing. It is important to emphasize that the ketogenic nutritional therapy requires proper medical supervision for patient selection, due to the complex biochemical implications of ketosis and the need for a strict therapeutic compliance, and an experienced nutritionist for proper personalization of the whole nutritional protocol. METHODS: This practical guide provides an update of main clinical indications and contraindications of ketogenic nutritional therapy with meal replacements and its mechanisms of action. In addition, the various phases of the protocol involving meal replacements, its monitoring, clinical management and potential side effects, are also discussed. CONCLUSION: This practical guide will help the healthcare provider to acquire the necessary skills to provide a comprehensive care of patients with overweight, obesity and obesity-related diseases, using a multistep ketogenic dietary treatment, recognized by the Club of the Italian Society of Endocrinology (SIE)-Diet Therapies in Endocrinology and Metabolism.

Testosterone supplementation and bone parameters: a systematic review and meta-analysis study.

BACKGROUND: The role of testosterone (T) replacement therapy (TRT) in subjects with late onset hypogonadism is still the object of an intense debate. METHODS: All observational studies and placebo-controlled or -uncontrolled randomized trials (RCTs) comparing the effect of TRT on different bone parameters were considered. RESULTS: Out of 349 articles, 36 were considered, including 3103 individuals with a mean trial duration of 66.6 weeks. TRT improves areal bone mineral density (aBMD) at the spine and femoral neck levels in observational studies, whereas placebo-controlled RTCs showed a positive effect of TRT only at lumber spine and when trials included only hypogonadal patients at baseline (total testosterone < 12 nM). The effects on aBMD were more evident in subjects with lower T levels at baseline and increased as a function of trial duration and a higher prevalence of diabetic subjects. Either T or estradiol increase at endpoint contributed to aBMD improvement. TRT was associated with a significant reduction of bone resorption markers in observational but not in controlled studies. CONCLUSION: TRT is able to inhibit bone resorption and increase bone mass, particularly at the lumbar spine level and when the duration is long enough to allow the anabolic effect of T and estrogens on bone metabolism to take place.

Selenium supplementation in the management of thyroid autoimmunity during pregnancy: results of the "SERENA study", a randomized, double-blind, placebo-controlled trial.

PURPOSE: Selenium is frequently in nutraceuticals for pregnancy, given its role on fertility and thyroid metabolism. However, most evidence rise from non-controlled studies. We aimed to evaluate the protective effect of selenium against thyroid autoimmunity during and after pregnancy. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was performed and promoted by the Young Italian Endocrinologists Group (EnGioI)-Italian Society of Endocrinology. Forty-five women with thyroiditis in pregnancy were enrolled and randomly assigned to L-selenomethionine (L-Se-Met) 83 mcg/day or placebo (PLB) and evaluated at 10 ± 2 (T1), 36 ± 2 weeks of gestation (T2) and 6 months after delivery (postpartum, PP). RESULTS: We measured a significant reduction of autoantibodies after pregnancy in L-Se-Met group [at PP: TgAb 19.86 (11.59-52.60), p < 0.01; TPOAb 255.00 (79.00-292.00), p < 0.01], and an antibodies titer's rebound in PLB group (TgAb 151.03 ± 182.9, p < 0.01; TPOAb 441.28 ± 512.18, p < 0.01). A significant increase in selenemia was measured in L-Se-Met group at T2 (91.33 ± 25.49; p < 0.01) and PP (93.55 ± 23.53; p = 0.02). Two miscarriage occurred in PLB. No differences were found in thyroid volume, echogenicity, quality of life, maternal/fetal complications. CONCLUSIONS: SERENA study demonstrated a beneficial effect of L-Se-Met supplementation on autoantibody titer during pregnancy and on postpartum thyroiditis recurrence.

Profiling of selenium absorption and accumulation in healthy subjects after prolonged L-selenomethionine supplementation.

PURPOSE: Autoimmune thyroiditis and its complications for the reproductive system are a growing problem. Selenium is a common ingredient in numerous food supplements recommended for thyroiditis and pregnancy. A fast, simple method to measure serum selenium concentration will improve knowledge of its pharmacokinetics and toxicity. AIM: To validate a useful method to measure serum selenium concentration and to study selenium absorption and accumulation in a prospective interventional study of prolonged treatment. METHODS: Thirty healthy volunteers received a single dose of L-selenomethionine one tablet (83 mcg) (Phase 1), a single dose of two tablets (Phase 2), and two tablets daily for 14 days (Phase 3). Total selenium and selenium time profiles were generated by serial sampling (T0, T3, T6, T12, and T24 hours after ingestion-Phases 1 and 2; and T0 and T24 hours-Phase 3). Selenium concentration was investigated by open-vessel acid digestion of small serum volumes followed by hydride generation atomic fluorescence spectroscopy analysis. RESULTS: There was a significant increase in serum selenium concentration (mcg/L) in all treatment phases. Significantly increased levels were reached at T3 in Phase 1 (baseline: 76.5 ± 2.47; T3: 82.8 ± 3.28) and at T6 in Phase 2 (83.8 ± 3.46). They remained significantly increased at T12 in Phase 1 and T24 in Phase 2 (79.03 ± 2.69). There was significant selenium accumulation after prolonged intake (14 days) (102.13 ± 5.61). CONCLUSIONS: Prolonged selenomethionine administration increases circulating blood selenium concentration and hydride generation atomic fluorescence spectroscopy enables its accurate quantification.

Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology.

OBJECTIVE: We developed clinical practice guidelines to assess the individual risk-benefit profile of androgen replacement therapy in adult male hypogonadism (HG), defined by the presence of specific signs and symptoms and serum testosterone (T) below 12 nmol/L. PARTICIPANTS: The task force consisted of eight clinicians experienced in treating HG, selected by the Italian Society of Endocrinology (SIE). The authors received no corporate funding or remuneration. CONSENSUS PROCESS: Consensus was guided by a systematic review of controlled trials conducted on men with a mean T < 12 nmol/L and by interactive discussions. The guidelines were reviewed and sequentially approved by the SIE Guidelines Commission and Executive Committee. CONCLUSIONS: We recommend T supplementation (TS) for adult men with severely reduced T levels (T < 8 nmol/L) to improve body composition and sexual function. We suggest that TS be offered to subjects with T < 12 nmol/L to improve glycaemic control, lipid profile, sexual function, bone mineral density, muscle mass and depressive symptoms, once major contraindications have been ruled out. We suggest that lifestyle changes and other available interventions (e.g. for erectile dysfunction) be suggested prior to TS. We suggest that TS should be combined with currently available treatments for individuals at high risk for complications, such as those with osteoporosis and/or metabolic disorders. We recommend against using TS to improve cardiac outcome and limited mobility. We recommend against using TS in men with prostate cancer, unstable cardiovascular conditions or elevated haematocrit. The task force places a high value on the timely treatment of younger and middle-aged subjects to prevent the long-term consequences of hypoandrogenism.

Selenium and reproductive function. A systematic review.

Selenium (Se) is an essential element involved in normal gonadal development, gametogenesis, and fertilization. Molecular studies show that the gonads actively take up and store Se, most of which is incorporated in the glutathione peroxidase enzymes. We provide a systematic review of the original molecular studies, prospective observational data and randomized controlled trials on the role of Se in reproductive function conducted in the past 30 years. A critical appraisal of these findings suggests that Se supplementation produces a bell-shaped response curve, with negative effects observed for both low and high concentrations. The few available clinical trials support the use of Se supplementation (<200 µg/d) to improve male infertility, although their pre-treatment assessment of Se levels in enrolled subjects is inconsistent and their quality and size are insufficient to enable general recommendations. In females, a putative role in oocyte maturation and fertilization is suggested, but no large controlled trials have yet been performed. The role of Se supplementation on pregnancy outcomes is promising, and ongoing studies and meta-analysis should soon enable proper recommendations to be suggested. How best to assess Se in terms of cut-off value, sample type (serum, semen, other fluids) and the specific outcome of interest remains to be clarified. In the meantime, assessment of serum Se levels followed by low-dose replacement therapy when necessary is a reasonable approach to improve male idiopathic infertility and gestational outcome.

Propionyl-L-carnitine, L-arginine and niacin in sexual medicine: a nutraceutical approach to erectile dysfunction.

The application of nutraceuticals in the field of male sexual function -in particular for erectile dysfunction (ED)--remains relatively underexplored. In a group of 54 unselected men (35-75 years), consecutively presenting to our ED clinic and naive to other ED treatments, we carried out a single-blind, one-arm study to evaluate the effects of a 3-month supplementation with propionyl-L-carnitine, L-arginine and niacin on their sexual performance. All patients had the short-international index of erectile function (IIEF) questionnaire, global assessment questions (GAQs) and routine laboratory testing, at baseline and 3 months afterward. 51 (92%) patients of 54 completed the entire study period. After 3 months of treatment, a small, but statistically significant improvement in total and single items of the IIEF was found (Δ = 5.7 ± 4.1 P < 0.01). Analyses on GAQs revealed that treatment improved erections in 40% of cases, with a partial response occurring in up to 77% of subjects enrolled. These preliminary findings indicate that the favourable cardiovascular effects of nutraceuticals might also reflect on male sexual function with possible implication in the treatment and prevention of ED. This study documents a considerable patient's interest toward nutritional supplementation--as first-line or adjunctive treatment to PDE5 inhibitors--that goes beyond the measurable increment in penile rigidity.