Myo-inositol Treatment Research Articles

Inositol and pulmonary function. Could myo-inositol treatment downregulate inflammation and cytokine release syndrome in SARS-CoV-2?

The outbreak of Sars-CoV-2 (COVID-19) poses serious challenges to people's health worldwide. The management of the disease is mostly supportive, and respiratory failure from acute respiratory distress syndrome is the leading cause of death in a significant proportion of affected patients. Preliminary data point out that dramatic increase in IL-6 and subsequent cytokine release syndrome may account for the development of fatal interstitial pneumonia. Inhibition of IL-6 by blocking its specific receptor with monoclonal antibodies has been advocated as a promising attempt. Here we assess the potential utility of myo-Inositol, a polyol already in use for treating the newborn Respiratory Distress Syndrome, in downregulating the inflammatory response upon Sars-CoV-2 infection. Myo-Inositol proved to reduce IL-6 levels in a number of conditions and to mitigate the inflammatory cascade, while being devoid of any significant side effects. It is tempting to speculate that inositol could be beneficial in managing the most dreadful effects of Sars-CoV-2 infection.

Inositols' Importance in the Improvement of the Endocrine-Metabolic Profile in PCOS.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and metabolic problems among women of reproductive age. The mechanism of PCOS is associated with concurrent alterations at the hormonal level. The diagnosis assumes the occurrence of three interrelated symptoms of varying severity, namely ovulation disorders, androgen excess, or polycystic ovarian morphology (PCOM), which all require a proper therapeutic approach. The main symptom seems to be an increased androgen concentration, which in turn may contribute to different metabolic disorders. A number of papers have demonstrated the significant role of inositol therapy in PCOS. However, there is a lack of detailed discussion about the importance of myo-inositol (MI) and d-chiro-inositol (DCI) in reference to particular symptoms. Thus, the aim of this review is to present the effectiveness of MI and DCI treatment for PCOS symptoms. Moreover, the review is focused on analyzing the use of inositols, taking into account their physiological properties, together with the mechanism of individual PCOS symptom formation.

Urinary myo-inositol is associated with the clinical outcome in focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) have similar initial histological findings; however, their prognoses are distinct. Therefore, it is of great importance to discriminate FSGS from MCD in the early phase of disease and predict clinical prognosis. A discovery set of 184 urine samples (61 healthy control, 80 MCD, and 43 FSGS) and a validation set of 61 urine samples (12 healthy control, 26 MCD, and 23 FSGS) were collected at the time of kidney biopsy. Metabolic profiles were examined using nuclear magnetic resonance spectroscopy. Of 70 urinary metabolites, myo-inositol was significantly higher in FSGS patients than in control patients (discovery set, 2.34-fold, P < 0.001; validation set, 2.35-fold, P = 0.008) and MCD patients (discovery set, 2.48-fold, P = 0.002; validation set, 1.69-fold, P = 0.042). Myo-inositol showed an inverse relationship with the initial estimated glomerular filtration rate (eGFR) and was associated with the plasma level of soluble urokinase-type plasminogen activator receptor in FSGS patients. Myo-inositol treatment ameliorated the decreased expression of ZO-1 and synaptopodin in an in vitro FSGS model, and as myo-inositol increased, myo-inositol oxygenase tissue expression decreased proportionally to eGFR. Furthermore, urinary myo-inositol exhibited an increase in the power to discriminate FSGS patients, and its addition could better predict the response to initial treatment. In conclusion, urinary myo-inositol may be an important indicator in the diagnosis and treatment of FSGS patients.

Long-Term Effects of Myoinositol on Behavioural Seizures and Biochemical Changes Evoked by Kainic Acid Induced Epileptogenesis.

Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain—a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or for modification of disease progression. We have previously shown that (i) myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration of MI for 4 weeks prevents certain biochemical changes triggered by SE. However it was not established whether such MI treatment also exerts long-term effects on the frequency of SRS. In the present study we have shown that, in KA-induced post-SE epilepsy model in rats, MI treatment for 28 days reduces frequency and duration of behavioural SRS not only during the treatment, but also after its termination for the following 4 weeks. Moreover, MI has significant effects on molecular changes in the hippocampus, including mi-RNA expression spectrum, as well as mRNA levels of sodium-MI transporter and LRRC8A subunit of the volume regulated anionic channel. Taken together, these data suggest that molecular changes induced by MI treatment may counteract epileptogenesis. Thus, here we provide data indicating antiepileptogenic properties of MI, which further supports the idea of developing new antiepileptogenic and disease modifying drug that targets MI system.

Treatment with myo-inositol attenuates binding of the carbohydrate-responsive element-binding protein to the ChREBP-β and FASN genes in rat nonalcoholic fatty liver induced by high-fructose diet

Dietary supplementation with the major lipotrope myo-inositol (MI) potently reduces triglyceride (TG) content and expression levels of the fatty acid synthesis genes, for example, fatty acid synthase (FASN), in rat nonalcoholic fatty liver induced by high-fructose diet. Fatty acid synthesis genes are regulated by the carbohydrate-responsive element-binding protein (ChREBP) that exists in 2 isoforms: ChREBP-α and ChREBP-β. The gene encoding the latter isoform is more responsive to fructose. Because MI repressed the induction of fatty acid synthesis gene expression by high-fructose diet, we hypothesized that MI may reduce binding of ChREBP to the carbohydrate response elements (ChoREs) in the ChREBP-β gene as well as in fatty acid synthesis genes in the liver. Rats were fed high-glucose, high-fructose, or high-fructose diets supplemented with MI (0.05% and 0.25%) for 2 weeks. Hepatic TG content and expression levels of the glucose-6-phosphate dehydrogenase, malic enzyme 1, FASN, acetyl-CoA carboxylase alpha, S14, and ChREBP-β were remarkably elevated in rats fed with high fructose compared with the corresponding levels in high-glucose group. Notably, elevated values of these parameters in high-fructose group were reduced by MI. Similarly, high-fructose–induced ChREBP binding to the ChoREs of the ChREBP-β and FASN genes was nominally decreased by MI. This study showed that treatment with MI reduced elevated TG content and expression of genes related to fatty acid synthesis, such as FASN and ChREBP-β, in rat nonalcoholic fatty liver induced by high-fructose diet. Furthermore, MI treatment nominally decreased increased binding of ChREBP to the ChoREs of ChREBP-β and FASN genes.

Melatonin and Myoinositol: A Foreword Step Toward IVF Success, a Prospective Clinical Trial

Many subfertile couples, who failed to conceive naturally, seek help by means of artificial reproduction techniques such as in vitro fertilization (IVF) to achieve pregnancy. It is clear that oocyte and embryo quality depression are widely considered to be the main challenge of IVF in assisted reproduction. The aim of the study was to assess the effect and the role of melatonin combined with myoinositol on oocyte quality and to investigate its correlation with pregnancy outcome. A total of 315 patient, aged between 30-40, in a 12 month study period from Jan. 2017 to Dec. 2017, with history of one or multiple unsuccessful IVF cycles due to poor oocyte quality were included in this study. The study group (group 1, n=166) was treated with melatonin combined with myoinositol (Seidivid plus, SEIDLAB) for 3 months prior to a new IVF cycle and the control group (group 2, n =149) just received a standard IVF cycle without melatonin and myoinositol. IVF outcomes were compared between the two groups. Primary endpoint was the number of morphologically mature oocytes retrieved (MII oocytes). Secondary endpoints were fertilization rate per number of mature oocytes, embryo quality and pregnancy rate. After treatment, the number of mature oocytes, the fertilization rate, the number of top-quality embryos transferred and pregnancy rate were statistically higher compared to the previous IVF cycle, while there was no difference in the number of retrieved oocyte. The mean number of oocytes retrieved differ between the two groups being (11.56) in group 1 and (10.9) in control one (1920 vs. 1629) and the percentage of mature oocytes was significantly higher in melatonin-treated group (77.03% vs. 69.1%). Concurrently, the mean number of immature oocytes (germinal vesicles) was reduced (22.9% vs. 39.9%). Furthermore, the melatonin –myoinositol treated group showed an increase in fertilization rate (80.2% vs. 77.7%) and the mean number of grade one embryos resulted was also higher (60.05% vs. 49.5%). Clinical pregnancy rate was in tendency higher in the group treated with melatonin and myoinositol (48.3% vs. 40.8%), In the current study It was concluded that Melatonin and myoinositol treatment is likely to become a significant option for improving oocyte and embryo quality in women who cannot become pregnant because of poor oocyte quality.

Effects of dietary myo-inositol on growth, chemical composition and plasma chemistry of Amur sturgeon Acipenser schrenckii

The present study was conducted to demonstrate the dietary myo-inositol requirement and its effects on the growth, proximate composition and blood chemistry of Amur sturgeon (Acipenser schrenckii). Triplicate groups of 30 fish (initial weight 11.90 ± 0.12 g) were fed different diets containing graded levels of myo-inositol (28.75, 127.83, 343.83, 565.81, 738.15 and 936.28 mg kg−1) until satiation for 56 days. The fish were weighed after a 24-h fast, and six fish were used for whole body composition analysis. Further, the liver and muscle were sampled from another six fish for lipid analysis. The blood and liver were sampled from the remaining six fish for haematology and fatty acid analysis. The weight gain of fish increased with myo-inositol content, from the 28.75- to 343.83-mg kg−1 myo-inositol treatment groups, and then stabilised. The liver lipid content and hepatosomatic index decreased significantly from 21.91 to 19.14% and from 3.20 to 2.76% with increased dietary myo-inositol supplementation, respectively. The whole body lipid content generally decreased from 6.33 to 5.55%. The content of liver-saturated fatty acids decreased significantly (28.13%) in the 936.28-mg kg−1 treatment group. The content of plasma non-esterified fatty acids increased with the increase in dietary myo-inositol supplementation from 0.77 to 1.17 mmol L−1, whereas the content of triglycerides significantly decreased from 4.62 to 3.28 mmol L−1. In conclusion, the optimum myo-inositol requirement was found to be 336.1 mg kg−1, based on weight gain in a two-slope quadratic broken-line model.

The Effects of MYO-inositol and Indole Butyric Acid (IBA) on the Formation of Pineapples Root (Ananas comosus L.) from Sipahutar North Sumatera In Vitro

Background: Rooting of pineapple from Sipahutar in vitro is an alternative to obtain superior seeds in large quantities to meet the needs of farmers and consumers.Objective: The purpose of this study was to investigate the effect of Myo-inositol and IBA on pineapple rooting (Ananas comosus L.) from Sipahutar in vitro.Methods: The research method used a completely randomized factorial design with two factors: Factor I: Myo-inositol consisted of [4] treatment concentrations: M0 = 0 g/l, M0.02 = 0.02 g/l, M0.04 = 0.04 gr/l, M0.06 = 0.06 gr/l. Factor II: IBA growth regulators consisted of [3] treatment concentrations: IB0 = 0 ppm, IB1.5 = 1.5 ppm, IB3 = 3 ppm. The parameters observed were time of root emergence, number of roots, number of leaves, time of leaf emergence, number of tillers, and time of its emergence observed each week, while the height of tillers, shoots, and whole shoots, root length, leaf width and leaf length were observed 12 weeks after planting (WAP).Results: The result of the research showed that root time appeared on [3] WAP. The increasing number of leaves and timing of the puppiesin 1 WAP. Myo-inositol had significant effects on root counts in the 0.06 gr/l and root length on Myo-inositol treatment in the 0.04 g/l. IBA did not have a real effect on the entire observation parameters. The interactions of Myo-inositol and IBA had significant effects on root number, number of leaves, leaf length and tiller height.Conclusions: Myo-inositol and IBA had significant effects on root number, leaf number, leaf length and shoot height of pineapple’s explant from Sipahutar.Â

Clinical and metabolic outcomes in pregnant women at risk for gestational diabetes mellitus supplemented with myo-inositol: a secondary analysis from 3 RCTs

Gestational diabetes mellitus is defined as carbohydrate intolerance that begins or is first recognized during pregnancy. Insulin sensitizing substances such as myo-inositol have been considered for the prevention of gestational diabetes mellitus and related complications. Because previous studies failed to show a clear reduction of gestational diabetes mellitus complications, the aim of this study was to evaluate clinical and metabolic outcomes in women who are at risk for gestational diabetes mellitus supplemented with myo-inositol since the first trimester. A secondary analysis of databases from 3 randomized, controlled trials (595 women enrolled) in which women who were at risk for gestational diabetes mellitus (a parent with type 2 diabetes mellitus, obese, or overweight) were supplemented with myo-inositol (4 g/d) throughout pregnancy. Main measures were the rate of adverse clinical outcomes: macrosomia (birthweight, ≥4000 g), large-for-gestational-age babies (fetal growth, ≥90 percentile), fetal growth restriction (fetal growth, ≤3 percentile), preterm birth (delivery before week 37 since the last menstruation), gestational hypertension, and gestational diabetes mellitus. A significant reduction was observed for preterm birth (10/291 [3.4%] vs 23/304 [7.6%]; P=.03), macrosomia (6/291 [2.1%] vs 16/304 [5.3%]; P=.04), Large-for-gestational-age babies (14/291 [4.8%] vs 27/304 [8.9%]; P=.04) with only a trend to significance for gestational hypertension (4/291 [1.4%] vs 12/304 [3.9%]; P=.07). Gestational diabetes mellitus diagnosis was also decreased when compared with the control group (32/291 [11.0%] vs 77/304 [25.3%]; P<.001). At univariate logistic regression analysis, myo-inositol treatment reduced the risk for preterm birth (odds ratio, 0.44; 95% confidence interval, 0.20-0.93), macrosomia (odds ratio, 0.38; 95% confidence interval, 0.14-0.98), and gestational diabetes mellitus diagnosis (odds ratio, 0.36; 95% confidence interval, 0.23-0.57). Myo-inositol treatment in early pregnancy is associated with a reduction in the rate of gestational diabetes mellitus and in the risk of preterm birth and macrosomia in women who are at risk for gestational diabetes mellitus.

Consequences of postnatal myo‐inositol supplementation on respiratory control and nucleus tractus solitarius (nTS) neurons

Myo‐inositol is a naturally occurring sugar derivative formed endogenously from the breakdown of glucose; it is also found in a variety of foods including breast milk and is commercially available as a nutritional supplement. Serum levels of myo‐inositol in infants decrease naturally over the first few postnatal weeks; prior studies in preterm infants have demonstrated improved pulmonary function, reduced incidence of respiratory distress, and increased survival rates following myo‐inositol supplementation. In support of a potential beneficial effect of myo‐inositol supplementation on respiratory control, we have shown previously that myo‐inositol treatment over the first 2 postnatal weeks enhances the acute hypoxic ventilatory response (HVR). In the present study, we tested the hypothesis that the enhanced HVR following myo‐inositol treatment would be associated with increased excitability of neurons within the area of brainstem chemoafferent integration, the nucleus tractus solitarius (nTS). Mouse pups received subcutaneous injections of myo‐inositol (80 mg/kg/day) for the first two postnatal weeks. Whole cell patch clamp recordings were then used to examine the excitatory properties of nTS neurons monosynaptically connected to the solitary tract. Compared to saline treated mice, myo‐inositol exposure increased the rheobase and the failure rate of nTS neurons, and decreased the paired pulse ratio following 20 Hz stimulation. Spontaneous activity (EPSC frequency, area, rise time, decay time), and basic neuronal properties (membrane resistance, capacitance, resting membrane potential) did not differ between groups. In conclusion, and contrary to our hypothesis, the enhanced HVR following postnatal myo‐inositol treatment was associated with decreased excitability of nTS neurons. We speculate the reduced nTS neuron excitability may be a compensatory response to increased chemoafferent (presumably the carotid body) inputs during hypoxia. These data may be important to our understanding of how myo‐inositol supplementation could influence development and function of brainstem respiratory neural control regions and may have implications for the pathophysiology of various respiratory morbidities in preterm infants.Support or Funding InformationThe Gerber FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Ameliorative effect of myo-inositol on red blood cell alterations in polycystic ovary syndrome: in vitro study

Polycystic ovary syndrome (PCOS)is a gynecological endocrine disorder which is associated with systemic inflammatory status inducing red blood cells (RBC) membrane alterations related to insulin resistance and testosterone levels which could be greatly improved by myo-inositol (MYO) uptake. In this study we aim to evaluate the effect of MYO in reducing oxidative-related alterations through in vitro study on PCOS RBC. Blood samples from two groups of volunteers, control group (CG, n = 12) and PCOS patient group (PG, n = 12), were analyzed for band 3 tyrosine phosphorylation (Tyr-P), high molecular weight aggregate (HMWA), IgG in RBC membranes, and glutathione (GSH) in cytosol, following O/N incubation in the presence or absence of MYO. PCOS RBC underwent oxidative stress as indicated by higher band 3 Tyr-P and HMWA and increased membrane bound autologous IgG. Twenty four hours (but not shorter time) MYO incubation, significantly improved both Tyr-P level and HMWA formation and concomitant membrane IgG binding. However, no relevant modification of GSH content was detected. PCOS RBC membranes are characterized by increased oxidized level and enhanced sensitivity to oxidative injuries leading to potential premature RBC removal. MYO treatment is effective in reducing oxidative related abnormalities in PCOS patients probably restoring the inositol phospholipid pools of the membranes.

Dietary supplementation with myo-inositol reduces hepatic triglyceride accumulation and expression of both fructolytic and lipogenic genes in rats fed a high-fructose diet

Excessive fructose ingestion drastically enhances hepatic lipid accumulation. The most prominent form of inositol—myo-inositol (MI)—remarkably reduces high sucrose–induced hepatic triglyceride (TG) accumulation. Because MI is a major and strong lipotrope, we hypothesized in this study that MI improves fatty liver more induced by excessive ingestion of fructose than sucrose. Rats were fed a high-glucose diet (HGD), a high-fructose diet (HFD), or an HFD supplemented with 0.2% MI for 12 days. Hepatic levels of TG and mRNAs for fructolysis (ketohexokinase and aldolase B), lipogenesis (pyruvate kinase, liver, and RBC; glucose-6-phosphate dehydrogenase; acetyl-CoA carboxylase alpha; fatty acid synthase; and stearoyl-CoA desaturase 1), and a key transcription factor for lipogenesis—carbohydrate-responsive element-binding protein—were significantly increased in the HFD group compared with the HGD group, and the increase was markedly decreased by MI supplementation. Similarly, HFD-induced pyruvate kinase, liver, and RBC and fatty acid synthase protein levels in the liver were reduced by MI treatment. On the other hand, hepatic levels of mRNAs for β-oxidation (acyl-CoA synthetase and carnitine palmitoyltransferase 1a) did not differ among the 3 groups. Taken together, this study showed that MI supplementation decreases the expression of fructolytic/lipogenic genes and lipogenic proteins as well as TG accumulation in high fructose–induced fatty liver in rats.

Identification and Functional Implications of Sodium/Myo-Inositol Cotransporter 1 in Pancreatic β-Cells and Type 2 Diabetes.

Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, although the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and, specifically, β-cells. Genetic or pharmacological inhibition of SMIT1 impaired glucose-stimulated insulin secretion by INS-1E cells, probably via downregulation of PI signaling. In addition, SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions. In corroboration, chronic MI treatment improved the disease phenotypes of diabetic rats and islets. On the basis of our results, we postulate that the MI transporter SMIT1 is required to maintain a stable PI pool in β-cells in order that PI remains available despite its rapid turnover.

Abstract 756: Myo-inositol modulates the tumor microenvironment in a mouse model of lung cancer chemoprevention

Abstract Background: Myo-inositol is a nutritional supplement that has been investigated as a chemopreventive agent for lung cancer. We have investigated the effect of myo-inositol in a CC-LR (CCSPCre/LSL-K-rasG12D) mouse lung cancer model. Blood, broncho-alveolar lavage fluid (BALF), and lungs were collected from CC-LR and LR littermate control mice at 14 weeks of age, when mice had a large number of premalignant lesions with only small foci of adenocarcinoma. Methods: Lesion burden and stage was quantified using macroscopically evident lung surface tumor counts as well as histology from paraffin sections. Serial paraffin sections were also used for immunohistochemistry. Plasma was analyzed using high-sensitivity liquid-chromatography coupled tandem mass spectrometry. Cytokine and chemokine concentrations in BALF were quantitated using multiplex immunobead assays. Results: Myo-inositol treated mice (n = 20) had fewer tumors (p &amp;lt; 0.0001) than mice raised on control diet (n = 23). Additionally, lesions were shifted towards lower grade, from adenomas and adenomatous alveolar hyperplasia to bronchial hyperplasia. Several host factors including cytokines and proteins produced by myeloid derived suppressor cells and macrophages were significantly impacted by myo-inositol treatment. In addition to changes in metabolic inflammation derived factors, proteins which are associated with both chronic inflammation and lung tumorigenesis were altered as well. Conclusions: Myo-inositol treatment both reduced tumor burden and lesion grade in a KRAS model of lung cancer. Our findings of a substantial impact of myo-inositol treatment on the host response suggests novel mechanisms for its chemopreventive activitiy. Citation Format: Nese Unver, Kirubel T. Zeleke, Ximing Tang, Samantha Holt, Seyed Javad M. Moghaddam, Hong Wang, Ignacio I. Wistuba, Samir M. Hanash, Edwin J. Ostrin. Myo-inositol modulates the tumor microenvironment in a mouse model of lung cancer chemoprevention. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 756.

A pilot study of gestational diabetes mellitus not controlled by diet alone: First-line medical treatment with myoinositol may limit the need for insulin

AimThis study assessed whether myoinositol might be a first-line medical treatment for gestational diabetes mellitus (GDM). MethodsFor 12 months, women with GDM not controlled by diet (n=32) were prospectively treated with myoinositol 1200mg and folic acid 400μg/day, while consecutive women (n=28) with insulin-requiring GDM treated during the previous year at our centre constituted the control group. Baseline characteristics and care were similar in both groups. ResultsInsulin was required in eight women (25%) in the myoinositol group who, compared with the 24 who did not need insulin, were older (37±5 vs. 32±5 years, respectively; P=0.018) and had a larger percentage of high self-monitored glucose values (45±8% vs. 32±14%; P<0.0001) during the week prior to the introduction of myoinositol treatment. All of the women had similar pregnancy outcomes regardless of their GDM management, although less labour induction was required in the myoinositol group (OR: 0.22 [0.07–0.65]), which had no side effects. ConclusionThis pilot study suggests that myoinositol may be a safe first-line medical treatment for uncontrolled GDM.

Myoinositol Attenuates the Cell Loss and Biochemical Changes Induced by Kainic Acid Status Epilepticus.

Identification of compounds preventing or modifying the biochemical changes that underlie the epileptogenesis process and understanding the mechanism of their action are of great importance. We have previously shown that myoinositol (MI) daily treatment for 28 days prevents certain biochemical changes that are triggered by kainic acid (KA) induced status epilepticus (SE). However in these studies we have not detected any effects of MI on the first day after SE. In the present study we broadened our research and focused on other molecular and morphological changes at the early stages of SE induced by KA and effects of MI treatment on these changes. The increase in the amount of voltage-dependent anionic channel-1 (VDAC-1), cofilin, and caspase-3 activity was observed in the hippocampus of KA treated rats. Administration of MI 4 hours later after KA treatment abolishes these changes, whereas diazepam treatment by the same time schedule has no significant influence. The number of neuronal cells in CA1 and CA3 subfields of hippocampus is decreased after KA induced SE and MI posttreatment significantly attenuates this reduction. No significant changes are observed in the neocortex. Obtained results indicate that MI posttreatment after KA induced SE could successfully target the biochemical processes involved in apoptosis, reduces cell loss, and can be successfully used in the future for translational research.

Treating Woman with Myo-Inositol Vaginal Suppositories Improves Partner's Sperm Motility and Fertility.

Motility is the feature that allows spermatozoa to actively reach and penetrate the female gamete during fertilization. When this function is altered, and especially decreased, troubles in conceiving may occur. In this study, we demonstrated that treating fertile women with myo-inositol (MI) vaginal suppositories ameliorated their partners' sperm motility and also positively affected their conceiving capacity, without changes in cervical mucus structural and biochemical characteristics. Indeed, by means of the postcoital test on female cervical mucus, a significant improvement especially in progressive sperm motility was recorded after MI suppository use. Concomitantly, after MI treatment, a reduction of immotile spermatozoa percentage was observed. Importantly, MI vaginal supplementation positively correlated with a pregnancy for 5 of the 50 couples enrolled in the study, leading us to speculate that this substance may substantially contribute to create in the cervical mucus an ideal milieu that makes spermatozoa more motile and functionally able to fertilize. Even though the detailed mechanism is still unclear, these results should encourage MI vaginal use for the clinical improvement of male infertility, through their partners.

A Potential Therapeutic Role of Myoinositol in the Metabolic and Cardiovascular Profile of PCOS Iranian Women Aged between 30 and 40 Years

Introduction. Polycystic ovary syndrome (PCOS) is a common disorder in reproductive age. This pilot study investigated the effects of myoinositol (MI) treatment on metabolic and cardiovascular profile in PCOS women over 30 years of age. Methods. Between 2015 and 2016, 50 women with diagnosis of PCOS by the Rotterdam Criteria were included in the study. All women received MI 2 g plus 200 μg of folic acid (Inofolic, Health Parsian, Iran; twice daily) for 3 months. Baseline and 3-month serum samples were taken after an overnight fast to evaluate the insulin resistance index (HOMA-IR), fasting glucose, and the levels of triglyceride, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine, systolic blood pressure, and diastolic blood pressure. Participants' weight was measured before and after treatment and body mass index (BMI) was calculated. Results. The data showed a significant improvement in the serum level of insulin sensitivity and a reduction of cholesterol, LDL, and homocysteine after three months of treatment. Furthermore, blood pressure was significantly reduced in the treated patients. Three participants became pregnant during treatment. Conclusion. Results showed that supplementation with MI and folic acid in PCOS patients over 30 years of age could decrease the risk of cardiovascular problems by normalizing the metabolic profile.

Myo-inositol may prevent gestational diabetes onset in overweight women: a randomized, controlled trial

Objective: To evaluate whether myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) rate in overweight women.Methods: In an open-label, randomized trial, myo-inositol (2 g plus 200 μg folic acid twice a day) or placebo (200 μg folic acid twice a day) was administered from the first trimester to delivery in pregnant overweight non-obese women (pre-pregnancy body mass index ≥ 25 and < 30 kg/m2). The primary outcome was the incidence of GDM.Results: From January 2012 to December 2014, 220 pregnant women were randomized at two Italian University hospitals, 110 to myo-inositol and 110 to placebo. The incidence of GDM was significantly lower in the myo-inositol group compared to the placebo group (11.6% versus 27.4%, respectively, p = 0.004). Myo-inositol treatment was associated with a 67% risk reduction of developing GDM (OR 0.33; 95% CI 0.15–0.70).Conclusions: Myo-inositol supplementation, administered since early pregnancy, reduces GDM incidence in overweight non-obese women.

Myoinositol improves sperm parameters and serum reproductive hormones in patients with idiopathic infertility: a prospective double-blind randomized placebo-controlled study.

Male infertility is a multifactorial disorder that affects a significant percentage of couples. Its etiology and pathogenesis remain elusive in about one-third of the cases; this is referred to as idiopathic infertility. Inositols mediate the sperm processes involved into oocyte fertilization, such as penetration of the ovum cumulus oophorus, binding with the zona pellucida and the acrosome reaction. The aim of this double-blind, randomized, placebo-controlled trial was to evaluate the efficacy and safety of myoinositol (the most abundant form of inositols present in nature) treatment in men with idiopathic infertility. To accomplish this, we evaluated the effects of myoinositol on sperm parameters and reproductive hormones at baseline and after 3months of treatment in men with idiopathic infertility. No adverse reaction was observed. Myoinositol significantly increased the percentage of acrosome-reacted spermatozoa, sperm concentration, and total count and progressive motility compared to placebo. In addition, myoinositol rebalanced serum luteinizing hormone, follicle-stimulating hormone, and inhibin B concentrations. The clinical improvement of idiopathic infertile patients should encourage myoinositol use for the treatment of this disorder, even though its detailed mechanisms at the testicular level remain still unclear.