Role Of Myo-inositol Research Articles

Myo-Inositol and D-Chiro-Inositol Reduce DHT-Stimulated Changes in the Steroidogenic Activity of Adult Granulosa Cell Tumors.

Considering the properties of myo-inositol (MI) and D-chiro-inositol (DCI), which are well known in polycystic ovary syndrome therapy, and the limitations of adult granulosa cell tumor (AGCT) treatment, especially for androgen-secreting tumors, we studied the role of MI and DCI in the androgen-rich environment of AGCTs. For this purpose, we analyzed the mRNA expression of steroidogenic genes and the secretion of progesterone (P4) and 17β-estradiol (E2) in an unstimulated and/or dihydrotestosterone (DHT)-stimulated environment under MI and DCI influence. Thus, we used the HGrC1 and KGN cell lines as in vitro models of healthy and cancerous granulosa cells. We found that DHT, the most potent androgen, increased E2 secretion and steroidogenic acute regulatory protein (StAR) and cytochrome P450 side-chain cleavage gene (CYP11A1) mRNA expression without affecting 450 aromatase (CYP19A1) in AGCTs. However, after the MI and DCI treatment of KGN cells, both compounds strongly reduced StAR and CYP11A1 expression. Interestingly, in DHT-stimulated KGN cells, only DCI alone and its cotreatment with MI reduced both CYP11A1 mRNA and E2 secretion. These findings suggest that CYP11A1 is responsible for the antiestrogenic effect of DCI in the androgen-rich environment of AGCTs. Therefore, MI and DCI could be used as effective agents in the adjuvant treatment of AGCT, but further detailed studies are needed.

New insights into the role of myo-inositol in regulating the skin immune response of grass carp (Ctenopharyngodon idella)

Myo-inositol (MI) is a crucial constituent of the cell membrane and has a pivotal role to play in transmembrane signal transduction, ion channel regulation, and cell transport. Fish skin is a vital mucosal immune organ, and there are few studies that have examined the effect of MI on fish skin.Therefore, the purpose of this study was to investigate the role of dietary MI in regulating the skin immune response of grass carp (Ctenopharyngodon idella). A total of 540 fish (221.33 ± 0.84 g) were fed six diets containing graded levels of MI (27.0, 137.9, 286.8, 438.6, 587.7, and 737.3 mg/kg) for 10 weeks. When the growth test was complete, a 14-day challenge was conducted with Aeromonas hydrophila in each group. Our results indicated that the most effective MI concentrations (approximately 438.6–737.3 mg/kg diet) resulted in the following outcomes: (1) MI reduced the morbidity of grass carp skin and increased the thickness of the dense dermis layer. (2) MI enhanced the physical barrier function of the skin, maybe via increasing antioxidant capacity, inhibiting apoptosis, and improving tight junction-related signaling pathways (nuclear factor erythroid 2-related factor 2, p38 mitogen-activated protein kinase, and myosin light chain kinase). (3) MI enhanced skin immune barrier function, possibly via regulating anti-inflammatory and pro-inflammatory cytokines, as well as the target of rapamycin (TOR) and nuclear factor kappa B (NFκB) pathways. This study led to the following conclusion based on its findings: the MI supplementation strengthened the fish skin barrier function and protected it against Aeromonas hydrophila. The dietary MI requirement in on-growing grass carp was estimated to be 370.90 mg/kg by a broken-line method analysis of skin morbidity.

Systematic analysis of the pharmacology of myoinositol and D-chiroinositola

The article presents an analysis of publications on myoinositol in order to clarify the possibilities of prescribing drugs based on it. Myoinositol is one of the endogenous human metabolites that has a significant effect on the functioning of cells and tissues of the whole body. The main function of myoinositol and its derivatives is to participate in intracellular signal transmission and ensure the functioning of such important receptors as insulin receptors, catecholamines, metabotropic receptors of various neurotransmitters, growth factors, etc. (Myoinositol is the basis for the synthesis of an important group of signaling molecules, inositol phosphates, which mediate signal transmission from growth factor receptors and neurotransmitters). Most inositol-dependent proteins with known functions are necessary for the vital functions of the cardiovascular, immune system, and connective tissue structure. Equally important is the role of myoinositol in maintaining the functioning of the central nervous system (including neurotrophic and neuroprotective roles), sugar metabolism (primarily the signaling cascade of insulin) and the functioning of the kidneys and liver. Myoinositol subsidies contribute to the prevention of folate-resistant malformations and neuroprotection of the brain under stress.

Exploring the potential of myo-inositol in thyroid disease management: focus on thyroid cancer diagnosis and therapy.

Thyroid cancer (TC) is a malignancy that is increasing in prevalence on a global scale, necessitating the development of innovative approaches for both diagnosis and treatment. Myo-inositol (MI) plays a crucial role in a wide range of physiological and pathological functions within human cells. To date, studies have investigated the function of MI in thyroid physiology as well as its potential therapeutic benefits for hypothyroidism and autoimmune thyroiditis. However, research in the field of TC is very restricted. Metabolomics studies have highlighted the promising diagnostic capabilities of MI, recognizing it as a metabolic biomarker for identifying thyroid tumors. Furthermore, MI can influence therapeutic characteristics by modulating key cellular pathways involved in TC. This review evaluates the potential application of MI as a naturally occurring compound in the management of thyroid diseases, including hypothyroidism, autoimmune thyroiditis, and especially TC. The limited number of studies conducted in the field of TC emphasizes the critical need for future research to comprehend the multifaceted role of MI in TC. A significant amount of research and clinical trials is necessary to understand the role of MI in the pathology of TC, its diagnostic and therapeutic potential, and to pave the way for personalized medicine strategies in managing this intricate disease.

Вторичные мессенджеры инсулина при синдроме поликистозных яичников и методы его патогенетической коррекции

The study of new mechanisms of insulin resistance (IR) formation is a prerequisite for the development of new pathogenetically-oriented therapies of polycystic ovary syndrome (PCOS) and the treatment of associated disorders of carbohydrate and fat metabolism. Important regulators of insulin signaling are its secondary messengers, namely myo-inositol (MI), D-chiro inositol (DCI), and α-lipoic acid (ALA), which mediate various effects of insulin. Consequently, MI induces cellular glucose uptake and enhances glycolysis, whereas DCI stimulates glycogenesis and regulates energy metabolism. The physiologic MI/DCI ratio for oocytes is crucial for oogenesis, steroidogenesis, and the regulation of the menstrual cycle. ALA provides insulinomimetic effects through the induction of glucose translocation into cells, antioxidant and anti-inflammatory effects on pancreatic cells, and the suppression of lipolysis and the reduction of triglyceride levels. A wealth of evidence from large-scale studies, meta-analyses, and systematic reviews has demonstrated the crucial role of MI, DCI, and ALA in the treatment of PCOS. A multitude of studies, including those conducted by the authors, have demonstrated that the administration of these substances results in a reduction in HOMA, levels of glucose, insulin, triglycerides, low-density lipoproteins, and body mass index. This, in turn, has been shown to restore ovulation and the menstrual cycle in women with PCOS, as well as to reduce the risk of cardiometabolic diseases, including diabetes and nonalcoholic fatty liver disease KEYWORDS: polycystic ovary syndrome, inositol, myo-inositol, D-chiro inositol, alpha-lipoic acid, insulin resistance, fat metabolism, nonalcoholic fatty liver disease FOR CITATION: Ivanov I.A., Tabeeva G.I., Smetnik A.A. Secondary messengers of insulin in polycystic ovary syndrome and its pathogenically- oriented treatment. Russian Journal of Woman and Child Health. 2024;7(2):135–143 (in Russ.). DOI: 10.32364/2618-8430-2024-7-2-8.

Role of myo-inositol in acute kidney injury induced by cisplatin

There is an increasing evidence suggesting that myo-inositol (MI) may be a renoprotective factor. Our previous study revealed that decreased MI concentrations and increased excretion are often observed in animal models of renal injury and in patients with nephropathy. However, the role of MI supplementation in renal injury remains unclear. In this study, we aimed to explore the role of MI in cisplatin-induced acute kidney injury (AKI). We established a model of acute kidney injury caused by cisplatin (CDDP). Male Kunming mice were randomly divided into six groups: Sham (normal saline), CDDP (15 mg/kg), + MI (150 mg/kg), + MI (300 mg/kg), + MI (600 mg/kg) and MI (600 mg/kg). Human renal tubular epithelial cell line HK-2 cells were likewise separated into six groups at random: Control (normal saline), CDDP (20 µM), + MI (200 µM), + MI (400 µM), + MI (800 µM) and MI (800 µM). After the model was established, renal function indexes were subsequently detected, and experiments such as pathological staining analysis and protein expression analysis were performed. Our results showed that cisplatin administration led to AKI and apoptosis in mice and HK-2 cells, accompanied by markedly increased levels of MIOX, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), whereas exogenous MI significantly attenuated kidney injury and HK-2 cell damage induced by cisplatin both in vivo and in vitro by inhibiting excessive apoptosis. Overall, our findings demonstrate that exogenous MI can reduce excessive apoptosis, thus playing a protective role in cisplatin-induced AKI, indicating that exogenous MI may be used as an adjunctive treatment modality in cisplatin-induced AKI.

Myoinositol Versus Metformin in the Treatment of Polycystic Ovarian Syndrome: A Systematic Review.

Polycystic ovarian syndrome (PCOS) is a widespread, complex, and multi-system hormonal disorder that occurs in women of reproductive age. The wide variation in practice in the treatment of PCOS is a direct consequence of the lack of sufficient evidence on alternative treatment strategies, as well as a poor understanding of the disorder itself. The aim of our systematic reviewwas to assess the therapeutic advantages and adverse effects of metformin (MET), a standard treatment modality, with myoinositol (MI), a recent substitute that may be used alone or in combination with other remedies to treat PCOS. A literature search was done using PubMed Central, PubMed, Medline, Cochrane, Science Direct, and Google Scholar. Studies were limited to those published in English between 2012 and 2022 that focused on the management of PCOS with both MET and MI. The systematic review complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Using standard quality assessment tools, two reviewers independently assessed the content of the incorporated studies. Three meta-analyses, eight randomized controlled trials (RCTs), and one non-randomized non-controlled trial (NN-RCT) were deemed eligible. Following extensive analysis, we found that MET and MI are comparable in their effects on clinical, hormonal, and biochemical profiles. MI, however, had a better safety profile and tolerance due to minimal side effects compared to MET. These results demonstrate the potential role of MI as a novel asset in the armamentarium in the management of PCOS.

The Attenuation of Insulin/IGF-1 Signaling Pathway Plays a Crucial Role in the Myo-Inositol-Alleviated Aging in Caenorhabditis elegans.

Myo-Inositol (MI) has been shown to alleviate aging in Caenorhabditis (C). elegans. However, the mechanism by which MI alleviates aging remains unclear. In this study, we investigate whether MI can modulate the PI3K so as to attenuate the insulin/IGF-1 signaling (IIS) pathway and exert the longevity effect. The wild-type C. elegans and two mutants of AKT-1 and DAF-16 were used to explore the mechanism of MI so as to extend the lifespan, as well as to improve the health indexes of pharyngeal pumping and body bend, and an aging marker of autofluorescence in the C. elegans. We confirmed that MI could significantly extend the lifespan of C. elegans. MI also ameliorated the pharyngeal pumping and body bend and decreased autofluorescence. We further adopted the approach to reveal the loss-of-function mutants to find the signaling mechanism of MI. The functions of the lifespan-extending, health-improving, and autofluorescence-decreasing effects of MI disappeared in the AKT-1 and DAF-16 mutants. MI could also induce the nuclear localization of the DAF-16. Importantly, we found that MI could dramatically inhibit the phosphoinositide 3-kinase (PI3K) activity in a dose-dependent manner with an IC50 of 90.2 μM for the p110α isoform of the PI3K and 21.7 μM for the p110β. In addition, the downregulation of the PI3K expression and the inhibition of the AKT phosphorylation by MI was also obtained. All these results demonstrate that MI can inhibit the PI3K activity and downregulate the PI3K expression, and the attenuation of the IIS pathway plays a crucial role for MI in alleviating aging in C. elegans.

P-612 Current understanding of polycystic ovary syndrome (PCOS) and potential interest in future trial to evaluate role of myo-inositol as ovulation induction agent – Stakeholder’s surveys

Abstract Study question To assess awareness amongst consumers and gynaecologists on various aspects of PCOS and to explore the willingness to participate in a future trial of myo-inositol as an ovulation induction agent. Summary answer Significant lack of awareness on various aspect of PCOS amongst consumers is concerning. Gynaecologists and consumers are keen on trial exploring myo-inositol in anovulatory PCOS. What is known already Initial studies have reported that Myo-inositol can increase the frequency of menstruation and ovulation along with benefit with androgenic and glycaemic parameters in women with PCOS. There is a need for large, well designed and powered randomised controlled trial to evaluate the role of Myo-inositol as a fertility enhancing agent on its own and as an adjunct to clomiphene/letrozole in women with anovulatory PCOS. There has been a growing interest in patient and public involvement in setting research priorities to reduce the risk of discrepancy between what stakeholder’s experience as important unanswered questions and those which are actually researched. Study design, size, duration The surveys were hosted using on-line survey tool (www.surveymonkey.com) between Dec 2020 and April 2021, in the UK. Bespoke questionnaires were designed for the survey of gynaecologists (comprising of 27 questions) and the women with PCOS (comprising of 20 questions). These were peer reviewed and included, multiple choice questions, questions with a Likert scale response and open format questions. Ethical approval was provided by Queen Mary University of London (QMUL) ethics committee (Ref: QMERC2014/76). Participants/materials, setting, methods The online clinician survey was a cross sectional study of gynaecologists who look after women with PCOS, and the consumer survey was a cross sectional study of the members of PCOS support organisation “Verity”. The data was collected using on-line survey tool and was summarised descriptively using numbers and percentages. For the descriptive statistics, we used absolute and relative frequencies, and we also used the median and the IQR to detect the most common answers. Main results and the role of chance There were 244 responses; 104 gynaecologists and 140 consumers. Majority of the consumers were aware that, women with PCOS struggle with irregular cycles (94%); to loss/maintain weight (83%); and to conceive (85%). 81% were aware of risk of subfertility, however, only half were aware of risks associated with irregular menstrual cycles (51%), gestational diabetes (57%) and long-term risks such as diabetes (62%). 96% felt subfertility was an important issue, however, only 2/5th were aware of treatment options, a third were aware of need for USS monitoring whilst taking clomid tablets and that clomid tablets can only be used for 6-12 cycles. The clinician survey showed that 70% of the gynaecologists chose life-style measurements for the first line option and the second line options were 35% for clomiphene, 29% for clomiphene + metformin, followed by 21% for letrozole. 79% use USS to confirm ovulation and 60% by measuring serum progesterone; 37% monitor all cycles of ovulation induction whereas 41% monitor index cycle. Two thirds of the gynaecologists (72%) and majority of consumers (88%) agreed on the need to research myo-inositol for ovulation induction in PCOS and were willing to participate in such a study. Barriers for recruitment and retention were also explored. Limitations, reasons for caution Clinician survey was unable to get the views of general practitioners and endocrinologists, who might have a different perspective particularly on non-reproductive outcomes. Consumer survey was online survey in English which can result in a selection bias and the views of women from other socio-economic and cultural backgrounds may differ. Wider implications of the findings These surveys provide vital information in planning a definitive RCT on the role of myo-inositol in women with anovulatory PCOS trying to conceive. Further research tools need to be explored to provide better information and education to the women with PCOS particularly on the long-term risks associated with PCOS. Trial registration number NA

Role of Myo-inositol and D-Chiro-Inositol in Improvement of Endocrine and Clinical Parameters in Girls affected by PCOS

Aim: To evaluate the effectiveness of Myo-inositol and D-chiro-Inositol combination therapy in improvement of Endocrine and clinical parameters in teenage girls affected by PCOS. Methods: This Prospective Cohort study was conducted in the Department of Gynaecology & Obstetrics, Avicenna Medical College and hospital after approval from Institutional ethical committee from January 2021 to June 2021. We have enrolled 106 teenage girls from 13 to 19 years with PCOS. Baseline clinical, ultrasound and biochemical parameters were noted and assigned them into two treatment groups (A & B) randomly. Group A was given MI plus DCI and Group B was given placebo for 6 months. Differences were analyzed in pretreatment and post treatment ultrasound findings and Clinical variable of BMI, Acne, hirsutism and menstrual irregularities. Biochemical parameters including LH:FSH ratio, 17-beta Estradiol and fasting glucose were also evaluated in both groups. Statistical Analysis was done using SPSS version 21. Results: A statistically significant improvement was observed in clinical & Laboratory parameters in treatment group showing reduced LH:FSH ratio, fasting glucose and increased Estradiol levels along with decreased BMI, Acne and hair growth and improved ultrasound parameters in same group as compared to placebo group. Conclusion: The current study showed promising results of combined therapy with MI plus DCI for treatment and improvement of clinical and lab parameters in teenage girls affected with PCOs as compared to placebo. Keywords: PCOS, Myo-inositol, D-chiro-inositol, Hirsutism, Acne.

The role of myo-inositol and calcium L-methylfolate in complex therapy of polycystic ovary syndrome

<h3></h3> Синдром поликистозных яичников (СПЯ) сопровождается комплексом нарушений, включающих гиперандрогению, инсулинорезистентность, ожирение, нарушения менструального цикла и, как следствие, ановуляторное бесплодие. Фенотипы A и D СПЯ, проявляющиеся олигоменореей и поликистозной структурой яичников (по данным ультразвукового исследования), продолжают привлекать внимание гинекологов, эндокринологов и репродуктологов, поскольку характеризуются наиболее выраженными симптомами и представляют наиболее сложную группу среди гетерогенной группы пациенток с СПЯ в отношении коррекции бесплодия и метаболических нарушений. <h3>ЦЕЛЬ ИССЛЕДОВАНИЯ</h3> Проанализировать фенотипы A и D СПЯ на основании данных пациенток, обратившихся в отделение репродуктологии ГБУЗ МО «МОНИИАГ» для лечения бесплодия, и определить частоту выявления у них инсулинорезистентности, ожирения, а также оценить эффективность терапии мио-инозитолом и L-метилфолатом кальция в комплексном применении различных методов восстановления естественной фертильности. <h3>МАТЕРИАЛ И МЕТОДЫ</h3> Обследованы 80 пациенток с фенотипами A и D СПЯ на наличие полиморфных вариантов генов фолатного цикла <i>MTHFR</i>, <i>MTRR</i>, <i>MTR</i>, гена рецептора фолликулостимулирующего гормона, на инсулинорезистентность. В контрольную группу включены 30 пациенток с мужским или трубно-перитонеальным фактором бесплодия, планирующих проведение экстракорпорального оплодотворения, обследованных на наличие инсулинорезистентности, полиморфных вариантов генов фолатного цикла и гена рецептора фолликулостимулирующего гормона. <h3>РЕЗУЛЬТАТЫ</h3> Доля обследованных женщин с фенотипом A СПЯ составила 37,5% (30 пациенток), с фенотипом D СПЯ — 62,5% (50 пациенток). Полученные данные продемонстрировали высокую частоту избыточной массы тела, ожирения и инсулинорезистентности у пациенток обеих групп. Однако ожирение чаще встречалось у пациенток с фенотипом A (56,7% по сравнению с 38% для фенотипа D). Инсулинорезистентность также выявлялась чаще у пациенток с фенотипом A (63,3% по сравнению с 14% для фенотипа D). В структуре фенотипа A инсулинорезистентность выявлена у 76,5% пациенток с ожирением, у 50% пациенток с избыточной массой тела, у 14,3% пациенток с нормальной массой тела. В структуре фенотипа D у большей доли пациенток была нормальная масса тела (36% по сравнению с 23,3% для фенотипа A). В структуре фенотипа D инсулинорезистентность выявлена у 31,6% пациенток с ожирением, у 7,7% пациенток с избыточной массой тела и не отмечена у пациенток с нормальной массой тела. <h3>ЗАКЛЮЧЕНИЕ</h3> Принимая во внимание полученные результаты, мы считаем, что Фертифолин (комбинация мио-инозитола и L-метилфолата кальция) следует включать в комплекс коррекции метаболических нарушений у пациенток с фенотипами A и D синдрома поликистозных яичников на этапе прегравидарной подготовки.

Role of Myo-Inositol in Treatment of Young Females Affected By Polycystic Ovarian Syndrome: Quasi Experimental Study

Objective: To determine the effects of Myo- inositol in young females with polycystic ovarian syndrome. Study Design and Setting: This was a quasi-experimental study and was conducted in United Medical and Dental College and Creek General Hospital from January 2017 to January 2018. Methodology: Total 100 patients were recruited based on the specific inclusion criteria of PCO diagnosed by symptoms (body mass index, menstrual irregularity, hirsutism, acne) biochemical markers (fasting insulin, random blood sugar) and ultrasound findings. Each subject in the study group was given sachet (Myo- inositol 2000mg and folic acid 400ug) once a day dissolved in glass of water for duration of 6 months. Improvement in symptoms, biochemical markers and ultrasound findings were reassessed after the completion of 6 months duration. The SPSS version 21 was used for data analysis. The paired T test was used to assess the effects of Myo-Inositol before treatment and after six months of treatment. Result: The significant relation (0.001) was observed between the intervention and PCO and its related symptoms. An evident effect was noticed in each individual after the intervention was provided to them. The relatable symptoms such as irregularities in menses, hirsutism,weight and insulin resistance were reduced by significant ratio. Conclusion: Myo – inositol has proven to be effective in reducing the PCO and its relatable symptoms in young females. Despite the limitations, enough evidence was collected that indicated a significant effect of the intervention

Role of myo-inositol during skotomorphogenesis in Arabidopsis

Myo-inositol is a ubiquitous metabolite of plants. It is synthesized by a highly conserved enzyme L-myo-inositol phosphate synthase (MIPS; EC 5.5.1.4). Myo-inositol is well characterized during abiotic stress tolerance but its role during growth and development is unclear. In this study, we demonstrate that the apical hook maintenance and hypocotyl growth depend on myo-inositol. We discovered the myo-inositol role during hook formation and its maintenance via ethylene pathway in Arabidopsis by supplementation assays and qPCR. Our results suggest an essential requirement of myo-inositol for mediating the ethylene response and its interaction with brassinosteroid to regulate the skotomorphogenesis. A model is proposed outlining how MIPS regulates apical hook formation and hypocotyl growth.

Myo-inositol mediates reactive oxygen species-induced programmed cell death via salicylic acid-dependent and ethylene-dependent pathways in apple

As a versatile compound, myo-inositol plays vital roles in plant biochemistry and physiology. We previously showed that exogenous application of myo-inositol had a positive role in salinity tolerance in Malus hupehensis Rehd. In this study, we used MdMIPS (the rate-limiting gene of myo-inositol biosynthesis) transgenic apple lines to gain new insights into the physiological role of myo-inositol in apple. Decreasing myo-inositol biosynthesis in apple lines by RNA silencing of MdMIPS1/2 led to extensive programmed cell death, which manifested as necrosis of both the leaves and roots and, ultimately, plant death. Necrosis was directly caused by the excessive accumulation of reactive oxygen species, which may be closely associated with the cell wall polysaccharide-mediated increase in salicylic acid and a compromised antioxidant system, and this process was enhanced by an increase in ethylene production. In addition, a high accumulation of sorbitol promoted necrosis. This synergetic interplay between salicylic acid and ethylene was further supported by the fact that increased myo-inositol accumulation significantly delayed leaf senescence in MdMIPS1-overexpressing apple lines. Taken together, our results indicated that apple myo-inositol regulates reactive oxygen species-induced programmed cell death through salicylic acid-dependent and ethylene-dependent pathways.

P1000URINE MYO-INOSITOL AS A NOVEL PROGNOSTIC BIOMARKER FOR DIABETIC KIDNEY DISEASE

Abstract Background and Aims Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESRD). Metabolomics has been increasingly applied to identify the cause of CKD, as it can present epigenetics and suggest corresponding treatment options. Only a few metabolomics studies were conducted in DKD patients, and the results are inconclusive. We investigated the association between urine metabolites and renal disease progression and mortality in DKD, using 800 MHz NMR spectroscopy based targeted metabolomics profiling. Method Prospectively stored urine samples from consecutive patients with DKD stage 1 to 5 (n=208) and their healthy controls (n=26) were analyzed. Cross-sectional associations were evaluated between eGFR or urine protein creatinine ratio (UPCR) and 26 urinary metabolites. Multivariable adjusted Cox models were conducted for the risk prediction of ESRD and mortality. The receiver-operating characteristic (ROC) analyses were used to assess the additive effect of each metabolite to predict the progression to ESRD. Results ESRD occurred in 103 (44.0%) patients and 65 (27.8%) deaths occurred during median 4.5 years (IQR, 2.06–6.58) follow-up period. The median fold change in 9 metabolites (glucose, mannose, myo-inositol, glycerol, lactate, fumarate, creatine, taurine and choline) in patient group revealed a trend corresponding to DKD stages. Linear regression showed that myo-inositol had a strongest association with eGFR. The relationship between the competitive metabolites and outcomes (ESRD and mortality) was investigated by multivariate Cox models after adjusting for the baseline covariates. Of these, 4 metabolites (myo-inositol, glycerol, fumarate, oxoisocaproate) had predictive values for ESRD, and among them, only myo-inositol retained predictive significance in mortality (adjusted HR 1.004, 95% confidence interval 1.002-1.006, P &amp;lt; 0.001). At ROC analysis, urinary myo-inositol had additive effect to serum creatinine concentration and UPCR in the prediction for ESRD progression (NRI = 2.9%, P = 0.03; IDI = 35.1%, P = 0.02). Conclusion These results suggest that myo-inositol can be a predictive biomarker for the risk of ESRD progression and mortality in DKD. Further studies are needed to elucidate the pathophysiological roles of myo-inositol in DKD.

Myo-Inositol's Role in Assisted Reproductive Technology: Evidence for Improving the Quality of Oocytes and Embryos in Patients With Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common causes of subfertility, and it is characterized by hormonal dysregulation like insulin resistance. Various measures have been taken in the past to overcome this insulin resistance to improve fertility treatment outcomes. The current paper aims to review and compare the existing studies and literature to assess the impact of myo-inositol (MI) on oocyte and embryo quality in assisted reproductive technology (ARTs). We thoroughly searched the PubMed and Google Scholar databases by using the keywords “PCOS, polycystic ovarian syndrome, inositol, oocyte quality, embryo quality, assisted conception, ART, IVF, and in vitro fertilization.” Nine articles were finalized for review in this paper. Many of the reviewed studies have shown a trend toward the improvement of embryo quality in women with PCOS after MI supplementation; however, there is a lack of statistically significant evidence to support the use of MI in enhancing the quality of oocyte and/or embryo. Clear evidence regarding the role of MI in enhancing the quality of oocyte and embryo in PCOS is limited. A well-controlled, large, randomized controlled trial is required to definitively accept or refute its role.

Efficacy and Safety of Tracnil™ Administration in Patients with Dermatological Manifestations of PCOS: An Open-Label Single-Arm Study.

Myo-inositol's role in improving acne by reducing hyperandrogenism has been demonstrated in PCOS patients. Inositol and associated molecules display inhibitory properties against 5-α reductase, COX-2, and lipase enzymes in addition to their antimicrobial and anti-inflammatory properties. However, the role of myo-inositol is not well established in women patients with normal hormone levels but with clinical manifestations of PCOS. In this study, we evaluate the efficacy of Tracnil™, a combination of myo-inositol with folic acid and vitamin D3, in resolving acne in overweight women of menstruation age displaying normal hormone levels. It is a single-arm study conducted at 2 centers including 33 women with acne, hirsutism, and menstrual irregularities. Acne and hirsutism were assessed by manual lesion count, modified Cook's scale, and modified Ferriman–Gallwey hirsutism score (mFGHS). Hormone levels and safety parameters were assessed throughout the study. Our results show that Tracnil™ monotherapy could drastically reduce acne-related lesions of both inflammatory and noninflammatory types as quickly as 8 weeks. Additionally, it improves hirsutism and menstrual irregularities. Adverse reactions were negligible during the whole study period with no drastic side effects reflected by a modulatory effect on hormone levels. Despite the subjects having normal hormone levels, the acne treatment with myo-inositol and vitamin D3 shows improvement in hirsutism and regularization of menstrual cycle. Therefore, we attribute the mechanism of action of Tracnil™ to modulation of receptor sensitivity to sex hormones or other downstream processing events. Tracnil™ may be considered as a first-line treatment for dermatological manifestations of PCOS even in the absence of significant hormonal abnormalities. This treatment is practically implementable in a dermatologists's office practise.

Myo-Inositol and Its Derivatives: Their Emerging Role in the Treatment of Human Diseases.

Myo-inositol has been established as an important growth-promoting factor of mammalian cells and animals. The role of myo-inositol as a lipotropic factor has been proven, in addition to its involvement as co-factors of enzymes and as messenger molecules in signal transduction. Myo-inositol deficiency leads to intestinal lipodystrophy in animals and “inositol-less death” in some fungi. Of late, diverse uses of myo-inositol and its derivatives have been discovered in medicinal research. These compounds are used in the treatment of a variety of ailments from diabetes to cancer, and continued research in this direction promises a new future in therapeutics. In different diseases, inositols implement different strategies for therapeutic actions such as tissue specific increase or decrease in inositol products, production of inositol phosphoglycans (IPGs), conversion of myo-inositol (MI) to D-chiro-inositol (DCI), modulation of signal transduction, regulation of reactive oxygen species (ROS) production, etc. Though inositol pharmacology is a relatively lesser-known field, recent years of research has generated a critical mass of information on the subject. This review aims to summarize our current understanding on the role of inositol derivatives in ameliorating the symptoms of different diseases.

Diet and Nutritional Interventions with the Special Role of Myo-Inositol in Gestational Diabetes Mellitus Management. An Evidence-Based Critical Appraisal.

Gestational Diabetes Mellitus (GDM), defined as glucose intolerance with onset or first recognition during pregnancy, represents one of the most common maternal-fetal complications during pregnancy and it is associated with poor perinatal outcomes. To date, GDM is a rising condition over the last decades coinciding with the ongoing epidemic of obesity and Type 2 Diabetes Mellitus (T2DM). The aim of this review is to discuss the role of diet and nutritional interventions in preventing GDM with the explanation of the special role of myo-inositol (MI) in this matter. We performed an overview of the most recent literature data on the subject with particular attention to the effectiveness of diet and nutritional interventions in the prevention of GDM with the special role of MI. Nutritional intervention and physical activity before and during pregnancy are mandatory in women affected by GDM. Moreover, the availability of insulin-sensitizers such as different forms of inositol has dramatically changed the scenario, allowing the treatment of several metabolic diseases, such as those related to glucose dysbalance. Although the optimal dose, frequency, and form of MI administration need to be further investigated, diet supplementation with MI appears to be an attractive alternative for the GDM prevention as well as for the reduction of GDM-related complications. More studies should be conducted to prove the most effective nutritional intervention in GDM. Regarding the potential effectiveness of MI, further evidence in multicenter, randomized controlled trials is needed to draw firm conclusions.

Non-pharmacological management of gestational diabetes: The role of myo-inositol.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder occurring in pregnancy. GDM plays an important role in the current diabetes epidemic: exposure to a high glycemic environment during the early stages of development increases the risk of the fetus to develop type two diabetes mellitus (T2DM) in adult life. Various cardiometabolic risk factors are linked to GDM. A thorough knowledge of the risk factors and genes involved in the development of GDM, along with an understanding of the underlying pathophysiological mechanisms are crucial to properly identify patients at risk of developing this condition. There is growing evidence showing that myo-inositol, combined with an appropriate therapeutic regimen for GDM, can provide additional benefits to the patient. The aim of this review is to analyze the role of inositol isomers - especially myo-inositol (MYO-INS) - in the treatment of patients with GDM.