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Androgen excess is a key feature of several clinical phenotypes of polycystic ovary syndrome (PCOS). However, the presence of FSH receptor (FSHR) and aromatase (CYP19A1) activity responses to physiological endocrine stimuli play a critical role in the pathogenesis of PCOS. Preliminary data suggest that myo-Inositol (myo-Ins) and D-Chiro-Inositol (D-Chiro-Ins) may reactivate CYP19A1 activity. We investigated the steroidogenic pathway of Theca (TCs) and Granulosa cells (GCs) in an experimental model of murine PCOS induced in CD1 mice exposed for 10 weeks to a continuous light regimen. The effect of treatment with different combinations of myo-Ins and D-Chiro-Ins on the expression of Fshr, androgenic, and estrogenic enzymes was analyzed by real-time PCR in isolated TCs and GCs and in ovaries isolated from healthy and PCOS mice. Myo-Ins and D-Chiro-Ins, at a ratio of 40:1 at pharmacological and physiological concentrations, positively modulate the steroidogenic activity of TCs and the expression of Cyp19a1 and Fshr in GCs. Moreover, in vivo, inositols (40:1 ratio) significantly increase Cyp19a1 and Fshr. These changes in gene expression are mirrored by modifications in hormone levels in the serum of treated animals. Myo-Ins and D-Chiro-Ins in the 40:1 formula efficiently rescued PCOS features by up-regulating aromatase and FSHR levels while down-regulating androgen excesses produced by TCs. [ABSTRACT FROM AUTHOR]

D-chiro-inositol (DCI) is a potential drug for the treatment of type II diabetes and polycystic ovary syndrome. In order to effectively synthesize DCI in Corynebacterium glutamicum, the genes related to inositol catabolism in clusters iol1 and iol2 were knocked out in C. glutamicum SN01 to generate the chassis strain DCI-1. DCI-1 did not grow in and catabolize myo-inositol (MI). Subsequently, different exogenous and endogenous inosose isomerases were expressed in DCI-1 and their conversion ability of DCI from MI were compared. After fermentation, the strain DCI-7 co-expressing inosose isomerase IolI2 and inositol dehydrogenase IolG was identified as the optimal strain. Its DCI titer reached 3.21 g/L in the presence of 20 g/L MI. On this basis, the pH, temperature and MI concentration during whole-cell conversion of DCI by strain DCI-7 were optimized. Finally, the optimal condition that achieved the highest DCI titer of 6.96 g/L were obtained at pH 8.0, 37 °C and addition of 40 g/L MI. To our knowledge, it is the highest DCI titer ever reported. [ABSTRACT FROM AUTHOR]

This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li2CO3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li2CO3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C–group). The INO was administered as a mixture of myo-inositol and d-chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease.

Introduction and purpose Polycystic ovary syndrome is a common reproductive disorder, accompanied primarily by hyperandrogenism and insulin resistance. Myo-inositol (MI) and D-chiro-inositol (DCI), have emerged as potential therapeutic agents due to their role as insulin sensitizers. This article examines the effects of inositol therapy on fertility in women with PCOS and its role in assisted reproductive technology (ART). Studies suggest that inositols alleviate irregular menstruation, reduce androgen levels and positively affect ovulation rates. MI supplementation has also shown positive effects during controlled ovarian hyperstimulation and IVF procedures, reducing the required FSH dose and cycle length. However, despite positive results on ovulation and menstrual regularity, the article indicates the need for further studies to establish inositol as standard ART therapy in patients with PCOS. Material and methods The following review was based on articles from the PubMed and Google Scholar databases. Key search terms included polycystic ovary syndrome; assisted reproductive treatment, insulin resistance, inositols, Myo-inositol, D-chiro-inositol. Conclusions Inositols are a promising therapeutic option for women with PCOS. They have been shown to have positive effects on improving insulin sensitivity and fertility. However, despite inositol's safety and easy availability, the ideal dose and timing of use, the appropriate MI/DCI ratio, as well as the potential side effects of excess DCI and the problem of inositol resistance, require further comprehensive studies. [ABSTRACT FROM AUTHOR]

Purpose: A prospective investigation to assess the impact of 3 months of treatment with epigallocatechin gallate (EGCG), vitamin D and D-chiro-inositol (DCI) in the treatment of uterine fibroids (UF) with laparoscopic myomectomy as evidenced by surgical outcomes and effect on liver function. Methods: Non-pregnant or lactating women aged between 30 and 40 years were scheduled for laparoscopic myomectomy to treat symptoms or looking to conceive. After enrollment, patients were assigned to either (1) intervention group, assuming a total of 300 mg EGCG, 50 μg vitamin D, and 50 mg DCI divided in 2 pills per day for 3 months, or (2) control group, including untreated women scheduled to undergo laparoscopic myomectomy after 3 months. Results: 91 patients completed the study. The comparison of the surgical outcomes between the intervention (n = 44) and the control (n = 47) groups revealed that the treatment significantly reduces the duration of surgery (41.93 ± 7.56 min vs 56.32 ± 10.63 min, p < 0.001). Moreover, the treatment also reduced blood loss during surgery (149.09 ± 25.40 mL vs 168.41 ± 21.34 mL, p < 0.001), resulting in treated patients having higher Hb levels at discharge 11.27 ± 0.82 mL vs 10.56 ± 0.82 mL, p < 0.01). The surgery induced an increase in AST and in total bilirubin regardless of the assigned group, and the treatment induced no change in liver function. Conclusions: Our data suggest that EGCG plus vitamin D, and DCI could represent a safe option for women with UF scheduled for laparoscopic myomectomy, improving surgical outcomes without affecting liver functionality. [ABSTRACT FROM AUTHOR]

Setting: Insulin resistance (IR) and compensatory hyperinsulinemia are considered contributing factors toward polycystic ovary syndrome (PCOS). Objectives: This study evaluates the frequency of metabolic abnormalities in PCOS patients and the effects of myo-inositol (MI) and D-chiro-inositol (DCI), in a 40:1 ratio on hormonal and metabolic parameters. Participants: Thirty-four women with PCOS phenotype A (endocrine-metabolic syndrome [EMS-type 1]) between the ages of 20–40. Design: Open prospective study with phenotype A (EMS-type I, n = 34) supplemented with 2,255 mg/day of inositol (MI and DCI in a 40:1 ratio) for 3 months. Methods: The following were measured before and after treatment: serum levels of follicular stimulating hormone, luteinizing hormone (LH), estradiol, total and free testosterone, sex hormone-binding globulin (SHBG), free androgen index (FAI), anti-Müllerian hormone, glucose, insulin, HOMA-IR, and body mass index (BMI). Results: 55.9% of the enrolled patients were overweight or obese, 50% affected by IR, 17.6% with a history of gestational diabetes mellitus, and 61.8% had familial diabetes mellitus. At the conclusion of the study, BMI (p = 0.0029), HOMA-IR (p < 0.001) significantly decreased, along with decreased numbers of patients with elevated insulin levels. The supplementation resulted in decreased total testosterone (p < 0.001), free testosterone (p < 0.001), FAI (p < 0.001), and LH (p < 0.001); increased SHBG (p < 0.001) and estradiol (p < 0.001). Limitations: The present analysis was limited to a 12-week follow-up, which precluded a long-term evaluation of the effects of MI and DCI combination. Also, this period was insufficient to achieve and analyze clinical changes such as restoration of the menstrual cycle, restoration of reproductive function, and clinical manifestations of hyperandrogenism. Conclusions: Supplementation improved metabolic and hormonal profile in PCOS phenotype A (EMS-type I) patients. This builds upon previous work that demonstrated that combined inositol treatment may be effective in PCOS. The study presented herein, used a reduced concentration than in prior literature; however, a significant change in hormonal and metabolic parameters was still observed. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) treatment in adolescents currently focuses on lifestyle interventions, with pharmacological treatment options often limited to hormonal contraceptives. Several of these carry broad side-effect profiles and are not always accepted by young girls. There is growing interest in non-hormonal therapies for PCOS. We aimed to collate the evidence on the use of myoinositol or D-chiro-inositol in the improvement of PCOS symptoms in symptomatic adolescents. A systematic literature review identifying key articles from inception to March 2023. Participants: Female adolescents (aged 12–19 years) with PCOS or PCOS-like features. Intervention: Myoinositol or D-chiro-inositol with or without additional interventions. Comparison: Any other treatment, including lifestyle interventions, hormonal therapy, metformin or no treatment. The main outcome measure were improvement in symptoms, quality of life and adverse effects. Eight studies were included: two randomised open-label trials, one quasi-randomised and three non-randomised interventional studies, one case-control study and one cohort study. All studies showed improvements in some biochemical markers, metabolic parameters or clinical symptoms, but these were not reproducible across all studies. The benefit of myoinositol in adolescents with PCOS remains unclear, with limited high-quality evidence. This review highlights the need for robustly conducted research to inform clinical practice. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is associated with cardiovascular risk factors, such as insulin resistance, dyslipidaemia, hypertension and abdominal obesity. Given the growing need to investigate food supplements with positive health effects, this study was aimed at testing the benefits of a specific supplement for people with MetS. Fifty-eight subjects with MetS and T2DM or impaired glucose tolerance assuming metformin, were randomly assigned to take a food supplement of glucomannan, D-chiro-inositol, Cinnamomum zeylanicum blume and inulin at a daily fixed dose of 4 g orally for four months. Body weight, waist circumference, plasma lipid profile (total cholesterol, LDL, HDL and triglyc-erides), plasma glycaemic profile and visceral adiposity index (VAI) were measured at baseline and after four months of supplementation. After 16 weeks, in subjects with T2DM or insulin resistance who took the supplement (+ metformin), there was a significant reduction in body weight and BMI (p < 0.0001), serum insulin (p < 0.05) and the HOMA index (p < 0.01), as well as in the lipaemic pattern, with a significant improvement in total serum cholesterol (p < 0.005), triglycerides (p < 0.03) and LDL (p < 0.02). Our study shows that the food supplement tested is a valid and safe alternative therapeutic approach in the management of MetS and all its resulting risk factors, as its efficacy has been demonstrated across anthropometric, glucose, lipid and hepatic parameters. [ABSTRACT FROM AUTHOR]

Inositols are insulin-sensitizing compounds that have also regulatory functions in human reproduction. In the ovary, myo-inositol (myo-ins) mediates the granulosa response to follicle-stimulating hormone stimuli and plays a crucial role in determining oocyte maturation. D-chiro-inositol, by contrast, is involved in the regulation of ovarian steroidogenesis and at high concentrations may be detrimental for oocyte quality due to its aromatase down-modulator activity. Supplementation with myo-ins during assisted reproductive technologies reduces the total amount of gonadotropins used in polycystic ovary syndrome (PCOS) and non-PCOS women and leads to improvements in oocyte quality and maturation and embryo development and an increase in the rate of successful pregnancies. Myo-ins also acts directly on spermatogenesis, improving sperm performance in vitro and in vivo. Inositols are insulin-sensitizing compounds of promising efficacy in the management of polycystic ovary syndrome (PCOS). On the one hand, myo-inositol (myo-ins) plays a regulatory role in male and female reproductive function, influencing the development of oocytes, spermatozoa, and embryos. On the other hand, high concentrations of D-chiro-inositol (D-chiro-ins) in the ovary may adversely affect oocyte quality. This review analyses the available literature, which encourages the clinical use of myo-ins in assisted reproductive technologies (ARTs) due to its beneficial effects on female and male reproduction. [ABSTRACT FROM AUTHOR]

This paper describes the development of a simple voltammetric biosensor for the stereoselective discrimination of myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) by means of bovine serum albumin (BSA) adsorption onto a multi-walled carbon nanotube (MWCNT) graphite screen-printed electrode (MWCNT-GSPE), previously functionalized by the electropolymerization of methylene blue (MB). After a morphological characterization, the enantioselective biosensor platform was electrochemically characterized after each modification step by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The results show that the binding affinity between myo-Ins and BSA was higher than that between D-chiro-Ins and BSA, confirming the different interactions exhibited by the novel BSA/MB/MWCNT/GSPE platform towards the two diastereoisomers. The biosensor showed a linear response towards both stereoisomers in the range of 2–100 μM, with LODs of 0.5 and 1 μM for myo-Ins and D-chiro-Ins, respectively. Moreover, a stereoselectivity coefficient α of 1.6 was found, with association constants of 0.90 and 0.79, for the two stereoisomers, respectively. Lastly, the proposed biosensor allowed for the determination of the stereoisomeric composition of myo-/D-chiro-Ins mixtures in commercial pharmaceutical preparations, and thus, it is expected to be successfully applied in the chiral analysis of pharmaceuticals and illicit drugs of forensic interest. [ABSTRACT FROM AUTHOR]

Introduction and purpose Polycystic ovary syndrome is a common reproductive disorder, accompanied primarily by hyperandrogenism and insulin resistance. Myo-inositol (MI) and D-chiro-inositol (DCI), have emerged as potential therapeutic agents due to their role as insulin sensitizers. This article examines the effects of inositol therapy on fertility in women with PCOS and its role in assisted reproductive technology (ART). Studies suggest that inositols alleviate irregular menstruation, reduce androgen levels and positively affect ovulation rates. MI supplementation has also shown positive effects during controlled ovarian hyperstimulation and IVF procedures, reducing the required FSH dose and cycle length. However, despite positive results on ovulation and menstrual regularity, the article indicates the need for further studies to establish inositol as standard ART therapy in patients with PCOS. Material and methods The following review was based on articles from the PubMed and Google Scholar databases. Key search terms included polycystic ovary syndrome; assisted reproductive treatment, insulin resistance, inositols, Myo-inositol, D-chiro-inositol. Conclusions Inositols are a promising therapeutic option for women with PCOS. They have been shown to have positive effects on improving insulin sensitivity and fertility. However, despite inositol's safety and easy availability, the ideal dose and timing of use, the appropriate MI/DCI ratio, as well as the potential side effects of excess DCI and the problem of inositol resistance, require further comprehensive studies.

Androgen excess is a key feature of several clinical phenotypes of polycystic ovary syndrome (PCOS). However, the presence of FSH receptor (FSHR) and aromatase (CYP19A1) activity responses to physiological endocrine stimuli play a critical role in the pathogenesis of PCOS. Preliminary data suggest that myo-Inositol (myo-Ins) and D-Chiro-Inositol (D-Chiro-Ins) may reactivate CYP19A1 activity. We investigated the steroidogenic pathway of Theca (TCs) and Granulosa cells (GCs) in an experimental model of murine PCOS induced in CD1 mice exposed for 10 weeks to a continuous light regimen. The effect of treatment with different combinations of myo-Ins and D-Chiro-Ins on the expression of Fshr, androgenic, and estrogenic enzymes was analyzed by real-time PCR in isolated TCs and GCs and in ovaries isolated from healthy and PCOS mice. Myo-Ins and D-Chiro-Ins, at a ratio of 40:1 at pharmacological and physiological concentrations, positively modulate the steroidogenic activity of TCs and the expression of Cyp19a1 and Fshr in GCs. Moreover, in vivo, inositols (40:1 ratio) significantly increase Cyp19a1 and Fshr. These changes in gene expression are mirrored by modifications in hormone levels in the serum of treated animals. Myo-Ins and D-Chiro-Ins in the 40:1 formula efficiently rescued PCOS features by up-regulating aromatase and FSHR levels while down-regulating androgen excesses produced by TCs.

Objective: Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting reproductive and metabolic indices in females. The present study was designed to compare the efficacy of metformin and D-chiroinositol in PCOS patients. Methods: In a tertiary care hospital in North India, prospective observational research was undertaken on 100 patients with PCOS, which was diagnosed based on European Society of Human Reproduction and Embryology Guidelines and ultrasound of lower abdomen. The study involves various clinical characteristics into consideration for the determination of statistical significance (P < 0.05) in PCOS patients. Student's t -test along with the association between PCOS and patients taking metformin and D-chiro-inositol, as well as their impact on various biochemical parameters, were investigated finally using Pearson Correlation Analysis. Results: This study comprises 50 patients taking metformin and 50 patients taking D-chiro-inositol in women suffering from PCOS. Body mass index (BMI) and waist-to-hip ratio (WHR) were statistically significant (P < 0.05) within the groups of both metformin and D-chiro-inositol. Biochemical parameters such as luteinizing hormone (LH), follicle stimulating hormone (FSH), anti-mullerian hormone (AMH) and glycated hemoglobin (HbA1c) were found to be statistically significant (P < 0.05) in both groups. LH, FSH and AMH (14.40 ± 0.52; 14.28 ± 0.53; 1.99 ± 0.10) were comparatively lower in patients taking D-chiro-inositol as compared to metformin group (14.17 ± 0.42; 19.88 ± 1.01; 2.61 ± 0.04). HbA1c (3.71 ± 0.08) with P < 0.05 was found to be decreased more in metformin group as compared to patients taking D-chiro-inositol (4.90 ± 0.09). A positive correlation was found between HbA1c and LH in metformin, & HbA1c and FSH in D-chiro-inositol groups, respectively. Conclusion: The results indicate that D-chiro-inositol shows better results in reducing clinical variables involved in causing PCOS as compared to metformin whereas metformin has better glycemic control in PCOS patients. [ABSTRACT FROM AUTHOR]

Background: Menstrual cycle disorders represent a prevalent cause for gynecological consultations. These disorders often encompass ovulatory dysfunction, accompanied by analytical and clinical anomalies linked to hyperandrogenism, collectively defining polycystic ovary syndrome (PCOS). However, a considerable subset of patients suffering from menstrual cycle disorders fails to meet the diagnostic criteria for any recognized PCOS phenotypes, leading to substantial debate in the field. This study aims to assess the impact of a commercially available combination of inositols, melatonin, folic acid, and vitamin D in patients experiencing menstrual disorders, characterized by oligo-anovulation (amenorrhea and abnormally long cycles), irrespective of their actual compliance with PCOS criteria. Methods: An observational, prospective, non-randomized study was devised to assess cycle regularity, satisfaction levels, and analytical alterations following the administration of the combination of inositols, melatonin, folic acid, and vitamin D (at baseline and at 6 months). Statistical analysis was executed using SPSS (version 22.0). Results: The assessed treatment demonstrated an enhancement in the regularity of menstrual cycles, accompanied by notable reductions in androstenedione and dehydroepiandrosterone (DHEA) levels, as well as basal insulin and the homeostatic model assessment for insulin resistance (HOMA), despite their initial values falling within the normal range. Furthermore, there was a substantial elevation in the serum levels of vitamin D (p < 0.05). Following 6 months of treatment, a high degree of patient satisfaction was observed, with no documented adverse effects within the selected sample. Conclusions: The combination of inositols, melatonin, folic acid, and vitamin D exhibits potential as an efficacious approach for managing menstrual disorders while maintaining a commendable safety profile. Additional investigations into the long-term efficacy and safety of this formulation are warranted, although initial results hold promise.

Endometrial hyperplasia is a threatening pathology driven by unopposed estrogen stimulus. Moreover, insulin may act on the endometrium, prompting further growth. We aimed at assessing whether D-chiro-Inositol, an insulin sensitizer with estrogen-lowering properties, might improve the condition of patients with simple endometrial hyperplasia without atypia. We enrolled women with simple endometrial hyperplasia without atypia and related symptoms, including abnormal uterine bleeding. We treated the patients with one tablet per day, containing 600 mg of D-chiro-inositol for six months. Patients underwent ultrasound to assess the thickness of the endometrium at baseline, after three months, and at the end of this study. Endometrial thickness went from 10.82 ± 1.15 mm to 8.00 ± 0.81 mm after three months (p < 0.001) and to 6.9 ± 1.06 mm after six months (p < 0.001 versus baseline; p < 0.001 versus three months). D-chiro-inositol treatment also improved heavy menstrual bleeding and the length of menstruation. Despite the fact that our data should be validated in larger studies with appropriate control groups, our promising results support the hypothesis that D-chiro-inositol may represent a useful treatment in the case of endometrial hyperplasia without atypia. [ABSTRACT FROM AUTHOR]

Diabetic osteoporosis (DO) has been increasingly recognized as an important complication of diabetes. D-pinitol, a natural compound found in various legumes, is known for its anti-diabetic function, but its effect on DO has not been investigated. Two doses of pinitol (50 and 100 mg/kg Bw/d) were administered orally to experimentally induce the DO mouse model for 5 weeks. The results indicated that pinitol suppressed fasting blood glucose levels and tended to enhance impaired pancreatic function. Pinitol also suppressed serum bone turnover biomarkers, and improved dry femur weight, cancellous bone rate, and bone mineral content in the DO mice. Based on the inositol quantification using GC-MS in serum, liver, kidney, and bone marrow, the pinitol treatment significantly recovered the depleted D-chiro-inositol (DCI) content or the decreased the ratio of DCI to myo-inositol caused by DO. In short, our results suggested that pinitol improved glucose metabolism and inhibited bone loss in DO mice via elevating the DCI levels in tissues. [ABSTRACT FROM AUTHOR]

White adipose tissue/brown adipose tissue trans-differentiation is one of the main study targets for therapies against obesity and metabolic diseases. In recent years, numerous molecules able to induce such trans-differentiation have been identified; however, their effect in obesity therapies has not been as expected. In the present study, we investigated whether myo-inositol and its stereoisomer D-chiro-inositol could be involved in the browning of white adipose tissue. Our preliminary results clearly indicate that both, at 60 μM concentration, induce the upregulation of uncoupling protein 1 mRNA expression, the main brown adipose tissue marker, and increase mitochondrial copy number as well as oxygen consumption ratio. These changes demonstrate an activation of cell metabolism. Therefore, our results show that human differentiated adipocytes (SGBS and LiSa-2), assume the features typical of brown adipose tissue after both treatments. Furthermore, in the cell lines examined, we proved that D-chiro-inositol and myo-Inositol induce an increase in the expression of estrogen receptor mRNAs, suggesting a possible modulation by these isomers. We also found an increase in the mRNA of peroxisome proliferator-activated receptor gamma, a very important target in lipid metabolism and metabolic diseases. Our results open new opportunities for the use of inositols in therapeutic strategies to counteract obesity and its metabolic complications. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women, in which, besides chronic anovulation/oligomenorrhea and ovarian cysts, hyperandrogenism plays a critical role in a large fraction of subjects. Inositol isomers—myo-Inositol and D-Chiro-Inositol—have recently been pharmacologically effective in managing many PCOS symptoms while rescuing ovarian fertility. However, some disappointing clinical results prompted the reconsideration of their specific biological functions. Surprisingly, D-Chiro-Ins stimulates androgen synthesis and decreases the ovarian estrogen pathway; on the contrary, myo-Ins activates FSH response and aromatase activity, finally mitigating ovarian hyperandrogenism. However, when the two isomers are given in association—according to the physiological ratio of 40:1—patients could benefit from myo-Ins enhanced FSH and estrogen responsiveness, while taking advantage of the insulin-sensitizing effects displayed mostly by D-Chiro-Ins. We need not postulate insulin resistance to explain PCOS pathogenesis, given that insulin hypersensitivity is likely a shared feature of PCOS ovaries. Indeed, even in the presence of physiological insulin stimulation, the PCOS ovary synthesizes D-Chiro-Ins four times more than that measured in control theca cells. The increased D-Chiro-Ins within the ovary is detrimental in preserving steroidogenic control, and this failure can easily explain why treatment strategies based upon high D-Chiro-Ins have been recognized as poorly effective. Within this perspective, two factors emerge as major determinants in PCOS: hyperandrogenism and reduced aromatase expression. Therefore, PCOS could no longer be considered a disease only due to increased androgen synthesis without considering the contemporary downregulation of aromatase and FSH receptors. Furthermore, these findings suggest that inositols can be specifically effective only for those PCOS phenotypes featured by hyperandrogenism. [ABSTRACT FROM AUTHOR]

Common buckwheat (Fagopyrum esculentum Moench) is the only crop that contains D-chiro-inositol (DCI) in significant contents in vegetative tissues and its a-D-galactosyl derivatives in seeds. Besides DCI, buckwheat tissues contain small contents of D-pinitol (PIN) and myo-inositol (MIN) and their a-D-galactosyl derivatives. D-chiro-inositol is a health-promoting cyclitol of increasing importance in the treatment of some human diseases. However, changes in DCI content in stems, leaves and maturing buckwheat seeds during plant vegetation and under desiccation were not known. The present study analyzed the concentration of cyclitols and their galactosides in the stems, leaves and seeds of plants harvested on 79th, 94th and 123th days after sowing (DAS) and after desiccation at ambient temperature (23° ±2°C). D-chiro-inositol content in stems and leaves increased with vegetation, while the opposite trend was found in developing and maturing seeds. In the seeds, the accumulation of mono-galactosyl DCI derivatives increased, but at the same time, the content of mono-galactosyl PIN and MIN derivatives decreased. The desiccation process drastically increased the content of di-galactosyl derivatives of DCI and MIN in the seeds. The obtained results suggest a protective role of DCI and MIN di-galactosides against desiccation stress in buckwheat tissues. [ABSTRACT FROM AUTHOR]

D-chiro-inositol (DCI) is an isomer of inositol, abundant in many foods, such as beans and buckwheat, with insulin-sensitizing, anti-inflammatory, and antioxidant effects. DCI has been used to relieve insulin resistance in diabetes and polycystic ovary syndrome in combination with inositol or D-pinitol. Here, we investigated the effect of DCI on aging and stress resistance in C. elegans. We found that DCI could prolong the lifespan of C. elegans by up to 29.6 %. DCI significantly delayed the onset of neurodegenerative diseases in models of C. elegans. DCI decreased the accumulation of Aβ1–42, alpha-synuclein, and poly-glutamine, the pathological causes of Alzheimer's, Parkinson's, and Huntington's diseases, respectively. DCI significantly increased the stress resistances against pathogens, oxidants and heat shock. Moreover, D-chiro-inositol reduced the content of ROS and malondialdehyde by increasing the total antioxidant capacity and the activity of superoxide dismutase and catalase. Above effects of DCI requires the transcription factors FOXO/DAF-16 and Nrf-2/SKN-1. DCI also increased the expression of downstream genes regulated by FOXO/DAF-16 and Nrf-2/SKN-1. In conclusion, DCI enhanced the antioxidant capacity and healthy lifespan of C. elegans by activating DAF-16, SKN-1, and HSF-1. Our results showed that DCI could be a promising antiaging agent that is worth further research on the mechanism and health supplemental application of DCI.

Metabolic syndrome (MetS) is associated with cardiovascular risk factors, such as insulin resistance, dyslipidaemia, hypertension and abdominal obesity. Given the growing need to investigate food supplements with positive health effects, this study was aimed at testing the benefits of a specific supplement for people with MetS. Fifty-eight subjects with MetS and T2DM or impaired glucose tolerance assuming metformin, were randomly assigned to take a food supplement of glucomannan, D-chiro-inositol, Cinnamomum zeylanicum blume and inulin at a daily fixed dose of 4 g orally for four months. Body weight, waist circumference, plasma lipid profile (total cholesterol, LDL, HDL and triglyc-erides), plasma glycaemic profile and visceral adiposity index (VAI) were measured at baseline and after four months of supplementation. After 16 weeks, in subjects with T2DM or insulin resistance who took the supplement (+ metformin), there was a significant reduction in body weight and BMI (p < 0.0001), serum insulin (p < 0.05) and the HOMA index (p < 0.01), as well as in the lipaemic pattern, with a significant improvement in total serum cholesterol (p < 0.005), triglycerides (p < 0.03) and LDL (p < 0.02). Our study shows that the food supplement tested is a valid and safe alternative therapeutic approach in the management of MetS and all its resulting risk factors, as its efficacy has been demonstrated across anthropometric, glucose, lipid and hepatic parameters.

Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and lipid alterations. Besides pharmacological treatment, lifestyle modifications and nutraceuticals can be used to manage glucose and lipid profiles, which is crucial for preventing, or avoiding, serious consequences associated with the condition. This randomized controlled clinical trial on 75 patients with T2DM evaluated the effects of a combination of myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc on glucose and lipid profile. The intention-to-treat analysis displayed no significant differences in glucose parameters between the groups; however, the study group displayed reduced levels of total cholesterol (p = 0.01) and LDL (p = 0.03) after 3 months of supplementation. A subgroup analysis involving patients who did not modify their antidiabetic therapy, after 6 months displayed improved levels of total cholesterol (p = 0.03) and LDL (p = 0.04) in the study group versus placebo, along with a greater body weight reduction (p = 0.03) after 3 months. Furthermore, within the study group, levels of HDL (p = 0.03) and triglycerides (p = 0.04) improved after 3 months. These findings support supplementation with myo-inositol and d-chiro-inositol (40:1), α-lactalbumin, Gymnema sylvestre, and zinc as an adjuvant and safe strategy to manage the lipid profiles of patients with T2DM.

This paper describes the development of a simple voltammetric biosensor for the stereoselective discrimination of myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) by means of bovine serum albumin (BSA) adsorption onto a multi-walled carbon nanotube (MWCNT) graphite screen-printed electrode (MWCNT-GSPE), previously functionalized by the electropolymerization of methylene blue (MB). After a morphological characterization, the enantioselective biosensor platform was electrochemically characterized after each modification step by differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). The results show that the binding affinity between myo-Ins and BSA was higher than that between D-chiro-Ins and BSA, confirming the different interactions exhibited by the novel BSA/MB/MWCNT/GSPE platform towards the two diastereoisomers. The biosensor showed a linear response towards both stereoisomers in the range of 2–100 μM, with LODs of 0.5 and 1 μM for myo-Ins and D-chiro-Ins, respectively. Moreover, a stereoselectivity coefficient α of 1.6 was found, with association constants of 0.90 and 0.79, for the two stereoisomers, respectively. Lastly, the proposed biosensor allowed for the determination of the stereoisomeric composition of myo-/D-chiro-Ins mixtures in commercial pharmaceutical preparations, and thus, it is expected to be successfully applied in the chiral analysis of pharmaceuticals and illicit drugs of forensic interest.

Background: Recent studies reported possible concerns following long-lasting treatments with high doses of D-chiro-inositol in women. However, to date, no clinical trial has investigated or validated these concerns. We addressed this issue both retrospectively and with a prospective pilot study. Methods: For the retrospective analysis, we searched our databases for insulin-resistant women who took 1200 mg/day D-chiro-inositol for 6 months. In our prospective study, we enrolled 10 healthy women to supplement with the same therapeutic scheme. We performed statistical analyses through the Wilcoxon Signed-Rank Test. A p-value < 0.05 was considered significant. Results: Twenty women underwent 6 months of 1200 mg/day D-chiro-inositol. The treatment significantly decreased BMI, glycemia, insulinemia, HOMA-IR, serum levels of LH, total testosterone, and DHEAS. Serum estradiol rose and menstrual abnormalities occurred following the treatment. In our prospective study, we observed increases in serum levels of total testosterone and asprosin in healthy women. Conclusions: This is the first clinical evidence demonstrating that long-term treatments with high dosages of D-chiro-inositol can predispose women to hormonal and menstrual abnormalities. Moreover, the accumulation of D-chiro-inositol following such treatment regimen may lead to detrimental effects in non-reproductive tissues, as demonstrated by the increase in asprosin levels. [ABSTRACT FROM AUTHOR]

• This work established and optimized a GC-MS/MS method for low content myo- and D- chiro -inositol measurement. • This GC-MS/MS method performed well, with precision, accuracy, linearity range, and limit of quantification satisfactory for serum sample. • This GC-MS/MS method was fast and convenient, sufficient for clinical practice. Myo -inositol (MI) and D -chiro -inositol (DCI) are two paramount isomers of inositol, both vital in glucose and steroid metabolism. Deficits in MI, DCI or MI/DCI ratio are expressly concerned with several pathological process, whereas MI and DCI lack practical measurement for human specimen. To quantify MI and DCI in serum samples simultaneously, a gas chromatography tandem mass spectrometry (GC-MS/MS) method was established. The process flow was optimized in ion source, derivative agent volume and reaction time. The performance characteristics were verified by commercial standards and clinical serums. This method was confirmed to be sensitive (LOD ≤ 30 ng/mL of MI, ≤3 ng/mL of DCI) and reproducible (RSD < 6 % for repeated analyses). Quantitative determinations performed good linearity within the measurement range of 0.500–10.00 and 0.005–0.500 μg/mL for MI and DCI respectively (R2 > 0.999). The recoveries of MI and DCI were 97.11–99.35 % and 107.82–113.09 %, respectively. This method was successfully applied to 114 clinical specimens. No significant matrix effect was observed in serum samples under current conditions. [ABSTRACT FROM AUTHOR]

This study investigates the effects of inositol (INO) supplementation on cardiac changes caused by Li in mice. The study involved 4 groups of C57BL6 mice (n=10 each): (i) mice orally administered with Li 2 CO 3 for 8 weeks, then 4 additional weeks without (Li_group) or (ii) with INO supplementation (Li_INOdelayed_group) (total of 12 weeks); (iii) mice given Li 2 CO 3 and INO supplementation concurrently for 12 weeks (Li+INO_group); (iv) one group left untreated (C–group). The INO was administered as a mixture of myo-inositol and d -chiro-inositol (80:1) in drinking water. The mice were characterised for heart morphology, function, electrical activity, arrhythmogenic susceptibility, and multiorgan histopathology (heart, liver and kidney). Cardiomyocyte size, protein expression of key signalling pathways related to hypertrophy, and transcription levels of ion channel subunits and hypertrophy markers were evaluated in the ventricle tissue. The study found that INO supplementation reduced the Li-induced cardiac adverse effects, including systolic impairment and increased susceptibility to arrhythmias. The positive effect on arrhythmias might be attributed to the restored expression levels of the potassium channel subunit Kv 1.5. Additionally, INO improved cardiomyocyte hypertrophy, possibly by inhibiting the Li-induced activation of the ERK1/2 signalling pathway and by restoring the normal expression level of BNP, and alleviated injury in the liver and kidney. The effect was preventive if INO supplementation was taken concurrently with Li and therapeutic if INO was administered after Li-induced cardiac impairments were established. These results provide new insights into the cardioprotective effect of INO and suggest a potential treatment approach for Li-induced cardiac disease. [Display omitted] • Lithium causes harmful effects on the heart of mice. • Inositol supplementation can help treat lithium-induced toxic effects. • Inositols have beneficial preventive effects when taken concurrently with lithium. • Inositols have a therapeutic effect on overt lithium-induced cardiac impairments. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome is an endocrine disorder often characterized by insulin resistance and hyperinsulinemia, especially in overweight/obese women. Among insulin sensitizers, the positive role of inositols has been increasingly established in recent years. The action of inositols not only concerns the metabolic parameters of these patients, but also the hormonal profile, resulting in beneficial effects on ovarian function. For this reason, many studies have tried to recognize their role in PCOS infertile women who underwent in vitro fertilization (IVF) procedures.

Despite the chemical similarities between myo-inositol and D-chiro-inositol and their synergistic effects on insulin sensitivity, they serve different functions. Insulin resistance is one of the etiological factors in the development of polycystic ovary syndrome (PCOS), diabetes mellitus, metabolic syndrome, infertility, menstrual irregularities and ovulation disorders, pregnancy complications, in particular, gestational diabetes. Myo-inositol plays an important role in the insulin transfer and hormone synthesis in the ovaries, in oocyte maturation, fertilization, implantation and post-implantation development. Many studies confirm the positive effect of inositol isomers on metabolic, hormonal and reproductive disorders, both in the form of monotherapy and in combination with other drugs to enhance the therapeutic effect and bioavailability. Myo-inositol has a favorable safety profile. Studies have shown that in patients with PCOS myo-inositol improves ovarian function and fertility, reduces the manifestations of hyperandrogenism, insulin resistance and normalizes weight. Myo-inositol and D-chiro-inositol have different mechanisms of action on insulin sensitivity and have different functions. The balance of the two isomers ensures the normal secretion of hormones and ovarian functioning, but it is currently unknown what the optimal ratio of these two isomers due to the small number of high quality studies and the difficulty of studying their isolated action. There are currently different combinations of myo- and D-chiro-inisotol, but they also have not been supported by enough high quality studies. When prescribing various isomers of inositol, it should be remembered that doses above 4000 mg are the most studied in patients with PCOS, but D-chiro-inositol concentration above 1200 mg/day has undesirable effects. Most studies indicate that D-chiro-inositol value is increased in PCOS, therefore oocytes are more sensitive to its overdose, and combination drugs require more study. Currently, there is no consensus in the literature on the advantage of combined supplements of myo- and D-chiro-inositol compared to monotherapy with myo-inositol. Today, myo-inositol monotherapy is more researched and safer.

Résumé Contexte Plusieurs articles de revues récents rapportent que le D-chiro-inositol (DCI), principalement connu sous le nom de second messager de l’insuline, influence la stéroïdogenèse. En particulier, de nouvelles preuves apparaissent sur la capacité du DCI à réguler l’expression de l’aromatase et la biosynthèse de la testostérone. À cet égard, l’administration de DCI pourrait représenter une bonne opportunité thérapeutique en cas de réduction des taux de testostérone. Les hommes d’âge avancé ont généralement des concentrations de testostérone plus faibles que celles d’hommes plus jeunes, et de récents essais contrôlés randomisés ont examiné, si le traitement par testostérone pourrait améliorer dans ce groupe d’âge les résultats en matière de santé. Il existe peu d’informations sur l’innocuité de cette thérapie de remplacement de la testostérone chez ces hommes ; le DCI pourrait ainsi constituer une intéressante alternative pour de futurs essais. Par conséquent, la présente étude vise à évaluer l’effet du traitement par DCI sur les taux de testostérone chez les hommes d’âge avancé. Résultats Dix hommes d’âge avancé ayant un faible taux basal de testostérone ont été recrutés dans la présente étude. Les patients ont pris 600 mg de DCI, deux fois par jour, pendant 30 jours. Nous avons évalué les paramètres hormonaux et glycémiques, le poids, le tour de taille et l’indice de masse corporelle au départ (T0) et après 30 jours (T1). Enfin, tous les patients ont également rempli le questionnaire normalisé de l’indice international de la fonction érectile et ont effectué le test de force de préhension (handgrip test) à T0 et T1. Les hommes prenant le DCI ont présenté des concentrations augmentées d’androgènes et réduites d’œstrogènes, ainsi qu’une amélioration des profils glycémiques. La prise de DCI était également associée à une réduction du poids, de l’indice de masse corporelle, du tour de taille, et à une amélioration de la force de préhension et de la fonction sexuelle autodéclarée. Tous ces effets ont conduit à une amélioration de la fonction sexuelle et de la force physique. Conclusions Dans cette étude pilote, le traitement par DCI a amélioré les taux de testostérone et d’androstènedione au détriment des œstrogènes chez des hommes d’âge avancé ayant de faibles taux de base de ces hormones, sans effets indésirables.

Inositol is a carbocyclic sugar polyalcohol and is found in many mammalian tissues mediating cellular signal transduction, where it is most often involved as a secondary messenger in response to various hormones, neurotransmitters, growth factors and many other processes. By epimerization of its hydroxyl groups, nine possible stereoisomers can be generated, two of which are of great physiological and clinical importance: myo-inositol and D-chiro-inositol. Myo-inositol and D-chiro-inositol are normally stored in the kidney, brain and liver and are required for functions such as signal transduction, metabolic flux, insulin signaling, regulation of ion channel permeability, stress response, and also take involvement in embryonic development as well. Inositol deficiency is involved in the pathogenesis of some diseases. Adding it as a therapy for various diseases improves the course of biological processes and leads to the restoration of the body's impaired functions. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is one of the most common disorders among women of reproductive age and can be diagnosed when at least two of the following criteria are present: chronic ovulatory disorder, clinical and/or biochemical hyperandrogenism, and polycystic ovaries. Diet and lifestyle modifications are the main therapeutic intervention and they can fully restore ovary function and avoid PCOS consequences in a certain number of patients. However, prescription of medications or dietary supplements is often needed. The literature has confirmed the significant role of inositol therapy in PCOS, with particular reference to Myo-inositol and D-chiro-Inositol. The aim of this review is to clarify the use of inositols for the treatment of PCOS and the recent scientific theories about D-Chiro-Inositol properties as an ovarian aromatase inhibitor. [ABSTRACT FROM AUTHOR]

ABSTRACT Inositols (cyclohexanehexols) comprise nine isomeric cyclic sugar alcohols, several of which occur in all domains of life with various functions. Many bacteria can utilize inositols as carbon and energy sources via a specific pathway involving inositol dehydrogenases (IDHs) as the first step of catabolism. The microbial cell factory Corynebacterium glutamicum can grow with myo-inositol as a sole carbon source. Interestingly, this species encodes seven potential IDHs, raising the question of the reason for this multiplicity. We therefore investigated the seven IDHs to determine their function, activity, and selectivity toward the biologically most important isomers myo-, scyllo-, and d-chiro-inositol. We created an ΔIDH strain lacking all seven IDH genes, which could not grow on the three inositols. scyllo- and d-chiro-inositol were identified as novel growth substrates of C. glutamicum. Complementation experiments showed that only four of the seven IDHs (IolG, OxiB, OxiD, and OxiE) enabled growth of the ΔIDH strain on two of the three inositols. The kinetics of the four purified enzymes agreed with the complementation results. IolG and OxiD are NAD+-dependent IDHs accepting myo- and d-chiro-inositol but not scyllo-inositol. OxiB is an NAD+-dependent myo-IDH with a weak activity also for scyllo-inositol but not for d-chiro-inositol. OxiE on the other hand is an NAD+-dependent scyllo-IDH showing also good activity for myo-inositol and a very weak activity for d-chiro-inositol. Structural models, molecular docking experiments, and sequence alignments enabled the identification of the substrate binding sites of the active IDHs and of residues allowing predictions on the substrate specificity. IMPORTANCE myo-, scyllo-, and d-chiro-inositol are C6 cyclic sugar alcohols with various biological functions, which also serve as carbon sources for microbes. Inositol catabolism starts with an oxidation to keto-inositols catalyzed by inositol dehydrogenases (IDHs). The soil bacterium C. glutamicum encodes seven potential IDHs. Using a combination of microbiological, biochemical, and modeling approaches, we analyzed the function of these enzymes and identified four IDHs involved in the catabolism of inositols. They possess distinct substrate preferences for the three isomers, and modeling and sequence alignments allowed the identification of residues important for substrate specificity. Our results expand the knowledge of bacterial inositol metabolism and provide an important basis for the rational development of producer strains for these valuable inositols, which show pharmacological activities against, e.g., Alzheimer’s disease, polycystic ovarian syndrome, or type II diabetes.

Introduction: Myo-inositol (MYO) and D-chiro-inositol are chemical compounds known to exert an impact on multiple signaling pathways of a human body. Due to its effects on insulin metabolism and ovaries’ hormone activity their use in polycystic ovary syndrome (PCOS) therapies has been highly recommended in the recent literature. In this article we aim to review the known and possible applications of inositol and its derivatives for treatment of various gynecological and endocrine disorders and to indicate possible directions of further investigations. Methods and materials: This article is based on the literature found in PubMed Database from the period of 2016-2022 with use of keywords such as “inositol”; “myoinositol”; “d-chiro-inositol”; “PCOS”; “insulin”. Results: The applications of myoinositol in the treatment of polycystic ovary syndrome (PCOS) are very well known in recent publications. It is reported that MYO supplementation improves the quality of oocytes, regulates the menstrual cycle and ovulation rates. Prevention of gestational diabetes (GDM) amongst the patients with risk factors is likely another use of inositols. Inositol takes part in phospholipase C pathway, thus its depletion may be the cause for hypothyroidism. Inositol inhibits the expression of aromatase, the enzyme which is responsible for the growth of endometrial tissue - it may constitute a targeting point in the treatment of endometriosis. So far, no adverse effects of inositol isomers have been reported. Conclusion: The use of inositol, its isomers and derivatives represents an interesting direction in the development of the treatment of many conditions associated with endocrine disorders. There is a need for further investigations and studies on larger groups of patients to exploit its potential.

The primary control of dysmetabolic patients is extremely challenging worldwide, with inadequate dietary habits and sporadic physical activity among the key risk factors for metabolic syndrome onset. Nowadays, there is no exclusive treatment for this condition, and considering that preventive measures usually fail, new therapeutic approaches need to be proposed and investigated. This present pilot study compared the effects of diet alone and in association with a combination of myo-inositol and d-chiro-inositol in their 40:1 ratio, α-lactalbumin, and Gymnema sylvestre on different metabolic parameters in obese dysmetabolic patients. To this purpose, 37 patients with BMI between 30 and 40 and fasting blood glucose between 100 and 125 mg/dL were divided into two groups: (i) the control group followed a hypocaloric Mediterranean diet, (ii) while the study group was also supplemented with a daily dosage of two sachets, each one containing 1950 mg myo-inositol, 50 mg d-chiro-inositol, 50 mg α-lactalbumin, and 250 mg Gymnema Sylvestre. After a 6-month treatment, all parameters improved in both groups. Nevertheless, the treated group experienced a greater improvement, especially concerning the variation from the baseline of HOMA index, triglycerides, BMI, body weight, and waist circumference. These findings support the supplementation with myo-inositol and d-chiro-inositol in the 40:1 ratio, α-lactalbumin, and Gymnema sylvestre as a therapeutical strategy to potentiate the beneficial effects induced via dietary programs in dysmetabolic patients.

Endometrial hyperplasia is a threatening pathology driven by unopposed estrogen stimulus. Moreover, insulin may act on the endometrium, prompting further growth. We aimed at assessing whether D-chiro-Inositol, an insulin sensitizer with estrogen-lowering properties, might improve the condition of patients with simple endometrial hyperplasia without atypia. We enrolled women with simple endometrial hyperplasia without atypia and related symptoms, including abnormal uterine bleeding. We treated the patients with one tablet per day, containing 600 mg of D-chiro-inositol for six months. Patients underwent ultrasound to assess the thickness of the endometrium at baseline, after three months, and at the end of this study. Endometrial thickness went from 10.82 ± 1.15 mm to 8.00 ± 0.81 mm after three months (p < 0.001) and to 6.9 ± 1.06 mm after six months (p < 0.001 versus baseline; p < 0.001 versus three months). D-chiro-inositol treatment also improved heavy menstrual bleeding and the length of menstruation. Despite the fact that our data should be validated in larger studies with appropriate control groups, our promising results support the hypothesis that D-chiro-inositol may represent a useful treatment in the case of endometrial hyperplasia without atypia.

Diabetic osteoporosis (DO) has been increasingly recognized as an important complication of diabetes. D-pinitol, a natural compound found in various legumes, is known for its anti-diabetic function, but its effect on DO has not been investigated. Two doses of pinitol (50 and 100 mg/kg Bw/d) were administered orally to experimentally induce the DO mouse model for 5 weeks. The results indicated that pinitol suppressed fasting blood glucose levels and tended to enhance impaired pancreatic function. Pinitol also suppressed serum bone turnover biomarkers, and improved dry femur weight, cancellous bone rate, and bone mineral content in the DO mice. Based on the inositol quantification using GC-MS in serum, liver, kidney, and bone marrow, the pinitol treatment significantly recovered the depleted D-chiro-inositol (DCI) content or the decreased the ratio of DCI to myo-inositol caused by DO. In short, our results suggested that pinitol improved glucose metabolism and inhibited bone loss in DO mice via elevating the DCI levels in tissues.

Introduction: Polycystic Ovarian Syndrome (PCOS) is known to be an endocrine state that is characterized by oligomenorrhea, hyperandrogenism, and highly cystic follicles in the ovaries. The use of food ingredients and traditional medicine in Asian countries is well known, and previous studies have shown that Ecklonia cava K. [Alariaceae] (EC) is able to alleviate PCOS symptoms. D-Chiro-inositol (DCI) administration in pathologies where steroid biosynthesis is a crucial factor, i.e., PCOS, has provided satisfactory results. Methods: Therefore, we studied the synergistic effects of the two previously known active compounds. In rats with letrozole-induced PCOS, we focused on alternative therapies using EC and/or DCI extracts to alleviate ovarian failure. Results: As a nonsteroidal aromatase inhibitor, letrozole inhibits the conversion of testosterone to estrogen and subsequently causes PCOS. We divided 6-week-old female mice into the following six groups and evaluated them: vehicle, PCOS, PCOS + MET (metformin), PCOS + DCI, PCOS + EC, and PCOS + DCI + EC. In our study, PCOS rats treatedwith EC and DCI had lowserumLH and T levels and lowserumlevels of inflammatory cytokines such as TNFa and IL-6. These treatments also appeared to regulate the production of factors that affect follicle formation and inflammation in the ovaries. Conclusion: We concluded that EC extract and/or DCI administration influenced aromatase production and reduced LH and T stimulation, and cotreatment with EC and DCI consequently restored ovarian dysfunction or anti-inflammatory responses in rats with PCOS-like symptoms. [ABSTRACT FROM AUTHOR]

This study was aimed at assessing the efficacy and safety of inositol nutritional supplementation during pregnancy for the prevention of GDM. PubMed, Embase, MEDLINE, and Cochrane library were systematically searched for randomized controlled trails (RCTs) in this field until May 2022. Primary outcomes were the incidence for GDM and plasma glucose levels by oral glucose tolerance test (OGTT). Pooled results were expressed as relative risk (RR) or mean difference (MD) with a 95% confidence interval (95% CI). Seven RCTs with 1321 participants were included in this study. Compared with the control group, 4 g myo-inositol (MI) supplementation per day significantly decreased the incidence of GDM (RR = 0.30, 95% CI (0.18, 0.49), p < 0.00001). It significantly decreased the plasma glucose levels of OGTT regarding fasting-glucose OGTT (MD = −4.20, 95% CI (−5.87, −2.54), p < 0.00001), 1-h OGTT (MD = −8.75, 95% CI (−12.42, −5.08), p < 0.00001), and 2-h OGTT (MD = −8.59, 95% CI (−11.81, −5.83), p < 0.00001). It also decreased the need of insulin treatment, and reduced the incidence of preterm delivery and neonatal hypoglycemia. However, no difference was observed between 1.1 g MI per day plus 27.6 mg D-chiro-inositol (DCI) per day and the control group regarding all evaluated results. In conclusion, 4 g MI nutritional supplementation per day during early pregnancy may reduce GDM incidence and severity, therefore may be a practical and safe approach for the prevention of GDM. [ABSTRACT FROM AUTHOR]

Increasing evidence shows that hypothalamic dysfunction, insulin resistance, and weight loss precede and progress along with the cognitive decline in sporadic Alzheimer’s Disease (AD) with sex differences. This study aimed to determine the effect of oral dietary administration of D-Chiro-inositol (DCI), an inositol used against insulin resistance associated with polycystic ovary, on the occurrence of metabolic disorders in the transgenic 5xFAD mouse model of AD (FAD: Family Alzheimer's Disease). DCI was administered from 6 to 10 months of age to male and female 5xFAD mice and control (non-Tg) littermates. Energy balance and multiple metabolic and inflammatory parameters in the hypothalamus, liver and plasma were evaluated to assess the central and peripheral effects of DCI. Results indicated that weight loss and reduced food intake in 5xFAD mice were associated with decreased neuropeptides controlling food intake and the appearance of a pro-inflammatory state in the hypothalamus. Oral administration of DCI partially restored energy balance and hypothalamic parameters, highlighting an increased expression of Npy and Agrp and female-specific downregulation of Gfap and Igf1. DCI also partially normalized impaired insulin signaling and circulating insulin, GLP-1, and GIP deficiencies in 5xFAD mice. Principal component analysis of metabolic parameters indicated the presence of a female-specific fatty liver in 5xFAD mice: DCI administration reversed hepatic fat accumulation, β-oxidation, inflammation and increased GOT and GPT levels. Our study depicts that metabolic impairment along with the cognitive decline in a mouse model of AD, which is exacerbated in females, can be ameliorated by oral supplementation with insulin-sensitizing DCI.

White adipose tissue/brown adipose tissue trans-differentiation is one of the main study targets for therapies against obesity and metabolic diseases. In recent years, numerous molecules able to induce such trans-differentiation have been identified; however, their effect in obesity therapies has not been as expected. In the present study, we investigated whether myo-inositol and its stereoisomer D-chiro-inositol could be involved in the browning of white adipose tissue. Our preliminary results clearly indicate that both, at 60 μM concentration, induce the upregulation of uncoupling protein 1 mRNA expression, the main brown adipose tissue marker, and increase mitochondrial copy number as well as oxygen consumption ratio. These changes demonstrate an activation of cell metabolism. Therefore, our results show that human differentiated adipocytes (SGBS and LiSa-2), assume the features typical of brown adipose tissue after both treatments. Furthermore, in the cell lines examined, we proved that D-chiro-inositol and myo-Inositol induce an increase in the expression of estrogen receptor mRNAs, suggesting a possible modulation by these isomers. We also found an increase in the mRNA of peroxisome proliferator-activated receptor gamma, a very important target in lipid metabolism and metabolic diseases. Our results open new opportunities for the use of inositols in therapeutic strategies to counteract obesity and its metabolic complications.

Polycystic ovarian syndrome (PCOS) is the most common endocrinological disorder in women, in which, besides chronic anovulation/oligomenorrhea and ovarian cysts, hyperandrogenism plays a critical role in a large fraction of subjects. Inositol isomers—myo-Inositol and D-Chiro-Inositol—have recently been pharmacologically effective in managing many PCOS symptoms while rescuing ovarian fertility. However, some disappointing clinical results prompted the reconsideration of their specific biological functions. Surprisingly, D-Chiro-Ins stimulates androgen synthesis and decreases the ovarian estrogen pathway; on the contrary, myo-Ins activates FSH response and aromatase activity, finally mitigating ovarian hyperandrogenism. However, when the two isomers are given in association—according to the physiological ratio of 40:1—patients could benefit from myo-Ins enhanced FSH and estrogen responsiveness, while taking advantage of the insulin-sensitizing effects displayed mostly by D-Chiro-Ins. We need not postulate insulin resistance to explain PCOS pathogenesis, given that insulin hypersensitivity is likely a shared feature of PCOS ovaries. Indeed, even in the presence of physiological insulin stimulation, the PCOS ovary synthesizes D-Chiro-Ins four times more than that measured in control theca cells. The increased D-Chiro-Ins within the ovary is detrimental in preserving steroidogenic control, and this failure can easily explain why treatment strategies based upon high D-Chiro-Ins have been recognized as poorly effective. Within this perspective, two factors emerge as major determinants in PCOS: hyperandrogenism and reduced aromatase expression. Therefore, PCOS could no longer be considered a disease only due to increased androgen synthesis without considering the contemporary downregulation of aromatase and FSH receptors. Furthermore, these findings suggest that inositols can be specifically effective only for those PCOS phenotypes featured by hyperandrogenism.

Estrogens and progestogens act on female reproductive tissues in opposite ways. As they counteract each other actions, the correct balance between these two classes of hormones is pivotal to avoid dangerous states. Unopposed estrogens occur when progestogen levels do not balance estrogens, primarily deriving from overproduction of estrogens via aromatase enzyme. In the endometrium, unopposed estrogens induce proliferative or invasive phenomena, which represent the first step toward different diseases. These pathologies include endometrial hyperplasia, endometrial polyps, endometriosis and adenomyosis. Endometrial hyperplasia and polyps are proliferative pathologies, while endometriosis and adenomyosis are characterized by the invasion of other tissues by endometrial cells. Current pharmacological treatments include Gonadotropin-Releasing-Hormone analogs, aromatase inhibitors and progestogens, either alone or in combination with estrogens. As these drugs usually lead to burdensome undesired effects, researchers seek to find new therapeutical molecules. Recent literature highlights the positive effects of metformin, an insulin sensitizing drug that reduces the insulin proliferative stimulus on the endometrium. d-chiro-inositol is an insulin second messenger with insulin sensitizing and mimetic properties, recently described as an aromatase down-regulator. Based on current evidence, d-chiro-inositol may be useful to treat the pathologies responsive to unopposed estrogens. [ABSTRACT FROM AUTHOR]

Subfertility is more than a quality-of-life problem as it has a substantial negative public health impact. Polycystic ovary syndrome (PCOS) is one of the most common causes of subfertility, affecting one out of 10 women in reproductive age. Among PCOS women undergoing assisted reproductive technology, treatment based on myo-inositol and high doses of D-chiro-inositol has been shown to increase pregnancy rate and number of live births, reduce ovarian hyperstimulation syndrome and improve oocyte quality. A preparation based on myo-inositol and high doses of D-chiro-inositol, together with antioxidants, vitamins, and minerals, could have beneficial effects and be an optimal strategy to improve female fertility in the general gynecologist's office. The aim of this review is to highlight the role of inositol and its isomers in improving fertility of women with PCOS. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a symptom complex associated with increased amounts of circulating androgens in females, increased insulin resistance and obesity. The drugs, Myo-inositol, D-chiro-inositol and Metformin, which are insulin sensitizers, are very helpful in taking care of one of the key components of PCOS that is insulin resistance. Myoinositol and D-chiro-inositol are isomeric forms of inositol that have insulin-like properties, acting as second messengers in the insulin intracellular pathway; both of these molecules are involved in the increasing insulin sensitivity of different tissues to improve metabolic and ovulatory functions. This study was done to compare the effects of combination of Myo-inositol and D-chiro-inositol with the use of metformin on clinical and biochemical profile in PCOS. Methods. A prospective, randomized, comparative study was conducted on 200 patients. The patients were randomly assigned into the two groups of 100 each. Group A receiving Tab. Myoinositol 550mg twice daily and Tab. D-chiro-inositol 13.8mg twice daily and Group B receiving Tab. Metformin 500mg thrice daily. The patients were assessed by menstrual cycle regulation, hirsutism score (Ferriman Gallwey), fasting and postprandial glucose and insulin levels, serum dehydroepiandrosterone levels, serum free testosterone levels and serum luteinizing and follicle stimulating hormone ratio. Results. In both the groups there was significant improvement in all the above mentioned parameters, however the group with Combination of Myo-inositol and D-chiro-inositol had statistically significant improvement over the Metformin group. Conclusions: Combination of Myo-inositol and D-chiro-inositol and use of metformin, significantly improved insulin sensitivity in PCOS women. But combination of Myo-inositol and D-chiro-inositol was effective in controlling the hormonal profiles (luteinizing/follicle stimulating hormone ratio and free testosterone) when compared to Metformin.

he aim of this paper is to critically analyze the composition of many inositol-based products currently used to treat polycystic ovary syndrome (PCOS). Several different combinations of myo-inositol and D-chiro-inositol, with and without additional compounds such as micro- and macroelements, vitamins, and alpha-lipoic acid, have been formulated over the years. Such therapeutic proposals do not take various features of inositol stereoisomers into consideration. As an example, it is important to know that D-chiro-inositol treatment may be beneficial when administered in low doses, yet the progressive increase of its dosage results in the loss of its advantageous effects on the reproductive performance of women and a deterioration in the quality of blastocysts created via in vitro fertilization. In addition, is necessary to consider that the intestinal absorption of myo-inositol is reduced by the simultaneous administration of D-chiro-inositol since the two stereoisomers compete with each other for the same transporter that has similar affinity for each of them. A decrease in myo-inositol absorption is also found when it is coadministered with inhibitors of sugar intestinal absorption and/or types of sugars such as sorbitol, maltodextrin, and sucralose. The combination of these may require higher amounts of myo-inositol in order to reach a therapeutic dosage compared to inositol administration alone, a particularly important fact when physicians strive to obtain a specific plasma level of the stereoisomer. Finally, we must point out that D-chiro-inositol was found to be an aromatase inhibitor which increases androgens and may have harmful consequences for women. Therefore, the inositol supplements used in PCOS treatment must be carefully defined. Clinical evidence has demonstrated that the 40 :1 ratio between myo-inositol and D-chiro-inositol is the optimal combination to restore ovulation in PCOS women. Therefore, it is quite surprising to find that inositol-based treatments for PCOS seem to be randomly chosen and are often combined with useless or even counterproductive molecules, all of which can weaken myo-inositol’s efficacy. Such treatments clearly lack therapeutic rationale.

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