The Effects of Myo-Inositol and D-Chiro-Inositol in a Ratio 40:1 on Hormonal and Metabolic Profile in Women with Polycystic Ovary Syndrome Classified as Phenotype A by the Rotterdam Criteria and EMS-Type 1 by the EGOI Criteria.

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.

A Markov-model simulation of IVF programs for PCOS patients indicates that coupling myo-Inositol with rFSH is cost-effective for the Italian Health System.

Accumulating evidence suggests that oral supplementation with myo-Inositol (myo-Ins) is able to reduce the amount of gonadotropins and days of controlled ovarian hyperstimulation (COS) necessary to achieve adequate oocyte maturation in assisted reproduction technology (ART) protocols, particularly in women affected by polycystic ovary syndrome (PCOS). We used computational calculations based on simulation modellings. We simulated in vitro fertilization (IVF) procedures-with or without intracytoplasmic sperm injection (ICSI)-with 100,000 virtual patients, accounting for all the stages of the entire IVF procedure. A Monte Carlo technique was used to account for data uncertainty and to generate the outcome distribution at each stage. We considered virtual patients with PCOS undergoing IVF cycles to achieve pregnancy. Computational data were retrieved from clinical experience and published data. We investigated three parameters related to ART protocols: cost of single procedure; efficacy to achieve ongoing pregnancy at 12 gestational weeks; overall cost per single pregnancy. The administration of oral myo-Ins during COH protocols, compared to the standard COH with recombinant Follicle Stimulating Hormone (rFSH) only, may be considered a potential strategy to reduce costs of ART for the Italian Health System.

Effect of Oral High Molecular Weight Hyaluronic Acid (HMWHA), Alpha Lipoic Acid (ALA), Magnesium, Vitamin B6 and Vitamin D Supplementation in Pregnant Women: A Retrospective Observational Pilot Study.

Background-Pregnancy represents a nutritional challenge, since macro- and micronutrients intake can affect mother' health and influence negative outcomes. The aim of this retrospective pilot study is to evidence whether the oral supplementation with high molecular weight hyaluronic acid (HMWHA), in association with alpha lipoic acid (ALA), magnesium, vitamin B6 and vitamin D, in pregnant women, could reduce adverse effects, such as PTB, pelvic pain, contraction and hospitalization. Methods-Data were collected from n = 200 women treated daily with oral supplements of 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6 and 50 mcg vitamin D (treatment group) and from n = 50 women taking with oral supplements of 400 mg magnesium (control group). In both groups, supplementation started from the 7th gestational week until delivery. Results-Oral treatment with HMWHA, in association with ALA, magnesium, vitamin B6 and vitamin D in pregnant women, significantly reduced adverse events, such as PTB (p < 0.01), pelvic pain and contractions (p < 0.0001), miscarriages (p < 0.05) and admission to ER/hospitalization (p < 0.0001) compared with the control group. Conclusions-Despite HMWHA having been poorly used as a food supplement in pregnant women, our results open a reassuring scenario regarding its oral administration during pregnancy.

Diet Plus Inositols, α-Lactalbumin and Gymnema sylvestre: The Successful Combo to Restore Body Weight and Metabolic Profile in Obese and Dysmetabolic Patients.

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.

Comparing the Efficacy of Myo-Inositol Plus α-Lactalbumin vs. Myo-Inositol Alone on Reproductive and Metabolic Disturbances of Polycystic Ovary Syndrome.

Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS.

Preventing Persistence of HPV Infection with Natural Molecules.

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence.

Inositols in the ovaries: activities and potential therapeutic applications.

INTRODUCTION: Myo-inositol (MI) and d-chiro-inositol (DCI) play a key role in ovarian physiology, as they are second messengers of insulin and gonadotropins. Ex-vivo and in-vitro experiments demonstrate that both isomers are deeply involved in steroid biosynthesis, and that reduced MI-to-DCI ratios are associated with pathological imbalance of sex hormones. AREAS COVERED: This expert opinion provides an overview of the physiological distribution of MI and DCI in the ovarian tissues, and a thorough insight of their involvement into ovarian steroidogenesis. Insulin resistance and compensatory hyperinsulinemia dramatically reduce the MI-to-DCI ratio in the ovaries, leading to gynecological disorders characterized by hyperandrogenism, altered menstrual cycle and infertility. EXPERT OPINION: Available evidence indicates that MI and DCI have very specific physiological roles and, seemingly, physiological MI-to-DCI ratios in the ovaries are crucial to maintain the correct homeostasis of steroids. Inositol treatments should be evaluated on the patients' specific conditions and needs, as long-term supplementation of high doses of DCI may cause detrimental effects on the ovarian functionality. In addition, the effects of inositol therapy on the different PCOS phenotypes should be further investigated in order to better tailor the supplementation.

The role of vitamin D in metabolic and reproductive disturbances of polycystic ovary syndrome: A narrative mini-review.

Vitamin D is a secosteroid hormone that plays a pivotal role in several metabolic and reproductive pathways in humans. Increasing evidence supports the role of vitamin D deficiency in metabolic disturbances and infertility in women with polycystic ovary syndrome (PCOS). Indeed, supplementation with vitamin D seems to have a beneficial role on insulin resistance (IR) and endometrial receptivity. On the other hand, exceedingly high levels of vitamin D appear to play a detrimental role on oocytes development and embryo quality. In the current review, we summarize the available evidence about the topic, aiming to suggest the best supplementation strategy in women with PCOS or, more generally, in those with metabolic disturbances and infertility. Based on the retrieved data, vitamin D seems to have a beneficial role on IR, insulin sensitivity and endometrial receptivity, but high levels and incorrect timing of administration seem to have a detrimental role on oocytes development and embryo quality. Therefore, we encourage a low dose supplementation (400-800 IU/day) particularly in vitamin D deficient women that present metabolic disturbances like PCOS. As far as the reproductive health, we advise vitamin D supplementation in selected populations, only during specific moments of the ovarian cycle, to support the luteal phase. However, ambiguities about dosage and timing of the supplementation still emerge from the clinical studies published to date and further studies are required.

D-chiro-inositol Induces Ovulation in Non-Polycystic Ovary Syndrome (PCOS), Non-Insulin-Resistant Young Women, Likely by Modulating Aromatase Expression: A Report of 2 Cases.

BACKGROUND Anovulation consists in the lack of oocyte release during the menstrual cycle, leading to an irregular menstrual cycle. Untreated chronic anovulation is one of the major causes of female infertility and can induce hypoestrogenism. Different etiological factors can contribute to anovulation; therefore, the clinical approaches to manage this condition should take into account the specific patient characteristics. Oral ovulation-inducing agents are first-line treatments for most anovulatory patients. Drugs used include selective estrogen receptor modulators (SERMs) such as clomiphene citrate and aromatase inhibitors (AIs) such as letrozole. The latter, in particular, halts the estrogen biosynthesis by blocking the activity of steroidogenic enzyme aromatase, which catalyzes the conversion of androgens to estrogens. Similarly, d-chiro-inositol (DCI) modulates the activity of aromatase by reducing the corresponding gene expression, and DCI supplementation was successfully used to induce ovulation in anovulatory PCOS patients. Here, we report the use of DCI to induce ovulation in non-PCOS anovulatory oligomenorrheic women. CASE REPORT Two young non-PCOS anovulatory oligomenorrheic women received treatment with high-dose (1200 mg) DCI for 6 weeks. Based on an initial evaluation, both patients had normal hormone levels and were non-insulin-resistant. Ovulation assessment was based on the increment of progesterone and LH levels, as well as on the endometrial thickening. Also, the treatment with DCI resulted in a reduction of testosterone levels relative to baseline values. CONCLUSIONS After the 6-week treatment with 1200 mg DCI, ovulation was restored in both women, as confirmed by increased progesterone and LH and endometrial thickening.

Inositols: From Established Knowledge to Novel Approaches.

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.

Oxidative Stress and Male Fertility: Role of Antioxidants and Inositols.

Infertility is defined as a couple's inability to conceive after at least one year of regular unprotected intercourse. This condition has become a global health problem affecting approximately 187 million couples worldwide and about half of the cases are attributable to male factors. Oxidative stress is a common reason for several conditions associated with male infertility. High levels of reactive oxygen species (ROS) impair sperm quality by decreasing motility and increasing the oxidation of DNA, of protein and of lipids. Multi-antioxidant supplementation is considered effective for male fertility parameters due to the synergistic effects of antioxidants. Most of them act by decreasing ROS concentration, thus improving sperm quality. In addition, other natural molecules, myo-inositol (MI) and d-chiro-inositol (DCI), ameliorate sperm quality. In sperm cells, MI is involved in many transduction mechanisms that regulate cytoplasmic calcium levels, capacitation and mitochondrial function. On the other hand, DCI is involved in the downregulation of steroidogenic enzyme aromatase, which produces testosterone. In this review, we analyze the processes involving oxidative stress in male fertility and the mechanisms of action of different molecules.

Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth.

Human pregnancy is a sequence of events finely tuned by several molecular interactions that come with a new birth. The precise interlocking of these events affecting the reproductive system guarantees safe embryo formation and fetal development. In this scenario, melatonin and myo-inositol seem to be pivotal not only in the physiology of the reproduction process, but also in the promotion of positive gestational outcomes. Evidence demonstrates that melatonin, beyond the role of circadian rhythm management, is a key controller of human reproductive functions. Similarly, as the most representative member of the inositol's family, myo-inositol is essential in ensuring correct advancing of reproductive cellular events. The molecular crosstalk mediated by these two species is directly regulated by their availability in the human body. To date, biological implications of unbalanced amounts of melatonin and myo-inositol in each pregnancy step are growing the idea that these molecules actively contribute to reduce negative outcomes and improve the fertilization rate. Clinical data suggest that melatonin and myo-inositol may constitute an optimal dietary supplementation to sustain safe human gestation and a new potential way to prevent pregnancy-associated pathologies.

Inositols Depletion and Resistance: Principal Mechanisms and Therapeutic Strategies.

Inositols are natural molecules involved in several biochemical and metabolic functions in different organs and tissues. The term "inositols" refers to five natural stereoisomers, among which myo-Inositol (myo-Ins) is the most abundant one. Several mechanisms contribute to regulate cellular and tissue homeostasis of myo-Ins levels, including its endogenous synthesis and catabolism, transmembrane transport, intestinal adsorption and renal excretion. Alterations in these mechanisms can lead to a reduction of inositols levels, exposing patient to several pathological conditions, such as Polycystic Ovary Syndrome (PCOS), hypothyroidism, hormonal and metabolic imbalances, like weight gain, hyperinsulinemia, dyslipidemia, and metabolic syndrome. Indeed, myo-Ins is involved in different physiological processes as a key player in signal pathways, including reproductive, hormonal, and metabolic modulation. Genetic mutations in genes codifying for proteins of myo-Ins synthesis and transport, competitive processes with structurally similar molecules, and the administration of specific drugs that cause a central depletion of myo-Ins as a therapeutic outcome, can lead to a reduction of inositols levels. A deeper knowledge of the main mechanisms involved in cellular inositols depletion may add new insights for developing tailored therapeutic approaches and shaping the dosages and the route of administration, with the aim to develop efficacious and safe approaches counteracting inositols depletion-induced pathological events.

Natural Molecules in the Management of Polycystic Ovary Syndrome (PCOS): An Analytical Review.

Polycystic ovary syndrome (PCOS) is a heterogenous disorder characterized by chronic ovulation dysfunction and hyperandrogenism. It is considered the most common endocrinological disorder, affecting up to 25% of women of reproductive age, and associated with long-term metabolic abnormalities predisposing to cardiovascular risk, such as insulin resistance (IR), dyslipidemia, endothelial dysfunction, and systemic inflammation. PCOS is also characterized by elevated serum levels of luteinizing hormone (LH), causing a condition of hyperandrogenism and a consequent altered ratio between LH and the follicle stimulating hormone (FSH). Over the years, several different approaches have been proposed to alleviate PCOS symptoms. Supplementation with natural molecules such as inositols, resveratrol, flavonoids and flavones, vitamin C, vitamin E and vitamin D, and omega-3 fatty acids may contribute to overcoming PCOS pathological features, including the presence of immature oocyte, IR, hyperandrogenism, oxidative stress and inflammation. This review provides a comprehensive overview of the current knowledge about the efficacy of natural molecule supplementation in the management of PCOS.

The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management.

Myo-Inositol (MYO) is the most abundant stereoisomer of inositols' family, cyclic polyols with 6 hydroxyl groups. Myo-Inositol has a relevant role in thyroid function and autoimmune diseases, as a precursor of phosphoinositides that takes part in the phosphatidylinositol (PI) signal transduction pathway. Among phosphoinositides, phosphatidylinositol 4,5- bisphosphate (PIP2) is the precursor of inositol triphosphates (IP3), second messenger of several hormones including thyroid-stimulating hormone (TSH). As a second messenger in the phospholipase C (PLC)-dependent inositol phosphate Ca2+/DAG pathway, Myo-Inositol is essential to produce H2O2 required for the synthesis of thyroid hormones. Consequently, depletion of Myo-Inositol or impaired inositol dependent TSH signaling pathway may predispose to the development of some thyroid diseases, such as hypothyroidism. Many clinical studies have shown that after treatment with Myo-Inositol plus Selenium (MYO+Se), TSH levels significantly decreased in patients with subclinical hypothyroidism with or without autoimmune thyroiditis. The TSH reduction was accompanied by a decline of antithyroid autoantibodies. Moreover, Myo-Inositol supplementation seemed to be involved also in the management of thyroidal benign nodules, with a possible effect in the size reduction. This review proposes a summary of the role of inositol, especially of Myo-Inositol, in the thyroidal physiology and its contribution on the management of some thyroid diseases.

Role of inositol to improve surfactant functions and reduce IL-6 levels: A potential adjuvant strategy for SARS-CoV-2 pneumonia?

To date, the spread of SARS-CoV-2 infection is increasing worldwide and represents a primary healthcare emergency. Although the infection can be asymptomatic, several cases develop severe pneumonia and acute respiratory distress syndrome (ARDS) characterized by high levels of pro-inflammatory cytokines, primarily interleukin (IL)-6. Based on available data, the severity of ARDS and serum levels of IL-6 are key determinants for the prognosis. In this scenario, available in vitro and in vivo data suggested that myo-inositol is able to increase the synthesis and function of the surfactant phosphatidylinositol, acting on the phosphoinositide 3-kinase (PI3K)-regulated signaling, with amelioration of both immune system and oxygenation at the bronchoalveolar level. In addition, myo-inositol has been found able to decrease the levels of IL-6 in several experimental settings, due to an effect on the inositol-requiring enzyme 1 (IRE1)-X-box-binding protein 1 (XBP1) and on the signal transducer and activator of transcription 3 (STAT3) pathways. In this scenario, treatment with myo-inositol may be able to reduce IL-6 dependent inflammatory response and improve oxygenation in patients with severe ARDS by SARS-CoV-2. In addition, the action of myo-inositol on IRE1 endonuclease activity may also inhibit the replication of SARS-CoV-2, as was reported for the respiratory syncytial virus. Since the available data are extremely limited, if this potential therapeutic approach will be considered valid in the clinical practice, the necessary future investigations should aim to identify the best dose, administration route (oral, intravenous and/or aerosol nebulization), and cluster(s) of patients which may get beneficial effects from this treatment.

Inositols in Polycystic Ovary Syndrome: An Overview on the Advances.

This review details the physiologic roles of two insulin sensitizers, myo-inositol (MI) and d-chiro-inositol (DCI). In the human ovary, MI is a second messenger of follicle-stimulating hormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment for polycystic ovary syndrome (PCOS) to be defined based on the combined administration of MI and DCI, where the best MI:DCI ratio is 40:1. Moreover, MI enhances the effect of metformin and clomiphene on the fertility of PCOS women seeking pregnancy. As impaired intestinal transport may lead to unsuccessful inositol treatment, we also discuss new data on the use of alpha-lactalbumin to boost inositol absorption. Overall, the physiological activities of MI and DCI dictate the dosages and timing of inositol supplementation in the treatment of PCOS.

Experts' opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond.

Introduction: This Experts' opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM).Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients.Expert opinion: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.

Iodine and Myo-Inositol: A Novel Promising Combination for Iodine Deficiency.

Despite universal salt iodization programmes implemented over the last decades, iodine deficiency remains a major public health problem in many countries worldwide. Endeavors are still required to ensure sufficient iodine intake in the populations at risk in order to eliminate deficiency. Iodine is crucial for the synthesis of thyroid hormones triiodothyronine (T3) and thyroxine (T4), as well as for the thyroid health. When iodine levels are insufficient, T4 attests toward the lower limit of the physiological range, causing subtle fluctuations in the T3:T4 ratio. Monitoring these variations may be an accurate way to assess patient's iodine status. Recently, a number of published clinical studies documented a growing interest toward the use of myo-inositol in thyroid diseases. Myo-inositol, a carbocyclic polyol, regulates the generation of hydrogen peroxide (H2O2) in thyrocytes, crucial for iodine organification and thyroid hormone biosynthesis. Thus, combined supplementation of iodine and myo-inositol may promote higher iodine availability in thyrocytes improving thyroid functionality. This review presents novel strategies for the diagnosis and the management of iodine deficiency, focusing on the potential role of myo-inositol combined with iodine.