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We conducted an observational descriptive study evaluating the effectiveness of therapeutic modification of lifestyle with adding of 1000 mg of myo-inositol and 200 mg of D-chiro inositol combination (ratio 5:1) for nutritional support in 104 women of reproductive age with polycystic ovary syndrome (classic phenotype and nonclassical phenotypes in the presence of hyperandrogenism) for 6 months. Revealed changes in anthropometric parameters (decrease in body mass index by 0.89 kg/m 2 ; p

D-chiroinositol (DCI) is one of the 9 inositol isomers that forms inositol phosphoglycans, which are mediators of the action of insulin. The metabolism of DCI and myo-inositol (MI) is impaired against the background of insulin resistance, including the patients with polycystic ovary syndrome (PCOS). Aim. Highlight the most characteristic pharmacological properties of DCI. Materials and methods. Systematic computer analysis of 45 600 publications on the biological roles of inositol by methods of the topological theory of pattern recognition and systems biology analysis of human proteome. Results. A complex of interactions between metabolic disorders of DCI, PCOS, ovulation disorders, obesity associated with numerous hormonal disorders is described. Supplements with DCI and MI increase the sensitivity of cells to insulin and normalize the metabolism of androgens. An important difference between DCI and MI is the presence of DCI in the composition of inositol phosphoglycans that mediate the action of insulin on cells, as well as its participation in the realization of the therapeutic effects of metformin. The use of the MI+DCI combination allows achieving positive dynamics in reducing excess body weight, normalizing blood lipids, glucose and insulin levels, restoring the ovulatory menstrual cycle, improving oocyte quality, and helps prevent gestational diabetes in pregnant women and macrosomia of the fetus. DCI is more effective than MI in reducing the risk of folate-resistant neural tube defects. Conclusion. The therapeutic potential of DCI in combination with MI for treating PCOS and hyperandrogenism is evident. Depending on the therapeutic expediency, various ratios of MI:DCI can be used for the treatment of PCOS and disorders of carbohydrate and lipid metabolism.A

The 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.

Analogues of the Ca2+-releasing intracellular messenger d-myo-inositol 1,4,5-trisphosphate [1, Ins(1,4,5)P3] are important synthetic targets. Replacement of the α-glucopyranosyl motif in the natural product mimic adenophostin 2 by d-chiro-inositol in d-chiro-inositol adenophostin 4 increased the potency. Similar modification of the non-nucleotide Ins(1,4,5)P3 mimic ribophostin 6 may increase the activity. d-chiro-Inositol ribophostin 10 was synthesized by coupling as building blocks suitably protected ribose 12 with l-(+)-3-O-trifluoromethylsulfonyl-6-O-p-methoxybenzyl-1,2:4,5-di-O-isopropylidene-myo-inositol 11. Separable diastereoisomeric 3-O-camphanate esters of (±)-6-O-p-methoxy-benzyl-1,2:4,5-di-O-isopropylidene-myo-inositol allowed the preparation of 11. Selective trans-isopropylidene deprotection in coupled 13, then monobenzylation gave separable regioisomers 15 and 16. p-Methoxybenzyl group deprotection of 16, phosphitylation/oxidation, then deprotection afforded 10, which was a full agonist in Ca2+-release assays; its potency and binding affinity for Ins(1,4,5)P3R were similar to those of adenophostin. Both 4 and 10 elicited a store-operated Ca2+ current ICRAC in patch-clamped cells, unlike Ins(1,4,5)P3 consistent with resistance to metabolism. d-chiro-Inositol ribophostin is the most potent small-molecule Ins(1,4,5)P3 receptor agonist without a nucleobase yet synthesized.

Inositol-containing drugs (stereoisomers of cyclohexane-1,2,3,4,5,6-hexol) are used to compensate insulin resistance, particularly in patients with menstrual and ovarian disorders. Inositols are effective in preventing folate-resistant fetal malformations. Objective. To analyze pharmacological differences between the four main biologically active stereoisomers of inositol: myoinositol (MI), D-chiro-inositol (DCI), neo-inositol (NI), and scylloinositol (SCI) using the comparative chemoreactomic method. Materials and methods. Chemoreactom analysis, PubChem / PHARMGKBb HMDB, STRING databases Results. DCI is more sufficient than MI for (1) processing of branched-chain amino acids, which promotes normalization of glucose metabolism, as well as (2) metabolism of folates, vitamin PP, vitamin B5, and magnesium, (3) activation of insulin-like growth factor 1 (IGF-1) receptor, whose activity is important for the prevention of sarcopenia, (4) antitumor effects (by inhibiting hyperproliferative effects, including those associated with excess glucose and an imbalance of androgens and estrogens), (5) inhibition of proinflammatory proteins (matrix metalloproteinase 15, ICAM1, and IRAK4 that mediate effects of interleukin-1). Conclusion. The profiles of pharmacological activity of DCI and SCI differ significantly from those of MI and NI. Therefore, combinations of MI and DCI are a more promising option to increase the sensitivity of cells to insulin than separate use of MI or DCI. Key words: insulin resistance, hyperandrogenism, polycystic ovary syndrome, post-genomic pharmacology, myo-inositol, D-chiro-inositol, neo-inositol, scylloinositol, Dikirogen

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.

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.

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., Несмотря на химическое сходство мио-инозитола и D-хиро-инозитола и их синергическое влияние на чувствительность к инсулину, они выполняют различные функции. Резистентность к инсулину – один из этиологических факторов развития синдрома поликистозных яичников (СПКЯ), сахарного диабета, метаболического синдрома, бесплодия, нарушений менструального цикла и овуляции, осложнений беременности, в частности гестационного диабета. Мио-инозитол играет важную роль в процессах передачи инсулина и синтеза гормонов в яичниках, а также в созревании ооцитов, оплодотворении, имплантации и развитии после имплантации.Многие исследования подтверждают положительное влияние изомеров инозитола на метаболические, гормональные и репродуктивные нарушения – как в виде монотерапии, так и в сочетании с другими препаратами для усиления терапевтического эффекта и биодоступности. Мио-инозитол обладает благоприятным профилем безопасности. Исследования показали, что его применение у пациенток с СПКЯ улучшает функцию яичников и фертильность, уменьшает проявления гиперандрогении, инсулинорезистентности и нормализует массу тела.Мио-инозитол и D-хиро-инозитол имеют разные механизмы воздействия на чувствительность к инсулину и выполняют разные функции. Сбалансированность двух изомеров обеспечивает нормальную секрецию гормонов и работу яичников, но в настоящее время неизвестно, каким должно быть оптимальное соотношение этих двух изомеров, ввиду небольшого количества исследований высокого качества и трудности изучения обособленного их действия.В настоящее время существуют разные комбинации мио- и D-хиро-инозитола, но их эффективность не подтверждена достаточным количеством исследований высокого качества. При назначении различных изомеров инозитола необходимо учитывать, что при СПКЯ наиболее изученными являются дозы от 4000 мг, но при концентрации D-хиро-инозитола от 1200 мг/сут наблюдаются нежелательные эффекты. Большинство исследований свидетельствуют, что при СПКЯ повышен уровень D-хиро-инозитола, поэтому ооциты более чувствительны к его передозировке, а комбинированные препараты требуют дополнительного изучения. На сегодняшний день в литературе нет единого мнения о преимуществе комбинированных препаратов мио- и D-хиро-инозитола перед монотерапией мио-инозитолом. Монотерапия мио-инозитолом является более изученной и безопасной., Незважаючи на хімічну схожість міо-інозитолу й D-хіро-інозитолу та їхній синергічний вплив на чутливість до інсуліну, вони виконують різні функції. Резистентність до інсуліну – один з етіологічних чинників розвитку синдрому полікістозних яєчників (СПКЯ), цукрового діабету, метаболічного синдрому, безпліддя, порушень менструального циклу й овуляції, ускладнень вагітності, зокрема гестаційного діабету. Міо-інозитол відіграє важливу роль у процесах передавання інсуліну та синтезу гормонів у яєчниках, а також у дозріванні ооцитів, заплідненні, імплантації та розвитку після імплантації. Багато досліджень підтверджують позитивний вплив ізомерів інозитолу на метаболічні, гормональні та репродуктивні порушення – як у вигляді монотерапії, так і в поєднанні з іншими препаратами для посилення терапевтичного ефекту й біодоступності. Міо-інозитол характеризується сприятливим профілем безпеки. Дослідження продемонстрували, що його застосування в пацієнток із СПКЯ покращує функцію яєчників і фертильність, зменшує прояви гіперандрогенії, інсулінорезистентності та нормалізує масу тіла. Міо-інозитол і D-хіро-інозитол мають різні механізми впливу на чутливість до інсуліну й виконують різні функції. Збалансованість двох ізомерів забезпечує нормальну гормональну секрецію та роботу яєчників, але наразі невідомо, яким має бути оптимальне співвідношення цих двох ізомерів, через недостатню кількість досліджень високої якості та труднощі вивчення саме відокремленої їхньої дії. Сьогодні існують різні комбінації міо- та D-хіро-інозитолу, але їхня ефективність не підтверджена достатньою кількістю досліджень високої якості. При призначенні різних ізомерів інозитолу необхідно враховувати, що при СПКЯ найбільш вивченими є дози від 4000 мг, але за концентрації D-хіро-інозитолу від 1200 мг/добу спостерігаються небажані ефекти. Більшість досліджень свідчать, що при СПКЯ підвищений рівень D-хіро-інозитолу, тому ооцити чутливіші до його передозування, а комбіновані препарати потребують додаткового вивчення. Наразі в літературі немає єдиної думки щодо переваги комбінованих препаратів міо- та D-хіро-інозитолу над монотерапією міо-інозитолом. Монотерапія міо-інозитолом є більш вивченою і безпечною.

Several recent journal articles report that D-chiro-inositol (DCI), primarily known as insulin second messenger, influences steroidogenesis. In particular, new evidence is arising on DCI ability to regulate aromatase expression and testosterone biosynthesis. In this regard, DCI administration could represent a good therapeutic opportunity in case of reduced levels of testosterone. Older men generally have lower testosterone concentrations than younger men, and recent randomized controlled trials have examined whether testosterone treatment might improve health outcomes in this age group. There is limited information about the safety of testosterone replacement therapy in these men, hence DCI could represent an interesting alternative for future trials. Therefore, this study aims to evaluate the effect of DCI treatment on testosterone levels in older male patient.Ten older men with basal low testosterone levels were enrolled in this study. Patients took 600 mg of DCI, two-times per day, for 30 days. We evaluated hormonal and glycaemic parameters, weight, waist circumference, and Body-Mass Index at baseline (T0) and after 30 days (T1). Finally, all patients also filled in the standardized International Index of Erectile Function questionnaire and performed the Handgrip test at T0 and T1. Men receiving DCI showed increased androgen and reduced oestrogen concentrations, and improved glycaemic profiles. DCI was also associated with reduced weight, Body-Mass Index, waist circumference, and improved grip strength and self-reported sexual function. All these effects led to the improvement of sexual function and physical strength.In this pilot study, DCI treatment improved the levels of testosterone and androstenedione at the expense of oestrogens in elder men with low basal levels of these hormones without adverse effects.Clinicaltrials.gov: D-chiroinositol Administration in Hypogonadal Males, NCT04708249.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.

D-chiro-inositol (DCI) is a natural compound detectable in cell membranes, which is highly conserved as a biological signaling molecule. In mammals, its function is primarily characterized in the intracellular transduction cascade of insulin. In particular, insulin signal promotes the release of pivotal DCI-containing molecules. In fact, impaired release of DCI is a common feature of insulin-resistant tissues, and insulin-sensitizing pharmaceuticals induce higher concentrations of free DCI. Moreover, it also plays important roles in several other processes. DCI is involved in the regulation of steroidogenesis, due to its regulatory effects on steroidogenic enzymes, including 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase, and aromatase. Such regulation of various enzymes indicates a mechanism by which the body regulates different processes via a single molecule, depending on its concentration. DCI also reduces the expression of integrin β3, which is an adhesion molecule involved in embryo implantation and cellular phenomena such as survival, stemness, and invasiveness. In addition, DCI seems to have important anti-inflammatory activities, like its 3-O-methyl-ether, called pinitol. In vitro evidence demonstrates that treatment with both compounds induces a reduction in pro-inflammatory factors—such as Nf-κB—and cytokines—such as TNF-α. DCI then plays important roles in several fundamental processes in physiology. Therefore, research on such molecule is of primary importance.

OBJECTIVE To compare the effect of myo-inositol and d-chiro-inositol in combination (MI + DCI) with combined hormonal contraceptive (CHC) on menstrual cycle regulation in young Indian women with polycystic ovary syndrome (PCOS). METHODS Seventy young women with PCOS aged 15-24 years with delayed cycles were randomized into two groups and were treated for 6 months with MI + DCI (550 + 150 mg, 3.6:1 ratio) twice a day and CHC (ethinyl estradiol 20 µg + drospirenone 3 mg) once a day. RESULTS Spontaneous menses resumed in 28 (84.85%) young women on MI + DCI, compared with withdrawal bleeding in 34 (100%) on CHC. The mean cycle length reduced with both MI + DCI (124.54 ± 8.08 to 57.75 ± 3.00 days, P

Study question Low doses of D-Chiro-Inositol are beneficial in the treatment of a PCOS mouse model. However, high doses are detrimental for ovarian histology/function. Is D-Chiro-Inositol toxic for the mammalian ovary? Summary answer Five mg/day D-Chiro-Inositol for 21 days produced PCOS-like histological/hormonal features. Ten/20 mg/day for 21 days induced ovarian/hormonal states resembling those typical of aged mice. What is known already Administration of Myo-Inositol and D-Chiro-Inositol combined according to their plasma molar ratio of 40:1 has beneficial effects in the management of human PCOS. We confirmed the efficacy of this formulation, containing 0.2 mg/day D-Chiro-Inositol, in a mouse model of PCOS. However, formulations containing higher amounts of DCIns had negative effects on ovarian histology and mouse fertility. We investigated possible ovarian toxicity of D-Chiro-Inositol, studying its effects after administration to 30-day-old female mice for 21 days. Young adult mice reproduced the condition of young women possibly facing reproductive/metabolic problems, such as PCOS. Study design, size, duration The effects of various doses of D-Chiro-Inositol were analysed on mouse ovarian histology, serum testosterone levels and expression of the ovarian enzyme aromatase. The 21-day period follows normal protocols of pharmacologic PCOS induction in the mouse and spans five ovulatory cycles. Doses employed, 5, 10, 20 mg/day, correspond to doses of 1200, 2400, 4800 mg/day in humans. The first dose is in the range of 1000–1500 mg/day currently prescribed to PCOS patients in clinical practice. Participants/materials, setting, methods Five mice/treatment were provided with water administering various doses of D-Chiro-Inositol or 0,5 mg/day letrozole as PCOS-positive controls, for 21 days. At the end of the period, ovulatory cycles were analysed by observations of vaginal cells after vaginal smears; ovarian histology was evaluated by sectioning, hematoxylin-eosin staining and light-transmission microscopy; serum testosterone levels were measured by ELISA; and expression of the ovarian enzyme aromatase was assayed by Western Blots. Main results and the role of chance The estrus cycle progressed normally in negative control mice, but was arrested at day 8–10 in the majority of mice under all pharmacologic treatments. Uteri of negative control mice displayed the typical aspect of mature and cycling animals. Uteri of all other mice had an immature/metestrus-diestrus-like aspect, typical of non-cycling animals. Ovaries of negative control mice showed a normal presence of primary, secondary and tertiary follicles containing a growing oocyte, and of corpora lutea. Ovaries from mice treated with 5 mg/day D-Chiro-Inositol or 0,5 mg/day letrozole had apparently normal primary and secondary follicles but also cystic tertiary follicles resembling those found in human PCOS. Ovaries from mice treated with 10 or 20 mg/day D-Chiro-Inositol had scarce primary and secondary follicles, a very limited number of tertiary follicles and no cystic follicles, but large follicles/areas with diffused cell proliferation. The typical ovarian structure was lost, especially in the highest dosage. Treatments with 5 mg/day D-Chiro-Inositol and 0,5 mg/day letrozole increased serum testosterone levels above those of negative control mice, but the former reduced, while the latter increased aromatase levels relative to negative controls. Other treatments had no apparent effects on either testosterone or aromatase levels. Our experimental paradigm makes the role of chance highly improbable. Limitations, reasons for caution The strength of our study relies on the use of an animal model representative of general human tissue organisation and physiological pathways. One weakness consists in the lack of data on serum estrogen levels, due to the paucity of blood provided by a single mouse and the ELISA sensitivity. Wider implications of the findings: Under all experimental conditions, D-Chiro-Inositol negatively affected ovarian histology and function. Notwithstanding physiological/biochemical differences between mice and humans, caution is therefore recommended when administering D-Chiro-Inositol to PCOS patients at doses corresponding to those we employed in the mouse and/or for long periods, since it may result ineffective or even toxic. Trial registration number Not applicable

In this study, the bioaccessibility of D-chiro-inositol (DCI) from water biscuits formulated from raw and roasted buckwheat flours originating from common buckwheat after liquid-state fermentation (LSF) by select lactic acid bacteria (LAB) and fungi Rhizopus oligosporus 2740 was studied. The LAB-dependent variation in DCI content in fermented buckwheat flours was noted. LSF by L. salivarius AWH and R. oligosporus 2740 significantly enhanced the DCI content, whereas most of the applied LAB reduced DCI in the fermented flours. Baking at 220 °C for 30 min significantly enhanced the DCI level; however, no correlation was found between the DCI content in fermented flours and the biscuits prepared from them. The potential bioaccessibility of DCI from water biscuits was low. It can be concluded that, by applying select LAB and R. oligosporus 2740 for LSF, the heat treatment and physical structure of biscuits were mainly responsible for the potential bioaccessibility of DCI.

The impact of two commercial enzyme preparations (Mats L Classic, Brewers Compass) used for mashing buckwheat malt was studied to assess their efficacies in releasing D-chiro- and myo-inosi...

Polycystic ovary syndrome (PCOS) is a common endocrine disorder that develops in 10–15% of reproductive aged women. Over the past two decades, the inositol effectiveness in normalizing the clinical and hormonal disorders associated with PCOS has been actively studied. Inositol and its stereoisomers are classified as insulin sensitizers and act as a second conductor for insulin transmission routes. Myo-inositol and D-chiro-inositol are two of the nine existing stereoisomers the most studied currently, which play an important role in the PCOS physiology and treatment. The aim of the study was to study the Protalis effectiveness in patients with PCOS. 40 women with PCOS (mean age 24.4 ± 0.8 years) who were resistant to previous treatment with clomiphene citrate were examined. Protalis was administered for three months, after the end of the drug intake clomiphene citrate was used according to the standard regimen to restore fertility. The levels of luteinizing hormone, follicle-stimulating hormone, sex hormone binding globulin, total testosterone, antiMullerian hormone, homocysteine, folic acid were determined, and free androgen index was calculated. Fasting insulin was tested in serum and 120 minutes after the glucose load, the HOMA-IR was calculated, and lipid metabolism parameters were studied. Monotherapy with Protalis normalized the menstrual cycle in 52.5%, restore ovulation in 40%, contributed to the pregnancy in 7.5% patients with PCOS, in combination with clomiphene citrate in 27.5% women previously resistant to clomiphene. No changes in body mass index, waist circumference/hip circumference or hirsutism were found. A decrease in hyperandrogenism due to a testosterone decrease and an sex hormone binding globulin increase was found, the carbohydrate, lipid metabolism, and folate status improved. Protalis monotherapy can be recommended for patients with PCOS as a preliminary preparation, potentiating the clomiphene citrate effects, on the background insulin resistance. It is advisable to consider the Protalis use in combination with drugs for standard treatment of PCOS.

Background Polycystic ovarian syndrome (PCOS) is a highly variable syndrome and one of the most common female endocrine disorders. Although the association inositols-glucomannan may represent a good therapeutic strategy in the treatment of PCOS women with insulin resistance, the effect of inositols on the metabolomic profile of these women has not been described yet. Results Fifteen PCOS-patients and 15 controls were enrolled. Patients were treated with myo-inositol (1.75 g/day), D-chiro-inositol (0.25 g/day) and glucomannan (4 g/day) for 3 months. Blood concentrations of glucose, insulin, triglycerides and cholesterol, and ovary volumes and antral follicles count, as well as metabolomic profiles, were evaluated for control subjects and for cases before and after treatment. PCOS-patients had higher BMI compared with Controls, BMI decreased significantly after 3 months of treatment although it remained significantly higher compared to controls. 3-methyl-1-hydroxybutyl-thiamine-diphosphate, valine, phenylalanine, ketoisocapric, linoleic, lactic, glyceric, citric and palmitic acid, glucose, glutamine, creatinine, arginine, choline and tocopherol emerged as the most relevant metabolites for distinguishing cases from controls. Conclusion Our pilot study has identified a complex network of serum molecules that appear to be correlated with PCOS, and with a combined treatment with inositols and glucomannan. Trial registration ClinicalTial.gov, NCT03608813. Registered 1st August 2018 - Retrospectively registered, . Electronic supplementary material The online version of this article (10.1186/s13048-019-0500-x) contains supplementary material, which is available to authorized users.

A growing body of research has investigated the association between inositol and diabetes. The purpose of this review is to report through a systematic way the current scientific evidence relating potential benefits of inositol isomers on diabetes/gestational diabetes. The screening of the studies published last decade was performed in 4 databases (Pubmed-Web of Science-The Cochrane Library-Lilacs). Among the 1640 studies identified in the search, only 26 studies had sufficient data to be included in the systematic review. The available literature suggests that inositol seems to be provide improvements in fasting blood glucose and other biochemical results, which are among the most important parameters in diabetic individuals. Although there are some studies demonstrating that inositol may be effective in prevention and treatment of diabetes/gestational diabetes, conduction of studies with larger sample and longer follow-up duration is required for it to be represented as an effective strategy in management of diabetes.

To evaluate the effects of the combination of d-chiro inositol and alpha lipoic acid on menstrual cycles and insulin sensitivity in women with polycystic ovary syndrome (PCOS). Forty-one women with PCOS and 31 controls have been enrolled in the study. The menstrual cycle, BMI, homeostasis model assessment index (HOMA-I), and insulin secretion in response to an OGTT were evaluated before and after 6 months of treatment. During the observation period, the patients have been asked to not modify their diet and physical activity. The menstrual cycle length improved in 76.7% of the women. Ovulation was restored in 40%. During treatment, BMI significantly decreased (p.002). The HOMA-I and insulin secretion were unchanged by treatment. However, when women were divided according to the presence of insulin resistance (IR; HOMA-I 2.5), in those with IR the HOMA-I and the insulin secretion significantly decreased (p.05 and p.006). The association of d-chiro-inositol and alpha lipoic acid improves menstrual cycle length, restoring ovulation in the majority of women. Insulin sensitivity improved in women with IR only, confirming that in presence of IR the d-chiro-inositol has a role in restoring the insulin action overcoming the inactivity of epimerase in transforming myo-inositol to d-chiro inositol.

Objective To compare the effects of metformin alone versus combined therapy of metformin with myoinositol (MI) plus D-chiro-inositol (DCI) in women with polycystic ovary syndrome (PCOS). Materials and methods This is a prospective, non-blinded randomized controlled trial conducted in newly diagnosed PCOS women aged 18 to 45 years. Group I received metformin 500 mg twice a day orally for 6 months while group II received metformin 500 mg twice a day orally along with MI 550 mg plus DCI 150 mg twice daily orally for six months. The primary outcome was a change in clinical, metabolic and hormonal parameters of the two groups from baseline to the end of six months of treatment. Results A total of 72 patients were randomized into two groups of 36 patients each. Statistically, a significant difference was seen in terms of mean global acne score (p=0.004) and cycle regularity (p=0.034) after six months of treatment in group II. A significant difference in values of luteinizing hormone (LH) (p=0.002), luteinizing hormone/follicle-stimulating hormone (LH/FSH) ratio (p=0.007), mean cholesterol (p=0.040), mean high-density lipoprotein (HDL) (p=0.049), mean low-density lipoprotein (LDL) (p=0.0001) and postprandial insulin (p=0.005) was also seen in group II at the end of treatment duration. No significant difference was seen between the two groups in terms of mean FSH, mean testosterone, mean dehydroepiandrosterone sulfate (DHEAS), mean triglyceride, mean fasting and postprandial blood sugar, fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR) index. Conclusion Combined therapy with metformin and MI plus DCI in women with PCOS and insulin resistance seems promising with the need for further studies with a greater sample size to evaluate the efficacy of this treatment.

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.

Hawthorn berry has been proved hypoglycemic effect due to the presence of some α-glucosidase inhibitors. Herein, screening and identifying of α-glucosidase inhibitors from hawthorn berry were conducted, and the results showed polyphenols mainly containing quercetin (74.58%) and hyperioside (9.58%) were responsible for its bioactivity. In order to enhance the hypoglycemic effect, the combined glucose-lowering complex (DEH) consisting of hawthorn polyphenols, D-chiro-inositol (DCI), and epigallocatechin gallate (EGCG) was prepared, where three ingredients exerted the synergistic hypoglycemic effect to enhance glucose consumption and glycogen levels and inhibit hepatic gluconeogenesis in IR-HepG2 cells. In STZ/HFD-induced mice, DEH effectively improved insulin resistance, reduced fasting blood glucose (FBG) and hepatic gluconeogenesis, and increased hepatic glycogen synthesis and storage via down-regulation of PI3K/Akt/FOXO1-mediated PEPCK and G6Pase and up-regulation of PI3K/Akt/GSK3-mediated GS activation in the liver. In summary, these findings indicate that DEH is a potential novel strategy for the treatment of type 2 diabetes. PRACTICAL APPLICATIONS: Glucose-lowering complex (DEH) with superior hypoglycemic effect, can effectively improve the insulin resistance, reduce the fasting blood glucose, hepatic gluconeogenesis and increase the hepatic glycogen synthesis and storage in mice, which represents a potential novel strategy for the treatment of type 2 diabetes.

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.

Administration of 1000–1500 mg/day D-Chiro-Inositol (DCIns) or a combination of Myo-Inositol (MyoIns) and DCIns in their plasma molar ratio (40:1) for three or more months are among recommended treatments for metabolic syndrome and/or Polycystic Ovary Syndrome (PCOS). We previously confirmed the efficacy of this formulation (8.2 mg/day MyoIns and 0.2 mg/day DCIns for 10 days) in a mouse PCOS model, but also observed negative effects on ovarian histology and function of formulations containing 0.4–1.6 mg/day DCIns. We therefore analyzed effects of higher doses of DCIns, 5, 10 and 20 mg/day, administered to young adult female mice for 21 days, on ovarian histology, serum testosterone levels and expression of the ovarian enzyme aromatase. Five mg/day DCIns (human correspondence: 1200 mg/day) altered ovarian histology, increased serum testosterone levels and reduced the amount of aromatase of negative controls, suggesting the induction of an androgenic PCOS model. In contrast, 10–20 mg/day DCIns (human correspondence: 2400–4800 mg/day) produced ovarian lesions resembling those typical of aged mice, and reduced serum testosterone levels without affecting aromatase amounts, suggesting a failure in steroidogenic gonadal activity. Notwithstanding physiological/biochemical differences between mice and humans, the observed pictures of toxicity for ovarian histology and function recommend caution when administering DCIns to PCOS patients at high doses and/or for periods spanning several ovulatory cycles.

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 stimulatinghormone (FSH) and DCI is an aromatase inhibitor. These activities allow a treatment forpolycystic ovary syndrome (PCOS) to be defined based on the combined administration of MIand DCI, where the best MI:DCI ratio is 40:1. In addition, MI plays a pivotal role in thephysiology of reproduction, and has beneficial effects on the development of oocytes,spermatozoa, and embryos. By contrast, DCI has little effect on spermatozoa, but highconcentrations in the ovary can negatively affect the quality of oocytes and the blastocyst.Overall, the evidence in the literature supports the beneficial effects of MI in both female andmale reproduction, warranting clinical use of MI in assisted reproductive treatment (ART)., Cette revue détaille les rôles physiologiques de deux sensibilisateurs à l’insuline, lemyo-inositol (MI) et le D-chiro-inositol (DCI). Dans l’ovaire humain, le MI est un secondmessager de l’hormone folliculostimulante (FSH) et le DCI est un inhibiteur de l’aromatase. Cesactivités permettent de définir un traitement du syndrome des ovaires polykystiques (SOPK)basé sur l’administration combinée de MI et de DCI, où le meilleur rapport MI:DCI est de 40:1.En outre, le MI joue un rôle essentiel dans la physiologie de la reproduction et a des effetsbénéfiques sur le développement des ovocytes, des spermatozoïdes et des embryons. Enrevanche, le DCI a peu d’effet sur les spermatozoïdes, mais des concentrations élevées dansl’ovaire peuvent avoir un effet négatif sur la qualité des ovocytes et du blastocyste. Dansl’ensemble, les données de la littérature confirment les effets bénéfiques du MI dans lareproduction féminine et masculine, ce qui justifie l’utilisation clinique du MI dans l’assistancemédicale à la procréation.

International audience; 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.

The regio- and stereospecific synthesis ofO-methyl-chiro-inositols andO-methyl-scyllo-inositol was achieved, starting fromp-benzoquinone. After preparing dimethoxy conduritol-B as a key compound, regiospecific bromination of the alkene moiety of dimethoxy conduritol-B and acid-catalyzed ring opening of dimethoxydiacetate conduritol-B epoxide with Ac2O afforded the desired newchiro-inositol derivatives andscyllo-inositol derivative, respectively. Spectroscopic methods were employed for the characterization of all synthesized compounds. The novel inositols (11-17) had effective inhibition profiles against human carbonic anhydrase isoenzymes I and II (hCA I and II) and acetylcholinesterase (AChE). The novel inositols11-17were found to be effective inhibitors against AChE, hCA I, and hCA II enzymes.K(i)values were calculated in the range of 87.59 +/- 7.011 to 237.95 +/- 17.75 mu M for hCA I, 65.08 +/- 12.39 to 538.98 +/- 61.26 mu M for hCA II, and 193.28 +/- 43.13 to 765.08 +/- 209.77 mu M for AChE, respectively. Also, due to the inhibitory effects of the novel inositols11-17against the tested enzymes, these novel inositols are potential drug candidates to treat some diseases such as glaucoma, epilepsy, leukemia, and Alzheimer's disease., Ordu University Scientific Research Projects Coordination Unit (ODU/BAP) [AR-1324], The authors are indebted to Ordu University Scientific Research Projects Coordination Unit (ODU/BAP, Grant No: AR-1324) for financial support of this study.

D-Chiro-Inositol (D-Chiro-Ins) is a secondary messenger in the insulin signaling pathway. D-Chiro-Ins modulates insulin secretion, the mitochondrial respiratory chain, and glycogen storage. Due to these actions D-Chiro-Ins has been proposed to correct defective insulin function in a variety of conditions characterized by metabolic dysfunction, such as polycystic ovary syndrome (PCOS), obesity, gestational diabetes and fat accumulation at menopause. Since it is unclear whether D-Chiro-Ins directly acts on adipocytes, we aimed to study D-Chiro-Ins’s actions on adipocyte viability, proliferation, differentiation, and insulin-related protein expression using a human adipocyte cell line derived from Simpson–Golabi–Behmel Syndrome (SGBS) which fully differentiates to mature adipocytes. Throughout differentiation, cells were treated with D-Chiro-Ins, 17β-estradiol (E2) or Insulin. Cell viability and proliferation were not affected by D-Chiro-Ins, then D-Chiro-Ins promoted cell differentiation only during the final days of the process, while E2 enhanced it from the first phases. D-Chiro-Ins stimulated lipid storage and the production of big lipid droplets, thus reducing the content of free fatty acids. We also found that D-Chiro-Ins, either alone or in combination with insulin and E2 increased the expression and activation of insulin receptor substrate-1 (IRS1) and glucose transporter type 4 (GLUT4). In conclusion, this work shows that D-Chiro-Ins plays a direct role in the differentiation and in the function of human adipocytes, where it synergizes with insulin and estrogen through the recruitment of signal transduction pathways involved in lipid and glucose storage. These findings give clear insights to better understand the actions of D-Chiro-Ins on fat metabolism in women in physiology and in a variety of diseases.

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., Синдром поликистозных яичников (СПКЯ) – это симптомокомплекс, связанный с увеличением количества циркулирующих андрогенов у женщин, повышением инсулинорезистентности и ожирением. Препараты мио-инозитол, D-хиро-инозитол и метформин, которые являются сенсибилизаторами инсулина, очень помогают в лечении одного из ключевых компонентов СПКЯ – резистентности к инсулину. Мио-инозитол и D-хиро-инозитол – изомерные формы инозита, которые имеют инсулиноподобные свойства, выступая вторыми мессенджерами во внутриклеточном пути инсулина; обе эти молекулы участвуют в увеличении чувствительности различных тканей к инсулину для улучшения обменных функций и овуляции.Это исследование было выполнено с целью сравнения эффектов комбинации мио-инозитола и D-хиро-инозитола против метформина в отношении клинического и биохимического профиля при СПКЯ.Методы. Проведено проспективное рандомизированное сравнительное исследование на 200 пациентках. Больные были случайным образом распределены на две группы по 100 человек в каждой. Группа A принимала мио-инозитол по 550 мг два раза в день и D-хиро-инозитол по 13,8 мг два раза в день; группа B принимала метформин 500 мг три раза в день. Пациенток оценивали по следующим параметрам: регуляция менструального цикла, показатель гирсутизма (по шкале Ферримана-Голлвея), уровень глюкозы и инсулина натощак и постпрандиальный уровень, уровень дегидроэпиандростерона в сыворотке крови, уровень тестостерона в сыворотке крови и соотношение лютеинизирующий/фолликулостимулирующий гормон в сыворотке крови.Результаты. В обеих группах наблюдалось значительное улучшение всех вышеупомянутых параметров, однако в группе с комбинацией мио-инозитола и D-хиро-инозитола было статистически значимое улучшение по сравнению с группой метформина.Выводы. Сочетание мио-инозитола и D-хиро-инозитола и применение метформина значительно улучшили чувствительность к инсулину женщин с СПКЯ. Дополнительно сочетание мио-инозитола и D-хиро-инозитола было эффективным в улучшении гормонального профиля (соотношение лютеинизирующий/фолликулостимулирующий гормон, свободный тестостерон) по сравнению с метформином., Синдром полікістозних яєчників (СПКЯ) – це симптомокомплекс, пов’язаний зі збільшенням кількості циркулюючих андрогенів у жінок, підвищенням інсулінорезистентності та ожирінням. Препарати міо-інозитол, D-хіро-інозитол і метформін, які є сенсибілізаторами інсуліну, дуже допомагають в лікуванні одного із ключових компонентів СПКЯ – резистентності до інсуліну. Міо-інозитол та D-хіро-інозитол – ізомерні форми інозиту, які мають інсуліноподібні властивості, виступаючи другими месенджерами у внутрішньоклітинному шляху інсуліну; обидві ці молекули беруть участь у збільшенні чутливості різних тканин до інсуліну для поліпшення обмінних функцій та овуляції.Це дослідження було виконано з метою порівняння ефектів комбінації міо-інозитолу та D-хіро-інозитолу проти метформіну стосовно клінічного та біохімічного профілю при СПКЯ.Методи. Проведено проспективне рандомізоване порівняльне дослідження на 200 пацієнтках. Хворі були випадковим чином розподілені на дві групи по 100 осіб у кожній. Група A приймала міо-інозитол по 550 мг два рази на день і D-хіро-інозитол по 13,8 мг два рази на день; група B приймала метформін 500 мг тричі на день. Пацієнток оцінювали за такими параметрами: регуляція менструального циклу, показник гірсутизму (за шкалою Феррімана-Голлвея), рівень глюкози та інсуліну натще і постпрандіальний рівень, рівень дегідроепіандростерону в сироватці крові, рівень тестостерону в сироватці крові та співвідношення лютеїнізуючий/фолікулостимулюючий гормон у сироватці крові.Результати. В обох групах спостерігалося значне поліпшення всіх вищезазначених параметрів, однак у групі з комбінацією міо-інозитолу та D-хіро-інозитолу було статистично значуще поліпшення порівняно з групою метформіну.Висновки. Поєднання міо-інозитолу і D-хіро-інозитолу та застосування метформіну значно покращили чутливість до інсуліну в жінок з СПКЯ. Додатково поєднання міо- інозитолу та D-хіро-інозитолу було ефективним у покращенні гормонального профілю (співвідношення лютеїнізуючий/фолікулостимулюючий гормон, вільний тестостерон) у порівнянні з метформіном.

Cyclitols are widely available natural sugars which do not exert toxic effects. Their anti-inflammatory and antioxidant properties may be used in the treatment of psoriasis. The aim of this placebo-controlled, double-blind study was to evaluate the clinical effects of D-chiro-inositol (DCI) in mild plaque psoriasis (46 psoriatic patients and 10 healthy volunteers). Three stable psoriatic plaques were selected for evaluation in every patient. Different samples were applied on each lesion twice a day: vehiculum without an active agent, containing 1% DCI and 0.25% DCI. The lesions were assessed using the PSI, VAS scale, and the objective measurement of hydration, transepidermal water loss (TEWL), elasticity, and thickness (DermaLab Combo) at 0, 3, and 6 weeks. PSI and VAS were improved in all groups without significant statistical differences. 1% DCI sample presented the highest statistically significant increase in the hydration of 50%, but it was still significantly lower than in healthy controls. TEWL increased for 1% DCI, which was a statistically significant difference compared to 0.25% DCI and still higher than in controls. An improvement in elasticity was observed in all lesions-it was statistically significant for 1% DCI. The thickness of the lesion decreased for 1% DCI, but the change was not statistically significant. Subepidermal low-echogenic band showed a decreasing tendency in all groups, but it was not statistically significant. Favorable 1% DCI sample results indicate that it may be used as an adjuvant to the local treatment of psoriasis.

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, withand 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., Целью данной работы является критический анализ состава многих препаратов на основе инозитола, которые сегодня используются для лечения синдрома поликистозных яичников (СПКЯ). В течение многихлет были сформулированы несколько различных комбинаций мио-инозитола и D-хиро-инозитола, с дополнительными соединениями и без них (такими как микро- и макроэлементы, витамины и α-липоевая кислота). Такие терапевтические предложения не учитывают различные особенности стереоизомеров инозитола. В качестве примера важно знать, что лечение D-хиро-инозитолом может быть полезным при его применении в низких дозах, однако постепенное увеличение дозы приводит к потере его положительного влияния на репродуктивные показатели женщин и ухудшает качество бластоцист, сформированных путем экстракорпорального оплодотворения.Кроме того, необходимо учитывать, что кишечная абсорбция мио-инозитола снижается при одновременном введении D-хиро-инозитола, поскольку два стереоизомера конкурируют между собой за один и тот же транспортер, который имеет подобное сродство к каждому из них. Снижение всасывания мио-инозитола также имеет место при одновременном применении с ингибиторами всасывания сахаров в кишечнике и/или различными типами сахаров, такими как сорбит, мальтодекстрин и сукралоза. При их сочетании для достижения терапевтической дозы может понадобиться большее количество мио-инозитола по сравнению с применением только инозитола, что является особенно важным фактом, когда врачи стремятся получить определенную концентрацию стереоизомеров в плазме крови.Наконец, было установлено, что D-хиро-инозитол является ингибитором ароматазы и тем самым повышает уровень андрогенов и может иметь неблагоприятные последствия для женщин. Поэтому добавки с инозитолом, применяемые при лечении СПКЯ, должны быть тщательно определены. Клинические данные показали, что соотношение 40:1 между мио-инозитолом и D-хиро-инозитолом является оптимальной комбинацией для восстановления овуляции у женщин с СПКЯ. Поэтому довольно странным является тот факт, что лечение СПКЯ препаратами на основе инозитола избирается случайным образом и часто сочетается с бесполезными или даже контрпродуктивными соединениями, которые могут ослабить эффективность мио-инозитола. Такие методы лечения явно не имеют терапевтического обоснования., Метою даної роботи є критичний аналіз складу багатьох препаратів на основі інозитолу, які на сьогодні використовуються для лікування синдрому полікістозних яєчників (СПКЯ). Протягом багатьох років було сформульовано кілька різних комбінацій міо-інозитолу та D-хіро-інозитолу, з додатковими сполуками та без них (такими як мікро- та макроелементи, вітаміни й α-ліпоєва кислота). Такі терапевтичні пропозиції не беруть до уваги різні особливості стереоізомерів інозитолу. Як приклад, важливо знати, що лікування D-хіро-інозитолом може бути корисним при його застосуванні в низьких дозах, проте поступове збільшення дози призводить до втрати його сприятливого впливу на репродуктивні показники жінок та погіршує якість бластоцист, сформованих шляхом екстракорпорального запліднення.Крім того, необхідно враховувати, що кишкова абсорбція міо-інозитолу знижується при одночасному введенні D-хіро-інозитолу, оскільки два стереоізомери конкурують між собою за один і той же транспортер, який має подібну спорідненість до кожного з них. Зниження всмоктування міо-інозитолу також має місце при його одночасному застосуванні з інгібіторами всмоктування цукрів у кишечнику та/або різними типами цукрів, такими як сорбіт, мальтодекстрин та сукралоза. При їх поєднанні для досягнення терапевтичної дози може знадобитися більша кількість міо-інозитолу порівняно із застосуванням лише інозитолу, що є особливо важливим фактом, коли лікарі прагнуть отримати певну концентрацію стереоізомеру в плазмі.Нарешті, було встановлено, що D-хіро-інозитол є інгібітором ароматази і тим самим підвищує рівень андрогенів та може мати шкідливі наслідки для жінок. Тому добавки до інозитолу, що застосовуються при лікуванні СПКЯ, повинні бути ретельно визначені. Клінічні дані показали, що співвідношення 40:1 між міо-інозитолом та D-хіро-інозитолом є оптимальною комбінацією для відновлення овуляції в жінок із СПКЯ. Тому досить дивним є факт, що лікування СПКЯ препаратами на основі інозитолу обирається випадковим чином і часто поєднується з марними або навіть контрпродуктивними сполуками, які можуть послабити ефективність міо-інозитолу. Такі методи лікування явно не мають терапевтичного обґрунтування.

D-pinitol is one of the major inositol found in plants and studies suggest its potential hypoglycemic and hypolipidemic actions in diabetic rodents. Here, we investigated the actions of D-pinitol on adiposity, and in lipid and glycemic homeostasis in monosodium glutamate (MSG)-obese mice. Swiss mice received daily subcutaneous injections of MSG [(4g/kg of body weight (BW)] or saline [1.25g/kg BW; control (CTL)] during their first five days of life. From 90-120 day-old, half of the MSG and CTL groups received 50 mg D-pinitol/kg BW/day (MPIN and CPIN groups) or vehicle (saline; MSG and CTL groups) by gavage. MSG mice displayed higher abdominal adiposity and hepatic triglycerides (TG) deposition, and increased hepatic expression of lipogenic genes (SREBP-1c, ACC-1 and FASN), but downregulation in AMPKα mRNA. MSG mice also exhibited hyperinsulinemia, islet hypersecretion and hypertrophy, glucose intolerance and insulin resistance. D-pinitol did not change adiposity, glucose intolerance, insulin resistance, but increased hepatic triglycerides (TG) content in MPIN mice, which was associated with increases in gene expressions of SREBP-1c and FASN, but reduction in AMPKα. Furthermore, D-pinitol enhanced insulin secretion in MPIN and CPIN groups. Therefore, D-pinitol enhanced glucose-induced insulin secretion, which may account to enhances hepatic lipogenesis and TG deposition in MPIN mice.