d-Chiro-Inositol in Clinical Practice: A Perspective from the Experts Group on Inositol in Basic and Clinical Research (EGOI).

BACKGROUND: d-Chiro-inositol is a natural molecule that, in association with its well-studied isomer myo-inositol, may play a role in treating various metabolic and gynecological disorders. OBJECTIVES: This perspective seeks to explore the mechanisms and functions of d-chiro-inositol, laying the foundations to discuss its use in clinical practice, across dysmetabolism, obesity, and hormonal dysregulation. METHODS: A narrative review of all the relevant papers known to the authors was conducted. OUTCOME: d-Chiro-inositol acts through a variety of mechanisms, acting as an insulin sensitizer, inhibiting the transcription of aromatase, in addition to modulating white adipose tissue/brown adipose tissue transdifferentiation. These different modes of action have potential applications in a variety of therapeutic fields, including PCOS, dysmetabolism, obesity, hypoestrogenic/hyperandrogenic disorders, and bone health. CONCLUSIONS: d-Chiro-inositol mode of action has been studied in detail in recent years, resulting in a clear differentiation between d-chiro-inositol and its isomer myo-inositol. The insulin-sensitizing activities of d-chiro-inositol are well understood; however, its potential applications in other fields, in particular obesity and hyperestrogenic/hypoandrogenic disorders in men and women, represent promising avenues of research that require further clinical study.

D-Chiro-Inositol in Endometrial Hyperplasia: A Pilot Study.

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

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.

The Association of High-Molecular-Weight Hyaluronic Acid (HMWHA), Alpha Lipoic Acid (ALA), Magnesium, Vitamin B6, and Vitamin D Improves Subchorionic Hematoma Resorption in Women with Threatened Miscarriage: A Pilot Clinical Study.

Background-We evaluated whether the oral intake of high-molecular-weight hyaluronic acid (HMWHA) in association with alpha lipoic acid (ALA), magnesium, vitamin B6, and vitamin D can improve the resorption of subchorionic hematoma in cases of threatened miscarriage. Methods-In this study, we enrolled 56 pregnant women with threatened miscarriage (i.e., subchorionic hematomas, pelvic pain/uterine contractions, and/or vaginal bleeding) between the 6th and the 13th week of gestation. They were treated with vaginal progesterone (200 mg/twice a day) (control group; n = 25) or vaginal progesterone plus oral 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6, and 50 mcg vitamin D (treatment group; n = 31; DAV®-HA, LoLi Pharma srl, Rome, Italy). An ultrasound scan was performed at the first visit (T0) and after 7 days (T1) and 14 days (T2) until hematoma resorption. Results-At the ultrasound scan, the treatment group showed faster resorption of the subchorionic hematoma compared with the control group, both at T1 (control group 140 (112-180), treated group 84 (40-112), p < 0.0031), and T2 (control group: 72 (48-112), treated group: 0 (0-0), p < 0.0001). Moreover, subjective symptoms, such as vaginal bleeding, abdominal pain, and uterine contractions, showed a faster decrease in the treatment group than in the control group. Conclusions-The association may more rapidly improve the resolution of threatened miscarriage and related symptoms compared to the standard local protocol.

Evaluating the Efficacy of Pervistop®, a New Combination Based on EGCG, Folic Acid, Vitamin B12 and Hyaluronic Acid on Patients with Human Papilloma Virus (HPV) Persistent Infections and Cervical Lesions: A Pilot Study.

BACKGROUND: The persistence of the HPV infection is a risk factor in the integration of viral DNA in the host genome, leading to transforming events. The lack of therapies for HPV-persistent infections determine an unmet medical need. METHODS: We enrolled forty patients with persistent HPV infections and cervical lesions and divided them into two groups. The women in the treated group received 200 mg epigallocatechin gallate (EGCG), 400 µg folic acid (FA), 1 mg vitamin B12, and 50 mg hyaluronic acid (HA) for 12 weeks. The control group received no treatment. RESULTS: 40 patients completed the study. Fifteen out of 20 women in the control group still had an LSIL at the end of the study. One woman had a decrease in the DNA load, while six had no change and eight had an increase in DNA content. In the treatment group, 17 out of 20 women achieved a full viral clearance. These women showed no cytological or histological evidence of lesions following the treatment. CONCLUSIONS: Our data highlight the possible effect of such combination on LSIL. Therefore, the evidence reported here supports the potential to carry out further randomized placebo-controlled studies with an adequate number of patients to verify our results.

Laparoscopic omental flap for the treatment of major sternal wound infection after cardiac surgery.

BACKGROUND: The ideal reconstructive procedure after sternal debridement is still a matter of debate. The omentum might be theoretically preferable for its favorable properties, but it is seldom used because it entails the added trauma of a laparotomy. METHODS: Three female patients with severe osteomyelitis after myocardial revascularization underwent sternal debridement and filling of the defect with a laparoscopically prepared omental flap. Sternal wound closure was achieved as a single-stage procedure in 2 patients. The third patient had a poststernotomy septicemia and required a 2-stage procedure. The abdominal procedures were conducted through 3 operating 5-mm ports. Omental flaps were developed by complete separation from the transverse colon and lengthening by division of some anastomosing arteries between gastroepiploic vessels and Barkow's arcade. Thoracic transposition of the omentum was achieved through a 5-cm diaphragmatic incision. The flaps were able to reach the base of the neck and fill the sternal defect in all patients. RESULTS: A smooth postoperative course was observed. Oral intake was started from day 2; sole oral nutrition was maintained from day 3 or 4. Optimal wound healing was observed with minimal or absent local discomfort. Minor transient paradoxical movements of the anterior chest wall disappeared within 1 month. Postoperative hospital stay was 9, 14, and 14 days, respectively. CONCLUSIONS: Laparoscopic omentoplasty, compared with the open procedure, entails several advantages for the treatment of sternal osteomyelitis. The introduction of minimally invasive techniques may widen the indications for the use of the omentum in the treatment of major sternal wound infections.

Successful endoscopic Nd-YAG laser treatment of endobronchial endometriosis.

Catamenial hemoptysis is a rare condition that is associated with the presence of intrapulmonary or endobronchial endometrial tissue. Diagnosis of and therapy for this condition are still a matter of debate. We describe a case of endobronchial endometriosis with catamenial hemoptysis. An endobronchial lesion was diagnosed by spiral CT scan, taken at the onset of the menses, and confirmed with flexible bronchoscopy. The patient was successfully treated with endoscopic Nd-YAG laser therapy with a 1-day in-hospital procedure. We suggest that endoscopic laser treatment should be the first line of therapy for central airway endometriosis, provided that the source of bleeding has been conclusively located and all of the lesions can be reached with the bronchoscope.

Updates on the myo-inositol plus D-chiro-inositol combined therapy in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting women of reproductive age. It is characterized by chronic anovulation, hyperandrogenism, and insulin resistance. It is the main cause of infertility due to the menstrual dysfunction and metabolic disorders. Women with PCOS also have an increased cardiovascular risk because of dyslipidemia and insulin resistance. So far, we have a lot of information about the etiology of PCOS, and many steps forward have been made about the diagnosis of this syndrome, but there is still no certainty about the therapy. Myo-inositol (MI) and D-chiro-inositol, two inositol stereoisomers, have been proven to be effective in PCOS treatment. However, only MI has been shown to have beneficial effects on reproductive function, whereas the administration of MI/D-chiro-inositol, in the physiological plasma ratio (i.e., 40:1) ensures better clinical results, such as the reduction of insulin resistance, androgens' blood levels, cardiovascular risk and regularization of menstrual cycle with spontaneous ovulation.

Potential effects of chocolate on human pregnancy: a randomized controlled trial.

OBJECTIVE: This trial was undertaken to evaluate the effects of high-cocoa-content chocolate supplementation in pregnancy on several haematochemical and clinical parameters. The study had as reference population the pregnant women requesting an obstetric control at Outpatient Clinic of Obstetrics and Gynaecology of the S. Maria della Misericordia University Hospital, Perugia, Italy. Candidates who participated in this study were all Caucasian women aged 18-40 years, who had a single gestation pregnancy between 11th + 0 and 13th + 0 week gestational age. METHODS: We conducted a single-center randomized controlled trial. The pregnant women selected were randomized into Group A, which received daily doses of 30 g of chocolate (70% cocoa), and Group B, which was free to increase their diet with other foods. RESULTS: Ninety women were randomized. Significant difference was found between the two groups for diastolic blood pressure (p = 0.05), systolic (p < 0.0001) and levels of liver enzymes, with values lower in Group A than in Group B. Total cholesterol levels and weight gain in Group A did not increase more than in Group B. CONCLUSIONS: A modest daily intake of high-cocoa-content chocolate contributes to reduce blood pressure, glycemic and liver pattern during pregnancy without affecting the weight gain.