PCOS and inositols: controversial results and necessary clarifications. Basic differences between D-chiro and myo-inositol

Myo-Inositol (myo-Ins) and its phosphate derivatives—including inositol phosphates (InsPs), inositol pyrophosphates (IPPs) and phosphatidyl-inositol phosphate (PtdIns)—are credited to act as second messengers, which accumulate rapidly and transiently in response to external or endocrine signals, a phenomenon that allows signaling to be discrete and regulated (1, 2). Noticeably, inositol is involved in the transduction of several endocrine signals, including insulin (3, 4), thyroid hormones (5), gonadotropins (6), lipids with hormone-like activity (as prostaglandins) (7), and many other endocrine systems (8). Namely, in the last decade, a growing body of clinical and experimental research provided robust evidence about the efficiency of inositol in reversing a few clinical, metabolic, and endocrine features of the Polycystic Ovary Syndrome (PCOS). Myo-inositol, alone or in combination with its isomer D-Chiro-Inositol (D-Chiro-Ins), showed to exert a variable—albeit significant—effect in improving both symptoms and outcome in PCOS patients (9). Experimental and pilot clinical studies pointed out that a combination of both isomers could provide a reliable rationale for establishing a proper treatment strategy, as first suggested by Beemster’s seminal study (10, 11). However, the proper formula—i.e., the respective percentage of myo-Ins and D-Chiro-Ins—is still a matter of debate. In several cases, no conclusive insights can be obtained from clinical trials based on unclear rational design, limited number of recruited patients and variable formula composition and dosage(s). First, it is improper to compare clinical results from studies in which commercial nutraceutical formulas involve a wide range of concentrations (Table 1), with the myo-Ins/D-Chiro-Ins ratio varying implausibly from 0.4:1 to 104:1. Current commercial preparations also contain D-Chiro-Ins alone at concentrations reaching 600 mg that can be administered once or twice a day. Therefore, the daily dose of D-chiro-Ins, alone or with myo-Ins, ranges from low (less than 300 mg/die), medium (300–600 mg/die) and high (600–1,200 mg/die)

Bioactivity of Inositol Phosphates

Inositol phosphates (IPs) are a huge and complex family of biomolecules, important in regulating vital cellular functions, signal transduction, energy transmission, and ion channels physiology and serving as structural components of cell membranes [...

Inositol Hexaphosphate (IP6) and Colon Cancer: From Concepts and First Experiments to Clinical Application

Multiple human health-beneficial effects have been related to highly phosphorylated inositol hexaphosphate (IP6). This naturally occurring carbohydrate and its parent compound, myo-inositol (Ins), are abundantly present in plants, particularly in certain high-fiber diets, but also in mammalian cells, where they regulate important cellular functions. However, the striking and broad-spectrum anticancer activity of IP6, consistently demonstrated in different experimental models, has been in a spotlight of the scientific community dealing with the nutrition and cancer during the last several decades. First experiments were performed in colon cancer 30 years ago. Since then, it has been shown that IP6 reduces cell proliferation, induces apoptosis and differentiation of malignant cells with reversion to normal phenotype, affecting several critical molecular targets. Enhanced immunity and antioxidant properties also contribute to the tumor cell destruction. Although Ins possesses a modest anticancer potential, the best anticancer results were obtained from the combination of IP6 + Ins. Here we review the first experimental steps in colon cancer, when concepts and hypotheses were put together almost without real knowledge and present clinical studies, that were initiated in colon cancer patients. Available as a dietary supplement, IP6 + Ins has been shown to enhance the anticancer effect of conventional chemotherapy, controls cancer metastases, and improves quality of life in cancer patients. Emerging clinical and still vast amount of experimental data suggest its role either as an adjuvant or as an “alternative” to current chemotherapy for cancer

Role of Inositols and Inositol Phosphates in Energy Metabolism

Recently, inositols, especially myo-inositol and inositol hexakisphosphate, also known as phytic acid or IP6, with their biological activities received much attention for their role in multiple health beneficial effects. Although their roles in cancer treatment and prevention have been extensively reported, interestingly, they may also have distinctive properties in energy metabolism and metabolic disorders. We review inositols and inositol phosphate metabolism in mammalian cells to establish their biological activities and highlight their potential roles in energy metabolism. These molecules are known to decrease insulin resistance, increase insulin sensitivity, and have diverse properties with importance from cell signaling to metabolism. Evidence showed that inositol phosphates might enhance the browning of white adipocytes and directly improve insulin sensitivity through adipocytes. In addition, inositol pyrophosphates containing high-energy phosphate bonds are considered in increasing cellular energetics. Despite all recent advances, many aspects of the bioactivity of inositol phosphates are still not clear, especially their effects on insulin resistance and alteration of metabolism, so more research is needed