madman
Super Moderator
Abstract
OBJECTIVE: D-chiro-inositol has been widely used in clinical practice to induce ovulation in women with polycystic ovary syndrome. Only recent evidence established that this molecule acts through two different mechanisms, with potentially different outcomes. On the one hand, from a metabolic perspective, D-chiro-Inositol improves insulin signaling, thus restoring physiological insulin levels in resistant subjects. On the other hand, at a cellular level, it downregulates the expression of the steroidogenic enzyme aromatase, which is responsible for the conversion of androgens to estrogens.
MATERIALS AND METHODS: We reviewed current literature in different databases, searching for D-chiro-inositol in relation with one of the following keywords: Myo-inositol, PCOS, infertility, insulin resistance, aromatase, androgen and inositol, testosterone, estrogen and inositol, estradiol, hypogonadotropic hypogonadism, fat tissue, estrogens and cancer, anovulation, uterine myoma, endometriosis, endometrial hyperplasia.
RESULTS: D-chiro-inositol treatment may be helpful in restoring physiological hormonal levels in various clinical disorders. However, D-chiro-inositol intervention should be carefully designed to avoid possible undesired side effects stemming from its multiple mechanisms of action.
CONCLUSIONS: We evaluated the optimal D Chiro-Inositol administration for different pathologies, defining dosages and timing. Even though further studies are required to validate our preliminary results, this paper is primarily intended to guide researchers through some of the pathways of D-Chiro-Inositol.
Introduction
Inositols make up a family of six-membered cyclic polyols that naturally occur as five different stereoisomers. Myo-Inositol (myo-Ins) represents approximately 99% of mammalian inositol pool, and contributes to various functions in different tissues1 ; the remainder of inositol molecules in mammals consists of dchiro-Inositol (dchiro-Ins), which mediates different functions than those mediated by myo-Ins2.
In the human body, Inositols are commonly found in almost every tissue and their absolute and relative concentration can strongly differ, depending on the milieu3. Inositols exist either in their free form or as phosphate derivatives. Inositol-phosphates are the active molecules that participate in intracellular signaling pathways4, being either a component of cell membranes as phosphatidyl-inositol-phosphates (PIP) or water-soluble molecules (IP). Myo-Ins is involved in the Follicle-Stimulating-Hormone (FSH) and the Thyroid-Stimulating-Hormone (TSH) pathways, while both myo-Ins and dchiro-Ins are insulin second messengers1,5.
dchiro-Ins administration must be well pondered because of its double mechanism of action, which depends on the dosage, likewise the dose-response behavior of many drugs. If on the one hand dchiro-Ins improves insulin signaling, on the other hand, it may inhibit estrogen synthesis in favor of androgens. The clinical effect of dchiro-Ins depends on three parameters: (1) the insulinemic condition of the patients; (2) the dosage of dchiro-Ins; )3) the treatment duration. Considering these parameters for each patient, the most suitable dchiro-Ins therapy could be evaluated for treating estrogen-sensitive pathologies or those involving impaired insulin signaling, hyperestrogenism, hypoandrogenism.
In the present paper, the authors try to evaluate the appropriate dchiro-Ins dosages and duration of treatment for different clinical pictures, based on the literature collected so far on the topic and on the authors’ clinical and experimental experience.
D-Chiro-Ins Treatment in Men
Increase of Androgens
*Hypogonadotropic hypogonadism
Our preliminary unpublished data support the use of dchiro-Ins in hypogonadotropic hypogonadal males, showing that short-term administration of high dosages may improve hormonal parameters in these patients. We investigated the effects of 1200 mg/die dchiro-Ins for 30 days in elderly hypogonadal male subjects. In patients currently enrolled, testosterone increased by approximately 20% after 30 days of dchiro-Ins administration (Table I). We observed comparable results in androstenedione, while estradiol levels were significantly lower, by 20% on average. Furthermore, testosterone increase seems to be associated with improved erectile function. Thus, dchiro-Ins treatment appears indicated to men who suffer from secondary hypogonadism, independently of their age.
*Psychological symptoms
Decrease of Estrogens
*Overweight and obese
*Estrogen-sensitive conditions
D-Chiro-Ins Treatment in Women
Increase of Androgens
*Anovulation
*Mood disorder
Decrease of Estrogens
*Uterine myoma
*Endometriosis
*Endometrial hyperplasia
Conclusions
Briefly, this paper aims to spread knowledge on dchiro-Ins use in medical treatments, collecting the most advanced experimental evidence to date. At the same time, we hope that it prompts researchers to undertake randomized, placebo-controlled, double-blind studies with a greater sample size to confirm our preliminary findings and to better understand dchiro-Ins pharmacokinetics.
OBJECTIVE: D-chiro-inositol has been widely used in clinical practice to induce ovulation in women with polycystic ovary syndrome. Only recent evidence established that this molecule acts through two different mechanisms, with potentially different outcomes. On the one hand, from a metabolic perspective, D-chiro-Inositol improves insulin signaling, thus restoring physiological insulin levels in resistant subjects. On the other hand, at a cellular level, it downregulates the expression of the steroidogenic enzyme aromatase, which is responsible for the conversion of androgens to estrogens.
MATERIALS AND METHODS: We reviewed current literature in different databases, searching for D-chiro-inositol in relation with one of the following keywords: Myo-inositol, PCOS, infertility, insulin resistance, aromatase, androgen and inositol, testosterone, estrogen and inositol, estradiol, hypogonadotropic hypogonadism, fat tissue, estrogens and cancer, anovulation, uterine myoma, endometriosis, endometrial hyperplasia.
RESULTS: D-chiro-inositol treatment may be helpful in restoring physiological hormonal levels in various clinical disorders. However, D-chiro-inositol intervention should be carefully designed to avoid possible undesired side effects stemming from its multiple mechanisms of action.
CONCLUSIONS: We evaluated the optimal D Chiro-Inositol administration for different pathologies, defining dosages and timing. Even though further studies are required to validate our preliminary results, this paper is primarily intended to guide researchers through some of the pathways of D-Chiro-Inositol.
Introduction
Inositols make up a family of six-membered cyclic polyols that naturally occur as five different stereoisomers. Myo-Inositol (myo-Ins) represents approximately 99% of mammalian inositol pool, and contributes to various functions in different tissues1 ; the remainder of inositol molecules in mammals consists of dchiro-Inositol (dchiro-Ins), which mediates different functions than those mediated by myo-Ins2.
In the human body, Inositols are commonly found in almost every tissue and their absolute and relative concentration can strongly differ, depending on the milieu3. Inositols exist either in their free form or as phosphate derivatives. Inositol-phosphates are the active molecules that participate in intracellular signaling pathways4, being either a component of cell membranes as phosphatidyl-inositol-phosphates (PIP) or water-soluble molecules (IP). Myo-Ins is involved in the Follicle-Stimulating-Hormone (FSH) and the Thyroid-Stimulating-Hormone (TSH) pathways, while both myo-Ins and dchiro-Ins are insulin second messengers1,5.
dchiro-Ins administration must be well pondered because of its double mechanism of action, which depends on the dosage, likewise the dose-response behavior of many drugs. If on the one hand dchiro-Ins improves insulin signaling, on the other hand, it may inhibit estrogen synthesis in favor of androgens. The clinical effect of dchiro-Ins depends on three parameters: (1) the insulinemic condition of the patients; (2) the dosage of dchiro-Ins; )3) the treatment duration. Considering these parameters for each patient, the most suitable dchiro-Ins therapy could be evaluated for treating estrogen-sensitive pathologies or those involving impaired insulin signaling, hyperestrogenism, hypoandrogenism.
In the present paper, the authors try to evaluate the appropriate dchiro-Ins dosages and duration of treatment for different clinical pictures, based on the literature collected so far on the topic and on the authors’ clinical and experimental experience.
D-Chiro-Ins Treatment in Men
Increase of Androgens
*Hypogonadotropic hypogonadism
Our preliminary unpublished data support the use of dchiro-Ins in hypogonadotropic hypogonadal males, showing that short-term administration of high dosages may improve hormonal parameters in these patients. We investigated the effects of 1200 mg/die dchiro-Ins for 30 days in elderly hypogonadal male subjects. In patients currently enrolled, testosterone increased by approximately 20% after 30 days of dchiro-Ins administration (Table I). We observed comparable results in androstenedione, while estradiol levels were significantly lower, by 20% on average. Furthermore, testosterone increase seems to be associated with improved erectile function. Thus, dchiro-Ins treatment appears indicated to men who suffer from secondary hypogonadism, independently of their age.
*Psychological symptoms
Decrease of Estrogens
*Overweight and obese
*Estrogen-sensitive conditions
D-Chiro-Ins Treatment in Women
Increase of Androgens
*Anovulation
*Mood disorder
Decrease of Estrogens
*Uterine myoma
*Endometriosis
*Endometrial hyperplasia
Conclusions
Briefly, this paper aims to spread knowledge on dchiro-Ins use in medical treatments, collecting the most advanced experimental evidence to date. At the same time, we hope that it prompts researchers to undertake randomized, placebo-controlled, double-blind studies with a greater sample size to confirm our preliminary findings and to better understand dchiro-Ins pharmacokinetics.
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