Sunday, 18 August 2019

A new family of insulin sensitizers: The Myo-inositol (MYO).


Substances such as inositol and N-acetylcysteine (NAC) have been recently shown to be effective in treatment of PCOS patients.

The aim of this prospective trial is to evaluate the efficacy of NAC + Inositol + folic acid on ovulation rate and menstrual regularity in PCOS patients with and without insulin resistance.
. The association NAC + Inositol + folic, regardless of insulin-resistance state, seems to improve ovarian function in PCOS patients.



A)       Among the 91 PCOS patients treated with NAC + Inositol + folic, insulin resistance was present in 44 subjects (A)
& &   and absent in 47 (B). The primary endpoint was the ovulation rate/year, determined by menstrual diary, serum progesterone performed between 21° and 24° days, ultrasound findings of growth follicular or luteal cysts, and luteal ratio.

 HOMA-index assessment after 6 and 12 months of treatment was evaluated as secondary endpoint.

 Results. In both groups there was a significant increase in ovulation rate and no significant differences were found in the primary outcome between two groups. In group A, a significant reduction of HOMA-index was observed.

Conclusions.
Therefore, inositol and NAC may have additional noninsulin-related mechanisms of action that allow achieving benefits also in those patients with negative HOMA-index.

[PubMed] 
PMCID:

PMC4021745
Polycystic ovary syndrome (PCOS) affects 5%-10% of women in reproductive age, and it is the most common cause of infertility due to ovarian dysfunction and menstrual irregularity.
Several studies have reported that

Cause of PCO:-insulin resistance is the most common etilogy of genesis in PCOS women, regardless of the body mass index, of which ovarian hyperandrogenism is an effect of IR. . Therefore as things stands Intra ovarian biosynthesis of androgens is exaggerated due to primary hyperinsulinaemia .Insulin resistance àmore IGF1à More thecal cell hyperplasiaà More ovarian hyperandrogenismà abnormal oocyte development .
What are the ill effect of insulin resiatnce??:-

What is the advantages / gain of by ingestion of  insulin-sensitizing compounds??  Ans:-Such agents have been proposed as putative treatments to solve the a) hyperinsulinemia-induced dysfunction of ovarian response to endogenous gonadotropins. Insulin sensitizers therefore cause a) rescue the ovarian response to endogenous gonadotropins by reducing  hyperandrogenemia and b) re-establishes menstrual cyclicity and c)  ovulation  d)  increasing the chance of a spontaneous pregnancy. Among the insulin-sensitizing compounds, there is myo-inositol (MYO). Many studies have demonstrated that MYO is capable of e) restoring   spontaneous ovarian activity, and  f) consequently fertility, in most patients with PCOS.  Not only improvement of ovarian function but myoinositol also g)  improves  metabolic and hormonal parameters in women with PCOS.

Indications of Myoinositol?? :-In  the treatment of menstrual irregularities, chronic anovulation, and female infertility in patients with polycystic ovary syndrome (PCOS) Myoinositol has been compared with metformin, in monotherapy or in association with recombinant follicle stimulating hormone (r-FSH),

How does exactly MI works??  Myoinositol acts as a second messenger in insulin signaling pathway Literature data suggest inositol deficiency in insulin-resistant women with the polycystic ovary syndrome. Supplementation of myo-inositol decreases insulin resistance as it works as an insulin sensitizing agent.The positive role of myo-inositol in the treatment of polycystic ovary syndrome has been of increased evidence recently .


The present review presents the effects of myo-inositol on the ovarian, hormonal and metabolic parameters in women with PCOS.
PMID:

24505965

[PubMed - indexed for MEDLINE]
 The aim of this study was to compare the effectiveness of myo-inositol (MYO) and metformin, in monotherapy or in association with recombinant follicle stimulating hormone (r-FSH), in the treatment of menstrual irregularities, chronic anovulation, and female infertility in patients with polycystic ovary syndrome (PCOS).
Materials and methodsOne hundred twenty patients were randomly treated with metformin . 1500 mg/day orally (n = 60), or 4 g MYO plus 400 μg folic acid daily (n = 60), continuously. If no pregnancy occurred, r-FSH (37.5 units/day) was added to the treatment for a maximum of three attempts.
Results.Fifty percent of the patients who assumed metformin restored spontaneous ovulation, 18.3% of these obtained pregnancy. The remaining 42 patients were treated with metformin plus r-FSH. Pregnancy occurred in a total of 11 women (26.1%). The total pregnancy rate was 36.6%.

Sixty-five percent of the patients treated with MYO plus folic acid restored spontaneous ovulation activity, 30% of these obtained pregnancy. The remaining 38 patients were treated with MYO, folic acid plus r-FSH. Pregnancy occurred in a total of 11 women (28.9%). The total  pregnancy rate was 48.4%.

Conclusions.Both metformin and MYO, can be considered as first line treatment for restoring normal menstrual cycles in most patients with PCOS, even if MYO treatment seems to be more effective than metformin


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Like to have a new relationship with an old family::Inositol

“Inositol” is a term used to refer to a group of naturally occurring carbohydrate compounds that exist in nine possible chemical orientations called stereoisomers. The most common being myo-inositol, which is often sold as a dietary supplement labeled simply as inositol.
Inositol, particularly myo-inositol and another less common stereoisomer called D-chiro-inositol, plays a critical, but underappreciated, role in insulin signaling. Conditions such as hyperglycemia and diabetes are associated with disrupted inositol signaling, leading many researchers to suggest that this may be a key pathologic feature of insulin resistance (Manning 2010, Larner 2010).
Research has shown that the three inositol family members help to ameliorate conditions in which insulin resistance plays an important role, especially PCOS.

D-chiro-inositol (DCI)

D-chiro inositol is perhaps the most promising inositol compound for PCOS. Our bodies produce D-chiro-inositol only after extensive inositol metabolism. DCI interacts with select sugars in the body to form conjugates known as inositiol phosphoglycans, which play a key role in mediating insulin actions. Low levels of DCI, and inositol phosphoglycans have been observed in individuals with impaired insulin sensitivity and PCOS (Susuki 1994, Jung 2005, Cheang 2008, Baillargeon 2010).
In one study, 44 overweight women with PCOS were given a daily 1,200 mg dose of D-chiro-inositol for six to eight weeks. During the course of the study, those who took DCI displayed significant improvements in insulin sensitivity, blood pressure, and triglyceride levels, as well as a marked decrease in serum testosterone levels. Moreover, 19 of 22 subjects receiving DCI ovulated during the study period, compared to only 6 of 22 in the placebo group. The investigators concluding statement highlights the efficacy of DCI in PCOS: “D-Chiro-inositol increases the action of insulin in patients with the polycystic ovary syndrome, thereby improving ovulatory function and decreasing serum androgen concentrations, blood pressure, and plasma triglyceride concentrations.” (Nestler 1999).
Similarly promising results were drawn from another study involving lean women with PCOS. Here, participants received 600 mg daily of DCI or a placebo for six to eight weeks. The DCI-treated participants improved significantly, displaying a large decrease of 73% in testosterone levels versus no change in the placebo group. Women taking DCI also experienced reductions in insulin and triglyceride levels and blood pressure, whereas none of these changes were evident in the placebo group (Luorno 2002).
Researchers looking at the effects of metformin in PCOS women concluded that the drug’s benefits could be related to its ability to improve the function of DCI phosphoglycans in the body. Thus, it appears that DCI may be highly effective when used in combination with metformin for PCOS (Baillargeon 2004).

Myo-inositol

Myo-inositol is a stereoisomer of DCI. Like DCI, it is a key factor in insulin signaling, and serves also as a precursor to DCI in endogenous inositol metabolism. It should then come as no surprise that studies using myo-inositol in women with PCOS produced results as promising as those obtained with DCI.
Double-blind, placebo-controlled investigations were carried out in 42 women with PCOS, subjects receiving myo-inositol fared much better when compared to the placebo group, displaying decreases in testosterone, triglycerides, and blood pressure; a significant improvement in insulin sensitivity; and a greatly increased frequency of ovulation (Costantino 2009).
In another study, 20 women with PCOS were given either 2 grams of myo-inositol plus 200 mcg folic acid, or a placebo of 200 mcg folic acid daily. After 12 weeks, the women taking myo-inositol showed improved insulin sensitivity and androgen levels. Strikingly, all the subjects receiving myo-inositol returned to normal menstrual cycles (Genazzani 2008).
In an Italian study of 92 PCOS patients, almost 50% showed significant weight loss and reduced leptin levels after receiving myo-inositol plus folic acid (4 g myo-inositol plus 400 mcg folic acid). After a 14-wk treatment, the myo-inositol plus folic acid group lost weight, whereas the placebo group gained weight (Gerli 2007).
A six-month study involving 50 PCOS women yielded similar results and gave researchers the time to evaluate the effects of myo-inositol on hirsutism. Along with decreases in testosterone and insulin levels, the participants who supplemented with myo-inositol experienced a reduction in hirsutism, and improvements in skin appearance, leading researches to conclude, “Myo-inositol administration is a simple and safe treatment that ameliorates the metabolic profile of patients with PCOS, reducing hirsutism and acne.” (Zacchè 2009).
In other well-designed clinical trials for follicular maturity and ovulation induction, myo-inositol has produced promising results, cementing its position as a novel therapy for PCOS management (Papaleo 2007, Papaleo 2009).

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