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Myo-inositol products in polycystic ovary syndrome (PCOS) treatment: Quality, labeling accuracy, and cost comparison

Authors:

Abstract

To evaluate the labeling accuracy of four myo-inositol products, designed for polycystic ovary syndrome (PCOS) treatment, available on the italian market and to perform a cost comparison based on myo-inositol content in milligrams for products analyzed. Four (4) myo-inositol products (3 sachet and 1 tablet formulations) were dissolved using water, and each sample was analyzed for myo-inositol content using a high-performance liquid chromatography (HPLC) method with index refraction detector. The amount of myo-inositol per purchased product was then divided into its purchase price in order to make cost comparisons between the products based on a 2 and 4 g/day dose. A significant difference in the myo-inositol content, compared with the labeling was found for the products. Only 1 product contained more than 95% of the myo-inositol content claimed on the label, and there was a product with less than 75% of the labeling amount. Based on a 2-g myo-inositol per day dose, the cost of a 30-day supply ranged from Euro 20,77 and Euro 71,86, after correction by actual amount of myo-inositol. There is a lack of conformity between declared and actual amount of myo-inositol among the products tested and the majority of the products contained less than 95% of labeled amounts. There should be a better control in the manufacturing process in order to ensure more quality and accuracy. Nowadays consumers cannot trust myo-inositol product labels to represent the product's content accurately or that product pricing is a reflection of myo-inositol content.
Abst ract . Objectives: To evaluate the
labeling accuracy of four myo-inositol products,
designed for polycystic ovary syndrome (PCOS)
treatment, available on the italian market and to
perform a cost comparison based on myo-inosi-
tol content in milligrams for products analyzed.
Materials and Methods: Four (4) myo-inosi-
tol products (3 sachet and 1 tablet formulations)
were dissolved using water, and each sample
was analyzed for myo-inositol content using a
high-performance liquid chromatography
(HPLC) method with index refraction detector.
The amount of myo-inositol per purchased prod-
uct was then divided into its purchase price in
order to make cost comparisons between the
products based on a 2 and 4 g/day dose.
Results: A significant difference in the myo-in-
ositol content, compared with the labeling was
found for the products. Only 1 product contained
more than 95% of the myo-inositol content claimed
on the label, and there was a product with less
than 75% of the labeling amount. Based on a 2-g
myo-inositol per day dose, the cost of a 30-day
supply ranged from 20,77 and 71,86, after cor-
rection by actual amount of myo-inositol.
Conclusion: There is a lack of conformity be-
tween declared and actual amount of myo-inositol
among the products tested and the majority of the
products contained less than 95% of labeled
amounts. There should be a better control in the
manufacturing process in order to ensure more
quality and accuracy. Nowadays consumers can-
not trust myo-inositol product labels to represent
the product’s content accurately or that product
pricing is a reflection of myo-inositol content.
Key Words:
Polycystic ovary syndrome, Insulin resistance, Myo-
inositol products, Labeling accuracy, Clinical efficacy.
Introduction
Polycystic ovary syndrome (PCOS) is the
most common cause of ovulatory disorders and
European Review for Medical and Pharmacological Sciences
Myo-inositol products in polycystic ovary
syndrome (PCOS) treatment: quality, labeling
accuracy, and cost comparison
E. PAPALEO, M. MOLGORA, L. QUARANTA, M. PELLEGRINO, F. DE MICHELE
Centro Natalità, Obstetrics-Gynaecologic Department, Vita-Salute San Raffaele, Milan (Italy)
Corresponding Author: Enrico Papaleo, MD; e-mail: papaleo.enrico@hsr.it 165
female infertility and affects approximately 6%-
10% of women of childbearing age1. It is a med-
ical condition that causes irregular menstrual cy-
cles, chronic anovulation most often manifested
as oligoamenorrhea, and androgen excess, with
typical ovarian ultrasound features2. However, its
pathogenesis is poorly understood.
Many investigators have focused on both im-
paired glucose tolerance, which affects 30%-40%
of patients with PCOS3, and on insulin resis-
tance, which is present in a significant proportion
of women with PCOS. Since 19804it has become
clear that PCOS is associated with hyperinsuline-
mia. Insulin in fact plays a direct role in the
pathogenesis of hyperandrogenemia in PCOS,
acting synergistically with LH to enhance andro-
gen production in theca cells5.
Accordingly, this association has led to the
treatment of PCOS women with insulin-sensitiz-
ing agents. Metformin is the most experienced in-
sulin-sensitizing drug in the treatment of PCOS6-8.
By increasing insulin sensitivity, metformin re-
duces insulin resistance, insulin secretion and hy-
perinsulinemia9. Since 90’s10 -14, studies suggest
that some abnormal action of insulin might be de-
pendent from inositolphosphoglycan (IPG) medi-
ators of insulin action, and evidence suggests that
a deficiency in a specific D-Chiro-inositol-con-
taining IPG (DCI-IPG) may contribute to insulin
resistance in individuals with impaired glucose
tolerance or type 2 diabetes mellitus15. The idea
that a deficiency in DCI- IPG, related perhaps to
an actual or functional deficiency of the precursor
DCI, contributes to the insulin resistance of
PCOS is further supported by evidence that ad-
ministration of metformin to PCOS women en-
hances insulin-stimulated release of DCI-IPG16.
Indeed, a defect in tissue availability or altered
metabolism of DCI or inositol phosphoglycan
mediators has been found in PCOS women and
may contribute to their insulin resistance17,18.
2011; 15: 165-174
After inofolic
Base-line 4 g N° of patients treated 120
Age (yr) 32 ± 4 Menstrual cycle after MYO treatment 84
(% patients) 84/120 (70%)
Body Mass Index 28.5 ± 2.4 N° patients with restored monthly ovulation 72
(kg/m2) (% patients) 72/120 (60%)
FSH (mUI/ml) 4.5 ± 2.8 N° pregnancy 34
LH (mUI/ml) 6.3 ± 3.1 N ° pregnancy/n° treated patients (%) 28.3%
Prolactin (ng/ml) 19.1 ± 2.7 N° pregnancy/n° patients with restored 47.2%
monthly ovulation
TSH 1.78 ± 0.85 Abortion (% abortion) 6
6/34 (17.6%)
Serum progesterone 1.8 ± 0.7 10.5 ± 1.8 Multiple pregnancy 0
(ng/ml)
Serum testosterone 95.6 ± 8.5 45.2 ± 6.7#
(ng/dl)
Serum free testosterone 1.0 ± 0.8 0.38 ± 0.1§
(ng/dl)
Serum androstenedione 230 ± 35 205 ± 28
(ng/dl)
Table Ia. Inofolic treatment.
E. Papaleo, M. Molgora, L. Quaranta, M. Pellegrino, F. De Michele
All published papers that focus on MYO ben-
fits in PCOS patients are performed using a prod-
uct put on the market since 2004 (Inofolic®).
Inofolic contains only myo-inositol and folic
acid (2 g myo-inositol and 200 mcg folic acid
each sachet) and has been properly studied and
positively tested for gynecological and obstet-
ric purposes. The indications reported in the
leaflet are: adjuvant in the treatment of PCOS,
insulin-resistance, type 2 diabetes and in con-
trolled ovarian hyperstimulation protocols.
Many studies investigated the effectiveness of
the product on PCOS women, even in ART proto-
cols, to ameliorate ovulation and pregnancy out-
comes and improving metabolic and hormonal pat-
terns25-29,31,33.
Recently, other products containing MYO
have been tested in patients, as well as Inofolic
(Prepart, Inocomplex, Redestop).
A retrospective evaluation of clinical efficacy
has suggested a critical debate on the importance
of phyto-nutrients alone or in co-treatment with
other drugs.
Daily administration of 4 g of MYO is useful
in restoring spontaneous ovulation in most
PC O S p atie nts (ESHR E-AS RM C onse nsus
Conference, 2004) and in spontaneous conceiv-
ing in a follow-up period of six months (n=120
patients, data in press).
In support of this idea, administration of D-
chiro-inositol has been demonstrated to improve
glucose tolerance and insulin sensitivity19, de-
crease serum androgens and improve ovulation
in both obese20 and lean21 women with PCOS.
Besides DCI, another isoform, myo-inositol
(MYO) has been reported to be greatly correlated
to ovarian function22. MYO, a precursor of DCI,
is widely distributed in nature whereas DCI is
relatively rare21. MYO is present in human follic-
ular fluid, where elevated concentrations appear
to play a positive role in follicular maturity and
provide a marker of good-quality oocytes23. Sup-
plementation of MYO in culture medium in-
creased meiotic progression of germinal vesicles
in mouse oocytes by enhancing the intracellular
Ca2+ oscillation24 . Recent studies reported that
MYO supplementation, similarly to DCI admin-
istration, reduces serum insulin, decreases serum
testosterone and enhances ovulation25,26. Further-
more, this particular isoform of inositol demon-
strated to be effective in controlling even the
metabolic syndrome27-29 and the coutaneous dis-
orders29 in women affected by PCOS, perhaps
more than other insulin-sensitising drugs (met-
formin)30. The administration of MYO seemed to
be more effective than metformin in restoring
normal ovulation activity and improving preg-
nancy outcomes31,32.
166
After
Base-line treatment N° of patients treated 40
Age (yr) 31 ± 3 Menstrual cycle after MYO treatment 12
(% patients) 12/40 (30%)
Body Mass Index 28.2 ± 2.6 N° patients with restored monthly ovulation 8
(kg/m2) (% patients) 8/40 (20%)
FSH (mUI/ml) 3.8 ± 1.8 N° pregnancy 2
LH (mUI/ml) 6.2 ± 2.8 N ° pregnancy/n° treated patients (%) 5%
Prolactin (ng/ml) 17.0 ± 2.6 N° pregnancy/n° patients with restored 20%
monthly ovulation
TSH 1.58 ± 0.75 Abortion (% abortion) 0
0/0 (0%)
Serum progesterone 1,5 ± 0,8 2.7 ± 0.8 Multiple pregnancy 0
(ng/ml)
Serum testosterone 94.6 ± 7.7 76.6 ± 5.7
(ng/dl)
Serum free testosterone 1.2 ± 0.6 1.0l ± 0.4
(ng/dl)
Serum androstenedione 220 ± 25 210 ± 29
(ng/dl)
Table Ib. Other MYO product treatment.
After
Base-line treatment N° of patients treated 40
Age (yr) 31.5 ± 3.1 Menstrual cycle after MYO treatment 5
(% patients) 5/20 (25%)
Body Mass Index 27.2 ± 2.5 N° patients with restored monthly ovulation 4
(kg/m2) (% patients) 4/20 (20%)
FSH (mUI/ml) 3.9 ± 1.7 N° pregnancy 2
LH (mUI/ml) 5.8 ± 2.6 N ° pregnancy/n° treated patients (%) 10%
Prolactin (ng/ml) 17.5 ± 2.4 N° pregnancy/n° patients with restored 50%
monthly ovulation
TSH 2.00 ± 0.85 Abortion (% abortion) 0
0/0 (0%)
Serum progesterone 1.4 ± 0,8 1.1 ± 0.7 Multiple pregnancy 0
(ng/ml)
Serum testosterone 92.6 ± 6.7 73.6 ± 5.1
(ng/dl)
Serum free testosterone 1.6 ± 0.7 0.9 ± 0.4
(ng/dl)
Serum androstenedione 225 ± 25 216 ± 26
(ng/dl)
Table Ic. Other MYO product treatment.
We found that preliminary clinical results
with the novel products tested resulted lower
than expected (Table I). Besides the similar de-
clared quali-quantitative composition of these
products comparing with Inofolic, we won-
dered if the low effectiveness found was due to
a scarse quality of the main component (MYO)
and if what declared on labeling was confirmed
by the quantitative analysis.
The aim of this study was to compare the quality,
the labeling accuracy and to perform price analysis
of these products based on their actual contents.
167
Myo-inositol products in polycystic ovary syndrome (PCOS) treatment
MYO
weight Price
Lot Expir. declared Units Price per unit
Product number date per unit (g per unit) (euro) (euro) Indications
Inofolic 10D034 gen-12 2000 mg 20 sachets (2 g) 13.50 0.675 PCOS, insulin-
resistance, type 2
diabetes, ART
Prepart 006B10 feb-13 2000 mg 30 sachets (2 g) 19.00 0.616 PCOS, insulin-
resistance, ART
Inocomplex 669265 sep-12 2000 mg 60 tablets (3 g) 22.50 0.375 PCOS, insulin-
resistance, type 2
diabetes
Redestop NF125 nov-11 1200 mg 20 sachets (4 g) 22.90 1.145 Pelvic inflammation
and pain from
oxidative stress
Table II. Profile, weight, price and indications of tested products.
E. Papaleo, M. Molgora, L. Quaranta, M. Pellegrino, F. De Michele
liquid chromatography (HPLC) analysis. All
vials were labeled and double checked by a sec-
ond person as transfer was made.
High-Performance Liquid
Chromatography Analysis Method
The myo-inositol samples were examined by
high-performance liquid chromatography using
Agilent 1090 system running a ChemStation
software that consisted of a quaternary pump,
ref r acti o n i n dex detec t or a nd a utosa mpler
(Wilmington, DE, USA). The main compo-
nent(s) was separated using a C18 column
(Aqua 5 µm, 150 ×4.6 mm; Phenomenex, Tor-
rance, CA, USA) with the following conditions:
flow rate, 1 mL/min; wavelength, 254 nm; mo-
bile phase, water. We allowed a 5-minute re-
equilibrium time between the end of a run and
the next injection.
Pure myo-inositol standard, at the same
diluition of the samples, was used to quantify
the content of myo-inositol in the samples ana-
lyzed.
Price Analysis
To determine price per milligram of the 4
products analyzed, each product price was
recorded upon purchase (Table II), and the mil-
ligram amount in each unit was determined by
HPLC analy sis. The milligram per unit was
multiplied by the number of units (sachets or
tablets) per purchase to yield the total mil-
ligrams of myo-inositol per purchase. The price
of each purchase in euros was divided by the
Materials and Methods
Materials
The following products were randomly obtained
from pharmacy outlets in Milan in April 2010:
Inofolic – LO.LI. Pharma, Rome, Italy
Prepart Mauser Farma, Sesto San Giovanni,
Milan, Italy
Inocomplex Energie Chimico Farmaceutiche,
Campagnano di Roma, Rome, Italy
Redestop Progine Farmaceutici, Calenzano
(Florence), Italy
In Table II, lot numbers, expiration date, myo-
inositol weight per unit declared, price and indi-
cations are reported for the products purchased
and analyzed.
The products were sent to CHELAB Laborato-
ries S.r.l. (Treviso, Italy) which are provided with a
good manufacturing practice (GMP)facility dedi-
cated to quality control of medicinal products. The
structure has been authorized by AIFA and by the
Italian Ministry of Health for chemical/physical,
biological and microbiological controls.
CHELAB Laboratories S.r.l. were engaged to
analyse the actual amounts of myo-inositol in the
products tested.
Sampling
Each sample was dissolved with a proper
amount of water and was placed in a 37°C incu-
bator for 20 minutes to ensure dissolution. The
final concentration of each sample was 2 mM.
The samples were vortexed and 1 mL was trans-
ferred into individual vials for high-performance
168
Figure 1. High-performance liquid chromatography chromatograms of 4 myo-inositol products. The highest line in the chro-
matograms marks the peak position of myo-inositol. The procedure for obtaining the profile is described in the Materials and
Methods section.
Inofolic Prepart
Inocomplex Redestop
Myo-inositol products in polycystic ovary syndrome (PCOS) treatment
169
Price/unit ×2000 mg/mg (declared or
actual)/unit = price (declared or actual)/day
Price (declared or actual)/day ×30 = price
(declared or actual)/month
A daily and a 30-day supply of 4 g/day price
was calculated for each product by the following
equations:
Price/unit ×4000 mg/mg (declared or
actual)/unit = price (declared or actual)/day
Price (declared or actual)/day ×30 = price
(declared or actual)/month
These calculations have been made for the de-
clared and the actual amount of myo-inositol.
total number of milligrams in the product to
yield price per milligram. The equations are as
follows:
mg/unit ×units/purchase = mg/purchase
price/purchase/unit/purchase = price/unit
price/purchase/mg/purchase = price/mg
To determine the price of each product for a dai-
ly and a 30-day supply, doses of 2 g/day and of 4
g/day were chosen because of the range of dose
recommended in many published studies. We cal-
culated consumer prices for product comparison.
A daily and a 30-day supply of 2 g/day price
was calculated for each product by the following
equations:
Declared amount Laboratory analysis
MYO MYO MYO Deviation
Product Sac/Tbs (g) Sac/Tbs (mg) Sac/Tbs (mg) g/100 g (%)
Inofolic 2 2000 1950 97.5 -2.50
Prepart 2 2000 1782 89.1 -10.90
Inocomplex 3 2000 1485 49.5 -25.75
Redestop 4 1200 956 23.9 -20.33
Table III. Amount of Myo-inositol declared and measured in the four products analyzed and % of deviation.
Figure 2. Myo-inositol content expressed as milligramms declared (solid line) and detected by laboratory (dotted line) in the
products analyzed. We reported even the % deviation between the values.
2000 2000
Declared amount Actual amount Deviation
Product
MYO (mg)
Inofolic
(2 g sachet)
Prepart
(2 g sachet)
Inocomplex
(3 g tablet)
Redestop
(4 g sachet)
2000
1500
1000
500
0
30.00%
20.00%
10.00%
0%
2000
1950
1782
956
1485
1200
E. Papaleo, M. Molgora, L. Quaranta, M. Pellegrino, F. De Michele
Myo-Inositol Content
Among all products tested, only Inofolic had
more than 95% (97.5%) of the labeled amount of
myo - inosi t ol. Pre p art h a d more th an 89%
(89.1%) of the labeled amount. The remaining 2
products: one (Redestop) had less than 80% of
the labeling amounts (79,66%) and the last one
(Inocomplex) contained less than 75% of the la-
beled amounts (74.25%) (Table III, Figure 2).
Price Analysis
We compared 4 products both for declared and
actual amount of myo-inositol, considering the
two therapeutic doses found in literature (2 and 4
Results
HPLC Profiles of Various Products
We analyzed each of the 4 products with
HPLC-RI analysis (Figure 1). Substantial differ-
ences between different products in their HPLC
profiles and amounts of myo-inositol present in
each product has been registered, comparing the
amount detected with the value reported on the
labels (Table III). Some products have also other
peaks than that of myo-inositol, and we classified
these peaks as impurities or as other components
detectable by HPLC analysis (see Redestop chro-
matogram).
170
Myo-inositol products in polycystic ovary syndrome (PCOS) treatment
171
The european and italian regulations for nutri-
tional supplements do not give strict rules to en-
sure a quality product manufacturing process.
The inadequate regulation of these products leads
to poor standardization and lack of reliable quali-
ty indicator, that in some cases could affect the
effectiveness of the components. Furthermore,
consumers are hard pressed to find out if they are
taking what is stated on the label and how much
of the said substances are contained in each prod-
uct. We were stimulated by the fact that not all
the products containing myo-inositol seemed to
be effective in the treatment of PCOS and so we
wondered if this was due to the quality of the
product administered or to the interference of
other components in the formulation. Some prod-
ucts in fact contain other components in addition
to myo-inositol that are described in literature to
have opposite effects. In particular, one of the
product we analyzed, that contains maca extract,
known to be effective to improve testosterone
and libido in male. Testosterone has been demon-
strated to be higher in women affected by PCOS,
and one of the effects of myo-inositol is reducing
testosterone levels20. So the effects of maca and
myo-inositol are opposite.
When we analyzed these four products for
their myo-inositol content, we found out that on-
ly one product containing more than 95% of the
labe led amount. The other pro ducts con tain
smaller amounts of actual myo-inositol. This in-
dicates the importance of uniform and control la-
beling for these supplements.
These differences could be also due to the fact
that the source of raw materials are not well con-
trolled. It could be interesting to analyze if differ-
ent lots of the same product, purchased in differ-
ent moments and in different places show the
same content of myo-inositol. In other words, if
there is a standarization and a reproduciblity in
the manifacturing process of these products.
We analyzed the content of myo-inositol prod-
ucts and determined the cost per milligram. A 2
and 4 mg/d dose was chosen for cost compar-
isons. Inofolic was the best value at 20.77 per
month, while at the other extreme the product
with low myo-inositol content was Redestop,
with a cost of 71.86 per month when extrapo-
lated and corrected to the 2 g dose/d. It is inter-
esting to note that the price comparison gave a
different result if the declared amount of myo-in-
ositol is considered. Therefore, cost analysis
could serve as an indicator of the product price
but not of the product quality.
g). Considering the declared amount on label, the
least expensive product was Inocomplex which
costs 0.38 for a daily supply and 11.25 for a
30-day supply of 2 g of myo-inositol, 0.75 and
22.5, respectively for a daily and a 30-day sup-
ply of 4 g of myo-inositol. Prepart costs 0.62
for a daily supply and 18.50 for a 30-day sup-
ply of 2 g of myo-inositol, 1.23 and 36.99,
respectively for a daily and a 30-day supply of 4
g of myo-inositol. Inofolic costs 0.68 for a dai-
ly supply and 20.25 for a 30-day supply of 2 g
of myo-inositol, 1.35 and 40.50, respectively
for a daily and a 30-day supply of 4 g of myo-in-
ositol. The most expensive was Redestop, which
costs 2.29 for a daily supply and 68,70 for a
30-day supply of 2 g of myo-inositol, 4.58 and
137.40 respectively for a daily and a 30-day
supply of 4 g of myo-inositol (Table IV).
On the other hand, considering the actua l
amount of myo-inositol found in laboratory analy-
sis, and then correcting the cost in order to reach at
least the therapeutic dose of myo-inositol (2 or 4
g), the price analysis overturned the results. In fact
we found that the least expensive product was Ino-
folic, which costs 0.69 for a daily supply and
20.77 for a 30-day supply of 2 g of myo-inositol,
1.38 and 41.54, respectively for a daily and a 30-
day supply of 4 g of myo-inositol. Prepart costs
0.71 for a daily supply and 21.32 for a 30-day
supply of 2 g of myo-inositol, 1.42 and 42.65,
respectively for a daily and a 30-day supply of 4 g
of myo-inositol. Inocomplex costs 0.76 for a
daily supply and 22.73 for a 30-day supply of 2
g of myo-inositol, 1.51 and 44.45, respective-
ly for a daily and a 30-day supply of 4 g of myo-in-
ositol. The most expensive was Redestop, which
costs 2.40 for a daily supply and 71.86 for a
30-day supply of 2 g of myo-inositol, 4.79 and
143.72 respectively for a daily and a 30-day sup-
ply of 4 g of myo-inositol (Table IV).
Discussion
Nutritional supplementation is the most com-
monly used form of alternative medicine, and it
is going to become more and more popular in the
clinical practice of many gynecologists. In par-
ticular in the treatment of PCOS symptoms,
myo-inositol has demonstrated to be effective, in
particular to reduce insulin-resistance, to restab-
lish hormonal and metabolic parameters and to
restore ovulation20-24.
172
E. Papaleo, M. Molgora, L. Quaranta, M. Pellegrino, F. De Michele
Therapeutic dose 2 g Therapeutic dose 4 g
Declared MYO amounts Actual MYO amounts Declared MYO amounts Actual MYO amounts
Daily Daily
MYO/ MYO/ Declared Daily Actual dose* Declared Daily Actual dose*
unit unit dose dose 30-day dose (2 g) 30-day dose dose 30-day dose (4 g) 30-day
declared actual MYO price price MYO price price MYO price price MYO price price
Product (mg) (mg) (unit) (euro) (euro) (unit) (euro) (euro) (unit) (euro) (euro) (unit) (euro) (euro)
Inofolic 2000 1950 1 0.6750 20.25 1 0.6923 20.77 2 1.3500 40.50 2 1.3846 41.54
Prepart 2000 1782 1 0.6166 18.50 1 0.7108 21.32 2 1.2332 36.99 2 1.4216 42.65
Inocomplex 2000 1485 1 0.3750 11.25 2 0.7576 22.73 2 0.7500 22.50 4 1.5152 45.45
Redestop 1200 956 2 2.2900 68.70 2 2.3954 71.86 4 4.5800 137.40 4 4.7908 143.72
Table IV. Price comparison of a daily and a 30-day supply with the products tested. We considered two therapeutic doses (2 and 4 g) for the treatment of PCOS, as reported in lit-
erature. Data are calculated on declared and actual amounts of myo-inositol for all the products analyzed.
MYO: myo-inositol. MYO/unit declared: amount of myo-inositol for unit (sachet of tablet) declared on the label. MYO/unit actual: actual amount of myo-inositol for unit (sachet
of tablet) measured by laboratory. Declared dose MYO: number of unit(s) to yeald therapeutic dose at declared amount of myo-inositol. Actual dose MYO: number of unit(s) to
yeald therapeutic dose at measured amount of myo-inositol. *The price has been corrected by actual amount in order to reach the therapeutic dose of myo-inositol (2 or 4 g).
We would like to stress that the purpose of this
paper was to observe the differences in marketed
myo-inositol products, not to endorse or demote
a particular product because this represents one
sampling at a particular time. Because supple-
ment products and prices usually vary over time,
it would not be surprising that the so-called “best
product” in this limited study would not be the
best the next time or viceversa.
In conclusion, the quality and composition of
the retail myo-inositol products appears to be
highly variable and prices of myo-inositol prod-
ucts do not reflect the amounts of myo-inositol or
the quality of the product as determined by the
consistency between labeled amounts and the ac-
tual amounts. Therefore, the myo-inositol sup-
plement makers and the Italian Ministry of
Health should provide consumers with much
more reliable quality indicator so that it can be
trusted to provide products that could really exert
a positive and expected benefit. In general, both
the supplement industry and consumers would
benefit from better quality control of the market-
ed supplements.
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E. Papaleo, M. Molgora, L. Quaranta, M. Pellegrino, F. De Michele
... Concerning myo-inositol, one study evaluated label accuracy of four myo-inositol products, designed for polycystic ovary syndrome (PCOS) treatment and available on the Italian market, and performed a cost comparison based on myo-inositol content in milligrams for products analyzed [20]. A significant difference in the myo-inositol content, compared with the labeling was found for the products. ...
... Inositol is a necessary component of all cellular membranes. It is a member of the inositols are marketed as beneficial nutraceutics for improving mood and for the treatment of polycystic ovary syndrome [20]. A significant difference in the myo-inositol content of available products, and there are no regulations to ensure homogenous quality and accuracy [20]. ...
... It is a member of the inositols are marketed as beneficial nutraceutics for improving mood and for the treatment of polycystic ovary syndrome [20]. A significant difference in the myo-inositol content of available products, and there are no regulations to ensure homogenous quality and accuracy [20]. ...
Article
Full-text available
In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology—these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol—some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims to distinguish between the truths and myths surrounding the clinical use of such nutraceuticals.
... Отже, завдяки позитивному впливу даного комплексу вітамінів на репродуктивну функцію можливо пропонувати продовження прийому препарату Міофолік і після настання вагітності з метою зниження ризику викидня на ранніх термінах, профілактики розвитку гестаційного діабету та прееклампсії, на відміну від препаратів DCI, прийом яких при вагітності слід негайно припинити [19,20]. ...
... Сравнительный анализ продуктов четырех препаратов мио-инозитола с помощью высокоэффективной жидкостной хроматографии показал, что только один продукт содержит мио-инозитола более чем 95% от заявленного на этикетке (рис. 8) [43]. ...
Article
Full-text available
Polycystic Ovarian Syndrome (PCOS) is the main infertility cause due to metabolic and hormonal dysfunctions of the ovaries. This syndrome is comorbid with insulin resistance and substantially increases the risk of endometrial hyperplasia, obesity, breast cancer, myocardial infarction and stroke. Women with PCOS have an increased risk of anovulatory cycles, infertility and miscarriage.One of the promising nutricial directions in the complex treatment of PCOS is the use of myo-inositol. A systematic analysis presented in this paper, showed that oral administration of myo-inositol at a dose of 2-4 g/day helps to reduce insulin resistance, excessive androgen secretion, the risk of hirsutism and acne, normalization of lipid profile and blood pressure. Its reception improves functioning of the reproductive axis in patients with PCOS, normalizes ovulation and formation of mature oocytes. Inclusion of myo-inositol in the process of preparing for the procedure of in vitro fertilization (IVF) can significantly improve the results in patients with PCOS and other disorders associated with infertility.
Article
Background: Subfertile women are highly motivated to try different adjunctive therapies to have a baby, and the widespread perception is that dietary supplements such as myo-inositol (MI) and D-chiro-insoitol (DCI) are associated with only benefit, and not with harm. Many fertility clinicians currently prescribe MI for subfertile women with polycystic ovary syndrome (PCOS) as pre-treatment to in vitro fertilisation (IVF) or for ovulation induction; however no high-quality evidence is available to support this practice. This review assessed the evidence for the effectiveness of inositol in subfertile women with a diagnosis of PCOS. Objectives: To evaluate the effectiveness and safety of oral supplementation of inositol for reproductive outcomes among subfertile women with PCOS who are trying to conceive. Search methods: We searched the following databases (to July 2018): Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, and AMED. We also checked reference lists and searched the clinical trials registries. Selection criteria: We included randomised controlled trials (RCTs) that compared any type, dose, or combination of oral inositol versus placebo, no treatment/standard treatment, or treatment with another antioxidant, or with a fertility agent, or with another type of inositol, among subfertile women with PCOS. Data collection and analysis: Two review authors independently selected eligible studies, extracted data, and assessed risk of bias. The primary outcomes were live birth and adverse effects; secondary outcomes included clinical pregnancy rates and ovulation rates. We pooled studies using a fixed-effect model, and we calculated odds ratios (ORs) with 95% confidence intervals (CIs). We assessed the overall quality of the evidence by applying GRADE criteria. Main results: We included 13 trials involving 1472 subfertile women with PCOS who were receiving myo-inositol as pre-treatment to IVF (11 trials), or during ovulation induction (two trials). These studies compared MI versus placebo, no treatment/standard, melatonin, metformin, clomiphene citrate, or DCI. The evidence was of 'low' to 'very low' quality. The main limitations were serious risk of bias due to poor reporting of methods, inconsistency, and lack of reporting of clinically relevant outcomes such as live birth and adverse events.We are uncertain whether MI improves live birth rates when compared to standard treatment among women undergoing IVF (OR 2.42, 95% CI 0.75 to 7.83; P = 0.14; 2 RCTs; 84 women; I² = 0%). Very low-quality evidence suggests that for subfertile women with PCOS undergoing pre-treatment to IVF who have an expected live birth rate of 12%, the rate among women using MI would be between 9% and 51%.We are uncertain whether MI may be associated with a decrease in miscarriage rate when compared to standard treatment (OR 0.40, 95% CI 0.19 to 0.86; P = 0.02; 4 RCTs; 535 women; I² = 66%; very low-quality evidence). This suggests that among subfertile women with PCOS with an expected miscarriage rate of 9% who are undergoing pre-treatment to IVF, the rate among women using MI would be between 2% and 8%; however this meta-analysis is based primarily on one study, which reported an unusually high miscarriage rate in the control group, and this has resulted in very high heterogeneity. When we removed this trial from the sensitivity analysis, we no longer saw the effect, and we noted no conclusive differences between MI and standard treatment.Low-quality evidence suggests that MI may be associated with little or no difference in multiple pregnancy rates when compared with standard treatment (OR 1.04, 95% CI 0.63 to 1.71; P = 0.89; 2 RCTs; 425 women). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected multiple pregnancy rate of 18%, the rate among women using inositol would be between 12% and 27%.We are uncertain whether MI may be associated with an increased clinical pregnancy rate when compared to standard treatment (OR 1.27, 95% CI 0.87 to 1.85; P = 0.22; 4 RCTs; 535 women; I² = 0%; very low-quality evidence). This suggests that among subfertile women with PCOS who are undergoing pre-treatment to IVF, with an expected clinical pregnancy rate of 26%, the rate among women using MI would be between 24% and 40%. Ovulation rates were not reported for this comparison.Other comparisons included only one trial in each, so for the comparisons MI versus antioxidant, MI versus an insulin-sensitising agent, MI versus an ovulation induction agent, and MI versus another DCI, meta-analysis was not possible.No pooled evidence was available for women with PCOS undergoing ovulation induction, as only single trials performed comparison of the insulin-sensitising agent and the ovulation induction agent. Authors' conclusions: In light of available evidence of very low quality, we are uncertain whether MI improves live birth rate or clinical pregnancy rate in subfertile women with PCOS undergoing IVF pre-treatment taking MI compared to standard treatment. We are also uncertain whether MI decreases miscarriage rates or multiple pregnancy rates for these same women taking MI compared to standard treatment. No pooled evidence is available for use of MI versus placebo, another antioxidant, insulin-sensitising agents, ovulation induction agents, or another type of inositol for women with PCOS undergoing pre-treatment to IVF. No pooled evidence is available for use of MI in women undergoing ovulation induction.
Chapter
This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the effectiveness and safety of oral supplementation with inositol on reproductive outcomes for subfertile women with polycystic ovary syndrome (PCOS).
Article
Full-text available
To investigate the effects of treatment with Myo-inositol (an insulin sensitizing drug), on circulating insulin, glucose tolerance, ovulation and serum androgens concentrations in women with the Polycystic Ovary Syndrome (PCOS). Forty-two women with PCOS were treated in a double-blind trial with Myo-inositol plus folic acid or folic acid alone as placebo. In the group treated with Myo-inositol the serum total testosterone decreased from 99.5 +/- 7 to 34.8 +/- 4.3 ng/dl (placebo group: from 116.8 +/- 15 to 109 +/- 7.5 ng/dl; P = 0.003), and serum free testosterone from 0.85 +/- 0.1 to 0.24 +/- 0.33 ng/dl (placebo group: from 0.89 +/- 0.12 to 0.85 +/- 0.13 ng/dl; P = 0.01). Plasma triglycerides decreased from 195 +/- 20 to 95 +/- 17 mg/dl (placebo group: from 166 +/- 21 to 148 +/- 19 mg/dl; P = 0.001). Systolic blood pressure decreased from 131 +/- 2 to 127 +/- 2 mmHg (placebo group: from 128 +/- 1 to 130 +/-1 mmHg; P = 0.002). Diastolic blood pressure decreased from 88 +/- 1 to 82 +/- 3 mmHg (placebo group: from 86 +/- 1 to 90 +/- 1 mmHg; P = 0.001). The area under the plasma insulin curve after oral administration of glucose decreased from 8.54 +/- 1.149 to 5.535 +/- 1.792 microU/ml/min (placebo group: from 8.903 +/- 1.276 to 9.1 +/- 1.162 microU/ml/min; P = 0.03). The index of composite whole body insulin sensitivity (ISI comp) increased from 2.80 +/- 0.35 to 5.05 +/- 0.59 mg(-2)/dl(-2) (placebo group: from 3.23 +/- 0.48 to 2.81 +/- 0.54 mg(-2)/dl(-2); P < 0.002). 16 out of 23 women of Myo-inositol group ovulated (4 out of 19 in placebo group). Treatment of PCOS patients with Myo-inositol provided a decreasing of circulating insulin and serum total testosterone as well as an improvement in metabolic factors.
Conference Paper
Despite significant advances in past years on the chemistry and biology of insulin and its receptor, the molecular events that couple the insulin-receptor interaction to the regulation of cellular metabolism remain uncertain. Progress in this area has been complicated by the pleiotropic nature of the actions of insulin. These most likely involve a complex network of pathways resulting in the coordination of mechanistically distinct cellular effects. Because the well-recognized mechanisms of signal transduction (i.e., cyclic nucleotides, ion channels) appear not to be central to insulin action, investigators have searched for a novel second-messenger system. A low-molecular-weight substance has been identified that mimics certain actions of insulin on metabolic enzymes. This substance has an inositol glycan structure, and is produced by the insulin-sensitive hydrolysis of a glycosylphosphatidylinositol in the plasma membrane. This hydrolysis reaction, which is catalyzed by a specific phospholipase C, also results in the production of a structurally distinct diacylglycerol that may selectively regulate one or more of the protein kinases C. The glycosyl-phosphatidylinositol precursor for the inositol glycan enzyme modulator is structurally analogous to the recently described glycosyl-phosphatidylinositol membrane protein anchor. Preliminary studies suggest that a subset of proteins anchored in this fashion may be released from cells by a similar insulin-sensitive phospholipase-catalyzed reaction. Future efforts will focus on the precise role of the metabolism of glycosyl phosphatidylinositols in insulin action.
Article
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). One hundred twenty patients were randomly treated with metformin 1500 mg/day orally (n = 60), or 4 g MYO plus 400 microg 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. 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%. 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.
Article
Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome. To assess the effectiveness of insulin sensitising drugs in improving reproductive outcomes and metabolic parameters for women with PCOS and menstrual disturbance. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008), the Cochrane Central Register of Controlled Trials (Cochrane Library, third Quarter 2008), CINAHL (searched September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008). All searches were rerun 13 August 2009 17 RCTs were located and await classification. Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent. Thirty one trials (2537 women) were included for analysis, 27 of them using metformin and involving 2150 women. There is no evidence that metformin improves live birth rates whether it is used alone (Pooled OR = 1.00, 95% CI 0.16 to 6.39) or in combination with clomiphene (Pooled OR = 1.48, 95% CI 1.12 to 1.95). However, clinical pregnancy rates are improved for metformin versus placebo (Pooled OR = OR 3.86, 95% C.I. 2.18 to 6.84) and for metformin and clomiphene versus clomiphene alone (Pooled OR =1.48, 95% C.I. 1.12 to 1.95) ). In the studies that compared metformin and clomiphene alone, there was no evidence of an improved live birth rate (OR= 0.67, 95% CI 0.44 to 1.02) but the pooled OR resulted in improved clinical pregnancy rate in in the clomiphene group (OR = 0.63 , 95% 0.43 to 0.92), although there was significant heterogeneity.There is also evidence that ovulation rates are improved with metformin in women with PCOS for metformin versus placebo (Pooled OR 2.12, 95% CI 1.50 to 3.0) and for metformin and clomiphene versus clomiphene alone (Pooled OR = 3.46, 95% CI 1.97 to 6.07).Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported. In agreement with the previous review, metformin is still of benefit in improving clinical pregnancy and ovulation rates. However, there is no evidence that metformin improves live birth rates whether it is used alone or in combination with clomiphene, or when compared with clomiphene. Therefore, the use of metformin in improving reproductive outcomes in women with PCOS appears to be limited.
Article
Polycystic ovary syndrome (PCOS) is characterised by anovulation, hyperandrogaenemia and insulin resistance. Hyperinsulinaemia is associated with an increase in cardiovascular risk and the development of diabetes mellitus. If insulin sensitising agents such as metformin are effective in treating features of PCOS, then they could have wider health benefits than just treating the symptoms of the syndrome. To assess the effectiveness of insulin sensitising drugs in improving clinical and biochemical features of PCOS. We searched the Cochrane Menstrual Disorders & Subfertility Group trials register (searched September 2008 ), the Cochrane Central Register of Controlled Trials (Cochrane Library, September 2008), MEDLINE (January 1966 to September 2008), and EMBASE (January 1985 to September 2008). Randomised controlled trials which investigated the effect of insulin sensitising drugs compared with either placebo or no treatment, or compared with an ovulation induction agent. Thirty nine trials (3576 subjects) were included for analysis, 31 of them using metformin and involving 2625 participants. Meta-analysis showed that metformin is effective in achieving ovulation in women with PCOS with odds ratios of 2.21(CI 1.57 to 3.10) for metformin versus placebo and 3.93(CI 2.32 to 6.65) for metformin and clomiphene versus clomiphene alone. An analysis of pregnancy rates suggests a significant treatment effect for metformin and clomiphene (OR 1.58, CI 1.20 to 2.07). Nevertheless, these benefits were not translated into live birth rates.Metformin has a significant effect in reducing fasting insulin levels (WMD -4.20 mIU/L, CI -7.68 to -0.73); however, the reduction was only significant in the non-obese group (BMI < 30 kg/m2). Treatment effect on serum testosterone concentration was observed; but the magnitude of the reduction was greater in the non-obese group compared with the obese group (WMD -1.79 versus. -0.30 nmol/L). Metformin has no effect on serum lipid profiles. Metformin was also associated with a significantly higher incidence of gastrointestinal disturbance, but no serious adverse effects were reported. In agreement with the previous review, metformin is still of benefit in improving ovulation and pregnancy rates. However, metformin does not improve live birth whether it is used alone or in combination with clomiphene. In addition, metformin has limited effect on metabolic parameters, especially in obese women with PCOS. Therefore, the use of metformin in improvement of reproductive outcomes or in reducing the risk of developing metabolic syndrome in women with PCOS appears to be limited.
Article
Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne and pattern alopecia, often characterised by ovulation disorders (usually manifested as oligo- or amenorrhea). In addition, 30-40% of women with PCOS have impaired glucose tolerance, and a defect in the insulin signalling pathway seems to be implicated in the pathogenesis of insulin resistance. For this reason, insulin-lowering medications represent novel approach in women with PCOS. The aim of this study was to evaluate the effects of myo-inositol (MYO), an isoform of inositol, belonging to the vitamin B complex, in the treatment of cutaneous disorders like hirsutism and acne. Fifty patients with PCOS were enrolled in the study. BMI, LH, FSH, insulin, HOMA index, androstenedione, testosterone, free testosterone, hirsutism and acne were evaluated at the baseline and after receiving MYO therapy for 6 months. After 3 months of MYO administration, plasma LH, testosterone, free testosterone, insulin and HOMA index resulted significantly reduced; no significant changes were observed in plasma FSH and androstenedione levels. Both hirsutism and acne decreased after 6 months of therapy. MYO administration is a simple and safe treatment that ameliorates the metabolic profile of patients with PCOS, reducing hirsutism and acne.
Article
Some actions of insulin are mediated by inositolphosphoglycan (IPG) mediators. Deficient release of a putative D-chiro-inositol-containing (DCI) IPG mediator may contribute to insulin resistance in women with polycystic ovary syndrome (PCOS). Previously, we demonstrated that oral DCI supplementation improved ovulation and metabolic parameters in women with PCOS. However, whether oral DCI mediates an increase in the release of the DCI-IPG mediator and an improvement in insulin sensitivity in women with PCOS is unknown. We conducted a randomized controlled trial of DCI supplementation vs placebo in 11 women with PCOS who were assessed at 2 time points 6 weeks apart. Plasma DCI, DCI-IPG release during oral glucose tolerance test (AUC(DCI-IPG)), and insulin sensitivity (S(i)) by frequently sampled intravenous glucose tolerance test were assessed at baseline and end of study. The study was terminated early because of a sudden unavailability of the study drug. However, in all subjects without regard to treatment assignment, there was a positive correlation between the change in AUC(DCI-IPG)/AUC(insulin) ratio and the change in S(i) during the 6-week period (r = 0.69, P = .02), which remained significant after adjustment for body mass index (P = .022) and after further adjustment for body mass index and treatment allocation (P = .0261). This suggests that, in women with PCOS, increased glucose-stimulated DCI-IPG release is significantly correlated with improved insulin sensitivity. The significant relationship between DCI-IPG release and insulin sensitivity suggests that the DCI-IPG mediator may be a target for therapeutic interventions in PCOS.
Article
We evaluated basal plasma total immunoreactive insulin (insulin), androstenedione, and testosterone in 14 obese women: 8 with polycystic ovarian disease (PCOD) and 6 obese controls. All 3 hormones were significantly elevated (P less than 0.02 to P less than 0.001) in PCOD patients. A significant correlation among basal levels of plasma insulin, androstenedione, and testosterone was demonstrated. The PCOD group had significantly higher levels of glucose at 1, 2, and 3 h, with similar significant increases in plasma insulin levels at 0, 2, and 3 h. A significant correlation was found between plasma insulin response areas and plasma testosterone (P less than 0.001) in the control and PCOD patients. These studies demonstrate that hyperandrogenism correlates with hyperinsulinism.
Article
The biguanide metformin (dimethylbiguanide) is an oral antihyperglycaemic agent used in the management of non-insulin-dependent diabetes mellitus (NIDDM). It reduces blood glucose levels, predominantly by improving hepatic and peripheral tissue sensitivity to insulin without affecting the secretion of this hormone. Metformin also appears to have potentially beneficial effects on serum lipid levels and fibrinolytic activity, although the long term clinical implications of these effects are unclear. Metformin possesses similar antihyperglycaemic efficacy to sulphonylureas in obese and nonobese patients with NIDDM. Additionally, interim data from the large multicentre United Kingdom Prospective Diabetes Study (UKPDS) indicated similar antihyperglycaemic efficacy for metformin and insulin in newly diagnosed patients with NIDDM. Unlike the sulphonylureas and insulin, however, metformin treatment is not associated with increased bodyweight. Addition of metformin to existing antidiabetic therapy confers enhanced antihyperglycaemic efficacy. This may be of particular use in improving glycaemic control in patients with NIDDM not adequately controlled with sulphonylurea monotherapy, and may serve to reduce or eliminate the need for daily insulin injections in patients with NIDDM who require this therapy. The acute, reversible gastrointestinal adverse effects seen with metformin may be minimised by administration with or after food, and by using lower dosages, increased slowly where necessary. Lactic acidosis due to metformin is rare, and the risk of this complication may be minimised by observance of prescribing precautions and contraindications intended to avoid accumulation of the drug or lactate in the body. Unlike the sulphonylureas, metformin does not cause hypoglycaemia. Thus, metformin is an effective antihyperglycaemic agent which appears to improve aberrant plasma lipid and fibrinolytic profiles associated with NIDDM. Possible long term clinical benefits of this drug with regard to cardiovascular mortality and morbidity are not yet established but are being assessed in a major ongoing study. Since metformin does not promote weight gain or hypoglycaemia it should be considered first-line pharmacotherapy in obese patients with NIDDM inadequately controlled by nonpharmacological measures. Metformin appears similarly effective for the pharmacological management of NIDDM in nonobese patients.