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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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