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Myo-inositol

Myo- Inositol ( i- inositol; meso- inositol; myo- inositol; 1,2,3,5-cis-4,6-cyclohexanehexol; dambose [1] ) is one of the 9 stereoisomers of inositol hexahydric alcohol. Myo- inositol and its derivatives act as important signal transmitters in intracellular signaling cascades in the form of various inositol phosphates and phosphatidylinositol lipids, participating in the regulation of intracellular calcium levels [2] , signal transduction from the insulin receptor [3] , fat breakdown and lowering cholesterol levels blood [4] , modulation of neurotransmitter activity.

Myo-inositol
Inositol structure.png
General
Systematic
name		cis-1,2,3,5-trans-4,6-cyclohexanehexol
Traditional namesCyclohexanehexol, phaseomannitol, myoinositol
Chem. formulaC₆H₁₂O₆
Physical properties
conditioncrystalline powder
Molar mass180.16 g / mol
Density1,752 g / cm³
Thermal properties
T. melt.225–227 ° C
T. decomp.315 ° C
Chemical properties
Solubility in water2.5 12 ; 4.15 15 g / 100 ml
Solubility in ethanolhardly soluble
Diethyl Solubilityinsoluble
Classification
Reg. CAS number87-89-8
PubChem
Reg. EINECS number
Smiles
Inchi
Chebi17268
ChemSpider
Security
Toxicitylow toxicity (intake of 2..4 g is completely safe)

Content

  • 1 Content in food
  • 2 Content in various preparations
  • 3 Brief history of the study of myo-inositol
  • 4 Bioinformational and systems-biological analysis
  • 5 Clinical studies
    • 5.1 Myoinositol and diabetes
    • 5.2 Myoinositol and CNS Function
    • 5.3 Myoinositol and Ovarian Function Support
    • 5.4 Myoinositol in preparation for in vitro fertilization (IVF)
    • 5.5 Myoinositol in the treatment of PCOS
    • 5.6 Reducing the excessive secretion of androgens, hirsutism and acne
    • 5.7 Myoinositol and malformations
  • 6 References

Food Content

Myo- inositol or its phosphate derivatives are found in fruits (especially melons and oranges) and are also found in legumes, grains, and nuts [5] .

In plants, myo- inositol is found mainly in the form of myo- inositol hexaphosphate (the so-called phytic acid ) and its salts, phytates, which serve as a source of phosphates for germinating seed. It should be noted that phytic acid is poorly absorbed by the human body. In addition, phytates also chelate many essential minerals (calcium, magnesium, iron, zinc), significantly reducing their bioavailability and contributing to the formation of mineral deficiencies and disturbances in the electrolyte balance of the body [6] .

Myo- inositol is present in a significant amount of food. However, in the tables describing the content of myo- inositol in various products, a distinction is not always made between the physiologically active form (that is, myo- inositol itself) and the low-active form - phytic acid [5] . The highest content of all forms of myo- inositol was found in wheat seedlings (700 mg / 100 g), rice bran (460 mg / 100 g), fresh green peas (240 mg / 100 g) and oranges (210 mg / 100 g).

Content in various formulations

Myo-inositol is included in a number of vitamin-mineral complexes: Actifert-Andro for increasing male fertility, Vitrum Beauty (20 mg / tab), Ladis Formula for skin, hair and nails (10 mg / tab). Myo-inositol is part of the hepatoprotective drug Progepar in an amount of 25 mg / dragee [7] . The manufacturer of chondroprotector "Alflutop" declares the presence of myo-inositol in the drug. In therapeutic dosages, myo-inositol is available in the form of the Miofolik complex (2000 mg / sachet) [8] [9] and the Fertina mono-preparations (1000 mg / sachet) [10] [11] and Inofert (1000 mg / sachet) [12] [13] .

It should be noted that the recommended daily intake of myoinositol for adults is 500 mg / day; for children 4-6 years old - 80-100 mg / day; for children 7-18 years old from 200 to 500 mg / day [14] . The upper level of consumption has not been established. In clinical practice, doses of 2000 ... 4000 mg / day (for polycystic ovary syndrome and preparation for IVF) and even 12000 mg / day (in psychiatric practice, see below) are used.

A Brief History of the Study of Myo-Inositol

1848 - the famous German chemist J. Liebig isolated from wheat seedlings and called it myoinositol.

1902 - myoinositol was included in the classification of vitamins as vitamin B8 or "vitamin of youth".

1941 - Gavin and McHenry established the lipotropic effect of inositol. [fifteen]

1986 - Rapiejko et al. found in myoinositol the ability to normalize cholesterol levels. [four]

2011 - Condorelli et al. found that myoinositol regulates osmolarity and seminal plasma volume, expression of proteins necessary for embryogenetic development and sperm motility, is effective in male infertility. [16]

2013 - Bioinformation analysis of the human proteome made it possible to systematize data on all known inositol-dependent proteins and their role in human physiology [17] .

Bioinformational and systems-biological analysis

Dozens of receptor species (e.g., metabotropic glutamate, histamine, GABA, etc.) that are located on the cell membrane, when activated, use special signaling proteins (usually kinase enzymes (including phosphoinositide-3-kinases PI3K, phospholipases, etc.), leading to the secretion of calcium from the endoplasmic reticulum of the cell into the cytosol. Calcium, diacylglycerol, cAMP and various phosphate derivatives of myoinositol (phosphatidylinositol and others) are essential "secondary messenges" er ") involved in the regulation of cascade mechanisms that exercise the biological roles of the corresponding receptors.

To date, dozens of proteins are known that are involved in intracellular signaling cascades from receptors with the participation of calcium and derivatives of myoinositol. Searches in the MEDLINE publication database and other databases made it possible to establish and systematically describe all of these proteins. Thus, the existence of 233 proteins that somehow take part in the transmission of intracellular signals through derivatives of myoinositol has been established. It should be noted that for most of these proteins, biological roles are not well understood. Nevertheless, in the course of further analysis, it was possible to isolate about 120 inositol phosphate-dependent proteins, for which there is reliable information about their specific participation in various physiological processes [17] . The total information on the physiological roles of these signaling proteins is presented in Fig.

 

The results of the system-biological analysis of human proteome protein analysis are confirmed by experimental and clinical studies. Myoinositol is indeed involved in supporting the vital functions of the cardiovascular system [18] , immunity (a decrease in autoimmune inflammatory reactions [19] ). No less important are the roles of myoinositol in the central nervous system (the regulation of the levels of the neuronal-glial metabolite of myoinositol is impaired in the case of cognitive impairment, depression and diabetes [20] ), sugar metabolism (primarily in the signaling cascade of insulin [21] ) and in the functioning of the kidneys [22] and liver. The interaction of inositol derivatives in interaction with specific proteins involved in the functioning of the reproductive system corresponds to the well-known obstetric-gynecological use of myoinositol preparations in the treatment of a disease known as polycystic ovary syndrome (PCOS) [23] .

Clinical

Myoinositol and Diabetes

Being the so-called. “Secondary signal”, phosphate derivatives of myoinositol, together with calcium and magnesium ions, transmit a signal from the insulin receptor into cells of various tissues. These intracellular processes increase the expression of the glucose transporter, initiate the adsorption of the insulin receptor, stimulate the processing of carbohydrates and fats to maintain energy metabolism of the cell, and are necessary to reduce the risk of insulin resistance, diabetes, overweight and obesity [17] .

In a study of group 101 diabetics and 212 healthy volunteers, urinary myoinositol levels in patients with diabetes were significantly higher (37 ± 37 ng / l) than in the control group (8 ± 13 ng / l, p <0.001). The average accuracy of recognition of patients with diabetes by the product of myoinositol levels by D-chiroinositol levels in urine was 84% ​​(confidence interval 79..89%, p <0.001) [24] .

The effects of taking myoinositol supplements on insulin resistance in patients with gestational diabetes were studied in a group of 69 patients. The group was randomized to receive myoinositol (4000 mg / day) and folic acid (400 μg / day) or folic acid alone (control). Myoinositol administration led to a decrease in fasting glucose and insulin glucose levels, so that the insulin resistance homeostasis model significantly decreased in 50% of the participants in the main group and only in 29% in the control group (P = 0.0001). Myoinositol also contributed to an increase in adiponectin levels (p = 0.009) [25] .

Myoinositol and CNS Function

Myoinositol is necessary to support neuronal function, including synaptic transmission and physiological effects of neurotransmitters such as serotonin, dopamine, GABA, neuromedin. Derivatives of myoinositol also provide energy metabolism in the central nervous system (through participation in the cascade of the insulin receptor) and are involved in the protection of neurons from cellular stress [17] .

A study of patients with moderate cognitive impairment by MR spectroscopy (1H MRS), which allows us to assess the levels of molecules such as N-acetyl aspartate, choline, myoinositol, glutamine in the brain tissue of patients, showed significant differences (p <0.05) in the ratio of myoinositol / water in the left frontal lobe with cognitive impairment when comparing data for healthy participants [26] .

The effect of myoinositol on the metabolism and biological activity of excitatory and inhibitory neurotransmitters suggests that myoinositol may be useful for patients with neurochemical disorders (as a rule, these are psychiatric patients). Preliminary research results have shown that high doses of purified myoinositol can help patients suffering from such problems bulimia, panic disorder, obsessive-compulsive disorder, agoraphobia, unipolar and bipolar depression. For example, in a double-blind study of 13 patients, myoinositol (18 g / day) reduced the symptoms of obsessive-compulsive disorder with the effectiveness of commonly used but more dangerous SSRIs (selective serotonin reuptake inhibitors), with almost no side effects [27] . In another double-blind, controlled study, myoinositol (18 g / day) showed better efficacy than fluvoxamine (in terms of reducing the number of panic attacks and other side effects) [28] . The use of 12 g / day myoinositol in a double-blind, placebo-controlled study of patients with depression led to a significant improvement in symptoms, without negative changes in the liver, kidneys, or hematological functions [29] .

Myoinositol and Ovarian Function Support

The specific effects of myoinositol on reproductive function are associated with the participation of derivatives of myoinositol in the signaling cascades of protein receptors of gonadoliberin (gonadotropin-releasing hormone, GNVH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The direct participation of myoinositol in the processes of hormonal regulation of the menstrual cycle determines the successful use of myoinositol in patients with anovulatory cycle [17] . If you follow a series of studies using different doses of myoinositol, there is a tendency to dose-dependent and long-term course administration. For example, taking myoinositol in an amount of 2 g / day for 24 weeks. admission allows you to reduce anovulatory cycles by 4 times, and admission at a dose of 4 g / day for 3-4 weeks [18] .

The participation of myoinositol in signal transmission from the insulin receptor and the implementation of the effects of GNVH, LH, FSH provides a more complete maturation of oocytes when taking myoinositol. A prospective, controlled, randomized study showed that myoinositol improves the functional state of oocytes in patients with PCOS who underwent cycles of intracytoplasmic sperm injection (ICSI) [30] .

Myoinositol in preparation for in vitro fertilization (IVF)

In vitro fertilization is assisted reproductive technology used in the event of infertility. During IVF, the egg is removed from the body of a woman and artificially fertilized, “in vitro” (conditionally, “in vitro”), the resulting embryo is kept in an incubator, where it develops for 2-5 days, after which the embryo is transferred to the uterine cavity for further development. The use of myoinositol in IVF preparation programs increases the maturity of oocytes, reduces hormonal load and increases the effectiveness of the procedure. The use of myoinositol in combination with D-chiroinositol in the physiological ratio (1.1 g / day of myoinositol, 27 mg / day of D-chiroinositol) during IVF was used to improve the quality of oocytes and embryos compared with taking only 500 mg of D-chiroinositol [31] .

The addition of myoinositol to folic acid in patients without PCOS undergoing follicle stimulation cycles for IVF reduces the number of mature oocytes used and the dosage of rFSH without reducing the number of clinical pregnancies. In a group of women (n = 100) aged <40 years without PCOS and with a basal FSH level <10 IU / ml, patients received rFSH (150 IU) for 6 days. 3 months before the start of IVF procedures, the group was randomized to receive myoinositol and folic acid (n = 50) or only folic acid (n = 50). The use of myoinositol allowed to reduce the total amount of gonadotropin, the number of oocytes used, and to increase the number of cases of successful oocyte implantation [32] .

It is important to note that myoinositol also affects the functioning of spermatozoa, regulating the osmolarity and volume of seminal plasma, expression of proteins necessary for embryogenetic development and sperm motility. Sufficient concentrations of myoinositol in the culture medium of cell culture significantly increase the percentage of motile spermatozoa in both healthy controls and patients with oligo-astheno-teratozoospermia. The improvement in motility in the latter group was associated, in particular, with a significant increase in the proportion of spermatozoa with high mitochondrial membrane potential [16] .

Myoinositol in the treatment of PCOS

Myoinositol and its derivatives are necessary for the effects of gonadopropin, luteinizing and follicle-stimulating hormones, thereby exerting a wide influence on the functioning of the reproductive system and fertility (trophoblast invasion during blastocyst fixation, ovarian function, oocytes, placenta). Polycystic ovary syndrome (PCOS) is the main cause of infertility due to metabolic, hormonal dysfunctions and ovaries [17] . In patients, PCOS is often comorbid with insulin resistance and compensatory hyperinsulinemia. Combined therapy for PCOS with the inclusion of myoinositol reduces the risk of metabolic disorders in PCOS in overweight patients, showing a beneficial effect on the level of metabolism, the state of hormonal regulation and ovarian function. The effects of myoinositol in women with PCOS were studied in a systematic analysis of randomized controlled trials. In general, the results of the analysis suggest the use of myoinositol for improving ovarian function, as well as metabolic and hormonal parameters in patients with PCOS [33] .

An observational study (Pedro-Antonio Regidor, Adolf Eduard Schindler) [34] of myo-inositol as a safe and alternative approach to the treatment of infertility in women with PCOS showed that the use of 2 × 2000 mg of myo-inositol + 2 × 200 μg of folic acid in day (which is contained in 2 sachets of Miofolik [35] ) is a safe and promising tool for the effective improvement of infertility symptoms in patients with polycystic ovary syndrome (PCOS).

Рандомизированное, двойное слепое, плацебо-контролируемое исследование эффектов миоинозитола в группе 92 женщин с СПКЯ указало на достоверное улучшение функций яичников. Пациентки контрольной группы (n=47) получали 400 мкг фолиевой кислоты в качестве плацебо, а пациентки основной группы (n=45) миоинозитол плюс фолиевую кислоту (4 г/сут миоинозитола, 400 мкг/сут фолиевой кислоты, в виде препарата «Иноферт», 1000 мг/саше)[8][9]. http://www.rlsnet.ru/baa_tn_id_54946.htm . Уровни эстрадиола достоверно были выше в основной группе начиная уже с первой недели лечения. Прием миоинозитола способствовал увеличению уровней липопротеинов высокой плотности. В основной группе частота овулирущих пациенток была выше (25 %, плацебо — 15 %), а время до первой овуляции существенно короче (25 сут, 95 % ДИ 18-31; плацебо — 41 сут, 95 % ДИ 27-54, Р<0.05). Существенного улучшения не было отмечено у пациенток с тяжёлой формой ожирения (ИМТ>37) [36] .

Снижение избыточной секреции андрогенов, гирсутизма и акне

Характерная для СПКЯ гиперинсулинемия способствует нарушениям метаболизма андрогенов, что проявляется как гирсутизм, акне и андрогенное ожирение. Взаимосвязь между нарушением прохождения сигнала по каскаду инсулинового рецептора [17] с андрогенными нарушениями при СПКЯ подтверждена в клинических исследованиях: у пациенток с СПКЯ отмечены характерные изменения уровней сигнальных белков, называемых «субстраты инсулинового рецептора» 1-го, 2-го и 4-го типов (IRS-1/2) в текальных клетках яичников, которые могут играть важную роль в гиперандрогенизме яичников и текальной гиперплазии [37] . Увеличение уровней фермента синтеза тестостерона 17-альфа-гидроксилазы при стимуляции текальных клеток яичников инсулином опосредовано сигнальным белком каскада инсулинового рецептора фосфатидилинозитол-3-киназой (PI3K) [38] .

Миоинозитол может использоваться для устранения андрогеновых нарушений. Например, 50 пациенток с СПКЯ получали 4 г/сут миоинозитола в течение 6 месяцев. Через 3 месяца приема миоинозитола уровни ЛГ, тестостерона, свободного тестостерона, инсулина в плазме существенно снизились. Гирсутизм и акне достоверно уменьшились после 6 месяцев терапии [39] . Изучение эффектов миоинозитола (4 г/сут, 12-16 нед.) в двойном слепом плацебо-контролируемом исследовании 42 пациенток с СПКЯ приводила к достоверным снижениям уровней тестостерона, триглицеридов, инсулина и способствовала нормализации АД и восстановлению овуляции. Уровень общего тестостерона снизился от 99±7 до 35±4 нг/дл (группа плацебо, от 116±15 до 109±8 нг/дл, p=0.003), свободного тестостерона сыворотки — от 0.85±0.1 до 0.24±0.33 нг/дл (группа плацебо: от 0.89±0.12 до 0.85±0.13 нг/дл, p=0.01) [40] .

Миоинозитол и пороки развития

Дефициты миоинозитола и цинка являются факторами риска для формирования расщелины губы и/или «волчьей пасти». Наблюдения за 84 беременными, родивших детей с такими дефектами, и 102 беременными, родивших здоровых детей показали, что риск пороков развития был достоверно связан с более низкими уровнями цинка в эритроцитах у детей (р = 0.003) и у их матерей (р=0.02). Низкие уровни миоинозитола сыворотки (<13.5 мкмоль/л) у матери соответствовали увеличению риска пороков развития в 3 раза (95 % ДИ 1.2-7.4). Низкий уровень миоинозитола сыворотки у детей (<21.5 мкмоль/л) соответствовал повышению риска пороков развития в 3.4 раза (95 % ДИ 1.3-8.6); низкие уровни цинка в эритроцита (<118 мкмоль/л) — повышению риска в 3.3 раза (95 % ДИ 1.3-8.0). Была установлена достоверная корреляция между уровнями миоинозитола у матери и у ребёнка (коэффициент корреляции 0.33, р=0.0006) [41] .

Дефицит миоинозитол был ассоциирован с повышенным риском расщелин позвоночника при наблюдении 63 матерей и 70 детей с расщелиной позвоночника в сравнении с контрольной группой (102 матери, 85 детей). Уровни миоинозитола в сыворотке матерей были на 5 % (95 % ДИ 1 %-11 %) меньше у матерей в основной группе. Квартиль самых низких концентраций миоинозитола соответствовал повышению риска расщеплен позвоночника в 2.6 раза (95 % ДИ 1.1-6.0). В группе детей с ДНТ, уровни миоинозитола сыворотки были, в среднем, на 7 % ниже (95 % ДИ 0 %-14 %) [42] .

У беременных с нарушениями метаболизма глюкозы и инсулинрезистентностью дети с пороками развития рождаются чаще. Роль миоинозитола в профилактике пороков развития связанных с нарушениями обмена углеводов трудно переоценить: производные миоинозитола участвуют в процессах передачи сигнала от инсулинового рецептора [43] (см. также выше). Низкие концентрации миоинозитола в ткани эмбриона на этапе органогенеза играют важную роль в индуцированнии эмбриопатий, вызываемых гипергликемией [44] .

Прием миоинозитола профилактирует риск возникновения гестационного диабета (ГД) даже у женщин с семейной историей диабета 2-го типа. Например, в проспективном, рандомизированном, плацебо-контролируемом исследовании одна группа пациенток получала 4 г/сут миоинозитола и 400 мкг/сут фолиевой кислоты разделённые на приема (n=110), начиная с конца первого триместра. Участницы в группе плацебо (n=110) получали только 400 мкг/сут фолиевой кислоты. Заболеваемость ГД была значительно ниже при приеме миоинозитола — 6 %, контроль — 15,3 % (О. Ш. 0.35, р=0.04). При приеме миоинозитола также было отмечено статистически значимое снижение частоты макросомии (масса плода>4000 г) и снижение средней массы плода в сторону середины интервала нормы [45] .

Links

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  2. ↑ Gerasimenko JV , Flowerdew SE , Voronina SG , Sukhomlin TK , Tepikin AV , Petersen OH , Gerasimenko OV Bile acids induce Ca2+ release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors. (англ.) // The Journal of biological chemistry. — 2006. — Vol. 281, no. 52 . — P. 40154—40163. — DOI : 10.1074/jbc.M606402200 . — PMID 17074764 .
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  4. ↑ 1 2 Rapiejko PJ , Northup JK , Evans T. , Brown JE , Malbon CC G-proteins of fat-cells. Role in hormonal regulation of intracellular inositol 1,4,5-trisphosphate. (англ.) // The Biochemical journal. — 1986. — Vol. 240, no. 1 . — P. 35—40. — PMID 3103610 .
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  9. ↑ Миофолик для повышения фертильности у женщин и лечения СПКЯ (рус.) (неопр.) ? . Амакса Україна. Дата обращения 10 мая 2019.
  10. ↑ Фертина Инозит 1000 мг Фолиевая кислота 100 мкг в Энциклопедии РЛС. Описание. (unspecified) . www.rlsnet.ru. Дата обращения 27 ноября 2018.
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  18. ↑ 1 2 Venturella R. , Mocciaro R. , De Trana E. , D'Alessandro P. , Morelli M. , Zullo F. Assessment of the modification of the clinical, endocrinal and metabolical profile of patients with PCOS syndrome treated with myo-inositol (итал.) // Minerva ginecologica. — 2012. — Vol. 64, n. 3 . — P. 239—243. — PMID 22635019 .
  19. ↑ Young GB , Hader WJ , Hiscock M. , Warren KG , Logan D. The role of myo-inositol in multiple sclerosis. (англ.) // Journal of neurology, neurosurgery, and psychiatry. — 1986. — Vol. 49, no. 3 . — P. 265—272. — PMID 3007676 .
  20. ↑ Haroon E. , Watari K. , Thomas A. , Ajilore O. , Mintz J. , Elderkin-Thompson V. , Darwin C. , Kumaran S. , Kumar A. Prefrontal myo-inositol concentration and visuospatial functioning among diabetic depressed patients. (англ.) // Psychiatry research. — 2009. — Vol. 171, no. 1 . — P. 10—19. — DOI : 10.1016/j.pscychresns.2008.03.006 . — PMID 19097871 .
  21. ↑ Hacibekiroğlu M. , Akçay T. The role of plasma, erythrocyte and platelet myo-inositol levels in the development of diabetic microangiopathy. (англ.) // Diabetes research (Edinburgh, Scotland). — 1994. — Vol. 25, no. 4 . — P. 173—179. — PMID 7648788 .
  22. ↑ Melmed S. , Lewin LM , Bank H. Myo-inositol clearance in renal failure and in patients with normal kidney function. (англ.) // The American journal of the medical sciences. — 1977. — Vol. 274, no. 1 . — P. 55—59. — PMID 900156 .
  23. ↑ Nordio M. , Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. (англ.) // European review for medical and pharmacological sciences. — 2012. — Vol. 16, no. 5 . — P. 575—581. — PMID 22774396 .
  24. ↑ Hong JH , Jang HW , Kang YE , Lee JH , Kim KS , Kim HJ , Park KR , Ku BJ Urinary chiro- and myo-inositol levels as a biological marker for type 2 diabetes mellitus. (англ.) // Disease markers. — 2012. — Vol. 33, no. 4 . — P. 193—199. — DOI : 10.3233/DMA-2012-0925 . — PMID 22960342 .
  25. ↑ Corrado F. , D'Anna R. , Di Vieste G. , Giordano D. , Pintaudi B. , Santamaria A. , Di Benedetto A. The effect of myoinositol supplementation on insulin resistance in patients with gestational diabetes. (англ.) // Diabetic medicine : a journal of the British Diabetic Association. - 2011. - Vol. 28, no. 8 . — P. 972—975. — DOI : 10.1111/j.1464-5491.2011.03284.x . — PMID 21414183 .
  26. ↑ Walecki J. , Barcikowska M. , Ćwikła JB , Gabryelewicz T. N-acetylaspartate, choline, myoinositol, glutamine and glutamate (glx) concentration changes in proton MR spectroscopy (1H MRS) in patients with mild cognitive impairment (MCI). (англ.) // Medical science monitor : international medical journal of experimental and clinical research. - 2011. - Vol. 17, no. 12 . — P. 105—111. — PMID 22129910 .
  27. ↑ Fux M. , Levine J. , Aviv A. , Belmaker RH Inositol treatment of obsessive-compulsive disorder. (англ.) // The American journal of psychiatry. — 1996. — Vol. 153, no. 9 . — P. 1219—1221. — DOI : 10.1176/ajp.153.9.1219 . — PMID 8780431 .
  28. ↑ Palatnik A. , Frolov K. , Fux M. , Benjamin J. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. (англ.) // Journal of clinical psychopharmacology. — 2001. — Vol. 21, no. 3 . — P. 335—339. — PMID 11386498 .
  29. ↑ Levine J. , Barak Y. , Gonzalves M. , Szor H. , Elizur A. , Kofman O. , Belmaker RH Double-blind, controlled trial of inositol treatment of depression. (англ.) // The American journal of psychiatry. — 1995. — Vol. 152, no. 5 . — P. 792—794. — DOI : 10.1176/ajp.152.5.792 . — PMID 7726322 .
  30. ↑ Papaleo E. , Unfer V. , Baillargeon JP , Fusi F. , Occhi F. , De Santis L. Myo-inositol may improve oocyte quality in intracytoplasmic sperm injection cycles. A prospective, controlled, randomized trial. (англ.) // Fertility and sterility. — 2009. — Vol. 91, no. 5 . — P. 1750—1754. — DOI : 10.1016/j.fertnstert.2008.01.088 . — PMID 18462730 .
  31. ↑ Colazingari S. , Treglia M. , Najjar R. , Bevilacqua A. The combined therapy myo-inositol plus D-chiro-inositol, rather than D-chiro-inositol, is able to improve IVF outcomes: results from a randomized controlled trial. (англ.) // Archives of gynecology and obstetrics. — 2013. — Vol. 288, no. 6 . — P. 1405—1411. — DOI : 10.1007/s00404-013-2855-3 . — PMID 23708322 .
  32. ↑ Lisi F. , Carfagna P. , Oliva MM , Rago R. , Lisi R. , Poverini R. , Manna C. , Vaquero E. , Caserta D. , Raparelli V. , Marci R. , Moscarini M. Pretreatment with myo-inositol in non polycystic ovary syndrome patients undergoing multiple follicular stimulation for IVF: a pilot study. (англ.) // Reproductive biology and endocrinology : RB&E. — 2012. — Vol. 10. — P. 52. — DOI : 10.1186/1477-7827-10-52 . — PMID 22823904 .
  33. ↑ Unfer V. , Carlomagno G. , Dante G. , Facchinetti F. Effects of myo-inositol in women with PCOS: a systematic review of randomized controlled trials. (англ.) // Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. — 2012. — Vol. 28, no. 7 . — P. 509—515. — DOI : 10.3109/09513590.2011.650660 . — PMID 22296306 .
  34. ↑ Adolf Eduard Schindler, Pedro-Antonio Regidor. Myoinositol as a Safe and Alternative Approach in the Treatment of Infertile PCOS Women: A German Observational Study (англ.) . International Journal of Endocrinology (2016). Дата обращения 10 мая 2019.
  35. ↑ Инновационный комплекс Миофолик | Официальный сайт (рус.) (неопр.) ? . Miofolic. Дата обращения 10 мая 2019.
  36. ↑ Gerli S. , Mignosa M. , Di Renzo GC Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial. (англ.) // European review for medical and pharmacological sciences. — 2003. — Vol. 7, no. 6 . — P. 151—159. — PMID 15206484 .
  37. ↑ Yen HW , Jakimiuk AJ , Munir I. , Magoffin DA Selective alterations in insulin receptor substrates-1, -2 and -4 in theca but not granulosa cells from polycystic ovaries. (англ.) // Molecular human reproduction. - 2004. - Vol. 10, no. 7 . — P. 473—479. — DOI : 10.1093/molehr/gah066 . — PMID 15155816 .
  38. ↑ Munir I. , Yen HW , Geller DH , Torbati D. , Bierden RM , Weitsman SR , Agarwal SK , Magoffin DA Insulin augmentation of 17alpha-hydroxylase activity is mediated by phosphatidyl inositol 3-kinase but not extracellular signal-regulated kinase-1 / 2 in human ovarian theca cells. (English) // Endocrinology. - 2004. - Vol. 145, no. 1 . - P. 175-183. - DOI : 10.1210 / en.2003-0329 . - PMID 14512432 .
  39. ↑ Zacchè MM , Caputo L. , Filippis S. , Zacchè G. , Dindelli M. , Ferrari A. Efficacy of myo-inositol in the treatment of cutaneous disorders in young women with polycystic ovary syndrome. (English) // Gynecological endocrinology: the official journal of the International Society of Gynecological Endocrinology. - 2009. - Vol. 25, no. 8 . - P. 508-513. - DOI : 10.1080 / 09513590903015544 . - PMID 19551544 .
  40. ↑ Costantino D. , Minozzi G. , Minozzi E. , Guaraldi C. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. (English) // European review for medical and pharmacological sciences. - 2009. - Vol. 13, no. 2 . - P. 105-110. - PMID 19499845 .
  41. ↑ Krapels IP , Rooij IA , Wevers RA , Zielhuis GA , Spauwen PH , Brussel W. , Steegers-Theunissen RP Myo-inositol, glucose and zinc status as risk factors for non-syndromic cleft lip with or without cleft palate in offspring: a case-control study. (English) // BJOG: an international journal of obstetrics and gynaecology. - 2004. - Vol. 111, no. 7 . - P. 661–668. - DOI : 10.1111 / j.1471-0528.2004.00171.x . - PMID 15198755 .
  42. ↑ Groenen PM , Peer PG , Wevers RA , Swinkels DW , Franke B. , Mariman EC , Steegers-Theunissen RP Maternal myo-inositol, glucose, and zinc status is associated with the risk of offspring with spina bifida. (English) // American journal of obstetrics and gynecology. - 2003. - Vol. 189, no. 6 . - P. 1713-1719. - PMID 14710103 .
  43. ↑ Carlomagno G. , Unfer V. Inositol safety: clinical evidences. (English) // European review for medical and pharmacological sciences. - 2011. - Vol. 15, no. 8 . - P. 931-936. - PMID 21845803 .
  44. ↑ Akashi M. , Akazawa S. , Akazawa M. , Trocino R. , Hashimoto M. , Maeda Y. , Yamamoto H. , Kawasaki E. , Takino H. , Yokota A. Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats. (English) // Diabetes. - 1991. - Vol. 40, no. 12 . - P. 1574-1579. - PMID 1756898 .
  45. ↑ D'Anna R. , Scilipoti A. , Giordano D. , Caruso C. , Cannata ML , Interdonato ML , Corrado F. , Di Benedetto A. myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. (English) // Diabetes care. - 2013 .-- Vol. 36, no. 4 . - P. 854-857. - DOI : 10.2337 / dc12-1371 . - PMID 23340885 .
Source - https://ru.wikipedia.org/w/index.php?title=Mio-inositol&oldid=101589378


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