Myoinositol is a natural supplement found to be useful in PCOS as an insulin sensitizer.1,11,27,28
One serving (4 capsules) contains 2g myo-inositol, 0.5 mg L-tyrosine, 0.2 mg folic acid, 55 mcg selenium, and 40 mcg chromium.
Supplementation with inositols, both myo-inositol (MI) and D-chiroinositol (DCI), a natural insulin sensitizer, in women with PCOS has been evaluated over the last decade2,3. Inositols are incorporated into cell membranes as phosphatidyl-MI, which is a precursor of inositol triphosphate (InsP3). They act as an intracellular second messenger and regulate several hormones such as thyroid-stimulating hormone (TSH), follicle stimulating hormone (FSH), and insulin4.
Myoinositol Myoinositol is the most abundant form of inositol in humans. Epimerase, an insulin-dependent enzyme, converts MI into DCI, depending on the specific needs of the tissue for these two molecules5. Myo-inositol is not only a prominent component of membrane-incorporated phosphatidylinositol, but participates with its isomers to a multitude of cellular processes, including ion channel permeability, metabolic homeostasis, mRNA export and translation, cytoskeleton remodeling, stress response6. The role of inositols in women with PCOS can be attributed to deficiency of inositols, which are mediators of insulin activity7. It is well established that different tissues have different ratios of MI/DCI and, in the case of PCOS patients, the conversion is impaired due to insulin-resistance (IR)8. It is reported that the inositols can reduce insulin resistance, improve ovarian function, and reduce androgen levels, thus enhancing the reproductive impairments associated with PCOS9,10. Moreover, the administration of MI is a safe and effective method to prevent and correct metabolic disorders in teenagers affected by PCOS with cutaneous disorders11.
L-tyrosine is a nonessential amino acid synthesized in the body from phenylalanine. L-tyrosine is found in many dietary sources, including lean proteins such as chicken, eggs, fish and whole grain oats, and dairy products including milk, cheese, and yoghurt. L-tyrosine is the precursor of thyroid hormones and many other neurotransmitters like adrenaline, noradrenaline, serotonin, and dopamine. It also helps in the production of melanin and in the function of organs in the body responsible for making and regulating hormones, including the adrenal, thyroid, and pituitary glands12. All these hormones regulate mood, therefore L-tyrosine is claimed to act as an effective antidepressant13.
Tyrosine kinase signaling pathways are integral parts of the mammalian ovulatory process but do not involve actions on the synthesis of steroids, plasminogen activator or prostaglandins14. The study conducted on the old female rats has shown that when they were given L-tyrosine they would have had their regular menstrual cycle and ovulation15
As L-tyrosine binds to free radicals, that can potentially cause damage to the cells and tissues, it is considered to work as a mild antioxidant. Findings from a range of clinical studies using allergy vaccines containing L-tyrosine showed the lack of toxicity seen in animal studies and they have showed evidence of enhanced immunostimulatory activity.
The absence of toxicological concerns in these findings supports the hypothesis that L-tyrosine is a safe adjuvant for human use16. In the United States L-tyrosine is Generally Recognized as Safe (GRAS). The Food and Nutrition Board of the Institute of Medicine reports that for every 1 g of protein in the diet, the body needs 47 mcg of tyrosine. Based on these recommendations, women need to intake 46 g of proteins; therefore, they need 2.2 g of tyrosine daily17. No exact dietary supplement recommendation for tyrosine exists. It just depends on diet, overall health, and what are the symptoms the patients are dealing with.
Selenium (Se) is a trace element that is naturally presented in many foods, like organic lean meat, fish, Brazil nuts, cheese, eggs, nutritional yeast, liver, butter, cold water fish, alliums, mushrooms, tomatoes, green vegetables18. Selenium, which is nutritionally essential for humans, plays a critical role in reproduction, DNA synthesis, protection from oxidative damage, and infection19. It is crucial for the several enzymes involved in thyroid function. What is more, it has been found that selenium diminishes thyroid autoantibody levels20. Selenium supplementation among PCOS women resulted in beneficial effects on reproductive outcomes21. The RDA for women is 55 mcg that rise in case of pregnancy to 60 mcg.
Chromium Picolinate (CrPic) is a widely used nutritional supplement for optimal insulin function22. Apparently, it has a role in maintaining proper carbohydrate and lipid metabolism in mammals23. As this role probably involves potentiation of insulin signaling, chromium dietary supplementation has been postulated to potentially have effects on body composition, including reducing fat mass and increasing lean body mass, especially in women with PCOS24.
The synergistic action of myoinositol, L-tyrosine, selenium, and chromium has been clinically studied for menstrual cycle re-initiation and ovulation, improvement of hyperandrogenism, and improvement of BMI in PCOS patients.1,11,27,28
One study11 involved 25 participants with PCOS and issues with infertility. Of the 25 participants, 88 percent had restored menstrual cycles, 72 percent achieved normal ovulation, and 40 percent actually became pregnant after treatment with Myo-inositol combined with folic acid for six months.
In a controlled clinical study performed in 2013,27 50 overweight patients with PCOS underwent a hormonal evaluation and glucose tolerance test before 12 weeks of therapy and then again after treatment with Myo-inositol and folic acid. In all patients, insulin and testosterone levels were reduced after treatment and menstrual cycles were restored.
A comparative study published in 201728 found that a combination of myoinositol and folic acid seemed to be as effective for PCOS as treatment with metformin. In that particular comparative study, both groups had similar beneficial outcomes: serum progesterone levels dropped, pregnancy rates increased, and menstrual cycle disorders seemed to stabilize. It is worth noting that even though both metformin and myoinositol may have similar efficacy, myoinositol is considered to be related to far fewer and far less worrisome side effects.
One hundred and eighty-six women, with a PCOS diagnosis, were divided in four groups according to their clinical features.1
Phenotype A: androgen excess + ovulatory dysfunction + polycystic ovarian morphology.
Phenotype B: androgen excess + ovulatory dysfunction.
Phenotype C: androgen excess + polycystic ovarian morphology.
Phenotype D: ovulatory dysfunction + polycystic ovarian morphology.
All patients were given a compound with 2 g myo-inositol, 0.5mg of L-Tyrosine, 0.2mg of folic acid, 55 mcg of selenium and 40 mcg of chromium daily for 6 months. Hormonal assessment, BMI, Ferriman-Gallway Gallway score, HOMA index, and follicular monitoring were reported before starting the therapy, three months and six months after.
Phenotype A: showed an improvement, consistent with restored ovulation: more regular length of the menstrual cycle, detection of periovulatory follicle at ultrasound, and rising of progesterone in the luteal phase. A total of 45 patients (65.2%) ovulated after six months. In the same period glucose and HOMA index decreased.
Phenotype B: 80% of patients ovulated after six months. An improvement of the clinical and biochemical sign of hyperandrogenism was also reported.
Phenotype C: after BMI had followed the treatment for six months, it decreased in a statistically significant manner.
Phenotype D: 49 out of 82 women (59.7%) restored their regular menstrual period and ovulated.
Myoinositol - 2 g myo-inositol, 0.5 mg L-tyrosine, 0.2 mg folic acid, 55 mcg selenium, and 40 mcg chromium was studied as a once daily treatment over a 6 month period for symptomology of PCOS.1
In the clinical studies of the combination supplement, side effects reported were gastrointestinal symptoms, such as nausea, heartburn, but are rare.
Based on individual ingredients, other side effects can include tiredness, headache, dizziness in some people; blood clotting problems, muscle tenderness, mood changes
Folic acid: methotrexate (moderate), sulfasalazine (minor)
Selenium: anticoagulants/antiplatelets (moderate), statins (moderate), niacin (moderate), barbiturates (moderate), birth control pills (minor)
Chromium: insulin (moderate), levothyroxine (moderate), NSAIDs (minor)
L-Tyrosine: levodopa (moderate), thyroid hormone (moderate)
Inositol: no information for drug interactions with inositol
Inositol is generally regarded as safe and can be used in pregnancy.25
Safety and effectiveness have not been established in this population and should be avoided.
Safety and effectiveness have not been established in pediatric patients and should be avoided.
- Oliva M, Zuev V. Efficacy of the synergic action of myoinositol, tyrosine, selenium and chromium in women with PCOS. Eur Rev Med Pharmaciol Sci 2019;23:8687-8694.
- Bizzarri M, Carlomagno g. Inositol: history of an effective therapy for polycystic ovary syndrome. Eur Rev Med Pharmacol Sci 2014; 18: 1896-1903.
- Milewska em, Czyzyk A, Meczekalski B, Genazzani ad Inositol and Human reproduction. From cellular metabolism to clinical use. Gynecol Endocrinol 2016; 32: 690-695.
- Thomas RM, Nechamen CA, Mazurkiewicz Je, Ulloa-aguirre A, Dias JA. The adapter protein AP-
- PL1 links FSH receptor to inositol 1,4,5-trisphosphate production and is implicated in intracellu- lar Ca(2+) mobilization. Endocrinology 2011; 152: 1691-1701.
- Heimark D, mcallister J, larner J. Decreased myo-inositol to chiro-inositol (M/C) ratios and in- creased M/C epimerase activity in PCOS the- ca cells demonstrate increased insulin sensitivity compared to controls. Endocr J 2014; 61: 111-117.
- Bizzarri m. Fuso a. Dinicola s. Cucina a. Bevilac- Qua a. Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease. Expert Opin Drug Metab Toxicol 2016; 12: 1181-1196.
- Nestler Je, jakubowicz DJ, reamer P, gunn rd, al- lan g. Ovulatory and metabolic effects of D-chi- roinositol in the polycystic ovary syndrome. N En- gl J Med 1999; 340: 1314-1320.
- Unfer v, carlomagno g, papaleo e, vailati s, can- Diani m, Baillargeon JP. Hyperinsulinemia alters myoinositol to d-chiroinositol ratio in the follicular fluid of patients with PCOS. Reprod Sci 2014; 21: 854-858.
- Facchinetti F, Bizzarri m, Benvenga s, d’anna r, lan- zone a, soulage c, Di renzo gc, hod m, cavalli P, chiu TT, Kamenov za, bevilacqua a, carlomagno g, gerli s, oliva mm, devroey P. Results from the international consensus conference on myo-inositol and d-chiro-inositol in obstetrics and gynecol- ogy: the link between metabolic syndrome and PCOS. Eur J Obstet Gynecol Reprod Biol 2015; 95: 72-76.
- Papaleo e, unfer v, Baillargeon JP, De santis l, Fusi F, brigante c, marelli g, cino i, redaelli a, Ferrari a. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol 2007; 23: 700-703.
- Pkhaladze l, barbakadze l, kvashilava n. Myo-Ino- sitol in the treatment of teenagers affected by PCOS. Int J Endocrinol 2016; 2016: 1473612.
- Venegas-meneses B, padilla JF, Juárez ce, morán Jl, morán c, rosas-murrieta nh, handal a, Domínguez r. Effects of ovarian dopaminergic receptors on ovulation. Endocrine 2015; 50: 783-796.
- Jongkees BJ, Hommel B, KüHn s, colzato ls. Ef- fect of tyrosine supplementation on clinical and healthy populations under stress or cognitive de- mands--A review. J Psychiatr Res 2015; 70: 50- 57.
- Matousek m, mikuni m, mitsube K, yoshida m, Bränn- ström m. Inhibition of ovulation by tyrosine kinase inhibitors in the in vitro perfused rat ovary. J Re- prod Fertil 1999; 117: 379-385.
- Cooper rl, linnoila m. Effects of centrally and sys- temically administered L-tyrosine and L-leucine on ovarian function in the old rat. Gerontology 1980; 26: 270-275.
- Baldrick P, richardson D, wheeler aw. Review of L-tyrosine confirming its safe human use as an adjuvant. J Appl Toxicol 2002; 22: 333-344.
- Van De rest o, bloemendaal m, De Heus r, aarts e. Dose-dependent effects of oral tyrosine adminis-8693
- Kieliszek M, błażejak s. Current knowledge on the importance of selenium in food for living organ- isms: a review. Molecules 2016; 21. Pii: E609.
- Negro r. Selenium and thyroid autoimmunity. Bi- ologics 2008; 2: 265-273.
- Razavi m, Jamilian m, kashan zf, heidar z, mohseni m, ghandi Y, bagherian T, asemi z. Selenium sup- plementation and the effects on reproductive out- comes, biomarkers of inflammation, and oxidative stress in women with polycystic ovary syndrome. Horm Metab Res 2016; 48: 185-190.
- Kowalczyk K, franik g, kowalczyk D, pluta D, bluk- Acz, madej P. Thyroid disorders in polycystic ovary syndrome. Eur Rev Med Pharmacol Sci 2017; 21: 346-360.
- Vincent JB. The potential value and toxicity of chromium picolinate as a nutritional supplement, weight loss agent and muscle development agent. Sports Med 2003; 33: 213-230.
- Broadhurst cl, Domenico P. Clinical studies on chromi- um picolinate supplementation in diabetes mellitus-a review. Diabetes Technol Ther 2006; 8: 677-687.
- Fazelian s, rouhani mh, bank ss, amani r. Chromium supplementation and polycystic ovary syndrome: a systematic review and meta-analysis. J Trace Elem Med Biol 2017; 42: 92-96.
- Carlomagno G, Unfer V. Inositol safety: Clinical evidences. Eur Rev Med Pharmacol Sci. 2011;15:931–6.
- Artini PG, Di Berardino OM, Papini F, Genazzani AD, Simi G, Ruggiero M, Cela V. Endocrine and clinical effects of myo-inositol administration in polycystic ovary syndrome. A randomized study. Gynecol Endocrinol. 2013 Apr;29(4):375-9. doi: 10.3109/09513590.2012.743020. Epub 2013 Jan 22.
- Nas K, Tűű L. A comparative study between myo-inositol and metformin in the treatment of insulin-resistant women. Eur Rev Med Pharmacol Sci. 2017 Jun;21(2 Suppl):77-82.
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