Inositol Powder

PCOS – Polycystic Ovarian Syndrome.

Effects of myo-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial.

Ciotta L, Eur Rev Med Pharmacol Sci. 2011 May;15(5):509

The administration of INOSITOL, a B complex vitamin, was associated with a decrease of serum testosterone and simultaneously, due to its ability to increase insulin sensitivity, women who received INOSITOL showed a great improvement of the ovulatory function. INOSITOL improved the oocyte’s quality and increases the number of oocytes collected after ovarian stimulation in patients undergoing IVF (in vitro fertilization). INOSITOL may be useful in the treatment of PCOS patients undergoing ovulation induction, both for its insulin-sensitizing activity, and its role in oocyte maturation.

Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial.

Costantino D,et al. Eur Rev Med Pharmacol Sci. 2009 Mar-Apr;13(2):105-10.

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.

Psychiatric conditions

Some preliminary results of studies on high-dose inositol supplements show promising results for people suffering from problems such as bulimia, panic disorder, obsessive-compulsive disorder (OCD), agoraphobia, and unipolar and bipolar depression (Palatnik A, Frolov K, Fux M, Benjamin J (2001). "Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder". Journal of Clinical Psychopharmacology 21 (3): 335–339. doi:10.1097/00004714-200106000-00014; Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, Kofman O, Belmaker RH. (1995). "Double-blind, controlled trial of inositol treatment of depression". American Journal of Psychiatry 152 (5): 792–794).

In a single double-blind study on 13 patients, myo-inositol (18 grams daily) has been found to reduce the symptoms of OCD significantly, with effectiveness equal to SSRIs and virtually without side-effects (Fux M, Levine J, Aviv A, Belmaker RH (1996). "Inositol treatment of obsessive-compulsive disorder". American Journal of Psychiatry 153 (9): 1219–21) In a double-blind, controlled trial, myo-inositol (18 grams daily) was superior to fluvoxamine for decreasing the number of panic attacks and other side-effects (Palatnik et al, 2001)

A double blind, placebo-controlled study of depressed patients showed that a high dose of inositol (12 grams daily) resulted in significant improvement of symptoms, with no changes noted in liver, kidney, or hematological function (Levine et al, 1995). A meta-analysis of randomized trials of inositol for depression was not able to determine if inositol is of benefit (Taylor MJ, Wilder H, Bhagwagar Z, Geddes J (2004). "Inositol for depressive disorders". In Taylor, Matthew J. Cochrane Database Syst Rev (2): CD004049. doi:10.1002/14651858.CD004049.pub2).

Older research suggests that lithium functions primarily by decreasing myo-inositol concentrations in bipolar patients; however, the conclusions of this research are unsupported and have been questioned (Silverstone, P. H.; McGrath, B. M.; Kim, H. (2005). "Bipolar disorder and myo-inositol: A review of the magnetic resonance spectroscopy findings". Bipolar Disorders 7 (1): 1–10. doi:10.1111/j.1399-5618.2004.00174.x; Harwood, AJ (2005). "Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited". Molecular Psychiatry 10: 117–126. doi:10.1038/sj.mp.4001618).

Other studies suggest that lithium treatment may further inhibit the enzyme inositol monophosphatase, leading to higher intracellular levels of inositol triphosphate (Einat H, Kofman O, Itkin O, Lewitan RJ, Belmaker RH (1998). "Augmentation of lithium's behavioral effect by inositol uptake inhibitors". J Neural Transm 105 (1): 31–8. doi:10.1007/s007020050035) an effect that was enhanced further by administration of an inositol triphosphate reuptake inhibitor.

Other conditions

Animal studies suggest inositol reduces the severity of the osmotic demyelination syndrome if given before rapid correction of chronic hypernatremia (Silver SM, Schroeder BM, Sterns RH, Rojiani AM (2006). "Myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats". J Neuropathol Exp Neurol 65 (1): 37–44. doi:10.1097/01.jnen.0000195938.02292.39) Further study is required before its application in humans for this indication.

Studies from in vitro experiments, animal studies, and limited clinical experiences, claim that inositol may be used effectively against some types of cancer, in particular, when used in combination with phytic acid (Vucenik, I; Shamsuddin, AM (2003). "Cancer inhibition by inositol hexaphosphate (IP6) and inositol: from laboratory to clinic.". The Journal of nutrition 133 (11 Suppl 1): 3778S–3784S).

Another small, placebo-controlled study has demonstrated that myo-inositol supplementation improves features of dysmetabolic syndrome in post-menopausal women, including triglycerides, HDL cholesterol, and diastolic blood pressure (Giordano D, Corrado F, Santamaria A, Quattrone S, Pintaudi B, DiBenedetto A, D’Anna R (2011). "Effects of myo-inositol supplementation in postmenopausal women with metabolic syndrome: a perspective, randomized, placebo-controlled study". Menopause: The Journal of The North American Menopause Society 18 (1): 102–104)

OCD: 18 Gms daily produced a mean improvement from baseline in six weeks over placebo

Bulimia & Binge Eating: 12 to 18 Gms daily showed significant effects on Clinical Global Impression scale.

Panic: 12 Gms daily produced significant reduction in attacks (all above: Belmaker et al., 2002) 

Depression: 15 Gms daily, an overall improvement in scores on the Hamilton. Depression Rating Scale was significantly greater for inositol than for placebo at week 4. No changes were noted in hematology or in kidney or liver function (Levine et al., 1995).

Inositol is a naturally occurring isomer of glucose, though it is generally considered to be a member of the B vitamin family. It is a key intermediate in the intracellular phosphatidyl inositol second messenger pathway activated by numerous serotonergic, cholinergic, and noradrenergic receptors (Belmake et al., 1995). In this capacity, it serves as an important signal transduction molecule, but inositol is also a structural component of cellular membrane phospholipids. (Hooper, 1997) Research indicates that inositol is an effective and safe option in the treatment of panic disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, binge eating and/or depression (Levine J, 1997, Levine et al., 1995, Benjamin et al., 1995a, Benjamin et al., 1995b, Gelber et al., 200, Levine et al., 1995, Benjamin et al., 1995a, Benjamin et al., 1995b, Gelber et al., 2001, Palatnik et al., 2001, Fux et al., 1996). Inositol's efficacy, in the absence of side effects, makes this nutrient an attractive addition to treatment plans for specific mood disorders. Inositol occurs naturally as phytic acid in the fiber component of numerous plant foods, especially whole grains, citrus fruit, nuts, and seeds, and as myo inositol in meat. In the intestinal tract, bacteria break down phytic acid into bioavailable inositol that is easily absorbed via the intestinal epithelium. Myo inositol is found to bioaccumulate most abundantly in the central nervous system, supporting a role for it in neurological function. 

Depression

Depressive patients generally have decreased levels of inositol in their cerebrospinal fluid (Levine J, 1997). Researchers now theorize that inositol produces positive clinical results in patients with depression due to intracellular phosphatidyl inositol serving as a second messenger for 5-hydroxytryptamine (5-H [T.sub.2]) receptor-signaling mechanisms. Serotonin selective reuptake inhibitors (SSRIs), a family of drugs commonly used to treat depression, have a similar therapeutic profile to inositol in that they inhibit serotonin reuptake in the synaptic cleft (Levine et al., 1999).

25-75% of patients with panic disorder discontinue drug treatment because of side effects, and these patients quickly relapse (Palatnik et al., 2001). This has led researchers to study the effects of inositol on patients suffering from this condition.

In one study, (Benjamin et al., 1995a) twenty-one patients diagnosed with panic disorder with or without agoraphobia were given 12 grams of inositol per day or placebo. In the treatment group, the severity and frequency of panic attacks declined significantly with minimal associated side effects. The average number of panic attacks per week in patients treated with inositol fell from 10 to 3.5 per week. The researchers concluded that these results were "clinically meaningful" in the management of panic attacks.

More recently, inositol was compared with the antidepressant fluvoxamine in the treatment of panic disorder (Palatnik et al., 2001). This study represents a more stringent test of the effects of inositol in treating panic disorder because it is the first to compare inositol with an established antidepressant drug. In this study of 20 patients with panic disorder, inositol was found to be slightly but significantly more effective than fluvoxamine in reducing the number of panic attacks (p<0.049). Otherwise, it was comparable to fluvoxamine on all other measures (HAS, phobia, and Clinical Global Impression (CGI) Scale). Since inositol appears to be as effective as fluvoxamine, patients may prefer it and continue to take it for the long term because side effects are extremely rare and mild.

Bulimia nervosa and Binge Eating

Gelber et al. 2001 conducted a double-blind crossover trial comparing 18 g inositol to placebo in 12 patients with bulimia nervosa and binge eating. They took each test substance for 6 weeks. Inositol was significantly better than placebo on the Global Clinical Impression, the Visual Analogue Scale, and the Eating Disorders Inventory. The study concluded, "Inositol is as therapeutic in patients with bulimia nervosa and binge eating as it is in patients with depression and panic and obsessive-compulsive disorders."

Carey et al. 2004 has recently demonstrated in 14 patients with OCD that improvement during inositol treatment parallels specific single photon emission computed tomography (SPECT) changes in certain areas of the brain. These findings suggest inositol's clinical effects are mediated through neuronal circuitry that is different from those involved with the SSRIs, implying an "overlapping but distinct mechanism of action."

Brink et al. 2004 explored the mechanism of action of mI in depression and related anxiety disorders, found both similarities and differences in the effects of myo-inositol (mI), fluoxetine and imipramine on serotonin 5HT2A and muscarinic acetylcholine receptors in human neuroblastoma cells. These findings may help to explain why mI seems to be effective exclusively in selective serotonin reuptake inhibitor-sensitive disorders.

Conclusion: Inositol's clinical efficacy coupled with the absence of significant side effects suggests that this nutrient may be an attractive addition to treatment plans for patients suffering from panic disorder, clinical depression, and/or obsessive-compulsive disorder. 

References

Belmaker RH, Bersudsky Y, Benjamin J, Agam G, Levine J, Kofman O. Manipulation of inositol-linked second messenger systems as a therapeutic strategy in psychiatry. Adv Biochem Psychopharmacol 1995. 49: 67-84. 

Benjamin J, Levine J, Fux M, Aviv A, Levy D, Belmaker RH. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. Am J Psychiatry 1995a. 152(7): 1084-1086. 

Benjamin J, Agam G, Levine J, Bersudsky Y, Kofman O, Belmaker RH. Inositol treatment in psychiatry. Psychopharmacol Bull 1995b. 31(1): 167-175. 

Brink CB, Viljoen SL, de Kock SE, Stein DJ, Harvey BH. Effects of myo-inositol versus fluoxetine and imipramine pretreatments on serotonin 5HT2A and muscarinic acetylcholine receptors in human neuroblastoma cells. Metab Brain Dis. 2004. 19(1-2):51-70.

Carey PD, Warwick J, Harvey BH, Stein DJ, Seedat S. Single photon emission computed tomography (SPECT) in obsessive-compulsive disorder before and after treatment with inositol. Metab Brain Dis. 2004. 19(1-2):125-34. 

Fux M, Levine J, Aviv A, Belmaker RH. Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry 1996. 153(9): 1219-1221. 

Gelber D, Levine J, Belmaker RH. Effect of inositol on bulimia nervosa and binge eating. Int J Eat Disord. 2001. 29(3):345-8. 

Hooper, N. Glycosyl-phosphatidylinositol anchored membrane enzymes. Clin Chim Acta 1997. 266(1): 3-12. 

Levine, J. Controlled trials of inositol in psychiatry. Eur Neuropsychopharmacol 1997. 7(2): 147-155. 

Levine J, Barak Y, Gonzalves M, Szor H, Elizur A, Kofman O, Belmaker RH. Double blind, controlled trial of inositol treatment of depression. Am J Psychiatry 1995. 152(5): 792-794. 

Levine J, Mishori A, Susnosky M, Martin M, Belmaker RH. Combination of inositol and serotonin reuptake inhibitors in the treatment of depression. Biol Psychiatry 1999. 45(3): 270-273. 

Palatnik A, Frolov K, Fux M, Benjamin J. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharmacol 2001. 21(3): 335-339.