Inositol is molecularly made up of nine steroisomers. Myo-inositol is the most active and studied steroisomer, and the one we will refer to in this article. It was once classified as a B-vitamin, but is now believed to be non-essential, as the body can synthesize it in adequate amounts from glucose.
The most compelling evidence for inositol as a supplement is in the treatment of polycystic ovarian syndrome (PCOS), with less conclusive evidence suggesting a use in anxiety, panic attacks, depression, and OCD. The way it works in PCOS is interesting, but not the subject of this article. If the reader is curious about this subject, they are encouraged to carry out their own research. It has also been shown in studies to be effective against psoriasis brought on by lithium treatment.
Because only large doses (6-14g) have been seen to be effective in anxiety disease models, it is a relatively unpopular supplement, that needs a very large dosage. Luckily, it is cheap and the powder has a pleasant sweet taste so it is easy to consume. There is some compelling but inconclusive evidence to suggest high doses of inositol may be effective for anxiety and certain anxiety-driven disorders.
Inositol and Normal Organ Function
Inositol is synthesized by the kidneys, from glucose, and in amounts around a few grams daily. It’s unclear whether PCOS, anxiety, and OCD involve a deficiency in inositol, or whether inositol has effects against these conditions due to other mechanisms only involved at supernormal or “mega” doses.
It is unclear why normal doses of 1-3g are not as statically effective for anxiety as seen in the mega-dose groups. This would suggest no role of inositol deficiency in these anxiety disorders. Therefore, it is implicated that enhanced inositol supplementation has some anterior mechanisms to the anxiolytic effects.
Inositol is involved in processes as diverse as insulin signaling, fat oxidation, cytoskeletal assembly, guiding branching of dendrites and axons, maintaining cell membrane gradient including calcium, chromatin uncoupling and gene expression. It is possible that enhancing some these functions or processes causes inositol to bring relief to anxiety. Scientists may not yet completely know the full mechanisms of inositol in these high doses. More research needs to be conducted.
Inositol: Anxiety, Panic Attacks, Depression, and OCD
As for therapy or treatment, the strongest evidence for inositol is in its use against PCOS and associated infertility. Next strongest evidence is against anxiety and panic attacks, with somewhat weaker evidence in treating depression and OCD.
It seems to be more effective against severe stressors, and less effective against mild stressors . So its effect against chronic mild stress may be weak. Its mechanism against severe anxiety may be in part due to conservation of lithium ions [4a]. Lithium can alleviate tricyclic-resistant panic and anxiety . It could also be due to increased GABA-A receptor function[4b]. GABA dysfunction is associated with anxiety, and the most common anxiety medicines, benzodiazepines, act on the GABA-A receptor sites. Inositol’s’ mechanism could involve the calcium gradient or growth of axons or dendrites.
The mechanisms of alleviating OCD are even less clear, but seem to be independent of the serotonin pathways involved in SSRI-treatment , and may involve cytoskeletal assembly or control of calcium gradient.
Inositol and Nutrient Absorption, a Potential Side Effect
Side effects of inositol supplementation may include diarrhea, dizziness, flushing, itching; loss of appetite, nausea, upset stomach, and vomiting.
Concerns have also been raised as to nutrient absorption, because phytate (found in beans) bears structural similar to inositol, and phytate is a known “chelator” of useful metals, including magnesium . Inositol may interfere with nutrient absorption by “chelating” metals, or forming a weak bond with metals and carrying them to the liver and kidneys for excretion. Because of its properties as a chelator, inositol may be effective against heavy metal toxicity, including lead, mercury, chromium, and nickel . By the same token, it may also leech useful metals away, including magnesium, calcium, and selenium. With long-term treatment, it would be wise to regularly monitor these levels via blood tests.
Although the concerns may be exaggerated, it is wise to monitor blood vitamin levels if considering prolonged, high dose inositol therapy. Other suspected “anti-nutrients” include phytates, oxalates and salicylates. These occur in legumes, vegetables and fruits at levels which do not normally interfere with nutrient absorption.
One reason inositol may not be totally effective against anxiety is by interfering with magnesium absorption. Magnesium deficiency has been linked to increased anxiety, and supplementation is associated with reduced anxiety. Short of blood tests, a magnesium and calcium supplement can be recommended. A diet optimized in zinc and selenium may also be a good idea. These important metals tend to be the most easily chelated.
 Effect of dietary phytate on magnesium bioavailability and liver oxidant status in growing rats. http://www.ncbi.nlm.nih.gov/pubmed/10069480
 Use of inositol triphosphate in the treatment of metal intoxication. http://www.google.com/patents/EP0252227A2?cl=en
 Inositol: Anxiety and Panic Disorders. http://examine.com/supplements/inositol/#summary3-3
[4a] Mechanism of inositol monophosphatase, the putative target of lithium therapy. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC44077/
[4b] Myo-inositol treatment and GABA-A receptor subunit changes after kainate-induced status epilepticus. http://www.ncbi.nlm.nih.gov/pubmed/22986984
 Rapid response of a disorder to the addition of lithium carbonate: panic resistant to tricyclic antidepressants. http://www.ncbi.nlm.nih.gov/pubmed/3085912
 Single photon emission computed tomography (SPECT) in obsessive-compulsive disorder before and after treatment with inositol. http://www.ncbi.nlm.nih.gov/pubmed/15214512
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