SUPPLEMENT MONOGRAPHS MYO-INOSITOL /433 Kuo YC, Tsai WJ, Shiao MS, et al. Cordyceps sinensis as an immunomodulatoryagent. Am J Chin Med. 1996; 24: 111-125. Myo- Inositol Ladanyi A, Timar J, Lapis K. Effect of lentinan on macrophage DESCRIPTION cytotoxicity against metastatic tumor cells. Cancer Immunol Myo-inositol, the major nutritionally active form of inositol, Immunother. 1993; 36: 123-126. is vital to many biological processes of the body, participat- ing in a diverse range of activities. Myo-inositol is one of Levy AM, Kita H, Phillips SF, et al. Eosinophilia and nine distinct isomers of inositol. It is essential for the growth gastrointestinal symptoms after ingestion of shiitake mushrooms. of rodents, but not for most animals, including humans. J Allergy Clin Immunol. 1998; 101:613-620. Humans can make myo-inositol endogenously, which they Manzi P, Pizzoferrato L. Beta-glucans in edible mushrooms. do from glucose, and, even though myo-inositol is sometimes Food Chemistry. 2000; 68:315-318. referred to as a vitamin, it is not a vitamin for humans or most animals. However, the dietary intake of myo-inositol Matsuoka H, Seo Y, Wakasugi H, et al. Lentinan potentiates can influence the levels of circulating and bound myo- immunity and prolongs the survival time of some patients. inositol in the body and may influence certain biological Anticancer Res. 1997; 17:2751-2755. activities. Nutritional supplementation of this cyclitol may Mitamura T, Sakamoto S, Suzuki S, et al. Effects of lentinan affect behavior and may have anti-depressant and anti- on colorectal carcinogenesis in mice with ulceractive colitis. anxiety activities~ For more information on Inositol supple- Oncol Rep. 2000; 7:559-60 I. mentation, see Inositol Hexanicotinate. Mizuno M, Minato K, Ito H, et al. Anti-tumor polysaccharide Myo-inositol intake from the average diet is approximately from the mycelium of liquid-cultured Agaricus blazei mill. one gram daily. The major dietary forms of myo-inositol are Biochem Mol BioI Int. 1999; 47:707-714. inositol hexaphosphate or phytic acid, which is widely found Murata T, Hatayama I, Kakizaki I, et al. Lentinan enhances in cereals and legumes and associated with dietary fiber, and sensitivity of mouse colon 26 tumor to cis- myo-inositol-containing phospholipids from animal and plant diamminedichloroplatinum (II) and decreases glutathionine sources. transferase expression. Jpn J Cancer Res. 1996; 87: 1171-1178. Myo-inositol is also known as inositol, hexahydroxycyclo- Nakano H, Namatame K, Nemoto H, et al. A multi-institutional hexane, cyclohexanehexol, mouse antialopecia factor and, prospective study of 1entinan in advanced gastric cancer patients chemically, as cis-l,2,3,5-trans-4,6-cyclohexanehexol. Myo- with unresectable and recurrent diseases: effect on prolongation inositol is abbreviated as Ins and sometimes as just 1. It is of survival and improvement of quality of life. Kanagawa represented by the following chemical structure: . Lentinin Research Group. Hepatogastroenterology.1999; 46:2662-2668. HO OH Nakumara T. Shiitake (Lentinus edodes) dermatitis. Contact Dermatitis. 1992; 27:65-70. Shouji N, Takada K, Fukushima K, Hirasawa M. Anticaries effect of a component from shiitake (an edible mushroom). Caries Res. 2000; 34:94-98. Tari K, Satake I, Nakagomi K, et al. [Effect of lentinan for advanced prostate carcinoma.] [Article in Japanese.] Hinyokika myo-Inositol Kiyo. 1994; 40:119-123. Another naturally occurring isomer of inositol, D-chiro- Wan K. [Effects of lentinan of peripheral blood mononuclear inositol, has been. found to have activity against insulin cell expression of interleukin-2 receptor in patients with chronic resistance. However, at present, D-chiro-inositol is neither hepatitis B in vivo and in vitro.] [Article in Chinese.] Hunan I available as a nutritional supplement nor as a drug. A Ko Ta Hsueh Hsueh. 1998; 23:90-92. hexanicotinate conjugate of myo-inositol, inositol niacinate Wasser SP, Weis AL. Therapeutic effects of substances or inositol nicotinate, is available in Europe as'a drug for the occurring in higher Basidiomycetes mushrooms: a modern treatment of circulatory problems. pr?spective. Crit Rev Immunol. 1999; 19:65-96. ACTIONS AND PHARMACOLOGY Yoon SY, Eo SK, Kim YS, et al. Antimicrobial activity of ACTIONS Ganoderma lucidum extract alone and in combination with Myo-inositol may have antidepressant and antianxiety some antibiotics. Arch Pharm Res. 1994; 17:438-442. activity. 434/ MYO-INOSITOL PDR FOR NUTRITIONAL SUPPLEMENTS MECHANISM OF ACTION RESEARCH SUMMARY The mechanism of action of myo-inositol has yet to be fully Inositol levels in cerebrospinal fluid are decreased, compared elucidated. However, much is known about the biological with general populations, in many suffering from depression. roles of myo-inositol and some speculation can be made. In one double-blind study, 28 depressed patients received Myo-inositol is metabolized to phosphatidylinositol, which placebo or high-dose (12 grams daily) myo-inositol for four makes up a small, but very significant, component of cell weeks. Overall, significant improvement was achieved in the membranes. Phosphatidylinositol can be converted to phos- treatment group but not in the placebo group. There was phatidylinositol-4,5-bisphosphate, a key intermediate in bio- improvement in both monopolar and bipolar depression in logical signaling. Phosphatidylinositol-4,5-bisphosphate is this pilot study. Myo-inositol, however, was not shown, in the precursor of at least three second-messenger molecules. another study, to enhance or speed the response of depressed These are inositol- I,4,5-triphosphate, which modifies intra- subjects to SSRls (selective serotonin reuptake inhibitors). cellular calcium levels, diacylglycerol, which regulates some More research is needed in this area. members of the protein kinase C family, and phosphatidyl- inositol-3,4,5-triphosphate, which is involved in signal In another double-blind study, 21 patients with panic transduction. disorder, with or without agoraphobia, received 12 grams daily of myo-inositol or placebo for four weeks. Again, the Some of the second-messenger activity is related to activa- treated group, overall, achieved improvement (frequency and tion of serotonin receptors. It is hypothesized that the severity of both panic attacks and agoraphobia declined mechanism of action of myo-inositoI's possible benefit in the significantly), compared with no significant improvement in management of depression, panic attacks and obsessive- the placebo group. compulsive behavior may be explained by myo-inositoI's role as a second-messenger precursor. And in a third double-blind study, this one with a crossover component, 13 patients with obsessive-compulsive disorder PHARMACOKINETICS (OCD) received 18 grams of inositol or placebo for six Myo-inositol is absorbed from the small intestine following weeks each. Subjects improved significantly more, as ingestion and is transported by the portal circulation to the reflected by significantly lower scores on the Yale-Brown liver and then by the systemic circulation to various tissues Obsessive Compulsive Scale, when taking myo-inositol than in the body, including the brain. Myo-inositol crosses the when taking placebo. Myo-inositol, in a subsequent study, blood-brain barrier. did not enhance the effects of SSRls in subjects with treatment-refractory OCD. Again, more research is needed to Within the liver and the various tissues of the body, myo- confirm and further elucidate myo-inositoI's role in treating inositol enters into a wide range of diverse biochemical OCD. Its effectiveness, to the extent demonstrated to date, pathways. Myo-inositol reacts with CDP-diacylglycerol to combined with its general lack of serious side effects, make form the phospholipid phosphatidylinositol, which can be it an attractive potential therapy in these psychiatric incorporated into membrane structure. Phosphatidylinositol, disorders. via kinase reactions, forms phosphatidyl-4,5-bisphosphate, which is the precursor to inositol- I,4,5-triphosphate, diacyl- Myo-inositol has not demonstrated the same promise in glycerol, phosphatidylinositol-3,4,5-triphosphate, myo-inosi- Alzheimer's disease, autism, schizophrenia and electrocon- tol 1,3,4-triphosphate and myo-inositol 1,3,4,5-tetrakis- vulsive therapy-induced memory impairment. Studies related phosphate, among others. The myo-inositol phosphates can to these conditions have produced negative results. And in be dephosphorylated via phosphatases. children with attention deficit disorder, myo-inositol aggra- vated rather than ameliorated symptoms in one small study. It is believed that the mechanism of action of lithium is due, in part, to its inhibition of the phosphatase that converts myo- In general, it appears that myo-inositol may be effective in inositol-monophosphate back to myo-inositol. many of the same disorders in which the SSRls have shown some usefulness. This may not be surprising since myo- INDICATIONS AND USAGE inositol has been shown to help reverse desensitization of Myo-inositol has exhibited positive effects in a number of serotonin receptors. studies related to depression, panic attacks and obsessive- compulsive disorder. On the other hand, it generally has not Myo-inositol is also being investigated for possible use in been effective in treating Alzheimer's disease, autism, pediatric respiratory depression syndrome and for prevention schizophrenia and electroconvulsive therapy-induced memo- of neural tube defects.