View source for Inositol

{{short description|Carbocyclic sugar}}
{{Chembox
| Watchedfields = changed
| verifiedrevid = 464369619
| Name = ''myo''-Inositol
| Reference =<ref>{{cite book |title=Merck Index |edition=11th |page=4883}}</ref>
| ImageFile = Inositol.svg
| ImageSize = 125px
| ImageName = ''myo''-Inositol
| ImageFile1 = Myo-inositol numbering.svg
| ImageSize1 = 160px
| ImageName1 = ''myo''-Inositol
| ImageFile2 = Myo-inositol-from-xtal-side-3D-bs-17.png
| IUPACName = ''myo''-Inositol
| SystematicName = (1''R'',2''S'',3''r'',4''R'',5''S'',6''s'')-Cyclohexane-1,2,3,4,5,6-hexol
| OtherNames = ''cis''-1,2,3,5-''trans''-4,6-Cyclohexanehexol<br />Cyclohexanehexol<br />Mouse antialopecia factor<br />Nucite<br />Phaseomannite<br />Phaseomannitol<br />Rat antispectacled eye factor<br />Scyllite <small>(for the isomer ''scyllo''-inositol)</small><br />Vitamin B<sub>8</sub>
|Section1={{Chembox Identifiers
| IUPHAR_ligand = 4495
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10239179
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 4L6452S749
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1222251
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D08079
| InChI = 1/C6H12O6/c7-1-2(8)4(10)6(12)5(11)3(1)9/h1-12H/t1-,2-,3-,4+,5-,6-
| InChIKey = CDAISMWEOUEBRE-GPIVLXJGBG
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C6H12O6/c7-1-2(8)4(10)6(12)5(11)3(1)9/h1-12H/t1-,2-,3-,4+,5-,6-
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CDAISMWEOUEBRE-GPIVLXJGSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 87-89-8
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 17268
| SMILES = O[C@@H]1[C@@H](O)[C@H](O)[C@H](O)[C@H](O)[C@H]1O
| PubChem = 892
  }}
|Section2={{Chembox Properties
| C=6 | H=12 | O=6
| MolarMass = 180.16 g/mol
| Density = 1.752 g/cm<sup>3</sup>
| MeltingPtC = 225 to 227
| MeltingPt_notes =
}}
| Section4       = {{Chembox Thermochemistry
| Thermochemistry_ref =<ref>{{cite journal |last1=Knyazev |first1=A.V. |last2=Emelʹyanenko |first2=V.N. |last3=Shipilova |first3=A.S. |last4=Zaitsau |first4=D.H. |last5=Lelet |first5=M.I. |last6=Knyazeva |first6=S.S. |last7=Gusarova |first7=E.V. |last8=Varfolomeev |first8=M.A. |date=2018 |title=Thermodynamic properties of myo-inositol |journal=The Journal of Chemical Thermodynamics |volume=116 |pages=76–84 |issn=0021-9614 |doi=10.1016/j.jct.2017.08.028 |bibcode=2018JChTh.116...76K |url=https://www.sciencedirect.com/science/article/abs/pii/S0021961417303075|url-access=subscription }}</ref>
| DeltaGf        = 
| DeltaHc        = −2747 kJ/mol
| DeltaHf        = −1329.3 kJ/mol
| Entropy        = 
| HeatCapacity   = 
  }}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = A11
| ATCCode_suffix = HA07
}}
|Section7={{Chembox Hazards
| NFPA-H = 1
| NFPA-F = 0
| NFPA-R = 0
| FlashPtC = 143
}}
}}

In [[biochemistry]], [[medicine]], and related sciences, '''inositol''' generally refers to '''''myo''-inositol''' (formerly '''''meso''-inositol'''), the most important [[stereoisomer]] of the [[chemical compound]] [[cyclohexane-1,2,3,4,5,6-hexol]]. Its [[elemental formula|formula]] is {{chem2|C6H12O6}}; the molecule has a ring of six [[carbon]] atoms, each with a [[hydrogen]] atom and a [[hydroxy group]] (–OH). In ''myo''-inositol, two of the hydroxyls, neither adjacent nor opposite, lie above the respective hydrogens relative to the mean plane of the ring.

The compound is a [[carbohydrate]], specifically a [[sugar alcohol]] (as distinct from [[simple sugar]]s like [[glucose]]) with half the [[sweetness]] of [[sucrose]] (table sugar). It is one of the most ancient components of living beings with multiple functions in [[eukaryote]]s, including structural lipids and [[secondary messenger]]s.<ref name=liyu2021/> A human kidney makes about two grams per day from [[glucose]], but other tissues synthesize it too. The highest concentration is in the brain, where it plays an important role in making other [[neurotransmitter]]s and some [[steroid hormone]]s bind to their receptors.<ref>{{cite journal |last1=Croze |first1=M. L. |last2=Soulage |first2=C. O. |title=Potential role and therapeutic interests of ''myo''-inositol in metabolic diseases |journal=Biochimie |volume=95 |issue=10 |pages=1811–1827 |date=October 2013 |pmid=23764390 |doi=10.1016/j.biochi.2013.05.011}}</ref> In other tissues, it mediates cell signal transduction in response to a variety of [[hormone]]s, [[neurotransmitter]]s, and growth factors and participates in [[osmoregulation]].<ref name="parthasarthy">{{cite book |last1=Parthasarathy |first1=L. K. |last2=Seelan |first2=R. S. |last3=Tobias |first3=C. |last4=Casanova |first4=M. F. |last5=Parthasarathy |first5=R. N. |title=Mammalian inositol 3-phosphate synthase: its role in the biosynthesis of brain inositol and its clinical use as a psychoactive agent |volume=39 |pages=293–314 |year=2006 |isbn=978-0-387-27599-4 |series=Subcellular Biochemistry |pmid=17121280 |doi=10.1007/0-387-27600-9_12}}</ref> In most mammalian cells the concentrations of ''myo''-inositol are 5 to 500&nbsp;times greater inside cells than outside them.<ref name="pmid33755975"/>

A 2023 meta-analysis found that inositol is a safe and effective treatment in the management of [[polycystic ovary syndrome]] (PCOS).<ref name="pcos2023"/> However, there is only evidence of very low quality for its efficacy in increasing fertility for IVF in women with PCOS.<ref name=showell2018>{{cite journal |year=2018 |last1=Showell |first1=M. G. |last2=Mackenzie-Proctor |first2=R. |last3=Jordan |first3=V. |last4=Hodgson |first4=R. |last5=Farquhar |first5=C. |title=Inositol for subfertile women with polycystic ovary syndrome |journal=The Cochrane Database of Systematic Reviews |volume=2018 |issue=12 |article-number=CD012378 |pmid=30570133 |doi=10.1002/14651858.CD012378.pub2 |pmc=6516980}}</ref>

The other naturally occurring stereoisomers of cyclohexane-1,2,3,4,5,6-hexol are [[scyllo-inositol|''scyllo'']]-, [[muco-inositol|''muco'']]-, [[1D-chiro-inositol|{{small|D}}-''chiro'']]-, [[L-chiro-inositol|{{small|L}}-''chiro'']]-, and [[neo-inositol|''neo''-inositol]], although they occur in minimal quantities compared to ''myo''-inositol. The other possible isomers are [[allo-inositol|''allo'']]-, [[epi-inositol|''epi'']]-, and [[cis-inositol|''cis''-inositol]].

==History==
''myo''-Inositol was first isolated from muscle extracts by Johanes Joseph Scherer (1814–1869) in 1850.<ref name=liyu2021/> It was formerly called ''meso''-inositol to distinguish it from the ''chiro''- isomers. However, since all other isomers are meso (non-[[chirality (chemistry)|chiral]]) compounds, the name ''myo''-inositol is now preferred (''myo''- being a [[list of medical roots, suffixes, and prefixes|medical prefix]] for "muscle").

Inositol was once considered a member of the [[vitamin B]] complex, namely [[vitamin B8|vitamin B<sub>8</sub>]] before the discovery that it is made naturally in the human body, and therefore cannot be a [[vitamin]] or [[essential nutrient]].<ref name=reyn1993/>

==Chemical properties==
''myo''-Inositol is a [[meso compound]], meaning it is [[optical rotation|optically inactive]] because it has a [[reflection symmetry|plane of symmetry]].<ref name=maju2006/> It is a white crystalline powder, relatively stable in the air. It is highly soluble in water, slightly soluble in [[glacial acetic acid]], [[ethanol]], [[glycol]], and [[glycerin]], but insoluble in [[chloroform]] and [[ether]].<ref name=liyu2021/>

In its most stable [[conformational isomerism|conformation]], the ''myo''-inositol isomer assumes the [[cyclohexane conformation|chair conformation]], which moves the maximum number of hydroxyls to the equatorial position, where they are farthest apart from each other. In this conformation, the natural ''myo'' isomer has a structure in which five of the six [[hydroxyl]]s (the first, third, fourth, fifth, and sixth) are [[equatorial bond|equatorial]], whereas the second hydroxyl group is [[axis of rotation|axial]].<ref>{{cite book |title=Basic Neurochemistry: Molecular, Cellular and Medical Aspects |last1=Brady |first1=S. |last2=Siegel |first2=G. |last3=Albers |first3=R. W. |last4=Price |first4=D. |date=2005 |publisher=Academic Press |isbn=978-0-08-047207-2 |page=348 |language=en |url=https://books.google.com/books?id=Af0IyHtGCMUC&pg=PA348}}</ref>

==Physiological roles==
''Myo''-Inositol plays an important role as the structural basis for a number of [[secondary messenger]]s in [[eukaryote|eukaryotic]] [[cell (biology)|cells]], the various [[inositol phosphate]]s. In addition, inositol serves as an important component of the structural lipids [[phosphatidylinositol]] (PI) and its various phosphates, the [[phosphatidylinositol phosphate (disambiguation)|phosphatidylinositol phosphate]] (PIP) lipids.

==Biosynthesis==
In humans, ''myo''-Inositol is [[de novo synthesis|synthesized ''de novo'']] but {{small|D}}-''chiro''-inositol is not.<ref name="pmid33755975"/> ''myo''-Inositol is synthesized from [[glucose 6-phosphate]] (G6P) in two steps. First, G6P is [[isomerization|isomerised]] by an [[inositol-3-phosphate synthase]] enzyme (for example, [[ISYNA1]]) to ''myo''-inositol 1-phosphate, which is then dephosphorylated by an [[inositol monophosphatase]] enzyme (for example, [[IMPA1]]) to give free ''myo''-inositol. In humans, most inositol is synthesized in the kidneys, followed by testicles, typically in amounts of a few grams per day.<ref name="parthasarthy"/>

At the peripheral level, ''myo''-inositol is converted to {{small|D}}-''chiro''-inositol by a specific epimerase. Only a minor fraction of ''myo''-inositol is converted into {{small|D}}-''chiro''-inositol.<ref name="pmid33755975"/> The activity of this epimerase is insulin dependent, causing a reduction of {{small|D}}-''chiro''-inositol in muscle, fat, and liver when there is [[insulin resistance]].<ref name="carlomagno">{{cite journal |last1=Carlomagno |first1=G. |last2=Unfer |first2=V. |last3=Roseff |first3=S. |title=The D-''chiro''-inositol paradox in the ovary |journal=Fertility and Sterility |volume=95 |issue=8 |pages=2515–6 |date=2011 |pmid=21641593 |doi=10.1016/j.fertnstert.2011.05.027 |doi-access=free}}</ref><ref name="pmid33755975"/> {{small|D}}-''chiro''-inositol reduces the conversion of testosterone to estrogen, thereby increases the levels of testosterone and worsening PCOS.<ref name="pmid33755975">{{cite journal |vauthors=Kiani AK, Paolacci S, Bertelli M |title=From Myo-inositol to D-chiro-inositol molecular pathways |journal=[[European Review for Medical and Pharmacological Sciences]] |volume=25 |issue=5 |pages=2390–2402 |year=2021 |pmid=33755975 |doi=10.26355/eurrev_202103_25279}}</ref>

===Phytic acid in plants===
[[File:Phytic acid.svg|alt=2D-structure of phytic acid|thumb|Inositolhexaphosphate, or phytic acid]]
Inositol hexaphosphate, also called [[phytic acid]] or IP6, is a [[phytochemical]] and the principal storage form of [[phosphorus]] in many [[plant]] [[biological tissue|tissues]], especially [[bran]] and [[seed]].<ref name="phytochemicals">{{cite web |title=Phytic acid |website=phytochemicals.info |url=http://www.phytochemicals.info/phytochemicals/phytic-acid.php |access-date=2018-05-02 |url-status=usurped |archive-url=https://web.archive.org/web/20180307183152/http://www.phytochemicals.info/phytochemicals/phytic-acid.php |archive-date=7 March 2018}}</ref> Phosphorus and inositol in phytate form are not generally [[bioavailability|bioavailable]] to non-[[ruminant]] animals because these animals lack the digestive [[enzyme]] [[phytase]] required to remove the phosphate groups. Ruminants readily digest phytate because of the phytase produced by microorganisms in the [[rumen]].<ref name="CAST">{{cite journal |last1=Klopfenstein |first1=T. J. |last2=Angel |first2=R. |last3=Cromwell |first3=G. |last4=Erickson |first4=G. E. |last5=Fox |first5=D. G. |last6=Parsons |first6=C. |last7=Satter |first7=L. D. |last8=Sutton |first8=A. L. |last9=Baker |first9=D. H. |date=July 2002 |title=Animal diet modification to decrease the potential for nitrogen and phosphorus pollution |journal=Council for Agricultural Science and Technology |volume=21 |url=https://digitalcommons.unl.edu/animalscifacpub/518/ |url-status=live |archive-url=https://web.archive.org/web/20110611164403/http://digitalcommons.unl.edu/animalscifacpub/518/ |archive-date=2011-06-11}}</ref> Moreover, phytic acid also [[chelation|chelates]] important minerals such as [[calcium]], [[magnesium]], [[iron]], and [[zinc]], making them unabsorbable, and contributing to mineral deficiencies in people whose diets rely highly on bran and seeds for their mineral intake, such as occurs in [[developing country|developing countries]].<ref>{{cite journal |last=Hurrell |first=R. F. |title=Influence of vegetable protein sources on trace element and mineral bioavailability |journal=The Journal of Nutrition |volume=133 |issue=9 |pages=2973S–2977S |date=September 2003 |pmid=12949395 |doi=10.1093/jn/133.9.2973S |doi-access=free}}</ref><ref>{{cite book |chapter=Phytates |title=Toxicants Occurring Naturally in Foods |author=Committee on Food Protection |author2=Food and Nutrition Board |author3=National Research Council |publisher=National Academy of Sciences |year=1973 |isbn=978-0-309-02117-3 |pages=[https://archive.org/details/toxicantsoccurri0000unse/page/363 363–371] |chapter-url=https://books.google.com/books?id=lIsrAAAAYAAJ&pg=PA363 |url=https://archive.org/details/toxicantsoccurri0000unse/page/363}}</ref>  Because of this, phytic acid is considered as an antinutrient.

Inositol penta- (IP5), tetra- (IP4), and triphosphate (IP3) are also called "phytates".

Inositol or its phosphates and associated lipids are found in many foods, in particular fruit, especially [[cantaloupe]] and [[orange (fruit)|oranges]].<ref name="foods"/> In plants, the hexaphosphate of inositol, [[phytic acid]] or its salts, the phytates, serve as phosphate stores in seed, for example in nuts and beans.<ref>{{cite web |title=Phytic acid |website=phytochemicals.info |url=http://www.phytochemicals.info/phytochemicals/phytic-acid.php |access-date=2017-10-02 |url-status=usurped |archive-url=https://web.archive.org/web/20170806114101/http://www.phytochemicals.info/phytochemicals/phytic-acid.php |archive-date=2017-08-06}}</ref> Phytic acid also occurs in [[cereal]]s with high [[bran]] content. Phytate is, however, not directly [[bioavailability|bioavailable]] to humans in the diet, since it is not digestible. Some food preparation techniques partly break down phytates to change this. However, inositol in the form of [[phospholipid]]s, as found in certain plant-derived substances such as [[lecithin]]s, is well absorbed and relatively bioavailable.

==Biological function==
Inositol, phosphatidylinositol, and some of their mono- and polyphosphates function as [[second messenger system|secondary messengers]] in a number of intracellular [[signal transduction]] pathways. They are involved in a number of biological processes, including:
* [[Insulin]] [[signal transduction]]<ref name="Larner J 2002 47–60">{{cite journal |last1=Larner |first1=J. |title=D-''chiro''-Inositol—its functional role in insulin action and its deficit in insulin resistance |journal=International Journal of Experimental Diabetes Research |volume=3 |issue=1 |pages=47–60 |year=2002 |pmid=11900279 |doi=10.1080/15604280212528 |pmc=2478565}}</ref>
* [[Cytoskeleton]] assembly
* Nerve guidance ([[epsin]])
* [[Intracellular]] [[calcium]] (Ca<sup>2+</sup>) concentration control<ref>{{cite journal |last1=Gerasimenko |first1=J. V. |last2=Flowerdew |first2=S. E. |last3=Voronina |first3=S. G. |last4=Sukhomlin |first4=T. K. |last5=Tepikin |first5=A. V. |last6=Petersen |first6=O. H. |last7=Gerasimenko |first7=O. V. |title=Bile acids induce Ca<sup>2+</sup> release from both the endoplasmic reticulum and acidic intracellular calcium stores through activation of inositol trisphosphate receptors and ryanodine receptors |journal=The Journal of Biological Chemistry |volume=281 |issue=52 |pages=40154–40163 |date=December 2006 |pmid=17074764 |doi=10.1074/jbc.M606402200 |doi-access=free}}</ref>
* Cell [[membrane potential]] maintenance<ref name="pmid9017197">{{cite journal |last1=Kukuljan |first1=M. |last2=Vergara |first2=L. |last3=Stojilković |first3=S. S. |title=Modulation of the kinetics of inositol 1,4,5-trisphosphate-induced [Ca<sup>2+</sup>]i oscillations by calcium entry in pituitary gonadotrophs |journal=Biophysical Journal |volume=72 |issue=2 Pt 1 |pages=698–707 |date=February 1997 |bibcode=1997BpJ....72..698K |pmid=9017197 |doi=10.1016/S0006-3495(97)78706-X |pmc=1185595}}</ref>
* Breakdown of [[fat]]s<ref name="pmid3103610">{{cite journal |last1=Rapiejko |first1=P. J. |last2=Northup |first2=J. K. |last3=Evans |first3=T. |last4=Brown |first4=J. E. |last5=Malbon |first5=C. C. |title=G-proteins of fat-cells. Role in hormonal regulation of intracellular inositol 1,4,5-trisphosphate |journal=The Biochemical Journal |volume=240 |issue=1 |pages=35–40 |date=November 1986 |pmid=3103610 |doi=10.1042/bj2400035 |pmc=1147372}}</ref>
* [[Gene expression]]<ref>{{cite journal |last1=Shen |first1=X. |last2=Xiao |first2=H. |last3=Ranallo |first3=R. |last4=Wu |first4=W.-H. |last5=Wu |first5=C. |title=Modulation of ATP-dependent chromatin-remodeling complexes by inositol polyphosphates |journal=Science |volume=299 |issue=5603 |pages=112–114 |date=January 2003 |bibcode=2003Sci...299..112S |pmid=12434013 |doi=10.1126/science.1078068 |doi-access=free |s2cid=8381889 |url=https://zenodo.org/record/1230822}}</ref><ref>{{cite journal |last1=Steger |first1=D. J. |last2=Haswell |first2=E. S. |last3=Miller |first3=A. L. |last4=Wente |first4=S. R. |last5=O'Shea |first5=E. K. |title=Regulation of chromatin remodeling by inositol polyphosphates |journal=Science |volume=299 |issue=5603 |pages=114–116 |date=January 2003 |bibcode=2003Sci...299..114S |pmid=12434012 |doi=10.1126/science.1078062 |pmc=1458531}}</ref>
In one important family of pathways, [[phosphatidylinositol 4,5-bisphosphate]] (PIP<sub>2</sub>) is stored in cellular membranes until it is released by any of a number of signalling proteins and transformed into various secondary messengers, for example [[diglyceride|diacylglycerol]] and [[inositol trisphosphate]].<ref>{{cite book |title=Biochemistry |last1=Mathews |first1=C. K. |date=2000 |publisher=Benjamin Cummings |last2=Van Holde |first2=K. E. |last3=Ahern |first3=K. G. |isbn=978-0-8053-3066-3 |edition=3rd |location=San Francisco, CA |page=855 |oclc=42290721}}</ref>

'''myo''-Inositol has very low toxicity, with a reported [[lethal dose|LD<sub>50</sub>]] 10,000 mg/kg body weight (oral) in rats.<ref name=liyu2021/>

==Industrial uses==

===Explosives industry===
At the 1936 meeting of the [[American Chemical Society]], professor [[Edward Bartow]] of the [[University of Iowa]] presented a commercially viable means of extracting large amounts of inositol from the phytic acid naturally present in waste corn. As a possible use for the chemical, he suggested 'inositol nitrate' as a more stable alternative to [[nitroglycerin]].<ref>{{cite news |last=Laurence |first=W. L. |title=Corn by-product yields explosive |newspaper=The New York Times |date=April 17, 1936 |page=7 |url=https://www.nytimes.com/1936/04/17/archives/corn-byproduct-yields-explosive-new-process-utilizes-wastage-in.html |archive-url=https://web.archive.org/web/20130512022104/http://select.nytimes.com/gst/abstract.html?res=F50B15F9395D13728DDDAE0994DC405B868FF1D3&scp=1 |archive-date=2013-05-12}}</ref> Today, inositol nitrate is used to gelatinize [[nitrocellulose]] in many modern explosives and solid rocket propellants.<ref>{{cite book |last=Ledgard |first=J. |title=The Preparatory Manual of Explosives |date=2007 |page=366 |publisher=Ledgard |isbn=978-0-615-14290-6 |url=https://books.google.com/books?id=J55D3HcgPuoC&q=Inositol%20explosive&pg=PA366}}</ref>

===Road salt===
When plants are exposed to increasing concentrations of [[road salt]], the plant cells become dysfunctional and undergo [[apoptosis]], leading to inhibited growth. Inositol pretreatment could reduce these effects.<ref>{{cite journal |last1=Chatterjee |first1=J. |last2=Majumder |first2=A. L. |date=September 2010 |title=Salt-induced abnormalities on root tip mitotic cells of ''Allium cepa'': prevention by inositol pretreatment |journal=Protoplasma |volume=245 |issue=1–4 |pages=165–172 |pmid=20559853 |doi=10.1007/s00709-010-0170-4 |bibcode=2010Prpls.245..165C |s2cid=9128286}}</ref>

==Research and clinical applications==

===Trichotillomania===
High doses of inositol have been explored for treatment of [[trichotillomania]] (compulsive hair-pulling) and related disorders, but no definitive evidence points to its effectiveness.<ref>{{cite journal |display-authors=3 |last1=Sani |first1=Gabriele |last2=Gualtieri |first2=Ida |last3=Paolini |first3=Marco |last4=Bonanni |first4=Luca |last5=Spinazzola |first5=Edoardo |last6=Maggiora |first6=Matteo |last7=Pinzone |first7=Vito |last8=Brugnoli |first8=Roberto |last9=Angeletti |first9=Gloria |last10=Girardi |first10=Paolo |last11=Rapinesi |first11=Chiara |last12=Kotzalidis |first12=Georgios D. |title=Drug Treatment of Trichotillomania (Hair-Pulling Disorder), Excoriation (Skin-picking) Disorder, and Nail-biting (Onychophagia) |journal=Current Neuropharmacology |date=25 July 2019 |volume=17 |issue=8 |pages=775–786 |pmid=30892151 |doi=10.2174/1570159X17666190320164223 |pmc=7059154}}</ref>

===Other illnesses===
D-''chiro''-inositol is an important messenger molecule in insulin signaling.<ref name="pmid29793496">{{cite journal |vauthors=Tabrizi R, Ostadmohammadi V, Asemi Z |title=The effects of inositol supplementation on lipid profiles among patients with metabolic diseases: a systematic review and meta-analysis of randomized controlled trials |journal=[[Q15756695|Lipids in Health and Disease]] |volume=17 |issue=1 |article-number=123 |year=2018 |pmid=29793496 |doi=10.1186/s12944-018-0779-4 |doi-access=free |pmc=5968598}}</ref> Inositol supplementation has been shown to significantly decrease [[triglyceride]]s and [[low-density lipoprotein|LDL cholesterol]] in patients with [[metabolic syndrome|metabolic diseases]].<ref name="pmid29793496"/>

''myo''-Inositol is important for [[thyroid hormones|thyroid hormone]] synthesis.<ref name="pmid34040582"/> Depletion of ''myo''-inositol may predispose to development of [[hypothyroidism]].<ref name="pmid34040582"/> Patients with hypothyroidism have a higher demand for ''myo''-inositol than healthy subjects.<ref name="pmid34040582">{{cite journal |vauthors=Benvenga S, Nordio M, Laganà AS, Unfer V |title=The Role of Inositol in Thyroid Physiology and in Subclinical Hypothyroidism Management |journal=[[Frontiers in Endocrinology]] |volume=12 |article-number=662582 |year=2021 |pmid=34040582 |doi=10.3389/fendo.2021.662582 |doi-access=free |pmc=8143049}}</ref>

Inositol should not be routinely implemented for the management of preterm babies who have or are at a risk of [[infant respiratory distress syndrome]] (RDS).<ref>{{cite journal |last1=Howlett |first1=Alexandra |last2=Ohlsson |first2=Arne |last3=Plakkal |first3=Nishad |date=8 July 2019 |title=Inositol in preterm infants at risk for or having respiratory distress syndrome |journal=The Cochrane Database of Systematic Reviews |volume=7 |issue=7 |article-number=CD000366 |issn=1469-493X |pmid=31283839 |doi=10.1002/14651858.CD000366.pub4 |pmc=6613728}}</ref> ''Myo''-inositol helps prevent [[neural tube defect]]s with particular efficacy in combination with [[folic acid]].<ref>{{cite journal |last1=Cavalli |first1=P. |last2=Ronda |first2=E. |title=Myoinositol: the bridge (PONTI) to reach a healthy pregnancy |journal=International Journal of Endocrinology |volume=2017 |article-number=5846286 |date=2017 |pmid=28243254 |doi=10.1155/2017/5846286 |doi-access=free |pmc=5274721}}</ref>

Inositol is considered a safe and effective treatment for [[polycystic ovary syndrome]] (PCOS).<ref name="pcos2023">{{cite journal |title=Inositol is an effective and safe treatment in polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials |date=2023 |last1=Greff |first1=Dorina |last2=Juhász |first2=Anna E. |last3=Váncsa |first3=Szilárd |last4=Váradi |first4=Alex |last5=Sipos |first5=Zoltán |last6=Szinte |first6=Julia |last7=Park |first7=Sunjune |last8=Hegyi |first8=Péter |last9=Nyirády |first9=Péter |last10=Ács |first10=Nándor |last11=Várbíró |first11=Szabolcs |last12=Horváth |first12=Eszter M. |journal=Reproductive Biology and Endocrinology |volume=21 |issue=1 |page=10 |pmid=36703143 |doi=10.1186/s12958-023-01055-z |doi-access=free |pmc=9878965}}</ref> It works by increasing insulin sensitivity, which helps to improve ovarian function and reduce [[hyperandrogenism]].<ref>{{cite journal |last1=Monastra |first1=G. |last2=Unfer |first2=V. |last3=Harrath |first3=A. H. |last4=Bizzarri |first4=M. |title=Combining treatment with ''myo''-inositol and D-''chiro''-inositol (40:1) is effective in restoring ovary function and metabolic balance in PCOS patients |journal=Gynecological Endocrinology |volume=33 |issue=1 |pages=1–9 |date=January 2017 |pmid=27898267 |doi=10.1080/09513590.2016.1247797 |hdl=11573/944617 |s2cid=24836559}}</ref> It is also shown to reduce the risk of [[metabolic disorder|metabolic disease]] in women with PCOS.<ref>{{cite journal |last1=Nordio |first1=M. |last2=Proietti |first2=E. |title=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 |journal=European Review for Medical and Pharmacological Sciences |volume=16 |issue=5 |pages=575–581 |date=May 2012 |pmid=22774396}}</ref> In addition, thanks to its role as FSH second messenger, ''myo''-inositol is effective in restoring FSH/LH ratio and menstrual cycle regularization.<ref>{{cite journal |last1=Unfer |first1=V. |display-authors=etal |title=Effects of ''myo''-inositol in women with PCOS: a systematic review of randomized controlled trials |journal=Gynecological Endocrinology |volume=28 |issue=7 |pages=509–15 |date=2012 |pmid=22296306 |doi=10.3109/09513590.2011.650660 |hdl=11380/744390 |s2cid=24582338}}</ref> ''myo''-Inositol's role as FSH second messenger leads to a correct ovarian follicle maturation and consequently to a higher oocyte quality. Improving the oocyte quality in both women with or without PCOS, ''myo''-inositol can be considered as a possible approach for increasing the chance of success in assisted reproductive technologies.<ref>{{cite journal |last1=Ciotta |first1=L. |display-authors=etal |title=Effects of ''myo''-inositol supplementation on oocyte's quality in PCOS patients: a double blind trial |journal=European Review for Medical and Pharmacological Sciences |volume=15 |issue=5 |pages=509–14 |date=2011 |pmid=21744744}}</ref><ref>{{cite journal |last1=Papaleo |first1=E. |display-authors=etal |title=Contribution of ''myo''-inositol to reproduction |journal=European Journal of Obstetrics & Gynecology and Reproductive Biology |volume=147 |issue=2 |pages=120–3 |date=2009 |pmid=19800728 |doi=10.1016/j.ejogrb.2009.09.008}}</ref> In contrast, {{small|D}}-''chiro''-inositol can impair oocyte quality in a dose-dependent manner.<ref>{{cite journal |last1=Isabella |first1=R. |last2=Raffone |first2=E. |title=Does ovary need D-''chiro''-inositol? |journal=Journal of Ovarian Research |volume=5 |issue=1 |date=2012 |page=14 |pmid=22587479 |doi=10.1186/1757-2215-5-14 |doi-access=free |pmc=3447676}}{{Expression of Concern|doi=10.1186/s13048-018-0431-y|pmid=29976256|http://retractionwatch.com/2018/07/23/journal-flags-fertility-paper-after-company-wins-court-order/ ''Retraction Watch''|doi-access=free}}</ref> The high level of DCI seems to be related to elevated insulin levels retrieved in about 70% of PCOS women.<ref>{{cite journal |last=Moghetti |first=P. |title=Insulin resistance and polycystic ovary syndrome |journal=Current Pharmaceutical Design |date=2016 |volume=22 |issue=36 |pages=5526–5534 |pmid=27510482 |doi=10.2174/1381612822666160720155855}}</ref> In this regard, insulin stimulates the irreversible conversion of ''myo''-inositol to {{small|D}}-''chiro''-inositol causing a drastic reduction of ''myo''-inositol. ''myo''-Inositol depletion is particularly damaging to ovarian follicles because it is involved in FSH signaling, which is impaired due to ''myo''-inositol depletion.<ref name="carlomagno"/> Recent evidence reports a faster improvement of the metabolic and hormonal parameters when these two isomers are administered in their physiological ratio. The plasmatic ratio of ''myo''-inositol and {{small|D}}-''chiro''-inositol in healthy subjects is 40:1 of ''myo''- and {{small|D}}-''chiro''-inositol respectively.<ref>{{cite journal |last1=Facchinetti |first1=F. |display-authors=etal |title=Results from the International Consensus Conference on ''myo''-Inositol and D-''chiro''-Inositol in Obstetrics and Gynecology: the link between metabolic syndrome and PCOS |journal=European Journal of Obstetrics & Gynecology and Reproductive Biology |volume=195 |pages=72–6 |date=2015 |pmid=26479434 |doi=10.1016/j.ejogrb.2015.09.024 |hdl=11380/1073867 }}</ref> The use of the 40:1 ratio shows the same efficacy of ''myo''-inositol alone but in a shorter time. In addition, the physiological ratio does not impair oocyte quality.<ref>{{cite journal |last1=Colazingari |first1=S. |display-authors=etal |title=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 |journal=Archives of Gynecology and Obstetrics |volume=288 |issue=6 |pages=1405–11 |date=2013 |pmid=23708322 |doi=10.1007/s00404-013-2855-3 |s2cid=45611717}}</ref>

The use of inositols in PCOS is gaining more importance, and an efficacy higher than 70% with a strong safety profile is reported. On the other hand, about 30% of patients could show as inositol-resistant.<ref>{{cite journal |last1=Kamenov |first1=Z. |display-authors=etal |title=Ovulation induction with ''myo''-inositol alone and in combination with clomiphene citrate in polycystic ovarian syndrome patients with insulin resistance |journal=Gynecological Endocrinology |volume=31 |issue=2 |pages=131–5 |date=2015 |pmid=25259724 |doi=10.3109/09513590.2014.964640 |hdl=11380/1075829 |s2cid=24469378}}</ref> New evidence regarding PCOS aetiopathogenesis describes an alteration in the species and the quantity of each strain characterizing the normal gastrointestinal flora. This alteration could lead to chronic, low-level inflammation and malabsorption.<ref>{{cite journal |last=González |first=F. |title=Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction |journal=Steroids |volume=77 |issue=4 |pages=300–5 |date=2012 |pmid=22178787 |doi=10.1016/j.steroids.2011.12.003 |pmc=3309040}}</ref> A possible solution could be represented by the combination of ''myo''-inositol and [[α-Lactalbumin|α-lactalbumin]]. This combination shows a synergic effect in increasing myo-inositol absorption.<ref>{{cite journal |last=Monastra |first=G. |display-authors=etal |title=''alpha''-Lactalbumin effect on ''myo''-inositol intestinal absorption: in vivo and in vitro. |journal=Current Drug Delivery |volume=15 |issue=9 |pages=1305–1311 |date=2018 |pmid=29745333 |doi=10.2174/1567201815666180509102641 |s2cid=13691602}}</ref> A recent study reported that the ''myo''-inositol and α-lactalbumin combination increases ''myo''-inositol plasmatic content in inositol-resistant patients with a relative improvement of hormonal and metabolic parameters.<ref>{{cite journal |last1=Oliva |first1=M. M. |display-authors=etal |title=Effects of ''myo''-inositol plus ''alpha''-lactalbumin in ''myo''-inositol-resistant PCOS women |journal=Journal of Ovarian Research |volume=11 |issue=1 |date=2018 |article-number=38 |pmid=29747700 |doi=10.1186/s13048-018-0411-2 |doi-access=free |pmc=5944130}}</ref>

==Use as a cutting agent==
Inositol has been used as an adulterant or [[lacing (drugs)|cutting agent]] for many illegal drugs, such as [[cocaine]], [[methamphetamine]], and sometimes [[heroin]],<ref>{{cite web |title=Inositol, Nerve guidance, Cutting agent manufacturer |publisher=Tianyu Feed Additive |url=http://feedadditivechina.com/6-16-inositol.html |access-date=2013-07-21 |archive-url=https://web.archive.org/web/20140908220315/http://www.feedadditivechina.com/6-16-inositol.html |archive-date=2014-09-08}}</ref> probably because of its solubility, powdery texture, or reduced [[sweetness]] (50%) compared to more common sugars.

Inositol is also used as a stand-in [[film prop]] for [[cocaine]] in [[filmmaking]].<ref>{{cite magazine |last=Golianopoulos |first=T. |title=Drug doubles: What actors actually toke, smoke and snort on camera |magazine=Wired |date=2012-05-12 |url=https://www.wired.com/underwire/2012/05/pl_drugs/ |access-date=2012-05-14 |archive-url=https://web.archive.org/web/20120514154908/http://www.wired.com/underwire/2012/05/pl_drugs/ |archive-date=2012-05-14}}</ref><ref>{{citation |title=How Fake Drugs Are Made For Movies {{!}} Movies Insider |date=12 December 2020 |language=en |url=https://www.youtube.com/watch?v=kwMuCwu-dqM |access-date=2022-09-26}}</ref>

==Nutritional sources==
''Myo''-inositol is naturally present in a variety of foods, although tables of food composition do not always distinguish between [[lecithin]], the relatively bioavailable lipid form and the biounavailable phytate/phosphate form.<ref name='foods'>{{cite journal |last1=Clements |first1=R. S. |last2=Darnell |first2=B. |title=''myo''-Inositol content of common foods: development of a high-''myo''-inositol diet |journal=The American Journal of Clinical Nutrition |volume=33 |issue=9 |pages=1954–1967 |date=September 1980 |pmid=7416064 |doi=10.1093/ajcn/33.9.1954 |doi-access=free |s2cid=4442333}}</ref> Foods containing the highest concentrations of ''myo''-inositol and its compounds include fruits, beans, grains, and nuts.<ref name='foods'/> Fruits in particular, especially oranges and cantaloupe, contain the highest amounts of ''myo''-inositol.<ref name='sugar alcohol'>{{cite journal |last1=Awuchi |first1=Chinaza |title=Sugar Alcohols: Chemistry, Production, Health Concerns and Nutritional Importance of Mannitol, Sorbitol, Xylitol, and Erythritol |journal=International Journal of Advanced Academic Research |volume=5 |issue=11 |pages=1954–1967 |date=2017 |url=https://www.researchgate.net/publication/336923362}}</ref> It is also present in beans, nuts, and grains, however, these contain large amounts of ''myo''-inositol in the phytate form, which is not bioavailable without transformation by [[phytase]] enzymes. ''[[Bacillus subtilis]]'', the microorganism which produces the fermented food [[natto]], produces phytase enzymes that may convert [[phytic acid]] to a more bioavailable form of inositol polyphosphate in the gut.<ref>{{cite journal |vauthors=Borgi MA, Boudebbouze S, Mkaouar H, Maguin E, Rhimi M |title=Bacillus phytases: Current status and future prospects |journal=Bioengineered |volume=5 |issue=4 |pages=233–236 |date=2015 |pmid=25946551 |doi=10.1080/21655979.2015.1048050 |pmc=4601277}}</ref> Additionally, ''[[Bacteroides]]'' species in the gut secrete vesicles containing an active enzyme which converts the phytate molecule into bioavailable phosphorus and inositol polyphosphate, which is an important signaling molecule in the human body.<ref>{{cite journal |vauthors=Stentz R, Osborne S, Horn N, Li AW, Hautefort I, Bongaerts R, Rouyer M, Bailey P, Shears SB, Hemmings AM, Brearley CA, Carding SR |title=A Bacterial Homolog of a Eukaryotic Inositol Phosphate Signaling Enzyme Mediates Cross-kingdom Dialog in the Mammalian Gut |journal=Cell Reports |volume=6 |issue=4 |pages=646–656 |date=27 February 2014 |pmid=24529702 |doi=10.1016/j.celrep.2014.01.021 |doi-access=free |pmc=3969271}}</ref>

''Myo''-inositol can also be found as an ingredient in [[energy drink]]s,<ref>{{cite journal |date=2019-08-01 |title=Risk assessment of energy drinks with focus on cardiovascular parameters and energy drink consumption in Europe |journal=Food and Chemical Toxicology |language=en |volume=130 |pages=109–121 |issn=0278-6915 |last1=Ehlers |first1=Anke |last2=Marakis |first2=Georgios |last3=Lampen |first3=Alfonso |last4=Hirsch-Ernst |first4=Karen Ildico |pmid=31112702 |doi=10.1016/j.fct.2019.05.028 |doi-access=free}}</ref> either in conjunction with or as a substitute for glucose.<ref>{{cite magazine |last=DiSalvo |first=David |title=We Know About Caffeine in Energy Drinks Like Monster, But What About the Other Ingredients? |magazine=Forbes |language=en |url=https://www.forbes.com/sites/daviddisalvo/2012/10/24/we-know-about-caffeine-in-energy-drinks-like-monster-but-what-about-the-other-ingredients/ |access-date=2020-12-22}}</ref>

In humans, ''myo''-inositol is naturally made from glucose-6-phosphate through enzymatic dephosphorylation.<ref name='sugar alcohol'/>

==Production==
As of 2021, the main industrial process for the production of ''myo''-inositol (mostly in China and Japan) started with phytate (IP6) extracted from the soaking water resulting from corn and rice bran processing. After purification, the phytate is hydrolized, and ''myo''-inositol is separated by crystallization.<ref name=liyu2021/>

Another route is microbial fermentation of carbohydrates by various organisms, such as the fungus ''[[Neurospora crassa]]'' (Beadle and Tatum, 1945), ''[[Candida boidini]]'' (Shirai et al., 1997), ''[[Saccharomyces cerevisiae]]'' (Culbertson et al., 1976), ''[[Escherichia coli]]'' (Hansen, 1999).<ref name=liyu2021/> Alternatively, enzyme extracts from microbial cultures can be used in vitro to obtain ''myo''-inositol from various substrates, including glucose, [[sucrose]], [[starch]], [[xylose]], and [[amylose]].<ref name=liyu2021/>

==References==
{{Reflist|
<ref name=liyu2021>Yunjie Li, Pingping Han, Juan Wang, Ting Shi, Chun You (2021): "Production of myo-inositol: Recent advance and prospective". ''Biotechnology and Applied Biochemistry'', volume 69, issue 3, pages 1101-1111. {{doi|10.1002/bab.2181}}</ref>

<ref name=maju2006>{{cite book |title=Biology of Inositols and Phosphoinositides |last1=Majumder |first1=A. L. |last2=Biswas |first2=B. B. |date=2006-10-03 |publisher=Springer Science & Business Media |isbn=978-0-387-27600-7 |language=en |url=https://books.google.com/books?id=vxoxBbmiLQUC&pg=PA3}}</ref>

<ref name=reyn1993>J. E. F. Reynolds (1993): '' Martindale: The Extra Pharmacopoeia'', volume 30. Quote (page 1379): "An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man". {{ISBN|978-0-85369-300-0}}</ref>
}}

==External links==
{{Commons category}}
*[http://gmd.mpimp-golm.mpg.de/Spectrums/21bdad4b-931e-453b-aa3e-1824c658c2f0.aspx Inositol MS Spectrum]
*[http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=INS Inositol bound to proteins] in the [[Protein Data Bank|PDB]]

{{Alcohols}}
{{Obsessive–compulsive disorder}}
{{Phospholipids}}
{{Purine receptor modulators}}

[[Category:Inositol| ]]
[[Category:Biology of bipolar disorder]]
[[Category:Biology of obsessive–compulsive disorder]]
[[Category:Chemopreventive agents]]
[[Category:Treatment of obsessive–compulsive disorder]]
[[Category:Xanthine oxidase inhibitors]]