Pharmacodynamics and pharmacokinetics of inositol(s) in health and disease

ABSTRACT

Introduction: Inositol and its derivatives comprise a huge field of biology. Myo-inositol is not only a prominent component of membrane-incorporated phosphatidylinositol, but participates in its free form, with its isomers or its phosphate derivatives, to a multitude of cellular processes, including ion channel permeability, metabolic homeostasis, mRNA export and translation, cytoskeleton remodeling, stress response.

Areas covered: Bioavailability, safety, uptake and metabolism of inositol is discussed emphasizing the complexity of interconnected pathways leading to phosphoinositides, inositol phosphates and more complex molecules, like glycosyl-phosphatidylinositols.

Expert opinion: Besides being a structural element, myo-inositol exerts unexpected functions, mostly unknown. However, several reports indicate that inositol plays a key role during phenotypic transitions and developmental phases. Furthermore, dysfunctions in the regulation of inositol metabolism have been implicated in several chronic diseases. Clinical trials using inositol in pharmacological doses provide amazing results in the management of gynecological diseases, respiratory stress syndrome, Alzheimer’s disease, metabolic syndrome, and cancer, for which conventional treatments are disappointing. However, despite the widespread studies carried out to identify inositol-based effects, no comprehensive understanding of inositol-based mechanisms has been achieved. An integrated metabolomics-genomic study to identify the cellular fate of therapeutically administered myo-inositol and its genomic/enzymatic targets is urgently warranted.

KEYWORDS:

• Myo-inositol
• inositol phosphates
• cell signalling
• phosphoinositides
• inositolphosphoglycans

Article highlights

• After enzymatic digestion of dietary IP6, myo-Ins is actively absorbed and transported by intestinal cells by two transport systems: sodium ion coupled (SMIT1/2) and proton coupled (HMIT1) inositol transporters.

• Myo-Ins undergoes a complex metabolic transformation, leading to inositol isomers, inositol phosphates (IPs), phosphatidylinositol (PI), phosphatidylinositides (phosphatidylinositol-phosphates PIP), glycosyl-phosphatidylinositols (GPI), and many other derivatives as inositol-phosphoglycans (IPG).

• Myo-Ins and its derivatives participate in several physiological processes, including calcium metabolism, proliferation, endocrine modulation, phenotypic determination, developmental processes, and stress response.

• Dietary inositol has been shown to inhibit lung tumorigenesis in rats and humans

• Myo-Ins may play a relevant role in preventing Respiratory Distress Syndrome in preterm infant, as well as other developmental defects.

• Myo-Ins counteracts the main features of the PCOS-associated metabolic syndrome, meanwhile it improves several ovarian functions: oocyte quality, frequency of ovulation, increased pregnancy rate.

• Myo-Ins and its derivatives represent possible therapeutic agents for the treatment of neurological disorders, including Alzheimer disease.

• An integrated metabolomics-genomic study to identify the cellular fate of therapeutically added myo-Ins and its genomic/enzymatic targets is urgently warranted.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

¹ Inositol isomers and inositol phosphate terminology continues to be misused, as complained by several scholars [Shears SB and Turner BL. Nomenclature and terminology of Inositol phosphates, in: Inositol phosphates: linking Agriculture and the Environment, BL Turner, AE Richardson, EJ Mullaney (Eds), CaB Intl, 2006, pp. 1–5]. Herein, after denominations and abbreviations were reported according to IUPAC recommendation [IUPAC. Compendium of Chemical Terminology, 2nd ed. (the ‘Gold Book’). Compiled by AD McNaught and A Wilkinson. Blackwell Scientific Publications, Oxford (1997). XML on-line corrected version: http://goldbook.iupac.org (2006-) created by M Nic, J Jirat, B Kosata; updates compiled by A Jenkins.]

² The systematic name of this class of enzyme is 1 d-myo-inositol-3-phosphate lyase. However, some confusion may arise, as other names are frequently in common use, including myo-inositol-1-phosphate synthase, d-glucose 6-phosphate cycloaldolase, inositol 1-phosphate synthetase, glucose 6-phosphate cyclase, inositol 1-phosphate synthetase, glucose-6-phosphate inositol monophosphate cycloaldolase, glucocycloaldolase.

Additional information

Funding

This paper was not funded.