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 formula is ; 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 sugars 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 eukaryotes, including structural lipids and secondary messengers. In other tissues, it mediates cell signal transduction in response to a variety of hormones, neurotransmitters, and growth factors and participates in osmoregulation. In most mammalian cells the concentrations of myo-inositol are 5 to 500 times greater inside cells than outside them.

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

History

myo-Inositol was first isolated from muscle extracts by Johanes Joseph Scherer (1814–1869) in 1850.

Physiological roles

Myo-Inositol plays an important role as the structural basis for a number of secondary messengers in eukaryotic cells, the various inositol phosphates. In addition, inositol serves as an important component of the structural lipids phosphatidylinositol (PI) and its various phosphates, the phosphatidylinositol phosphate (PIP) lipids.

Biosynthesis

In humans, myo-Inositol is synthesized de novo but -chiro-inositol is not.

Phytic acid in plants

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 tissues, especially bran and seed. Phosphorus and inositol in phytate form are not generally 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. Moreover, phytic acid also 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 countries. 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 oranges. Phytic acid also occurs in cereals with high bran content. Phytate is, however, not directly 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 phospholipids, as found in certain plant-derived substances such as lecithins, is well absorbed and relatively bioavailable.

Biological function

Inositol, phosphatidylinositol, and some of their mono- and polyphosphates function as secondary messengers in a number of intracellular signal transduction pathways. They are involved in a number of biological processes, including:

  • Insulin signal transduction
  • Cytoskeleton assembly
  • Nerve guidance (epsin)
  • Intracellular calcium (Ca<sup>2+</sup>) concentration control
  • Cell membrane potential maintenance
  • Breakdown of fats
  • Gene expression

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 diacylglycerol and inositol trisphosphate.

myo-Inositol has very low toxicity, with a reported LD<sub>50</sub> 10,000 mg/kg body weight (oral) in rats. Today, inositol nitrate is used to gelatinize nitrocellulose in many modern explosives and solid rocket propellants.

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.

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.

Other illnesses

D-chiro-inositol is an important messenger molecule in insulin signaling. Inositol supplementation has been shown to significantly decrease triglycerides and LDL cholesterol in patients with metabolic diseases.

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). Myo-inositol helps prevent neural tube defects with particular efficacy in combination with folic acid.

Inositol is considered a safe and effective treatment for polycystic ovary syndrome (PCOS). It works by increasing insulin sensitivity, which helps to improve ovarian function and reduce hyperandrogenism. It is also shown to reduce the risk of metabolic disease in women with PCOS. In addition, thanks to its role as FSH second messenger, myo-inositol is effective in restoring FSH/LH ratio and menstrual cycle regularization. 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. In contrast, -chiro-inositol can impair oocyte quality in a dose-dependent manner. The high level of DCI seems to be related to elevated insulin levels retrieved in about 70% of PCOS women. In this regard, insulin stimulates the irreversible conversion of myo-inositol to -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. 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.

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. 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. A possible solution could be represented by the combination of myo-inositol and α-lactalbumin. This combination shows a synergic effect in increasing myo-inositol absorption. 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.

Use as a cutting agent

Inositol has been used as an adulterant or cutting agent for many illegal drugs, such as cocaine, methamphetamine, and sometimes heroin, 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.

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. Foods containing the highest concentrations of myo-inositol and its compounds include fruits, beans, grains, and nuts. 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. 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.

Myo-inositol can also be found as an ingredient in energy drinks, either in conjunction with or as a substitute for glucose.

In humans, myo-inositol is naturally made from glucose-6-phosphate through enzymatic dephosphorylation.

  • Inositol MS Spectrum
  • Inositol bound to proteins in the PDB