Inositol

Absorption

Inositol is absorbed from the small intestine. In patients with inositol deficiency, the maximal plasma concentration after oral administration of inositol is registered to be of 4 hours. Inositol is taken up by the tissues via sodium-dependent inositol co-transporter which also mediates glucose uptake. Oral ingestion of inositol is registered to generate a maximal plasma concentration of 36-45 mcg.

Toxicity

Consumption of high doses of inositol is reported to only cause some gastrointestinal effects.

Description

Inositol (hexahydroxycyclohexane) is a widely distributed natural constituent of plant and animal tissues. The animal tissues richest in inositol are brain, heart, stomach, kidney, spleen, and liver, where it occurs free or as a component of phospholipids. Among plants, cereals are rich sources of inositol, particularly in the form of polyphosphoric acid esters, called phytic acids. Although there are several possible optically active and inactive isomers, considerations of inositol as a food additive refer specifically to optically inactive cis-1,2,3,5-trans-4,6-cyclohexanehexol, which is preferably designated myo-inositol. Pure inositol is a stable, white, sweet, crystalline compound. The Food Chemicals Codex specifies that it assay not less than 97.0 percent, melt between 224 and 227°, and contain not more than 3 ppm arsenic, 10 ppm lead, 20 ppm heavy metals (as Pb), 60 ppm sulfate, and 50 ppm chloride. Inositol was thought for a time to be a vitamin because experimental animals on a synthetic diet developed clinical signs that were corrected by inositol supplementation. However, no cofactor or catalytic function for inositol has been found; it can be synthesized and occurs in relatively high concentration in animal tissues. These factors argue against its classification as a vitamin. A dietary requirement in man has not been established.

Chemical properties

white powder

Originator

Inositol,Comm. Solvents,US,1949

The Uses of Inositol

Myo-Inositol is a growth factor for animals and microorganisms. It is the most abundant form of polyols that serves as a structural element of secondary messengers in eukaryotic cells. It is used as an adulterant in many illegal drugs like cocaine and methamphetamine. Further, it is used as a stand-in for cocaine on television and film.

The Uses of Inositol

The structural basis for a number of signaling and secondary messenger molecules including; insulin signal transduction, cytoskeleton assembly, nerve guidance, membrane potentials, serotonin activity and the breaking down of fats and reducing cholesterol.

The Uses of Inositol

A growth-factor and structural element of secondary messengers in eukaryotic cells

Background

Inositol is a collection of nine different stereoisomers but the name is usually used to describe only the most common type of inositol, myo-inositol. Myo-inositol is the cis-1,2,3,5-trans-4,6-cyclohexanehexol and it is prepared from an aqueous extract of corn kernels by precipitation and hydrolysis of crude phytate. These molecules have structural similarities to glucose and are involved in cellular signaling. It is considered a pseudovitamin as it is a molecule that does not qualify to be an essential vitamin because even though its presence is vital in the body, a deficiency in this molecule does not translate into disease conditions. Inositol can be found as an ingredient of OTC products by Health Canada but all current product whose main ingredient is inositol are discontinued. By the FDA, inositol is considered in the list of specific substances affirmed as generally recognized as safe (GRAS).

Indications

Inositol may be used in food without any limitation. As a drug, inositol is used as a nutrient supplement in special dietary foods and infant formula. As it presents a relevant role in ensuring oocyte fertility, inositol has been studied for its use in the management of polycystic ovaries. Inositol is also being researched for the treatment of diabetes, prevention of metabolic syndrome, aid agent for weight loss, treatment of depression, psychiatric disorder and anxiety disorder and for prevention of cancer.

Definition

ChEBI: Inositol is an inositol having myo-configuration. It is a natural sugar found in cell membrane phospholipids, plasma lipoproteins, and (as the phosphate form) in the nucleus with potential chemopreventive properties. As one of a number of intracellular phosphate compounds, inositol is involved in cell signaling and may stimulate tumor cell differentiation.

Manufacturing Process

Inactive inositol may be prepared from starch factory steep water which is the liquid in which corn is steeped to soften the covering of the corn kernel and to thoroughly soften the entire kernel. It contains approximately 1% sulfurous acid (H2SO3) in solution. A typical example of such treatment consists in adding to the acid steep water, lime Ca(OH)2 or CaO to approximate neutrality, or to a pH of 6.0 to 8.0, at which range the insoluble "phytin" is precipitated. This precipitate of impure "phytin" or calcium phytate is removed by suitable means, as stated before, and may be mixed with (1) 1 to 10% acid solution; or (2) diluted with water; or (3) the solution may be made alkaline. This alkaline or neutral or acid mixture is placed in a suitable container in an autoclave or steam digester, and the steam turned on whereupon the reaction is allowed to proceed as long as desired. The autoclave in which the mixture has been placed may be heated by generating steam therein, by means of an electric heater, or by suitable heat from outside. A pressure of from 1 to 200 pounds steam for 1 to 18 hours may be used, the time required being correspondingly less for higher pressures. A suitable pressure is 80 pounds. The time expected for 80 pounds is three hours.
autoclave cooled, the mixture removed, diluted, and made alkaline with Ca(OH)2, Ba(OH)2,etc., brought to boiling, thoroughly agitated with steam, the insoluble sludge allowed to settle, and the supernatant liquid removed by decantation, siphoning or filtration. The supernatant liquid is concentrated in an open vessel, or in vacuum, to remove the precipitating inorganic impurities as calcium carbonate (CaCO3), magnesium carbonate (MgCO3), etc. The liquid is concentrated until it becomes thick and syrupy. The concentrated solution is filtered, cooled, and agitated by a suitable mechanical means to precipitate iinositol. The iI-inositol is removed by filtration, the mother liquor concentrated, and the process repeated until the solution becomes too thick to filter advantageously. A filter press may be employed to remove furtherquantities of i-inositol, or the thick residue may be diluted with a reagent in which i-inositol is insoluble; as, for example, acetic acid (CH3COOH) and alcohol-acetic acid (C2H5OH, CH3COOH, etc.). On cooling and stirring the solution, additional i-inositol, etc., results and can be removed by filtration or other mechanical means. The i-inositol may be recrystallized by dissolving the crude product in boiling water, and reprecipitated by cooling and stirring. The final crystallization from a hot water solution to which an equal volume of alcohol is added with cooling and stirring, gives a purer product.

Therapeutic Function

Vitamin, Lipotropic

General Description

Myoinositol is a stereoisomeric form of inositol, and is very often found in many plants and in tissues of animals and plants. It acts as a second messenger, thereby is very important for the signal pathways of cells. It generally finds application in being used as a natural insulin sensitizer in PCOS (Polycystic Ovarian Syndrome) patients. Myoinositol acts in a PCOS pathway by improving insulin sensitivity, thereby sequentially increasing intracellular glucose uptake.

Biochem/physiol Actions

A component of membrane phospholipids, glycosyl-phosphatidyl-inositol anchors that bind glycoproteins to cell membranes, and inositol phosphate second messengers.

Side Effects

Mild side effects have been reported with doses of 12 grams per day or higher. These include nausea, gas, difficulty sleeping, headache, dizziness and tiredness.

Benefits

Inositol can stimulate glucose uptake in skeletal muscle cells, which allows a decrease in blood sugar levels. This effect is later seen as a reduction in urine glucose concentration and indicates a decrease in high blood sugar levels.
In PCOS, the administration of inositol has produced the remission of symptoms as well as a reduction in male hormone secretion, a regulation of the cholesterol level, and a more efficient fat breakdown, which allows for a significant reduction in body mass and appetite. In the cases of infertility, inositol has been proven to increase sperm count and motility, as well as increase the overall quality of oocytes and embryos.
In the brain, inositol has been shown to produce an increase in serotonin receptor sensitivity. This activity produces an increase in GABA release. Some of the effects observed in the brain produced a relief in symptoms of anxiety and obsessive-compulsive disorders. In high doses, it has been shown to even reduce panic attacks.
In cancer research, inositol has gained interest as it can act as an antioxidant and anti-inflammatory, and it seems to enhance immune properties.

Source

It is the most definitive list of high-inositol foods: fresh fruits, eg citrus and rock melon/ cantaloupe; beans, eg pinto beans, kidney beans and peas; grains, eg bran; nuts eg almonds (or peanut butter).

Metabolism

It is thought that inositol is metabolized to phosphoinositol and then converted to phosphatylinositol-4,5-biphosphate which is a precursor of the second-messenger molecules. Inositol can be transformed to D-chiro-inositol via the actions of an epimerase. The normal modifications to inositol structure seem to be between all the different isomers.

Side Effects

People may experience certain mild side effects while taking the inositol supplement, including: Diarrhea, Nausea, Abdominal pain, Fatigue, Headache, and Dizziness.

Purification Methods

Recrystallise myo-inositol from aqueous 50% ethanol or H2O forming a dihydrate, or anhydrous crystals from AcOH. The dihydrate is efflorescent and becomes anhydrous when heated at 100o . The anhydrous crystals are not hygroscopic. Its solubility in H2O at 25o is 14%, at 60o it is 28%; it is slightly soluble in EtOH but insoluble in Et2O. [Ballou & Anderson J Am Chem Soc 7 5 748 1953, Anderson & Wallis J Am Chem Soc 70 2931 1948, Beilstein 6 II 1157, 6 IV 7919.]

Clinical claims and research

Some researches have found that inositol enhanced cisplatin-induced histopathological improvements in the uterus and ovaries, raising progesterone and estradiol serum levels. Hence,  Inositol shield against cisplatin-related infertility by reducing oxidative stress and apoptosis in the uterus and ovaries. Inositol stereoisomers are naturally occurring molecules that readily cross the blood-brain barrier . It may represent a viable treatment for AD through the complexation of Abeta and attenuation of Abeta neurotoxic effects[1-2].

References

[1] Moslehi A, et al. Fertility-enhancing effects of inositol & vitamin C on cisplatin induced ovarian and uterine toxicity in rats via suppressing oxidative stress and apoptosis. Food and Chemical Toxicology, 2023; 179: 113995.
[2] McLaurin J, et al. Inositol stereoisomers stabilize an oligomeric aggregate of Alzheimer amyloid beta peptide and inhibit abeta -induced toxicity. Journal of Biological Chemistry, 2000; 275: 18495-18502.