Quasi vitamins myoInositol Domina Petric MD Chemical nature

Quasi vitamins: myo-Inositol Domina Petric, MD

Chemical nature Myo-inositol is a water-soluble, hydroxylated, cyclic six-carbon compound (cis-1, 2, 3, 5 -trans-4, 6 -cyclohexanehexol). It is the only one of the nine possible stereoisomeric forms of cyclohexitol with biological activity. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 2

Biosynthesis from glucose • Mammals can synthesize myo-inositol de novo ultimately from glucose. • Biosynthetic capacity has been found in kidney and other tissues in humans. • The biosynthesis involves the cyclization of glucose 6 -phosphate to inositol 1 -phosphate by inositol-1 -phosphate synthase, followed by a dephosphorylation by inositol-1 -phosphatase. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 3

Dietary sources myo-Inositol occurs in foods in three forms: • free myo-inositol • phytic acid • inositol containing phospholipids 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 4

Dietary sources The richest sources of myo-inositol are the seeds of plants (beans, grains and nuts). The predominant form occurring in plant materials is phytic acid. Most mammals have little or no intestinal phytase activity and phytic acid is poorly utilized as a source of either myo-inositol or phosphorus. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 5

Dietary sources In animal products, myo-inositol occurs in free form as well as in inositol-containing phospholipids (primarily phosphatidylinositol). Free myo-inositol predominates in brain and kidney. Phospholipid inositol predominates in skeletal muscle, heart, liver and pancreas. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 6

Human milk is relatively rich in myo-inositol: • Colostrum, 200 -500 mg/liter • Mature milk, 100 -200 mg/liter 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 7

Vegetables Vegetable Myo-Inositol mg/g Asparagus 0, 29 -0, 68 Green beans 0, 55 -1, 93 White beans 2, 83 -4, 40 Red beans 2, 49 Broccoli 0, 11 -0, 30 Cabbage 0, 18 -0, 70 Carrot 0, 52 Pea 1, 16 -2, 35 Okra 0, 28 -1, 17 Potato 0, 97 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 8

Diary products, eggs and nuts Diary product/eggs/nuts Milk Ice cream Cheese Whole egg Egg yolk Almond Peanut 2/16/2022 Myo-inositol mg/g 0, 04 0, 09 0, 01 -0, 09 0, 34 2, 78 1, 33 -3, 04 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 9

Fruits and cereals Fruits/cereals Myo-inositol mg/g Apple 0, 10 -0, 24 Cantaloupe 3, 55 Grape 0, 07 -0, 16 Grapefruit 1, 17 -1, 99 Orange 3, 07 Peach 0, 19 -0, 58 Pear 0, 46 -0, 73 Strawberry 0, 13 Watermelon 0, 48 Rice 0, 15 -0, 30 Wheat 1, 42 -11, 5 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 10

Meats and fish Meats/fish Myo-Inositol mg/g Beef 0, 09 -0, 37 Chicken 0, 30 -0, 39 Lamb 0, 37 Pork 0, 14 -0, 42 Turkey 0, 08 -0, 23 Beef liver 0, 64 Chicken liver 1, 31 Pork liver 0, 17 Tuna 0, 11 -0, 15 Trout 0, 11 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 11

Absorption The enteric absorption of free myo-inositol occurs by active transport. The uptake of myo-inositol from the small intestine is virtually complete. The enteric absorption of phytic acid depends on the ability to digest that form and on the amounts of divalent cations in the diet/meal. Most mammals do not absorbe phytic acid. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 12

Transport myo-Inositol is transported in the blood predominantly in the free form. The normal circulating concentration of myo-inositol in humans is about 30 µM. A small but significant amount of phosphatidylinositol (PI) is found in association with the circulating lipoproteins. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 13

Transport Free myo-inositol is taken up by an active transport process in some tissues (kidney, brain) and by carrier-mediated diffusion in others (liver). The active process requires Na+ and energy, and is inhibited by high levels of glucose. Untreated diabetics show impaired tissue uptake and impaired urinary excretion of myo-inositol. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 14

Metabolism Free myo-inositol is converted to PI within cells either by de novo synthesis by reacting with the liponucleotide cytidine diphosphate (CDP)-diacylglycerol, or by an exchange with endogenous PI. Phosphatidylinositol can, in turn, be sequentially phosphorylated to the monophosphate (phosphatidylinositol 4 -phosphate, PIP) and diphosphate (phosphatidylinositol 4, 5 diphosphate, PIP 2) forms by membrane kinases. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 15

Metabolism • In tissues, myo-inositol is found as the free form, as PI, PIP and PIP 2. • The myo-inositol-containing phospholipids tend to be enriched in stearic acid (predominantly at the 1 -position) and arachidonic acid (predominantly at the 2 position) in comparison with the fatty acid compositions of other phospholipids. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 16

Metabolism • The turnover of the myo-inositol phospholipids is accomplished intracellularly. • Phosphatidylinositol phosphates can be catabolized by cellular phosphomonoesterases (phosphatases), ultimately to yield PI. • In the presence of cytidine monophosphate, PI synthetase functions (in the reverse direction) to break down that form to yield CDP-diacylglycerol and myo-inositol. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 17

Metabolism • The kidney appears to perform most of the further catabolism of myo-inositol, first clearing it from the plasma and converting it to glucose and, then, oxidizing it to CO 2 via the pentose phosphate shunt. • The metabolism of myo-inositol appears to be relatively rapid. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 18

Metabolic functions The metabolically active form of myo-inositol is phosphatidylinositol, which is thought to have several physiologically important roles: ● Effecter of the structure and function of membranes ● Source of arachidonic acid for eicosanoid production ● Mediator of cellular responses to external stimuli 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 19

Health effects 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 20

Preterm infants Three randomized, clinical trials have found inositol supplementation to improve survival and reduce retinopathy of prematurity, bronchial dysplasia and intraventricular hemorrhage. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 21

Psoriasis A small, randomized clinical trial with psoriasis patients found supplementation with inositol to reduce the severity of symptoms. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 22

Psychiatric disorders Because mood stabilizers such as lithium, valproate and carbamazepine function by the stabilization of inositol signaling, it has been suggested that inositol may have value in the treatment of depression and other psychiatric disorders. 2/16/2022 Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 23

Literature • Combs GF. The Vitamins. Fundamental Aspects in Nutrition and Health. Elsevier Inc. 2008. 2/16/2022 24