Inositol

Inositol is a small molecule structurally similar to glucose. Foods rich in inositol include whole grains, citrus fruits, and beans. It is a vitamin-like compound (pseudovitamin) that forms a compononent of cell membranes and is involved in cellular signalling. There are nine different inositol stereoisomers of which myo-inositol is the most common and most well-understood form.

Inositol has been known to have some anti-anxiolytic properties, and since it is a naturally occurring compound, it is favored over pharmaceuticals for anxiety.

In fact, the most studied usage of inositol has been for lowering anxiety. Medical indications for inositol include diabetic nerve pain, panic disorder, high cholesterol, insomnia, cancer, Alzheimer's, ADHD, and for treating side effects of lithium.

Is it safe? Are there side effects?

Inositol is approved as a dietary supplement component under provisions of the Dietary Supplement Health and Education Act of 1994.

Potential side effects include diarrhea. However this is only seen when inositol is taken in overly large dosages.

Effects on Cognition

There are limited robust scientific studies looking at the effect of inositol on cognition in normal people. It is an area with huge potential for research.

Memory

A 2001 study observed the effects of an energy drink blend (1 g taurine, 600 mg glucuronolactone, 80 mg caffeine, 5.25 mg glucose, 21.5 mg sucrose, 50 mg inositol, 20 mg niacin, 5 mg vitamin B6, 5 mg vitamin B5, 1.5 mg vitamin B2 and 0.005 mg vitamin B12) on mood, memory and information processing. It found no signficant effect on short-term memory (as measured by the delayed word recall task), but there were positive effects on mood and attention.1

Mood

One study in 2001 observed the effects of an energy drink blend (1 g taurine, 600 mg glucuronolactone, 80 mg caffeine, 5.25 mg glucose, 21.5 mg sucrose, 50 mg inositol, 20 mg niacin, 5 mg vitamin B6, 5 mg vitamin B5, 1.5 mg vitamin B2 and 0.005 mg vitamin B12) on mood, memory and information processing found that there was a significant effect of inositol on mood as measured by the Bond-Lader scale. The participants that took the energy drink blend reported values on the Bond-Lader scales that were skewed towards the positive attitudes.1

Attention

The 2001 study saw a significant effect of inositol on attention as measured by the rapid visual information processing task.1

Effects on Medical Conditions

There have been a number of studies measuring the effect of inositol on diseases. In particular, there's a growing body of clinical research behind inositol as an anxiolytic.

Panic Disorder

A double blind study in panic disorder patients found that taking inositol reduced the number of panic attacks in the patients per week around 4 attacks.2

Another double blind study in 21 panic disorder patients found that ingestion of 12g/day inositol for 4 weeks, leads to lower number of panic attacks.3

Obsessive Compulsive Disorder

A study in patients with obsessive compulsive disorder, showed that inositol ingestion of 18g/day for 6 weeks resulted in improved condition in patients with obsessive compulsive disorder (OCD). The patients were evaluated with the Yale-Brown Obsessive Compulsive Scale.4

In one study, 13 patients with OCD completed a double-blind controlled crossover trial of 18 g inositol or placebo for six weeks each. Inositol significantly reduced scores of OCD symptoms compared with placebo.5

Schizophrenia

A controlled double-blind crossover trial of 12 g daily of inositol for a month in twelve anergic schizophrenic patients, did not show any beneficial effects.5

Bulimia Nervosa

A study in patients with bulimia nervosa found that ingestion of 18g/day of inositol for 6 weeks, led to significant improvement of symptoms of bulimia nervosa and binge eating as based on the tests Global Clinical Impression, the Visual Analogue Scale, and the Eating Disorders Inventory.6

Alzheimer's Disease

The use of inositol has been proposed as a therapeutic for people with Alzheimer's disease. Studies in animals have shown that scyllo-inositol inhibits cognitive deficits in mice with expression of TgCRND8, an amyloid precursor in mice. In particular, it has been shown that mice treated with scyllo-inositol exhibited lower levels of insoluble Aβ40, Aβ42, and plaque accumulation, which are items that are thought to be involved with the pathogenesis of Alzheimer's.7

A double-blind controlled crossover trial of 6 g of inositol daily vs. glucose for one month each was carried out in eleven Alzheimer patients, with no clearly significant therapeutic effects.5

A study in Alzheimer's patients found that inositol for 6g/day for a period of one month was helpful in improving performance on orientation and language based tasks compared to placebo.8

Depression

Depressed patients are known have decreased inositol, indicating that it might be a useful therapeutic.

A study found that 12g daily of inositol, taken over 4 weeks, resulted in an improvement of symptoms based on the Hamilton Depression Scale.5

A meta-analysis showed that inositol did not carry a statistically significant effect for improving symptoms in depressed patients. However, inositol resulted in significant improvement of depressed temperament in patients with premenstrual dysmorphic disorder.9

Attention Deficit Hyperactivity Disorder

Eleven children, mean age 8.9±3.6 years were enrolled in an eight week trial of inositol or placebo at a dose of 200 mg/kg body weight. Results show a trend for aggravation of the syndrome with myo-inositol as compared to placebo.5

Autism

There is some interest in exploring inositol's effects on autism symptoms. However a controlled double-blind crossover trial of inositol 200 mg/kg per day showed no benefit in nine children with autism.5

ECT-induced Memory Impairment

Cholinergic agonists have been reported to ameliorate electroconvulsive therapy (ECT)-induced memory impairment. Inositol metabolism is involved in the second messenger system for several muscarinic cholinergic receptors. Inositol 6 g daily was given in a crossover–double-blind manner for five days before the fifth or sixth ECT to a series of twelve patients, without effect.5

Structure & Synthesis

Inositol is found in various foods. The foods that contain inositol include: citrus fruits, beans, cantaloupe, lecithin (e.g., from sunflower seeds, soy, eggs), bananas, kiwi, peaches, pears, cabbage, okra, tomatoes, eggplant, pumpkin, bell peppers, potatoes, carrots, whole grains, fish, and breast milk.10

Inositol can be synthesized in the lab from glucose (see figure below). The synthesis can be conducted in yeast.11,12

Synthesis of inositol from glucose.

Mechanisms of Action

Inositol is taken up into tissue via a sodium-dependent inositol co-transporter. This co-transporter also mediates glucose uptake, which means it can competitively inhibit inositol uptake. In human neural tissue, myo-inositol is around 3.93+/-1.13mM in youth and 4.69+/-0.69mM in older subjects. Trials have shown that inositol has effective anti-anxiety properties on par with RX-only fluvoxamine for reducing anxiety and panic symptoms.

  1. Warburton, D. M., Bersellini, E., & Sweeney, E. (2001). An evaluation of a caffeinated taurine drink on mood, memory and information processing in healthy volunteers without caffeine abstinence. Psychopharmacology, 158(3), 322-328.

  2. Palatnik, A., Frolov, K., Fux, M., & Benjamin, J. (2001). Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. Journal of clinical psychopharmacology, 21(3), 335-339.

  3. Benjamin, J., Levine, J., Fux, M., Aviv, A., Levy, D., & Belmaker, R. H. (1995). Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. American Journal of Psychiatry, 152(7), 1084-1086.

  4. Fux, M., Levine, J., Aviv, A., & Belmaker, R. H. (1996). Inositol treatment of obsessive-compulsive disorder. The American journal of psychiatry, 153(9), 1219.

  5. Levine, J. (1997). Controlled trials of inositol in psychiatry. European Neuropsychopharmacology, 7(2), 147-155.

  6. Gelber, D., Levine, J., & Belmaker, R. H. (2001). Effect of inositol on bulimia nervosa and binge eating. International Journal of Eating Disorders, 29(3), 345-348.

  7. Fenili, D., Brown, M., Rappaport, R., & McLaurin, J. (2007). Properties of scyllo_inositol as a therapeutic treatment of AD-like pathology. Journal of Molecular Medicine, 85(6), 603-611.

  8. Barak, Y., Levine, J., Glasman, A., Elizur, A., & Belmaker, R. H. (1996). Inositol treatment of Alzheimer's disease: a double bund, cross-over placebo controlled trial. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 20(4), 729-735.

  9. Mukai, T., Kishi, T., Matsuda, Y., & Iwata, N. (2014). A meta_analysis of inositol for depression and anxiety disorders. Human Psychopharmacology: Clinical and Experimental, 29(1), 55-63.

  10. Clements, R. S., & Darnell, B. (1980). Myo-inositol content of common foods: development of a high-myo-inositol diet. The American journal of clinical nutrition, 33(9), 1954-1967.

  11. Dean-Johnson, M., & Henry, S. A. (1989). Biosynthesis of inositol in yeast. Primary structure of myo-inositol-1-phosphate synthase (EC 5.5. 1.4) and functional analysis of its structural gene, the INO1 locus. Journal of Biological Chemistry, 264(2), 1274-1283.

  12. Loewus, F. A., & Loewus, M. W. (1983). Myo-inositol: its biosynthesis and metabolism. Annual Review of Plant Physiology, 34(1), 137-161.

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