Inositol (Vitamin B8) as Natural Remedy for Clinical Depression



Administration of inositol decreased signs of depression in two animal studies. Several small human studies suggest that inositol may be of value in the treatment of depression, particularly for those who do not respond to antidepressant medications.
(Harry Croft, MD (Psychiatrist) Medical Director)





What is Inositol?

Inositol, or Vitamin B8, is a water soluble fatty lipid that is required by the body for the formation of healthy cells. Inositol has been shown to be effective in treating some cases of depression, anxiety, OCD and other psychological disorders that respond to serotonin uptake inhibitors.

Inositol is a naturally occurring isomer of glucose, though it is generally considered to be a member of the B vitamin family. It is a key intermediate in the intracellular phosphatidyl inositol second messenger pathway activated by numerous serotonergic, cholinergic, and noradrenergic receptors. In this capacity it serves as an important signal transduction molecule, but inositol is also a structural component of cellular membrane phospholipids. Research indicates that inositol is an effective and safe option in the treatment of panic disorder, obsessive-compulsive disorder (OCD), bulimia nervosa, binge eating and/or depression. Inositol's efficacy, in the absence of side effects, makes this nutrient an attractive addition to treatment plans for specific mood disorders. Following is a scientific review of inositol for the treatment of mood disorders, including a discussion of its anecdotal use for the treatment of insomnia and its cautioned use by pregnant women for the prevention of neural tube defects and embryopathies.

Among other reported benefits of inositol in clinical settings are:
  • Reduction in the need for pain medication when patients are given inositol.
  • Reduction of edema in treatment of scald burns.
  • Relieving the symptoms of diabetic neuropathy.

According to an abstract published by Lisa Colodny, Pharm D. and Ronald L. Hoffman, M.D. about the clinical applications of inositol, “Inositol is now established as a significant mediator of calcium mobilization in the endoplasmic reticulum. Modifying this mobilization of calcium may be effective in treating some CNS disorders like Alzheimer's disease, depression, panic disorder, obsessive compulsive disorder, and as an analgesic for pain control. Likewise, its use to alleviate lithium-induced adverse reactions is also promising.”

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What inositol  Does?

Inositol is used in the production of inositol triphosphate and diacylglycerol, both of which are molecules involved in the system that allows communication between neurotransmitters and the interior of cells. It is believed that a decrease in inositol could lead to a shortage of these two molecules, causing mood-regulating neurotransmitters - such as serotonin, dopamine and norepinephrine - not to be able to properly communicate with the interior of brain cells. Supplementation with inositol could help depression by improving the functioning of this.

So, Inositol is a ‘second messenger’, triggering the release of calcium in cells. It also is involved in the transmission of messages between neural cells and the transport of fats within cells. It’s most important role seems to be in the central nervous system, where it serves to help transmit messages along neural pathways. Various studies have shown its efficacy in treating a number of psychological disorders that seem to have a chemical basis, including bulimia, OCD, depression and bipolar mood disorder. Inositol seems to be present in greater concentration in the cells in and around the central nervous system, including brain cells and retinal cells, and in other specialized cells such as bone marrow and intestinal cells. It is also found in high concentration in mother’s milk, leading to the possibility of a link to the immune system.

Because of its role in cell health and neurotransmission, inositol is considered an important nutrient, even though it is not technically a ‘vital’ nutrient or a vitamin.

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Health Benefits of inositol

Inositol has been used for some time in the treatment of several neurologically based disorders. These include:
  • Mild to moderate depression. Patients treated with supplements of inositol showed a definite improvement in several studies of depression.

    Depressive patients generally have decreased levels of inositol in their cerebrospinal fluid. Researchers now theorize that inositol produces positive clinical results in patients with depression due to intracellular phosphatidyl inositol serving as a second messenger for 5-hydroxytryptamine (5-H[T.sub.2]) receptor signaling mechanisms. Serotonin selective reuptake inhibitors (SSRIs), a family of drugs commonly used to treat depression, have a similar therapeutic profile to inositol in that they inhibit serotonin reuptake in the synaptic cleft.

    Levine et al. performed a double-blind, placebo-controlled trial for 28 days on 28 depressed patients using a large dose (12 grams per day) of inositol. The Hamilton Depression (HAMD) Scale was used to evaluate patients after the 28-day trial period, and a significant overall benefit was confirmed in the inositol group compared to the placebo group. No changes were noted in liver, kidney, or hematological function as a result of the high-dose inositol supplementation.

  • Obsessive-compulsive disorder (OCD). In several studies, patients suffering from OCD and related disorders showed relief of their symptoms when given supplements of inositol.

Levine completed a review of research studies using inositol on psychiatric patients. The review highlighted some interesting findings with OCD patients. Serotonin plays a definitive role in obsessive-compulsive disorder as confirmed by the effectiveness of SSRIs in OCD patients and the fact that serotonin agonists exacerbate the syndrome. Rahman and Neuman effectively reduced serotonin receptor desensitization via the administration of myo-inositol.

These research findings, coupled with the knowledge that SSRIs have proven beneficial in the treatment of OCD, influenced Fux et al. to complete a double-blind, placebo-controlled, random, crossover treatment trial of inositol on OCD. Thirteen patients, all of whom met DSM-III-R criteria for OCD, completed the trial. Six patients began the trial on placebo and seven began the trial on inositol (18 grams per day) for a total of six weeks for the first phase and six weeks for the crossover phase. The researchers administered 18 grams of inositol rather than 12 grams (typical dose for depressive patients) because OCD patients generally respond to higher relative doses of SSRIs than is needed to effect change in most depressives. The OCD patients were free of drug and alcohol abuse and had no evidence of diabetes or GI disorder. OCD was assessed using the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and depression and anxiety were assessed using the Hamilton Depression Scale (HDS) and Hamilton Anxiety Scale (HAS). The mean improvement in OCD symptoms from baseline to six weeks was 5.9 for inositol versus 3.5 for placebo. This indicates a measurable positive response of OCD patients to inositol.

  • Panic attacks. Clinical evidence suggests that large doses of inositol may reduce the number and severity of panic attacks.

Panic attacks are recurring attacks of severe anxiety without an apparent cause. Agoraphobia (irrational fear and avoidance of crowds, travel, and multiple situations), depression, alcohol abuse, and suicide are common symptoms and may be exacerbated by post-traumatic stress. Current treatments usually consist of antidepressant drugs and cognitive-behavioral therapy.

Antidepressant medications affecting serotonin metabolism are effective about 70% of the time for dramatic, short-term improvement of anxiety symptoms. However, chronic residual symptoms often persist in the long term. 25-75% of patients with panic disorder discontinue drug treatment because of side effects, and these patients quickly relapse.

In one study, twenty-one patients diagnosed with panic disorder with or without agoraphobia were given 12 grams of inositol per day or placebo. In the treatment group, the severity and frequency of panic attacks declined significantly with minimal associated side effects. The average number of panic attacks per week in patients treated with inositol fell from 10 to 3.5 per week. The researchers concluded that these results were "clinically meaningful" in the management of panic attacks.

More recently, inositol was compared with the antidepressant fluvoxamine in the treatment of panic disorder. This study represents a more stringent test of the effects of inositol in treating panic disorder because it is the first to compare inositol with an established antidepressant drug. In this study of 20 patients with panic disorder, inositol was found to be slightly but significantly more effective than fluvoxamine in reducing the number of panic attacks. Otherwise, it was comparable to fluvoxamine on all other measures (HAS, phobia, and Clinical Global Impression (CGI) Scale). Since inositol appears to be as effective as fluvoxamine, patients may prefer it and continue to take it for the long term because side effects are extremely rare and mild.

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Inositol in Diet

Fruits and vegetables that are especially rich in inositol include: cabbage, beans, legumes, seeds, nuts, cantaloupe, bananas, raisins, oranges and other citrus fruits. It is also found in wheat, cereal, oat flakes, wheat bran, wheat germ, brown rice, brewer's yeast and unrefined molasses.

Inositol is also found in organ meats, such as brain, heart and liver.

Dosage

The recommended doses for inositol generally fall in the range of 6 to 20g per day, with 12g being the more usual dose. It is taken in divided doses, two to four times a day.

Due to the potential risk of cycling, patients with bipolar disorder should consult with their physician before supplementing with inositol.

Side Effects and Limitations

Inositol is well-tolerated and appears to be quite safe. Side effects may include: mild decreases in plasma glucose, flatulence (gas), nausea, sleepiness, insomnia, dizziness and headache. There have been some case reports of inositol-induced mania in bipolar patients. To date, there have been no reports of toxicity or drug-drug interactions with inositol.

Inositol supplementation is not recommended for pregnant women due to the fact that there is a risk of inducing uterine contractions. It is not known if it is safe for breastfeeding women.

Is Inositol an Effective Treatment for Depression?

Inositol is readily available in most health food stores without a prescription and recommended for the treatment of a variety of mental disorders, including depression.

Thus far, inositol has mainly been investigated as an add-on to mood stabilizers and antidepressants for the treatment of the depressive symptoms of bipolar disorder. Findings suggest that it may be at least somewhat helpful for these patients.

It is not known whether inositol could also help unipolar depression. Although two studies conducted using unipolar patients had negative results, their sample sizes were too small to draw any definitive conclusions. More research is still needed to consider Inositol as effective solution for depression relief. The good thing, however, to come of the trials was that the supplement was absolutely safe and was not associated with any side effects.

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