Inositol Supplementation – Recent Research in Mood Disorders: Part 2

​In part 1 of this blog post, we discussed the use of inositol for insulin resistance and related conditions. However, in the late 1990s and early 2000s researchers were largely focused on the effects of inositol on mood. A link between insulin resistance and depression has been established since, and may eventually provide one possible mechanism of action. (1)

​A 2014 meta-analysis suggested that inositol may be beneficial in depression, particularly premenstrual dysphoric disorder. (2) Numerous smaller studies found inositol to be effective for a spectrum of disorders that usually respond to selective serotonin reuptake inhibitors (3), including panic (4) and obsessive-compulsive disorder [OCD] (5), as well as bulimia and binge eating (6).  At dosages of 12 to 18g per day used in clinical trials, it was not necessarily the most practical therapy, but was nevertheless well-tolerated with mainly mild gastrointestinal (GI) side effects reported.

A more recent double-blind, controlled, crossover trial demonstrated that 18g of inositol had similar efficacy to 150 mg of fluvoxamine in patients with panic disorder and agoraphobia, reducing the number of panic attacks by four per week in the first month, with lower incidence of side effects such as nausea and tiredness. (7) As a natural component of the diet with few known side effects, inositol remains a viable therapy to consider for patients who are ambivalent about or intolerant of psychiatric medication for panic disorder, with larger studies needed to demonstrate long-term efficacy.

Dosing and Administration

The best way to determine the appropriateness of supplementing with inositol is to use lab testing in combination with clinical presentation.

Average dietary intake of inositol from beans, grains, nuts, and fresh produce in the US is estimated at around 1g per day. Because doses used in studies tend to be in the range of 4 to 18g per day, inositol as a supplement is often delivered in a powder form. Fortunately, this substance readily dissolves in water and has a slightly sweet taste – roughly half the sweetness of sucrose – allowing for flexibility in dosing and making it an easy addition to water, tea, or other beverages.

Adverse Effects and Contraindications

Across studies, adverse effects from inositol have been reported as mild, with no serious adverse events reported. As a sugar alcohol, inositol’s primary side effects are GI including gas, bloating and diarrhea, and may decrease over time or with gradual introduction.

However, it is important to note that any therapy that improves insulin sensitivity and glucose disposal may lower blood sugar, and should be used cautiously and under medical supervision especially in people taking other glucose-lowering medications. Close monitoring of blood sugar levels and medication dosages may be required to avoid hypoglycemia.

Test, Don’t Guess

The best way to determine the appropriateness of supplementing with inositol is to use lab testing in combination with clinical presentation. ZRT Laboratory offers minimally invasive testing in saliva and dried blood spot, including profiles that assess fasting insulin, cardiometabolic markers, and levels of sex hormones. Individuals with PCOS often benefit from the Fertility Profile or Wellness Metrics Profile. In addition, the NeuroAdvanced Profile offers dried urine testing and can help assess whether imbalances in neurotransmitters such as serotonin are contributing to symptoms of depression, anxiety, OCD, or panic disorder that may benefit from inositol or other interventions.

Related Resources

References

  1. Watson KT, Simard JF, Henderson VW, et al. Incident major depressive disorder predicted by three measures of insulin resistance: a Dutch cohort study. Am J Psychiatry. 2021;178(10):914-920.
  2. Mukai T, Kishi T, Matsuda Y, et al. A meta-analysis of inositol for depression and anxiety disorders. Hum Psychopharmacol. 2014;29(1):55-63.
  3. Levine J. Controlled trials of inositol in psychiatry. Eur Neuropsychopharmacol. 1997;7(2):147-155.
  4. Benjamin J, Levine J, Fux M, et al. Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder. Am J Psychiatry. 1995;152(7):1084-1086.
  5. Fux M, Levine J, Aviv A, et al. Inositol treatment of obsessive-compulsive disorder. Am J Psychiatry. 1996;153(9):1219-1221.
  6. Gelber D, Levine J, Belmaker RH. Effect of inositol on bulimia nervosa and binge eating. Int J Eat Disord. 2001;29(3):345-348.
  7. Palatnik A, Frolov K, Fux M, et al. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. J Clin Psychopharmacol. 2001;21(3):335-339.