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Inositol For Anxiety Disorders: An Effective Treatment?

Inositol (cyclohexane-1,2,3,4,5,6-hexol) is a non-essential nutrient synthesized within the body from glucose and is abundant within spinal fluid.  Although inositol exists in the form of 9 distinct stereoisomers, the most abundant format within cellular membranes is myo-inositol, accounting for approximately 95% of free inositol within the body.  Myo-inositol was initially isolated by researchers in 1849, and by the mid-1900s, it was discovered to play a critical role in biological processes; hence its [premature] classification as an “essential” B-vitamin (vitamin B8).

Years later researchers realized that the human body is capable of manufacturing sufficient inositol on its own, leading to a retraction of its status as vitamin B8; it is no longer considered an “essential” nutrient.  However, it is a mistake to assume that inositol lacks biological importance simply because it is non-essential.  Adequate inositol levels are associated with favorable health, whereas deficiencies have been linked to a myriad of psychiatric conditions including: ADHD, depression, insomnia – and perhaps most strongly – anxiety disorders.

Preliminary evidence suggests that correcting inositol deficiencies via increasing inositol intake may attenuate anxious symptoms.  Though inositol can be attained via dietary sources (e.g. organ meats, fruits, nuts, seeds, beans, etc.), modification of one’s diet to specifically include inositol-rich foods is generally insufficient to reap therapeutic anxiolytic effects.  As a result, a subset of individuals diagnosed with anxiety disorders have resorted to high-dose myo-inositol supplementation.

Inositol for Anxiety Disorders

The mechanism by which myo-inositol attenuates symptoms of anxiety isn’t fully elucidated.  Researchers know that individuals with severe anxiety (and depression) often exhibit abnormally low concentrations of inositol within spinal fluid.  It remains unclear as to whether inositol deficiencies cause anxiety, whether anxiety disorders cause inositol deficiencies, or if perhaps there’s a symbiotic relationship between the two.

That said, it is important to avoid assuming, [even in cases when inositol proves efficacious in reducing symptoms of anxiety], that an inositol deficiency is the sole underlying cause of an individual’s anxiety.  While insufficient inositol may prove anxiogenic, there are likely other underlying mechanisms (gene expression, hormones, neurotransmitters, regional activation, etc.) that influence one’s arousal and perceived level of anxiety.  Discussed below are some hypothetical mechanisms by which inositol may aid in the attenuation of anxiety disorders and/or anxious states.

How Inositol May Help Anxiety Disorders (Mechanism of Action)

Though the specific pharmacodynamic mechanisms by which inositol attenuates anxiety aren’t fully elucidated, many suspect that high-dose exogenous myo-inositol administration may enhance monoaminergic neurotransmission.  Specifically, some hypothesize that inositol mediates serotonergic signaling within nerve cells to elicit an anxiolytic effect.  Since inositol elicits an array of other neurophysiologic effects (e.g. calcium ion release, protein kinase C activation, and fat transport) – these may be necessary to consider as potentially contributing to its anxiolytic mechanism.

Ca2+ modulation: Inositol mediates release of Ca2+ into cytoplasm, which could play a direct or indirect role in the mitigation of anxious symptoms.  Inositol is utilized to manufacture IP3 (inositol triphosphate) and DG (diacylglycerol), thereafter, the IP3 induces IP3 receptor binding, altering calcium concentrations.  An upregulation of calcium, accompanied by DG, is known to activate protein kinase C; which has actually been linked to anxiogenic effects.

However, it is possible that a cascade of other mechanisms stemming from Ca2+ modulation facilitate reductions in anxiety.  Perhaps insufficient release of calcium may alter mitochondrial function and/or inadequate Ca2+ release could cause anxiety – possibly as a result of downstream cascade effects.  It is possible that anxiolysis associated with inositol stems from its ability to alter gating characteristics and/or pharmacology of voltage-dependent Ca2+ channels.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/1326296
  • Source: http://www.ncbi.nlm.nih.gov/pubmed/2542110

Fat transportation: In addition to mediating intracellular calcium release, inositol aids in the transportation of fat.  Inositol is believed to shuttle fats within cells and influences formation of lecithin, another fat transporter. When co-administered with choline, inositol is known to stimulate fat metabolism by accelerating the process.  The implications of inositol’s fat transport/burning may be therapeutic in regards to reducing “bad” cholesterol, but it remains unclear as to whether fat transport contributes (in any way) to inositol’s anxiolytic mechanism.

Neuronal signaling: Inositol may generate substantial anxiety relief via its ability to enhance intracellular signaling.  Neurons are understood to interact with surface proteins and other receptor complexes by sending out specific, targeted signals.  When there’s plenty of inositol (as opposed to a low amount), the neuronal signaling may be improved.

In turn, this may improve functionality of various important neurotransmitter systems including: acetylcholine, dopamine, norepinephrine, and serotonin.  Since deficits in monoaminergic signaling could be a cause of anxiety, it is possible that correcting inadequate signaling via signal strengthening may improve anxious symptoms.  Although inositol may not elevate extracellular concentrations of monoamines (e.g. increase serotonin), adequate neuronal signaling may be of equal (or perhaps greater) importance.

Serotonergic mediation: Serotonin is well-documented to play a role in development of some mood disorders and anxiety – nearly everyone is familiar with the [neurobiologically myopic] serotonin hypothesis.  We all are aware of the fact that serotonergic-based agents (e.g. SSRIs) are considered first-line options for the treatment of anxiety.  Administration of inositol may pack the biggest pharmacodynamic punch (in terms of attenuating anxiety) by mediating the serotonin system.

Researchers of inositol have discovered that following administration, inositol is metabolized into a substance that mediates 5-HT (serotonin) activation within nerve cells.  It should be speculated that mediation of serotonergic activation within nerve cells is the principal mechanism by which it alleviates anxiety.  This serotonergic mediation is thought to induce a soothing effect within cerebrospinal fluid, spinal nerves, as well as the brain.

Additionally, although inositol mediates serotonergic activation within nerve cells, it is believed to affect pathways distinct from those affected by SSRIs.  It is perhaps this distinction that results in fewer (unwanted) side effects associated with inositol when compared to serotonergic antidepressants.  Some speculate that since inositol interacts with 5-HT2 receptors, modification of 5-HT2A, 5-HT2B, and/or 5-HT2C receptors may be responsible for its anxiolytic effect.

Note: It is necessary to highlight the fact that the aforestated pharmacodynamics associated with inositol’s anxiolytic effect are entirely hypothetical.  Inositol interacts with an array of receptors (and receptor subtypes) that modulate signal transduction.  Pinpointing the specifics of inositol hasn’t been conducted – likely because inositol isn’t a pharmaceutical – meaning it will not generate the same degree of funding as a patented drug.

Benefits of Inositol for Anxiety Disorders (Possibilities)

There are many benefits associated with using inositol for anxiety disorders.  Various benefits include: its efficacy for depression, few contraindications, minimal side effects, and its unique mechanism of action (pharmacodynamics).  Understand that not everyone taking inositol is likely to reap the full list of hypothetical benefits; your mileage may vary.

  • Adjunctive option: Inositol is thought to be safe when administered as an adjunct to psychiatric medications such as SSRIs. For this reason, it was actually studied as an SSRI adjunct for the treatment of OCD.  Although it was found ineffective in that particular study for further reducing OCD symptoms, it was considered safe with low risk of contraindications.  Some individuals may derive additional anxiolytic benefit when using inositol as a medication adjunct.
  • Comorbid depression: Many individuals diagnosed with anxiety disorders suffer from comorbid depression. Often anxiety can provoke depression when an individual feels powerless in the quest to control this anxiety; this perceived loss of control leads to learned helplessness and depressive emotions.  Additionally, some individuals suffer from an anxious-depression in which they feel severely anxious and depressed simultaneously.  In any regard, there’s emerging evidence to suggest that inositol may be an effective antidepressant.
  • Decreases negative thoughts: Persistent negative thoughts are a major problem for many individuals with anxiety. Anecdotal reports have suggested that inositol may decrease automatic negative thoughts (ANTs) or counteract the effect of negative thinking.  Although you may not feel like jumping for joy after taking inositol, it may lessen the impact negative thinking has over your physiology.  Decreasing negative thoughts may be related to modulation of neurotransmitters to yield antidepressant and/or anxiolytic effects.
  • Efficacy: Despite the fact that there’s limited evidence to confirm inositol’s therapeutic efficacy in the treatment of anxiety disorders, there is some suggesting that it provides benefit. In particular, it appears effective for the treatment of panic disorder (it reduces weekly panic attacks more than an approved anti-panic drug Luvox).  There is also evidence to suggest that it is likely effective for the treatment of OCD.
  • Fast-acting: It isn’t known how quickly inositol “kicks in” but many anecdotal accounts indicate that it works from the very first dose. Clinical studies suggest it provides anxiolytic relief after several weeks of treatment.  It is necessary to consider that inositol may be faster-acting than standardized serotonergic-based medications (e.g. SSRIs) for anxiety relief.
  • Few contraindications: The contraindications associated with inositol are considered minimal. In fact, many sources imply that inositol has zero known contraindications – even when taken at high doses.  That said, it is still always recommended to consult a medical professional to verify safety of inositol administration.  Since most supplemental and/or pharmaceutical anxiolytics pose substantial contraindication risk, inositol may be a safer option – especially when administered with other agents (drugs or supplements).
  • Insomnia reduction: Excessive anxiety and fear can trigger sympathetic overactivation and parasympathetic underactivation, leading to a fight-or-flight response, and all sorts of neurophysiologic changes. Inositol is thought to decrease anxiety, which in turn may prove beneficial for overcoming insomnia.  This may be a positive-feedback loop in that once insomnia is reduced, anxiety may be further reduced; the better one’s sleep, the less their anxiety (usually).
  • Low cost: The cost of inositol is considerably cheaper than new psychiatric medications, which may be favorable for some individuals. As of now, you can purchase 1 lb of inositol online for around $25.  Assuming you were to take 15 grams of inositol per day, this would last you for 30 days.  Most new, patented psychiatric anxiolytics cost hundreds of dollars for a prescription which may be problematic for those without insurance.  Most people can afford inositol and will gladly try it for less than $1 per dose.
  • Minimal side effects: Some evidence suggests that there may be mildly unpleasant inositol side effects. However, in scientific studies examining high-dose inositol for the treatment of anxiety, no significant side effects were reported.  Based upon the available literature, side effects derived from inositol are practically non-existent.  Since many users struggle with unwanted side effects from SSRIs (e.g. weight gain, sexual dysfunction, amotivational syndromes, etc.) – inositol may be a welcome alternative.
  • Non-existent withdrawal: There is no current evidence to suggest that inositol is associated with withdrawal symptoms. Many popular anxiolytic agents (e.g. benzos, SSRIs, etc.) are associated with horrendous discontinuation symptoms.  In many cases, patients are forced by default to keep taking a medication that is no longer working simply because they don’t want to endure the psychological pain associated with discontinuation.  Discontinuation of pharmaceuticals usually results in worse anxiety than pre-treatment baseline levels – sometimes for a period of months after a final dose.
  • Pharmacodynamics: Inositol’s mechanism of action isn’t well-understood, however, it is believed to function differently than SSRIs. Many speculate that inositol enhances signaling of neurotransmitters such as acetylcholine, dopamine, norepinephrine, and serotonin.  Bolstered serotonergic signaling in particular may prompt a soothing effect that induces an anxiolytic effect.  Since many people fail to respond to SSRIs, this alternative mechanism may prove beneficial to first-line non-responders.
  • Sleep quality: In addition to reducing insomnia for some individuals, inositol may improve sleep quality and quantity. Many people with anxiety struggle to get sufficient, deep sleep because they’re overly stimulated and constantly primed with anxious thoughts.  On an EEG (electroencephalograph), anxious individuals typically exhibit excess beta waves and insufficient slow waves (e.g. alpha, theta, delta) – which may compromise their ability to attain the deepest, most restorative sleep.  Improved sleep quality from inositol may also be beneficial in that better sleep may effectively reduce anxiety.
  • Treats different subtypes: Although it is unclear as to whether inositol can effectively treat many types of anxiety as a “jack-of-all-trades” anxiolytic, it has been noted as therapeutic for reducing symptoms of: panic disorder and OCD. Other evidence suggests it may be effective for PTSD and anxiety associated with eating disorders.  Anecdotal accounts have documented its efficacy for reducing social phobia and generalized anxiety disorder (GAD).

Drawbacks of Inositol for Anxiety Disorders (Possibilities)

There are some possible drawbacks associated with inositol as a treatment for anxiety disorders.  The biggest drawbacks are that its efficacy is questionable and that high-dosages are typically required for therapeutic relief.  This means that you could end up trying inositol thinking it’ll work only to derive no benefit.

  • High dosages required: A notable drawback associated with inositol supplementation is the high daily dosage that may be required for symptom management. Although some individuals may effectively manage anxiety with low-dose inositol, clinical research suggests that high-doses of up to 18 grams per day may be necessary for significant symptomatic relief.  That said, when considering that inositol is relatively cheap, most users end up paying less than $30 for a month’s supply of high-dosing.
  • Questionable efficacy: The efficacy of inositol as an anxiolytic remains scrutinized by professionals due to the fact that published studies are small-scale and results are contradictory. Some studies suggest that it works, while others note that it is ineffective.  Due to the fact that there is evidence suggesting that inositol may fail to provide clinically significant anxiolytic relief, it is important to realize that not all users may derive benefit from its usage.  Some users may take high doses of inositol and notice no change from homeostatic, pre-treatment baseline level of anxiety.
  • Tolerance: Although tolerance to inositol hasn’t been reported, some users may notice diminishing anxiolytic effects after an extended term of inositol administration. An individual’s neurophysiology may adjust from homeostasis to accommodate the exogenously administered inositol, and eventually, tolerance is developed.  Though tolerance onset is unclear and unlikely to be rapid, this may be viewed as a drawback associated with inositol.
  • Unwanted side effects: Despite the fact that no significant side effects have been reported among high-dose inositol users in clinical trials, it is unlikely that inositol has zero side effects. Anecdotal reports of inositol usage report side effects such as: agitation, apathy, brain fog, decreased self-awareness, diarrhea, libido reduction, and sweating.  Consider that inositol may not be completely devoid of side effects as the literature suggests.
  • Unknown long-term implications: The general health implications associated with long-term inositol usage aren’t well understood. This is largely due to the fact that no long-term trials of exogenous inositol administration (particularly at high doses) have been conducted.  It is possible that a long-term inositol user may experience deleterious health effects, dwindling efficacy, or notice onset of adverse reactions (after an extended term of administration).
  • Worsening of anxiety: Although no evidence from research suggests that inositol may worsen anxiety, this is a necessary outcome to consider. Many individuals with anxiety disorders take supplements and/or drugs that are thought to only provide significant anxiolytic benefit, yet they experience elevated anxiety.  Inositol is known to activate protein kinase C, which is associated with increased anxiety.  Additionally, it is believed to mediate serotonergic transmission, which could heighten anxious symptoms in a subset of users.

Inositol for Anxiety Disorders (Review of Scientific Research)

In attempt to elucidate the therapeutic efficacy of inositol for the treatment of anxiety disorders (and anxious symptoms) it is necessary to examine the available scientific literature investigating it as a potential anxiolytic agent.  Unfortunately, few large-scale, robustly-designed studies investigating inositol as an anxiolytic have been published for obvious reasons: there’s limited previous research to warrant additional inositol investigation and financial incentives to determine its efficacy are low (as inositol is not a patentable pharmaceutical).  That said, available preliminary evidence suggests that inositol may be as effective as first-line serotonergic anxiolytics (e.g. SSRIs) for certain types of anxiety.

2014: In 2014, Mukai et al. published a paper entitled, “A meta-analysis of inositol for depression and anxiety disorders.”  Their research involved digging through scientific databases including: PubMed, Cochrane Library, and PsycINFO – for studies published prior to August 2013.  Inclusion criteria for their meta-analysis required the trials to be double-blinded, randomized, and placebo-controlled and involved examining inositol’s efficacy in treating individuals diagnosed with clinical anxiety and/or depression.

Researchers were able to find a total of 4 randomized-controlled trials (RCTs) investigating inositol for anxiety disorders among 70 participants.  Two of the studies specifically examined inositol’s efficacy for OCD (obsessive compulsive disorder), while the remaining two examined its efficacy for PTSD and panic disorder, respectively.  Results from the meta-analysis suggested that inositol did not significantly improve symptoms of anxiety.

Authors noted that their meta-analysis is relatively limited due to the fact that only a small number of studies fit inclusion criteria.  Moreover, with a meager number of 70 total participants in anxiety trials, it is nearly impossible to completely write-off inositol as ineffective.  That said, it is important to err on the side of evidence – this trial suggests inositol is relatively useless for anxiety.

Perhaps an important limitation to mention associated with this study (that wasn’t discussed by authors) is the generalization of “anxiety disorders.”  Simply clustering OCD, PTSD, and panic disorder together is misleading in that inositol may be more effective for one particular subtype of anxiety disorder compared to another.  Therefore, when accounting for participant pool size, as well as clumping distinct anxiogenic disorders together, this meta-analysis may be considered impractical and useless in determining the anxiolytic efficacy of inositol.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/24424706

2001: A paper entitled “Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder” by Palatnik et al. was published in 2001.  It examined the efficacy of inositol compared to the serotonergic antidepressant fluvoxamine (brand name “Luvox”) for those with panic disorder.  Researchers noted that investigating alternative anxiolytic treatments such as inositol may be necessary due to the fact that 30% of panic disorder patients are non-responders to traditional pharmaceuticals.

Since previous studies of myo-inositol demonstrated efficacy compared to a placebo for panic disorders and OCD, researchers wanted to make a direct comparison with an FDA-approved agent (Luvox).  They set up a double-blind, controlled, random-order crossover study in which 20 patients participated over a 2-month span.

Prior to the study, participants were assessed at baseline with the Hamilton Rating Scale for Anxiety (HAM-A), agoraphobia scores, and Clinical Global Impressions Scale (CGI-S). During the first month of treatment, the 20 patients received inositol (up to 18 grams per day).  For the second month of treatment, the 20 patients received fluvoxamine (Luvox) at a dosage of 150 mg per day.

Assessments were conducted after the 1-month term of inositol, and after the 1-month term of luvox.  Within the first month, inositol effectively decreased the number of panic attacks per week by 4; this was more effective than Luvox in the second month which only decreased them by 2.  Furthermore, the fluvoxamine was associated with unwanted side effects such as nausea and lethargy, whereas inositol wasn’t.

Although this was a small-scale study, it provides some evidence to suggest that high-dose inositol may be superior to an already-established serotonergic agent (SSRI) for the treatment of panic disorder.  In addition to providing superior efficacy, the inositol was associated with a superior side effect profile.  Improvements on all tests including the: HAM-A, agoraphobia assessment, and CGI-S – were evident among inositol users.

This study may have been limited in that it was not placebo-controlled, as well as that the transition from inositol to fluvoxamine may not have been neurophysiologically seamless.  It is possible that lingering effects from inositol carried over into the first week or two of the second month, even if inositol had been eliminated from systemic circulation.  Perhaps another study should be conducted with a placebo control and/or with a washout period (e.g. weeks) between the inositol and the SSRI.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11386498

2001: Although data from animal studies is relatively low on the evidence pyramid for scientific research, it is not entirely useless.  There are many substances that decrease anxiety in animals similar to humans.  In 2001, Einat and Belmaker published a report entitled, “The effects of inositol treatment in animal models of psychiatric disorders” in which they examined inositol’s efficacy in mitigating symptoms of psychiatric symptoms among animals.

Authors report that inositol’s pharmacodynamic effects may be akin to selective serotonin reuptake inhibitors (SSRIs) for anxiety reduction.  They note that inositol is a precursor in the phosphatidylinositol cycle and a second messenger system that interacts with 5-HT2 receptors.  Administration of inositol to animal models notably: increased activity levels, reduced immobility in a forced-swim test, and decreased anxiety-like behaviors in an elevated plus-maze.

In monkeys, inositol did not appear to counteract amphetamine-induced hyperactivity nor did it improve memory task performance; this suggests perhaps that psychostimulant-induced anxiety may be unchanged by inositol.  Authors mentioned that although inositol demonstrates preliminary efficacy for the treatment of anxiety in animal models, as well as humans, further research is warranted.  The existing small-scale human trials of inositol for anxiety are incapable of validating its clinical efficacy (or lack thereof), and hence, larger studies are necessary.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11172878

2001: A bulk of individuals (~66%) diagnosed with eating disorders exhibit comorbid symptoms of anxiety and/or have been diagnosed with clinical anxiety disorders.  It is unclear as to whether an underlying anxiety disorder promotes disordered eating and/or whether neurobiological commonalities are shared between the two conditions.  However, research suggests that 42% of individuals diagnosed with eating disorders suffered from an anxiety disorder prior to the manifestation of their eating disorder.

Knowing that there’s a strong link between eating disorders and anxiety disorders, it may be helpful to examine a study investigating the efficacy of inositol for the treatment of bulimia nervosa and binge eating disorder.  Since inositol is efficacious in treating panic disorder (superior to fluvoxamine), and SSRIs are commonly administered to treat eating disorders, we could hypothesize that inositol reduces anxiety (or its shared neurobiological underpinnings).  It may be the anxiolytic effect that is specifically responsible for improving disordered eating.

A study published by Gelber, Levine and Belmaker in 2001 entitled “Effect of inositol on bulimia nervosa and binge eating” – examined inositol’s therapeutic efficacy as a treatment for disordered eating habits.  In the study, 12 participants received either 18 grams of inositol or a placebo for 6 weeks (in each arm).  To gauge inositol’s efficacy, researchers assessed severity of eating disorders at pre-treatment baseline, and after inositol administration with the: Global Clinical Impression, Visual Analogue Scale, and Eating Disorders Inventory.

Results indicated that inositol treated eating disorders significantly better than a placebo.  Authors concluded that it is as therapeutic for patients with bulimia nervosa and binge eating disorders.  It would’ve been interesting if they also examined patient anxiety levels throughout the study.

There may be a correlation between inositol’s anxiolytic efficacy and its propensity to normalize disordered eating.  It should be speculated that decreases in anxiety resulting from inositol may be directly associated with its degree of therapeutic efficacy for eating disorders.  Although this study was small scale (and is therefore questionable in terms of accuracy), improved eating habits may be an implication of decreased anxiety.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11262515

2000: Another report by Kofman et al. (2000) entitled, “The anxiolytic effect of chronic inositol depends on the baseline level of anxiety” investigated inositol as an anxiolytic among rats.  Researchers noted that inositol is a precursor for membrane phosphoinositides, and as a result, plays an important role in transduction of cellular signals.  Researchers note that inositol was previously (1997) found to reduce anxiety among elevate plus models of anxiety, leading them to test chronic intraperitoneal and dietary administration in rats across 4 experiments.

Results indicated that there was no clinically significant effect of inositol on anxiety when given to the rats via dietary administration (food), but there was a significant effect when administered exogenously via chronic injections.  The rats that received inositol injections exhibited increases in closed arm and total arm entries – indicating reduced anxiety-like behavior.  In another set of experiments, researchers examined the effect of chronic dietary inositol.

One experiment involved administration of saline injections to induce anxiety in an elevated plus maze.  The anxiety among rats receiving these injections was only modestly reduced by chronic dietary inositol.  The other experiment involved 3 weeks of 5% dietary inositol administration to rats that were pre-exposed to a cat.  Increases in open arm entries were noted, indicating that dietary inositol may decrease anxiety.

That said, it is important to realize that comparative research suggests that exogenously administered inositol in the form of injections (and/or supplements) yields superior anxiolytic effects compared to chronic dietary intake.  Although results from this rodent study cannot be generalized to humans, it should be hypothesized that quantity of inositol (dosage) may influence anxiolytic effects.  It is unlikely that dietary inositol intake (even if chronic) is capable of providing sufficient inositol for anxiolytic efficacy.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/10847563

1999: A study published in 1999 by Fux, Benjamin, and Belmaker investigated the efficacy of inositol as an antidepressant augmentation strategy compared to a placebo for the treatment of OCD (obsessive compulsive disorder).  The impetus for this study stemmed from the fact that treatment of OCD with an SSRI often fails to sufficiently manage symptoms, as well as that previous research indicates that inositol effectively treats OCD as a standalone agent.  Researchers set up a double-blind, crossover design for 10 patients that had been diagnosed with OCD.

Prior to the study, as well as each week during the study, severity of patient OCD symptoms were assessed with the Yale-Brown Obsessive-Compulsive Scale (YBOCS) and Hamilton Depression and Anxiety Scales (HAM-D and HAM-A).  The study incorporated a double-blind, cross-over design and patients received 18 grams of inositol per day or a placebo (daily) for 6 weeks in addition to an SSRI.  Results noted that no significant difference was noted between the group receiving the inositol compared to the placebo adjunct.

An obvious limitation associated with this study is the small sample size of just 10 individuals – which could skew results significantly.  Additionally, one should consider that inositol may not be synergistic as an adjunct to an SSRI for OCD.  Perhaps it still offers some benefit, but certain mechanisms of inositol may have been attenuated by the SSRI.  That said, it is also possible that inositol lacks clinical efficacy for the treatment of OCD.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/11281989

1997: A study published by Benjamin et al. (1997) documented the efficacy of inositol in blocking pharmacologically-induced anxiety, specifically “panic attacks.”  Assuming inositol is truly an effective anxiolytic agent for the treatment of panic disorder, it should theoretically be effective in attenuating any form of panic, regardless of whether pharmacologically induced.  Previously, chronic dosing of inositol had demonstrated efficacy in mitigating panic disorder symptoms.

In this study, researchers administered a single 20-gram dose of inositol to 7 individuals with panic disorder that were provoked with pharmacologically-induced anxiety with the agent m-CPP (meta-Chlorophenylpiperazine).  The single-dose administration of (20 grams) inositol was deemed ineffective for reducing panic attacks following m-CPP administration.  Unfortunately, there are some major limitations associated with this study.

Not only was the study small-scale, but it may not be helpful to assume that inositol should be able to treat drug-induced panic.  Perhaps endogenously manifesting panic attacks would benefit from the single 20-gram dose.  Additionally, there was no prior evidence to suggest that a single-dose of inositol would effectively treat m-CPP (drug)-induced panic.  It may be necessary to conduct a similar study with chronic administration of high-dose inositol prior to m-CPP administration (in attempt to replicate results).

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/9352475

1996: A study by Fux et al. (1996) entitled, “Inositol treatment of obsessive-compulsive disorder” – investigated its therapeutic efficacy among those with OCD.  Researchers noted that inositol is a simple polyol second messenger precursor and demonstrated previous efficacy among individuals with depression and panic.  For this study, researchers recruited 13 individuals diagnosed with OCD and set up a double-blind, controlled crossover design.

Participants were slated to receive either 18 grams of inositol (per day) or a placebo (daily) for 6 weeks, followed by the opposite for an additional 6 weeks.  Obsessive compulsive symptoms were assessed with the Yale-Brown Obsessive Compulsive Scale.  Results indicated that during 6 weeks of inositol administration (18 grams per day), OCD scores were significantly improved (as measured by the Yale-Brown OCS).

Authors propose that inositol may be effective in treating related psychiatric conditions responsive to SSRIs (e.g. depression and panic disorders).  It is important to note that this was yet another very small-scale study and results may differ in a larger trial.  However, this provides evidence to suggest that inositol may be a viable non-pharmaceutical alternative for the treatment of OCD.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/8780431

1995: An early study entitled, “Double-blind, placebo-controlled, crossover trial of inositol treatment for panic disorder” was published in 1995 by Benjamin et al.  Authors of this study suggested that since inositol was an important intracellular messenger precursor, and that earlier literature suggested its efficacy in attenuating depressive symptoms – it may be effective in treating panic disorder.  For this study, researchers recruited 21 individuals diagnosed with panic disorder (with or without comorbid agoraphobia).

The study was double-blinded, placebo-controlled, randomized, and implemented a crossover design.  The 21 individuals received either inositol (12 grams per day) or a placebo and symptoms of panic disorder were measured.  Each was then crossed over to receive the opposite of their first treatment (e.g. those receiving inositol now received the placebo and vice-versa) and panic disorder symptoms were reassessed.

Results noted that severity of panic disorder (and comorbid agoraphobia among those diagnosed) significantly declined among those receiving inositol (12 grams per day) compared to those receiving the placebo.  Additionally, researchers noted that side effects associated with inositol were minimal and that it may be an appealing therapeutic option for the treatment of panic disorder.  This provides additional evidence that inositol is likely an effective anti-panic agent with anxiolytic properties.

  • Source: http://www.ncbi.nlm.nih.gov/pubmed/7793450

Limitations associated with research of inositol for anxiety

Based on the available scientific literature, it is difficult to gauge inositol’s efficacy as an anxiolytic agent due to a host of blatant limitations associated with the research.  Notable limitations associated with research of inositol as an anxiolytic include: generalization of anxiety subtypes, study designs, few participants, and contradictory results.  When considering these limitations, it is relatively irresponsible to suggest inositol’s anxiolytic efficacy or lack thereof.

Small sample sizes: The most obvious limitation associated with research of inositol as an anxiolytic is the sample sizes in available research.  The largest sample in a study of inositol as a treatment for anxiety was 21 patients diagnosed with panic disorder.  In other studies, the number of participants range from 7 to 20; no currently-available studies exceed 21 participants.

It is well-understood that small sample sizes may not accurately portray the anxiolytic efficacy of a substance like inositol in the general population.  Even with a well-designed small-scale study, results could be inaccurate simply because sample size was too small to observe an effect.  Though outright dismissal of studies incorporating small sample sizes is irresponsible, there is a clear need for larger samples to validate inositol’s efficacy.

Study designs: Ideally, all inositol research would incorporate robust placebo-controlled, double-blinded, and randomized designs.  However, due to the fact that inositol research is still in its infancy, study designs may deviate from the scientific gold-standard.  Since not all study designs are placebo-controlled, randomized, and double-blinded – no matter their results – some will be rightfully skeptical of the evidence.

Study duration: In addition to the general design of various inositol studies, many fail to consider that the duration of most studies is relatively short.  Although some studies are conducted over a period of weeks and/or months, some are conducted over a period of days, or even a single-day.  Perhaps future studies should opt for longer-term inositol administration.  Longer-term administration will elucidate inositol’s long-term anxiolytic efficacy, safety, and adverse effect profile.

Failure to consider anxiety subtypes: It is well-known that there are numerous subtypes of anxiety disorders, each of which involves a specific symptom set and subtype-specific neurophysiological footprint (e.g. neural activation, neurotransmission, etc.).  Although nearly all types of anxiety disorders are associated with the user experiencing anxious and/or fearful emotions, assuming that each anxiety subtype will respond to the same treatment (e.g. inositol) is a mistake.  Even pharmaceutical drugs that are approved to treat social phobia are not necessarily effective in treating OCD; and vice-versa.

Premature meta-analysis: The latest 2014 meta-analysis notes that using inositol for anxiety disorders is ineffective, however, it failed to consider that not all subtypes of anxiety disorders may respond to the same treatment.  Additionally, the entire meta-analysis was premature in that there were no large-scale studies conducted to justify a review of evidence.  There was no high-quality evidence to review, but researchers went ahead and reviewed it anyway.  Rather than conducting a meta-analysis, researchers would’ve been better off conducting a larger-scale trial of inositol for a specific subtype of anxiety (e.g. for OCD).

Mixed evidence:  If you were to gloss over the results of each study investigating inositol’s anxiolytic efficacy, you’d likely be unable to definitively decide whether its effective or ineffective.  This is due to the fact that results from most inositol research is mixed; some studies suggest that it works, while others document no clinically significant effect.  Of the evidence I reviewed, I was able to find 6 studies supporting inositol’s efficacy and 3 suggesting its lack of efficacy for anxiety.

Since all studies are small-scale, may have issues with their design, and may be studying different subtypes of anxiety – there’s inadequate evidence to support or dismiss inositol’s anxiolytic properties.  Until a larger study is published, evidence of inositol’s anxiolytic efficacy will remain relatively ambiguous.

Negligible incentive: There’s no significant [financial] incentive to motivate researchers to investigate the efficacy of inositol for anxiety disorders.  If inositol research was heavily funded, we’d likely understand its actual efficacy based on larger-scale studies.  However, inositol is not a non-essential nutrient that cannot be patented by a pharmaceutical company, so it makes no sense for a big pharma company to fund research of inositol as an anxiolytic.

In fact, some may argue that pharmaceutical companies may benefit from the lack of inositol research.  Assuming that inositol could be an effective anxiolytic devoid of side effects, it may decrease sales of pharmaceutical anxiolytics.  It may take years (or perhaps longer) for researchers to reinvestigate inositol as an anxiolytic in a large sample while implementing a robust (placebo-controlled, double-blind, randomized) study design.

Verdict: Inositol may be therapeutic for those with anxiety

Upon review of the available literature investigating inositol’s anxiolytic efficacy, we must conclude that inositol may be therapeutic for those with anxiety.  Staunch inositol supporters may automatically conclude that inositol is universally effective for anxiety disorders based on early research with larger sample sizes.  Nearly all of the largest sample sizes (21, 20, 13, 12) found inositol effective for the treatment of a particular subtype of anxiety.

Additionally, the number of studies that support inositol’s anxiolytic efficacy outnumber those that document its lack of efficacy (6 to 3).  Studies that suggest inefficacy of inositol as an anxiolytic include: a 1997 study suggesting that it fails to attenuate drug-induced panic (in 7 patients), another from 1999 that found it ineffective as an SSRI adjunct for OCD (in 10 patients), and a third that found it ineffective for attenuation of drug-induced anxiety in monkeys.  If comparing the evidence in support of inositol’s anxiolytic properties with that suggesting against it, it would be logical to hypothesize that it’s likely effective.

Research dismissing its inositol’s anxiolytic efficacy noted that inositol fails to treat drug-induced panic and doesn’t improve OCD outcomes when administered as an SSRI adjunct.  Research in support of inositol’s anxiolytic efficacy suggests that it treats panic disorder (equally as effective as an approved pharmaceutical, Luvox), OCD, and decreases anxiety behavior in animals.  Since no research has been conducted for other types of anxiety, it is unclear as to whether inositol would improve symptoms of social phobia, generalized anxiety, PTSD, etc.

Due to the aforestated research limitations, it is important to remain cautiously optimistic when interpreting inositol’s anxiolytic efficacy.  Preliminary evidence implies that inositol is likely effective, especially for the treatment of panic disorder, and possibly for the treatment of OCD.  However, until research limitations are overridden with larger-scale, higher-quality designs – inositol should not be recognized as a first-line anxiolytic.

How much Inositol should you take to treat an anxiety disorder?

There is no clear-cut recommended dosage of inositol for the treatment of anxiety disorders.  The amount of inositol necessary for symptomatic attenuation may be contingent upon several factors including: specific inositol brand administered, its bioavailability, whether an individual is taking other medications or supplements, dietary inositol intake, etc.  If you’ve considered taking inositol for an anxiety disorder, it is recommended to consult a medical professional for dosing advice.

That said, most users of any exogenous substance, including inositol, should endeavor to take the minimal effective dose.  Adverse effects are thought to be more common among those taking high-doses rather than lower ones; this is due to the fact that high doses exert greater influence over neurophysiology.  Additionally, low dose usage is cheaper (in terms of finances) over a long-term than high-dose usage; this allows low-dose users to save themselves money.

As a standard dietary supplement, many users take between 1 and 3 grams per day – however, there’s no evidence to suggest that such low doses provide significant anxiolytic relief.  Clinical research suggests that effective doses of inositol for the treatment of anxiety range between 12 and 18 grams per day.  That said, many users report therapeutic relief with lower dosages than 12 grams, therefore, it may be wise to start with a small dosage and titrate upwards until you attain an anxiolytic effect.

Not everyone will necessarily require large doses of inositol to attain an therapeutic anxiolytic benefit.  Therefore, by starting low and titrating upwards, you can find the optimal dose for anxiolytic relief without jumping to a dosage (or range) that is potentially too potent for your physiology.  Many anecdotal reports have reported anxiety reduction from just 2 to 6 grams per day.

Have you tried Inositol to treat anxiety?

If you’ve tested inositol as a treatment for your anxiety disorder, leave a comment below discussing its efficacy.  To help others get a better understanding of your situation, discuss: the particular brand of inositol that you tested, the duration over which you took (or have been taking) it, as well as how long into your usage you noticed an anxiolytic effect (assuming you noticed one).  Mention whether the inositol provided clinically significant anxiolytic relief, whether it exacerbated anxious symptoms, and/or whether you observed no effect.

For those that derived significant therapeutic benefit from inositol, feel free to share whether there were any trade-offs associated with its usage (e.g. inability to focus).  Since inositol may be more effective for certain subtypes of anxiety compared to others, note the particular type(s) of anxiety you endeavored to treat with inositol (e.g. social phobia, panic disorder, OCD, etc.).  Also document whether you’re taking inositol as a standalone treatment, as a pharmaceutical adjunct, and/or as part of a supplement “stack.”

Do you believe that inositol is a viable alternative to pharmaceutical FDA-approved anxiolytic drugs?  Based on the research, it would be logical to conclude that inositol is likely to provide most significant benefit to those with anxiety disorder diagnoses of panic disorder or OCD.  However, it remains unclear as to whether inositol would improve symptoms of social phobia, generalized anxiety disorder, and PTSD.

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{ 8 comments… add one }
  • Sandy February 27, 2016, 2:51 am

    51 year old woman. My experience with inositol over the past 9 days has been very promising. From the first dose of 650 mg, I noticed how calm my thoughts became, I was very relaxed for the first time in 27 years. I have been diagnosed with so many mental health issues, including bipolar, seizures, GAD, psychoses, you name it, it’s what I supposedly have.

    It all started when I was 24 years old, had an extremely high fever, with a stiff neck. One of the many doctors had told me it was probably encephalitis that I had at that time. Back to the inositol, I am currently taking 2.5 grams, along with depakote, klonopin,paxil, and cholesterol meds. This is the vitamin shoppe brand. 650 mgs. Side effects are loose stools, and slight headache.

    It seems to help me from obsessing with worry, and negative thoughts. I wish more studies were done as I can tell you this is the thing that’s helped me so far. I would advise working together with your doctor.

    • trapach August 12, 2016, 10:08 pm

      Not a chance. That dose is too low to have any effect, and you’re on strong meds.

  • FoxBadger April 15, 2016, 12:39 pm

    27-year-old female here; been taking inositol consistently for approx. 3 months, due to fairly severe OCD symptoms. I don’t have any other health conditions or mental health difficulties – it’s just standalone OCD that’s been plaguing me off and on for the past 4 years. I take the powdered Swanson form, stirred into a drink, usually 6g 3 times a day or so (18g daily total), and it’s had a very definite effect.

    It gives me more strength/optimism to keep fighting off the OCD, it reduces the severity and frequency of intrusive thoughts, it reduces the string of constant doubting ‘what-if?’ thoughts that characterise OCD (this is a huge bonus. Actually being able to let a thought go feels magical when you’ve suffered years of OCD), it makes it harder to experience sudden ‘spikes’ of extreme panic when an intrusive thought hits.

    I don’t take any kind of prescription medication, as although I don’t have any problem with it, I don’t think there’s particularly good evidence that the substances I would be prescribed for my OCD here in the UK would actually help me get my symptoms down to a low level. I could be wrong, but from experience consulting with OCD charities, speakers at OCD conferences, support groups and scientific papers, there doesn’t seem to be much that would act efficiently and quickly and without counter-productive side-effects in my particular situation.

    However, I did get some side-effects from the inositol for a while, after using it for about a months – tingly hands and feet, sore ringing/pressure in my ears, brain fog, lethargy, tight feeling in my chest etc. I don’t know exactly what caused these but I’ve heard inositol can block uptake of other minerals – and interestingly, when I tested this hypothesis and tried taking inositol with 200-400mg of magnesium citrate, all the side-effects vanished. They haven’t come back, provided I always take the inositol with a little magnesium.

    I didn’t change the type, dosage or anything else of the inositol; I just added magnesium. Although I have no way of telling for sure, I’m inclined to blame the inositol side-effects on temporary magnesium deficiency, because experiencing ringing/pressure in my ears is very unusual for me, but it’s apparently common effect of low magnesium (and if I forget to take magnesium with the inositol, my inner ear starts to get a little sore again and my chest feels a little tight).

    Another possible side-effect – if it IS true that inositol inhibits absorption of other minerals; it might depend on which form of inositol it is specifically – is that every month I become low in iron due to heavy blood loss, and it seems harder to restore normal levels of iron. Even with supplements, anemia symptoms persist. I feel that this could be overcome by perhaps taking the inositol at different times of the day to iron-rich meals, or only taking it before bed, etc., but so far I haven’t quite managed to sort out the correct timing of this (it’s quite frustrating!

    I need that iron!). If I try to re-jig the inositol by lowering dosage or only taking a little once a day, my OCD symptoms seem to shoot up in severity again. It’s intensely unpleasant and debilitating. The effect is very noticeable. I know there are those who might attribute this to expectation and placebo, but OCD actually isn’t known to respond to placebo treatments very well, and the effect on an uncontrollable bodily function (the brain endlessly throwing up repetitive images/words like a broken record) really seems too marked.

    Once I resume taking inositol at full dosage again, the OCD symptoms show a marked reduction within one to two hours. The full 18g dosage, throughout the day, has so far been necessary for me to control symptoms. However, this is one interesting mysterious caveat to this I’d like to mention: there WAS one occasion where my ordered inositol became held up in the post for six days, and I ended up going ‘cold turkey’ without it, BUT symptoms remained very low despite a stressful life event, apparently due to something else I was taking.

    By rights I should have been non-functional. But, I’d been taking prebiotics for a while and continued to take them all though the period that the inositol ran out, and I’m guessing something must have happened with the gut-brain axis and intestinal bacteria. It appears that there’s more than one way to influence inositol and serotonin levels in my body, and it could have been via gut bacteria, maybe.

    OR an alternative explanation is that a level of inositol had built up in my body and this was enough to last 6 days (seems a little unlikely, but maybe). There could be other explanations for this, however. I don’t get side-effects from the inositol now. No digestive pains, no sleepiness or brain fog, no loose stools and the headache is so mild it’s kind of debateable and could probably be attributed to not being fully hydrated.

    I don’t stack the inositol with choline, as is commonly done, because choline seems to make me worse (I hear other people with OCD have reported this too). I take a few other supplements to plug gaps in my diet when anxiety makes it hard to eat/cook properly (Vitamin D3, iron for the blood loss, the magnesium as I’ve mentioned, and sometimes irregularly L-Theanine when I’m experiencing very severe anxiety out-and-about) but inositol is the one I take consistently.

    So far I haven’t got my OCD symptoms down to a very low/almost gone level consistently, but I’ve managed it a few times during the course of this three-month experiment. I’ve had a couple of days with zero intrusive thoughts and zero ‘spikes’ of fear, and they’ve all been days I was taking 12 – 18g inositol. I just need to find a way of integrating taking it into my day and with the other things I eat/take, for the long term.

  • Nick Earl May 14, 2016, 4:18 am

    Great article Gloom, you’ve created a valuable resource with this site, and I really appreciate your research! @FoxBader, if you’re reading this, thanks for your valuable and extensive comment, I found that useful. I have been experiencing anxiety on and off my whole life, and depression too, but more recently I’ve been dealing with a LOT of intrusive OCD type thoughts.

    I just started taking inositol about 2 weeks ago, started off with 2g x 3 per day (6g) the affects were very subtle if there at all from that dosage, and so I just increased it to 18g daily. I’m noticing a noticeable difference in resistant/OCD thoughts already, though it’s a bit too early to tell if that’s from the inositol.

    Just curious, do you take it away from food, or with? I’m curious about this problem of it messing with other mineral intake, as that’s a bit problematic for me too… I’d love to hear your feedback on that, and please keep us posted with your progress after some more time using inositol! Cheers!

  • Nick June 14, 2016, 4:45 am

    Update from above, I used 6g 3x daily for a few weeks, and didn’t really see any difference. I think there are biological issues that are causing my anxiety and obsessive thinking, and I need to address those before I’ll see any big changes.

  • Andrew June 23, 2016, 12:08 am

    I starting taking Insositol a month ago for anxiety for intrusive thoughts and automatic negative thinking. Starting on low doses, now taking 12g twice daily within the last few days. Some side effects such as diarrhea flactucence, brain fog. I will give another few weeks. I am also taking L-theanine 200mg a night. May stop that now. Should I take Insositol with food or on a empty stomach? Great informative article as ever. Andrew

  • Kathleen July 30, 2016, 7:13 pm

    Tried it for anxiety, it just gave me a whopper of a headache.

  • Curt September 30, 2016, 2:55 pm

    Have recommended 18 grams per day of inositol to 4 different people for panic attacks. All four reported significant benefits in 1-4 weeks.

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