…lack of inositol may cause diminished neurotransmitter signalling causing depression, anxiety and OCD…
…in bipolar mania there’s a build-up of inositol in the brain causing excessive neurotransmitter signalling...

Inositol for Mental Health Problems

PeterSmithUK.com © 2014 (#2)
Inositol is a vitamin like substance with many functions in the body, the function we are interested in here is that inositol is used by the neurones in our brain transfer messages and communicate. You probably know that neurotransmitters transfer messages or signals from one neuron to another outside the cell across a tiny gap called a synapse, inositol on the other hand continues to transfer the message inside the brain cell. This is called the second messenger system and without healthy levels of inositol second messenger activity you won’t have enough healthy signalling and messaging throughout the brain so even if you had healthy levels of say serotonin in your synapses if you don’t have enough inositol to act as a secondary messenger inside the cells you will have diminished signalling through the serotonin pathways of your brain causing depression; the same applies to all the other neurotransmitters, dopamine, norepinephrine, GABA, acetylcholine phenylethylamine et. Al. Of course it could always be worse, you could have both low levels of neurotransmitter signalling in your synapses and low levels of inositol second messenger activity.
Inositol is a very safe substance to take with no known drug interactions or significant side-effects and so you can simply try it on yourself and see if you find it helpful.

You could consider trying inositol for:-
  • Depression particularly treatment resistant depression, maybe the reason drugs that boost neurotransmitter levels haven’t worked in you is because you don’t have enough secondary messenger activity.
  • Bipolar depression.
  • Maybe suicidal depression because inositol levels were found to be low in victims of suicide so I would add hefty doses of inositol to the rest of the prescription when depression becomes life-threatening.
  • OCD.
  • Panic and anxiety disorders.
  • Premenstrual dysphoric disorder PMDD
The overall scientific review (meta-analysis) of the benefits of supplementing inositol have produced mixed results, sometimes showing useful antidepressant effects and other times not, similarly in one study inositol benefited women with premenstrual dysphoric disorder PMDD[i] however in another study it didn’t; and that simply hasn’t been very many scientific studies on inositol for other conditions such as OCD although what there has been looks very promising.
The science is in keeping with my clinical observations which have been that inositol seems to be very helpful for a few people but not at all helpful for others presumably because deficient inositol second messenger activity either is or is not involved in contributing to the problem.
In my practice I adopt a “try and see what happens” approach, you cannot predict or work out which remedies are going to be effective in your individual case through laboratory blood or genetic testing at least not yet and the best way to work out if a remedy is going to help you and in what way it specifically affects you is through personal experimentation, this is how I personally learned how to overcome and live well with bipolar syndrome.
If you try inositol and find it helpful you would want to supplement inositol when you want to increase neurotransmitter activity to combat depression, anxiety and OCD, however there’s a theory that inositol activity becomes excessive in bipolar mania so you would want to deplete inositol levels with lithium (see my pages on how to safely take low-dose lithium without the side-effects) when you want to decrease neurotransmitter activity and combat bipolar mania.

Inositol and Depression

In depression (both unipolar and bipolar) it appears there are depleted levels of inositol in the frontal lobes of brain and this results in diminished neurotransmitter signalling even if there is adequate levels of neurotransmitters in the synapses.
In the future a new type of antidepressant drugs may be developed that specifically focus on boosting the second messenger system, in the meantime you can try supplementing inositol to perform a do-it-yourself experiment to see if low levels of inositol secondary messenger activity is your hampering healthy neurotransmitter activity in your brain. Furthermore you can combine inositol with neurotransmitter boosting remedies and antidepressant drugs which may enhance their effectiveness, in my practice I always ‘stack’ remedies together so I might for example combine inositol with tryptophan, EPA, uridine or SAM-e and essential cofactors magnesium, B complex and a multimineral to boost serotonin activity in the brain; if this proves effective at some point in the future you would try omitting the inositol to see if it’s making a difference.

The Inositol Theory of Bipolar Syndrome

In very simplistic terms the inositol theory of bipolar syndrome is that during depressive phases inositol activity becomes deficient and during phases of mania and hypomania inositol concentration builds up in the brain causing excessive dopamine and glutamate signalling.
As I discussed elsewhere knowing how to use natural remedies to dampen down excessive dopamine and glutamate activity in the brain are real practical ways of managing bipolar syndrome that I use both in my practice and to manage my own bipolar.
It is believed one of the mechanisms by which lithium exerts its therapeutic effects is that it combats the buildup of inositol in the bipolar brain, this is called the inositol depletion hypothesis and this one of the reasons by advocate using low-dose lithium. See my Lithium pages.
The practical way you could use inositol for bipolar syndrome is when you notice yourself slowing down significantly (the speed at which you talk becoming slower, the speed of your body movements, how quickly you do things, how quickly you think etc. all slowing down) and or you begin to notice the return of the depressed state then you could add supplemental inositol to your prescription to increase neurotransmitter activity.
There are other antidepressant remedies you could turn to and you may not need the inositol, such as tyrosine/DLPA, Rhodiola, NAC cysteine and for very quick results: SAM-e and acetyl-L-carnitine. If however you have prolonged bipolar or unipolar depression that fails to respond to other treatments try inositol to see if your problem is a lack of inositol second messenger signalling. If neither of these strategies work try improving your neuroplasticity with my BDNF boosting treatment.
If you have bipolar syndrome must be cautious using any antidepressant therapy whether natural or pharmaceutical including inositol as there is the possibility that it could flip you into mania, in my opinion however this does not mean that we should refrain from using antidepressant treatments with bipolar syndrome, to do so would be to condemn some of us to long periods or even a lifelong repeating bouts of depression, I know this from personal experience, from my early teens to my mid 40s I spent a little over 50% of those years with depression ranging from dysthymic to life-threatening. Now however I understanding how to counterbalance antidepressants treatments with anti-mania treatments and I live completely free from both depression and mania.
During phases of mania you would obviously stop taking any inositol supplements however I wouldn’t worry about the small amount in a multivitamin or B complex, when would have bipolar mania I would still continue taking a multivitamin which may deliver just a small dose of 50-100 mg.
With ultra-rapid cycling and mixed-states I would also not supplement inositol other than small amount already contained in a multivitamin; with rapid-cycling and mixed type states you just have to jump in somewhere and start treating and my strategy is always to bring the manic side under control first so you don’t want inositol pushing up your dopamine and glutamate activity.
I always recommend people with bipolar take a low dose lithium but I especially encouraging to take low-dose lithium as a mood stabilising counterbalance if you supplement antidepressant inositol; you might think that if you take lithium and inositol together they will simply cancel each other out using opposing therapies simultaneously in combination is often highly effective, I call this combination therapy.
Again you’ll have to experiment to work out inositol is a useful remedy to help you maintain a balanced state, even if you find it too volatile and manic inducing it could still be something useful for depressive emergencies. If you take too much inositol and induces mania you should be able to quickly antidote the effects by temporarily increasing the dosage of lithium (from lithium orotate) to perhaps 20 mg a day.

Inositol for depression and choline for mania

You often see inositol sold together in the same capsule with choline. Choline is a precursor building block for the neurotransmitter acetylcholine and some people find that taking choline improves their memory and cognitive function, however there’s a theory that depression can be due to elevated levels of acetylcholine and some people find choline has a depressant effect.
Taken at the right dosage the depressant effect of choline can be used to antidote bipolar mania; generally I’ve prescribed and used myself high doses of lecithin to deliver the choline. Although lecithin does contain some phosphatidylinositol and you think of wanting to avoid inositol with mania, the predominant ingredient in lecithin is phosphatidylcholine which counteracts mania by increasing acetylcholine activity in the brain.
One of the side effects of taking high doses of lecithin is that it makes you sleepy and this is exactly what you want to introduce during periods of bipolar mania; the combination of high phosphatidylcholine and low phosphatidylinositol in lecithin can be useful to induce sleep, bring down a manic state and yet give you a soft landing so you don’t drop out of mania straight into depression. When I first experimented with high doses of lecithin I was symptom-free neither manic nor depressed, what happened was over a period of five days or so time I spent the sleep went up to a whopping 16 hours! I wouldn’t want to live my life sleeping that long every day but just a few nights sleeping 12 to 14 hours in total darkness immersion can be a great antidote to bipolar mania.
When I still had rapid cycling bipolar about six times a year I would go from taking no lecithin to 7000-9000 mg a day for a few days at the first sign of a manic hijacking and together with a stack of other remedies I could switch off a manic hijacking in 1 to 2 days (or more precisely in 1 to 2 good nights sleep), this would be followed by perhaps a day or two of completely tolerable mild depression before resuming a symptom-free healthy psychological state. I’m going off at a tangent but as I write this however I have not had a single attempted manic hijacking in over three years since I treated myself for several months with a stack of remedies to boost BDNF, see my BDNF boosting treatment; so as of three years I no longer have rapid cycling :-) See Lecithin and Choline and Bipolar Syndrome
I recommend avoiding lecithin and choline supplements if you have any form of suicidal depression, the small amounts of choline or lecithin found in a multivitamin supplement are not a problem.

Inositol for OCD, Panic and Anxiety Disorders

Many of my patients have found inositol to be very helpful for these conditions, however it does have to be taken in quite high doses to achieve results, in the region of 15 to 18 g (15,000-18,000 mg)[ii]. In one study 18 g of inositol a day outperformed 150 mg a day of fluvoxamine (and SSRI), inositol also produced less nausea and tiredness than fluvoxamine[iii].
To take this amount I would buy it in powder form rather than capsules. Take it with meals dividing the daily total between at least two meals.
I suppose hypothetically you could continue taking 18 g of inositol a day indefinitely as opposed to taking a drug but I would strongly encourage you to do a lot more besides that so that hopefully in the future you would no longer needed at all or perhaps only on an occasional basis. Firstly you should always combine a nutrient supplement with a multivitamin/multimineral to provide both cofactors and also prevent the high dose of the main nutrient from displacing and upsetting the balance of other essential nutrients in the body, I would also always add magnesium on top of the multi. So for example you could take 18 g of inositol powder with 800 mg of magnesium (from magnesium citrate) with a multivitamin/mineral that contains L-methylfolate and not folic acid such as Doctor’s Best Best Multiple. In my practice I would probably stack this up with ashwagandha, Gastrodia, taurine, glycine, tryptophan, et al.
For more information see: GABA Deficient Anxiety, Natural Treatment for OCD.

Inositol and Suicide

Low levels of inositol have been found in the frontal lobes of brain scans of people with unipolar and bipolar depression and the autopsied brains of bipolar victims of suicide[iv].
As already mentioned it’s believed that one of the ways lithium exerts a therapeutic effect on the bipolar brain is that it depletes excessive levels of inositol[v][vi], but lithium has a specific anti-suicidal effects and low levels of inositol are associated with suicide so this seems contradictory. Hypothetically an explanation could be that lithium regulates and balances both excess and deficient levels of inositol, or that lithium may have different effects on inositol in different regions of the brain, or simply that lithium is anti-suicidal effects may outweigh its inositol lowering effects; as ever brain chemistry turns out to be extraordinarily complicated.
So if you have suicidal unipolar depression you can safely flood your brain with inositol alongside any other treatments you’re doing at the same time you should also add low-dose lithium because it has specific anti-suicidal affect, as I explain elsewhere lithium isn’t only for bipolar syndrome it can also be helpful for unipolar depression.
If you have suicidal bipolar depression I would still recommend using inositol -save life first- but you must also be ready to immediately treat the manic side of your condition just in case using strong antidepressant treatments end up flipping you straight up into mania.
To counteract the manic side immediately set up and start using Darkness Immersion Therapy, but if you have bipolar syndrome you should already be using darkness immersion therapy even if you are stable and not suicidal for maintenance. In an emergency you can create a temporary setup using cardboard from cardboard boxes, thick black plastic and duct tape to immediately blackout your windows and doors while you wait for the proper total blackout blinds to arrive.
Also you’re not already on lithium I would immediately add low-dose lithium orotate (see How to Make Low-Dose Lithium Orotate Effective) because of its anti-suicidal benefits even though lithium and inositol appear to oppose each other my advice is take them both together at the same time with suicidal bipolar depression, in addition to the darkness immersion therapy and low-dose lithium orotate you should have branched-chain amino acids, glycine, taurine, high-dose vitamins C, all sitting ready for use in your medicine cabinet. See Managing Mania.
If you are suicidal because of depressive illness please click here.

Inositol for Women … but maybe men too…

Inositol may be helpful for female infertility, polycystic ovarian syndrome PCOS, and as mentioned premenstrual dysphoric disorder so if you have any of these conditions or even you notice your mental health problem has a hormonal component and is significantly worse at certain times of the month then it might be that you have an overall widespread imbalance in your metabolism of inositol throughout your body and to me that suggests that inositol would definitely be worth trying in your case.
This is an example of how to think about constructing a nutritional therapy prescription, what you look for first are the natural remedies with a range of therapeutic effects that match the range symptoms/conditions, it doesn’t matter that there is a lack of scientific evidence because inositol is so safe and you can simply conduct ‘an experiment of one’ and tested for yourself.
Just because inositol may be specifically beneficial for women with fierce signs of hormonal imbalances doesn’t mean to say that a guy could not also have an imbalance in inositol metabolism contributing to his mental health problem so don’t let the above put you off guys inositol does not have estrogenic effects it won’t make you grow breasts or pay more attention to your fingernails.

Side Effects and Interactions

No serious side-effects or drug interactions have been observed, however it is probably ill-advised to take it high doses during pregnancy.
Side-effects include drowsiness, nausea and loose bowels.
[i] PMID:24424706
[ii] Am J Psychiatry. 1996 Sep;153(9):1219-21. Inositol treatment of obsessive-compulsive disorder. Fux M1, et al PMID: 8780431 DOI: 10.1176/ajp.153.9.1219
[iii] J Clin Psychopharmacol. 2001 Jun;21(3):335-9.
Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder. Palatnik A1, et al PMID:11386498
[iv] Am J Psychiatry 1997; 154:1148–1150 Reduced Fron tal Cortex Inositol Levels in Postmortem Brainof Suicide Victims and Patients With Bipolar Disorder Hady Shimon, M.Sc., Galila Agam, Ph.D., R.H. Belmaker, M.D., Thomas M. Hyde, et.al.
[v] Meeting of Minds 2010 Lithium in the Treatment of Bipolar Disorder: Evidence of Intracellular Mechanisms that SubstantiateTwo Prominent Theories of Action Hayley Amsbaugh Faculty Advisor: Keith Williams Department of Psychology Oakland Universit
[vi] J Neural Transm. 1998;105(1):31-8. Augmentation of lithium's behavioral effect by inositol uptake inhibitors. Einat H1, Kofman O, Itkin O, Lewitan RJ, Belmaker RH.
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