GABA Deficiency Anxiety
The Nature of GABA
GABA: The Brains Natural Valium
In simple terms the way GABA works is it makes synapses less likely to fire, so it dampens down activity in the brain. When stimulators neurotransmitters like dopamine and serotonin are released into a synapses they make the receiving neuron more positivity charged the receiving neuron will only fire when it reaches a certain level (called threshold potential) of positive electric charge; when GABA is released into a synapse it makes the receiving neuron more negatively charged and therefore less likely to be activated.
Glutamate has the opposite effect to GABA it increases the positive charge in receiving neurones making then more likely to fire. You could say glutamate is like the gas pedal in a car, it speeds up transmission of information throughout the brain and GABA is like the brake pedal. Whe we have too little GABA and too much glutamate our brain over fires, the mind can race; this can manifest different symptoms in different brains, in some people the anxiety circuits are the most affected in others it’s involved in bipolar mania (which I have) and in others it contributed to psychosis and schizophrenia. When GABA activity drops very low as it can during withdrawal from benzo drugs our neutrons can fire so easily and excessively thet it not only causes horrendous agitation but it can even cause seizures.
Balancing the level of excitement in every neuron is so critical that GABA and glutamate are made in every single neuron of the brain unlike other neurotransmitters such as serotonin and dopamine that are only made in specific areas of the brain and then distributed. Glutamate and GABA together account for over 80 percent of brain activity together they keep the level of activity in the brain at the right level not too fast, not too slow.
Symptoms of lack of GABA include:-
- anxiety, feeling fearful, general (free floating) anxiety disorder or GAD,
- panic attacks,
- nervy/stressed disposition,
- persistent worrying thoughts going around and around in your mind, inability to switch your mind off,
- feeling of dread,
- feeling of inattention, inability to relax,
- insomnia due to an anxious mind or cannot switch off the mind,
- physical aches and pains because the nerves keep firing, possibly causing/contributing to fibromyalgia,
- IBS (although this can also be for other reasons such as SIBO and lack of vagus nerve tone)
- craving carbohydrate (although there can be other reasons for this)
Without adequate GABA and serotonin levels not only can worrying thoughts persist longer than they need to, but as they go around and around they can gain momentum, escalate and grow into enormous, disturbing levels of fear, stress and anxiety. Persistent anxiety can ruin a person's life experience, it can debilitate their ability to function normally engaging in work, relationships and recreation.
Before discussing the natural remedies you can use to increase GABA let’s considered two things:
- What’s causes GABA deficiency in the 1st place?
- Is GABA deficiency the main reason for your anxiety?
What Causes GABA Deficiency in the 1st Place
Glutamic Acid Decarboxylase GAD AntibodiesUnfortunately, the enzyme glutamic acid decarboxylase or GAD that converts glutamate into GABA is vulnerable to attack from our own immune system. Various things can stimulate our immune system to make antibodies that attack GAD and reduce our ability to make GABA. To make matters worse still the lack of GAD means the stimulatory neurotransmitter glutamate is not broken down into GABA and builds up further over stimulating the brain.
You can also have GAD SNP genetic mutation a variation that diminishes your GABA production.
GAD requires the cofactors magnesium and B6, magnesium deficiencies common and even if B6 is not deficient supplementing it to above minimum requirements but still safe levels can have an antianxiety therapeutic effect. My personal anecdote is that when I don’t take P5 P (the bioavailable form of B6) with breakfast and more anxious and socially withdrawn.
Gluten Sensitivity can Reduce GABA ProductionThe most common thing I’m aware of that can provoke our immune system to make GAD antibodies is gluten contained principally in wheat but also in other grains. This will occur in people with coeliac disease but also can occur in the less serious non-coeliac gluten sensitivity. It would be helpful to have a gluten sensitivity intolerance test to determine if eliminating gluten from your diet is likely to improve your GABA production, unfortunately however laboratory tests for gluten sensitivity are unreliable; because of the unreliability of gluten sensitivity tests I have to ask all my patients to start their GABA rebalancing treatment to eliminate gluten containing grains for the first 6 weeks of treatment, after 6 weeks circulating antibodies should have subsided, after this you can try introducing all grains except for wheat and see if you continue to make progress, and then maybe try introducing wheat and see how it affects you. You can do some home testing to see if wheat and gluten provoke inflammation and your immune system
See: GABA Blood-Brain Barrier Test
Home Allergy Testing using the Pulse Method
Stress GABA and Anxiety
Stress doesn’t decrease levels GABA directlyYou will see a lot of websites saying that stress causes or at least contributes to anxiety and that you should avoid stress but you may be surprised to hear that stress neither short-term or long-term does not appear to decrease GABA levels or increase glutamate[i]
Short-term stress may however directly increase the sensitivity of glutamate receptor sites[ii] and perhaps this could worsen anxiety, stress also decreases serotonin production[iii][iv].
Long-term stress can desensitise the amygdala to GABALong-term chronic stress however may inhibit the sensitivity of the amygdala to GABA[v], this will result in the amygdala becoming hyperactive and a hyperactive amygdala plays a central role in anxiety.
Mice subjected to daily stress for 10 days showed a marked decrease in GABA inhibition of their amygdala and displayed anxiety-like behaviours, the effects persisted for 10 to 30 days after the stress ended.
Translating this into a human timescale 10 days in mouse time is roughly the equivalent to 375 days or about a year in human time, therefore a year of chronic stress may result in your amygdala becoming hyperactive and increase anxiety, and the effects could last from 1 to 3 years after the stress had ceased. There are obviously a lot of variables in making such estimates about human effects from mouse experiments so these number should be taken with a pinch of salt, nevertheless the comparison sound interesting and plausible.
Why Does Stress Trigger Anxiety in some People Depression in others or have Little Effects?I think neuroscience can now answer this question and at least in some ways it’s not very complicated. To start with psychological stress triggers physiological stress responses and one of the consequences of chronic physiological stress responses is increased levels of inflammation in the brain; now the inflammation attacks the brains dendrites and synapses and if you have a poor neuroplastic ability to protect your dendrites and synapses you may lose connections in key areas of the brain that control mood resulting in depression, it’s typical and depression to see a loss of volume in connections in the hippocampus and cortex. Inflammation can change tryptophan metabolism so that you end up making less serotonin and more toxic inflammatory quinolinic acid, this may also be a typical feature of depression in some individuals.
In other people with more robust protective neuroplastic abilities chronic stress and distress will not overwhelm their neurobiology in a way that produces depression.
In other people their brain may be inherently (genetically) more wired towards anxiousness, their brain may have also developed an enlarged amygdala from exposure to chronic stress in early childhood (see below) and when a brain with this combination is exposed to chronic stress making the (enlarged) amygdala less sensitive to GABA and dropping their serotonin levels it could produce anxiety.
Chronic Stress in Childhood Grows Bigger Amygdala Increasing Your Risk of Developing AnxietyThere are other studies showing that long-term chronic stress during childhood lead to long-term changes in the size and wiring of the amygdala such that you end up with a lifelong tendency to increased amygdala activity and risk of developing anxiety[vi]
Anxiety Causes Harmful Stress in the BodyFinally there is evidence that anxiety and low GABA/high glutamate causes activation of the body’s stress physiology i.e. anxiety causes stress physiology particularly over activation of the hypothalamic pituitary adrenal stress pathway resulting in increased neuro-inflammation and is a lot of evidence that this can cause depression which often exists together with anxiety. Furthermore neuro-inflammation inhibits neuroplasticity and when I’m working with somebody recovering from benzo withdrawal boosting neuroplasticity is a top priority, so reducing stress physiology with brain training is also a priority.
Deficient Brain Energy Causes Deficient GABAAll neurotransmitters need energy to be manufactured but GABA is actually a bi-product of energy production metabolism in neurons; the significance of this is if your brains energy production is poor your GABA production will be poor. Two important things that often let down energy production are deficient blood sugar and deficient oxygen.
Deficient Blood SugarI discuss blood sugar regulation at length elsewhere but briefly if you regularly consume carbohydrates with a high glycaemic index, or too much protein and fat on its own without any carbohydrates and inadequate fibre and polyphenols you get spikes or rapid rises in your blood glucose levels, your pancreas then produces a lot of insulin to control despite in blood glucose and this causes a rapid drop in blood sugar leading to a spate of what is called hyperglycaemia or low blood sugar.
The lack of glucose in the brain diminishes GABA production and this state could persist for several hours a day triggering anxiety.
One common mistake is to think that because carbohydrates are broken down into glucose if we stop eating carbohydrates altogether and follow a ketogenic (high-protein, high-fat, no carbohydrates) diet then we will not get spikes in blood glucose, but surprisingly when you eat meat and especially fish protein on its own without the presence of a little carbohydrate you can actually get a significant spike in blood glucose i.e. a steak with broccoli and spinach will produce a higher spike in blood glucose than the same meal with a small portion of let’s say quinoa. I do actually advocate the ketogenic diet at least for a short initial period for some people it suits their metabolism and temperament and has some therapeutic merits for brain health. The optimum diet for stabilising blood sugar and GABA status however is a low to very low carbohydrate but not know carbohydrate diet.
The choice of carbohydrates is incredibly important firstly they must have a GI less than 70, they must also either contain a lot of fibre will be consumed at the same time as a lot of polyphenols rich fibre. I’m often surprised and amused when people tell me they have a good diet and then they tell me what they actually eat, I remember a young man coming to see me with anxiety and I asked him what he had for dinner the night before he said “oh healthy you know” he then said he a chicken and rice with peas, so that was non-organic corn-fed non-grass fed chicken high in Omega 6 arachidonic acid that increases inflammation in the brain that contains pesticide residues and female sex hormones and can produce spikes in blood sugar with quick cook white rice that produces spikes in blood sugar and contains little polyphenols and fibre and some frozen microwaved peas providing woefully inadequate amounts of polyphenols and fibre Getting the diet right is important to GABA production, if you make just one mistake in your diet it may be sufficient to inhibit your recovery.
This is what matters with regard to GABA eat a diet that stabilises your blood sugar, and if you want provide the brain with alternative sources of fuel from MTC oils. I can tell you from personal experience I used to have very unstable blood sugar levels and changing my diet to provided a steady supply of fuel to my brain giving me continuous or they brain energy feels great.
See: Eating for Energy
Deficient Oxygen, Exercise, Iron Anaemia, B12 Pernicious Anaemia,To make energy cells has to burn fuel and this requires oxygen, you might think Julia brains getting enough oxygen if your breathing but not if you have anaemia and there are many things that can cause anaemia; in addition to anaemia you may not have a great network of blood vessels in parts of your brain as is the case in some people with ADHD where the network of blood vessels to the frontal cortex is poorly developed.
Oxygen is carried around the body attached to a substance called haemoglobin in our red blood cells; anaemia is having too few red blood cells or an abnormally low amount of haemoglobin inside your red blood cells.
Anaemia is surprisingly common, I’ve seen estimates suggesting almost a quarter of the world’s population may have anaemia and don’t think that you wouldn’t have it if you live in a developed part of the world because we sometimes have the worst diets There are several different types of anaemia and each one has a different cause, you may be consuming too little iron in your diet, you may be consuming sufficient iron but not absorbing adequately from your intestines, you may be low in the folate or B12 needed to build the iron containing molecule haemoglobin, you may be fine on all these fronts but losing excessive amounts of blood through heavy menstrual flow or intestinal bleeding and other causes. You can also have anaemia because your body is breaking down red blood cells to quickly or your body manufactures misshapen blood cells as in the case of sickle-cell anaemia.
The bottom line is if you suspect you have low GABA status you should rule out the possibility that you have anaemia with blood tests and appropriate treatment. Unfortunately testing for anaemia is not always that straightforward, begin with a complete blood cell count CBC and then if you’re not getting the results you hoped have a Reticulocyte Count test, mean corpuscular volume MCV test which is also a marker for low B12 and folate, blood smear and iron panel; while the labs got your blood also have them look at your folate and B12 levels. Sorry if this is more complicated than you wanted to be but this is medicine and biology is complicated!
The MTHFR Gene MutationThe MTHFR gene mutation interferes with folate (the natural form of folic acid) metabolism and this could interfere with your body’s ability to manufacture haemoglobin.
Dampening down excess Glutamate: the brains primary stimulatory neurotransmitterBesides low GABA levels there’s another neurotransmitter to consider which is glutamate, GABA inhibits activity in synapses and glutamate stimulates activity if you have an overexcited brain with overactivity in the fear circuits you want to dampen down excess glutamate as much as buildup inhibiting GABA.
It's a bit more complicated than this but in simple terms you can think of glutamate as perpetuating anxious thoughts going around and around in the brain and GABA as extinguishing them.
I’ll discuss the remedies you can use to attenuate excessive glutamate activity in the section: natural remedies you can use to increase GABA
Important GABA Anxiety SummaryIn the next section I’ll discuss how to boost your GABA levels with natural remedies but before or at the same time as using natural remedies to boost GABA levels make sure you eliminate all the things discussed in this section that causes GABA deficiency in the 1st place; but equally important is to consider whether or not GABA deficiency is the main reason for your anxiety.
With anxiety disorders the something that is more important working on your neurotransmitter balance and that is changing the way your brain circuits and brain structures are working. I’ve never seen anyone fully overcome anxiety by boosting GABA and attenuating glutamate alone, what is equally and I now believe far more important is to change the neuro circuits (wiring) and structures such as the amygdala involved in the amygdala. We now know that thanks to neuroplasticity we can gradually rewire our brain. We can dampen down overactivity in the default mode network a neuro circuits involved in anxiety particularly social anxiety, we can strengthen the anterior cingulate cortex a structure involved in processing emotions particularly connected to anxiety, we can shrink an enlarged amygdala and change the anxiety triggers programmed into the amygdala; these changes are possible with the application of many hours of brain training. See:
- Is GABA deficiency the main reason for your anxiety?
Benzodiazepines Increase GABA Activity but at a Terrible CostThe main pharmaceutical treatment for anxiety is benzodiazepine drugs, the way these work is they attach to GABA receptor sites and change the way the receptor site works so that when GABA attaches to the receptor site it has a much stronger effect; unfortunately benzodiazepines rapidly lead to our synapses becoming desensitised to the effects of GABA, firstly the drugs become less effective so you may need to take more of them to maintain the effects until eventually you reach the maximum allowed dosage and eventually even this stops working. When you then try coming off benzos it can produce horrendous withdrawal effects because your desensitised synapses no longer have enough working GABA-B receptor left.
During benzo withdrawal the extremely low levels of GABA activity in your brain results in your brain going into a HYPER-stimulated state with terrible agitation, anxiety and often physical symptoms; benzo withdrawal can be dangerous, people can have seizures it can even be fatal. I think benzo drugs should only be used for very short periods of time perhaps to tranquilize somebody actually having seizures but they shouldn’t and are not a solution for chronic long-term anxiety disorders.
Thanks to neuroplasticity a healthy brain should be able to re-sensitising itself to GABA and recover, unfortunately however for many people this process takes not just weeks but many months and sometimes a few years; for some very unfortunate individuals their brain remains permanently damaged. There is a belief online that there is nothing you can do to speed up this process but I totally disagree, I’ve been developing systems to up regulate neuroplasticity for years and the recovery from benzo is just a natural function of neuroplasticity, if you up regulate neuroplasticity he speed up recovery. But before you brush online to read up how to up regulate your neuroplasticity please listen when I say that what’s more important than up regulating neuroplasticity is eliminating the things that are preventing it in the 1st place; I’ve treated a lot of people with difficulties recovering from benzo’s and up regulating neuroplasticity without 1st eliminating the things that are inhibiting it is like putting your foot on the gas pedal with your foot still pressing down the brake pedal.
For more information how to come off benzos see:
Benzo Withdrawal How to Speed up Recovery
Are Natural Remedies Safe Benzodiazepine Withdrawal?
How to taper off benzos the right and Wrong Way
Benzo Withdrawal Treatment with Natural Remedies
[i] Neuroimage Clin. 2017; 14: 195–200. Published online 2017 Jan 4. doi:[10.1016/j.nicl.2017.01.001] PMCID: PMC5280001 PMID: 28180078 Acute stress effects on GABA and glutamate levels in the prefrontal cortex: A 7T 1H magnetic resonance spectroscopy study L.C. Houtepen et al
[ii] Mol Psychiatry. 2007 Nov;12(11):988-1000. Epub 2007 Apr 24. The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Müller N1, Schwarz MJ. PMID: 17457312 DOI: 10.1038/sj.mp.4002006
[iii] Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):702-21. doi: 10.1016/j.pnpbp.2010.12.017. Epub 2010 Dec 23. The new '5-HT' hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Maes M et al PMID: 21185346 DOI: 10.1016/j.pnpbp.2010.12.017
[iv] Stress. 2008 May;11(3):198-209. doi: 10.1080/10253890701754068. A link between stress and depression: shifts in the balance between the kynurenine and serotonin pathways of tryptophan metabolism and the etiology and pathophysiology of depression. Miura H, et al PMID: 18465467 DOI: 10.1080/10253890701754068.
[v] Mol Brain. 2014; 7: 32. Published online 2014 Apr 24. doi: [10.1186/1756-6606-7-32] PMCID: PMC4012764 PMID: 24758222 Chronic stress impairs GABAergic control of amygdala through suppressing the tonic GABAA receptor currents Zhi-Peng Liu et al
[vi] PUBLIC RELEASE: 20-NOV-2013 Size, connectivity of brain region linked to anxiety level in young children, Stanford study shows STANFORD UNIVERSITY MEDICAL CENTER