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The Gut-Brain Axis

The ‘Brain-Gut Axis’ is a term used to describe the two-way communication system between our digestive tract and the brain.  A growing body of research into this axis demonstrates how much influence the gut can have over the brain and vice versa.  When we speak about reactions to foods, we most commonly understand them as immediate and often dangerous allergic responses, such as the constriction of the throat and trouble breathing, or dizziness and fainting.  It is usually easy to pinpoint the food that causes these reactions because of the immediate immune system response, caused by a type of immune cell known as IgE antibody.  In contrast to this, food intolerances are mediated by IgG antibodies and these reactions can take up to 48 hours to have an effect.  Symptoms related to IgG reactions can often be manifested as chronic issues like joint ache, IBS and depression or anxiety, which are often overlooked and not associated with what we eat.

How Bacteria Influence Communication Between the Gut and the Brain

Communication between the gut and the brain is controlled via our immune system, our endocrine system (hormones) and our central nervous system, which are all under the influence of the bacteria in our gut.  The types and amount of these bacteria, known as our gut microbiome, can be directly impacted by factors such as diet, stress, pollution and medications and the composition of the microbiome is also understood to affect one’s susceptibility to food sensitivities and intolerances.

Leaky Gut = Leaky Brain

To understand further about how food intolerances can impact our mental health, it is important to explain the relationship between our gut microbiome, the immune system and our brain in a little more detail.  The walls of our digestive tract provide a barrier between what we eat and the rest of our body and an unhealthy gut microbiome can lead to increased levels of inflammation, leaving the walls vulnerable to structural damage. Our intestinal wall is composed of cell junctions that prevent bacteria and large food molecules from entering the bloodstream, however, if these become damaged, proteins from foods that should not be circulating in our bloodstream can enter and an immune response is mounted as a reaction. This response is mediated by IgG, an antibody, that helps to protect against bacterial and viral infections as well as food antigens and is the most abundant immune cell in the body. Whilst food antigens are usually quickly cleared by an intelligent system called the reticuloendothelial system, with structural damage and a poor gut microbiome, this immune response can keep reoccurring. It is suggested that a chronic immune response such as this can have a negative impact on the brain, damaging its own structural barrier, called the Blood Brain Barrier. 

The Brain’s High Fortress – The Blood Brain Barrier

The Blood Brain Barrier (BBB) is similar in structure to the intestinal barrier and is usually highly selective, allowing certain required metabolic products, such as short chain fatty acids and amino acids to pass into the brain from our wider circulation but protecting the brain from potentially damaging components. When the BBB is compromised, unwanted translocation may occur such as allowing a bacterial invasion, which can alter the function of immune cells that are responsible for regulating inflammation. Chronic inflammation is associated with many mental and physical health problems, so it is therefore suggested that poor gut health can have a direct correlation to poor mental wellbeing. This is as a result of a compromised intestinal barrier and the negative impact this has on our brain’s own structural barrier (BBB), resulting in inflammation.

The Link Between Inflammation and Depression

Large scale studies have shown the association between chronic low-grade inflammation and depression. For example, in a study that examined data from 14,275 people who were interviewed between 2007 and 2012, they found that people who had depression had 46% higher levels of C-reactive protein (CRP), a marker of inflammatory disease, in their blood samples. Studies like these are paving the way towards a new understanding of the pathology of mental health conditions and how diet and stress can alter bodily systems, such as digestive function and consequently impact mental wellbeing. 

Measuring IgG antibodies in food intolerance tests has been implicated as a popular strategy to tackle symptoms related to sensitivities such as IBS, joint pain, fatigue, migraines, anxiety and depression. A recent survey on 708 people commissioned by Allergy UK, demonstrated how 81% of those with elevated IgG levels, as well as psychological symptoms, reported an improvement in their condition after following a food-specific IgG elimination diet. Taking this all into account, health professionals and those with poor mental health may want to consider the potential role of food intolerances in mental well-being and in managing common mood-related disorders, such as depression and anxiety.

How to Heal a Leaky Gut

Foods that are rich in collagen and its amino acids, like glycine and proline, are great for healing connective tissue, which is what the intestines are made up of. A traditional food, rich in these amino acids, that has made its way into our kitchens again after rediscovering its therapeutic properties is bone broth. Another example of a group of traditional foods that can be used therapeutically in building digestive health, are fermented foods such as kefir, sauerkraut and kimchi. These are abundant in probiotics, which are the ‘good’ bacteria our digestive system needs to help keep a good balance and protect the intestinal barrier from pathogens, toxins and parasites. Once these foods have been introduced on an everyday basis along with eating a healthy nutrient-dense diet and the possible use of supplements to help restore balance, it may be possible to reintroduce foods that were previously triggering an IgG response carefully, one at a time, whilst monitoring symptoms.

After the festive period, many will be feeling the negative impact of alcohol and food indulgence. In an effort to allow the body to recalibrate and shake-off the resulting low energy, brain fog and low mood, taking up Dry January is often a key strategy to start the year off on a good foot. 

However, those susceptible to alcohol cravings may find that a month off the booze is harder than expected. Symptoms such as poor sleep, sugar cravings and a long-winded hangover, are just some of the experiences that people have reported. One of the most common symptoms is an increase in anxiety, perhaps due to the reduction of a very important neurotransmitter called GABA, which is stimulated by alcohol. 

What is GABA?

GABA is the body’s main inhibitory neurotransmitter, meaning that it helps the body and brain to relax and promotes feelings/sensations of calm and tiredness. It does this by preventing excitatory neurotransmitters like dopamine and noradrenaline from over-stimulating the brain and helps to slow down the heart rate and breathing, as well as relaxing muscles. 

In those who are deficient in GABA, feelings of anxiety, stress and worry can be common symptoms, leading to alcohol cravings. Alcohol targets GABA receptors and mimics the effect of this neurotransmitter, helping to relax the mind and body. 

Have you ever craved alcohol after a stressful day and used a glass of wine to help calm the nerves and decompress the mind? This is your body’s way of telling you that GABA needs to be switched on! Whilst alcohol facilitates this, unfortunately the negative side effects of chronic alcohol use far outweigh the temporary feelings of calm and relax. 

The Relationship Between GABA and Alcohol 

Alcohol can cross  the blood brain barrier incredibly quickly – the brain’s very own protective mechanism that prevents things like toxins, bacteria and unwanted hormones from entering the brain and causing damage. This is why after drinking alcohol, its effects can be felt almost instantly. 

The brain has a very intelligent way of preventing overstimulation of neurotransmitters, so that balance is maintained. For example, when alcohol intake is high, in an effort to avoid an excessive accumulation of GABA (as well as other neurotransmitters), receptor response is dampened. Meaning  that over time, you’ll need more of the substance to provide the same effect, which may lead to potential addiction and alcohol dependency . This can make Dry January almost impossible to achieve, if other ways of increasing GABA aren’t employed. 

Below is a list of safe and natural ways you can help activate GABA, which will also enhance overall health and mental wellbeing. 

4 Ways to Increase GABA Naturally… 

1. Magnesium – nature’s relaxant

Magnesium has been shown to modulate GABA activity in the brain. It does this by acting on GABA receptors to help facilitate GABA neurotransmission and its consequent effects of relaxation. 

Magnesium also helps to relax the central nervous system, as well as the body’s muscles. It does this by helping to activate the parasympathetic nervous system – the branch of our autonomic nervous system that is responsible for helping us to relax, down-regulating cortisol output and for regenerating cells and tissues. 

We can find magnesium in foods such as avocado, nuts and seeds, legumes and some wholegrains. However, some studies have shown that supplementing with magnesium (around 300mg a day), can be very effective in reducing symptoms of anxiety. 

2. Consider a B6 Supplement 

GABA is produced via the activity of an enzyme called glutamic acid decarboxylase (GAD) and GABA transaminase, which require vitamin B6 as a cofactor. Studies show that the B6 status of an individual has significant effects on the central production of both GABA and serotonin, neurotransmitters that control pain perception, and for preventing symptoms of depression and anxiety. Whilst B6 is found abundantly in the diet, studies show that common deficiencies of B12 and B9 (Folate), can also indicate B6 deficiency, so it’s important to take into consideration if you have a history of anemia. In addition, those who have chronic alcohol intake are also at risk of B6 deficiency. 

B6 can be found in all animal products, as well as grains, pulses, eggs and dairy. However, you may want to consider a supplement that contains all the B vitamins to help boost B6 levels temporarily.

3. Increase Exercise

Researchers have found that vigorous bouts of exercise can increase GABA. In addition, exercise helps to switch on a regenerative substance in the brain called Brain-Derived Neurotrophic Factor (BDNF) – helping create new and healthy brain cells and increases neuroplasticity, which prevents anxiety and depression. Engaging in just a small amount of exercise on a daily basis, as well as remembering to take ‘walking’ breaks away from the desk or the sofa is enough to switch on this ‘brain-protective’ mechanism.

4. Engage in a Mind-Body Movement 

There is a significant body of evidence that demonstrates how practices such as yoga, can help increase levels of GABA in the brain. For example, in a study comparing the effects of walking and yoga in two separate groups, MRIs that were taken following these activities demonstrated significant differences. Participants in the two control groups did these activities for one hour, three times a week, over a period of 12 weeks. The MRIs revealed a larger increase in GABA levels in a part of the brain called the thalamus amongst yoga practitioners. The yoga practitioners also reported improved mood and anxiety compared to the waking control group.  

A final word… 

These findings give us clues as to what our bodies need in order to maintain health and mental wellbeing. These simple, practical steps are easy to implement and can help reduce alcohol cravings and increase GABA in the brain. In addition, eating a balanced diet that helps to stabilise blood sugar levels, is also essential for preventing cravings. 

To help provide a sustainable source of energy, eating three meals a day which contain protein-rich foods such as poultry, fish, eggs and pulses, as well as complex carbohydrates, such as sweet potatoes, butternut squash, other root vegetables and brown rice, and a wide variety of vegetables, is essential. This helps to prevent anxiety caused by blood sugar lows and highs, which can also leave you vulnerable to craving alcohol and other substances. 

In the UK, at any one time about 220,000 people are being treated for schizophrenia by the NHS. Whilst it is a less common mental health condition, statistics show that there is a higher risk associated to suicide and greater vulnerability to physical conditions like diabetes, perhaps due to medications such as antipsychotics. Due to this, statistics show that people with schizophrenia die on average 10 – 20 years earlier than the general population.

Schizophrenia is characterised by two different groups of symptoms, which are classified as ‘positive’ and ‘negative’. Positive symptoms are the changes in behaviour and thoughts described as hallucinations (hearing voices or seeing things that others don’t), delusions and paranoia. The negative symptoms include feeling disconnected from other people, less interested in life, emotionless and sometimes disorganised thought and speech. 

The exact cause of schizophrenia is still misunderstood, with various theories pointing to a number of different biochemical imbalances, including genetic mutations that can provide the foundations for the disorder to develop. 

What causes schizophrenia?

One of the most popular theories on the cause of schizophrenia, which is widely accepted by the scientific and medical community, is the dopamine excess hypothesis, that is, too much dopamine in the brain that can cause the positive symptoms of psychosis to occur. Antipsychotics are the most commonly prescribed medications to target positive symptoms and prevent psychosis. Whilst they have proven to be critical in targeting excessive dopamine signalling in the brain, antipsychotics can also lead to health complications such as metabolic syndrome, the worsening of negative symptoms and nutrient depletion, which overall can be detrimental to a patients’ health over a long period of time. Studies show that common antipsychotics such as clozapine can lead to the depletion of selenium and l-tryptophan. Both nutrients are incredibly important to maintain health – selenium is an essential mineral, which is a precursor to glutathione, the body’s most important antioxidant and l-tryptophan is an amino acid precursor to serotonin, which is known to prevent depression and enhance mental wellbeing.

Another key theory, founded by the late Dr Abraham Hoffer and his colleagues Humphrey Osmand and John Smythies in 1954, is the adrenochrome theory. This theory initially came about after studying the symptoms caused by hallucinogenic drugs such as LSD, mescaline and amphetamines. The researchers noted these symptoms were similar to those experienced by schizophrenics including euphoria, derealisation and hallucinations, accompanied by paranoia and depression. They then discovered that the chemical structure of adrenaline was also similar to mescaline and LSD, which lead them into researching the effect of adrenochromes on the brain. 

What are adrenochromes? 

Adrenochromes are metabolites of adrenaline, the hormone and neurotransmitter that is responsible for our body’s ‘fight or flight’ response. It is believed that derivatives of adrenaline and other similar compounds such as dopaminochrome and noradrenochrome, can be neurotoxic in large quantities and cause mood-altering effects. 

The adrenochrome theory is further supported by studies that have shown how in those with schizophrenia, the enzyme glutathione s-transferase, (responsible for clearing the brain from neurotoxic compounds such as adrenochrome, dopaminochrome and noradrenochrome) is commonly defective, thus leading to an accumulation of these substances in the brain. 

What is niacin’s (B3) role in preventing symptoms of schizophrenia? 

Abraham Hoffer and his team theorised that in order to reduce the production of adrenochromes, a methyl acceptor such as B3 would be needed. Methyl acceptor is the name for nutrients, mainly in the B vitamin family, which each play an important role in a biochemical process known as methylation. This process is needed for a variety of biochemical reactions, such as building and breaking down neurotransmitters, supporting liver detox pathways and DNA repair, to name a few.  

Upon studying the pathway for adrenaline production in the brain and the cofactor nutrients supporting and inhibiting this pathway, Hoffer deduced that by giving large doses of vitamin B3, which is a methyl acceptor, this would effectively prevent the conversion of noradrenaline to adrenaline, and by limiting the amount of adrenaline, this would then prevent the build up of adrenochromes. 

In addition, B3 is also a precursor to nicotinamide adenine dinucleotide (NAD), a compound that is involved in redox reactions, which prevents oxidative stress caused by free radicals. These are unstable molecules that scavenge electrons from other molecules, causing a chain reaction that can eventually damage tissues in the body. NAD prevents the oxidation of adrenaline, which is what turns adrenaline into adrenochromes, therefore preventing the production of these neurotoxins that over time can damage the brain.


How reliable is the adrenochrome theory? 

Between the years 1953 to 1960, Hoffer researched and studied patients with schizophrenia, publishing a total of six double-blindclinical trials. In one study, conducted in 1962, 82 patients (39 in the niacin group and 43 in the placebo group) were involved and were given niacin throughout a period of 33 days. The results showed that 79.5% in the niacin group improved significantly in comparison to the placebo group, which was 41.9%. 

Despite the positive results that these 6 studies showed, other studies on patients with chronic schizophrenia who had been suffering for longer periods of time, demonstrated how B3 was not as effective. In one particular study using 32 patients, after two years of niacin use no positive effect was registered. However, Hoffer realised after performing initial studies that niacin treatment needed to be carried out for longer periods of time in those with chronic schizophrenia. 

A recent meta-analysis of the effects of vitamins and minerals on schizophrenia identified 18 clinical trials in which 832 patients on antipsychotics were involved. The analysis found that high dose B vitamins (including B3, B6 B9 and B12) were consistently effective for reducing psychiatric symptoms, in comparison to studies where low dose B vitamins were used. 

How safe is niacin treatment? 

Doses of niacin for schizophrenia are recommended between 3,000mg – 18,000mg a day in order to have a substantial effect. It should be noted, however, that niacin treatment must be monitored by a qualified health professional or doctor and should not be self-prescribed. Due to niacin’s side-effects, which are characterised by hot flushes and red skin rashes, many may choose to opt for a ‘no-flush’ version of the niacin supplement. However, studies have shown the risk of liver toxicity with high doses of the timed release and no-flush version of niacin, so this should be avoided. 

In addition, niacin on its own is rarely enough to address symptoms of schizophrenia. Each person is unique, and therefore there are many other factors which should be taken into consideration, such as digestion and inflammation.