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MSG Excites Us, But How About Glutamine and Glutamate?

Should we ban all forms of MSG from food and take L-glutamine supplements instead? A number of conflicting professional views on MSG (monosodium glutamate) makes it difficult to take sides based on hearsay, scholarly articles or the internet. I noticed that MSG-based condiments were recently removed from our supermarket shelves, yet I found a jar of L-glutamine selling at ten times the price in a health shop next door. Both of these products are precursors to free-form glutamate. As a neurotransmitter, glutamate activates over 45% of the brain's neural synapses and thereafter it is used as a precursor for the inhibitory neurotransmitter known as GABA (gamma aminobutyric acid) to inhibit the stimulus. Glutamate provides both the accelerator as well as the brakes of our neural synapses. Most people with mental disorders or poor muscle control are primarily suffering from the effects of excessive neural stimulation called excitotoxicity that destroys neurons. Normally, glutamate and GABA are not allowed to cross the blood brain barrier, so what is the problem? It has a lot to do with a leaky brain. (1-3)

Glutamate/MSG plus a lack of its processing and controlling factors in the food chain--as well as the body --affect excitotoxicity. Glutamate is assembled and broken down within the brain; and ideally, no other glutamate should be present after a neural synapse activation takes place. Calcium activates channels on dopamine receptors to allow glutamate to stimulate or excite the neuron. To end the synapse, magnesium deactivates or blocks the calcium channels. The remaining glutamate is processed in two ways. Either it is transformed into GABA, assisted by pyridoxine (vitamin B6) and the decarboxylase enzyme, or it reverts to glutamine and is returned to the glial cells for future use. GABA is an inhibitory neurotransmitter, the antithesis of the glutamate and calcium combination that stimulates (or over excites) neurons. Most of the GABA that calms us down, induces sleep, and alleviates depression is made in the gut out of glutamate that comes from the food we eat. (4,5)

Some practitioners treat motor neuron diseases with drugs that remove glutamate from the brain; but an overdose will cause neural stimulation as well as the GABA production to fail. It is not a cure for a leaky gut or brain! There is no one off-patent remedy for a disturbed glutamate/GABA axis. Muscle spasms, jerking, twisting, writhing, tics, rigidity, falling and difficulty in speaking or swallowing typify symptoms of both Huntington's and Parkinson's disease whereby neurons are over- or under-activated. The signalling between the brain and muscles depends on the supply of glutamate in the right amount at the right time. Doctors who embrace alternative or complementary modalities prefer to investigate the patient's causative factors--the ones that drugs can't alleviate. For instance --gut health, diet, genetics, nutritional deficiencies, and toxic load to track down the effects that glutamate/GABA imbalances have on particular ailments. (6-8)

Within the brain the excitotoxicity potential of glutamate arouses justifiable concern in cases where the conversion of glutamate into GABA is impeded or when the glutamate influx and engagement is excessive. However, not everybody is affected by these chemical imbalances, so it makes no sense to universally condemn all sources of glutamate. For some, a glutamate deficiency can impede GABA production --leading to depression, anxiety and insomnia. Afew people, especially those with a leaky brain may have an adverse reaction to MSG and they do experience headaches, heart palpitations, blood pressure fluctuations or even asthma. They may be particularly vulnerable to excitotoxicity. At the same table, others enjoy the umami or savoury taste that is imparted by MSG or free glutamate. Whether supplied by condiments, food sources, glutamine supplements, or made in the body, glutamate plays a key role in many essential neural, motor and metabolic processes. (5-7,9-11)

The Glutamic Acid-Glutamine-Glutamate-MSG Family Tree

Glutamine is the most abundant free-form amino acid in the human body. Depending on how its chemical structure is modified, glutamine can convert to glutamic acid or to glutamate. There are glutamate receptors throughout the body; and the digestion of food, especially, is stimulated by those that are present on the tongue. We need to understand that the body uses glutamate--lots of it every day, whether it comes from glutamine, the MSG shaker, or from a plate of food. The digestive system breaks down MSG into glutamate and sodium. Getting to grips with the basic chemistry will give us a better overview of the relationship between these controversial chemicals. (4,12-14)

Glutamate is part of our food chain as well as body chemistry--and it tastes good! During digestion MSG loses its sodium atom and receives one of hydrogen to release free glutamate that is taken up by the bloodstream. Two forms of glutamate--both bound and free--can be present in the same food sources, but only free glutamate enhances its flavour. It augments (excites) the savoury sensation on glutamate receptors that are present on the tongue. The savoury taste is called umami and is different to the sweet, sour, bitter or salty signals we get from our taste buds. As a result of the savoury sensation, the brain orchestrates the release of digestive enzymes, hydrochloric acid, and insulin to help us digest the incoming food. Glutamate derived from either L-glutamine supplements or MSG also helps the gut to ferment and break down fibre. (This also helps to reduce the gassy effects of baked beans I discovered. I believe that it is unwise to eat them without a dose of glutamate.) (15,16)

When food manufacturers are told to remove MSG from their ingredients, they often add others that are rich in natural sources of glutamate such as yeast extracts, hydrolysed protein, and so on. MSG forms naturally when fermented food dries out and those controversial white crystals appear. Fermented food like yoghurt, kimchi, and pickles are rich in glutamate; and during digestion gut bacteria set the glutamate free to aid digestion and supply the body with glutamate that is mainly used by muscles. Cabbage, when fermented into sauerkraut, is a good source of glutamate as well as vitamin C and valuable probiotics like Lactobacillus plantarum. Scientists have found this microbe to be one of the best for releasing glutamate. There is 10 times more free glutamate present in breast milk as opposed to cow's milk. An infant can detect the taste of naturally occurring free glutamate and ingests more of it per kilogram of body weight than during any other period of its life. The baby prefers mother's milk to MSG-free infant formulas. (2,8)

They say that the Japanese brought MSG to America to be sold as a flavour enhancer, but the MSG pettifoggers accuse them of causing the excitotoxicity problem. Sugar beets and sugar cane are typically used as raw materials to harvest MSG crystals that are formed out of molasses. Ironically, in the USA, the same sugar cane and sugar beets are used to excite our taste buds in a different way. They produce white crystals that excite sweetness --to make us addicted to sugar and consume vast quantities of it, leading to insulin resistance in many cases. Sugar addicts are morbidly obese as a result of consuming too many calories and refined carbohydrates. Yet some medical experts say that MSG is one of the worst food additives on the market. Worse than sugar or high fructose corn syrup? What causes insulin resistance, heart disease, obesity, cancer, liver failure and tooth decay--sugar or MSG? (3,15)

What happens to neurons during a spell of excitotoxicity? Glutamate levels rise in the brain for a number of reasons. Firstly, we know that MSG can trigger excitotoxicity within a leaky brain whereby a damaged blood brain barrier allows toxins, microbes and especially glutamate to enter the grey matter. When a large quantity of foreign glutamate floods onto a dopamine receptor, the antagonists and anti-agonists, GABA conversion, and glial uptake mechanisms will fail to shut down the synapse. Another reason for synapses to be overwhelmed by glutamate happens within the brain when glial cells are damaged. These cells store glutamine that is converted temporarily by the enzyme glutaminase into glutamate during synapse activation, and then it reverts to glutamine for uptake and storage. If glial cells are injured or die due to a lack of oxygen or glucose, they spew out their glutamine and it reverts to glutamate. As a result of trauma from head injuries, concussion or extreme emotional stress, strokes or a diabetic coma that lead to the destruction of glial cells, glutamate will inappropriately form inside the brain--regardless of blood brain barrier protection. (18-21)

From either cause, the unsolicited glutamate will remain in the extracellular fluid, and unopposed will continue to stimulate cells to death--a state of excitotoxicity. A lack of magnesium and an excess of calcium contributes to the mayhem. A cascade of glutamate arises when surrounding glial cells also begin to die off and spill out their contents. This is what happened, as I discovered, when a friend of mine -already traumatised by his failed marriage--collapsed as a result of a blood sugar-related incident. He was insulin resistant, and as a result of a perpetual stress-related Cortisol overload, he began to suffer from bouts of hypoglycaemia (low blood sugar) alternating with hyperglycaemia (high blood sugar). Stress and trauma can trigger inflammation and may also damage the blood brain barrier. (20,22)

Glial cells throughout the body, especially in muscles that are starved of glucose (hypoglycaemia) will die, spilling out their carefully guarded reserves of glutamine and the enzyme glutaminase --a deadly duo that becomes glutamate and joins up with calcium, its excitable partner. Excitotoxicity is the result. Excessively high blood sugar also damages nerves. Their outer myelin coating can degenerate, resulting in neuropathy. The nerves are no longer properly insulated, and fingertips, toes, and extremities are the first to feel the stinging and the pain. Then the numb feeling as the nerves begin to die. Some cells are very sensitive to an overload of glucose and do not develop enough insulin resistance over time. They are thus unable to prevent a burnout within the mitochondria. Retinal cells are especially vulnerable to hyperglycaemia. Whenever nerves die, the glial cell at the synapse will provide a lethal dose of glutamate and this excites the neurons to death, causing a domino effect on neighbouring cells. My friend never fully recovered from this setback; despite the attempts of his doctor friends, our endless suggestions and bottles of supplements. When you have experienced excitotoxicity to this extent, what can you do? (23)

GABA Helps to Control Excitotoxicity

The body is protected from excessive glutamate exposure in a number of ways within the brain and on its neuro receptors throughout the body. GABA helps control excitotoxicity and calms us down, alleviates insomnia, and uplifts depression. While the glutamate/GABA axis mechanism helps to forestall neural excitotoxicity, it is also the target of abuse. Unfortunately, the class of depressant pharmaceutical drugs, such as barbiturates (sleeping pills), and anti-anxiety, anti-depressant drugs as well as alcohol, that target GABA receptors tend to reduce their sensitivity. Constant consumption of these downers also destroys GABA receptors and leads to an increased dependence on drugs. GABA levels are also vulnerable to stress, loud noises, radiation, toxins, and trauma. Within the gut, the Bacterioles fragilis KLE1758 microbe consumes GABA. In 2011 an American university rat trial aimed at increasing gut levels of GABA succeeded by introducing the Lactobacillus rhamnosus (JB-1) strain. The conclusion was that it lowered stress-related behaviour such as anxiety and depression. (24-27)

Our brain is connected to the gut via the vagus nerve and when this channel was severed in the newly de-stressed rats, they reverted to a stressful and anxious condition. Certain Lactobacilli strains have the highest GABA production potential. They reside in a healthy bowel and the best natural source comes from fermented dairy products. The supplementation of Lactobacillus rhamnosus and the Bifidobactera strains especially can improve all types of mental and neurological disorders. It is also important to attend to micronutrients and their food sources that assist the precursors of GABA such as magnesium, zinc, vitamin B6, progesterone, and taurine. (28,29-33)

Other Ways to Prevent Excessive Neuro-Excitability

Glutamate receptors or landing sites are distributed throughout the body--wherever there are bundles of nerves--as for example, in muscles, the digestive system, and also the brain. Glycine that shares some types of glutamate receptor sites also provides an inhibitory effect and is called an anti-agonist. In other words, glycine also helps to shut down the excitement caused by glutamate activated by its agonist--calcium. Magnesium is an antagonist, a substance that opposes glutamate. It is present at the entrance of calcium channels as a natural glutamate blocker as well as a calcium channel blocker. Magnesium keeps both glutamate and calcium under control and guards their transportation channels to prevent nerve cells from exciting themselves to death. People who are deficient in magnesium are more prone to headaches, blood sugar imbalances, muscle cramps, dyskinesia, and insomnia. Diabetics, especially, are deficient in magnesium. (34)

The Day I Excited My Digestion with L-Glutamine and Discovered a Way to Treat Diabetes

L-glutamine powder that people take as a health supplement can also have some remarkable effects on blood sugar. What glutamine does when you lick, taste and then swallow a teaspoon (5 grams) of it mixed with water caught me by surprise. At the time I did not realise that glutamate receptors on the tongue respond to glutamine, to excite the digestive system as they do with MSG and glutamate. After tasting the L-glutamine powder and finding it to be slightly savoury, I had inadvertently stimulated my digestive system, between meals, and it caused a nasty hypoglycaemic episode. I am not sure if it was the teaspoon (5 grams) of the powder, the tongue stimulation or the combination of the two that caused the whoosh of insulin and a flood of digestive enzymes. According to the label on the jar, the five-gram serving of L-glutamine was best taken between and not with meals. There were no warnings or contraindications. (35,36)

Half an hour after tasting and ingesting the glutamine, I began to lose my mojo. My head was spinning, the lights were flickering. I felt limp, blurry, and began to get the shakes. My tummy was growling, I was starving and along came the familiar feeling of hypoglycaemia--this time a near blackout. If you eat sugar on an empty stomach, it may cause reactive insulin spikes and hypoglycaemia for people like me, with average but sometimes low blood sugar. But why did this happen after a dose of glutamine? I am not sure what taking 5 grams of MSG would have done to me on an empty stomach because we usually only have it with food. So, watch out for glutamine supplements because tasting them also triggers the glutamate receptors on the tongue. I can only assume that glutamine mimics the effects of glutamate and MSG in this respect. (37)

I had a similar experience when I tested a new formulation I was working on to use as a pain supplement. The main ingredients were MSM (methylsulphonylmethane) mixed with vitamin C in equal quantities. I mixed a teaspoon of it with water on an empty stomach, 2 hours before lunch and also had a serious bout of hypoglycaemia. I figured that if it did that to somebody with normal to low blood sugar, it could be of benefit to diabetics. A doctor tried it to help a patient with gestational diabetes. It lowered her blood sugar to an acceptable level after other medications had failed. That was many years ago; and although I cannot make such claims, yet I have to warn customers that this product has a, well, beneficial side effect! These simple, albeit naive observations of patients and laymen are often overlooked by scientists in their obsession to patent drugs that do the same thing.

Blood Sugar Regulation with L-Glutamine Supplementation

I thought that perhaps diabetics could also take advantage of my recent discovery and use glutamine or glutamate (or MSG) to help regulate their blood sugar. They could also introduce it directly to the tongue and taste buds. I was joking at the time, but it is true that diabetics often suffer from sub-optimal levels of glutamate. About 2 kg of our body weight is made up out of glutamate where it is mainly present in muscles, the brain, kidneys and the liver. Our reserves are rapidly depleted during exercise, illness, trauma and other stressful conditions. Doctors recommend L-glutamine supplementation for patients with intestinal disorders, to boost immunity, and to help patients with AIDS and cancer. Sportsmen take extra glutamine to compensate for the loss of muscle tissue during exercise. (38)

Not many people (including me) knew that diabetics respond favourably to glutamate, and it helps to lower their fasting blood sugar and improve HbAlc readings. In 2014 after a six-week placebo controlled study in Iran, the diabetics who took 30 grams of glutamate with their meals experienced improved blood sugar as well as blood pressure control. Their muscle mass increased and waistlines were trimmer. Glutamine converts to glutamate, as we now know and stimulates the pancreas to lower blood sugar by improving insulin release and sensitivity. In this case 30 grams a day with meals was recommended, but it is best for your practitioner to determine the ideal dose. This discovery about glutamine helps to clear up the mystery of why I experienced a bout of hypoglycaemia when I took it between meals! (35)

A healthy natural diet also provides tongue-tingling umami enhanced foods that provide adequate sources of glutamate. That's why babies love breast milk, and we love tomatoes, dairy products, meat, fish and green vegetables. Other sources include hydrolysed vegetable protein, yeast and soy extracts and protein isolate. If you are sensitive to glutamate, there is little point in avoiding MSG and all these food items and then supplementing with L-glutamine. If you have a leaky brain and are wary of an attack of excitotoxicity, it is important to attend to the blood brain barrier, otherwise glutamate will keep on flooding in. (39,40)

Having a leaky brain is like leaving your front door open to allow your house (brain) to be invaded by the neighbourhood, then trying to chase them all out. Only your family belongs inside your house, so close the door to keep out the strangers. (2)

Let glutamate be in your food and let it also be your (dose-related) medicine. Glutamate remains elusive--troublesome in excess yet essential for survival. It needs to be present in the right proportion at the right time, in the right place. From latching onto a neuro receptor to healing the gut, mopping up ammonia and helping muscles to move, this versatile yet controversial chemical is a true multitasker. Glutamate also bucks up the brain, enhances the taste of food and relieves flatulence, as does MSG its precursor--the notorious scapegoat of excitotoxicity. (41)


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by Sue Visser

Sue Visser is a natural health researcher, product developer, writer, and Agony Aunt. She specialises in nutrition and herbal medicine with a working knowledge of most of the popular modalities of natural/alternative medicine. She has contributed to the world of radio, television and journalism for over 20 years. Sue wrote, illustrated and published her popular book: Healthy Happy Eating for all blood types followed by The Holistic Guide to a Healthy Happy Heart. The second book was co-authored by Dr James Liddell. Sue is also a product developer and has formulated a wide range of alternative health products based on her unique insight and research.
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