PART 1: GLUTAMATE SENSITIVITY REAL? MYTHS ABOUT GLUTAMATE, MSG AND MORE

Dietary glutamates, particularly MSG, have been glorified for their amazing flavor profile and simultaneously vilified for potentially promoting adverse effects.

While most evidence highlights the safety of ordinary glutamate consumption, some studies have shown that a fraction of the population may be at risk for glutamate sensitivity. These results have encouraged many health advocates to avoid dietary glutamates entirely; despite very little being known about glutamate sensitivity in general.

This article aims to review the current literature available to disentangle fact from fiction regarding dietary glutamates, MSG and glutamate sensitivity:

• Part 1 (below) introduces glutamate and its functions in the body, possible benefits, and myths pertaining to MSG consumption.
• Part 2 covers safety and toxicity of glutamate, possible side effects, risk factors and tips for supporting optimal glutamate metabolism.

What is Glutamate?

Glutamate is the salt of glutamic acid, a non-essential amino acid. Both can be synthesized in the body from a variety of amino acid precursors belonging to the glutamate family of amino acids, including glutamine, proline, and arginine. Approximately one quarter of dietary proteins are derived from this amino acid family.

In the body, glutamate serves as both a vital neurotransmitter and cellular signaling peptide, with a broad range of actions across various body tissues. Glutamate may also be made from GABA (Gamma-Aminobutyric Acid), to which it is the main precursor. Foods may contain glutamate in free and bound forms, or may offer glutamate precursors.

Roles of Glutamate in the Body

The roles of glutamate in the body are extensive and still being studied[1]. A few of its better known functions are detailed below:

• Cellular Respiration. Glutamate can be used to generate alpha-ketoglutarate, an intermediate in Krebb’s cycle that is involved in cellular respiration. Other areas of study suggest that glutamate (along with its family of amino acids) is likely to be important for maintaining ionic gradients in all cells pertaining to calcium signaling and mitochondrial function.
• Digestive Tract. Dietary glutamate is mostly consumed by the gut and used as fuel for enterocytes, in conjunction with GABA and butyric acid. Studies reveal that glutamine is required for enterocyte growth and for regulating their metabolism. [2] [3]  This indicates that glutamate is essential for the turnover and repair of the gut, a process that occurs every 2-5 days on average.
• Gut Microbiome. Lactic acid bacteria make use of glutamate in order to produce GABA. Through this process, a charge gradient is generated that enhances their metabolism and promotes their growth.[4] Other organisms make use of glutamate in order to produce metabolites, some of which exert antibiotic actions.[5]
• Umami Taste. Glutamate is thought to be one of the main proteins known to trigger umami taste. It is also known to improve the flavor of foods due to the way it stimulates the tastebuds. It is also likely to play a role in the transmission of taste in general.
• Liver. In the liver, glutamate is an important component of protein metabolism and urea synthesis. It is one of the main donors of nitrogen used during the production of complex proteins in the liver and gut, including ammonia[6] and nitric oxide[7].
• Nervous System. Glutamate constitutes the main excitatory neurotransmitter in the brain and nervous system. It is a requirement for nerve impulses to take place and also facilitates neuronal growth and plasticity. As it is the precursor to the main inhibitory neurotransmitter, GABA, it is also required for reducing activity in the nervous system[8].
• Immune System. In the right physiological concentrations, glutamate increases the growth and activity of immune cells, as well as being a central component of glutathione, a vital cellular antioxidant.
• Bone. Bone cells require glutamate in order to function, as it plays a critical role in the signaling required for maintaining adequate bone mineral density.

Forms of Glutamate

There are many forms of glutamate found in food, which are typically classified according to whether they are free or bound to other proteins.

Bound Glutamates are found prolifically in all foods throughout the diet at varying quantities. Animal protein contains roughly between 11-22% glutamate and plant-based protein can contain up to 40%, comprising mainly of bound glutamate. They are not associated with any known adverse effects and are usually bound to complimentary nutrients that regulate glutamate’s actions. The gut makes short work of bound glutamates, which have been shown to have little-to-no effect on blood glutamate concentrations[9].

• Monoglutamate and Polyglutamate are common bound glutamates found mostly in plant-based food sources. These are present in small quantities and often paired with folate in ratios conducive to heath.[10]

Free Glutamates are found naturally in a wide variety of foods in negligible amounts, as well as directly added to refined foods as a flavor enhancer. They activate glutamate receptors in the tastebuds to signal for umami taste. Free glutamates (including MSG) can be found in higher quantities in various food additives, including hydrolyzed protein, protein isolates (especially soy), yeast extracts, and maltodextrin. When consumed in large concentrations, they are the most likely to be associated with adverse effects, such as mood swings[11] and pain in both the stomach and intestines[12].

Glutamate Isomers. In nature, free glutamates are present in two forms: L-glutamate and D-glutamate. They are chemically identical yet represent “left-handed” and  “right-handed” 3D orientations (chirality). L-glutamate is responsible for activating receptors, while D-glutamate is non-compatible. Natural sources contain both isomers, lessening the bioactivity of the total free glutamate found in wholefoods. Glutamates found in additives typically contain higher levels of L-glutamate for flavor enhancement.

• MSG (monosodium glutamate) is the most famous of the free glutamates found in the diet, both naturally and added as a flavor enhancer. It consists of 99.6% L-glutamate. As MSG is the most studied free glutamate and has been a topic of potential concern for decades, it will be one of the main focuses of this article.

Are There Actual Benefits to Consuming Glutamate?

In a healthy diet plan, the majority of ingested glutamate is either neutral or beneficial for heath. A few possible benefits include:

• Enhancing Metabolism. Bound glutamate serves as a healthy fuel for most of the cells in the digestive tract. Consuming wholefoods high in glutamate can be beneficial when the gut is in need of repair. The body can make use of glutamine during periods of intensive activity to replenish reserves, including for muscle building, neurogenesis and tissue repair. Glutamine can become an essential amino acid when depleted, as seen in intensive surgery, trauma, chemotherapy and sepsis.[13]
• Lowering Acidity. Glutamine and glutamate also play important roles in regulating the acid-base balance in the body, through producing ammonia (an alkali). This is in direct contrast to the majority of dietary proteins (acidic in nature), which require the assistance of glutamate to be metabolized properly.[14]
• Aiding Enteral Nutrition. Dietary free glutamate may be able to protect against diarrhea induced by consuming a diet consisting of liquids.[15] This makes it an attractive ingredient for terminally ill patients requiring enteral nutrition.

3 Myths About MSG: Health Claims or Health Hype?

If looking at research on the topic, nobody can argue that MSG is completely free of adverse health effects. However, many of the potential negatives have been greatly inflated by health enthusiasts and should be taken into consideration with a grain of salt!

Below is a discussion of three of the biggest health myths pertaining to MSG.

1. MSG will make you fat

There may be some truth to this myth, yet much remains to be explored on the topic.

Unreal Quantities of MSG Can Cause Obesity. It is a well-known fact that MSG is one of the main agents used to induce obesity in lab rats when studying the condition. The quantities of MSG used are typically a lot larger than what one would consume in a natural setting and in some studies, it’s even injected into the test subjects. Therefore, the scientific model of MSG-induced obesity alone is not enough to suggest that ordinary MSG consumption can produce the same result in humans.

Long-Term MSG Intake May Increase Obesity Risk. Despite reports about its absolute safety as a food additive, there is a possible connection between MSG consumption and obesity:

• MSG and the Spleen. Recent studies highlight that MSG is able to alter the profile of immune cells in the spleen directly after ingestion, as well as splenocytes. When inflamed, the spleen is able to induce systemic inflammatory changes through acting on the vagus nerve[16]  (and indirectly on the brain). If substantial enough, disruption of the spleen-vagus axis can result in excess weight gain, as highlighted in lab models of MSG-induced obesity.
• Hypothalamus. Rise in blood concentrations of MSG can potentially damage areas of the hypothalamus (e.g. arcuate nucleus) involved in regulating appetite[17]. These areas lie outside the blood-brain barrier. The quoted study used injected MSG, whereas real intake does not usually affect blood levels. More research is required to see whether generally elevated blood glutamate may induce similar effects.

Long-Term Consumption is Underexplored. If made into a long-term chronic feature, the above effects may predispose the individual to excessive inflammation, metabolic imbalance and rapid weight gain. The time it might take for ordinary consumption to achieve this effect and to what degree in each individual are unknown. Some studies have revealed an association between chronic intake at safe levels and being overweight[18]. More data is required regarding long-term consumption of MSG and obesity.

Nutrition Serves to Regulate Potential Side Effects. It has been noted that the adverse effects of MSG in the spleen can be offset to a degree by dietary antioxidants and optimal immune responses[19].

Thus, MSG is highly unlikely to pose an immediate concern when consumed in the context of a balanced diet. Long-term intake may become problematic if chronically coupled with poor nutrition. It’s also not a secret that many MSG-fortified foods are lacking in nutrition!

Those with digestive disorders, compromised immunity, inflammatory conditions and metabolic diseases are likely to be at an increased risk for MSG-induced obesity.

2. A diet high in glutamate is neurotoxic

While in vitro experiments clearly show the connection between glutamate overload and neurotoxicity, it is not necessarily true that dietary sources will pose the same adverse effects.

The Brain Glutamate Cycle. Glutamate production is tightly regulated in the central nervous system[20]. It typically relies on the cycling of glutamic acid from a finite store that is conserved across neuronal cell types. In order for dietary glutamate to pose a risk, the glutamate cycle of the individual would already need to be disrupted.

Brain Glutamate Uptake Appears Limited. Ingesting excess glutamate over a prolonged period of time would most certainly disrupt the gut glutamate cycle. However, only a few individuals will experience a rise in blood glutamate after consumption[21] and not others[22]. Even in such cases, glutamate is unable to pass the blood-brain barrier[23]. Blood glutamate may enter the brain if the blood-brain barrier is severely compromised.

Glutamate May Promote Neuroinflammation and Eventual Toxicity. Dietary glutamate may be able to exert an indirect inflammatory effect on the nervous system through several mechanisms:

• Vagal Stimulation. Ingested glutamate is able to affect the activity of the vagus nerve via the spleen. This in turn can lead to many of the effects ascribed to consuming large amounts of glutamate, including pain, headaches, and neurotoxicity. Some studies show that large-dose MSG may be able to induce lesions in the hypothalamus of rats through vagus nerve-induced neuroinflammation.
• Blood Ammonia. Excess glutamate and protein intake are able to increase blood ammonia concentrations in some individuals. Blood ammonia can pass the blood-brain barrier and get converted into glutamate or glutamine[24] in the brain. Excessive concentrations may lead to neuroinflammation[25] [26]. The body normally maintains strict physiological concentrations of blood ammonia for urea metabolism, with little able to pass into the brain. Therefore, it is unlikely that ingested MSG would be able to cause an ammonia excess in healthy individuals.
• Direct Brain Exposure. Elevated neuronal glutamate (non-dietary) has been shown to increase the permeability of the blood-brain barrier[27]. This may make an individual more sensitive to elevated blood glutamate, as it could contribute towards a pre-existing imbalance that serves to increase neurotoxicity. Abnormal glutamate metabolism has been seen in those with neurodegenerative diseases, who are prone to excess brain glutamate irrespective of dietary consumption. Research is scarce regarding the impact of dietary glutamate on such individuals.

Despite these effects, dietary glutamate is unlikely to promote neurotoxicity in healthy individuals.

3. Eating Chinese Food is Unhealthy

Chinese food has a reputation for inducing Chinese Restaurant Syndrome in a handful of unlucky consumers. Whether this can be blamed on the MSG-enriched food or not is still a matter of debate.

Chinese Restaurant Syndrome was first reported about over 50 years ago, landing up in the editorial of a journal at that time. Someone who consumed a large amount of Chinese food ended up with all the classic symptoms, including a headache, neck pain, and digestive complaints. Since that time, other reports have emerged, denoting similar symptoms in a small subset of individuals frequenting Chinese restaurants. Breathing problems, sinus, fatigue, flushing, skin rashes and swelling of the glands have also been observed in these individuals[28]. These symptoms were ascribed to the glutamate in the food, which is known to be higher, on average, in Chinese cuisine.[29]

Chinese Food is not the Problem. This has been giving Chinese food a bad reputation ever since, despite the fact that the vast majority consuming such do not experience any symptoms at all. It should be noted that Chinese food itself is not inherently unhealthy due to the glutamate content. On the contrary, Chinese vegetables and traditional Chinese foods have a reputation for their health benefits. Therefore, MSG-related symptoms are likely only relevant in the context of refined foods high in free glutamates. Chinese Restaurant Syndrome was renamed to MSG sensitivity, or the MSG symptom complex.

MSG Sensitivity is Debatable. Researchers are still debating whether this phenomenon is a valid health concern or not. Most studies have drawn neutral results regarding MSG consumption, even when exploring the highest average intakes amongst frequent consumers. Other studies point to sensitive individuals that experienced a reaction when consuming MSG; irrespective of the dose, frequency of consumption, the route of administration and other confounding variables.[30] Consequently, the results are difficult to interpret and prone to inaccuracy.[31] Much remains to be explored.

MSG May Enhance Immune Reactivity in High-Risk Individuals. It may be that MSG alone is not able to trigger a reaction, and that it has the propensity to increase immune reactivity in response to other allergens. Some refined MSG-enhanced products contain a whole host of other ingredients that may also trigger allergic reactions in sensitive individuals[32]. More research is required before it can be ascertained why MSG may serve as a trigger or increase reactivity in some individuals and whether other factors are involved or not.

Toxicity & Safety: Are there Side Effects to Consuming Glutamate?

Continue to part 2 for more.

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