“No MSG”—two simple words plastered across food packaging and restaurant windows have consumers feeling relieved. MSG has long been criticized by consumers; some charge it as guilty for causing a plethora of adverse reactions, while others have the preconceived notion that MSG is bad but have no idea why. Despite being frowned upon for decades, MSG was not always cuffed to its bad reputation.

Journey to the West – MSG’s Successes and Falls

Many people believe that MSG was introduced to the American palate via Chinese food, which can often contain added MSG  [1]  . However, the true debut of MSG into the lives of Americans occurred in the processed food industry after World War II. Most notable was the Campbell’s Soup Company’s recognition of MSG as a potential flavor enhancer. MSG’s popularity went uncontested for many years until the 1960s, when the safety of food additives was questioned  [1]  . In the same period, a letter written by Dr. Robert Ho Man Kwok to the New England Journal of Medicine also placed MSG on trial  [2]  . In his letter, Dr. Kwok informed the editors of the journal that he experienced a specific set of symptoms whenever he ate Chinese food. He described it as “numbness at the back of the neck, gradually radiating down to both arms, general weakness and palpitation.”These symptoms were then dubbed “Chinese Restaurant Syndrome,” or more commonly referred to as the MSG Symptom Complex, a collective term used to describe the symptoms associated with MSG consumption  [2, 3]  . With an influx of similar reports by other medical professionals, researchers began to investigate the health effects of MSG  [4]  . To better understand how MSG might affect the body and what the studies on MSG conclude, we must take a step back to discuss what MSG is and where it came from.

The Birth of MSG & Umami

MSG is an abbreviation for monosodium glutamate, a compound that was first discovered in 1908 by Kikunae Ikeda  [5]  . When dissolved in water, the molecule dissociates into a sodium ion and glutamate, an amino acid produced by the body that acts as an essential neurotransmitter  [3]  . The glutamate component of MSG is responsible for activating the fifth taste of umami, which was uncovered along with the discovery of MSG  [5]  . MSG was originally made by extracting and crystallizing glutamate from a seaweed broth, but today, fermentation is the commercially preferred method of production  [5, 6]  . Although the flavor enhancer is most popularly linked with Asian, specifically Chinese, cuisine, it is found in a variety of foods. Garlic, onions, carrots, eggs, cow’s milk, and protein-rich foods all contain naturally occurring glutamates  [7]  . Additionally, packaged and processed foods such as chips, canned soups, and frozen foods contain added MSG  [8]  . MSG can be masked under other names as well—for example, hydrolyzed vegetable protein, autolyzed yeast extract, and sodium caseinate are all indicators that MSG is present  [7]  .

Keeping it Low

There was an especially great interest in studying the effects of MSG on the brain since glutamate is a neurotransmitter involved in excitatory neuronal signaling in the central nervous system (CNS), the neural connection network comprised of the brain and spinal cord  [9]  . The major concern with MSG consumption lies in the hypothesis that consuming too much MSG will elevate the free glutamate concentration level in the blood, leading to high concentrations of glutamate in the extracellular fluid (ECF) surrounding brain cells. An increase in glutamate in the ECF will also increase the exposure of CNS neurons to glutamate  [9]  . Low glutamate concentration in the ECF is vital for proper neuronal

functioning, as it prevents the build-up of glutamate in neuronal synapses  [10]  . Previous research shows that exposure to high concentrations of glutamate overexcites neurons of the CNS by opening channels that allow calcium to enter the cell  [9]  . The result is intracellular calcium overload and the activation of pathways that lead to neuronal death via a process known as excitotoxicity  [9]  .

Although excitotoxicity is a concern, the likelihood of this occurring as a result of MSG consumption is minute. After ingestion of MSG, the free glutamates are broken down in the small intestine to be used as an energy source  [10]  . Even with relatively high MSG ingestion in food, only small changes in blood glutamate concentration have been observed. A significant amount of glutamate reaching the brain is therefore unlikely. Even if glutamate reaches the brain, the body has complex mechanisms involving the blood brain barrier (BBB) that prevent the build-up of glutamate in the ECF. The BBB protects the brain from many harmful substances circulating in the blood. This highly selective, semipermeable barrier is composed of a single layer of closely packed cells called endothelial cells, which line the capillary walls. These cells have two distinct membranes, the luminal (blood-facing) membrane and the abluminal (brain-facing) membrane, and they contain different transporters on each side to allow for the maintenance of glutamate levels in the ECF  [10]  . The combined effort of intestinal degradation and the protection of the BBB ensures low glutamate concentrations in the ECF, thereby preventing a glutamate overdose simply from MSG consumption.

MSG on Trial

One of the earliest studies on MSG was conducted by John W. Olney at Washington University School of Medicine, who studied the effects of MSG in mice by injecting it under the skin  [11]  . Light microscopy revealed neuronal death in multiple areas of the brain, including the arcuate nucleus of the hypothalamus, neurons in the median eminence, and the subfornical organs  [11]  . One possible explanation for these observations could be that these brain regions lack the protection of the BBB and are thus more prone to neurotoxicity  [12]  . Prior to Olney’s study, there was a lack of research regarding MSG’s impact on the central nervous system, and his findings were alarming  [11]  . However, at the time, many did not draw attention to the fact that the dosage Olney used on the mice was 50 times higher than the average MSG consumption in humans  [11, 8, 13]  . This high dosage could be substantial enough for the glutamate to cross the BBB, as well as impact any brain regions not protected by the BBB, resulting in the lesions observed. The findings from Olney’s study caused an increased interest in MSG research and its reported associated symptoms. Some of these symptoms include general weakness, muscle tightness and twitching, flushing, sweating and burning sensations, headaches and migraines, chest pain, palpitations, and numbness or tingling  [14]  .

In 1970, researchers at the Institute of Pharmacological Research in Milan, Italy conducted a study on the effects of MSG in healthy individuals who did not experience symptoms after eating food containing MSG  [15]  . The study involved 24 participants and two treatments: beef broth with and without MSG, delivered two days apart. Participants then rated their symptoms associated with the MSG Symptom Complex. The study concluded that there was no difference between the treatments in the symptoms reported or the frequency at which each symptom occurred  [15]  .

Taking the research on MSG one step further, Raif S. Geha conducted a carefully controlled study in 2000 on the reported reactions to MSG consumption  [14]  . The study began by recruiting volunteers who had self-reported experiencing the MSG Symptom Complex after eating Asian meals that they believed contained added MSG. The volunteers were then screened and became participants in the study if they reported experiencing two out of the ten MSG-associated symptoms within four hours of eating a meal that contained MSG.  Central to this research was the consistency of the participants’ reports  [14]  . If MSG was truly a culprit in causing these symptoms, it was expected that the participants would report symptoms when they ingested a MSG-containing pill but not report any symptoms when taking placebo pills.

Findings from this study showed that in people with the reported MSG Symptom Complex, large doses of MSG given without food were sufficient to elicit symptoms  [14]  . Upon repeated experimentation, however, the responses were inconsistent. To explain this inconsistency, the researchers suggested a demand bias at work  [14]  . The participants in this study were selected based on the criteria that they reported experiencing symptoms after eating MSG-containing Asian meals. Because of this, they could have interpreted that the purpose of the study was to look at the reactions to MSG consumption and unconsciously change their responses to fit their interpretation.

Despite the evidence presented above indicating that MSG is safe to consume, it is critical to note that there could be subgroups of people who are sensitive to MSG, and the symptoms associated with the MSG Symptom Complex have been reported to be more prevalent in these individuals  [3]  . The subgroups include people with asthma and vitamin B-6 deficiency, infants, and women taking contraceptives. Although there are links between these subgroups and MSG sensitivity, no sufficient evidence exists to strengthen the correlation  [3]  .

The Final Verdict

After many years of careful investigations, the U.S. Food and Drug Administration has marked MSG as being “generally recognized as safe” when consumed in amounts less than 30 mg per kilogram of body weight  [15, 16, 17]  . This limit is approximately three times the amount of MSG that an average person would consume  [8, 13]  . A common theme in most MSG research is that it rarely reflects the way that MSG enters the human body. Studies often use MSG injections, MSG in liquids, or MSG pills, and they usually require that participants fast before the experiment to control for other factors that could influence the results  [11, 15, 14]  . According to a meta-analysis published in 1995, the dosage and method of MSG delivery into the body has been found to have an impact on blood glutamate levels  [3]  . Of importance are the findings that indicate MSG in water causes a greater rise in blood glutamate levels than MSG seasoning in food. Furthermore, participants who fasted are more likely to report symptoms than those who did not fast  [3]  . The need to control for confounds in these experiments is one of the limiting factors in MSG research.

The misconceptions about MSG have taken strong roots in American culture. The phrase “MSG is bad for you” has been presented to the public by media and by word-of-mouth for so long that this thought has become second nature in our society. A bias against Asian foods could also be an underlying factor in the MSG uproar. Rarely are Doritos and Campbell’s chicken noodle soup blamed for causing any adverse symptoms. So, the final verdict? MSG does not seem to be a culprit in causing neurotoxicity or the MSG Symptom Complex when consumed appropriately and it can be enjoyed safely as a flavor enhancer in a variety of cuisines across the world.

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