December 20, 2020

Nutritional Biochemistry

Should we still be worried about MSG?

Read Time 7 minutes

I recently bought a food product that had a “no MSG” label on the front of it. This strikes me as an odd selling point—the sticker is front and center like a shiny gold star. I presume it’s meant to ensure safety and reassure the buyer. But for what? Do people really still believe that monosodium glutamate (MSG) is harmful? It turns out there is a widely held belief that MSG is bad for us. 

You may have heard MSG can make you sick or have seen similar “no MSG” signs in restaurant windows and on food packaging. Yet all the research I’ve seen says otherwise. MSG is not a harmful substance. Further, The U.S. Food and Drug Administration (FDA) designated MSG as a Generally Recognized As Safe (GRAS) ingredient long ago in 1958. Despite requests over the years to remove the GRAS designation, the FDA kept it on the list given the available evidence. But the additive continues to be the subject of controversy, and many still question its safety. A GRAS designation does not mean that a substance does not cause any harm—just reference what I wrote regarding sweeteners and high fructose corn syrup, which I likewise talk about in AMA#18. But the controversy over the safety of MSG has been largely overblown. There’s no evidence to substantiate the claim that MSG causes ill effects in most people who consume it. A minority of people are hypersensitive to glutamate and MSG in food—added or natural—and in a study where MSG was given at 3 grams, in the absence of food, sensitive individuals had short-term, transient adverse reactions. With that said, the story I’m about to share shows how science can say one thing, but strongly held beliefs remain. But before I tell it, let’s start with a little MSG primer, and its presence in the food supply. 

MSG is the sodium salt of an amino acid called glutamic acid. Glutamic acid is a nonessential amino acid, meaning that our bodies can produce it. It has two carboxyl groups consisting of a carbon atom, two oxygen atoms, and a hydrogen atom (COOH).  When a carboxyl group loses its hydrogen atom, it becomes negatively charged (COO-) and can bond with a positively charged ion. MSG is formed when a positively charged sodium ion (Na+) binds to the negatively charged carboxyl group (COO-) (Figure).

Figure. Structures of glutamic acid and monosodium glutamate. 

In 1908, a Japanese biochemist, Dr. Kikunae Ikeda, attributed the distinct taste of seaweed broth to glutamic acid. He named it umami, translated as savory. Umami is one of five basic tastes, which also include: sweet, sour, salty, and bitter. From that point on, the newly isolated glutamic acid was mass-produced and used as seasoning to enhance the flavor of food. Isolated or not, the sodium salt of glutamic acid is found naturally in foods such as tomatoes, cheese, and in vegetables like broccoli and cabbage. So the sodium salt form of glutamic acid both occurs naturally and synthetically—it makes food taste extra tasty. But how did it become the subject of warning labels and shrouded in controversy?  

It’s a strange story about how public media picked up and ran with questionable information. The NPR podcast This American Life dedicated part of an episode to the account. In 1968, a Letter to the Editor warning readers about “Chinese Restaurant Syndrome” (CRS) appeared in the New England Journal of Medicine (NEJM). You may know about CRS. Maybe you’ve experienced it yourself—the syndrome refers to the complex of symptoms, often attributed to MSG, like burning sensations in the mouth, facial pressure, headache, maybe some chest pain. And if it sort of sounds like what could happen with elevated sodium intake, think again. MSG is not high in sodium and actually allows for far less added salt given its flavor-enhancing properties. It contains one-third the amount of sodium as sodium chloride (table salt), about 12% versus 39%. The ratio means very little if more MSG is added to a given food in order to make up the difference. However, MSG in excess has been reported to lose the umami taste and make food less-palatable. Further, one study suggests that adding MSG to soup requires less sodium (note this study seems to have been unblinded).

The letter was signed by a physician and Chinese immigrant named Dr. Robert Ho Man Kwok, who claimed to feel numbness and palpitations after eating in Chinese restaurants in the US, speculated that MSG was the cause, and called for further research. Fifty years later, an elderly white orthopedic surgeon named Howard Steel claimed that he had made up the name and written the letter himself as a prank after he made a bet with a friend. However, there was an actual doctor named Robert Ho Man Kwok who at the time worked at the research institute named in the letter, and though he was dead by the time Steel made his claim, Kwok’s family maintained that he had indeed written the letter. It seems unlikely that Steel, who is also now dead, was the actual author, especially given that Kwok’s family confirmed that Kwok wrote it. Nonetheless, one of the replies to the original letter speculated that it was a joke, and regardless, it took on a life of its own thereafter.

The most practical way to determine the reaction to Kwok’s letter decades later was to dig through old print journals, and several researchers who searched found numerous reply letters in subsequent issues. They found that some letters were clearly tongue-in-cheek, and most seemed to be part of a lighthearted NEJM tradition in which letters to the editor jokingly described quotidian symptoms using excessively technical medical terminology. Though most of the response letters in NEJM were no doubt meant to be humorous, the joke was completely lost on the media, which dutifully reported on this new “health concern.” Six weeks after its publication, the New York Times ran an article on this so-called “Chinese restaurant syndrome,” including interviews with defensive Chinese restaurant owners. Several major newspapers quoted from one of the satirical response letters to the NEJM as if it were a scientific document. The article did not mention that MSG is also widely used in many foods associated with the west rather than China, such as flavored potato chips, parmesan cheese, frozen dinners, and fast food. The inconsistency—symptoms occur after eating “Chinese” restaurant food with added MSG, but not in others—further suggests the entire argument is devoid of merit.   

The reporters who covered the story did not understand the difference between a letter to the editor and a peer-reviewed research article. The national news took an inside joke among physicians and presented it as scientific fact. They set the stage for decades of misunderstanding about a widely used additive, and provided an unfortunate example of what happens when science, personal anecdotes, and cultural bias collide.

However, this case allows us to observe how the scientific method can operate—confirming or refuting a hypothesis or, in this case, something held as true with nothing empirical behind it. Remember that study replicability, irrespective of conclusion, is critical for accepting what it comes to conclude. No single study and especially no group of study of the same kind (i.e., uncontrolled, observational) are sufficient. And even then, conclusions can change. After all, the easiest person to fool is ourselves. 

“The first principle is that you must not fool yourself—and you are the easiest person to fool. So you have to be very careful about that. After you’ve not fooled yourself, it’s easy not to fool other scientists. You just have to be honest in a conventional way after that.” — Richard Feynman 

We can trace how, in the wake of the original 1968 letter to the NEJM, scientists began to look critically at MSG. The published findings have varied in degrees of rigor in experimental design and results have been inconsistent. In the late 1960s, Dr. John Olney raised the most significant concerns regarding MSG, conducting research on infant mice and found that MSG had toxic effects on the brain and it was associated with other health issues. However, the levels of MSG that he found to be toxic resulted from force feeding over a short time period, so the data’s applicability to human infants in real-life situations was unclear, and many other studies could not replicate his results. In contrast, the work of Richard Kenney found no support for the notion that MSG consistently caused specific symptoms. Kenney found that symptoms were not consistent day-to-day and did not correlate with plasma glutamate levels or other physiological markers. Other studies showed similar results. Further, the published conclusions of Mark Friedman from a symposium evaluating MSG’s purported relationship to obesity and abnormal fat metabolism found no effect on body weight and rodent MSG injection studies that reported toxic neural effects were not applicable to humans. Almost no ingested MSG passes the blood-brain barrier, meaning that dietary MSG does not gain access to the brain. 

The MSG case shows how susceptible we are to confirmation bias and other cognitive biases which I have discussed in previous emails and in discussion with Dr. Carol Tavris and Dr. Elliot Aronson. In scientific research, it is why double-blind studies are so important. One study that asked about CRS and Chinese food consumption used two questionnaires: when the questionnaire did not specifically mention CRS, 3-7% reported symptoms. But when the syndrome was mentioned by name, 31% reported CRS symptoms. The list of published studies evaluating MSG-related symptoms goes on and on. However, a 30,000-foot view shows that decades of research demonstrated no danger from MSG consumption. Many separate scientific reviews—by the Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization (FAO), the World Health Organization (WHO) from 1987, the European Communities’ Scientific Committee for Foods in 1991, and the Federation of American Societies for Experimental Biology (FASEB) from 1995—all concluded that concentrations of MSG in food are not hazardous to human health. As mentioned, the latter showed safety for the general public, but suggested that a small percent of the population may have adverse effects from large quantities of MSG in the realm of 3 grams. For reference, the average daily intake of added MSG in the U.S. is about 0.55 grams. A 2006 review of 40 years of data concluded that clinical trials have failed to identify a consistent relationship between the consumption of MSG symptoms associated with the so-called CRS. Similarly, a 2009 review noted the lack of a consistent relationship between MSG ingestion and clinical effects. 

We can learn a lot from the MSG myth that continues to persist. This story shows it’s very difficult to dispel longstanding cultural myths, even when scientific evidence dismantles them. As MSG researcher Robert Kenney told the Washington Post, “No amount of evidence will ever get rid of an anecdote.” Or as Jonathan Swift, the 17th century satirist and author of Gulliver’s Travels, said, “A lie can travel halfway around the world while the truth is still putting on its shoes.” 

 

—Peter

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45 Comments

  1. Glutamate is the most abundant neurotransmitter in our bodies. So what could be the harm in extracting it or chemically manufacturing it and feeding it widely around the world? I live in China where people drop it by the spoonful in their soup at cheap noodle shops everywhere. But many people absolutely hate the stuff here and no decent cook with his or her salt would ever use the stuff that is known to make bad food taste meatier.

    I am extremely sensitive to it. That is only the unnatural purified stuff. The worst part is it gives me extreme insomnia. Not exactly sure why only the artificial glutamate does this. Maybe because of its purified form, or that there are other impurities in MSG that cause the problem, or if it is the chemical processing causes the formation of d-glutamate which is wholly unnatural to our bodies vs the l-glutamate form found in nature.

    FYI – there is an epidemic of insomnia in China as well as in the USA. It is commonly advised to stay away from junk food if you suffer from insomnia. Junk food is a sweeping category. Just exactly what is it in junk food that is causing or exacerbating insomnia? Perhaps MSG?

    • I agree MSG might be safe when it found naturally in food. I have observed multiple tiles when i consume Added MSG in snacks i experience severe bout of insomnia. So i am absolutely convinced of its toxicity. Also genetics might play its role people from Chinese, Japanese races have greater tolerance to it

  2. My understanding is that “hydrolized vegetable protein”, such as that found in “Better than Bullion” broth paste, is indeed a new way of listing MSG without actually using the acronym. Sneaky. I’m not sensitive to MSG, but I’m highly sensitive to food producers attempting to foil consumers by switching jargon.

    • Autolysed yeast extract is another common name for MSG much like natural flavors or even just flavoring. This article is nothing mire than someone’s agenda.

    • Except maybe when they know that something has been unfairly targeted and call it something else to get around an undue stigma?

  3. I and my sister and her family can not eat anything with MSG in it as we all get very sick from this and I always get Server Migraine headaches from it as well and that cripples me big time! I have ran into a great many people who are extremely sensitive to MSG! So this report is not 100 percent accurate! This I believe is a bias study that was done on this! People like me have a right not to buy food that doesn’t have MSG and any kind of Corn Syrup in it as well!

    • I am the same way and agree 100 percent! Bogus article. I have also read scientific studies that when mice were fed a diet full of msg that they became extremely obese. Hmmm. Anything that is manipulated by mankind will have some kind of error.

      • Then you’re in for a rude surprise when you discover how many fruits and vegetables you can’t eat.

        Nothing you but in the produce section hasn’t been manipulated into palatability by mankind.

        This is probably not a valuable rubric to evaluate food choices by

  4. No MSG labels are a god send to me! My symptoms if I eat anything containing MSG are: Red rash on chest and throat, inside of my cheeks and tongue swell up, my lips tingle and swell too, my whole body starts shaking uncontrollably, I feel light headed and very unwell and it all happens within 10-15 mins of consuming it. It is very scary and although hospital have said it may feel like and present similar reactions to that of anaphylaxsis, I should be ok but I have to carry an epi-pen incase! So MSG may not harm most people but there are some who it affects seriously so any labelling that can help is essential. Also if we are eating good, flavoursome food why on earth should we be adding MSG anyway? It’s a cook’s cheat and really not needed in the food we consume.

    • Claire,
      Gives me the worst Belly issues. If I get msg early in the day, I can handle the paint is better than waking up from the pain which is crippling for several minutes. Then the Belly needs to you know. Keep reading the labels and watch for other things like anything Hydrolyzed, Autolyzed or added proteins , i.e soy, corn, pea , whey etc.
      Take Care

  5. You are misleading people and pushing your own agenda. You should be ashamed. MSG is like poison to me, I have severe migraines and I am highly sensitive to glutamate rich foods. MSG, which is synthetic unbound glumate wreaks havoc on me and causes cortical spreading depression, which leads to migraine.

    • The MSG agenda?

      Does everyone who reports research findings that disagree with you have a devious ulterior motive?

  6. MSG gives me migraines – extreme head pain that leaves me bedridden in a dark quiet place for 9-17 hours. I don’t cry, or move, or even think because of the agony. And you are telling us there’s nothing wrong with MSG? When I was diagnosed as a child the doctor told my parents that it’s a common triggar. If I get a migraine with none of my other known triggers present, I check the food labels of what I’ve eaten and there will be MSG listed by some other sneaky name.

  7. Here’s an interesting journal article from 2018 discussing OCD specifically, but also the accumulating evidence connecting OCD (and perhaps other neurological symptoms – headaches, brain fog) with a genetic disorder glutamatergic neurotransmission.

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