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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43 Comments

  1. Funny – I get a guaranteed 48-hour headache after one bowl of miso soup. Trace amounts in other foods are generally not a problem. So if not MSG, what is the most likely cause of the headache? It is absolutely not sodium or salt.

    • Excellent article and research.
      MSG is safe.
      The food it adorns isn’t.
      Beyond the scope of this article, I see MSG accomplishing two things: 1. Making food taste amazing; 2. Leading us to overeat highly refined foods.
      I’d be hard-pressed to eat four baked potatoes at dinner. But I can eat, in one sitting, the equivalent in the form of MSG-laced chips.

    • I find it funny that the guy that wrote this article and several other people think that just because they don’t get a reaction or as they say the majority don’t then they think it doesn’t do some kind of damage. I get a pounding heart,headache and don’t sleep for about 15hrs after consuming this poison.

  2. One thing that has bothered me is the modern (maybe/probably arrogant) idea we can isolate this or that ingredient that is found naturally and it’s the same. WRT MSG I suspect we ingest much more than we ever could if we just ate umami foods. So many of our additives and medicines etc we “think” we isolate the most important ingredients BUT the other compounds and chemicals that mother nature created maybe important too. Evolution was the the ultimate experimentation….. Once we industrialize our foods/medicines we consume much more than we would if nature was “in charge” 🙂

  3. While the majority of people can eat Doritos and not get a migraine, I am unfortunately one of those sensitive to it and will get a migraine headache if I eat Doriotos or Ramen Noodles. It used to be listed under “natural ingredients” which made it difficult for me to know if it was present. Most store-bought chicken broth contain it. Thus, I cook my own chicken broth at home. I am greatful that it must now be listed as a seperate ingredient so I can avoid it. I understand that I’m in the minority but I do matter and I’d like to avoid unnecessary migraine headaches as much as possible. I don’t believe my headaches are power of suggestion. I was able to eat Doritos in my youth. I used to brag in my family that the sensitivity skipped a generation, then it onset after puberty.

    • Of my mother’s siblings (10 kids) the females with blond hair and lighter eye coloring got the sensitivity while the females with brown hair and brown eye coloting did not. The males did not. I’m very suprised scientific studies have not been definitive in identifying the cause of the migraine headaches in sensitive types.

    • Thank you for your post. I feel like I’m crazy when I read these articles. Like what am I allergic to then? I stopped eating msg one year ago and I havent had to take my medication since. I’ve suffered migraines for 10+ yrs.

  4. I have unwittingly run an experiment over the last 30 years. Whenever I (used to) eat at a Chinese food restaurant, and forget to ask if there is MSG in the dish, 3 – 5 hours later I have a headache, and tightness in the throat. Happens like clockwork – it will wake me up at 3 in the morning it is so severe.

    I’m up to about 15 episodes now. So, at least for some people like me, MSG is highly toxic or allergic.

  5. Can you speak specifically to MSG as a migraine trigger? Is this the small percentage of people referenced? Two female family members experience a clear connection between MSG consumption and severe migraines. (More than just “headaches.”) And it’s not a placebo effect or confirmation bias, because it’s migraine post mortems (checking food ingredients after the fact) that exposed the connection. We avoid MSG to avoid debilitating migraines. And we thought from subsequent reading that the MSG migraine connection was well-established in migraine literature. MSG may not be generally harmful to long-term health, but it’s not clear your analysis answers the short-term wellness question of MSG as a migraine trigger. P.S. Recently got an Ouraring and impressed after my first couple of weeks of experience. And doing intermittent fasting. Respect your analytical skills.

  6. Great post, Peter. My stories on this are at least as colorful. So, my friend worked next door to Dr. X with whom I will check on the veracity of this story. X worked on MSG and when my friend came into his lab one day,, they asked him to “drink this.” Somebody in the lab said “wow. We never gave anybody a dose like this.” He reported all the symptoms of CRS in the extreme and told me that X himself had MSG synthesized — not too hard to do unless you start with two carbon compounds as those problems in Organic Chemistry classes — and mainlined it. According to my friend, X staggered down the hall to the organic chemist and like some Shakespearean hero announcing his own death said “You bitch. You’ve killed me” and collapsed and was taken to the hospital but recovered soon after. While my fried is a great story teller and exaggerates and I personally never have CRS — they used to use a lot of MSG but I assumed I was simply not sensitive — glutamate is, of course, an excitatory neurotransmitter and I guessed that it was actually spinal and some people were sensitive. So, I will check with Dr. X.

  7. Great article, thank you for this. I understand that there are people who say they are sensitive to MSG, and that may well be the case. But the MSG-phobia is kind of like the low-fat craze.

    I have used a seasoning salt for many years called “Johnny’s”, and it contained MSG. Then they came out with a no-MSG formula, and eventually discontinued the one with MSG. The new version was nearly the same, but they had added some sugar to the mix. Since I eat very minimal sugar, I could tell. So I bought some MSG and mixed it in. Not as good as the original, but it’s better with MSG! And now I have MSG to add to other foods. It only takes a little, it’s great stuff to have around.

  8. I use dashi all the time, then I reduce salt. If someone really is sensitive to MSG, give it a try. If it causes a problem try dried shiitake mushrooms with anchovy paste, Flor de Garum, and a couple of drops of Worcester Sauce. Rehydrate the shrooms in hot water, teaspoon of fish sauce, dab uf paste, etc. Then cook with it. If your ok, then MSG effects are probably in your head, or by some magic the natural version behaves differently due to combination. All said, the umami version will taste better anyway.

  9. I can’t help but wonder how many of the people who are convinced that their problem is with MSG have truly isolated the various additives to confirm that their problem is indeed the MSG. A particularly additive that my wife has conclusively isolated and confirmed causes migraines for her is yellow dye # 5. It seems to me that there is a significant overlap between yellow dye # 5 and MSG, i.e. a significant number of food items with added MSG also have yellow dye # 5, e.g. Doritos.

    • Have her look up the connection of yellow dye and aspirin. She is probably allergic to aspirin. I have issues with msg and aspirin/yellow dye 5 and associated food with natural aspirin in it like peaches, tomatoes, etc. have her search on it.

  10. Reads like a press release from the Glutamate Association whis has been working for years to assure the public that MSG is safe and beneficial.

    For the minority of people that are sensitive to MSG, and we do exist, you do a great disservice. If manufacturers and restaurants wish to remove MSG from their products, they should be respected for being considerate of their customers.

    If MSG does not affect you and you are happy to be served inferior flavor enhanced food, so be it. Leave the issue alone and enjoy your dinner.

    • Right on. I am one of those people. Look up “excitotoxins” and how they literally burn out pieces of the brain over time. That is because of constant overstimulation of certain neurons. MSG is found in nature, but not in the level of concentration found in our adulterated foods. When prepared food became more readily available after WWII, we created a whole generation of people who are now dying of dementia due to additives in prepared foods. Plus, excitotoxins are highly addictive, so if you make a snack food that contains one or more of them, people will tend to buy and eat more of your product. I personally can no longer eat anything “hydrolyzed” as in “hydrolyzed protein” and other hydrolyzed substances. I also cannot tolerate yeast extract which is in most soups and prepared gravies. I get severe headaches.

    • Thank you FR, those of us who have MSG migraines, as stated in some comments, usually do not know the cause until after we get the headache and start looking closely at what we recently ate. The pattern repeats. So it is clearly NOT “in our heads”, meaning our imaginations. It is insulting to hear those who do not have this sensitivity ascribe it to our…fears.

      BTW I have not gotten a response to my question: what else is in miso soup that can cause a migraine?

    • I am very happy to see “no msg” as i too get massive headaches and will not buy a product with it. So i agree that your article is a disservice to many who have problems.

  11. I get frequent migraines, and over the years have discovered quite a few food triggers. I used to think that MSG was a consistent trigger, but have since figured out that it, by itself isn’t so reliable at that. MSG is often included in “intensely flavored” foods with other ingredients (which are often just called “natural flavorings”). I’ve found more consistent triggers with yeast extracts. The pattern seems to be with protein or amino-acid derived flavorings. Even garlic, uncooked, can be a trigger for me. Given the speed of the reaction, I feel most of the triggers are actually from the flavor and sensory experience of eating these foods than the ingredients themselves, but there are some things that do seem to persist.

    Overall, migraine triggers seem difficult to narrow down. Not only is self-perception tricky, but the triggers aren’t consistent, and I have a tendency to avoid things that I think might even have a possibility of being a trigger.

  12. Hmm. A bit disappointed in this article. No real talk about why, without a doubt, MSG has an instant effect on your “hunger.” People always stuff their faces when eating MSG foods, such as Chinese or Thai. Doesn’t MSG block your bodies ability to say “I’ve eaten enough – please stop feeding me now!”?

    However, it’s a little dubious when the “studies” here are from organizations like the WHO.

    I’ll stick with my own personal observations. There are zero health benefits to it. Avoid MSG at all costs.

  13. I recently read an article in Neuroscience about glutamate and migraines.
    I am a chronic migraine sufferer and have found avoiding MSG very helpful.
    This article did not share any new light on the sibject.

  14. There are a small percentage of people that are allergic and/ or sensitive to MSG. I have been extremely sensitive to MSG for most of my life. I have to be vigilant about checking the contents of food that I do not eat normally, otherwise I become very sick the following day. If I ingest MSG by accident, the following day my whole body is so uncomfortable, that I roll and writhe in bed in total discomfort until the MSG has worked its way out of my body. It feels like I want to crawl out of my skin. The feeling is so terrible that I have to monitor the ingredients of all the food that I eat.
    MSG is dangerous to me and many other people that are highly allergic and sensitive to it. So the matter of MSG in food is VERY IMPORTANT to me and to many other people. I actually know some people that are so sensitive to MSG, it is deadly to them. We don’t take MSG in food lightly!!!

  15. My take on this is that MSG and other glutamates are well established excitotoxins. Regular exposure can lead to overstimululation of the brain (eventually destroying synapses??? is a claim from some scientists). The allergy idea is a different matter, unless the brain activity is somehow triggering it, I suppose. Cheers!

  16. I am highly sensitive to MSG, which has been verified by genetic testing. I know that MSG is generally safe for most of the population but, in my case, I suffer strong heart palpitations, dizziness and other nasty side effects when I consume it. To say that harmful effects from MSG are a myth, in my opinion, is wrong. When MSG precipitates a bout of Afib proves that.

  17. I typically really like Peter’s analysis but this was upsetting to read. I would have liked to see more analysis around sensitive people and possible ways to become less sensitive or what to do if you do start feeling bad from it.

    I’m in the MSG sensitive camp. Chicken Rice in singapore which is basically msg, rice and chicken made my mouth tingle immediately after, followed by me wanting to drill into my skull to releive a 20 hour migraine. Same thing happened in Hong Kong, and a few chinese restaurants. I had frequent headaches as a kid and ate a lot of ramen noodles and doritos.

    I tried to get Allergy tested for MSG and my allergist said people can not actually be allergic to and can not test for it, however one can be sensitive to it but would require willfully ingesting it. He explained that I have a threshold and if I go over it I could get symptoms. Not willing to try that approach as it’s too painful.

    I would love if they outlawed the stuff as it makes me nervous eating at places that probably use it.

    If anyone has resources around what to do to counteract it if you find out you have ate some or any other ideas around avoidance, testing, etc. I would be very interested.

    • I believe it is likely that those sensitive to MSG are also sensitive to other additives. I know I have an immediate headache after drinking 1/2 of a diet soda (aspartame), and a 24 hour bout of terrible depression (hard to describe) after 2 bites of anything sweetened with sucralose (Splenda). Is there any relationship between these substances?

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