MSG and the “Chinese restaurant syndrome”

If you’ve gone to a Chinese restaurant sometime in the last 20 years, chances are you’d have noticed a sign hanging in the window assuring you that they don’t add any MSG to their meals. Various other restaurants and products also tout this “feature” (we noticed Coles brand corn chips stating this – they replaced it with additive 635, which is almost the same thing!). The reason they say this is  because there’s lot of people who reckon they’re allergic to MSG. You probably even know someone who thinks they’re allergic to MSG, I certainly do. So what exactly is MSG?

According to Wikipedia, “Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids. MSG is also known as flavour enhancer 621 (in Australia) and is added to food because it has the flavour of umami.”

What this means is that once MSG is dissolved, it becomes a sodium ion (the MS part), like when table salt dissolves, plus a glutamate ion (the G part), which is the same as when glutamic acid dissolves. It’s the glutamate that’s the tasty bit of MSG, but the sodium ion also helps. So often glutamic acid is used somewhat interchangeably with glutamate.

This bit of a review we found makes it sound delicious! –

Although MSG is naturally occurring in many foods, it is frequently added as a flavour enhancer… Saki, for example, has a significant glutamate content; hence, the Japanese belief that Saki compliments and enhances a meal (Birks, 2005).

As it turns out, glutamate is the substance which causes the flavour sensation known as umami, which is one of the 5 basic types of taste. No glutamate, no umami.

Allergies and Amino Acids

Since glutamate is an amino acid, it’s technically impossible to be “allergic” to it, as the term “allergy” is reserved for hypersensitivity of the immune system to certain proteins and glutamate is an amino acid, not a protein. However, most people would call any abnormal adverse reaction to any substance an “allergy”.

Also, glutamate is a non-essential amino acid. This means that it is actually produced by humans inside our own body. It would seem, therefore, that we could not have a negative reaction to glutamate itself, or we wouldn’t be doing to well at all. However, as we know, it’s the dose that makes the poison.

Despite the fact that we constantly have all the amino acids in our body, we do  know of disease which is caused by ingestion of an amino acid in people who are susceptible. This disease is called phenylketonuria. It occurs when people have a genetic disorder which prevents the body from creating the enzyme which turns the essential amino acid phenylalanine into another (normally non-essential) amino acid, tyrosine. This disease can lead to mental retardation, seizures, and other major health problems. That’s why there’s the warning on sugar-free soft drinks and chewing gum – people with the disorder need to carefully restrict their intake of phenylalanine.

However, the big difference between this disease and the CRS is that phenylketonuria seems to be well studied, mechanistically explained and epidemiologically verified, whereas CRS so far seems to be largely baseless speculation.

So, is there really something to worry about?

Chinese restaurant syndrome

A Google search for ‘MSG symptoms’ will yield many results that talk of “Chinese Restaurant Syndrome” (CRS) or “MSG symptom complex” of which the general list of symptoms seems to be:

• Headache
• Flushing
• Sweating
• Facial pressure or tightness
• Numbness, tingling or burning in the face, neck and other areas
• Rapid, fluttering heartbeats (heart palpitations)
• Chest pain
• Nausea
• Weakness

(this particular list was taken from here)

A few questions that need to be asked at this point are:

1. Is it biologically plausible for MSG to cause these symptoms?
2. Have these symptoms been reproduced in a randomised DBPC (double blind placebo controlled) study on MSG?
3. Could there be another explanation for the symptoms?
4. How much glutamate is in common foods?

TL;DR:

1. Perhaps.
   There’s a couple of leads that might provide a theoretical base for MSG to cause the symptoms. 
2. No.
   None of the studies or reviews we found provided any statistically significant correlation between MSG and any of the symptoms.
3. Yes.
   There are a lot of alternative explanations for those symptopms. For example, high levels of salt or wine in the same dishes, hypernatraemia, histamine toxicity, dehydration, etc.
   
4. Lots.
   It is an amino acid, one of the building blocks of life; it is in a lot of stuff.  For example, parmesan, peas and marmite all have a buttload of glutamate.

1: Is it biologically plausible for MSG to cause these symptoms?

I mentioned earlier that it’s the dose that makes the poison. So let’s have a look at just how big a dose makes MSG into a true poison. To do that we’ll look at the amount of MSG required to have a 50% chance of killing you (or an approximation of you), so we’ll look at the LD50 of MSG in rats and mice:

From Wikipedia:

The oral lethal dose to 50% of subjects (LD50) is between 15 to 18 g/kg body weight in rats and mice respectively, five times greater than the LD50 of salt (3 g/kg in rats).

That’s a LOT of MSG! And, you wouldn’t consume 15g of MSG in one sitting anyway, let alone per kg of body weight! Furthermore, that’s a shiteload of sodium anyway(MSG is 12% sodium, by weight). Anyway, you’re not going to be able to consume enough to get within a few orders of magnitude of risking death, unless you were really really trying.

The big takeaway here is that it appears that it is at least less toxic than regular table salt.

Excitotoxicity

Excitotoxins are substances which stimulate nerve cells to the point where they are damaged and killed. Glutamate is apparently an excitotoxin. This seems to me like it’s probably the reason for the idea that MSG will put a hole in your brain.

From Wikipedia page on glutamic acid (flavour)

Because glutamate is absorbed very quickly in the gastrointestinal tract (unlike glutamic acid-containing proteins in foods), glutamate could spike blood plasma levels of glutamate.^[14][15][16] Glutamic acid is in a class of chemicals known as excitotoxins, high levels of which have been shown in animal studies to cause damage to areas of the brain unprotected by the blood–brain barrier and that a variety of chronic diseases can arise out of this neurotoxicity.^[17][18]

That’s kinda scary. Glutamate, making up 88% of MSG, will cause your neurons to die when in high enough doses. However, the article continues:

There has been debate among scientists on the significance of these findings since the early 1970s, when John Olney found that high levels of glutamic acid caused damage to the brains of infant mice.^[19] The debate is complex and has focused mainly on whether the increase in plasma glutamate levels from typical ingestion levels of glutamate is enough to cause neurotoxicity and on whether humans are susceptible to the neurotoxicity from glutamic acid seen in some animal experiments.

So there’s some doubt about whether normally ingested levels of MSG are high enough to cause any excitotoxity in humans in particular:

Some scientists believe that humans and other primates are not as susceptible to excitotoxins as rodents and therefore there is little concern with glutamic acid as a food additive.^[21][22] While they agree that the combined effects of all food-based excitotoxins should be considered,^[23] their measurements of the blood plasma levels of glutamic acid after ingestion of monosodium glutamate and aspartame demonstrate that there is not a cause for concern.^[24]

Other scientists around John Olney believe that primates are susceptible to excitotoxic damage^[25] and that humans concentrate excitotoxins in the blood more than other animals.^[26] Based on these findings, they claim that humans are approximately 5-6 times more susceptible to the effects of excitotoxins than rodents are.^[27] While they agree that typical use of monosodium glutamate does not spike glutamic acid to extremely high levels in adults, they are particularly concerned with potential effects in infants and young children^[28] and the potential long-term neurodegenerative effects of small-to-moderate spikes on plasma excitotoxin levels.^[29]

All in all, it seems like there’s some cause for concern, but there’s almost no chance you could eat enough MSG to have this particular problem arise, unless perhaps you are a small child.

Acetylcholinosis

Acetylcholinosis is an increase in levels of Acetylcholine, and seems to cause symptoms similar to anaphylaxis, which accounts for the list of symptoms of the Chinese Restaurant Symptom.

The review we found looks at a study which was done to test the hypothesis that CRS was simply acetylcholinosis:

Ghadimi, Kumar, and Abaci (1971) hypothesized that CRS was secondary to acetylcholinosis. The symptoms of CRS are similar to acetylcholinosis: flushing, chest pain, feelings of warmth; furthermore, glutamate is converted to acetylcholine via the tricarboxylic acid cycle. In order to demonstrate his theory, Ghadimi et al. (1971) administered MSG alone to one test group and administered prophylactic atropine to other test groups. Those who received atropine in advance did not experience the characteristic CRS symptoms. Despite the biologic plausibility of Ghadimi et al.’s study, one must consider that the study only included 14 subjects.

Food Standard Australia and New Zealand have released an article on MSG, in which they discuss the same article:

Ghadimi et al (1971) suggested that CRS was the result of an increase in acetylcholine caused by the ingestion of MSG in large doses with the glutamate being converted to acetylcholine via the tricarboxylic acid (TCA) cycle. A similarity between the symptoms of CRS and those occurring after injection of acetylcholine (flushing, feeling of warmth, throbbing in the head, palpitations, and substernal constriction) was noted and it has also been observed experimentally that in humans there is a 28% decrease in cholinesterase after MSG is ingested. The symptoms of CRS were also found to be capable of modulation using drugs affecting the cholinergic mechanisms.

There indeed seems to be some plausibility for this theory, but there doesn’t seem to be much to find on the topic to verify it at this point. So yes, it is somewhat biologically plausible that MSG may theoretically cause adverse effects to a very small percentage of the population after eating sufficiently large, but not insane, amounts of MSG.

2. Can these symptoms be reproduced in a randomised DBPC study?

No.

According to the review we’ve mentioned a few times now, which looked at around 25 papers from the last 40 years of research, few large DBPC studies have tested the CRS hypothesis, though there have been a few decent studies and many smaller studies. All of the studies mentioned in the review report no significant results.

One fairly in depth DBPC study discussed in the review had 130 participants with reported CRS showing no significant results. Out of the 130, only 2 had a consistent response to MSG, which is not significant.  Interestingly, the review also discusses the possibility of MSG causing asthma. Many of the studies have difficulty with their methods and so the research isn’t great and any significant findings have not been replicable. Still, it seems unlikely that MSG causes asthma.  The more commonly reported symptom of CRS are developing a headache or migraine. Unfortunately there haven’t been any definitive studies done. However, they do go on to discuss the possibility of Chinese food causing headache with or without MSG, due the generally high fat and sodium content of the food.

The review gives us some insight on why the studies might be lacking:

There are significant measurement issues that affect one’s ability to evaluate MSG with a robust experimental design. For example, MSG is not routinely consumed on its own; instead, it is served with food. A researcher must therefore separate the confounding effects of each food substance consumed with MSG. But studies in the absence of food perhaps cannot be extrapolated to the general population because one does not routinely consume MSG in significant  quantities without food.

It would appear to us that the severe lack of quality studies that support the CRS hypothesis would suggest that if there is indeed biological plausibility, that it’s very rare indeed to be someone susceptible to it!

3. Could there be another explanation for the symptoms?

Yes.

There have been a few explanations offered for the set of symptoms experienced by a small percentage of the population. They include B6 deficiency, Histamine toxicity (AKA scombroid poisoning) or the more simple explanation of high salt and fat content of the food the MSG is in.

Vitamin B6 deficiency

From the review:

Other researchers posited differing theories on the origin of CRS. Folkers et al. (1981) suggested CRS symptoms were a result of a vitamin B6 deficiency. Although supplemental B6 appeared to prevent CRS symptoms, the study was small and has not been replicated since.

From wikipedia:

PLP (B6) is also used to create physiologically active amines by decarboxylation of amino acids. Some notable examples of this include: histidine to histamine, tryptophan to serotonin, glutamate to gamma-aminobutyric acid (GABA), and dihydroxyphenylalanine to dopamine.

So some positive results, but again, not enough support to draw a conclusion.

Sodium and fat content

Another suggestion is that the sodium and fat contents of the food may be causing the symptoms. From the review:

Chinese food is exceptionally high in both sodium and fat. Hurley and Schmidt (1993) found that an average serving of Kung Pao chicken contained 76 g of fat; a dish of lo mein noodles contained 3460 mg of sodium. Sensitive to MSG or not, one would most certainly be thirsty after consuming 3.5 g of sodium, and most would probably have an uneasy stomach after 76 g of fat.

Hypernatraemia

This is the term for abnormally high levels of sodium in the blood. Again, Wikipedia gives a good explanation:

Hypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood.^[1] Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body. For this reason, hypernatremia is often synonymous with the less precise term, dehydration.

If the amount of water ingested consistently falls below the amount of water lost, the serum sodium level will begin to rise, leading to hypernatremia. Rarely, hypernatremia can result from massive salt ingestion,^[2][3] such as may occur from drinking seawater.

So, simply ingesting the sheer amount of sodium in typical Chinese dishes could lead to the symptoms reported, through hypernatraemia.

Scombroid poisoning

This is yet another fascinating possibility that I had never heard of. Scombroid food poisoning is an illness usually caused by eating spoiled fish. Spoiled fish can contain bacteria which converts the normal levels of histidine in the fish into high levels histamine, which is the regulator of allergic reactions. The histamine is not destroyed by normal cooking processes, so it can result symptoms comparable to serious allergic reactions. So what’s the relation to foods containing MSG?

The report done by FSANZ explains:

Chin et al (1989) suggested that there are similarities between CRS and scombroid poisoning, caused by naturally occurring histamine in foods and they therefore undertook assays of  several common Chinese restaurant dishes and condiments for histamine content. It was concluded that while the histamine content of most of the foods assayed was not sufficient alone to cause histamine toxicity, in certain situations histamine intake over the course of an entire meal could approach toxic levels.

4. How much glutamate is in common foods?

A lot.

As previously noted, glutamate is an amino acid, it’s really quite common, your body makes it itself. Let’s have a look at exactly how much is in common foods.

(Bound glutamate is that which is found in protein, free glutamate is that which is found in amino acid form).

Here’s a little more context from the FSANZ report:

A typical Chinese restaurant meal contains between 10 and 1500mg of MSG per 100 g. A condensed soup typically contains between 0 and 480mg, Parmesan cheese contains 1200mg, and packaged sauces or seasonings contain 20 to 1900 mg. A meal in a Chinese restaurant is therefore likely to contain more MSG than one might typically consume in a Western restaurant, but does this difference carry a clinical significance?

Youtuber c0nc0rdance‘s video on MSG jokingly recommends taking that friend who refuses to eat at Chinese because of MSG to an Italian restaurant and eat loads of tomatoes, mushrooms and especially parmesan cheese; see if they complain about the same things after eating a bunch more MSG than they would have if they went to Chinese.

Conclusion

So we believe that there’s almost no chance that anyone you know that reckons they’ve got an allergy to MSG actually has an adverse reaction to MSG. The fact that there’s some theoretic biological plausibility is brought into question by the fact that there’s been no significant positive results in high quality DBPC studies so far.

Our conclusion is that MSG is safe for the average person. FSANZ says so, the peer-reviewed literature says so, so I’m going to continue eating delicious food like Doritos and twisties and other junk.