Key points
- Since the 1960s MSG has been linked to symptoms collectively known as ‘Chinese Restaurant syndrome’
- High dose studies in animals suggested that MSG could cause symptoms in humans
- Some high dose, isolated studies in humans also suggested this
- Inconsistency in trial results and test-retest results cast doubt on MSG being a problem for most people
- Focus on Chinese and other Asian cuisines results in part from racist stereotypes and Western foods containing MSG have not come under the same scrutiny
- In amounts usually consumed by humans, there are unlikely to be adverse effects from MSG but some people might have sensitivities to high doses
What is MSG?
Monosodium glutamate or MSG is the sodium salt of glutamic acid. In other words, it is a combination of sodium (a salt, and what is known as ‘table salt’ when combined with chloride as sodium chloride) and the non-essential amino acid glutamic acid. It is found naturally in some foods including tomato and cheese in small amounts and imparts an umami taste which is a general flavour enhancer for savoury foods.
Why is it controversial?
It was first synthesised for use in food by Kikunae Ikeda in the first decade of the twentieth century and became an increasingly popular addition to savoury foods, especially in Asian cuisines. In 1968, Dr Robert Ho Man Kwok suggested in a letter to the New England Journal of Medicine that MSG might be the culprit for food additive reactions he coined as “Chinese Restaurant Syndrome”. Since that time, controversy has surrounded MSG and it has become a much-stigmatised food additive.
What does the evidence tell us?
It has been suggested that MSG can lead to increased reactive oxygen species and micronuclei – biomarkers for cancer formation.1 High-dose studies in animals have also suggested that MSG may play a role in increasing obesity and reproductive injury (reduced sperm counts and motility, changes in reproductive morphology, reduced glutathione and increased oxidation).2 Preclinical trials have also associated MSG with cardiac, liver, and kidney damage, neurotoxicity, low-grade inflammation, metabolic impairment, and cancer formation, along with behavioural changes.3 However, in vitro and (animal) in vivo research by Takumi et al., has demonstrated no mutagenic or genotoxic effects of MSG, at even relatively high doses (2000mg/kg BW).4
In an early placebo-controlled, randomised controlled trial Drs Kenney and Tidball noted that when MSG (as 1.32% solution in tomato juice) was administered, reports of any symptoms were no different to a control tomato juice. However, symptoms were more apparent with heavier concentrations of MSG (3.33%).5 Follow up studies by Kenney also suggested that higher doses provoke greater symptoms in those reactive to MSG.5
More recent placebo-controlled studies have shown no difference in symptom occurrence between placebo and doses of either 1.5 or 3 g of MSG.6
A double-blind, placebo-controlled trial looking into dose-response to MSG in people who self-reported as sensitive to MSG found that only 36.1% of participants responded to MSG alone. The total and average severity of symptoms was significantly higher after ingestion of MSG compared to placebo[i] with a suspected threshold of ~2.5 g to elicit symptoms.7 Symptoms that occurred with a significantly greater frequency after MSG vs placebo ingestion included7:
- Headache
- Muscle tightness
- Numbness or tingling
- General weakness
- Flushing
Note: Symptoms are not thought to be related to (IgE-mediated) allergy.7
In a 2000 trial of people who believed themselves to be MSG-reactive, significantly more responded to MSG (38.5%) than either placebo (13.1%), or both (14.6%)[ii] and increasing doses of MSG were associated with increased response rates. However, there was inconsistency in results and the authors concluded that ‘large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, neither persistent nor serious effects from MSG ingestion are observed, and the responses were not consistent on retesting.’8Of note, this and other commentaries by the authors suggests that responses to MSG are not observed when it is given with food.9
Discussion
The evidence arising from animal or in vitro studies has little relevance to free-living humans, as the dosages used and methods of administration are inconsistent with the frequency and quantity of intakes normally consumed in foods.3 While randomised controlled studies have shown some increases in symptoms with high doses of MSG, amounts typical of human ingestion are unlikely to cause issues and interestingly, the evidence suggests that MSG when given with food (as it always appears in the diet), does not provoke symptom responses. Furthermore, the inconsistency in symptom provocation in those purportedly MSG-reactive and the inconsistency in test-retest responses within individual cases cast doubt on MSG being an absolute cause of symptoms. While there might be some people hyper-sensitive to MSG and it is possible that high doses, in isolation might provoke symptoms, it is unclear whether this is a unique property of MSG or whether they result from an enhanced placebo response, some type of psychoneurophysiological event or because of higher dose glutamic acid or sodium ingestion.
It has also been noted that attention is focussed on Asian and particularly Chinese cuisine and that in early academic and mainstream reports of ‘Chines Restaurant syndrome’ there was both overt and latent racism at play and similar attention was not levelled at other (particularly European) foods and cuisine that also included MSG.10
MSG does increase food palatability and might interfere with carbohydrate metabolism, thus, as part of the hyper-palatable food environment of ultra-refined foods, it has been suggested that MSG might predispose people to a greater risk of obesity. However, recent reviews cast doubt on MSG independently being a risk factor for obesity or metabolic anomalies in humans.11
Conclusion
Overall, the evidence doesn’t support MSG consumed as part of a ‘normal’ diet being a causative factor for the constellation of symptoms known by the racially charged name ‘Chinese Restaurant syndrome’. However, extremely high doses might provoke symptoms in some people.
References
1. Aghaei N, Grigorescu T, Katani N. Investigating DNA Damage Mechanism Induced by Monosodium Glutamate and Associated DNA Repair Cell Machinery: A Literature Review. Undergraduate Research in Natural and Clinical Science and Technology Journal. 2021:1-7.
2. Kayode OT, Rotimi DE, Kayode AAA, Olaolu TD, Adeyemi OS. Monosodium Glutamate (MSG)-Induced Male Reproductive Dysfunction: A Mini Review. Toxics. 2020;8(1):7.
3. Zanfirescu A, Ungurianu A, Tsatsakis AM, Nițulescu GM, Kouretas D, Veskoukis A, et al. A Review of the Alleged Health Hazards of Monosodium Glutamate. Comprehensive Reviews in Food Science and Food Safety. 2019;18(4):1111-34.
4. Takumi A, Kawamata Y, Sakai R, Narita T. In vitro and in vivo genotoxicity studies on monosodium L-glutamate monohydrate. Regulatory Toxicology and Pharmacology. 2019;107:104399.
5. Kenney RA. Placebo-controlled studies of human reaction to oral monosodium L-glutamate. Glutamic Acid: Adv Biochem Physiol. 1979:363-73.
6. Prawirohardjono W, Dwiprahasto I, Astuti I, Hadiwandowo S, Kristin E, Muhammad M, et al. The Administration to Indonesians of Monosodium L-Glutamate in Indonesian Foods: An Assessment of Adverse Reactions in a Randomized Double-Blind, Crossover, Placebo-Controlled Study. The Journal of Nutrition. 2000;130(4):1074S-6S.
7. Yang WH, Drouin MA, Herbert M, Mao Y, Karsh J. The monosodium glutamate symptom complex: Assessment in a double-blind, placebo-controlled, randomized study. Journal of Allergy and Clinical Immunology. 1997;99(6, Part 1):757-62.
8. Geha RS, Beiser A, Ren C, Patterson R, Greenberger PA, Grammer LC, et al. Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate. Journal of Allergy and Clinical Immunology. 2000;106(5):973-80.
9. Geha RS, Beiser A, Ren C, Patterson R, Greenberger PA, Grammer LC, et al. Review of Alleged Reaction to Monosodium Glutamate and Outcome of a Multicenter Double-Blind Placebo-Controlled Study. The Journal of Nutrition. 2000;130(4):1058S-62S.
10. LeMesurier JL. Uptaking race: Genre, MSG, and Chinese dinner. Poroi. 2017;12(2):7.
11. Brosnan JT, Drewnowski A, Friedman MI. Is there a relationship between dietary MSG obesity in animals or humans? Amino Acids. 2014;46(9):2075-87.
[i] p = 0.026, 0.018 resp.
[ii] p < 0.05
