Without pregnant women passing excitotoxic – brain damaging – free glutamic acid to fetuses and neonates, there would be no obesity epidemic.

Eat too much and you get fat.  Everyone knows that.

Sixty-plus years ago, there were thin people and those who were overweight.  Although the numbers filling out each category changed over time, the fluctuations could be accounted for.

But all that changed in the years following 1957.  By 1970, unprecedented numbers of people had become overweight – with many being considered morbidly obese. Changes in eating habits and lifestyles were the go-to explanations at the time, but they really didn’t hold water.  By 1980, the surge in obesity had become so great that the term “obesity epidemic” was being applied to the phenomenon.

And that wasn’t the only peculiar thing that happened in the 1970s.  Although it wasn’t immediately obvious, the number of people with infertility problems were similarly growing.

The elephant in the room

Although today glutamate is understood to be essential for normal body function being both a building block of future protein and the principal neurotransmitter in humans, it wasn’t always that way.  Glutamate was discovered/recognized as an amino acid by Ritthauser only in 1866 with its structure established in 1890 by Wolff.

It was not until 1968, that neuroscientist John Olney began to suspect that glutamate might be a neurotransmitter capable of destroying neurons in the arcuate nucleus of the hypothalamus, somehow affecting obesity.  So, it is understandable that in 1969 when Olney published evidence that ingested free glutamate could causes brain damage in mice, few others even considered the idea that delivery of free glutamate to humans through diet could cause brain damage. 

Moreover, Olney’s focus was on the role that glutamate might play in abnormalities such as Alzheimer’s disease, multiple sclerosis, and depression without giving thought to glutamate-induced obesity.  Remember that in the 1970s, it had been demonstrated that obesity followed brain damage that was induced by free glutamate administered or fed to neonatal animals in quantities that would produce brain damage – quantities far greater than those that would ever be found in a single serving of any glutamate-enhanced ingredient.

It was not until 50 years later that the role that glutamate-induced brain damage might play in human obesity was given serious consideration (1).

Essential to understanding the role that glutamate plays in obesity and other glutamate-induced abnormalities is the fact that the glutamate-induced brain damage was not damage in the broad sense of the term, but actual obliteration of neurons.  Some of those obliterated neurons would have regulated appetite had they not been destroyed. In other words, for those suffering glutamate-induced obesity, the switch designed to turn off eating would be missing.

From animals to humans

For there to be glutamate-induced brain damage, be it in animals or humans, three conditions have to be met.  There must be:

1) a vulnerable brain (immature or damaged), 2) sufficient free glutamate to produce the excesses needed to cause glutamate to become excitotoxic, and 3) a way to deliver quantities of free glutamate to the vulnerable brain.

In the early animal studies, the vulnerable brain was the arcuate nucleus of the hypothalamus of the brain of a neonatal animal – a newborn animal whose brain would not yet have been fully developed and would not have been protected by a blood brain barrier (BBB) (2-3).

The poison was the free glutamic acid component of monosodium glutamate, which was delivered in the experimental diet (4-13).

In humans, a vulnerable brain could be one that had suffered a blow to the head or some other traumatic circumstance. Alcohol and/or drug abuse would also make the brain vulnerable.  The vulnerable brain could also be the undeveloped brain of a fetus or newborn.

In this last case, the poison would be excitotoxic glutamic acid and/or one of the two other excitotoxic amino acids used in processed and ultra-processed foods.

The poison would be delivered by pregnant or lactating women who were consuming enough free glutamate to cause it to be excitotoxic when delivered across the placenta to the fetus or to the neonate though mothers’ milk.

We know from animalstudies done in the 1970s that brain damage as described above will be followed by gross obesity (4). Indeed, monosodium glutamate is routinely used by researchers to produce obesity in experimental animals being used to study a wide variety of abnormalities (14-15).


To complete this scenario, the question of availability of glutamate in amounts sufficient to become excitotoxic must be addressed.

At one time it would have been meaningful to note that the amount of excitotoxic material in a particular ingredient would not be sufficient to cause brain damage or adverse reactions. But since the 1957 change in method of MSG production, there are so many products that contain excitotoxins that it is easy for a consumer to ingest an excess of excitotoxic material during the course of a day (16-21).

During 1957, the method used for producing the free glutamate that makes up the excitotoxic portion of MSG was switched from extracting glutamate from a protein source, a slow and costly method, to a process of bacterial fermentation (22). This allowed virtually unlimited production of free glutamate and MSG.

It didn’t take long for industry to add dozens more excitotoxic food additives to the American diet. Following MSG’s surge in production and aggressive advertising, it was realized that profits could be significantly increased if companies produced their own flavor-enhancing additives. Since that time, the market has been flooded with flavor enhancers and protein substitutes that contain manufactured free glutamate (MfG) such as hydrolyzed proteins, yeast extracts, maltodextrin and soy protein isolate, as well as MSG (16-21). To that has been added the toxic load contributed by excitotoxic aspartic acid, approved by the FDA for use in aspartame, equal, and related products starting in 1974.

Soon after 1957, when use of genetically modified bacteria in the production of MSG began, availability of MSG and other MfG-containing products increased to the point where there was more than sufficient MfG to become excitotoxic if a number of processed and ultra-processed foods were consumed during the course of a day.

Thus, a pregnant woman could easily become a vehicle for delivering brain-damaging free glutamate to her fetus and neonate.

It is not disputed that there are other ways to produce obesity but without pregnant women passing excitotoxic – brain damaging – free glutamic acid to fetuses and neonates, there would be no obesity epidemic.


With the first suggestion that MSG might have toxic potential, those with financial interest in promoting MSG as a valuable flavor-enhancer launched a well-funded, well-articulated, campaign to promote their product, and deny any hint of toxicity. That included rigging studies to come to the foredrawn conclusion that MSG is a harmless food additive and securing the active cooperation of regulators as well as the help of medical professionals who appeared to be more than happy to look the other way. It is felt by some that this was influential in suppressing information about the toxic effects of MSG and the free glutamate contained in it (23).

References and resources

1. Samuels A. (2003). It wasn’t Alzheimer’s, it was MSG. (Kindle). p187, Appendix 3. https://bit.ly/2URGEBx

2. Saunders, N.R., Liddelow, S.A., and Dziegielewska, K.M. Barrier mechanisms in the developing brain. Front Pharmacol3:46, 2012. Published 2012 Mar 29. doi:10.3389/fphar.2012.00046

3. Haddad-Tóvolli, R., Dragano, N.R.V., Ramalho, A.F.S., and Velloso, L.A. Development and Function of the Blood-Brain Barrier in the Context of Metabolic Control. Front Neurosci  Apr 21;11: 224, 2017.  doi: 10.3389/fnins.2017.00224. PMID: 28484368; PMCID: PMC5399017.

4. Olney, J.W. Brain lesions, obesity, and other disturbances in mice treated with monosodium glutamate. Science164: 719-721, 1969.

 5. Olney, J.W. Glutamate-induced neuronal necrosis in the infant mouse hypothalamus. J Neuropathol Exp Neurol 30: 75-90, 1971.

6. Burde, R.M., Schainker, B., and Kayes, J. Acute effect of oral and subcutaneous administration of monosodium glutamate on the arcuate nucleus of the hypothalamus in mice and rats. Nature(Lond) 233: 58-60, 1971.

7. Olney, J.W., Sharpe, L.G., and Feigin, R.D. Glutamate-induced brain damage in infant primates. J Neuropathol Exp Neurol 31: 464-488, 1972.

8. Burde, R.M., Schainker, B., and Kayes, J. Monosodium glutamate: necrosis of hypothalamic neurons in infant rats and mice following either oral or subcutaneous administration. J Neuropathol Exp Neurol 31: 181, 1972. 

9. Olney, J.W., Ho, O.L. Brain damage in infant mice following oral intake of glutamate, aspartate or cystine. Nature(Lond) 227: 609-611, 1970.

10. Lemkey-Johnston, N., and Reynolds, W.A. Incidence and extent of brain lesions in mice following ingestion of monosodium glutamate (MSG). Anat Rec 172: 354, 1972.

11. Takasaki, Y. Protective effect of mono- and disaccharides on glutamate-induced brain damage in mice. Toxicol Lett 4: 205-210, 1979.

12. Takasaki, Y. Protective effect of arginine, leucine, and preinjection of insulin on glutamate neurotoxicity in mice. Toxicol Lett 5: 39-44, 1980.

13. Lemkey-Johnston, N., and Reynolds, W.A. Nature and extent of brain lesions in mice related to ingestion of monosodium glutamate: a light and electron microscope study. J Neuropath Exp Neurol 33: 74-97, 1974.

14. Hernández Bautista, R.J., Mahmoud, A.M., Königsberg, M., and López Díaz Guerrero, N.E. Obesity: Pathophysiology, monosodium glutamate-induced model and anti-obesity medicinal plants. Biomed Pharmacother. 111:503-516, 2019. doi: 10.1016/j.biopha.2018.12.108. Epub 2018 Dec 28. PMID: 30597304.

15. Islam, M.S., and Loots, du T. Experimental rodent models of type 2 diabetes: a review. Methods Find Exp Clin Pharmacol. 31(4):249-61, 2009. doi: 10.1358/mf.2009.31.4.1362513. PMID: 19557203.

16. Hashimoto S. Discovery and History of Amino Acid Fermentation.  Adv Biochem Eng Biotechnol. 159:15-34, 2017. https://pubmed.ncbi.nlm.nih.gov/27909736/

17. Sano C. History of glutamate production. Am J Clin Nutr. 90(3):728S-732S, 2019.  https://pubmed.ncbi.nlm.nih.gov/19640955/

18. Market Research Store. Global Monosodium Glutamate Market Poised to Surge from USD 4,500.0 Million in 2014 to USD 5,850.0 Million by 2020.https://www.globenewswire.com/news-release/2016/03/17/820804/0/en/Global-Monosodium-Glutamate-Market-Poised-to-Surge-from-USD-4-500-0-Million-in-2014-to-USD-5-850-0-Million-by-2020-MarketResearchStore-Com.html  (Accessed 5/29/2020.)

19. Open PR Worldwide Public Relations for Verified Market. Global Flavor Enhancers Market. https://www.bccresearch.com/partners/verified-market-research/global-flavor-enhancers-market.html (Accessed 5/29/2020.)

20. Dataintelo. Global Food Flavor Enhancer Market Report, History and Forecast 2014-2025, Breakdown Data by Manufacturers, Key Regions, Types and Application.  https://dataintelo.com/report/food-flavor-enhancer-market   (Accessed 5/29/2020)

21. Onaolapo, A.Y., and Onaolapo, O.J. Dietary glutamate and the brain: In the footprints of a Jekyll and Hyde molecule. Neurotoxicology. 80:93-104, 2020. doi: 10.1016/j.neuro.2020.07.001.

22. Khan, I.A., and Abourashed, E.A. Leung’s Encyclopedia of common natural ingredients used in food, drugs, and cosmetics (Third Edition).  New Jersey: Wily, 2010. Pp 452-455.

23. Samuels, A. The toxicity/safety of processed free glutamic acid (MSG): a study in suppression of information. Account Res. 6(4):259-310, 1999. doi: 10.1080/08989629908573933. PMID: 11657840.