INTRODUCTION:

Mono Sodium Glutamate (msg):

The abbreviation of Monosodium glutamate is MSG, is a sodium salt of glutamic acid.MSG is represented by chemical formula C5H8NO4Na [Figure 1] and IUPAC name is sodium 2-aminopentanedioate.¹

Chemically, MSG seems to be a salt like bright and white powder. It is manufactured by fermenting starch, sugar cane, or molasses followed by purifying and drying.²

Monosodium glutamate (MSG) or (E621), the sodium salt of l-Glutamic acid being constituent of protein, used as a taste/flavor enhancer.

The Molar Mass of MSG Anhydrous is: 169.11 gm/mol.

Melting Point: 232^oC.³

The interest of using MSG has been growing rapidly with respect to food processing industry since last 30 years. Many researchers have identified MSG as the most controversial food ingredients for its negative impact towards the animal and human²⁰. It is greatly found in frozen entrees, crackers, canned, soups, processed meats, cosmetics, dietary supplements, vaccines, and in many other food products.⁴

Monosodium glutamate is associated with metabolic syndroms in humans and causes several symptoms such as headaches, tingling sensations, and burning sensations.¹ Also glutamate receptor can be stimulated excessively to cause diabetes and cancer.²¹ These symptoms are collectively referred to as the “Chinese restaurant syndrome”.¹

Many researchers have identified MSG as the most controversial food ingredients for its negative impact towards the animal and human.²⁸

Figure 1: Structure of MSG

History:

1. In the early 1970s, manufacturing companies voluntarily replaced MSG with hydrolyzed vegetable protein and autolyzed yeast in baby food.⁵ Concentrations of MSG in different foods are listed in table no. 1

2. For the first time (1908), MSG was discovered in Japan from seaweed as a flavor enhancer and in pesticide/fertilizer as AuxiGro WP Metabolic Primer (AuxiGro). Earlier times, the extraction of MSG wasslow and costly method. It was first introduced in the United States in the late 1940s. Later on (1956), large-scale production of MSG and glutamic acid was successfully achieved by fermentation. Since 1957, in the United States MSG, was produced by bacterial fermentation involving genetically modified bacteria which secrete glutamic acid through their cell.⁵

3. MSG production capacity is maximum in Asia where feedstock and labor are abundant and inexpensive and where demand is highest. Asian production capacity accounted for approximately 94% of world MSG production capacity in 2021 [Figure 2].⁶

4. Monosodium glutamate (MSG) (E621), the sodium salt of l-Glutamic acid being constituent of protein, used as flavor enhancer. It is used to enhance the natural flavors of poultry, meats, snacks, seafood, soups and stews MSG, a prototypical umami ligand, is frequently added in Asian cuisine for improving the taste of food (Li et al., 2013).⁷

Table 1: Concentration of MSG in variety of common foods

Food	Concentration (mg/100g)
Cow milk	2
Apple	13
Human milk	22
Egg	23
Beef	33
Chicken	44
Almond	45
Carrot	54
Onion	118
Garlic	128
Potato	102
walnut	757

Figure 2: World consumption of MSG- 2021

Side effect/adverse effect of msg on various body systems: Various factors have been causing the progression of reproductive dysfunction, including poor nutrition, drug side effects, disease states, and toxicant ingestion. The MSG as a food additive that has been found to be potent at initiating reproductive anomalies in males. Monosodium glutamate is widely used as a taste enhancer in several diet.⁸

Male reproductive system:

The different mechanisms by which it may induce reproductive dysfunctions include spermatogenic alteration resulting in a low sperm count, high sperm abnormality, reduced live sperm and decreased sperm pH, oxidative damage (increased lipid peroxidation and reduced antioxidant enzyme activities), histological alteration (blood hemorrhage, distorted germ and Sertoli cells), as well as gonadotropin imbalance (reduced testosterone, luteinizing hormone, and follicle-stimulating hormone concentrations).⁸

Several evidence were showing the risk of lead toxicity on male reproductive system²⁴

Female reproductive system:

In this study, ovarian sections of rats treated with MSG for 14 days showed considerable structural changes, including degenerated follicles, oocytes, degenerated medulla with vacuoles having congested blood vessels. The ovaries contained many atretic follicles with no corpora lutea. Furthermore, the severe atretic state reported in this study may be indicative of the high dose of annular MSG used. The degeneration of ovarian follicles and their oocytes detected in this study may be due to oxidative stress caused by MSG.⁹ In the uterus, the endometrial glands were mere degenerated and dysfunctional.²⁹The ovarian follicle showed structural disparity in the ovarian cells and granulose cells.²³ It agrees with the results of Ismail and colleagues that attributed ovarian pathologies after MSG administration to oxidative damage.⁹

MSG induced a significant decrease in fetal weights, CVL lengths, placental weight, and ghrelin expression in both treatment groups compared to the control group. Various parts of the fetal skeleton showed incomplete ossification and delayed chondrification in which high-dose maternally treated fetuses were more affected. Various degenerative changes were detected in both maternal and fetal liver and kidney tissues in MSG-treated groups.¹⁰

Fibrosis is the most common disease observed in females due to effect of MSG²² Emblica officinalis contains uterine fibroid protective phytochemicals and may be useful in preventing uterine fibroids induced by MSG. This activity can be attributed to phenolic and other constituents and one of the mechanisms could be by balancing of oxidative stress, acting as anti-oxidant.²²

Excretory system:

Globally chronic kidney disease (CKD) is identified as a salient noncommunicable disorder; additionally, gut microbiota plays a crucial role in protecting human health, but the gut microbiota’s alteration is associated with chronic diseases like CKD. However, Megamonas, Faecalibacterium, Blautia in gut microbiota are decreased by ingestion of MSG mixed diet simultaneously with an increase of Collinsella [83]. On the other hand, the last stage of the patients with CKD lacks Faecalibacterium, which is also associated with decreased glomerular filtration rate.

A significant risk factor of CKD is an unhealthy diet mixed with MSG, which led to obstructive nephropathy, including complete or incomplete blockage of kidneys with a reduced level of stone inhibitors (e.g., citrate, magnesium, etc.) followed by alkalinization of urine.¹¹

Nervous system:

MSG is known as an "excitotoxin" or neurotoxin. Research studies have found that it has devastating and degenerative effects on the brain and the nervous system¹². The brain in delicious organ of the body so, it is necessary to protect them. Also, it a complex system of the body²⁶ The neurons or brain cells overstimulate and fatigue to their death. MSG enters the brain through the membranes in the mouth and the throat.¹²

In mammals, excitatory neurotransmitters like glutamate play a significant role in the different processes related to physiology and pathology in the central nervous system.¹¹

Research studies indicate that MSG is the reason for neurological diseases like Alzheimer's disease, Huntington's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. Neuroscientists have explained that MSG attacks the blood-brain barrier of the neurons which is responsible for the regulation of the fragile chemical exchange inside the brain cells.¹²

MSG can cross the blood-brain barrier, which means it can affect brain function. Some studies suggest that MSG may increase the release of certain neurotransmitters, such as glutamate and dopamine, which can cause overexcitation of neurons and lead to headaches, migraines, and seizures. It can also disrupt sleep and cause fatigue.¹³

Digestive system: The influence of prolonged administration of monosodium glutamate (MSG) on basal gastric acid secretion, body weight and gastric mucosa in rats was studied.

It is concluded that the stimulating effect of MSG on the basal secretion of hydrochloric acid in the stomach may be implicated in the pathogenesis of a number of acid-dependent diseases. More consumption of MSG can cause a "Chinese Restaurant Syndrome" and gastritis, gastric and duodenal ulcers. Therefore, the excessive dose of MSG should be reconsidered taking into account its influence on the secretory capacity of the stomach. We also conclude that long-term, excessive and systemic consumption of MSG causes obesity.¹⁴

The length of the small intestinal villi and the depth of crypts are essential indicators of the functions of intestinal digestion and absorption. The ratio of villus length/crypt depth (V/C ratio) is the most frequently used index for evaluation of overall intestinal function. In mice in the L-MSG group, the ileum showed a healthy histological morphology, but the V/C ratio was significantly increased.¹⁵

Moreover, inflammation and damage in the lining of the small intestine are associated with changes in the absorption of lipid on intraduodenal administration of MSG.¹³

Immune System: in vitro study has been directly linked with the impact of MSG on the immune system by establishing embryonic cell culture models. There was no significant evidence on replication and nuclear division in MSG causes chromosomal aberrations and exchange in sister chromatids on human lymphocytes. This report has found that MSG induces genotoxicity on human peripheral blood lymphocytes at the cellular level. Additionally, a more concentration of MSG exerted a dose-dependent impact on the viability of B cells.¹³

MSG leads to increasing the generation of free radicals in the body, which leads to a decrease in the body's antioxidant production. This results in oxidative damage throughout the body. On the other hand, the health and function of the immune system are closely related to nutritional status.¹⁶

The immunity and system functions to fight against infections square measure considerably wedged by inappropriate food and nutrition.²⁵

To prevent disease, it is not enough to eliminate only modifiable factors but it is also necessary to identify patients at a preclinical stage, when physiological parameters are still within normal limits, but there is an excess stress on the regulation systems.²⁷

Immunomodulators are becoming very popular in the worldwide natural health industry as people start to realize the importance of a healthy immune system in the maintenance of health and the prevention and recovery of disease.³⁰

Cardiovascular system:

Monosodium glutamate significantly reduced body weight, force of cardiac muscle contractility, serum level of high-density lipoprotein, and superoxide dismutase activity in cardiac muscle, while it significantly elevated heart rate, serum levels of total cholesterol, low-density lipoprotein, triacyl glycerides, atherogenic index and troponin T, activities of serum lactate dehydrogenase and creatine kinase-MB, malondialdehyde concentration, and P53 protein expression in cardiac muscle. In addition, it causes myocardial degeneration, cellular infiltration, deposition of collagen in cardiac muscle, and periodic acid-Schiff staining reaction.¹⁷

Endocrine system:

MSG can affect the endocrine system by disrupting the production and function of hormones. This is because it can interfere with the function of the hypothalamus, which regulates hormone production. It can also affect the production of insulin, which can lead to insulin resistance and type 2 diabetes.¹³

The exposure to MSG can have effects on the regulation of gut hormone secretion and consequently, glucose and weight homeostasis and highlights its potential to act as an endocrine disruptor.¹⁸

As a result, monosodium glutamate cause decrease in body weight, carcass fat increase, endocrine glands atrophy, and pituitary hormone content decrease.¹⁹

CONCLUSION:

It was concluded that MSG was used as flavor enhancer and preservative in various food industries and certainly in common household. By adding this the person gets more urge to eat food as it gives pleasant taste and it also helps to maintain the appetite of the person having anorexia. Many administrative comities had mentioned that it is safe for limited usage and enlist several potential side-effects linked to increased MSG consumption. Cardiac, circulatory, gastrointestinal, muscular, neurological and reproductive disorders are some of the common examples. Excess of everything was bad, so MSG utilization up to certain level does not have any adverse effects because glutamate is a nutritionally indispensable amino acid. Thus, increased consumption of monosodium glutamate may be associated with harmful health effects. So, it is recommended to use common salt instead of it.

REFERENCES:

1. PubChem [Internet]. Bethesda (MD): National Library of Medicine (US), National Center for Biotechnology Information; 2004-. PubChem Compound Summary for CID 23676143, Monosodium L-glutamate; [cited 2023 Oct. 2]. Available from: https:// pubchem.ncbi.nlm.nih.gov/compound/Monosodium-L-glutamate

2. Mahfoudh A.M. Abdulghani, Salah Abdulrazak AL Shehade, Sareh Kamran, Mohammed Abdullah Alshawsh, Effect of monosodium glutamate on serum sex hormones and uterine histology in female rats along with its molecular docking and in-silico toxicity, Heliyon. 2022; 8(10): e10967 https://doi.org/10.1016/ j.heliyon.2022.e10967. (https://www.sciencedirect.com/science/ article/pii/S2405844022022551)

3. Wikipedia contributors. Monosodium glutamate. Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 21 Sep. 2023. Web. 2 Oct. 2023.

4. Niaz K, Zaplatic E, Spoor J. Extensive use of monosodium glutamate: A threat to public health? Excli J. 2018; 17: 273-278. doi: 10.17179/excli2018-1092.

5. Zehra Kazmi, Iffat Fatima, Shaghufta Perveen and Saima Shakil Malik. Monosodium glutamate: Review on clinical reports. International Journal of Food Properties. 2017; 20(Sup2): 1807-1815. DOI: 10.1080/10942912.2017.1295260

6. https://www.spglobal.com/commodityinsights/en/ci/products/monosodium-glutamate-chemical-economics-handbook.html

7. Nazmiye Ataseven, Deniz Yüzbaşıoğlu, Ayten Çelebi Keskin, Fatma Ünal, Genotoxicity of monosodium glutamate, Food and Chemical Toxicology. 2016; 91: 8-18. https://doi.org/10.1016/j.fct.2016.02.021. (https:// www.sciencedirect.com/science/article/pii/S0278691516300540)

8. 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. doi: 10.3390/ toxics8010007.

9. Oladipo, I. C., E. A. Adebayo, and O. M. Kuye. Effects of monosodium glutamate in ovaries of female Sprague-Dawley rats. Int J Curr Microbiol App Sci. 2015; 4(5): 737-745.

10. Shosha HM, Ebaid HM, Toraih EA, Abdelrazek HMA, Elrayess RA. Effect of monosodium glutamate on fetal development and progesterone level in pregnant Wistar Albino rats. Environ Sci Pollut Res Int. 2023; 30(17): 49779-49797. doi: 10.1007/s11356-023-25661-x.

11. Arnab Banerjee, Sandip Mukherjee, Bithin Kumar Maji. Worldwide flavor enhancer monosodium glutamate combined with high lipid diet provokes metabolic alterations and systemic anomalies: An overview. Toxicology Reports. 2021; 8: 938-961 https://doi.org/10.1016/j.toxrep.2021.04.009. (https://www.sciencedirect.com/science/article/pii/S2214750021000858)

12. https://www.linkedin.com/pulse/functional-neurology-msg-neurological-diseases-jimenez-

13. https://www.healthkart.com/connect/monosodium-glutamate/

14. Falalieieva TM, Kukhars'kyĭ VM, Berehova TV. [Effect of long-term monosodium glutamate administration on structure and functional state of the stomach and body weight in rats]. Fiziol Zh (1994). 2010; 56(4): 102-10. Ukrainian. PMID: 20968043.

15. Jinzhao Xu, Mengqi Tang, Yini Liu, Jinghan Xu, Xiaoxi Xu, Safety assessment of monosodium glutamate based on intestinal function and flora in mice, Food Science and Human Wellness, 2022; 11(1): 155164 https://doi.org/10.1016/ j.fshw.2021.07.016. (https://www.sciencedirect.com/science/ article/pii/S2213453021000823)

16. Das D, Banerjee A, Bhattacharjee A, Mukherjee S, Maji BK. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model. Open Life Sci. 2022; 17(1): 22-31. doi: 10.1515/biol-2022-0004.

17. Hazzaa SM, El-Roghy ES, Abd Eldaim MA, Elgarawany GE. Monosodium glutamate induces cardiac toxicity via oxidative stress, fibrosis, and P53 proapoptotic protein expression in rats. Environ Sci Pollut Res Int. 2020; 27(16): 20014-20024. doi: 10.1007/s11356-020-08436-6.

18. Maeve Shannon, Brian Green, Gary Willars, Jodie Wilson, Natalie Matthews, Joanna Lamb, Anna Gillespie, Lisa Connolly The endocrine disrupting potential of monosodium glutamate (MSG) on secretion of the glucagon-like peptide-1 (GLP-1) gut hormone and GLP-1 receptor interaction, Toxicology Letters. 2017; 265: 97-105 https://doi.org/10.1016/ j.toxlet.2016.11.015. (https://www.sciencedirect.com/science/ article/pii/S037842741633315X)

19. T.W. Redding, A.V. Schally, A. Arimura, I. Wakabayashi; Effect of Monosodium Glutamate on Some Endocrine Functions. Neuroendocrinology. 1971; 8(3-4): 245–255. https:// doi.org/10.1159/000122011

20. Arup Datta, Aslam Hossain, Sanjay Roy. An Overview on Monosodium Glutamate: Its direct and indirect effects. Research J. Pharm. and Tech. 2019; 12(12): 6187-6192.

21. Nasser Hadal Alotaibi, Abdulaziz I. Alzarea, Nabeel K. Alruwaili, Dibya sundar panda, Mohamed A. Abdulwahab, Mohammed Gamal, Mohemed M. El Sanea, Ehab M. Mostafa, Mohamed M. Rowezak. Awareness among Saudi Arabian parents of the relationship between Monosodium Glutamate intake and increasing Body Weight. Research Journal of Pharmacy and Technology. 2021; 14(10): 5270-3.

22. Cite:Inshah Ahmed, Nishat Ahmed, Saleha Ahmed, Fazil Ahmad, Abeer Mohammed Al-Subaie. Effect of Emblica officinalis (Amla) on Monosodium Glutamate (MSG) Induced Uterine Fibroids in Wistar Rats. Research J. Pharm. and Tech. 2020; 13(6): 2535-2539.

23. Pingle Shubhangi, Patil Mandakini, Duragkar Nandkishore, Bhongade Subhash, Nimbekar Tulsidas, Katolkar Parimal. Antifertility Activity of Ficus bengalensis Linn: Special Emphasis on Histoarchitecture Changes of Female Reproductive System of Rat. Research J. Pharm. and Tech. 2010; 3(4): 1285-1287.

24. Santhosh Kumar R, Asha Devi. S. Lead Toxicity on Male Reproductive System and its Mechanism: A Review. Research J. Pharm. and Tech. 2018; 11(3): 1228-1232.

25. Dattaprasad N. Vikhe. Ten food that boost Immune System: A Review. Research Journal of Science and Technology. 2021; 13(4): 244-2.

26. Manoj K. Baladaniya, Ankit P. Karkar, Nirav V. Patel. Review on Drug Delivery to the Central Nervous System: Novel Approaches. Res. J. Pharm. Dosage Form. and Tech. 2014; 6(4): 253-266.

27. M. V. Dementyev, S.M Chibisov, M. V. Abramova, S.D. Beeharry, M.L. Blagonravov, S.P. Syatkin, E.V. Neborak, I.P. Smirnova, G.I. Myandina, V.I. Kuznetsov. Study of Criteria of Cardiovascular System Desynchronization in Locomotive Drivers’ Brigade in Russia. Research J. Pharm. and Tech. 2017; 10(3): 891-895.

28. Arup Datta, Aslam Hossain, Sanjay Roy. An Overview on Monosodium Glutamate: Its direct and indirect effects. Research J. Pharm. and Tech. 2019; 12(12): 6187-6192.

29. Pingle Shubhangi, Patil Mandakini, Duragkar Nandkishore, Bhongade Subhash, Nimbekar Tulsidas, Katolkar Parimal. Antifertility Activity of Ficus bengalensis Linn: Special Emphasis on Histoarchitecture Changes of Female Reproductive System of Rat. Research J. Pharm. and Tech. 2010; 3(4): 1285-1287.

30. Sukhbir Lal Khokra, Bharat Parashar, Hitesh Kumar Dhamija, Manju Bala. Immunomodulators: Immune System Modifiers. Research J. Pharm. and Tech. 2012; 5(2): 169-174.

Received on 06.11.2023 Modified on 21.02.2024

Asian J. Research Chem. 2024; 17(3):174-178.

DOI: 10.52711/0974-4150.2024.00032