Suspected Health Hazards of Monosodium Glutamate -Review

Abstract

Monosodium glutamate (MSG) is a flavour enhancer commonly used in many food products, particularly in Asian cuisine. While generally recognized as safe by regulatory agencies, some research has suggested potential health hazards associated with MSG consumption. Here's a summary of the alleged health hazards: Headaches and Migraines: Some individuals report experiencing headaches, migraines, or other adverse reactions after consuming MSG-containing foods. Neurological Effects: Animal studies have suggested potential neurotoxic effects, including damage to nerve cells and disruption of neurotransmitter function. Obesity and Metabolic Disorders: Research has linked high MSG intake to an increased risk of obesity, insulin resistance, and metabolic syndrome. Allergic Reactions: Some individuals may be allergic to MSG, experiencing symptoms like hives, itching, and difficulty breathing. Asthma and Respiratory Issues: MSG consumption has been linked to asthma exacerbation and other respiratory problems in sensitive individuals. Gastrointestinal Symptoms: Some people report experiencing nausea, vomiting, diarrhoea, or stomach discomfort after consuming MSG-containing foods. Cancer Concerns: Early studies suggested a potential link between MSG and cancer, but more recent research has found no conclusive evidence. It’s essential to note that many of these alleged health hazards are based on animal studies, case reports, or small-scale human trials. The scientific consensus is that MSG is generally safe when consumed in moderate amounts. Regulatory agencies like the FDA, WHO, and European Food Safety Authority have established acceptable daily intake levels.

Keywords

Introduction

Table 1: Natural glutamate content of fresh food -the values is expressed in mg/100g food [6].

Properties of MSG

       
           
           
1.1 Oxidative Stress

       
           
       
MSG- induced kidney damage

       
           
       
An overview of the long-term kidney changes caused by MSG. Renal injury from chronic MSG use and alkaline urine may occur through unidentified pathways. ROS and inflammatory cytokines produced by urolithiasis can also exacerbate interstitial fibrosis. [19]

3.Cancer

The occurrence of tumours is the result of a comprehensive influence of multiple factors, not only the impact of the internal factors of the organism, but also the result of external environmental factors such as dietary factors. In a study of colorectal cancer (CRC), researchers found that the viability of cancer cells increased after 24 h of incubation with different concentrations of MSG, as well as an increase in the expression levels of adenomatous polyposis coli (APC) and beclin 1, which are involved in the development and progression of CRC. Therefore, it can be inferred that MSG may exert a promoting effect on the proliferation of CRC cells. Tumours are the consequence of a complex interplay between internal and external environmental elements, including nutrition, in addition to the organism's internal components. Researchers observed an increase in the expression levels of adenomatous polyposis coli (APC) and beclin 1, two factors involved in the initiation and progression of colorectal cancer (CRC), as well as an increase in the viability of cancer cells following a 24-hour incubation period with varying concentrations of MSG. Consequently, it follows that MSG might have a stimulating effect on the growth of colorectal cancer cells.[20]

3.1 Colorectal cancer

Globally, colorectal cancer (CRC) is the second most common cause of cancer-related fatalities. Studies conducted in several parts of Saudi Arabia indicate that the younger generation is becoming more susceptible to colorectal cancer. A malignant tumour composed of colon and/or rectum epithelial cells is known as a colorectal cancer (CRC). Numerous variables, both hereditary and environmental, may contribute to it. It has been discovered that 35 percent of CRC causes are either entirely or partially hereditary. Environmental factors that have been linked to an increased risk of cancer include food intake, smoking, obesity, sedentary lifestyles, and exposure to pesticides and changes in the environment. It has also been suggested that these factors, along with lifestyle choices, may trigger genetic changes that can result in cancer. Genetic anomalies have been linked to the development of colorectal cancer in both familial and sporadic cases. Tumour Protein p53 (TP53), Beclin1 (BECN1), and Adenomatous Polyposis Coli (APC) are a few of the genes implicated in the onset and course of colorectal cancer (CRC).As the most frequently altered gene in all tumours, TP53 is a focus of cancer research. There is mounting proof that a person's food and lifestyle have an impact on their chance of colorectal cancer. Food has direct touch with the colonic epithelium, which allows it to directly alter colon health. Due to potential harmful effects, monosodium glutamate (MSG), a major food flavour enhancer used worldwide, has been the subject of extended research. There is evidence, according to some academics, that eating MSG puts people at risk, particularly young ones. Monosodium glutamate has been shown to have a notable neurotoxic effect on rats' short-term spatial memory through oxidative stress-induced brain tissue apoptosis and degenerative alterations, along with continuous systolic hypotension. Because of its distinct umami flavour, MSG is frequently added to meals as a flavour enhancer. The stomach, small intestine, and colon are among the gastrointestinal tract tissues where it has been discovered that the umami taste receptors T1R1 and T1R3 are expressed. The administration of subcutaneous MSG to mice resulted in hyperinsulinemia, diabetes, hypertriglyceridemia, obesity, hyperlipidaemia, and insulin resistance, according to a study by Hata and colleagues. These abnormalities increased the mice's susceptibility to colon cancer caused by azoxymethane. Furthermore, Shoji et al. used quantitative reverse transcription PCR (qRT-PCR) to measure changes in T1R1 and T1R3 gene expression following MSG stimulation of the tongue. [21,22,23,24]

3.2 Lung cancer

In a lung cancer investigation, tissue samples from individuals with non-small cell lung cancer showed a considerable up-regulation of the glutamate receptor SLC1A1. In order to enhance the uptake of cystine by XC- and hence improve the formation of reduced glutathione (GSH) and mitigate the oxidative stress produced during cancer cell proliferation, cancer cells actively ingest glutamate through SLC1A1. Walker-256 cells were subcutaneously implanted after newborn Wistar rats received a 400 mg/kg MSG injection. The findings demonstrated that the tumour volume in the MSG group was greater than that of the control group. Additionally, when MSG (2 mg/kg) and azoxymethane (AOM) were administered to newborn mice, the MSG-AOM group's mRNA expression of the insulin-like growth factor-1 (IGF-1) receptor was higher than that of animals that received AOM alone. These findings suggested that mice treated with MSG are more vulnerable to AOM-induced colon cancer. Gln's conversion to glutamate by glutaminase and subsequent conversion to ?-ketoglutarate via the tricarboxylic acid cycle may be linked to this cancer-promoting process. This reprogramming mechanism is essential for ATP generation, preserving redox equilibrium, and controlling cancer cells' energy use.[20]

4.Effects of MSG on the immune system

Through research with cell cultures, the impact of MSG on the immune system was evaluated directly. The frequency of sister-chromatid exchanges and chromosomal abnormalities in human cells were considerably and dose-dependently elevated by MSG (250–8000 ?g/ml). Nevertheless, there was no change in the indices of nuclear division and replication. Based on these findings, MSG may be able to damage human peripheral blood cells genetically.

B cell viability responded dose-dependently to exposure to escalating MSG doses (1–100 mM). Glutamate increased apoptosis in both naive and memory B cell groups; metabotropic glutamate receptor (mGluR) 7 receptors are most likely the mechanism mediating this action. Similarly, glutamate receptors expressed by naive and memory cells differ. Induction of oxidative stress and death in immune cells is facilitated by differential expression patterns of glutamate receptors.[18]

5.MSG  on  pregnant  and  lactating  women

Pregnant women usually eat a varied, well-balanced diet, making sure to ingest enough calories to support a healthy pregnancy. The majority of amino acids actively cross the placenta to support fetal growth and development. According to research, the fetus has higher amounts of amino acids than the mother does, irrespective of what she eats. The metabolism and transport of amino acids—particularly glutamate—are critical for fetal development, and these functions are shared by the placenta and fetal liver. Researchers examined the effects of MSG consumption on reproduction and birth in rodent trials. The experiment examined three generations of mice given up to 7.2 g/kg of MSG every day.

No negative impact was noted in any generation, and there was no proof that any newborns had ever experienced brain damage. Researchers have looked into the effects of MSG consumption on breastfeeding and breastfed newborns in addition to studies on the pregnancy. Researchers examined nursing mothers who took 100 mg/kg of body weight of MSG and found no increase in the amount of glutamate in human milk or impact on the infant's glutamate consumption. Baker et al. claim that a newborn baby consumes more free glutamate per kilogram of body weight when nursing than at any other time in its life. The American Academy of Pediatrics Committee declared that MSG does not affect lactating or endanger the consuming child.[25]

Throughout their 23-day breastfeeding period, sows receiving experimental diets from day 112 of pregnancy forward. 48 hours following farrowing, litters were standardized. Using the Howema computerized feeding system, sows were fed intermediate diets made by combining high and low diets. The feed was then weighed for each sow and given to each feeding hopper individually, allowing the system to track the daily feed consumption of the sows during lactation. Using the PROC MIXED technique of SAS, data were analysed in a randomized complete block design, with parity serving as the random effect and treatment serving as a fixed effect. The sow served as the experimental unit.

The findings were regarded as trending at P > 0.05 and P ? 0.10 and as significant at P ? 0.05. The sows' ADFI values (5.2, 5.2, 5.2, 5.0, and 5.4 ± 0.15 kg/d, respectively) did not differ substantially. Sows drank approximately 45 g of SID Lys day on average. The sows that were weaned to estrus at 5.2, 4.7, 5.3, 5.5, and 4.5 ± 0.32 days, respectively, did not exhibit any variation in theVal:Lys ratio. There were no variations in the average daily litter growth (2.66, 2.64, 2.76, 2.61, and 2.62 ± 0.08 kg; P > 0.10) when theVal:Lys ratio was increased. Across the dietary treatments, there were no variations in the weight loss of the sows or the number of babies born. SID Val:Lys levels did not, in general, affect sow reproductive efficiency or piglet growth rate.[26]

Important issue related to MSG is exposure during pregnancy.

adverse health effects on kids following MSG supplementation during pregnancy, including reduced serum levels of insulin growth factor and growth hormone, increased body weight, weakened convulsion threshold, and poor Y-maze discriminating learning. The progeny exposed to MSG in utero displayed altered cerebral morphology and function, as well as elevated expression of genes linked to apoptosis and genetic damage.[27]

Natural Product as Safeguards Against Monosodium Glutamate Induced Toxicity .

Vitamins

Vitamin E

One of the most significant antioxidants found in a regular diet is vitamin E, which offers protection against a number of diseases that affect humans (. Rats were given 0.6 mg/g bw of MSG, which caused oxidative stress and hepatotoxicity by inducing LPO, lowering GSH levels, and increasing the activities of GST, SOD, and catalase in the liver. When Vitamin E (0.2 mg/g bw) and MSG (0.6 mg/g bw) were given together, the LPO improved, the GSH level rose, the hepatic SOD activities of GST and catalase were decreased, and the serum activities of ALT, AST, and GGT were decreased . A considerable reduction in MDA levels and the number of atresia follicles, as well as an increase in FSH levels and the number of primary follicles, indicate that the administration of combination vitamin C and E protected MSG-induced ovarian damage (. The significant concentrations of vitamin E, polyunsaturated fatty acids, and lignans found in herbal oils, including sesame oil, account for their potent antioxidant properties . Rats that received sesame oil orally saw a reduction in MSG-induced liver damage, as seen by a drop in AST and ALT as well as oxidative stress markers, and an improvement in lipid profile. Moreover, ?-tocopherol, the primary component of vitamin E, protected against MSG-induced nephrotoxicity for 180 days at a dose of 200 mg/kg. This was demonstrated by a marked decrease in oxidative stress and lipid peroxidation (reduced MDA and conjugated dienes), an improvement in renal function (reduced urea, uric acid, and creatinine), and an increase in antioxidant defense systems (SOD, CAT, GPx, GST, and GSH) Stated differently, ?-tocopherol administered at a dose of 200 mg/kg for 180 days considerably decreased the oxidative stress and cardiac toxicities caused by MSG. As a strong free radical scavenger, ?-tocopherol may inhibit the onset of oxidative stress-related illnesses by boosting reduced glutathione levels and lowering lipid peroxidation in the body. Thus, foods containing MSG may benefit from the presence of vitamins, particularly C, D, and E, as protection against MSG-induced toxicity. [28]

Vitamins C

Due to the possibility of both vitamins and MSG in the human diet, it is important to assess how they interact to determine whether vitamins will worsen or lessen the negative effects of MSG. Given in conjunction with MSG for 45 days, vitamin C (500 mg/kg) demonstrated a hepatoprotective effect on the liver's parenchymal architecture in rats by lowering cellular proliferation, as demonstrated by a decrease in ki-67 expression and a mutation in a tumour suppressor gene . Based primarily on its extracellular action, induction of apoptosis, induction of cell cycle arrest, and suppression of the expression of genes involved in protein synthesis, vitamin C has anti-proliferative properties. The injection of MSG at a level of 6 mg/g bw for 10 days caused hepatotoxicity and oxidative. When vitamin C (500 mg/kg) and MSG were taken together, there was a substantial reduction in oxidative stress, hepatic toxicity, liver weight, LPO, ALT, and AST activity, as well as decreased hepatic catalase activity. Another study found that giving rats 100 mg/kg of vitamin C orally reduced the toxicity of 2 and 4 mg/kg of MSG on testicular and epididymal weight, sperm motility, sperm count, and abnormalities of the sperm head. Additionally, vitamin C reduced the cytotoxicity that MSG caused in rat thymocytes by upregulating the expression of the Bcl-2 protein. These findings support the conclusion that MSG has a cytotoxic effect on the germ cells in adult rats' testicular tissue. However, vitamin C, at a dosage of 150 mg/kg, has an advantageous effect on reducing the cytotoxicity caused by the administration of MSG because of its antioxidant properties. A number of other MSG-induced toxicities, such as histological alterations in the rat oviduct, hepatotoxicity, sperm toxicity, obesity, and neurobehavioral alterations in adolescent rats, have been shown to be protected against by vitamin C.[29]

Vitamin D

It was discovered that vitamin D protects against obese rats produced by MSG. MSG-administered rats displayed increased body weight and water and food intake. On the other hand, taking MSG and vitamin D together dramatically reduces the rate of weight growth (176). Elbassuoni et al. reported similar outcomes, stating that vitamin D and L-arginine prevent oxidative stress, reduce food consumption, and lower body weight to prevent liver and kidney damage caused by MSG. Renal function indicators, urea, and creatinine levels in rats increased, indicating both kidney injury and the MSG-induced oxidative liver, which was demonstrated by an increase in renal MDA and a decrease in liver TAC.

The liver and kidney were protected against hepatic and renal impairment caused by MSG by concurrently administering vitamin D or L-arginine. This was demonstrated by a decrease in blood ALT and AST levels as well as a decrease in serum urea and creatinine, which are markers of renal injury. Furthermore, vitamin D may be useful in preventing MSG-induced steatohepatitis in nascent and adult animals. Additionally, it has been proposed that a diet high in vitamin D may help minimize liver damage in expectant mothers who eat MSG-containing foods.[30]

Solanum Lycopersicon (Tomato)

Reproductive toxicity and infertility are among the issues raised by MSG use in the food business, as was previously highlighted. When mice were given tomatoes, their spermatozoa's motility and morphology improved after being exposed to MSG. The primary mechanism was previously proposed to be the antioxidant properties of tomato content, specifically lycopene . Of all the carotenoids, lycopene—a naturally occurring bioactive component found in tomatoes—is the most effective at scavenging free radicals .

It was demonstrated that lycopene had exceptional neuroprotective properties against Bcl-2/Bax imbalance, neurotoxicity, and cholinergic dysfunction brought on by MSG . Badawi has recently investigated lycopene's ability to shield against MSG-induced nephrotoxicity in vivo. Adult male albino rats were given an oral dose of 4 mg/kg/day of lycopene for 14 days. This demonstrated that lycopene had protective effects against MSG-induced nephrotoxicity by lowering blood urea nitrogen and serum creatinine levels, inhibiting apoptosis (by increasing Bcl2 and decreasing Bax), and preventing kidney damage .[31]
Green tea

It is well established that obesity poses a significant risk for developing chronic illnesses, including metabolic, lung, and colon/breast malignancies , as well as cardiovascular complications. It has been shown that green tea has anti-obesity properties in both experimental and clinical investigations . In order to study obesity and its implications, MSG-induced obesity is an often utilized experimental model. MSG-induced obesity has been linked primarily to its toxic effects on neurons in the hypothalamus's sections that regulate body mass and energy metabolism . Furthermore, a different study has also suggested that GTE may lessen insulin and leptin concentrations and ameliorate obesity generated by MSG . MSG may harm female rats' ovaries, leading to sterility, according to a number of research.Because of its strong antioxidant properties, GTE can shield the ovary from harm caused by MSG. with a different trial, taking MSG orally for 60 days resulted with higher levels of plasma total cholesterol, LDL cholesterol, and triglycerides. On the other hand, after 60 days of treatment with 1.5 ml/rat/day of GTE, there was less rise in body weight in those groups . By improving the liver enzyme activity (significantly reduced activities of LDH, ALT, AST, ALP, and ?-GT in the serum) and the lipid profile (significantly decreased activities of LDH, ALT, AST, TC, ?-GT, TG, LDL-C, and VLDL-C), GTE conjugated with zinc oxide nanoparticles (ZnO/NPs) significantly recovers the hepatotoxicity developed by MSG.[32,33]

Zingiber officinale (Ginger)

Since 2000 years ago, ginger has been used as a spice. Furthermore, it has a well-known anti-emetic effect because of its anti-5HT3 receptor action; this effect is mostly utilized during pregnancy . Ginger was shown to have protective properties against MSG-induced neurotoxicity in a study by Hussein et al. By raising the activity of antioxidant enzymes and lowering MDA, a measure of lipid peroxidation, ginger was able to minimize oxidative stress. Additionally, ginga (500 mg/kg oral) treated rats reduced MSG-induced higher levels of Na+ and Ca+2 in the brain while increasing K+ concentration .

When MSG causes neurotoxicity in male albino rats,  has investigated the neuroprotective properties of ginger aqueous extract. Significant increases in the levels of dopamine, serotonin (5-HT), adrenaline, and norepinephrine were observed following a prolonged treatment of 100 mg/kg of ginger extract, according to his observations. The antioxidant and neuroprotective properties of ginger have been verified in a prior study . Because ginger contains zingerone, which has strong anti-inflammatory and antioxidant properties, as well as 6-gingerol and its derivatives, such as 6-shogaol and 6-paradol, it may have these positive effects. [34]

Curcuma longa

Numerous health benefits of C. longa, particularly its bioactive component curcumin, have been well-documented. These effects include neuroprotective and anticancer qualities . Curcumin has been demonstrated by Khalil and Khedr  to provide protection against MSG-induced neurotoxicity in rats. In rats given MSG, therapy with curcumin significantly reduced TNF? and AChE activity. They proposed that the neuroprotective effect of curcumin could be explained by its anti-inflammatory properties. Another study by Vucic and colleagues found that curcumin therapy of rat thymocytes reduced ROS generation and MSG-induced apoptosis, restored MMP, and increased the Bcl-2/Bax protein ratio . It was also suggested that curcumin's primary method of anti-apoptotic actions was the suppression of the PI3K/Akt signaling pathway in MSG-induced apoptosis. In conclusion, curcumin demonstrated its protective properties against MSG-induced reproductive damage by reducing the frequency of aberrant sperm in male rats and restoring testis weight and sperm count. [35].

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