Authors: Dr. Amod Sharma

Introduction

Monosodium glutamate (MSG), popularly known as “Ajinomoto” is gaining a central role as a flavor enhancer in modern-day cuisine,particularly of Asian Pacific countries. It has become an integral part of industrially processed foods such as noodles, potato chips and others. MSG is used to increase foods palatability due to its umami taste, a fifth taste sense. MSG was discovered by a Japanese biochemist Kikunae Ikedain 1908 from sea weeds. Now days, it is produced by bacterial fermentation. Chemically, it is sodium salt of glutamic acid;one of the most abundant naturally occurring non-essential amino acids.MSG dissociate into glutamate and sodium ions in solution. About 90% of the glutamate is metabolized by the intestinal cells and rest by the liver.

Acceptable Daily Intake

TheMSG consumption is growing worldwide with average daily intake estimated as 3-4 g/day [1]. The Food and DrugAdministration (FDA) has determined MSG as safe for the general population and accordingly stated that an AcceptableDaily Intake (ADI) is not specified. At present, an acceptable daily intake for MSG in humans remains undetermined and intakes of 0-120 mg/kg body weightwere suggested in 1974 by the WHO. Accordingly, the Scientific Committee for Food (SCF) at the European Commission mentioned in 1991 that MSG is associated with an “ADI not specified” and this remains the current indication in the European Union.However, a dose of 150 mg/kg body weight has been mentioned as safe and has been tested in healthy volunteers[2].

MSG and Adverse Effects

The permissible intake amount of MSG and its adverse effects on human health need to be determined by dedicated studies. In 1968, the first ever adverse effect of MSG consumption was reported as a Chinese restaurant syndrome, characterized by numbness at the back of the neck,general weakness and palpitationsafter an American-Chinese meal. Since then ahost of studies have established and explained glutamate-induced brain or neuronal damage.Recent studies in animals have shown that MSG is not only toxic to brain but also to various other organs such as the liver, thymus, pancreas and kidneys. Furthermore, other studies support the hypothesis that MSG consumption may beassociated with overweight, the metabolic syndrome, renal damage, decreases in pancreatic β-cells or arterial hypertension albeit these conclusions remain debated. This article aims tohighlight the MSG induced renal damages.

MSG Caused Renal Damages

The association between MSG and the risk of kidney disease has been hypothesized innumerous studies. In 2013, an animal study has demonstrated that high oral MSG intake for 9 months significantly increases serum creatinine, indicating decreased kidney function. However, blood urea nitrogen levels were noticed within the normal limits.

MSG-treated rats were also reported to have significantly higher level of serum potassium levels. MSG intake do not altered all other electrolytes (Na+, Cl-, HCO3-, Ca2+, PO42-, Mg2+).

Figure 1.Macroscopic appearance of one representative case of urolithiasis in rats on oral MSG (a).Virtual scanning of H&E kidney sections of MSG treated animal with moderate hydronephrosis (5x) in 9 months (b). Crystal in the kidney tissue under dark field illumination with polarized microscope (Olympus BX51) in 9 months MSG-treated animal (200X) (c). doi: 10.1371/journal.pone.0075546.g002


Figure 2.An outline of chronic MSG-induced renal alterations in the kidney. Alkaline urine and oxidative stress due to chronic MSG intake may damage the kidneys by unknown mechanisms. Urolithiasis can also contribute to the interstitial fibrosis by producing inflammatory cytokines and ROS. doi 10.1186/s12929-015-0192-5


Furthermore, MSG causes higher daily urinary excretion of sodium and creatinine and low urinary excretion of ammonium and magnesium [3]. It is to mention that citrate and magnesium are stone formation inhibitors.Importantly, MSG dose applied in the study was quite high, about 5-6 times the reported highest MSG intake by humans, however it has to be considered that the metabolic rate of the animals is 10-100 times higher than the humans. Dietary MSG in experimental animalsalso increases the urine pHabout 9 [3].

Alkaline urine may influence the kidney capacity to secrete or reabsorb metabolites that contribute to stone formation. It has been noted that urine pH exceeding 6.8 enhances the precipitation of urine constituents like calcium phosphate by 3-fold [4].An elevated ion activity product of calcium phosphate in the alkaline urine increases the risk of calcium-phosphate stone formation. As such, minute numerous white colored kidney stones localized in the calyx andpelvis areawere observed in rats fed with MSG for 9 months (Figure 1).Chronic dietary MSG is also known to cause obstructive nephropathy (and hydronephrosis),probably due to alkaline urine and decreased levels of stone inhibitor such as magnesium in the urine [3]. Moreover, chronic consumption of MSG is associated with renal fibrosis [3].

The kidneys of MSG fed rats exhibit significantly high levels of renal fibrosis compared to rats without MSG. Oxidative stress is believed to be the main cause of MSG induced kidney fibrosis and injury [5].Nutrition metabolism and several extracellular and intracellular factors such as hormones, cytokines, and detoxification processes contribute to the oxidative stress. Therefore, excessive renal metabolism of glutamate as in chronic MSG intake can be a source of reactive oxygen species.

A decreased level of major anti-oxidant enzymes and increased lipid peroxidation in the kidneys of chronic MSG-exposed rats supports the theory of MSG induced oxidative stress [6]. High doses of glutamate have also been shown to induce significant toxicity in renal culture cells.A summary of chronic MSG-induced renal alterationsis illustrated in Figure 2.

Conclusion

It became apparent from animal studies that the chronic intake of MSG has potential effects in the kidneys. However, studies to observe such associations in human are crucial.

References

  1. Insawang T, Selmi C, Cha'on U, Pethlert S, Yongvanit P, et al. (2012) Monosodium glutamate (MSG) intake is associated with the prevalenceof metabolic syndrome in a rural Thai population. NutrMetab (Lond) 9: 50. doi:10.1186/1743-7075-9-50.
  2. Walker R, Lupien JR (2000) The safety evaluation of monosodium glutamate. J Nutr 130: 1049S-1052S. PubMed: 10736380
  3. Sharma A, Prasongwattana V, Cha’on U, Selmi C, Hipkaeo W, et al. (2013) Monosodium glutamate (MSG) consumption is associated with urolithiasis and urinary tract obstruction in rats. PLoS One 8:e75546.
  4. Kamel KS, Shafiee MA, Cheema-Dhadli S, Halperin ML (2007) Studies to identify the basis for an alkaline urine pH in patients with calciumhydrogen phosphate kidney stones. Nephrol Dial Transplant 22: 424-431. PubMed: 17107965.
  5. Sharma A (2015) Monosodium Glutamate-Induced Oxidative Kidney Damage and Possible Mechanisms: A Mini-Review. Journal of Biomedical Science, 22 (95). doi:10.1186/s12929-015-0192-5
  6. Paul MV, Abhilash M, Varghese MV, Alex M, Harikumaran Nair R (2012) Protective effects of alpha-tocopherol against oxidative stressrelated to nephrotoxicity by monosodium glutamate in rats. ToxicolMech Methods 22: 625-630. doi:10.3109/15376516.2012.714008.PubMed: 22827614.

More References are available on request