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Comments (Letter to the Editor) made by M. Hermanussen on the paper “No consensus on glutamate” by Beyreuther et al.
to the Editor
European Journal of Clinical Nutrition
advance online publication 30 May 2007;
No consensus on glutamate
University of Kiel Germany, Altenhof, Germany
Sir, with irritation I took notice of the consensus meeting paper, 'monosodium glutamate an update', by Beyreuther et al., published in Eur J Clin Nutr, 2006. The authors conclude, 'a maximum (GLU) intake of 16.000 (sixteen dot triple zero) mg/kg body weight is regarded safe'. The number is misleading. It might be interpreted as 16 mg/kg body weight or 16 000 mg/kg, that is 16 g/kg body weight. Reading the manuscript itself, the confusion increases. When addressing the question, 'can we define a safe level of intake regarding adding GLU?' the authors state, 'based on dietary animal studies (metabolic control), a 'no observed adverse effect level' of 16000 mg/kg body weight was calculated in weaning animals ...'. Yet, on page 7, evidence is cited that 'the oral dose that is lethal to 50% of subjects (LD50) in rats and mice is 15 00018 000 mg/kg bw, respectively'. This is difficult to understand.
Even when disregarding misprints, the consensus paper is far from being a consensus. In 1995, Monno et al. (1995) studied the effect of high doses of monosodium glutamate (MSG) on the extracellular concentration of glutamate (GLU) in the hypothalamus and in the hippocampus of freely moving rats. MSG at 4 g/kg (40% solution) given by gavage caused a significant increase in plasma (5.30.4-fold, P<0.01) and extracellular GLU in the hippocampus (4.20.6-fold, P<0.01) and in the hypothalamus (8.91.7-fold, P<0.01) compared to control rats receiving a 40% sucrose solution (10 ml/kg). The peak increase was found within 40 min after MSG administration, then declining to baseline in the next 80 min. In 1995, Currie et al. (1995) examined paraventricular nucleus extracellular amino-acid concentrations in awake, freely behaving rats following gavage of equicaloric loads of a balanced amino-acid mixture, glucose (0.89 g) or water. Dialysate levels of GLU, isoleucine, leucine, methionine, threonine, tyrosine and valine showed reliable increases after amino-acid treatment. The authors concluded that specific brain regions may respond uniquely to amino-acid ingestion and further imply that dietary composition may influence the amino-acid profiles of the extracellular fluid in brain.
We studied the effect of oral administration of MSG to pregnant rats on birth weight of the offspring (Hermanussen et al., 2006). Maternal feeding with 5 g MSG per day resulted in severe birth weight reduction (P<0.01). Also growth hormone (GH) serum levels were affected in animals that received MSG during prenatal life via maternal feeding. Animals that are kept on high-MSG diet (5 g MSG per day) continue to show serum GH levels that are as low or even lower than those of MSG-injected animals (P<0.05), both at day 30 and at day 90 of life. Animals that were kept on medium-MSG diet (2.5 g MSG per day) showed low serum GH levels at day 30 of life (P<0.01), but seemed to partially recover before day 90.
In summary, current evidence suggests that orally administered GLU passes into the circulation and enters the central nervous system, possibly even in fetuses whose mothers are fed GLU. Very recent evidence has been added by Cheunsuang et al. (2006), who showed that the medial arcuate nucleus, that is an area that attributes to feeding control, belongs to those regions of the CNS that take up molecules from the circulation.
Thus, I must disagree when it is stated that, 'as long as BBB is intact there is no risk for GLU transfer across BBB'.
Cheunsuang O, Stewart AL, Morris R (2006). Differential uptake of molecules from the circulation and CSF reveals regional and cellular specialisation in CNS detection of homeostatic signals. Cell Tissue Res 325, 397402.
Currie PJ, Chang N, Luo S, Anderson GH (1995). Microdialysis as a tool to measure dietary and regional effects on the complete profile of extracellular amino acids in the hypothalamus of rats. Life Sci 57, 19111923.
Hermanussen M, García AP, Sunder M, Voigt M, Salazar V, Tresguerres JAF (2006). Obesity, voracity and short stature: the impact of glutamate on the regulation of appetite. Eur J Clin Nutr 60, 2531.
Monno A, Vezzani A, Bastone A, Salmona M, Garattini S (1995). Extracellular glutamate levels in the hypothalamus and hippocampus of rats after acute or chronic oral intake of monosodium glutamate. Neurosci Lett 193, 4548.