Obesity, voracity, and short stature: the impact of glutamate on the regulation of appetite.
BACKGROUND
World-wide obesity has risen to alarming levels. We present experimental support for a new and very challenging hypothesis linking obesity, voracity, and growth hormone (GH) deficiency, to the consumption of elevated amounts of the amino-acid glutamate (GLU). Supraphysiological doses of GLU are toxic for neuronal cells.


METHODS
Human data were obtained from 807,592 German conscripts born between 1974 and 1978, and from 1,432,368 women of the German birth statistics (deutsche Perinatalerhebung) 1995-1997. The effects of orally administered monosodium glutamate (MSG) were investigated in 30 pregnant Wistar rats and their offspring. Pregnant animals either received no extra MSG, or 2.5 g MSG, or 5 g MSG per day, up to the end of the weaning period. In all, 2.5 g, respectively 5 g, MSG accounted for some 10%, respectively 20%, of dry weight of the average daily food ration. After weaning, MSG feeding was continued in the offspring.


RESULTS
Morbid obesity associates with short stature. Average stature of conscripts progressively declines when body mass index increases above 38 kg/m2. Also morbidly obese young women are shorter than average though to a lesser extent than conscripts. Oral administration of MSG to pregnant rats affects birth weight of the offspring. Maternal feeding with 5 g MSG per day results in severe birth weight reduction (P<0.01). Weight increments remain subnormal when MSG feeding to the mothers is maintained during weaning (P < 0.01). GH serum levels are 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. Almost identical results were observed in IGF-1 serum levels. Oral MSG resulted in dose dependent voracity. The animals fed 5 g MSG per day increased water uptake by threefold (P < 0.01), and food uptake by almost two-fold (P < 0.01). The influence of MSG is in general more marked in males than in females.


CONCLUSIONS
GLU is a widely used nutritional substance that potentially exhibits significant neuronal toxicity. Voracity, and impaired GH secretion are the two major characteristics of parenterally administered GLU-induced neuronal damage. GLU maintains its toxicity in animals even when administered orally. Males appear to be more sensitive than females. The present study for the first time demonstrates, that a widely used nutritional monosubstance--the flavouring agent MSG--at concentrations that only slightly surpass those found in everyday human food, exhibits significant potential for damaging the hypothalamic regulation of appetite, and thereby determines the propensity of world-wide obesity. We suggest to reconsider the recommended daily allowances of amino acids and nutritional protein, and to abstain from the popular protein-rich diets, and particularly from adding the flavouring agents MSG.
Hermanussen
M
M
Aschauhof Altenhof Germany. hermanussen.aschauhof@t-online.de
García
A P
AP
Sunder
M
M
Voigt
M
M
Salazar
V
V
Tresguerres
J A F
JA
D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001069:Appetite Regulation / Q000187:drug effects*; D001724:Birth Weight / Q000187:drug effects; D001827:Body Height / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005421:Flavoring Agents / Q000008:administration & dosage / Q000494:pharmacology; D005503:Food Additives / Q000008:administration & dosage / Q000494:pharmacology*; D005858:Germany / Q000453:epidemiology; D018698:Glutamic Acid / Q000097:blood / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology; D009767:Obesity, Morbid / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D012970:Sodium Glutamate / Q000008:administration & dosage / Q000494:pharmacology*
D005421:Flavoring Agents; D005503:Food Additives; D018698:Glutamic Acid; D013006:Growth Hormone; D012970:Sodium Glutamate