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Effects of Early Exposure to MSG and Phenobarbitol |
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January 1, 2003
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Newspaper and television ads extol the benefits of a multitude of drugs and supplements, diet products, and flavor enhancers. People take herbal remedies to fight everything from a cold to depression, and if those don't work, obtain a prescription for one of the many drugs to elevate or alter their mood. Nobody knows yet the long-term effects of all these substances on the human body, and in particular on the highly vulnerable perinate. What may be therapeutic or safe for the mother could be toxic to the fetus and nursing infant. Many of these compounds are too new to have been studied for a long period of time.
There are two substances, widely available for many years, that have for 25 years been subjects of Dr. Bernard Shapiro's funded research. Shapiro, professor of biochemistry at the University of Pennsylvania School of Veterinary Medicine, has studied the influence of MSG on prenatal and perinatal development. Fifteen years ago, he added the drug phenobarbital to his investigations. Why those two? MSG, commonly known as monosodium glutamate, is a food additive that cannot be avoided. It's in prepared foods, and has been widely used in the United States since the 1940s as a flavor enhancer -- it is estimated that Americans consume 200 million pounds of MSG or related products annually. Phenobarbital, a barbiturate, is frequently prescribed to infants in intensive care and to pregnant women for a variety of commonly occurring maladies, among them convulsive disorders that complicate one out of every 200 pregnancies. Prescriptions for pregnant women were particularly common between the 1950s and 1970s, exposing more than 23 million children in the United States alone. Neither MSG nor phenobarbital produce visible birth defects, but it is thought that they interfere with the production of a number of liver enzymes known as CYPs, which are vital to the body's ability to metabolize drugs and other potentially toxic substances.
The expression of these drug-metabolizing enzymes is controlled by growth hormones produced by the pituitary. Levels of the hormone in males and females are different: Males secrete the hormone in an episodic on-off rhythm with periods where the hormone cannot be detected. Women produce growth hormone continuously, and it is always present in circulation. Because of these profiles, the levels of drug-metabolizing enzymes are different in males and females. This may in part explain the difference in response to drugs; for example, women take longer to emerge from anesthesia than men. To complicate matters, levels of growth hormone decline as a person ages.
In earlier studies, Dr. Shapiro's group had shown that neonatal administration of normal, exposure-like levels of both phenobarbital and MSG to laboratory animals can produce delayed, but permanent defects in hormone secretion and drug metabolism, contributing to serious long-term health consequences. Another study found that prenatal administration of either one of the two substances can result in a multitude of long-term reproductive, growth, hepatic and neural dysfunctions. One finding, in particular, is disturbing: Neonatal administration of phenobarbital can induce a delayed but permanent elevation in the activities of several hepatic drug-metabolizing enzymes. These enzymes break down specific substances; when their activities are elevated, these drugs are broken down faster. One would expect such elevated activity right after administration of phenobarbital, but not much later. However, it appears that at sexual maturity, when gender-dependent differences in drug metabolism appear, the hepatic drug metabolizing enzymes are induced again and remain overexpressed for the rest of life. In rats exposed as neonates to phenobarbital this results in a shorter lifespan, and a great increase in tumor formation.
Neonatal exposure to MSG has a different effect on growth hormone production. It causes a permanent reduction in the secretion of growth hormone, which leads to a reduced production of the drug-metabolizing enzymes. This hampers the metabolization of drugs and toxic substance. The reduced quantity of growth hormone leads to stunted growth and irreversible obesity. Like phenobarbital, defects resulting from neonatal exposure to MSG are not apparent until adulthood.
Dr. Shapiro and his group are currently working to answer these questions: How do the chemicals induce the defects? How are the defects expressed? The group has observed that when the production of growth hormone is disturbed, the level of drug-metabolizing enzymes is affected. They found that in male and female rats exposed pre-natally to phenobarbital, there were permanent defects in the expression of these enzymes. The mechanism by which the abnormal profile of growth hormone disrupts the enzyme expression is not known, and the group proposes to investigate it.
It is known that men exposed perinatally to phenobarbital have a considerably higher incidence of delayed puberty, undescended testes, and genital abnormalities. In women this exposure leads to irregular menstrual cycles and problems during pregnancy. Both sexes score lower on IQ tests as adults. Further, phenobarbital is a known carcinogen that induces the overexpression of selected hepatic enzymes that can increase the metabolism of innocuous compounds into carcinogenic and toxic metabolites. Perinatal exposure to the barbiturate has been reported to subsequently increase the risk of cancer in adult rats and children.
Phenobarbital and MSG are just two substances that can have an impact on drug metabolism. There are many other compounds that are in drugs or food whose impact on human metabolism is unknown. One of these, aspartame, is used widely as a sweetener.
"Our studies with rats have shown that the sweetener, containing an amino acid like MSG, could produce subtle developmental defects in growth hormone secretion," explains Dr. Shapiro. "It is estimated that children consume almost 100 milligrams of aspartame per kilogram of body weight per day, a level approaching the adverse doses found in animal studies. Children under the age of 5 are particularly vulnerable: Their hepatic and neuroendocrine differentiation are still incomplete and early, constant exposure to low levels of food additives could permanently alter hormone secretion, the expression of hepatic drug metabolizing enzymes, and/or their responses to inducing agents. Such effects could unknowingly affect the efficacy of drug therapy or the susceptibility to chemically induced cancers in adulthood." |
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Source:
For Additional Information Contact:
University Communications
at 215-898-8721.
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