Now, how relevant is this? Even though the study used brain cells from a mouse and those findings cannot always be translated into human physiology, the study was very relevant. First of all, the concentration range included the normal range seen in people not using AAS and extended beyond what is conceivably practiced by athletes and other AAS users. Secondly, the AAS chosen represented some of the most commonly used steroids, as well as one related to the designer drug, THG (the clear). Third, the inclusion of an aromatase inhibitor is important, as many AAS-users include Arimidex or Femara in their stacks to reduce the risk of gynecomastia or other estrogenic side effects. Fourth, the chemical toxin they chose (NMDA) causes cell death by overstimulating a class of glutamate receptor in brain cells. Glutamate receptors are also stimulated by the taste enhancer MSG (commonly used in Oriental cuisine and responsible for the headaches some get from Chinese food), as well as the amino acid L-aspartate. The artificial sweetener aspartame (NutraSweet, Equal) breaks down into three compounds: methanol, L-phenylalanine and L-aspartic acid. Some diet soda drinkers complain of chronic headaches; many of these may be related to caffeine, but L-aspartate could certainly contribute to this effect as well. Fifth, chronic, neurodegenerative disease develops slowly and is usually irreversible once it becomes detectable. Alzheimer’s, Parkinson’s and many other neurodegenerative disorders are becoming increasingly prevalent in our aging society.

    NMDA was a wise choice for the investigators, as it causes cell death by flooding the brain cells with calcium. As an ion, calcium activates many enzymes in cells when its concentration rises. At low concentrations, many of these enzymes are related to cell function, and the calcium can be “flushed away” once it has accomplished its goal. However, high calcium concentrations cause the cell to respond by “committing suicide” because other enzymes are activated that are destructive. NMDA is capable of forcing calcium to reach these “suicidal” levels.

    How then do AAS increase the cells’ vulnerability to NMDA? It has been shown with nerve cells and muscle cells that androgens are able to stimulate receptors on the cell membrane allowing calcium to enter. At normal concentrations, this effect is beneficial and promotes cell growth and development. However, when concentrations escalate well above normal, the calcium influx continues and the cell is unable to clear out the buildup of the stimulating ion. In mature nerve cells, surrounded by their supporting cast of astrocytes, this buildup does not reach critical levels by itself. In the natural state, testosterone protects against the androgenic stimulation by providing its own antagonist, estradiol, via the aromatase enzyme present in astrocytes. Even nonaromatizing AAS do not cause cell death in a pure environment.