Now let us put all of this together. First, what do we know; Ephedrine stimulates lipolysis by increasing noradrenaline (NA) release from sympathetic nerve terminals. This increase in noradrenaline activates adrenergic receptors which increases cAMP levels in fat cells and muscle cells. This has the effect of increasing lipolysis in fat cells and increasing protein synthesis in muscle tissue. Negative feedback mechanisms are activated as well, and involve the production of phosphodiesterases, adenosine, and prostaglandins. Caffeine has the ability to inhibit phosphodiesterase activity and interfere with the adenosine receptor. This combined with its ability to prevent some NA re-uptake12 increase the effectiveness of ephedrine in a synergistic fashion. Aspirin has been shown to increase the effectiveness of ephedrine in some individuals presumably by its actions as a prostaglandin inhibitor.
Maximum effectiveness is achieved when taking 20 mg ephedrine with 200 mg caffeine and 300 mg aspirin three times a day about one half hour before meals. Common side effects are associated with its sympathetic activity namely, anorexia, initial rise in blood pressure, initial tachycardia, slowed GI motility (constipation), insomnia, agitation, anxiety, nervousness and depression- like withdrawal symptoms. Most all of these symptoms exhibit tachyphylaxis after about 4-6 weeks. Thermogenic activity seems to last upwards of 20 weeks due to its low desensitization properties and beta-3 affinity. About 75% of ephedrine’s effects on weight loss in the obese are due to appetite control.
Anyone considering taking ephedrine, caffeine and aspirin should educated themselves first about the potential side effects. Individuals with pre-existing high blood pressure should not use sympathomimetics such as ephedrine. When taking herbal forms of ephedrine, be sure you understand just how much is in each serving. Be aware that herbal preparations are standardized but you still can not be sure exactly how much you are taking with each capsule.
The future of fat loss for the bodybuilder will not, or should not, focus on appetite alone. It should focus on enhancing lipolysis and overcoming the regulatory mechanisms designed to prevent rapid and substantial fat loss. Ephedrine, caffeine and aspirin are effective but are still limited by inhibitory mechanisms built into our physiology. Gaining better understanding of the mechanisms involved in lipolysis and gaining funding for appropriate research is critical. The pharmaceutical industry already recognizes the profitability of weight loss agents unfortunately they are focusing at present on appetite control. Perhaps as these strategies continue to fail they will focus more on body composition instead of just "body weight". When this happens you can be sure that adrenergic receptors and the second messenger system will be the focus of attention.
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