There’s a very thorough paper published in the American Journal of Epidemiology, “Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study”, DOI: 10.1093/aje/kwn191
Apparently, and this really surprised me,
“Use of prescribed ephedrine in Denmark — Letigen was a pharmaceutical product containing 20 mg of synthetic ephedrine and 200 mg of caffeine, available only by prescription. Its recommended dose was 1–3 tablets per day, depending on the user’s tolerance. It was approved for sale in Denmark in 1990. During the peak of its use in 1999, some 110,000 persons, corresponding to 2% of the Danish population, were treated. In 2002, the marketing license was suspended, after a number of reports had suggested a safety problem.”
So there’s a pretty big sample there.
Now note, I’m not a doctor and this just my opinion — it seems that some people should never take ephedrine under any circumstances (certain heart problems or family history of certain heart problems, etc) and anyone else ought to be really quite careful taking it if it’s legal and approved in one’s jurisdiction.
Ephedrine increases metabolic activity and thermogenesis — heat production — and it’s more dangerous when it’s hot outside, when you’re doing any aerobic activity, or if you’ve had any other stressors on one’s heart or get into other contraindication with stressors.
Speculatively, it seems possible that safety rates in Denmark might be higher than elsewhere since it doesn’t get very hot there. If you compared someone using ephedrine/caffeine in Siberia in the winter to Dubai in the summer, the increased thermogenesis and physically radiating more heat might seem like a beneficial side effect in an arctic blizzard whereas both uncomfortable and dangerous under a desert sun.
RAND reviewed adverse events reported in 52 published randomized controlled clinical trials. No serious adverse events (death, myocardial infarction, cerebrovascular/stroke events, seizure, or serious psychiatric events) were reported in the clinical trials. However, evidence from the trials was sufficient to support the conclusion that the use of ephedrine, ephedrine plus caffeine, or ephedra plus caffeine is associated with 2-3 times the risk of nausea, vomiting, psychiatric symptoms such as anxiety and change in mood, autonomic hyperactivity, and palpitations. The contribution of caffeine to these symptoms cannot be determined.
There seems to be a disagreement in the literature about the facts. This one had randomized controlled trials. Maybe the sample size was too small though? In that case, are the “suggestions” of a safety problem enough to be a concern? How strong were these suggestions? Obesity also increases risk of death. Perhaps ECA still wins on net cost-benefit. Maybe the risks are very small. Death is a very serious side effect, to be taken very seriously, unfortunately, many over-the-counter medications we use routinely carry this risk. Degrees of risks matter. Maybe the ephedrine was correlated but wasn’t the cause. We’d need the numbers, and maybe more statistical know-how than I’ve got.
There’s a very thorough paper published in the American Journal of Epidemiology, “Use of a prescribed ephedrine/caffeine combination and the risk of serious cardiovascular events: a registry-based case-crossover study”, DOI: 10.1093/aje/kwn191
Apparently, and this really surprised me,
“Use of prescribed ephedrine in Denmark — Letigen was a pharmaceutical product containing 20 mg of synthetic ephedrine and 200 mg of caffeine, available only by prescription. Its recommended dose was 1–3 tablets per day, depending on the user’s tolerance. It was approved for sale in Denmark in 1990. During the peak of its use in 1999, some 110,000 persons, corresponding to 2% of the Danish population, were treated. In 2002, the marketing license was suspended, after a number of reports had suggested a safety problem.”
So there’s a pretty big sample there.
Now note, I’m not a doctor and this just my opinion — it seems that some people should never take ephedrine under any circumstances (certain heart problems or family history of certain heart problems, etc) and anyone else ought to be really quite careful taking it if it’s legal and approved in one’s jurisdiction.
Ephedrine increases metabolic activity and thermogenesis — heat production — and it’s more dangerous when it’s hot outside, when you’re doing any aerobic activity, or if you’ve had any other stressors on one’s heart or get into other contraindication with stressors.
Speculatively, it seems possible that safety rates in Denmark might be higher than elsewhere since it doesn’t get very hot there. If you compared someone using ephedrine/caffeine in Siberia in the winter to Dubai in the summer, the increased thermogenesis and physically radiating more heat might seem like a beneficial side effect in an arctic blizzard whereas both uncomfortable and dangerous under a desert sun.
The safety information I had came from here.
There seems to be a disagreement in the literature about the facts. This one had randomized controlled trials. Maybe the sample size was too small though? In that case, are the “suggestions” of a safety problem enough to be a concern? How strong were these suggestions? Obesity also increases risk of death. Perhaps ECA still wins on net cost-benefit. Maybe the risks are very small. Death is a very serious side effect, to be taken very seriously, unfortunately, many over-the-counter medications we use routinely carry this risk. Degrees of risks matter. Maybe the ephedrine was correlated but wasn’t the cause. We’d need the numbers, and maybe more statistical know-how than I’ve got.