If Laura Fraser, the Good Houskeeping writer who recently surveyed the most popular natural diet aids, 1 wanted to be objective about ephedra, she could have looked up the word in a Chinese dictionary. Ephedra, roughly translates to “astringent” and “yellow.” Instead, Fraser likes another definition for the Chinese herb: “legalized speed.” Mainstream America has discovered a better, nonprescription fat-burning pill than the recently withdrawn dexfenfluramine (Redux), but a barrage of government-sponsored misinformation—paid for by our tax dollars—is contradicting 75 years of scientific research, not to mention 5,000 years of safe use in Chinese medicine! It’s time to set the record straight, starting with giving credit where credit is due: The man who turned on the American public to this thermogenic health food is Paul Delia, a bodybuilder and gym owner from Pascagoula, Mississippi, who’s also the owner of the supplement company AST Research.
Coulda Been Kazabol
“Matter of fact, I wasn’t thinking about thermogenesis,” Paul said. “I just wanted to be kick-ass strong in the gym, but I didn’t wanna go fruitcake with amphetamine use, so I started looking into the body’s closest thing: adrenaline. I stumbled onto ephedrine back in ’87. I read that it was a milder but longer-lasting form of adrenaline, the body’s numero-uno fright, flight or fight hormone. So I asked the Food and Drug Administration (FDA) how I could sell ephedrine, which was an over-the counter asthma medicine at the time. What a pain! The label had to have specific words, in a type that was a certain size. I even had to have an FDA-approved label glued on—and it had to be bombproof so it wouldn’t fall off. I was determined, though, and Dymetadrine 25 was launched.”
The problem with over-the-counter, refined ephedrine, is that you can’t stack just anything in the tablet with it, unless you get an FDA approval for the combination, like the ephedrine-and-theophylline combinations in Bronkaid and Primatene tablets. Right after AST’s Dymetadrine 25 sales started shooting through the roof, Cybergenics put out an herbal capsule stack containing ephedra, the unrefined—and, more important, unregulated— herb stacked with caffeine and called it Cyber- Blast. Before then I’d thought that all Cybergenics products were crap, but I had to admit that Cyber-Blast was pretty good. It was a sneaky way of stacking ephedrine and caffeine without the FDA’s butting in—and keep in mind that up to this point nobody had yet mentioned fat burning. I knew that many health food stores were reluctant to sell pure ephedrine, and even Cyber-Blast looked too drug like for them; so in 1992 Next Nutrition’s David Jenkins and I resurrected my 10-year-old Ultimate Orange and called it “Tang With a Bang.”
In the ’80s hardcore bodybuilders had this maxim: Real bodybuilders don’t read—let alone believe—scientific research. It was very hard to look things up back then—before at-home Internet Medline access. We had to go to the medical libraries and pour over hundreds of bound volumes called Index Medicus—and all we found out was that “Steroids don’t work.” If I’d been really on the ball back then, I would have known about the extensive history and refinement of the ephedrine and-caffeine theromogenic stack, but I was a know-it-all, a dumbshit. Rather than discuss the research in the haphazard way I discovered it, here’s a chronological outline of the scientific developments regarding ephedra and ephedrine.
It’s Not Some Pinko-Commie Plot
Ephedrine is a white, refined nonprescription drug. Ephedra is a soot-colored herbal, and there are numerous ephedra varieties—about 40—that are grown in many desert like climates. In America we have a variant called Ephedra nevadensis, also known as Mormon tea. Unrefined ephedra has two distinct isomers, lephedrine and d-pseudoephedrine. For example, the Chinese mahuang (Ephedra sinica) is mostly l-ephedrine. Mormon tea, though, is mostly the much-less-stimulating d-pseudoephedrine. So, when you buy the herbal variety, you get some pseudoephedrine with your ephedrine. The ephedrine alkaloid (2-methylamino-1-phenyl-1-propanol) was introduced in the Western medical community in 1923.2,3 As its potency is about 85 percent that of the body’s noradenaline (in itself a weak adenaline), people tried ephedrine for a host of illnesses over the years: asthma, heart block, narcolepsy, depression, hypotension4 and some forms of insulin-induced edema.5 At present the approved use of ephedrine is for mild asthma.
Dr. Eriksen, a general practitioner working in the small town, had noticed that many of his asthmatic patients had reduced appetites when they used a triple stack of ephedrine, caffeine and Phenobarbital.
Hamlet’s Hometown Hits the Big Time!
The first instance of ephedrine being used as a weight-loss drug took place in Ellsinore, Denmark, in 1972.6 Dr. Eriksen, a general practitioner working in the small town, had noticed that many of his asthmatic patients
had reduced appetites when they used a triple stack of ephedrine, caffeine and Phenobarbital. The narcotic was included to quell the jitters—or it was a canny business move aimed at hooking the patients into buying more. By 1977, 70,000 people were taking the so-called Ellsinore pill. That same year the Danish government issued a “cease prescribing” warning to all doctors about the product after a number of skin rashes, attributed to the Phenobarbital. were reported.
Dissin’ Doc Eriksen
The revival of ephedrine and caffeine as an obesity-fighting drug has been an unusually long and cautious process, considering there are numerous studies from 1923 onward showing the effects of ephedrine and methylxanthines (caffeine and theophylline) on bronchial dilation in humans. Even Dr. Eriksen didn’t make the connection that ephedrine and caffeine formed a thermogenic compound that increased energy expenditure. He thought it was simply an appetite suppressant. It wasn’t until 1981 that a traditional research study “proved” that ephedrine with caffeine reduced appetite.6 Before that academia stalled the research, invoking the infamous NIH clause: Not-Invented-Here. Poor Doc Eriksen was the Rodney Dangerfield of the fat-loss field.
Bat-Man (No, Not the Pedophile in the Comic Books)
From the late ’70s the research was showing that ephedrine causes energy expenditure in various laboratory animals, but it took about nine years for human studies to tart appearing.7,2,8,9 Obscuring the central issue was a debate that was going on at the same time about the existence in humans of brown adipose tissue (BAT), which is a heat regulator in many mammals. Some of the initial research was incorrect in showing that humans had BAT between their shoulder blades, as the heat increase that appeared to take place was due to increased blood flow. Humans do have a small amount of BAT surrounding their kidneys, 10 but its thermogenic effect on the whole body is small.
When scientists agreed that ephedrine was thermogenic in humans, they still had no firm recommendations of ephedrine dosage. Some studies showed the best thermogenic response at the lowest dosage, 10 milligrams.2 Others showed that 20 milligrams created no increase in heat.
They tried other ratios but discovered that 20 milligrams of ephedrine gets a maximal thermogenic effect with 200 milligrams of caffeine. Note that those were the amounts used in the ’92 study.
If It Works for Asthma…
You’d think that a scientist would have thought of the obvious sooner: If ephedrine and caffeine combinations work well together in treating asthma, they should be similarly effective for thermogenic benefits. Caffeine is thermogenic at the higher dosages, 11,12,13,5 so the ephedrine and caffeine stack should have at least an additive thermogenic effect. 14,15,16,17,9,18 It was only in 1992 that a team of Danish researchers established the ideal synergistic ratio of ephedrine to caffeine at 1-to-10.2 They tried other ratios but discovered that 20 milligrams of ephedrine gets a maximal thermogenic effect with 200 milligrams of caffeine. Note that those were the amounts used in the ’92 study. Many bodybuilders tend to double the dose to 40 milligrams and 400 milligrams, but there’s no evidence that the greater amounts cause a greater energy expenditure. Then, again, some people do it that way because they like it.
The ECA Stack Is Iffy
Methylxanthines weren’t the only substances that showed promise when they were stacked with ephedrine. There was also aspirin. The studies are wildly conflicting on that subject.19,20 An initial study in the ’80s showed a doubled thermogenic response in obese women, but another similar experiment showed no enhanced effect in lean women. What’s more, although many of the popular herbal ephedrine stacks include the aspirin precursor white willow bark, there are no published studies showing that ephedrine, caffeine and aspirin are any better than ephedrine and caffeine alone.
Although many of the popular herbal ephedrine stacks include the aspirin precursor white willow bark, there are no published studies showing that ephedrine, caffeine and aspirin are any better than ephedrine and caffeine alone.
So What’s the Damn Problem?
If ephedrine has been around for so many years, and the research shows it to be effective and safe for weight loss, why is it that Good Housekeeping and the FDA have a vendetta against the ephedrine-and caffeine stack? Many doctors like to say that it’s dangerous, but they’re the same doctors who embraced dexfenfluramine, even though the published research showed that ephedrine and caffeine was not only more thermogenic but was longer lasting as well (50 weeks vs. Redux’s six-month-only effects).10 I don’t usually cast stones, but we wouldn’t have an ephedrine problem if Herbal Ecstasy hadn’t become so popular.
When ephedrine was used only by asthmatics, truck drivers, athletes and dieters, it was pretty much below the horizon of public scrutiny, but the Herbal-X variants appealed to the worst possible segment of the population: adolescents. Many teenagers have a veneer of invulnerability, especially if a powerful stimulant is declared to be “all natural” and so, presumably, safe. Teenagers plus natural high equals abuse plus emergency room visits. Although I’m no friend of the FDA, I feel that the agency could have moved faster against those Herbal-X-type products, the way it did when the herbal fen-phens hit the market.
The FDA can’t ban ephedrine outright, but it can control the claims made on the labels. The agency has been threatening to take control of herbal ephedra—calling for a maximum dose of eight milligrams, not allowing it to be combined with additional stimulants and requiring with a label warning that users should take no more than three doses a day. The way the FDA arrived at those doses is not, obviously, based on any published research. Fortunately, at this point ephedrine-and-caffeine stack is still here.
How Ephedrine Really Works
If you didn’t have a sympathetic nervous system, which branches off your middle spinal column, ephedrine wouldn’t work. No matter, as you’d be dead anyway. The sympathetic nervous system controls all those automatic bodily functions you don’t think about: heart rate, respiration, perspiration, even bowel movements. One of the more interesting aspects of the sympathetic nerves is what they do when you eat too many carbohydrates. Beyond the digestion energy and glucose being converted into either glycogen or triglyceride, some of the extra calories are burned off as heat.22,7,8 It’s the thermogenic effect of carbohydrates— though, technically, it’s insulin that trips the thermogenic switch. The sympathetic nerves secrete a milder form of adrenaline called noradrenaline, which needs hormone receptors to work. The receptors in question are called andrenergic receptors, and the human body has two main types and a number of further subdivisions: alpha (1 and 2) and beta (1, 2, 3, and 4).
In animals, switching on the beta-receptors with noradrenaline via insulin burns excess fat calories in beta-1, -2 and -3 receptors, especiallyin the BAT areas. Humans, having very little BAT, mostly burn glucose and glycogen in skeletal muscle and the liver in something called the Cori cycle, in which carb calories are converted to lactate, and recycled back into glucose and glycogen in the liver.23,10 Ephedrine was originally thought to be simply a stimulator of noradrenaline secretion from the sympathetic nerves. Further research showed that it also acted directly on the andrenergic receptors—mostly the betas but with some alpha effects as well. Ephedrine’s span of activity is about six hours. Although a water-insoluble alkaloid in its natural state, it’s modified with a hydrochloride
or sulfate salt in the refined forms for faster absorption. Herbal ephedras take longer to reach the bloodstream. The odd thing is that ephedrine is considered a fat burner, but it does that by using up the glucose and the glycogen in the skeletal muscle and liver. Only an insignificant amount of direct fat burning occurs in the BAT around the kidneys. Ephedrine actually raises both blood glucose and insulin.24 Most low calorie diets can cause increased nitrogen excretion, but just the opposite happens when you add ephedrine to the low-calorie equation. The effects are similar to those of growth hormone or people on a low-calorie diet: It makes the body rely on fat calories without sacrificing amino acids in the muscle for glucose production.
Ephedrine’s span of activity is about six hours. Although a water in soluble alkaloid in its natural state, it’s modified with a hydrochloride or sulfate salt in the refined forms for faster absorption. Herbal ephedras take longer to reach the bloodstream.
Where Does Caffeine Fit In?
The body has built-in regulating mechanisms so that noradrenaline secreted from the sympathetic nerves is modulated in its effect. Methylxanthines all seem to work on one of the energy precursors in the cells, cyclic andenosine-monophosphate (cAMP), in conjunction with the increase in cAMP due to the effect of noradrenaline on the beta-2 receptors. There was a debate over the years as to what the primary action of the methylxanthines are: They either block adenosine or inhibit phoshodiesterase (PDE), the enzyme that degrades the phosphate in cAMP. Caffeine has both effects, but PDE turned out to be the primary substance that intensifies ephedrine’s thermogenic effect.
Chemists have produced better caffeines that have greater PDE inhabitation (the most promising is enprofylline), which doesn’t influence heart rate as much, but none of the methylxanthine derivatives have been approved yet. Other substances, like forskolin, can potentiate ephedrine, forskolin has a greater adenosine-blocking effect while affecting the heart more.24
What About Aspirin?
The transient autocrine hormones called prostaglandins can, in some cases, inhibit the release of noradrenaline. As mentioned above, some obese women respond dramatically to aspirin stacked with the ephedrine in studies, while less obese women didn’t fare as well. You don’t have to wait for further studies to find out what works for you. Once you’ve established a consistent body temperature rise with ephedrine and caffeine (a $6 digital mouth thermometer will give you the info nicely), you can try adding 300 milligrams of aspirin and see if your body temperature shows an increase from the previous ephedrine and-caffeine elevation.
Thyroid hormone is elevated after about four weeks of chronic ephedrine use. Get this, however: After 12 weeks of ephedrine use thyroid hormone is lower than normal—but thermogenesis is greater than it was during the initial metabolic rise.
The Really Weird Stuff About Ephedrine
The andrenergic receptors are distributed through most cells and organs in the body. At times the beta stimulation from ephedrine can actually increase some hormones. For example, thyroid hormone is elevated after about four weeks of chronic ephedrine use. Get this, however: After 12 weeks of ephedrine use thyroid hormone is lower than nor- mal—but thermogenesis is greater than it was during the initial metabolic rise. What the hell is happening? Eventually, many of the beta-1 and beta-2 receptors will resist the ephedrine and noradrenaline stimulation, but the body won’t freeze you solid. when beta-1s and beta-2s are down regulated, another thermogenic receptor increases. When that odd effect was reported in humans in 1995, the researchers assumed it was the fat-burning beta-3 receptor.26 Recently, however, the beta-3 premise was discounted when the human-specific beta-4 receptor was discovered.
More Information
Studies have shown that only caffeine–and none of its metabolites, the chief one being paraxanthine—is thermogenic with ephedrine. What’s more, research shows that part of the grapefruit rind called naringin puts off the breakdown of caffeine to paraxanthine—and grapefruit blossomed are even better—so some ephedra stacks have that additive.
One of the chief drawbacks to most low-calorie diets is the reduction of high-density lipoprotein (HDL), the so-called good cholesterol. Adding ephedrine to a low-calorie diet restores HDL to near normal levels.
The DEA Plays Hardball
The United States Drug Enforcement Agency (DEA) doesn’t like ephedrine. Technically, a smart criminal chemist can make ephedrine into amphetamine. To thwart that, many of the refined ephedrines contain another ingredient that makes them almost impossible to convert: guaifenesin (a mucous-expeller, yuck!). Since the summer of 1997 the DEA has required that all interstate shippers of ephedrine register with the agency. A health food store doesn’t need a DEA license to sell ephedrine for in-store sales, but anyone who wants to sell it to out-of state customers via mail order has to have that license. the punch line is, the DEA stopped the issuing licenses after August ’97.
One of the chief drawbacks to most low calorie diets is the reduction of high-density lipoprotein (HDL), the so-called good cholesterol. Adding ephedrine to a low-calorie diet restores HDL to near normal levels.
Worst-Case Scenario
What will happen if the FDA gets every one of its proposed regulations governing ephedra approved? Will products like Ultimate Orange or Twinlab’s Ripped Fuel become illegal? Not to worry: There are plenty of other naturally occurring compounds just as potent as ephedrine and caffeine—or more so.
What About Herbal Fen-Phen?
In essence, the various herbal fen-phens are in the spirit of the original Ellsinore pill: two stimulants (ephedra and caffeine) with a mild antidepressant (Saint-John’s-wort). While there’s no research showing that the antidepressant makes a stack more thermogenic, over stimulation caused by the ephedrine and caffeine is a very valid complaint from many users. I wouldn’t be surprised if one of the anti-anxiety herbs like red ginseng didn’t turn out to be a better choice.
Bottom Line: The Best Ephedra Stack, Bar None
Here are some tip for finding a good product.
1) Read the label thoroughly. Ephedras can vary in potency. Multiply the total ephedra per does by the potency percentage to determine the amount of active ephedrine (335 milligrams of raw ephedra times 6 percent gives you 20 milligrams of active ephedrine). The ideal does for the thermogenic effect is to take about 20 milligrams three times a day, or every six hours. If you use more, you may get a better workout due to more contractile force in the muscles, but you won’t necessarily get a better thermogenic effect.
2) The caffeine dose should be 10 times the ephedrine dose. You’ll have to do the same arithmetic to arrive at the active caffeine content. The two chief sources of herbal caffeine are kola nut and guarana.
3) Once you establish a consistent body temperature elevation with ephedrine and caffeine, you can try 300 milligrams of aspirin to see if you get a further thermal enhancement.
4) Refined naringin is not generally available. If you want to try a grapefruit juice chaser, the more bitter the better.
5) Take the product continuously for a while—don’t stop for a while. Ephedrine-caffeine thermogenesis is better at 12 weeks and is still significant at week 50! If the animal-based research holds true, down regulating the beta-1 and beta-2 receptors creates more true fat-burning receptors in the body.
6) The ephedrine-and-caffeine combination has proven unusually safe over the years. Some individuals who are prone to cardiac ailments, hypertension and other medical conditions should stay away from all stimulants. Yes, strokes and heart attacks have occurred while people were using ephedrine—and some cases the victims were seemingly healthy individuals. It appears to be a random occurrence. One case of death from stroke involved a man who used 10 to 20 25-milligram ephedrine tablets a day for 23 years, while another fatality occurred with a healthy 15-year-old football player.
Just remember that herbs and plants are potent drugs. Bodybuilders and dieters have access to a vast unregulated pharmacy called a health food store; however, the drugs are only safe when used with caution and common sense. But don’t wait for the Good Housekeeping Seal of Approval.
Once you establish a consistent body temperature elevation with ephedrine and caffeine, you can try 300 milligrams of aspirin to see if you get a further thermal enhancement.
