Supplements purported to promote fat loss are among the most popular sold today. The biggest-selling over-the-counter fat-loss supplements in recent years contained ephedra or ephedrine combined with caffeine. Ephedrine and caffeine promoted the release of catecholamines, such as norepinephrine, which help convert fat calories into heat. Ephedrine-based supplements also promoted thyroid hormone activity while helping to maintain lean mass. When used properly, ephedrine supplements worked well for most people, with a low incidence of side effects.
Activating catecholamines, however, also stimulated the heart and slightly raised blood pressure. In a person not afflicted with cardiovascular disease, the changes were minor and produced no adverse effects. The most common side effect was similar to that of drinking a few cups of coffee. Prominent warnings on the labels of every bottle warned that the supplements were contraindicated for those with certain medical conditions, especially any cardiovascular problem.
Despite the warnings, some people either overdosed on the substance or should not have taken ephedrine supplements in the first place. A few suffered side effects, though in many cases the cause-and-effect relationship between ephedrine use and the onset of symptoms was never definitively proved. That didn’t stop avaricious lawyers from filing countless lawsuits against companies selling ephedrine.
The Food and Drug Administration eventually banned the sale of ephedrine in April 2004. A year later, however, a federal judge said that the ban had a weak scientific foundation and ruled against it. Still, don’t expect ephedrine or ephedra to return to the market. The legal sharks are still swimming, and the insurance rates for a company selling ephedrine would be enormous.
Since ephedrine and ephedra were removed from the market, other substances have been touted for their alleged fat-loss-promoting effects. Some of them, such as green tea, Garcinia cambogia and yohimbe, offer legitimate fat-loss effects under certain conditions. Other natural substances, however, have been overlooked or perhaps not recognized for their fat-loss properties.
One is forskolin, which is found naturally in a plant called coleus. The coleus, which grows in Nepal, India and Thailand—and on windowsills all over the United States—has been used in traditional Ayurvedic medicine to treat various ills, such as skin rashes, asthma, bronchitis and insomnia. The forskolin in the plant can activate cyclic AMP, which then initiates a cascade of biochemical events that result in everything from fat release to hormone release.
Forskolin differs from ephedrine in that it doesn’t interact with beta-receptors in fat cells, so it has none of the stimulation effect associated with ephedrine. In effect, forskolin is a biochemical shortcut as far as fat release is concerned.
Several studies have shown significant fat-loss effects with human subjects who took a forskolin-based supplement. Unfortunately, they were sponsored by the company that holds the forskolin use patent, Sabina Corporation. While such sponsorship may not negate the results of the studies, it does engender a degree of skepticism, since Sabina has much to gain financially from them.
Some critics have noted that the mechanism through which forskolin works, activating cyclic AMP, can have far-reaching effects throughout the body. But toxicity studies have shown no serious side effects or any adverse changes in cardiovascular function. If anything, forskolin appears to offer beneficial effects by lowering blood pressure and increasing beneficial high-density lipoprotein, or HDL.
The most recent study found an additional bonus.1 Thirty subjects were divided into a forskolin group and a placebo group. The study lasted 12 weeks. Those in the first group took a supplement containing 250 milligrams of 10 percent forskolin extract twice daily.
Forskolin produced a significant improvement in fat loss compared to the placebo. But those in the forskolin group also showed a significant increase in levels of free testosterone, the active form of the hormone. Total T levels remained unchanged, but the elevated free-testosterone levels may be a bonus of using forskolin.
Another possible ingredient for an effective OTC fat-loss supplement may be raspberry ketones, which are the compounds that impart the characteristic fruity odor and that new research shows exert a potent fat-loss effect.2 Raspberry ketones are already used as a fragrance in cosmetics and as a food flavoring agent, but scientists found that they structurally resemble capsaicin (from red peppers) and synephrine, found in the Chinese bitter orange.
Both capsaicin and synephrine have thermogenic effects due to their stimulation of norepinephrine release. Synephrine is a major ingredient in many current fat-loss supplements and is touted as the replacement for ephedrine. Since raspberry ketones look a lot like those other compounds, scientists tested the fat-loss effects of raspberry ketone extract in animals.
The experiments clearly showed that raspberry ketones prevented the onset of obesity in mice even when the animals were on a high-fat diet. Using a higher percentage of raspberry ketones (5 percent) prevented the increase in blood triglyceride, or fat, that occurs after you eat a high-fat meal. Raspberry ketones also prevented fat synthesis when rats were overfed fructose, a simple sugar linked to the current obesity epidemic. They appear to help prevent fat deposition—at least in rodents.
Raspberry ketones differ from synephrine in that they enhance norepinephrine-induced fat loss not by activating hormone-sensitive lipase but by promoting the relocation of HSL from the cytosol of cells directly to fat deposits. They also enhance brown-adipose-tissue thermogenesis, though that is far more active in rodents than it is in humans.
Another new study found that an ingredient in licorice, glycyrrhetinic acid, fosters the loss of subcutaneous fat, or fat just under the skin, when applied directly to the skin in a topical cream form.3 Glycyrrhetinic acid appears to work by inhibiting an enzyme that increases cortisol levels in bodyfat; increased cortisol promotes fat deposition. Another version of the same enzyme is promoted by glycyrrhetinic acid in other parts of the body, increasing cortisol levels and leading to a retention of sodium and a loss of potassium, which can result in rapid high blood pressure.
The other form of the enzyme doesn’t exist in fat, however, and applying glycyrrhetinic acid as a cream to fat can block the effects of the enzyme that does, thus preventing cortisol and fat buildup. Blocking the enzyme also leads to localized fat loss, as the study showed. Eighteen women ages 20 to 33 were assigned to a group that used a glycyrrhetinic acid cream of 2.5 percent (80 milligrams) or to a group that used a placebo cream. Both groups rubbed the creams on one thigh for a month.
At the end of the month measurements showed that the thighs of the women who’d used the active cream had lost subcutaneous fat. Only the top, or superficial, layer of fat was affected, however. That was good in a way, since it pointed to a lack of absorption into the internal organ system. The mineralocorticoid receptors that are linked to potassium loss and sodium retention don’t exist in subcutaneous fat, so no adverse effects occurred.
None of the female subjects in this study were fat. The researchers think that the cream would produce more dramatic effects in those with heavier fat deposits. Obese people produce more of the cortisol-producing enzyme, which helps maintain and increase fat deposits.
Licorice itself also produces estrogenlike and antiestrogen effects in different tissues of the body. But they’re from components of licorice that weren’t in the cream used in the study. Licorice blocks androgen synthesis at the level of the adrenal glands, which is more significant to women than men. But that enzyme doesn’t exist in fat either, which makes it a nonissue with the glycyrrhetinic acid cream.
The authors suggest that glycyrrhetinic acid creams may be useful for people who want to reduce excessive fat in a specific location, such as the thighs or abdomen. The cream also offers some obvious bodybuilding benefits for those who experience difficulty in removing fat in isolated areas, such as the thighs and lower abs. You’d still need to diet and exercise to burn the deeper-lying, or visceral, fat deposits, but a glycyrrhetinic acid–based cream might be useful for precontest purposes.
Clenbuterol: Dangerous
Even at Low Doses
Clenbuterol is a beta-2 adrenergic agonist, which means that it interacts with adrenergic beta-2 receptors. In plain English, clenbuterol mimics the effects of catecholamines, such as epinephrine and norepinephrine. Those hormones dilate bronchial tubes. Clenbuterol also dilates them, explaining its primary use to treat asthma.
Although clenbuterol is available in other countries, such as Mexico, under various trade names, it was never approved for use in the United States and isn’t likely to be in the future. The lack of interest by American drug companies is related to clenbuterol’s long half life in the body. Unlike other beta-2 agonists used to treat asthma, which degrade in about six hours, clenbuterol takes nearly two days to fully degrade. That considerably increases the chances of side effects. What’s more, clenbuterol isn’t superior to other available drugs for treating asthma.
Bodybuilders and other athletes became interested in clenbuterol after research showed that it promotes a gain in muscle mass and a loss of bodyfat in various animals. In their enthusiasm over those findings, however, most athletes and “drug gurus” failed to read the small print: The animals were given doses that would kill a human.
Despite that considerable problem, clenbuterol quickly gained a reputation as a muscle-building fat-loss drug. Users soon realized that its active life could be measured in just a few weeks. The beta-2 receptors that clen interacts with were extremely sensitive and shut down after about a month. When that happened, clen did little or nothing.
As the research continued, some disturbing facts emerged. Case reports pointed to clen as being the probable cause of such adverse effects as tachycardia (rapid heartbeat), heart attack and even kidney failure in athletes who abused it. Clen may have played a major role in the death of a popular pro bodybuilder a few years ago. That bodybuilder, who died from heart failure, was known to have injected large doses.
Other animal studies showed that clen and aerobic exercise were a bad combination, since clen seemed to interfere with aerobic endurance. Some animals had sudden heart failure when given clen and then forced to exercise. Autopsies of the animals found an abundance of collagen in their hearts, pointing to production of scar tissue, which in the heart is a signal of failure.
While much of the damage clenbuterol causes is ascribed to using large doses, a recent study that used rats as subjects found that even in low doses it promotes cellular death in both the heart and slow-twitch muscles.4 The implication is that there’s no such thing as a safe dose. Since the drug doesn’t promote muscle size increase in people and works only short-term for fat loss, you can safely conclude that there’s no rational health reason for any athlete to use it.
References
1 Godard, M.P., et al. (2005). Body composition and hormonal adaptations associated with forskolin consumption in overweight and obese males. Med Sci Sports Exer. 37:S39.
2 Morimoto, C., et al. (2005). Anti-obese action of raspberry ketone. Life Sci. 77:194-204.
3 Armanini, D., et al. (2005) Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application. Steroids. (2005). 70:538-42.
4 Burniston, J., et al. (2005). B-2 adrenergic receptor stimulation in vivo induces apoptosis in the rat heart and soleus muscle. J App Physio. 98:1379-86.
©,2013 Jerry Brainum. Any reprinting in any type of media, including electronic and foreign is expressly prohibited.
