Mary Linnen, George Korizis, Rosanna Porras, Metabolife, synergy, fenfluramine, ephedra, Redux, bitter orange, synephrine, stimulants, yerba mate, anhydrous caffeine, guarana, yohimbe, MAO inhibitor, St. John’s wort,

Weight Loss Roulette

Weight Loss Roulette

Twenty-nine year old Mary Linnen was like many brides to be. She wasn’t obese (she was a tennis player and had captained her high school swim team), but she still wanted to shed a few pounds before her wedding so that she would look her best in a simple wedding gown.

To facilitate weight loss, Mary obtained a prescription for the popular weight-loss drug combination Fen-phen from her personal physician. She lost ten pounds in just 23 days on the drugs, but discontinued them due to the appearance of a rapid heart rate and shortness of breath.

After stopping the fen-phen her symptoms slowly resolved. They returned five months later, however. Studies revealed that she had developed primary pulmonary hypertension, a rare, but nearly always fatal, condition. She died suddenly and unexpectedly six weeks later. She never purchased the wedding dress she had lost weight to wear.

George Korizis was pursuing his Master’s degree in mechanical engineering at Tuft’s University. He was a health-food enthusiast who never smoked and rarely drank alcohol. He worked out regularly, and used Ripped Fuel, a supplement containing ephedra, to induce fat loss and help build muscle. He died unexpectedly. An autopsy revealed that his heart contained multiple small areas of dead tissue, a known complication of stimulant use.

Rosanna Porras was an active 15 year old who enjoyed playing soccer. She found that taking a weight loss supplement containing ephedra would give her a competitive edge. On April 8, 1998, Rosanna collapsed during practice and never regained consciousness.

The untimely deaths of Mary Linnen, George Korizis, and Rosanna Porras are only a few that have been associated with the use of stimulants for weight loss or increased energy. Mary Linnen’s story was reported in the August 28, 1997 issue of New England Journal of Medicine and was one of many that led to the withdrawal of fenfluramine (Pondimin – the “fen” of “fen-phen”) and dexfenfluramine (Redux) from the U.S. market in September 1997. The February 2003 death of Baltimore Orioles’ pitching candidate Steve Bechler created a firestorm that led to a ban of ephedra sales in 2004.

The leading distributor of ephedra products in the United States was a company called Metabolife. Its best-selling formulation, Metabolife 356, combined ephedra with another herbal stimulant, guarana. Another, Metabolite-Plus, combined ephedra with caffeine.

When substances are combined, a phenomenon called synergy often occurs. Synergy describes a situation in which the effect of the whole compound is greater than the sum of its individual parts. If substance A has an effect of 3 and substance B produces an effect of 4, for example, the synergistic combination might produce an effect of 9.

Synergy can be and often is used to amplify the beneficial results of a product. Unfortunately, synergy is also capable of dramatically increasing the adverse effects of substances when they are used in combination. This was certainly the case with fen-phen and ephedra/guarana and ephedra/caffeine combinations.

Fenfluramine (Pondimin – the fen of fen-phen) had been marketed in the United States since the early 1970s, but had never risen to more than 10,000 prescriptions per year. That changed dramatically when Dr. Michael Weintraub reported success in treating obesity using a combination of fenfluramine and phentermine. Sales of Pondimin jumped to $173 million in 1996 and it is estimated that 6 million people in the United States took the drug combination.

Adverse effects rose accordingly. Memory difficulties and mood changes were quite commonly reported. Blood pressure elevation was often seen. Reports of pulmonary hypertension and heart valve abnormalities appeared with increasing frequency.

On October 7, 1999, the American Home Products Corporation agreed to pay $3.75 billion in compensation to individuals who believed they were injured by taking fen-phen. It was one of the largest product liability settlements ever recorded.

Ephedra had been used in herbal medicine for centuries, but sales of ephedra did not take off until Michael Ellis and Michael Blevins, who had been found guilty of conspiracy to manufacture methamphetamine in 1991, discovered that combining ephedra with guarana could produce amphetamine-like effects. At its peak Metabolife 356 sales topped $ 900 million annually.

Although no safety studies had been conducted on the products, Metabolife executives assured customers that the products were safe. In 1998, Michael Ellis told federal investigators that they company had never received any communication from a consumer questioning the safety of Metabolife products. Metabolife executives repeated this statement in 1999, but in 2002, under mounting pressure, they released 13,000 consumer complaints dating back to 1997, including 80 allegations of serious injury or death related to use of Metabolife products.

Faced with falling sales along with hundreds of personal injury lawsuits, Metabolife filed for bankruptcy protection in June 2005. Personal injury claims against the company, its retailers and its insurers exceed $1 billion.

At least 150 companies were manufacturing dietary supplements containing ephedra at the time it was banned. The status of ephedra-containing products in the United States is muddy at the present time. In April 2005 a Utah judge overturned the FDA ruling banning the sale of all ephedra-containing products. In 2006, California, New York, and Illinois reinstated sales of ephedra products. In September 2006 a 3 judge panel of the 10th circuit court of appeals overruled the Utah decision, and an appeal to the entire 10th circuit court has been requested. If the appeal is allowed, the case could ultimately go to the United States’ Supreme Court, with the decision having wide ramifications regarding FDA oversight of manufacturers of nutritional supplements.

It should be noted that ephedra, as a stand-alone agent, is safer than most drugs on the market today. While I discouraged people from using high-dose ephedra combined with other stimulants for energy or weight loss, I did recommend low dose ephedra as an asthma management tool on several occasions. It was very helpful in lessening the degree of airway restriction, and did so with fewer side-effects than bronchodilating drugs. The FDA would have been wiser to ban stimulant combinations rather than single out ephedra. Unfortunately, governmental bureaucracies are not noted for their ability to exhibit wisdom and common sense.

If Pondimin, Redux, and ephedra had been the problem, I would not be writing this newsletter. Ironically, the withdrawal of fen-phen and the ban on ephedra have resulted in the development of stimulant combinations that are, in many cases, more dangerous than those that are no longer available.

The demand for pills that boost energy and promote weight loss is still present, and there is no shortage of companies that are willing to supply them. Just as I spent many hours in the 1990s counseling individuals to avoid fen-phen and ephedra-caffeine combinations, I am finding myself advising ever increasing numbers of individuals to avoid stimulant weight loss products and helping others who are experiencing health challenges resulting from the use of the formulations.

As the old saying goes, “De Nile ain’t jus’ a river in Egypt!” Metabolife owners maintained to the bitter end that their herbal combinations were safe. Shortly before Redux was withdrawn from the United States marketing due to the appearance valvular heart disease and pulmonary hypertension in people using the drug, Dr. Richard Wurtman, the researcher whose work led to its release, stated, “In the end, truth will win out and Redux will have a major impact on obesity in America because it works and it's safe.”

Promoters of the current wave of stimulant combinations also insist that their products are safe. The owner of a company promoting one of the most dangerous herbal combinations on the market recently responded to my advice to an individual that she and her husband not take the product by saying, “This is a dream come true for weight loss . . .This is all natural as if it were someone out eating a plant in a field.”

The “All natural” argument is patently ridiculous. Socrates committed suicide by consuming hemlock, a plant. We eat the fruit of tomatoes and the tubers of potatoes, but the leaves of both plants are poisonous. Children die from eating mistletoe berries, and the leaves are also toxic. One castor bean can kill a child and three can kill an adult. Oleander, containing over 50 toxic compounds is so dangerous that using its branches in a cooking fire is enough to cause poisoning.

Some argue that the herbal energy/weight loss products are safe because similar stimulants are readily available in decongestant cold medications. It is true that ephedrine and synephrine are found in dozens of over-the-counter cold preparations, but that does not mean that those products do not produce undesirable side effects. We live in a society that has a tremendous tolerance for pharmaceutical side effects, including death. Individuals can and do die from reactions to decongestant preparations. If the stimulants in cold medications were herbs rather than patented chemicals they would be banned immediately.

The argument that serious reactions to stimulant diet products are “rare” is also specious. It is impossible to predict in advance who is going to develop a life-threatening complication from using a product or when the challenge will occur. Relying upon statistical odds as a measure of safety is deceiving. It is playing weight loss roulette. Statistics do not apply to individuals. If you are the 1:1000 that becomes disabled or dies from using the product your personal incidence of an adverse event is 100%!

Even before the ban on ephedra sales was announced, the search was on for alternative substances. The energy/weight loss supplement industry quickly settled upon Citrus aurantium fruit as the stimulant of choice. The fruit is referred to as zhi shi in traditional Chinese herbal medicine and it is also known as green orange, sour orange, and bitter orange. It may be listed by any of those names on a product label, so it is important to look for each of them. Nearly all stimulant weight loss products use citrus aurantium extract as the primary ingredient.

The primary active compound in bitter orange is synephrine. Synephrine is chemically similar to ephedrine and pseudoephedrine, which are found in many cold preparations. Ephedrine and pseudoephedrine are potent stimulants. It is of interest to note that the State of Oklahoma restricted the sale of these drugs to discourage the proliferation of methamphetamine labs in the state, an action that has been very successful in limiting “meth” production.

Like ephedra, citrus aurantium has traditionally been used to ease chest tightness or congestion. As was true of ephedra, citrus aurantium has the potential to cause adverse effects including heart arrhythmias and high blood pressure. Like all stimulants, bitter orange will lead to adrenal fatigue if used on a continuous basis. Used alone, in low dosage, and for short periods of time it, like ephedra, is safer than most drugs used for congestion. Used in this manner, however, the herb is of little benefit in creating energy or promoting weight loss.

It is when zhi shi is combined with other stimulants that an amphetamine-like effect is created. This produces a chemical rush or high along with a decrease in appetite. It also increases the metabolic rate, which improves weight loss. As the energy and weight loss effects increase so do the severity and frequency of undesirable effects.

Approximately a year ago I was contacted by a man in his early forties. He had always been active and enthusiastic, but he had come to the point where he was struggling just to get through each day. He had developed high blood pressure and had experienced a serious irregularity of his heart. He had been placed on several blood pressure medications, a potent anti-arrhythmic drug, and the blood-thinning agent, Coumadin. He had been told that he would need to remain on the drugs for the rest of his life, but they were severely compromising his ability to function and he was looking for alternatives.

While taking his medical history I learned that his current challenges had begun after he had been taking an energy supplement for a number of months. He had felt great when he started the supplement and he loved the extra energy he felt while taking it. The supplement contained zhi shi, but other stimulants were also present. These included yerba mate’, anhydrous caffeine, and guarana. It is currently marketed under the trade name Adimene.

Yerba mate’ is obtained from the leaf of a South American evergreen. The leaves have a very high caffeine content. Side effects include difficulty sleeping, nervousness, restlessness, stomach upset, nausea and vomiting, an irregular heartbeat, and increased blood pressure. It also contains substances that are believed to be carcinogenic (cancer-causing) and capable of producing liver failure. The substance is addictive. All of its adverse reactions are increased in the presence of other stimulants, and it increases the risks of side effects with many drugs including asthma medications, quinalone antibiotics, Tagamet, decongestants, MAO inhibitors, diabetic medications and several blood pressure medications.

Anhydrous caffeine is pure, pharmaceutical grade caffeine that has been extracted from plant sources. It is used as a stimulant and is often combined with aspirin or acetaminophen to enhance their pain-relieving properties. Caffeine’s stimulant effects are quite pronounced and side effects are common. These include diarrhea,dizziness a fast or irregular heartbeat, sleep difficulties, nervousness, irritability, and high blood pressure as well as many others.

Guarana is obtained from a low-lying vine that grows in the Amazon basin. Its seeds have been used to produce a beverage for centuries and soft drinks containing guarana are very popular in South America. Taken alone, it is less stimulating than coffee, and has fewer adverse effects. It can still trigger nervousness, sleeplessness, and an irregular heartbeat, however. It produces a marked synergistic effect when combined with other stimulants.

I reasoned that most, if not all, of the challenges the man was facing were due to the effects of the combined stimulants. I encouraged him to stop the energy supplement and begin providing his body basic nutrients needed for maintenance and repair. Within three months he was able to stop all medications, and he is once again pursuing his activities with enthusiasm and vigor.

Recently, I have learned of a particularly dangerous turn being taken by some energy/weight loss supplement manufacturers. That is the addition yohimbe or St. John’s wort, herbs that inhibit the action of an enzyme called monoamine oxidase, to stimulant combinations. At least one company is marketing a product that combines both yohimbe and St. John’s wort with multiple stimulants.

Monoamine oxidase breaks down neurotransmitting chemicals including serotonin, dopamine, adrenaline (epinephrine), and non-adrenaline (nor-epinephrine). Drugs or herbs that block the action of monoamine oxidase are called MAO inhibitors. They are generally used for treatment of depression that does not respond to other agents. This is because MAO inhibition can lead to sudden and potentially fatal elevations of blood pressure if certain foods are eaten or if MAO inhibitors are combined with cough and cold medications.

Adding a substance that slows the breakdown of adrenaline and nor-adrenaline can significantly potentiate and prolong the effects of stimulants. This can dramatically boost the “kick” obtained from energy/weight loss products, but it is a dangerous game to play.

Yohimbe is obtained from a tree bark. Yohimbe has been known to induce excessive stimulation, anxiety, panic attacks, high blood pressure, increased heart rate, irritability, headache, nausea, skin flushing, sweating, dizziness, frequent urination, water retention, a rise in body temperature, hyperactivity, weakness, paralysis, gastrointestinal problems, hallucinations, psychosis and even death. Combining the herb with the common over-the-counter cough suppressant, dextromethorphan, can be fatal. Yohimbe should not be mixed with any food or drink that contains high amounts of tyramine (all wines, beer and ale; cheese, products made with large amount of yeast, salami, sausage, bologna, pepperoni, pickled herring, meat extracts, chicken liver, salted dried fish, avocado, tomato, green bean pods, eggplant, Italian broad beans, banana, red plums, oranges, figs, raisins, soy sauce, bouillon cubes, soya, stored beef). A fatal reaction can occur if it is combined with the amino acids tyrosine or phenylalanine. (Incredibly, Re-Charge, a product that combines yohimbe and St. John’s wort also contains L-tyrosine.)

St. John’s wort has a long traditional use as an antidepressant, probably because it has an MAO inhibiting action. When used as a stand-alone substance its active agent, hypericum, is relatively safe, but when it is combined with stimulants the same risks as those listed for yohimbe apply. Using it in combination with yohimbe is a recipe for disaster because of the synergistic effects on MAO inhibition.

I am under no illusion that people will stop seeking short cuts to increased energy and weight loss, nor do I expect there to be a shortage of companies eager to supply them and reap the high profits associated with addictive products that provide instant gratification. I sincerely hope, however, that you will recognize the dangers of stimulant combinations and avoid products that boast two or more synergistic substances such as bitter orange, caffeine, yerba mate’, cola nut, ginseng, guarana, yohimbe, and St. John’s wort. If in doubt, leave the bottle on the store shelf.

Don’t play weight loss roulette. If you lose, you may not live to enjoy the temporary boost of energy and transient weight loss combination stimulants provide.