Tatyana

The lab I did a lot of my training in had been assisting one endocrinologist in investigating the super elevated heart rate of one woman.

He asked her was she taking anything, and she always said NO, while her hubby was there, however one time when he wasn't, she did admit to taking chinese 'herbal' remedies for weight loss.

Doc asked her to bring them in, and they were supposedly Ma Huang. When we ran analysis on them, it was found that they were contaminated with fenfluroamine, or FEN FEN, an amphetamine that HAS been banned in the US and UK for causing heart valve defects and elevated heart rate.

Loads of these 'little yellow pills' from across the country were investigated and most were found to be contaminated with Fen Fen.

SO, it was not really a 'herbal' remedy afterall.

Make sure you get herbal remedies from a good manufacturer, and one that does screen for impurities.

I did check with Muscle Tech and Universal, often they do have statements of their screening and quality control on their websites.

x
x
x
T

Tatyana

---

The Biological Dangers of Fen-Phen and Subsequent Political and Social Issues

Molecular Neurobiology and Neurochemistry

MCB 165

May 6, 1999

Keywords: Fenfluramine, Phentermine, Heart Disease

Abstract

Fenfluramine-Phentermine (fen-phen) and dexfenfluramine (Redux) have been shown to cause primary pulmonary hypertension (PPH) and valvular disease of the heart.

The latter, more detrimental side effect was discovered when noticing the connection between carcinoid syndrome, ergotamine overdose, fen-phen consumption, and dexfenfluramine intake. All of these conditions led to peculiar heart valve defects, and all involved an increase in serotonin concentrations. Phentermine, fenfluramine, and dexfenfluramine were all individually approved by the Food and Drug Administration (FDA), but the agency never approved the fen-phen combination. At the same time, they did not actively intervene and conduct safety tests regarding fen-phen use either. The FDA, various weight loss clinics, negligent physicians, and overall social issues are among those at fault for this medical mishap. Diet pills should only be administered to medically obese patients. The solution is to promote public health measures that focus on preventative measures and educate the public.

Introduction

As technology has progressed over the years, the abundance and supply of food have scarcely posed a dilemma in industrialized, modern societies. Consequently, the question is no longer a matter of "if" we are going to eat, but more so "what" we are going to eat. By virtue of our abundant standard of living and various other factors, it is no surprise that many individuals fall victim to obesity. Obesity in this context is defined in terms of a biomedical perspective, versus relative connotations involving social stigmas and values. More specifically, this paper will address three particular widespread pharmaceutical treatments people have embraced in order to achieve weight loss, and the intricate medical, social and political implications involved.

The diet pills of interest are fenfluramine (Pondimin), phentermine (Ionamin, Fastin, Adipex), and dexfenfluramine (Redux). The combined use of fenfluramine and phentermine ("fen-phen") has been especially popular amongst individuals seeking to combat their weight through simple drug medications. Fen-phen's popularity can be attributed to the efficacious weight reduction therapy it exhibits, in other words, it successfully sheds pounds off the body. Not surprisingly, "Up to 10 million obese people have been treated, reversing the trend in recent years toward increasing obesity in the US population (Griffen and Anchors 1998). Unfortunately, fen-phen and dexfenfluramine have been shown to cause primary pulmonary hypertension (PPH) and various heart conditions (Rheingold 1998; Fackelmann 1997).

Primary Pulmonary Hypertension

Phentermine, fenfluramine, and dexfenfluramine (the purified d-isomer of fenfluramine) have all been categorized as pulmonary hypertensives (Connolly et al. 1997). In addition to suppressing hunger by perturbing the limbic system, these amphetamine derivatives possess serious side effects. Each of these drugs induces high blood pressure within the lungs.

The lungs are important for the respiratory functions they perform. This vital organ is highly vascularized in order to provide all of the body's cells with needed oxygen and excrete waste products such as carbon dioxide. Thus, it is evident that high blood pressure within this region is both unfavorable and unhealthy. Studies have shown that these diet pills "cause pulmonary hypertension through the vasoconstrictor action of serotonin or by altering the depolarization of pulmonary vascular smooth-muscle membrane" (Connolly et al. 1997). PPH was considered a rare side effect until widespread use of the drug began to take place and more cases started to unfold (Rheingold 1998). Although all three of these drugs play a role in PPH, the main culprits of this side effect are fenfluramine and dexfenfluramine. Both have been linked to a staggering thirty-fold increased risk for developing cardiopulmonary symptoms characteristic of PPH (Griffen and Anchors 1998).

One of the dangers of PPH besides the disease itself, is that it is often very difficult to diagnose PPH symptoms when treatment is necessary. Some of these obscure symptoms include loss of stamina, swelling in the extremities, and difficulty breathing. An example of the dangers of PPH can be seen in actions taken by the French government in 1995. The pervasive use of dexfenfluramine (Redux) in France gave rise to so many cases of PPH that the government strictly enforced limited use to severely obese patients (Rheingold 1998). In addition, a documented case of a young, 29-year-old woman who died of PPH eight months after a 23 day regimen of fen-phen, further delineates the dangers of these drugs (Fackelmann 1997).



Fen-Phen, Dexfenfluramine, and the Heart

The possible detrimental side effects of PPH did not lead to a recall of fenfluramine (Pondimin) and dexfenfluramine (Redux). Rather, a more astonishing side effect of these drugs brought about such action. Researchers found that fen-phen users exhibited "waxy deposits on their heart valves" which prevent the valves from normal closure and alter the complex pumping mechanism of the heart (Cowley and Springen 1997). The findings of the Mayo Clinic in Rochester shed deeper light into the dangers of consuming these drugs.

The physicians at the Mayo Clinic discovered 24 cases of women (in their thirties and forties), who had been using fen-phen for about a year, that manifested heart valve damage (Rheingold 1998). Initial tests showed that the women suffered from fatigue, breathing abnormalities, and heart murmurs. A more in depth survey of the problem using an echocardiogram (which shows the dynamics of the heart through the use of sonographic images) confirmed the presence of damaged (leaky) heart valves (Fackelmann 1997). Since heart valve disease can be categorized as either rheumatic, degenerative, myxomatous, or congenital, rare deviances (as seen in this particular case) foster much curiosity (Boughner 1997). The Mayo Clinic noticed that the women all had very similar types of heart impairments, pointing to the idea that these damages were the result of fen-phen intake. The women's heart valves "appeared thickened, with reduced leaflet or cusp motion, implying rigidity" (Boughner 1997). Furthermore, all of the women who had impaired heart valves showed forth resembling symptoms of "murmur, dyspnea, edema, palpitations, congestive heart failure, chest pain, and in one case, supraventricular tachycardia" (Rheingold 1998). Valve damage in the heart is a serious condition. These valves serve to prevent the backward flow of blood from the ventricles to the atrium and other regions, allowing for efficient pumping to take place. Leaky or damaged valves force the heart to work at a higher degree of intensity, which can ultimately lead to heart failure.

How did the Mayo Clinic come to the decision to gather 24 women who had taken fen-phen, in order to analyze their heart conditions? A Mayo clinician recalled a woman that was on a fen-phen regimen, who underwent surgery for her damaged heart valve. The clinician distinctly remembered the surgical chart, which described the valves as having a waxy, glistening white appearance, a strong indication of an ergotamine overdose. However, the Mayo doctor learned that the patient was never prescribed ergotamine, a migraine therapy drug. Ergotamine is homologous to the serotonin neurotransmitter. Well aware of the fact that phentermine and fenfluramine change the body's serotonin levels, Mayo doctors hypothesized that these diet drugs damaged the heart by perturbing serotonin circuits (Fackelmann 1997). Moreover, the distinct waxy appearance of damaged heart valves as seen in fen-phen users was also observed in patients with carcinoid syndrome. Carcinoid syndrome is a rare cancer that leads to impaired heart valves as a result of high serotonin concentrations within the body. Hence, the connection was made between carcinoid syndrome, ergotamine overdose, fen-phen consumption, and dexfenfluramine intake. All of these conditions led to peculiar heart valve defects, and all involved an increase in serotonin concentrations.

Although these findings are very suggestive, no absolute conclusions can be made. Pondimin (fenfluramine) and Redux (dexfenfluramine) patients were only given echocardiograms after beginning their medication. As a result, it is impossible to make comparisons between echocardiographic data both before and after drug intake. However, there is a definite correlation between the effects of these diet pills and excess endogenous serotonin levels (Cowley and Springen 1997).



The Food and Drug Administration (FDA) and Fen-Phen

Why did the Food and Drug Administration (FDA) allow the use of fen-phen and dexfenfluramine (Redux) to take place? One misconception regarding this issue is that the FDA approved the consumer use of fen-phen. However, the FDA did not disapprove of



this combined concoction either. Phentermine, fenfluramine, and dexfenfluramine all had the "FDA's blessing as stand-alone treatments for obesity, but the agency had never approved the combination [fen-phen]" (Fackelmann 1997).

How did the fenfluramine-phentermine duo gain it's widespread popularity despite the absence of a formal FDA endorsement? In 1992, the "fen-phen craze" sky-rocketed after experimental results became available to the public eye in the form of an "obscure" medical journal. The experiment boasted of an average loss of 30 pounds in 121 overweight patients as a result of taking both fenfluramine and phentermine in combination (Rheingold 1998). Embracing the findings of this experiment as "gospel", thousands upon thousands of people began to take these pills together as part of their diet. In essence, many individuals, agencies, researchers, and doctors failed to take into consideration that this same finding which promised rapid weight loss, never examined the overall safety of consuming these drugs concurrently. Once again, it must be reiterated that the FDA individually approved the use of fenfluramine and phentermine as appetite suppressants for individuals deemed obese by medical standards (Connolly et al. 1997). In a sense, the FDA committed a sin of omission rather than a sin of commission. They failed to do what they ought to have done, which should have been to prohibit the combined use of fen-phen until thorough studies on it's safety could be performed.



Basic Mechanisms of Fen-Phen and Redux

How do fen-phen and dexfenfluramine (Redux) bring about weight loss in individuals? These drugs function primarily by means of the body's nervous system. Phentermine, an amphetamine relative, is a noradrenergic agent that works on dopamine and norepinephrine circuits. It has the effect of increasing the body's metabolism.

Fenfluramine is a sympathomimetic amine, which is a substance that enhances sympathetic functions in the body. It increases the concentration of serotonin neurotransmitters within the brain, allowing satiety centers to be stimulated. Thus, it is deemed an appetite suppressant (Rheingold 1998). Although fenfluramine has been available in the United States for over 25 years, it's sales have increased exponentially within the span of a few years after "researchers found that the stimulant phentermine could offset the fatigue fenfluramine induced" (Cowley and Springen 1997). The fen-phen combination decreases the need for higher dosage levels of each drug, while hampering unwanted side-effects and mitigating patient intolerance (Connolly et al. 1997).

Dexfenfluramine, the purified d-isomer of fenfluramine, has the same overall mechanism of action as fenfluramine in that it functions through serotonin pathways. However, it has increased selectivity for the central serotonergic system (Connolly et al. 1997).

As mentioned earlier, these drugs induce weight loss at a costly price. The main ingredients responsible for causing dangerous side effects to be manifested, are fenfluramine and dexfenfluramine. They both operate on serotonergic circuits and wreak havoc on the body's physiology by maintaining high serotonin neurotransmitter levels in the brain and other vital regions. Animal studies have shown that fenfluramine and dexfenfluramine produce long term neurotoxic effects by stimulating nerve terminal degeneration (Rheingold 1998).



Who's at Fault?

Who is to blame for all the negative consequences that have come upon consumers taking these diet pills? As stated previously, the FDA failed to prohibit the combined use of fen-phen until thorough studies on it's safety could be performed. They were well aware of the fact that countless people were taking their individually approved drugs in combination, yet there was no government intervention. An interesting political aspect of this issue can be observed when noting that:



In 1995, the FDA's advisory committee initially voted against approving the drug, but later that year the committee recommended approval by a 6-5 vote. Lawyers who have studied the minutes of the two meetings have found that many doctors warned of serious risks from abuse of Redux, and there is some evidence that the second vote was taken when the doctors who were most vehemently opposed to approval were absent. (Rheingold 1998)



Although the FDA's negligence in handling this situation was rather serious, the pharmaceutical companies deserve much of the blame as well. The FDA approved the use of Redux for medically defined obese patients (with standard body-to-mass indexes). Those who were administered the drug had to be under careful supervision from medical personnel who specialized in the field of weight loss therapy, and patients were required to complement their drug consumption with proper diet and exercise plans.

Nevertheless, Wyeth-Ayerst Laboratories (the producers of Redux and Pondimin) sent company representatives to doctors from all kinds of specialty fields, not just physicians working specifically with obesity, in order to promote their new miracle drug (Rheingold 1998). These drug companies were extremely negligent in that they failed to warn consumers of the potential dangers associated with the use of their products. Instead, these drugs were promoted as being efficacious in their functions while being free of any side effects.

Many doctors and countless weight loss clinics are just as guilty of this diet pill epidemic. Clinics across the nation often used these drugs as a criteria for joining their weight loss programs, without communicating the risks involved in using such medications. The doctors who were employed in these rash clinical programs prescribed these diet pills with little or no patient examinations (Rheingold 1998). To make matters worse, "many diet clinics hired doctors who were willing to prescribe the fen-phen treatment not just for obese people, but for the mildly overweight as well" (Fackelmann 1997). It is evident that various clinics sought after capital gain at the cost of ethical medical practice as outlined by the FDA in distributing these drugs. In other words, both these clinics and their doctors were intentionally negligent.

It is not surprising, therefore, that many women who developed severe complications associated with the use of these drugs were not morbidly obese, but rather they merely wanted to "slim down" a little (SoRelle 1997). Many clinics and doctors exacerbated the situation by distorting the existing negligent boundaries set forth by the FDA regarding the "proper" use of these diet drugs.



The Exception

Are all FDA approved diet medications unsafe to the consumer? It must not be forgotten that the use of these diet pills was geared toward medically obese patients, not to self conscious individual seeking to shed a few unwanted pounds. Many people who suffer from medically defined obesity are at high risk for developing severe hypertension and heart disease and would benefit from certain FDA approved diet drugs, despite their potential dangers (Fackelmann 1997). More specifically, physicians should prescribe drug weight loss therapy for patients whose body mass index exceeds 30, or exceeds 27 for individuals with existing obesity related medical conditions (Griffen and Anchors 1998).

Presently the FDA has made it clear that physicians should not administer any forms of fenfluramine or dexfenfluramine. As a result of this particular drug embargo, many "obesity specialists are touting a new Prozac-based concoction as a safe alternative to fen-phen" (Cowley and Springen 1997). Prozac, or fluoxetine, is an antidepressant that raises serotonin levels in the nervous system and aids in decreasing appetite. However, many argue against this "phen-Pro" combination by claiming that it is merely another untested mixture that might prove to be harmful as well (Fackelmann 1997). Their rationale is that Prozac functions in a similar mechanism as fenfluramine. Proponents of the phen-Pro duo counteract these claims by pointing out that Prozac acts on serotonin circuits in a milder fashion than fenfluramine.



The Solution

As we can see the issues are extremely complicated and they involve millions of people across the United States and the entire globe. In general, the underlying problem is the attitude many have taken in regards to health care. This is highlighted in the fact that, "Millions of overweight Americans saw fen-phen and Redux as magic bullets (Napier 1997). The trend in recent years has been to associate the concept of health care with disease care. Less emphasis is being placed on effective preventative measures, while the demand for disease treatment increases. Individuals must cease to place their hopes on "magic bullets" that will painlessly zap excess fat without a change in diet and overall lifestyle. Society must stop the futile search for a quick fix. At the same time, we must be cautious not to engage in a "blame the victim" mentality toward obese patients who have suffered the consequences of dangerous, quick fix diet pills. Rather, society should promote social awareness, prevention, and be weary of rapidly embracing the next FDA approved magic bullet.

References

Aurigemma, G.P., Gaasch, W.H. Valve disease and diet pills - where do we stand? American Family Physician 57 (4): 656-658 (1998).

Boughner, D.R. A dangerous duo? A combination of common diet drugs (fen-phen) may lead to heart valve disease. Canadian Medical Association 157 (6): 705-706 (1997).



Connolly, H.M., Crary, J.L., McGoon, M.D., Hensrud, D.D., Edwards, B.S., Edwards, W.D., & Schaff, H.V. Valvular Heart Disease Associated with Fenfluramine- Phentermine. The New England Journal of Medicine 337 (9): 581-588 (1997).



Cowley, G., Springen, K. After Fen-Phen. Newsweek 130 (13): 46-48 (1997).



Fackelmann, K. Diet drug debacle. Science News 152 (16): 252-253 (1997).



Griffen, L., Anchors, M. Asymptomatic Mitral and Aortic Valve Disease Is Seen in Half of the Patients Taking 'Phen-Fen'. Archives of Internal Medicine 158 (1): 102 (1998).



Napier, K. No more diet pills - what now? Prevention 49 (12): 39-40 (1997).



Rheingold, P.D. Fen-phen and Redux: a tale of three drugs. Trial 34 (1): 78-82 (1998).



SoRelle, R. Fen-Phen and Risk of Valvular Disease. Circulation 96 (6): 1705-1706 (1997).


Ok so phen-fen caused IRREVERSIBLE DAMAGE to the heart. There are also studies on how diet drugs are messing up the brain's neurochemistry.

IMHO, just a quick fix to 'cut up for a holiday' or to 'look good for the summer, is really quite a silly reason to take a T3/clen stack.

I think it would be far better to acutally look at why you are NOT motivated to eat in a healthy manner or do cardio. And then just get on with it.

The long term medical implications of LOADS of self-medicating drugs may not surface for a number of years...................................

No offence, some of you lads are really clued up, but how many found A-level biology a bit difficult? And now you are going to self prescribe some of the most potent drugs like steroids and fat burners. And I think I am blonde.

Respect

x
x
x
T

hackskii

I had a friend on that crap along time ago (fen fen), he did lose alot of weight but I swear looking at him it was muscle.
He was commenting on how many inches he lost in his weight.
This was about 10 years ago and I was doing a zone type diet. At that time I was losing 1 inch for every 5 lbs of weight loss, he lost 1 inch for every 10 lbs of weight loss.
His shoulders disappeared and he looked like he lost alot of muscle.
He was happy with the success and I didnt have the heart to tell him he looked like crap and his diet was rubbish.
After comming off he gained all the weight back, now I wonder if his heart has any left over implications of damage? Hmmmmm
Not worth it.

__________________
Scott

ONE SMART COOKIE

Epherdrine is banned in the UK and can carry a long term in the clink, the main reason being that it can and has been converted into other recreational drugs through the use of a few household items......

I think it is 7 years if you are caught dealing in the stuff.....