Ask Dr. Dan: PPA and the FDA

Q: What’s the latest on PPA? Did the FDA ban it?

A: PPA is the active ingredient in many over-the-counter weight-loss products. The best known PPA product is, or was, Dexatrim. PPA has been used for decades with what has been considered an excellent safety record. Obesity, which is now recognized as a strong risk factor for a variety of diseases, has become more prevalent in the past 10 to 20 years. Factors for its growth rate include changes in occupational and recreational trends (sedentary jobs and hobbies) as well as nutritional and dietary factors (portion sizes, calorie content and so on).

Obesity now affects 54 percent of adults in the United States, and there has been a dramatic increase among children as well. The obvious solution for 85 to 90 percent of obese people is to alter their diet and exercise; however, it requires a level of commitment and willpower that many people lack.

There are chemical means of treating some of the triggers that lead to weight gain. Some of them are stimulants that increase the rate of calorie burning, which leads to weight loss. Others act by suppressing appetite, leading to slower weight gain or even weight loss if you create a calorie-deficient state.

The chemicals may be herbal, like mahuang; over-the-counter pharmaceuticals, such as PPA or caffeine; or pharmaceuticals requiring a prescription, such as the now withdrawn fenfluramine and dexfenfluramine (the ‘fen’ in fen-phen).

What differentiates the classes is the source of the agent and its safety record. Propensity for abuse may also cause an agent to be named a controlled substance. GHB, for example, became a controlled substance due to the harm caused by those who abused the drug. The market for weight-loss products in the United States is huge. Billions of dollars are spent annually on weight-loss pills, supplements, sugar substitutes, low-calorie meals, health club memberships and so on. PPA reportedly sold at a rate of more than 6 billion doses per year. Ephedrine was taken from the market, although it has been subsequently returned in many states. Mahuang will be next to go and should have gone first, if you want my opinion. Frankly, I consider a USP-grade, metered dose to be more reliable and predictable than a plant extract of considerable variability. Even the big companies can’t control their ephedra products; however, ephedrine was abused as a party drug and did have a record of adverse events, so it has rightly been subjected to greater scrutiny.

Fen-phen was one of the hottest-selling prescriptions of all time. It was wonderfully successful. Patients who had previously failed numerous diets were able to drop 20, 30 even 50 or more pounds without having to apply any more willpower than it takes to pop a couple of pills twice a day. Then, of course, the problem of pulmonary hypertension came along. It was discovered that fenfluramine products may cause heart valve problems or blood vessel pathology that leads to pulmonary hypertension. Pulmonary hypertension could lead to compromised lung function’meaning people could basically suffocate because their lungs became unable to exchange gases (good oxygen in, bad carbon dioxide out). That association is still being studied, but the evidence appears to justify the withdrawl of fenfluramine products from the market. The companies behind the products have agreed to settle the class action lawsuit that ensued.

The fat blockers and other products that have come out have been failures. The only exception is the time-proven PPA. Suddenly, concern was raised over PPA. Over the years a number of case reports have appeared in the medical literature associating it with hemorrhagic stroke, an injury to the brain caused by bleeding into the brain tissue. They started popping up in the medical literature in the 1970s, possibly earlier. Many of the early cases included people who were buying ‘street speed,’ which consisted of high doses of PPA along with caffeine and other stimulants. Despite those early reports, expert panels recommended PPA for GRAS (generally recognized as safe) status as a nasal decongestant in 1976 and as a weight-control product in 1982. The Food and Drug Administration states that it did not finalize the GRAS status for PPA because of concerns about the occasional reports of hemorrhagic strokes associated with it.

Thus, the FDA commissioned a study. It was conducted by experts from the pharmaceutical industry and was presented to the FDA earlier this year. It is available at www.fda.gov/ohrms/dockets/ac/00/backgrd/3647b1’tab19.doc

The study was composed of 702 patients and 1,376 control subjects. I haven’t reviewed it sufficiently to critique it, although I have questions relative to subject selection and the time definition of PPA exposure.

The results showed a greater risk for hemorrhagic stroke in women using PPA as a weight loss aid or as a decongestant, although it was significantly higher for women who used the product as a weight-loss aid. Interestingly, the average dose used by the people who had suffered a hemorrhagic stroke in association with PPA use’i.e., taken it within three days prior to the event’was 82 milligrams in the last dose taken before the stroke. Only 27 of the 702 subjects who suffered a hemorrhagic stroke took the PPA within three days of the stroke. Any longer than that and the drug would likely have been metabolized and cleared. Of the 27, eight exceeded the manufacturer’s directions, and the 18 or 66 percent also had known stroke risk factors, such as smoking and hypertension.

This study, while it may have some valuable information, is not clear in defining the risk of hemorrhagic strokes associated with PPA. What’s more, I’m not sure that asking the pharmaceutical industry to evaluate a product that holds such a dominant market position provides a truly objective review.

I’m not one to yell, ‘Cover up,’ or look for men in black in unmarked helicopters; however, there’s sufficient reason for the pharmaceutical industry to create public demand for an effective weight-loss product. With the withdrawal of PPA and the public scare over ephedra products, the disaster of fen-phen and the demographics of obesity, there’s a very attractive market for the next pharmaceutical weight-loss product. I think that situation is perplexing. It appears that the PPA industry rolled over in response to pressure from the FDA and the possibility of litigation following the withdrawal of GRAS status. I’m going to review the study more closely and may submit some questions for clarification to the researchers. Maybe I’m wrong, but if 27 people, 18 of whom have strong risk factors and eight of whom exceeded the manufacturer’s recommendations, had strokes out of 30 billion doses (6 billion doses per year for five years), it seems like a very minimal risk. In light of the known health consequences of using tobacco and alcohol, the manufacturers of which continue to be among the strongest publicly traded stocks, I think this issue deserves close scrutiny.

Editor’s note: Daniel Gwartney, M.D., is a clinical pathologist and a graduate of the University of Nebraska College of Medicine. He’s been bodybuilding for more than 18 years. The material presented in this column is for general-information purposes only and is not to be construed as medical advice or an individual recommendation. Consult with your physician or health care provider before embarking on any fitness, training, diet or supplementation program. The author and IRONMAN assume no liability for the information contained in this column. IM