How a Nasal Decongestant Became the Biggest Appetite Suppressant of All-Time

It’s startling to think that the elimination of a single medically approved ingredient could bring two distinct pharmaceutical industries to a grinding halt. It’s also startling to think that the pharmaceutical product in the most popular appetite suppressants of all time — phenylpropanolamine, more commonly shortened to PPA — made its initial breakthrough as a nasal decongestant. 

And yet, that’s exactly what happened. 

PPA first hit the market in the mid-1930s with the kind of blood-vessel-tightening properties that staved off nasal congestion, only for users to report the side effect of not feeling hungry. The diet industry, of course, quickly seized on this, and for the next 60 years it played a game of chicken with the Food and Drug Administration and other prominent health experts, before it all came tumbling down — almost taking every cold and flu medication down with it. 

PPA Officially Enters the Market as an Appetite Suppressant

The real surge in PPA as an appetite suppressant started in the 1950s when its patent protection lapsed — especially in terms of the sheer volume of newspaper advertising for it. Although sold under brand names like Curb-wate and Trimet, the majority of the ads were transparent in disclosing that the foremost active ingredient was none other than PPA. In fact, Trimet’s ads went to great lengths to explain why an approved nasal decongestant had come to be utilized in an appetite-eliminating capacity.

“There is a well-known drug called Phenylpropanolamine Hydrochloride, which has won widespread recognition and use in the control of symptomatic hay fever allergy and bronchial asthma,” once such ad from 1957 read. “However, patients often complained that it seemed to depress their appetites. This led some doctors to try it as an appetite depressant for obese patients who found it difficult to control their eating. Found free of objectionable side effects, it was considered safe for use without medical supervision.”

In response, the National Better Business Bureau quickly issued a statement disparaging the marketing of PPA as a “no-diet wonder drug” as “false, deceptive and a gross disservice to the public.” But the legitimate prescriptive usefulness for PPA as a nasal decongestant seemed to offer it a level of protection against more stringent regulations rarely enjoyed by other appetite suppressants. 

With no true competitors on the appetite-suppressant front who enjoyed similar shielding from regulation, PPA’s proliferation continued relatively unabated throughout the next several decades, making its way into an increasing number of products, including a greater range of cold medications and appetite suppressants. The drug also received some unexpected support from within the Food and Drug Association.

In December 1972, the director of the FDA’s Bureau of Drugs, Henry E. Timmons, testified before a Senate subcommittee and resisted encouragement from the subcommittee’s members that he should dismiss the appetite suppressants of the era — nearly all of which contained a combination of PPA and benzocaine — as ineffective. “Obesity is a serious disease and there is nothing effective except diet, if you can get a patient to stay on a diet,” he argued. “These drugs are very successful for some people. They should be available for those who need something; otherwise they would have nothing to turn to.”

Meanwhile, the manufacturers of appetite-suppressant drugs filled the void of FDA inaction with unflinching statements about the effectiveness of their products. “We have a lot of ladies who write in to us that have tried our product and say they have lost 5, 10 or 15 pounds and are satisfied with that,” claimed Duane Nickless, the sales manager of the Gobese Company, in an April 1974 article from the Courier-Post. 

PPA’s Appetite-Suppressant Effects Are Proven

Finally, in February 1979, the results of two tests performed at the University of Pennsylvania and Princeton University seemed to confirm that PPA did indeed have appetite-reducing properties. Ironically, the concern of the Princeton researcher, Bartley G. Hoebel, was rooted in identifying whether or not customers of cold and allergy medications were having their appetites unnecessarily curbed as a result of the uninformed consumption of drugs with hidden side effects. 

Another pharmaceutical researcher who refused to be named shared similar concerns with the Courier-Post: “Too many people take over-the-counter medications and aren’t aware of their unlisted side effects. Whether it’s dangerous to them individually or not, people have the right to know that a cold tablet they’re taking contains an appetite suppressant.”

And yet, again, certain voices inside of the FDA — this time an internal advisory panel — continued to claim that phenylpropanolamine was a “safe and effective means of controlling appetite to lose weight.” The producers of appetite suppressants seized on this statement, quickly appending the descriptions of their products with “FDA-approved” labels, despite knowing full well that an internal FDA panel wasn’t tantamount to official approval by the agency as a whole. 

In fact, the larger FDA declared PPA to be a drug that was still under official review, and the agency firmly established 37.5 milligrams as the maximum recommended single dose of PPA, with 75 milligrams as the maximum daily dose. Furthermore, the FDA requested that manufacturers offering larger doses voluntarily remove their products from the market.

Their plea, though, pretty much fell on deaf ears, as revenues from appetite suppressants containing PPA doubled from $100 million to $200 million between 1979 and 1980.

PPA on the Hot Seat

Now that PPA’s effectiveness as an appetite suppressant could no longer be contested, several of its opponents sought to ban it on the grounds that it might prove to be harmful. By the middle of 1985, it appeared that PPA’s days were numbered, as the FDA was conducting public meetings around the country soliciting comments from those who would prefer to see it banished from all appetite-suppressant remedies. At the same time, The Medical Letter, a biweekly, peer-reviewed publication that provides reviews of pharmaceutical drugs, began to report on serious cases of illness and death among heart patients who took PPA for its noncontroversial use as a remedy for cold symptoms, with some even citing incidents of kidney failure. 

Still, the issue continued to linger for several years while the manufacturers of weight-loss supplements developed even more elaborate methods to administer PPA — e.g., adhesive patches that delivered PPA through the skin. As reported by the New York Daily News in May 1988, “Most patches use an herbal potpourri, but one company — the North Carolina-based Perfect Combination — relies on the drug PPA, which is approved by the FDA for use in pills and sold by other companies in pill form as Dexatrim and Accutrim.”

But again, PPA had never officially been approved for use as an appetite suppressant by the FDA; the agency had simply refused to provide an official ruling on that count. In the meantime, the Washington Post reported in June 1988 that the FDA had already enacted the seizure of diet patches that supplied motion-sickness medication as their active ingredient.

Eventually, in August 1991, the FDA took action by banning 111 ingredients from being sold or marketed as weight-loss aids, including alcohol, caffeine, guar gum, ascorbic acid, sodium and yeast. However, no ruling was leveled against PPA, which managed to linger in regulatory limbo for almost another decade.

The Last Days of PPA

In October 2000, Yale researchers presented the FDA with the results of a five-year study that indicated how users of cough, cold and allergy remedies containing PPA were 50 percent more likely to suffer a hemorrhagic stroke than those who hadn’t used them, also noting that women appeared to be particularly susceptible. In total, the study estimated that between 200 and 500 people were suffering strokes annually as a direct consequence of ingesting PPA for its approved medical purpose.

“It’s a cardiac and brain stimulant,” explained Raymond Woosley, chairman of pharmacology at Georgetown Medical School, to Gannett News Service. “It’s a weak one, but there are some people who are exquisitely sensitive to it.”

As an official response, the FDA swiftly issued a public warning over the health threat posed by PPA, and requested that every drug manufacturer voluntarily remove their PPA-enriched products from pharmacy shelves and reformulate those medications prior to a market return. Simultaneously, several national pharmacy chains, including Walgreens and Rite Aid, preemptively pulled PPA products from shelves — a serious undertaking since PPA was an active ingredient in nearly every cough, cold and allergy remedy on the market back then (from Alka Seltzer Plus to Robitussin). 

Not everyone, however, agreed with the FDA’s decision or its repercussions. When Health Canada took the FDA’s request a step further and issued an outright ban on more than 60 drugs containing PPA until reformulations could be completed, Steven Milloy of the National Post declared the entire ordeal to be an act of “statistical malpractice” in light of the billions of doses of the blacklisted products that were being doled out every year compared to the small number of presumed strokes. 

But at least in the States, it proved to be an unconvincing argument. The FDA applied the “non-monograph” label to PPA in 2005, officially declaring it to be “not generally recognized as safe and effective,” unofficially issuing it a death sentence. And that was more or less it. Cold and sinus medication went back to being primarily cold and sinus medication (sans PPA), and the diet industry was forced to look elsewhere for pharmaceutical solutions it could market as wonder drugs — the two seemingly very different paths having never crossed since.