Get Slim Quick!

If Botticelli's Venus were alive today, she would be shopping in the plus-size department. The Flemish painter Peter Paul Rubens, from whose work we have the euphemism Rubenesque, had a good eye for what was beautiful, which at the time was stylish stout. His painting Allegory on the Blessings of Peace, which hangs in London's National Gallery, depicts both a cornucopia and a woman with a healthy appetite. His painting of Bacchus in the Hermitage in St. Petersburg depicts an obese god, no question, but Bacchus's mood is anything but morbid.

This was as it should be. Over most of human history, food was scarce. Fat was the embodiment of conspicuous consumption. Anyone could be thin, but only the very richest people could afford to be fat. The author/historian Alison Weir has suggested that the yeoman warders of the Tower of London earned the name Beefeater not from their diet, since there wasn't enough beef to go around, but from the fact that they guarded the buffet, the royal dishes and cutlery, so that Beefeater is derived from Buffetier.

Beyond that, fat was a symbol of good health. These were times when heart disease and cancer were minor health problems. The greatest concern was getting through the winter. Those people who could store energy with the greatest efficiency had the greatest chance of making it through the next famine or the next locust infestation. For centuries, fat was beautiful.

All this changed in the second half of the 19th century, when the great plains of North America were opened to farming and ranching. For the first time, food was plentiful. Even with the methods of farming available at the time, the grain harvest was great enough to not only feed the population but to overfeed them.

As soon as it became easy to be fat, it became desirable to be thin.

Introducing Thyroid

The first weight-reduction products were offered for sale in the late 19th and early 20th centuries. Perhaps the most notorious product was Kellogg's Safe Fat Reducer. Its purveyor was Frank Jonas Kellogg. Though he wasn't related to William Kellogg, the creator of corn flakes or to Dr. John Harvey Kellogg, who ran a sanitarium in Battle Creek, Michigan, Frank Jonas was willing to take advantage of his famous (and legitimate) namesakes by setting up a business in the same city. In 1902, Frank Jonas placed an ad in Collier's magazine, with a cartoon of a man who looked rather like a balloon and claimed his product would get rid of fat. Through a combination of aggressive advertising and questionable ethics, Kellogg grew rich from Safe Fat Reducer. The success wasn't to last.

The American Medical Association (AMA) started a campaign to stamp out the worst of the great nostrum evil and revealed that Safe Fat Reducer was a combination of thyroid, some laxatives, and breadcrumbs. The thyroid, the active ingredient in "Safe" Fat Reducer, had the risk of causing hypertension, cardiac arrest, and stroke. Long-term use would result in loss of normal thyroid function. The AMA was successful in getting the dangerous formula revised. The remaining components were sold simply as a laxative.

Later … Bath Salts?

Thyroid extract had been the mainstay of popular weight-loss remedies, and, without it, the marketers had a serious problem. But one entrepreneur who found a way to make a sale operated under the name Marjorie Hamilton. As she presented her story, here greatly simplified, Ms. Hamilton was a happily married woman until, with age, her beauty began to fade. As her husband became progressively less attentive, she began studying the problems of weight control. From her studies, she made two important discoveries. The first was the law of the jungle: "The hovels are filled with the starving women who didn't care or couldn't understand what it meant to them to grow fat and lose their attractiveness – who believed that men loved them for the sake of the woman herself." The second discovery was: "Fat is simply thickened nutrition."

Armed with that information, Ms. Hamilton offered a weight-loss system that relied heavily on bath (Epsom) salts to "draw" the fat out through the skin and leave it floating atop the bath water. By any logic, a powder that dissolves fat and causes it to pour out through the skin should be quite enough, but Marjorie Hamilton had some extra advice: take long walks, exercise, and avoid eating bread, potatoes, and pastries. As a diet guru, Ms. Hamilton was 100 years ahead of her time, but who could have known?

The Amphetamine Party

By the mid-20th century, science had marched on, and there were new theories of how to use drugs to reduce weight. According to these theories, the sensation of satiety was triggered by two things: high blood sugar and abdominal distention. Blood sugar could be raised by having a piece of candy before a meal, while a simple bulk laxative could fill the stomach. Neither method worked. What did work were the adrenergic amines, most notably dextroamphetamine – drugs which are similar to the hormones epinephrine and norepinephrine that are naturally produced by the human body, and, among other effects, reduce appetite.

For years, amphetamines were the mainstay of weight-loss therapy and for good reason. They not only reduced appetite, making dieting almost painless, they felt good. A generation of college students got their diplomas by studying all night, relying on amphetamines to keep them awake and alert. Supermodels depended on their supply of amphetamines to maintain their anorexic figures. Amphetamines became not part of the drug culture, but part of culture itself. In the August 1966 The Atlantic, Bruce Jackson wrote "Think for a moment: how many people do you know who cannot stop stuffing themselves without an amphetamine and who cannot go to sleep without a barbiturate …?"

The party ended in the early 1970s, when, all over the world, governments placed tighter restrictions on drugs with the potential for abuse. John Williams, a writer from Liverpool, England described it as: "a Frankenstein, an ogre to be destroyed, regardless of the wishes of the monster's victims." Even so, the stimulant drugs were well established in treatment of obesity, and both amphetamine sulfate and methamphetamine sulfate are still approved for use in most countries, albeit under tight restrictions.

The Infamous Fen-Phen

While amphetamine was closely controlled, and in most nations classed alongside morphine as an addictive drug, other drugs in the same class, but with less pleasant effects, remained available. One of the most important was fenfluramine, which had the appetite-suppressant effects of amphetamine but lacked the stimulant properties in normal doses. In fact, far from being a stimulant, fenfluramine often caused drowsiness or dizziness.

In the 1990s, fenfluramine was studied in combination with another anorexic agent, phentermine, leading to the popular term fen-phen. While the initial rationale for the combination was that the two drugs would provide an additive action, allowing the use of lower, safer doses of each drug, reviewers from Texas A&M University concluded that the combination was not merely additive but synergistic – more effective together than simply doubling the dose of either drug alone. The drug combination was very widely used, until a report from the Mayo Clinic linked 24 cases of heart valve disease to use of the drug combination. A follow-up report showed that of 291 patients who had taken fen-phen, 271 showed abnormal electrocardiograms. In 1997, American Home Products (now Wyeth), the manufacturer of both fenfluramine (Pondimin) and dexfenfluramine (Redux), removed both drugs from the market.

Other adrenergic amines haven't fared much better. Phenylpropanolamine (PPA), which was widely used as a decongestant as well as an over-the-counter (OTC) weight-loss drug was linked to strokes and removed from the United States market. In June 2001, Health Canada issued a warning against use of products combining ephedrine with caffeine, and, in June 2003, ordered a recall of ephedrine combination products. On February 4, 2004, the US Food and Drug Administration (FDA) issued regulations banning the sale of ephedrine.

Is Sibutramine Better?

While the adrenergic amines were being taken off the market, new approaches to weight loss were being developed. In 1996, the FDA approved the marketing of sibutramine (Meridia) for the treatment of obesity, a drug that, while not an adrenergic amine, extends the activity of the adrenergic compounds already circulating in the body. The British National Institute for Clinical Excellence recommended approval of the drug in October 2001. But, while sibutramine remains popular, it has had its share of problems, essentially the same ones that were seen with the adrenergic amines. In 2002, the Italian Health Ministry suspended sales of the drug after 50 reports of adverse effects (seven of which were considered serious) and two deaths. In France and England there have also been warnings about the safety of this product. However, in 2002, the European Union's Committee for Proprietary Medicinal Products issued a report that, when used according to directions, sibutramine had a favorable risk-benefit ratio. Sibutramine should be used only by people who are at least 30 pounds overweight, who do not have cardiovascular problems, and who are not taking drugs that would alter its action.

Drugs of the Future …

In April 1999, the FDA approved the sale of orlistat (Xenical), a drug that inhibits digestion of fat, which leads to lower caloric absorption. The drug, which is sold by Hoffman-LaRoche, was approved for sale in Canada the following year. To date, orlistat has not shown any untoward risks.

What's next? Improbably, the next major drug for weight loss may arrive by way of the OTC shelves and health food stores. Health food stores particularly have been sources of questionable remedies: medicinal plants that worked in the past but have been supplanted by more modern products and botanicals that might be effective in large enough doses but were sold in doses that assured safety at the price of effectiveness. OTC and mail-order weight-loss remedies have offered worthless products while making impossible claims, or, more recently, making exaggerated claims for standard drugs such as phenylpropanolamine. Now, many of these formulations, deprived of PPA and ephedrine, have turned to Citrus aurantium, also known as Bitter Orange, Kuang Chu, and Seville Orange.

Bitter Orange has a history of use throughout the world. It has been promoted as both a sedative and a stimulant. In China, the plant has been reported to be useful for diarrhea, while, in Haiti, it has been used as a laxative. But, in 2002, the Georgetown University Medical Center evaluated three studies of Citrus aurantium for weight loss. Although the studies were small and conducted over a short period, they did show significantly greater weight loss with the Bitter Orange products than with a placebo. The studies also showed a greater basal metabolic rate among those patients using Bitter Orange than those taking placebo. The authors of this paper concluded that although more research is called for, Bitter Orange, in combination with programs of diet and exercise, may be the best product to replace ephedrine in weight-loss regimens.

In the end, it's worth remembering that all of the weight-loss drugs, at least all those that worked, were sold "as an adjunct to a program of diet and exercise." I believe it was Cher who once said: "If great bodies came in a bottle, everybody would have one."

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