What's That Smell?

Science News, May 15, 1999 by Damaris Christensen

Modern science puts its mark on a rare but ancient body-odor disease

"What have we here? A man or a fish? Dead or alive? He smells like a fish; a very ancient and fish-like smell ..."

--William Shakespeare, "The Tempest"

Shakespeare's description of the socially rejected island dweller, Caliban, aptly demonstrates that people have long been aware of a particularly offensive smell. Today, body odors are among the most sensitive of topics and figure into some of the deadliest insults.

Inspired by advertising, most people avoid having a socially unacceptable smell thanks to frequent showers and deodorants, perfumes, or colognes. However, for people with a rare genetic disorder known as fish odor syndrome, none of these is enough.

Since few health professionals are aware of this disease, also called trimethylaminuria, people experiencing its characteristic body odor may spend years seeking relief. They often acquire a long list of inaccurate diagnoses, ranging from poor hygiene to psychiatric problems. These people may withdraw from the outside world to avoid ridicule or try to mask their odor with strong perfumes and cigarettes. Many of those with the disorder also report symptoms of depression.

"People think this disease is a laughing matter, but for the people who have it, it is not. This syndrome can be highly destructive to a person's personal and social life and to their work and career," says Robert L. Smith, a molecular toxicologist at the Imperial College School of Medicine in London who recently cochaired the first-ever scientific meeting on trimethylaminuria. Held in late March at the National Institutes of Health in Bethesda, Md., the conference gathered from around the globe about 30 researchers studying trimethylaminuria--many of them without funding--and a few of the people who have been diagnosed with the disorder.

The first case of trimethylaminuria was described in the medical literature in the 1970s, but literary references may go back a thousand years. For example, an ancient Hindu tale describes a maiden who "grew to be comely and fair, but a fishy odor ever clung to her."

Although they show no apparent lack of hygiene or obvious medical symptoms, most people with the disorder report having foul body odors, bad breath, or a bad taste in their mouths. Studies in the last few years have shown that trimethylaminuria results from defects in an enzyme that breaks down trimethylamine, a byproduct of protein digestion released by bacteria living in the gut. This small molecule--the compound that gives fish their fishy odor--smells foul or garbagelike at low concentrations and fishy in larger amounts.

People with the disorder can release trimethylamine through breath, sweat, and urine. A few have a strong odor all the time, but most others experience a less severe smell that fluctuates over time. Researchers speculate that the variability of symptoms indicates that a range of genetic mutations can cause the disease and that stress and diet play a role in triggering symptoms.

There is no cure for fish odor syndrome, but a special diet can alleviate the worst of the odor problems. This low-protein regime restricts the amino acid choline, a building block of protein naturally found in high concentrations in fish, eggs, beans, and organ meats. Some people also report that limiting lecithin, a common food additive that is also naturally found in eggs, soybeans, and corn, helps reduce odor.

Because bacteria in the gut produce most of the trimethylamine in the body, some people have found that low doses of antibiotics, which kill off these bacteria, temporarily help keep odor down.

Although only about a hundred cases have been described in the scientific literature worldwide, the syndrome may not be as rare as that number suggests. Estimates of the disease's prevalence are sketchy at best.

Odor problems are such a sensitive topic that many people may be wary of talking about their symptoms to a doctor, says Harry W. McConnell of King's College Hospital in London. "The name [fish odor syndrome] contributes greatly to the stigma of this disorder," he says, adding that the name "is misleading since the odor is variable."

Because the disease is practically unknown by any name, it may take years for a person with trimethylaminuria to find a doctor who can recognize the problem. In a survey given to 22 people who had been identified as having the syndrome, McConnell found that it typically took them 5 to 10 years to seek medical care after their symptoms appeared. The correct diagnosis then required, on average, another 10 years.

Trimethylaminuria is only occasionally identified during childhood. The affected children, however, are likely to become disturbed and even suicidal because of the problems their odor causes in schools, says Ertan Mayatepek of the University Children's Hospital in Heidelberg, Germany. The odor problems in some children seem to disappear as they age, but researchers don't know why.

Nor do they know why the syndrome seems to be more common in women than in men. Scientists suspect that sex hormones exacerbate symptoms. A variety of reports say that the disease in women gets worse around puberty, just before and during menstrual periods, after taking oral contraceptives, and around menopause.