A cure for chronic fatigue?

If new research proves right, some sufferers have nothing more than an easy-to-fix blood pressure problem

Give me your tired, your poor. . ." had special meaning for John Friedlich when he visited the Statue of Liberty two years ago. Tired? Friedlich had been exhausted for the past five years-sick and tired with chronic fatigue syndrome. Poor? Well, not quite, but the 44-year-old had been forced to close his medical illustrating business while trying to recover from the debilitating ailment.

Months would go by with Friedlich lacking the strength to leave his house in Ashland, Massachusetts. But during one of his better weeks, he and his wife had organized a brief trip to New York. And now his six-year-old daughter, Sarah, wanted desperately for him to trek with her to Lady Liberty's crown.

"After that climb I was on my back in a hotel room," Friedlich says. "Then I was bed-bound in my home for a month." People with chronic fatigue syndrome call it payback. For just a few minutes you manage to overcome the leaden weights of weariness. And for days, weeks, or months afterward you are more of a wreck than ever.

Today all that has changed. Friedlich is racing Sarah across a grassy field without fear of payback. And to the astonishment of the eight-year-old, who never knew what it was like to have a healthy father, he gets to the finish line first. "You beat me!" she shouts. "You never could even keep up with me!"

The difference between then and now can be traced to a surprising discovery last fall by researchers at Johns Hopkins University, in Baltimore. Hugh Calkins, a cardiologist, and Issam Botti-Holaigah, a pediatrician, reported with two colleagues that many people diagnosed with chronic fatigue are apparently afflicted with nothing more than an easily treated blood pressure abnormality. Now Friedlich is one of scores of patients who, after years of trying everything from antidepressants to herbal remedies, have recovered in a matter of weeks or months by taking a drug that adjusts salt levels in the body.

Chronic fatigue syndrome is not the kind of disease that would seem to lend itself to a simple solution. In addition to severe fatigue lasting more than six months, victims suffer from such a diverse and varied array of symptoms (headache, chills, sore throat, depression, forgetfulness, allergic skin reactions, and sleep disturbances) that many doctors have suspected it's not a real disease at all.

In the past few years, though, a growing number of researchers have concluded that chronic fatigue is a serious, albeit mysterious, medical problem. Some believe it's caused by a virus, since many people come down with the syndrome soon after a flulike illness. Other sufferers get chronic fatigue after a psychological trauma or a period of intense work, suggesting it may be caused by stress hormones. Frustratingly, scientists have found no proof for these theories and no reliable treatment.

As a cardiologist, Calkins was not particularly interested in that puzzle. Instead, he was intrigued by an equally peculiar syndrome called neurally mediated hypo-tension (NMH), whose most striking symptom is a tendency in otherwise healthy people to suddenly faint.

The problem, Calkins says, has to do with the nerves that regulate blood pressure. Normally, when a person has been standing for more than a few minutes, blood begins to pool in the legs and feet. In response, so-called autonomic nerves tell the heart to pump harder and blood vessels to contract, perking up blood pressure. In perhaps 10 percent of the population, however, the nerves overstimulate the heart, making it contract prematurely, before it has filled with blood. And that causes a chain reaction: Blood vessels dilate, the heart slows, and blood pressure drops, leaving the brain starved for oxygen. Victims quickly become lightheaded and can faint.

People with mild cases may never feel symptoms, especially if they have subconsciously learned to keep fidgeting just enough to prevent serious blood pooling-wiggling fingers or shifting weight is often sufficient. But many sufferers get referred to cardiologists to see if their lightheadedness is due to a heart rhythm abnormality. And in Calkins's examinations of such patients, the doctor had noticed something interesting: After recovering from the fainting spells, many suffered an intense exhaustion for hours or days afterward that looked very much like chronic fatigue payback.

Curious about a possible link, Calkins and his coworkers turned to the definitive test for NMH: The patient is strapped securely to a table that is tilted repeatedly to a nearly upright position for as long as 45 minutes at a time. With the person unable to wriggle or move, blood pools at the feet. Almost invariably in those with the disorder, the face goes white and blood pressure drops; a wave of nausea may arise, and then it's the big Lights Out. Of 14 healthy volunteers whom Calkins tested, nearly all passed the test with no discomfort. But ten of 23 chronic fatigue patients passed out on the first tilt, and another 12 got lightheaded or fainted by the third time the table went vertical.

Even more remarkable was what happened when 19 of these patients were given the standard treatment for the blood pressure disorder: increased salt in their diet, along with one or both of two drugs--florinef acetate (which causes salt and fluid retention, ensuring there will always be some blood in the heart) and beta blockers (blood pressure drugs that reduce heartbeat intensity, preventing the overreaction that triggers the blood pressure collapse). Nine patients saw nearly all their symptoms vanish within a month.

"It's very exciting--and surprising," says Stephen E. Straus, who leads a number of chronic fatigue studies at the National Institutes of Health. Straus cautions that it's not clear how many chronic fatigue cases are really caused by the blood pressure problem; estimates range from 10 to more than 70 percent. Nor is it clear how many can be cured by the heart medications. People with chronic fatigue are notorious for responding briefly to all kinds of medicines, Straus says, only to fall ill again after a few weeks or months.

"Over the 16 years I've been studying these complaints, people have tried every drug you can think of," he says. "A lot of times people say they are better when it's really a placebo effect. It doesn't last." Straus is now collaborating with Calkins, giving cardiac drugs or dummy pills to large numbers of chronic fatigue patients.

With heart drugs widely available, however, many people aren't waiting. That worries Jay Levy, a researcher at the University of California, San Francisco. Levy warns that people with chronic fatigue should take florinef, beta blockers, or other cardiac drugs only after a tilt test shows NMH--and then only under a doctor's strict supervision. "These drugs can cause dangerously high blood pressure in some individuals and hormone imbalances in others," he says.

Calkins's study holds one final surprise: Many current therapies for chronic fatigue may actually be making the condition worse. "Most of these patients are on 'healthy' diets, which include no or low salt," the cardiologist says. "That may not be a good idea." Similarly, many chronic fatigue patients take tricyclic antidepressants, such as amitriptyline (Elavil) or imipramine (Tofranil), which can exacerbate the glitch in the nervous system that causes the drop in blood pressure.

Friedlich is one of the lucky ones. He fainted shortly after the tilt-table test began, so his doctor prescribed gradually increasing doses of florinef and told him to begin salting his food liberally. A month later, Friedlich came fully alive for the first time in more than six years. "It was a Sunday morning," he says. "I woke up and it felt like the first day of spring."

Last fall, Friedlich threw a party. Celebrating his recovery, he danced with his wife, and then he asked eight-year-old Sarah for a turn. She looked up at him and smiled. "We've never really danced together," she said. And so they did.

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By Rick Weiss

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