The night belongs to asthma.

If you’re one of America’s 10 million asthmatics, you may find that your symptoms vary like, well, night and day, with the odds of an attack vastly greater in the wee hours — about 4 a.m.– than in daylight.

But if it’s heart attacks and strokes that worry you, early morning is definitely prime time. That’s when cardiovascular problems — as well as more minor troubles like allergies and rheumatoid arthritis — are most likely to strike.

And if pain is your worst enemy, you probably already know when the witching hour comes: late evening.

For years, scientists have known that nearly everything in biology seems to be imbued with its own distintive circadian — or daily — rhythms, from the lowliest bacterial colony to the deadliest of cancer cells to the most complicated human hormones that ebb and flow through our veins according to timetables laid down long ago by evolution.

They’ve found, for instance, that adrenal glands in a test tube secrete hormones at precise times of day, just as they do in the body. And that plants, stashed in closets, furl and unfurl their leaves according to deep, genetically-set rhythms.

Researchers are now making the leap from chronobiology, the study of these basic rhythms, to chronotherapy, the tailoring of drugs to the rhythms of the body and of disease.

“In the old days, doctors used to think that a `steady state’ of drugs in the system was best,” says Michael Smolensky, a physiologist at the University of Texas-Houston School of Public Health, largely because they had been indoctrinated with concept of homeostasis — the idea that the body likes to keep its internal milieu reasonably constant.

But with 24-hour monitoring of blood pressure, hormone secretion and other variables, chronobiologists have shown that homeostasis is more complicated than that. It’s now clear there is fluctuation in many body rhythms every 24 hours — and that it can pay to synchronize treatments to these rhythms.

This insight has led to a such a scramble among researchers and drug companies that doctors are struggling to keep up. According to a Gallup survey done for the American Medical Association, only one doctor in 20 really understands chronobiology.

But most said they were eager to learn, recognizing there’s more to chronotherapeutics than, say, just popping a sleeping pill or even melatonin, the popular but controversial hormone, in the evening to get a better night’s sleep.

Consider asthma, for instance, an inflammatory lung disease with a clear circadian pattern — and treatment strategy.

One reason asthma flares at night is adrenalin, a stress hormone that is also a bronchodilator, or airway opener. Adrenalin peaks in mid-afternoon, then sinks to its nadir 12 hours later, so that airway function is best in mid-afternoon and worst at 4 a.m., says Dr. Richard Martin, head of the division of pulmonary medicine at the National Jewish Center for Immunology and Respiratory Medicine in Denver.

Histamine, a natural substance that constricts airways, makes things worse. At night, when adrenalin is low, histamine soars, adding to the tendency of airways to narrow.

And then there’s cortisol, a hormone that dampens immune response and inflammation. Cortisol peaks in the early morning, but during the night, when it would help to have cortisol available to curb inflammation in the airways, levels are low.

The result is that airway function varies somewhat in everybody over a 24-hour period. In people with severe asthma, the difference can be as much as 50 percent — potentially the difference between life and death.

To combat this pattern, researchers years ago developed the first genuine chronotherapeutic drug, Uniphyl. If the drug is taken in the evening, its efficacy peaks when it’s needed most — in the middle of the night — then wanes during the day.

Other asthma remedies have also been shown to be most effective at particular times of day, including oral steroids, which seem to work best when given around 3 p.m., says Martin. But he cautions that patients should not alter the timing of these medications without talking to their doctors.

Other chronotherapeutics are fast becoming available.

Last month, Searle, the pharmaceutical arm of Monsanto — began marketing its recently-approved drug, Covera-HS, for high blood pressure and the chest pain of angina.

Doctors have long known that the odds of heart attack, angina or stroke peak in the early morning, as blood pressure soars and platelets become sticky and more likely to form clots.

One obvious solution is to get blood pressure medications into the patient’s system before he wakes up and enters this danger zone. But this can be trickier than it sounds, says Dr. William B. White, chief of hypertension and vascular disease at the University of Connecticut Health Center in Farmington.

Taken at bedtime, some anti-hypertensive drugs may lead to a too-severe drop in blood pressure during sleep, when blood pressure is already comparatively low, and leave too little in the system to be effective in the morning, he says.

Covera-HS, a once-a-day bedtime drug, is designed to get around that problem. The pill has coatings that delay absorption for four to five hours, so that it kicks in early in the morning, says White, who has studied the drug.

Other studies show it can help to take cholesterol-lowering drugs at night, when the liver is busiest making cholesterol.

And just 10 days ago, a Charlestown company, Ergo Science, released tests of a new diabetes drug designed with chronobiology in mind.

Scientists have long known, say Ergo physiologists Anthony Cincotta and Albert Meier, that in healthy, lean animals, certain brain chemicals — notably dopamine — surge in the early morning, then taper off at night. The same pattern is believed to hold for people.

But in Type II diabetes, a condition in which the body becomes resistant to the sugar-transporting hormone insulin, the body clock seems to go haywire: Dopamine drops in the morning.

Ergo’s new drug, still unapproved, seems to fix this errant biorhythm. Taken at breakfast, it dissolves fast, providing a quick blast of a dopamine substitute just as the body needs it.

In 400 people with diabetes, the drug has improved blood levels of glucose, cholesterol, triglycerides and fatty acids.

Timing of treatment may also be important in cancer chemotherapy, says Dr. William Hrushesky, senior attending oncologist at the Samuel S. Stratton Department of Veterans Affairs Medical Center in Albany.

Hrushesky, a pioneer in the study of biorhythms in cancer treatment, says there is a distinct rhythm for cell division, for cell suicide, for the growth of new blood vessels around tumors and for the metabolism of drugs given to combat cancer.

Because of these rhythms, he says, “timing is everything” — with different drugs having different windows of effectiveness.

Adriamycin, for instance, may work best in the early morning, 5-FU (Fluorouracil) does best at night and platinum-based drugs like Cisplatin in late afternoon, he says. Pumps worn by the patient make it relatively easy, he adds, to take drugs on a schedule that’s most effective, not just convenient for doctors.

Though the timing of chemotherapy to fit biorhythms is not yet mainstream practice, Hrushesky and French researchers have evidence that survival rates can be quadrupled in ovarian cancer and doubled in advanced colon cancer if chemotherapy is timed right.

And Canadian researchers have shown that children in remission from acute lymphoblastic leukemia who take the drug 6-MP (mercaptopurine) in the evening are three times less likely to relapse than those who take it in the morning.

As with any other new field, of course, much research still needs to be done. But the field is clearly exploding, says Smolensky of Texas. Ten to 15 years ago, when chronobiologists began promoting their findings, “people would look at us as if we had stepped out of a spaceship,” he says.

Now, they’re eager to know more.

SIDEBAR:

With medication, timing is everything

While researchers are developing new drugs to take advantage of the daily rhythms of the body or to fix errant rhythms, research in chronobiology suggests you may be able to enhance the effectiveness of old ones by taking them at just the right time.

If you suffer from hot flashes, for instance, taking estrogen replacement therapy at night — when hot flashes can wake you — may make sense, says Dr. Gary Richardson, director of the neuroendocrine clinic at Brigham and Women’s Hospital.

Rheumatoid arthritis, an inflammatory disease, is often worst in the morning, says Dr. Martha Barnett, a rheumatologist at Beth Israel Hospital. Though she believes morning stiffness stems from inactivity at night, others think it may be a result of circadian rhythms in hormone secretions and other factors.

Whatever the reason, taking nonsteroidal anti-inflammatory drugs (NSAIDS) may help most in the evening. But be sure to take them with food, to help prevent ulcers and other stomach problems. In fact, ulcers have their own circadian rhythms, with many flare-ups occuring during the early hours of sleep.

On the other hand, osteoarthritis, which results from wear and tear on joints, is worse at night, after a day of activity, so taking medications in the morning may be most effective.

Runny noses, colds and nasal allergies are often worst in the morning, notes Michael Smolensky, a physiologist at the University of Texas-Houston School of Public Health. Thus, time-release anti-histamines taken at nighttime may help.

Aerobic exercise, while not a drug, does impact health and can also be timed for optimal effect. Studies by the US and German armies suggest that the biggest increase in endurance comes if you exercise in the afternoon and early evening, says Dr. William Hrushesky, a chronobiologist in Albany, N.Y. It’s also much easier to exercise at this time of day, he adds.

Sunlight isn’t exactly a drug, either. Though it can increase the risk of skin cancer, it is also beneficial because it suppresses the sleep hormone melatonin and helps re-set circadian rhythms so you sleep better at night, says Dr. Michael Holick, chief of endocrinology at the Boston Medical Center.

In fact, one explanation for “winter depression” is that the weaker sunlight in winter may not suppress melatonin well enough.

And there’s another reason sunlight may make you happy. In skin cells at least, sunlight boosts levels of the feel-good hormone, beta-endorphin.

Three years ago, Ruth Hertz, 66, a self-described “LOL” or little old lady, began feeling lousy.

A normally avid tennis player, she found herself dragging around the court. “The tiredness sort of seemed to come on suddenly,” she recalled last week.

In fact, Hertz, who lives in Framingham, was “more than tired. I was lethargic. I was doing a lot of sleeping,” she says, “and I was beginning to be a little depressed.”

She finally confided her growing list of symptoms to another woman in her water aerobics class who immediately — and correctly — diagnosed her problem: an underactive thyroid gland.

Thyroid troubles, especially the mild, early stages of hypothyroidism or underactive thyroid, are among the most common and easily missed of medical problems, especially for older women, whose complaints of fatigue or malaise may be dismissed as anxiety, loneliness or part of menopause.

Yet more than 6 million Americans, most of them women, suffer from hypothyroidism. Another million have the opposite problem, hyperthyroidism, in which the butterfly-shaped thyroid gland in the neck makes too much, not too little, hormone.

And while some women do encounter thyroid problems right after childbirth, many more — an estimated 10 to 20 percent — first begin having thyroid abnormalities around age 60.

But increasingly, doctors are getting better not just at diagnosing these problems, but also at avoiding what used to be a major pitfall: Overtreating hypothyroidism, which can cause osteoporosis, or bone loss.

Today, thanks to increasingly sophisticated versions of a sensitive test called TSH, doctors can adjust medications precisely, allowing virtually all patients to maintain normal thyroid function.

Researchers also have a more detailed picture of what causes most thyroid troubles in the first place. As we age, the immune system, for unclear reasons, sometimes begins to attack organs in the body, especially in women.

In hypothyroidism, immune cells mistakenly attack the thyroid gland, a process known as Hashimoto’s thyroiditis.

Hyperthyroidism can also be caused by an auto-immune disorder — Graves’ disease — in which proteins called antibodies attack the thyroid.

The half-ounce thyroid gland is far more important than its diminutive size would suggest. In fact, the iodine-laced hormone it makes, thyroxine, is essential — and not just in humans.

It is thyroxine that turns tadpoles into frogs, notes Dr. Reed Larsen, chief of the thyroid division at Brigham and Women’s Hospital. If tadpoles’ thyroid glands are removed, they keep growing — up to a foot long — but never change into frogs.

Thyroid hormone makes kids grow, too, and is essential for normal brain development as well. A baby born with a defective thyroid will, unless treated, develop cretinism, a form of mental retardation endemic in parts of the world where iodine deficiency causes goiter, an enlargement of the thyroid.

Thyroid hormone is also essential for bone growth and for maintaining the basal metabolic rate — the speed at which the body uses sugars, fats and proteins.

With increasing age, many of us — perhaps 50 percent — develop nodules in the thyroid that doctors can feel. These usually do not interfere with thyroid function and are almost always benign, but occasionally, larger nodules may contain cancer. This is rarely fatal and can be treated by removing the affected part of the gland and treating with replacement hormones.

For most of us, however, it’s the more mundane problems that are the biggest troublemakers in later life.

If your aging immune system goes bonkers and attacks your thyroid, you may suffer fatigue, weight gain, intellectual dullness, depression, a tendency to feel cold, constipation, dry skin and other signs of an underactive thyroid. An overactive thyroid is no better — it can cause fatigue, heart failure and heart palpitations, mood swings, nervousness, weight loss, heat intolerance and other problems.

Either way, you may be miserable, though it’s worth remembering that few people die of either over- or underactive thyroid problems.

But in rare caes, hypothyroidism can cause such a sluggish metabolic rate that coma and death result. And hyperthyroidism can produce a fatal “thyroid storm,” in which the heart races and temperature soars.

But it’s usually the tiny, non-life-threatening changes in hormone function that cause most people misery. And how much hormone you produce is controlled by chemical signals sent out by the pituitary gland, which lies just underneath the brain.

If the pituitary senses that the thyroid gland is not making enough hormone, it puts out extra TSH, or thyroid stimulating hormone. If the pituitary senses the thyroid is making too much hormone, it decreases TSH to damp the system down.

In the old days, before TSH testing allowed doctors to measure miniscule changes in thyroid function, the only way doctors could assess function was by measuring blood levels of a thyroid hormone called T4. And the only rememdy they could offer was a dessicated powder made from the thyroid glands of pigs or cows, which varied greatly in strength from dose to dose.

“But now there are better ways both to test for and treat thyroid problems,” says Dr. Gilbert Daniels, co-director of Thyroid Associates at Massachusetts General Hospital.

Now, most patients’ blood is tested for TSH levels, which is “much more sensitive” than T4 testing at detecting miniscule changes in thyroid function, he says. If the test shows you have hypothyroidism, the solution is straightforward.

“Just give back thyroxine,” says Larsen of the Brigham. Nowadays, most doctors prescribe synthetic hormones such as Synthroid, which costs roughly $10 for a month’s supply, or Levoxyl and Levothroid, which cost $5 and $7 respectively.

But getting the dose right can be tricky, so doctors advise taking the hormone for 4 to 12 weeks, then having your TSH measured again. Once you’re on a medication, some doctors say you should stick with that brand, because formulations vary, though others say all the major drugs are equivalent.

“Don’t let people play musical brands with you, because one brand may not be 100 percent equivalent to another,” says Dr. Harold Rosen, an endocrinologist at Beth Israel Hospital.

And definitely don’t fool around with the dosage. If you take too much thyroid hormone, you may wind up with hyperthyroidism.

“Some people think overtreating is a neat way to lose weight,” says Rosen, and some people do feel better if they are slightly hyperthyroid.

But thyroid therapy rarely turns a chubby person into a svelte one. Even if you lose five or 10 pounds on hormones, you may gain the weight back. Overtreating with thyroid hormone can also cause dangerous thickening of the heart muscle.

And hyperthyroidism, whether it arises spontaneously or from overtreatment of hypothyroidism, can also cause osteoporosis, the bone-thinning disease that women already face at menopause from falling levels of another hormone, estrogen.

Thyroid hormone acts directly on bone, and too much can result in bone loss, says Dr. Meryl Le Boff, director of the Brigham’s skeletal health and osteoporosis program. The rate of loss can be slowed by estrogen therapy or other drugs.

For hyperthyroidism not caused by overtreatment, the best long-term solution is often radioactive iodine, says Larsen of the Brigham. Some patients panic at the idea of taking radioactive chemicals, he says, but this treatment “has been used for 50 years without any radiation-related side effects.”

For some patients, surgery to remove the thyroid gland can also help. And others benefit from drugs like propylthiouracil (PTU) or methimazole (Tapazole) that block the thyroid from making hormone.

The take-home lesson, says Larsen, is that because thyroid problems are so common and the symptoms can be so easily dismissed, patients should not be afraid to ask their doctors for a TSH test.

Ruth Hertz emphatically agrees. Taking thyroid hormone, she says, has “changed my life. It gave me much more energy. And I’m more interested in doing things.”

Kelly Ames, a staff assistant at Harvard Business School, is only 28 years old.

But in the six years that she’s had MS, a neurological disease that causes loss of coordination, partial blindness, even paralysis, she’s tried nearly every remedy in sight.

Drugs — steroids — helped some, she says, but she hated the side effects: “I’d eat like there was no end.”

At her mother’s urging, she went to France to bathe in the holy water in Lourdes, to no avail. Finally, when she could barely walk, she joined a support group, where one woman spoke of a horrifying remedy Ames had never thought of: bee stings.

Susan Graber, a 37-year-old South Carolina woman with MS, wouldn’t go near a bee, she says, because she’s “chicken to explore something where there’s nothing proven.”

She’s put her faith in mainstream science, becoming one of 301 human guinea pigs in a study of a new drug likely to be approved soon by the US Food and Drug Administration.

For years, MS patients had few options beyond steroids to soothe acute attacks, physical therapy and drugs to manage symptoms of the disease, which in some cases progresses steadily and in others, waxes and wanes mysteriously.

But recently, the tide has been turning for the 300,000 Americans with MS, two-thirds of them women in their 20s, 30s and 40s.

Doctors now have better tools to diagnose and track the disease, like MRI (magnetic resonance imaging), for instance.

They also have a firmer grip on the mechanisms by which this debilitating, though rarely fatal, disease gets started in the first place.

A leading theory now is that multiple sclerosis starts when the immune system gears up to fight a virus. Then, mistaking tiny markers on the myelin sheath surrounding nerve fibers in the brain and spinal cord for the virus, the immune system keeps up its attack, destroying the body’s own tissue.

But most important to people fighting MS, researchers have a whole slew of new remedies in the pipeline designed to slow progression of disease and reduce flareups.

Some of these drugs, like Betaseron, approved in 1993 by the Food and Drug Administration, and AVONEX, awaiting approval now, tinker with components in the immune system, suppressing levels of natural, inflammatory substances that contribute to MS flareups and boosting levels of anti-inflammatory chemicals.

“The net effect of both these beta-interferons is to dampen down an overactive immune system,” says Dr. Howard L. Weiner, co-director of the center for neurologic diseases at Brigham and Women’s Hospital.

The drugs may work by decreasing levels of gamma interferon and boosting anti-inflammatory substances like interleukin-4 and interleukin-10, among other effects.

Other drugs, like Copaxone, which is also awaiting FDA approval, work through somewhat different means to stop immune cells from attacking the myelin sheath around nerve fibers.

Still other drugs increasingly used against MS are old standbys on the market for other uses, like cancer remedies methotrexate and cyclophosphamide. These drugs work by attacking rapidly-dividing cells, like tumor cells and immune cells that attack myelin.

And other medications, like Myloral, a kind of vaccine, use a totally different approach, taking advantage of a phenomenon called oral tolerance.

The theory here is this: When a person swallows Myloral, which is made of proteins from the myelin sheath, immune cells in the intestines become programmed to recognize the myelin.

When these cells then travel through the bloodstream to the myelin sheath in the brain and spinal cord, they secrete anti-inflammatory substances that should stop the immune attack against myelin. Curiously, notes Weiner, if these same proteins were injected instead of swallowed, the response could be just the opposite — immune cells could attack the myelin sheath.

For many people like Graber of South Carolina, these drugs offer hope for a vastly improved quality of life, despite MS.

During the 2-year AVONEX study, researchers purposely did not tell Graber or any other participants which patients were getting Avonex and which, a harmless placebo.

But Graber, who had no feeling in her legs and could barely walk when the study began, knew right away. Each time she got an injection, she had flu-like symptoms — and relief from MS.

She also “started to fail tremendously” when the test was over and she had to stop taking the drug. Now taking the drug again in a follow-up study, Graber is thrilled.

“I have done so well on this drug,” she says. She still can’t work, but she no longer needs a cane to walk.

But it’s not just mainstream drugs that have people with MS buzzing these days — it’s honeybees.

When Ames first heard of bee venom therapy, she was appalled, especially when the woman in her group who’d been stinging herself “never showed up again. . . We thought she had died.”

But Ames was curious, too, and desperate. So she bought honeybees from a local beekeeper and began stinging herself — “screaming and crying” — every other day.

Popularized in recent years by alternative medicine gurus, among them, 90-year old Vermont beekeeper Charles Mraz, author of the self-published “Health and the Honeybee,” the idea of using bee venom medicinally is probably as old as Hippocrates.

But it was not until the 1950s that scientists, chiefly in Bulgaria and Germany, began taking bee venom seriously. Later, researchers at the Walter Reed Army Institute of Research got interested, too, among them Robert Brooks, a Pennsylvania beekeeper and pharmacologist.

Bee venom contains about 40 ingredients, says Brooks, including anti-inflammatory substances, one of which may be 1,000 times stronger than indomethacin, a nonsteroidal anti-inflammatory drug.

And two ingredients in bee venom, and bee venom as a whole, may stimulate release of cortisol, an anti-inflammatory chemical made in the body that also damps down immune response.

But Brooks warns that “the action of bee venom is much more complicated than the simple release of cortisol,” and Dr. Christopher Kim, a pain researcher in Red Bank, N.J., agrees.

In one study of 180 patients with arthritis and similar diseases, Kim found that injections of true venom reduced pain significantly more than injections of “sham” venom. But “bee venom therapy is not pleasant,” he says, and should be used only by patients who do not respond to conventional therapy.

Bee venom can also cause fatal anaphylactic shock, though this is rare. There are 40 reported deaths a year from all stinging insects, including bees and yellow-jackets, according to the National Institute on Allergy and Infectious Diseases.

To be safe, Kim tests patients first with a small dose of venom to see if they are allergic and keeps antidotes on hand.

Still, there is no scientific evidence that bee venom therapy helps in MS, says Stephen Reingold, vice president for research at the National Multiple Sclerosis Society.

But that could change.

Dr. Fred Lublin, acting chairman of neurology at Thomas Jefferson University in Philadephia, is now studying bee venom in mice, though he, too, stresses that the data are not yet in.

“Just the stress of being stung, as opposed to what’s in the venom,” could stimulate cortisol, he says. And “the placebo effect seems to be especially strong because of the nature of the disease,” which waxes and wanes on its own.

But try telling that to Kelly Ames or her friend Karen Davies, 32, who brings her own bees — obtainable by mail or from beekeepers — three times a week so Ames can sting her. She puts the bees on spots of the body that are also acupuncture points, thus triggering — perhaps — a double-whammy effect.

“I’ll try anything,” says Davies, who gets 120 stings a week. “I feel great,” she says. But she also takes Betaseron.

Ames, however, uses nothing but bee stings. “My eyesight came back and I stopped using a cane,” she says, as soon as she worked her way up to 13 stings every other day.

“I know it works for me. . .I don’t have MS anymore.”

SIDEBAR

What’s new for MS

These are among the new drugs recently approved, likely to be approved soon or under investigation for MS:

• Betaseron (interferon beta-1b), an every-other-day injection made by Berlex Laboratories, was approved by the FDA in 1993.
• AVONEX (interferon beta-1a), a weekly injection, made by Biogen, Inc., expected to be approved soon.
• Copaxone, by Teva Pharmaceuticals, a daily injection, also awaiting FDA approval.
• Myloral, a vaccine developed by AutoImmune Inc., now in clinical trials.
• Linomide, by Pharmacia & Upjohn, Inc., now in clinical trials.
• Cladribine, by Ortho Biotech, Inc., also in clinical trials for MS. It is on the market for leukemia, but can be toxic.
• Fampridine (4-aminopyridine), by Elan Pharmaceuticals, in clinical trials for management of symptoms of MS.
• Zanaflex, by Athena Neurosciences, Inc., to treat spasticity, is awaiting FDA approval.

For more information on MS and treatments, call:

• National Multiple Sclerosis Society, 1-800-FIGHT-MS.(1-800-344-4867); for Massachusetts residents, 617-890-4990.
• Multiple Sclerosis Association of America, 609-488-4500 or 1-800-LEARN-MS.
• American Apitherapy Society, 1-802-436-2708.
• MS support group for people using or considering bee venom therapy, 617-641-3109.
• For books on bee venom therapy, Honeybee Health Products, 1-800-603-3577.