The Body Clock Guide to Better Health: How to Use your Body's Natural Clock to Fight Illness and Achieve Maximum Health

1

It’s about TIME

In 1996 the American Medical Association (AMA) asked the Gallup Organization to see if the nation’s physicians and the general public knew that symptoms of many common illnesses worsen at predictable times of day or night, and improve at other times. When do heart attacks and asthma attacks occur most often? When are stuffiness, runny nose, sneezing, and other allergy and hay fever symptoms worst? When is blood pressure highest?

• Most physicians got every answer wrong.

• The typical adult flunked, too.

• Even persons with the target illnesses lacked vital facts that could improve their health, and possibly save their lives.

• Both doctors and patients wanted more information about how time of day affects illness and well-being.¹

This book addresses that quest for knowledge. It starts with this claim: Most of us don’t know how to tell time. Body time.

We pay more attention to watches we wear on our wrists than to clocks we acquire in the womb.

A wristwatch tells only one kind of time: world time. You must heed world time if you are getting married in the morning, have to catch a train, or want to see the six o’clock news. But no wristwatch tells when you think fastest, add numbers best, or swing a tennis racquet most deftly. A glance at your watch might make you think time to eat, or time for bed, even if your stomach isn’t rumbling, or you haven’t started to yawn. Feeling hungry or sleepy, however, requires a watchful brain, a brain with its own clock. A biological clock. A hard-wired program that ties your daily behavior to the rhythms of our planet and runs in the background of your life, adjusting automatically, as circumstances demand.

Most of us think we run our lives by the world’s clock. Indeed, we often protest that this clock runs us, griping, as did Shakespeare’s King Richard III, time is wasting me. Life in the fast track both seduces and enslaves us. At work, we churn out faxes and E-mail, sometimes even to the person in the office next door. We’ve revved up our pace to Internet Time, fretting at the few seconds’ delay signaled by the icon on our computer screens depicting the now obsolete hourglass.

Who has time to visit with friends? To read the books and magazines piled on the nightstand? Where do we find so-called quality time for our partners or children? Some 47 million Americans now work at paid jobs on weekends.

Recognition that nighttime is the right time for sleep has faded with the availability of hundreds of television channels at any hour, and the ease of ordering pizza around the clock even in small towns. If we can’t fall asleep or stay asleep, or can’t get going in the morning, we grumble about bad sleep, but the real problem may be bad timing. Most people don’t know they can fix this broken clock themselves.

While we drive, we gulp coffee, gobble fast-food meals, and gab on the phone. Some cars now boast fax machines. Cats nip the heels of dogs as Americans’ favored pets; cats don’t need to be walked.² A New York woman earns her living as a personal shopper. She picks out clothes for her busy clients … from catalogs. We’re under the sway of what Stephen Bertman, author of Hyperculture, calls the power of now.³ We mimic the March hare, constantly complaining, I’m late. I’m late, for a very important date.

The brain’s clock governs whether or not you’re crabby before you have your morning coffee, how quickly you can write a letter and how accurately you can proofread it, how long it takes you to bike ten miles, whether or not you fall asleep at the symphony, when your ulcers act up, and more. Like the crocodile in Peter Pan, we carry this clock around inside of us. Many of us don’t hear it tick.

Sara Discovers Her Body Clock

• Sara liked to bound out of bed in the morning, pull on her jogging clothes, and go for an easy run. When her knees and back started hurting, she added ten minutes of warm-ups and cool-downs. The pain, unfortunately, did not go away. To give herself more time to stretch, she put off running until she came home from work. Happily, her pain disappeared. What’s more, Sara could run faster and farther. She certainly enjoyed her exercise more.

A specialist in chronobiology, the science of body time, could tell Sara why. Peak performance in most sports occurs in late afternoon and early evening, when body temperature reaches its daily high. Respect for this body rhythm may decrease your likelihood of injuries, whether you’re a neighborhood jogger or an elite athlete. Training and competition times may influence who wins Olympic games and other high-powered sporting events. Stanford University scientists found that players’ biological rhythms predicted winners of Monday Night Football games better than the Las Vegas point spread did.

If Sara wants to maintain or lose weight, or become a partner in her law firm, tuning into her body rhythms can help her achieve those goals more effectively. If she develops a cold, suffers from hay fever, or becomes pregnant, body rhythms will move to center stage in her life.

These findings represent a major leap in scientific understanding: a new way to maintain and optimize health, and to prevent and treat illness. Known as chronomedicine, it holds implications for vastly improving all of our lives.

What Chronomedicine Means to You

Chronomedicine can help you cope better with short-lasting illnesses such as colds and flu, episodic ones such as headaches and back pain, and persistent ailments such as arthritis, high blood pressure, heart disease, cancer, and more. This book details important recent advances to help you in your everyday life.

We report evidence from studies at leading medical centers worldwide showing that:

• Many illnesses disrupt normal body rhythms. Upsets in the body’s most dominant rhythm, the daily wake/sleep cycle, provide an important clue to alert you that something is wrong. Complaints about fatigue and poor sleep trigger visits to the doctor for diseases as diverse as AIDS, diabetes, depression, and multiple sclerosis.

• The signs and symptoms of many illnesses vary across the twenty-four-hour day, over the month, and around the year. Some disorders peak in the morning; heart attacks, strokes, cluster headaches, hay fever, and rheumatoid arthritis are some examples. Others flare at night, including asthma, gout, colic in infants, gastric ulcers, and heartburn. Most chronic illnesses in women worsen in the days just before a menstrual period. Over the year, premenopausal women are most likely to discover a cancerous lump in a breast in the springtime, and men to find a testicular cancer in the winter.

• Time of day patterns help identify causes of many illnesses. Bringing symptom patterns to your doctor’s attention may help your doctor figure out what’s wrong faster and more accurately. The predictable morning spurt in blood pressure and clotting of red blood cells, for instance, make heart attacks and strokes peak in the morning, too. Disruptions in the flow of oxygen to the brain in sleep may produce morning headaches.

• Chronotherapy, or timed treatment, aims to correct these underlying causes or reduce their adverse impact. Knowing symptoms’ time of origin may enable your doctor to use more precise and effective treatment.

• Glitches in the body clock itself may undermine health, making you fall asleep too late, wake up too early, or suffer blue moods. Chronotherapy offers new ways to reset your body clock and resolve such problems.

• The time of day you take diagnostic tests or undergo medical procedures alters the results. If you have asthma, for example, your airway function will vary over the day. It probably is best in midafternoon, and poorest in the early morning. If you routinely go for a checkup in the afternoon, your doctor may think your treatment is working fine. But if you routinely go for a checkup first thing in the morning, the severity of your illness will be more apparent.

• Time-of-day norms are known for many rhythms. In the majority of the population, persons who stay awake in the daytime and sleep at night, who follow fairly regular schedules, the ups and downs of most daily rhythms prove quite predictable from day to day. Some labs already report findings with a time-of-day correction factor. New ambulatory monitoring devices can show your doctor how your blood pressure, heart rate, activity/rest cycle, and other indicators of your health change around the clock. Computer programs can analyze the data, making its collection and assessment practical.

• The time you take medicine matters. Taking the right medicine at the right time for your body and your illness may boost the medicine’s efficacy and cut its unwanted side effects. The upshot is that you probably will feel better, be more willing to continue taking the medicine, need to see the doctor less often for symptom flare-ups or adverse drug reactions, and need fewer hospitalizations for chronic illnesses.

• Nondrug treatments may help correct underlying disturbances in the body clock. Exposure to sunlight-equivalent light, as one example, is now held to be the treatment of choice for persons with winter depression. Light exposure also benefits elderly persons who sleep poorly and wander at night, as well as shift workers and jet-lagged travelers.

• How you organize your daily life, with respect to sleep, meals, exercise, and other factors may make symptoms better or worse, and hasten or slow your recovery. If you have insomnia but stick to a regular wake-up time seven days a week, however bad the night, for instance, you’ll probably sleep better in the long run than if you succumb to the impulse to sleep in.

How This Book Can Help You

We will show you

• the time of day, month, and year that symptoms flare in asthma, arthritis, diabetes, headaches, and many other common diseases

• how to observe and chart your personal symptom patterns by using do-it-yourself tests and diaries

• which times are best for many medical tests and procedures

• when to take your medicine to ensure that it works best and causes the fewest unwanted side effects

• how to monitor your own treatment

• which times are best for different types of exercise

• how to instill good sleep habits in young children, why not to hassle your teenagers when they sleep late on weekends, and how to get a good night’s sleep yourself

• how to reach and maintain your ideal body weight

• what time of day is best for intercourse if you want to conceive

• how to prevent or minimize jet lag

• how to cope with working outside the traditional 9 to 5 hours

This information has never before been gathered in one place for both doctors and the general public. This book aims to be the first comprehensive guide to chronomedicine and chronotherapy.

What Doctors Don’t Know about Health and Body Time

Chronomedicine is a brand-new concept, not only to the average person but also to most doctors. More than half of the 320 primary care physicians surveyed in 1996 for the American Medical Association said they were not familiar with chronobiology. One in four asserted that biological rhythms are not important in diagnosis or treatment.

Most of the doctors—even those who claimed to know something about chronobiology—did not know that some common illnesses predictably flare in the morning, afternoon, evening, or night, or they picked the wrong time. They did not know that blood pressure varies significantly over the day or that labor pains spontaneously start most often at night. They thought that diagnostic tests give the same results whenever they are performed, and that medications and other treatments work equally well, and are equally likely to cause unwanted side effects whenever they are given. They were wrong. We will show you why.

These were experienced physicians in their peak professional years. Most were under age fifty and had been practicing general family medicine or internal medicine for ten years or more. Nearly all saw 400 patients or more each month, persons with all of the illnesses or conditions included in the survey. Yet they knew only slightly more than their patients about the time patterns for high blood pressure, arthritis, respiratory allergies, asthma, chest pain, heart attacks, and migraine headaches.

Only one out of three physicians, most under age forty, said they had learned about chronobiology in medical school. Most of those who had at least some familiarity with the topic said they had gotten their information from reading medical journals. In 1996, the year of the survey, about two thousand articles on chronobiology were published in the world’s scientific journals, far more than any one doctor was likely to read, but perhaps still not a critical mass.

Doctors and their patients also learned about chronobiology from news media reports. In recent years, The New York Times, The Washington Post, The Wall Street Journal, Time, Newsweek, and many other leading newspapers and magazines have reported advances in chronobiology. All of the television networks have produced stories on such topics as timed treatment for cancer and other illnesses, drowsy driving, the genetics of the biological clock, sleepy teenagers, jet lag’s impact on athletes, melatonin, light therapy, and more.

Such stories still may be too infrequent, or too diverse and seemingly unconnected, to reshape attitudes and behavior. Among the general public, even persons who had the illness in question rarely recognized the predictability of its time course.

• Now that you mention it, I do often wake up with a migraine.

• My hay fever is worse in the morning.

• My osteoarthritis acts up in late afternoon. Guess I try to do too much early in the day.

• I just got to work when wham! The pain hit me. It’s lucky I wasn’t driving when I had my heart attack that morning.

What Do You Know about Health and Body Time?

The American Medical Association wanted to know what American physicians and the general public knew about body time. Compare your answers to those from the AMA’s 1996 Gallup survey:

Same Dose of Medicine Sometimes Too Much or Too Little

Think how often a doctor has handed you a prescription, saying, Take this medicine three times a day. By linking pill-taking to mealtimes, the doctor knows you’ll be more likely to remember to take your medicine. A four times a day prescription adds bedtime to the list. This approach is obsolete.

In prescribing equal doses over the day, your doctor presumes that your need for medication is the same all day, and that a consistent amount of medication confers a uniform benefit at all times. This belief is wrong.

If your symptoms wax and wane over the day, you need proportionately more medication to control them at some times, and less at others. Moreover, the way your body absorbs, uses, and excretes drugs varies over the day. The same dose of medicine may be too much at one time, and too little at another. Medicine that may help you at one time may not work as well at another. It may not even work at all. At some times, it may even be harmful.

Consider aspirin, the staple of the family medicine cabinet and one of the world’s most widely used medications. Aspirin has a high safety record, particularly when taken in relatively small doses now and then. The problems come mainly with prolonged use, since aspirin may irritate the lining of the stomach and cause stomach ulcers and bleeding. These effects may occur even with the baby aspirin dosage (75 to 100 milligrams) that millions of Americans, particularly those in their forties and older, take once a day to prevent a heart attack or stroke. Taking aspirin at the proper time dramatically lowers your risk of developing stomach irritation and injury. Aspirin is least likely to cause irritation if you take it at night, and most likely to do so if you take it in the morning. Some persons who cannot tolerate aspirin when they take it in the morning have little or no difficulty when they take it at night.⁴ (See here.)

Asthma attacks are one hundred times more frequent at night than in the day. Persons with severe unstable asthma who live on a conventional awake-in-the-daytime, asleep-at-night schedule get the most relief and greatest protection at night by taking their tablet steroid medication around 3 P.M. If you are a night worker, your doctor will need to synchronize treatment time with your schedule. (See here.)

Most medications used to ease peptic ulcers work best when taken once a day, around 6 P.M., with dinner. Taken at this time, they help block the normal late-night peak in daily secretion of stomach acid. (See here.)

In cancer, cells are most vulnerable to damage when they are dividing. Anticancer medications attack different stages of the cell reproduction rhythm. Some, such as 5-fluorouracil, which is used to treat cancers of the intestinal tract, are best tolerated and cause the fewest side effects when given by infusion while the patient sleeps at night. Others, including adriamycin and doxorubicin, which are used to treat bladder, ovarian, and other cancers, are best tolerated when given in the morning. When cancer medications are given in a chronobiological manner, that is, according to body rhythms, patients may be able to tolerate higher, more potent doses than would be possible otherwise.⁵ (See here.)

Monthly Rhythms May Alter Symptoms, Too

In the AMA’s 1996 survey, only three out of four doctors agreed that the menstrual cycle is a biological rhythm. All doctors should know this is true. Women know it: most recognize that their weight, energy, mood, sleep, cravings for particular foods, interest in sex, skin eruptions, frequency of migraines, asthma attacks, and symptoms of other illnesses predictably wax and wane over the month. Numerous factors, including stress, work, sleep, diet, and even the weather, may make some months more troublesome than others. Some women suffer more intensely than others, a reason some physicians and even some women dismiss or trivialize these symptoms.

Being tuned into these rhythms, however, can afford women a hardy measure of equanimity. A woman who is watching her weight may feel less guilty about nibbling a brownie right before her period starts. For many women, this is the chocolate time of month, a few days with increased craving for chocolates and other sweets. A female athlete or actor may tolerate slight slips in performance, if she knows it’s normal to be less coordinated, less together, when she’s menstruating.

Many women don’t know that a routine test for cervical cancer, the Pap smear, gives the most accurate results if performed near ovulation. A woman can boost her odds of having this cancer detected at its earliest, most curable stage simply by scheduling this exam midway between her periods. (See chapter 11: Time for Sex.)

Many chronic illnesses flare around the time of menstruation. Consider asthma: three out of four adults admitted to the hospital for treatment of life-threatening asthma attacks are female. Their hospital admissions occur four times more often just before or after menstruation than at any other time of month. Knowing that this is a more vulnerable time should heighten women’s attention to their symptoms, and prompt physicians to fine-tune treatment. That won’t happen until both patients and doctors focus their attention on body clocks. (See chapter 15: Sickness and Health from A to [nearly] Z.)

The time of month also may influence the success of treatment. Fifteen studies involving more than 5,000 women with breast cancer show that those whose surgery is performed in the early part of the later half of their menstrual cycle live longer on average than women who undergo surgery earlier or later in the month.⁶ But many cancer experts still are skeptical about these findings, and most operations for breast cancer are scheduled according to the surgeon’s convenience. (See here.)

Ancient Cultures Recognized Body Time

Of themselves, diseases come among men, some by day and some by night the Greek poet Hesiod wrote in 700 B.C.⁷ Whoever wishes to pursue the science of medicine in a direct manner, the great Greek physician Hippocrates observed three hundred years later, must first investigate the seasons of the year and what occurs in them.⁸ Yet generations of physicians have paid little heed.

Nei Ching, the classic Chinese medical text written in 300 B.C., set forth the notion of health as a balance of opposites: cold and warm, moist and dry, passive and active. Yin and Yang, moon and sun, night and day, wife and husband, together represent the whole universe. Yin/Yang remains a central concept in Chinese medicine. It is represented pictorially by a circle that shows the moon and sun embracing. The American Academy of Sleep Medicine, the sleep field’s leading professional organization, uses this symbol to signify its goal of optimizing both sleep and wakefulness.

Monuments built by ancient civilizations reflect knowledge of body time as well as planetary time. Shadows cast by the sun on the towering slabs at Stonehenge constructed in southwestern England some 4,000 years ago show changes in day length over the year. One circle at Stonehenge holds the correct number of markings to calculate the length of a woman’s menstrual cycle or the likelihood of pregnancy, chronobiologist Sue Binkley reports.⁹

Twenty-four baboons carved into the face of a cliff at Abu Simbel 3,200 years ago guard the entrance to a temple to Pharaoh Ramses II. The baboons represent the twenty-four hours of the day, a way of dividing up time the ancient Egyptians devised some 400 years earlier. The baboons symbolize the Pharaoh’s round-the-clock rule, gaining this honor by dint of the Egyptians’ belief that they urinated once an hour: an overstatement, researchers who specialize in baboon behavior today say.

The words of Ecclesiastes remind us that our ancestors took rhythmic behavior for granted: To every thing there is a season, and a time to every purpose under the heaven. The list includes a time to be born, and a time to die, as well as a time to heal.

Even the notion of body clocks is not brand new. The English writer Robert Burton observed, in the seventeenth century, Our body is like a clock; if one wheel be amiss, all the rest are disordered, the whole fabric suffers: with such admirable art and harmony is a man composed.¹⁰

Early in the twentieth century, most physicians in the United States attended to all sorts of ills. When called in the late evening, they could predict their patient might have a flare of a peptic ulcer. If roused closer to dawn, they could anticipate seeing a patient with an asthma attack or a woman about to give birth. The morning brought heart attacks. Today, a person with stomach ulcers might see a gastroenterologist; one having trouble breathing, an allergist or lung specialist; and one with chest pain, a cardiologist. Births more often are induced, typically at the convenience of mother and doctor, and in the daytime. Only the sickest patients go to hospitals, where activity around the clock blurs the distinction between night and day. The present-day lack of appreciation for body time thus is a relatively recent phenomenon. The rise of specialization in medicine has eroded physicians’ recognition of the ubiquity and significance of daily rhythms for health and disease.

The history of medicine is studded with facts that were known, lost, and later rediscovered. Body rhythms are hot again today. Some formidable hurdles, however, still stand in the way of their widespread acceptance.

2

Your Body Is a Time Machine

In 1925 one in four Americans lived on farms. People rose with the sun and worked in the daytime. When it was dark, they slept. They planted seeds in the spring, tended crops in summer, and harvested in the fall. The natural cycles of the day and year shaped daily life and even determined the nine-month school calendar we still use.

That same year, 1925, the great physiologist Walter Cannon of Harvard Medical School introduced the principle of homeostasis, or steady state. Cannon drew on the work of the French physiologist Claude Bernard, who suggested in 1885 that the body strives to maintain constancy in its milieu interieur, its internal environment. Cannon asserted that the body continually fine-tunes itself to adapt to demands placed upon it, maintaining equilibrium. When thirsty, we drink. When hot, we sweat. So far, so good. The notion of health as equilibrium goes back to ancient times. The work of Cannon quickly became part of the canon, the body of principles that guide medical practice. Homeostasis still dominates medical school teaching today. Its overarching reach is the key reason doctors overlook rhythmicity.

Constancy Is an Illusion

Here is the problem with homeostasis: it is incomplete. As an explanation of how the body works, it tells the truth, but not the whole truth. In any one person, in all of us, body temperature, blood pressure, pulse and breathing rates, concentrations of hormones in the blood, hand dexterity, sensitivity to pain, and all other bodily functions differ markedly over the twenty-four-hour day. These variations are not random. They occur in synchrony with our habitual daily pattern of activity and rest. (See the chart, "The Best of Times".) Variations also occur in women across the menstrual cycle, and in both sexes over the year. Age brings about further changes.¹

These changes do not simply reflect a fine-tuning process. More than a thousand rhythmic bodily functions, the musicians in the body’s orchestra, each have a role as distinct from the others as that of a violin from a tuba. They play softer or louder, faster or slower, as the score dictates. All follow their own music, sometimes rearranged as circumstances require. Harmony ensues only when all work together. A simple example: your brain anticipates your usual lunchtime, making you think about food. Your stomach might rumble. Secretion of digestive juices starts, readying your stomach for the cheese sandwich you just ordered. Before you take your first bite, your pancreas starts to manufacture the hormones insulin and glucagon, which you will need to derive energy from the food you eat.

Cannon recorded some variations in bodily activities, including ups and downs in body temperature and blood pressure. But he thought these variations were akin to static on a radio dial, noise caused by interference from sleep, activity, or diet. He did not see their time-of-day patterns, and he viewed the differences as meaningful only when they strayed far afield, outside a range he categorized as normal.

Certainly, large variations are important. Body temperature of 104° Fahrenheit (F), for example, indicates disease. But the widely held belief that normal body temperature is 98.6° F is wrong. This reading is simply an average. Body temperature ranges from about 96° F to about 100° F over the day. It is lowest two to three hours before you habitually awaken, about 4 A.M. to 5 A.M. in someone who sleeps at night and arises around 7 A.M. It starts rising before the normal wake-up time, plateaus in early afternoon, dips a fraction of a degree in midafternoon, and then inches up slightly, hitting its high at about 7 P.M. At 4 A.M., a reading of 98.6° F in such a person would not be normal at all. It would reveal a fever. What’s more, recent studies using improved thermometers and taking repeated measurements across the day, show that the daily average for young adults is 98.2° F. You can see your own pattern by taking your temperature every two hours, starting when you wake up and before you get out of bed.

The daily pattern of body temperature is the most commonly measured rhythm in chronobiology studies. It offers a useful way to tell what time it is on the body clock, and offers an easy reference point for comparisons with other rhythmic body functions.

In Cannon’s day, the technology necessary to easily make round-the-clock measurements did not exist. It took a pint of blood to determine hormone levels then. Today, a drop of blood will suffice. Scientists now know, for example, that people typically secrete ten to twenty times more of the stress hormone cortisol in the morning, at their habitual wake-up time, than they do at night. Night workers who regularly sleep in the daytime secrete their highest amount of cortisol in the afternoon, when they usually arise.

Blood pressure similarly varies over the day. It often is 20 percent higher in the late afternoon than in the morning. Suppose you have been told that you have high blood pressure. If you routinely go for a checkup in the afternoon, your doctor may think your problem is worse than it really is. If you routinely go for a checkup in the morning, your doctor may not appreciate the severity of your illness. If you see the doctor at markedly different times from one visit to the next, the doctor may find it hard to tell how well your treatment is working.

Constancy and Change Coexist in the Body

Both homeostasis and chronobiology are valid. Homeostatic mechanisms reveal the body’s impressive facility for self-correction in the face of momentary changes in our internal environment. Chronobiologic mechanisms help us respond successfully to predictable variations in daily activities triggered by waking, sleeping, eating, and, in women, shifts in hormones across the menstrual cycle. While temperature, blood pressure, cell division, and other bodily functions display set points, sometimes called normal limits, these set points vary across the day, menstrual cycle, and year, often markedly.

In formulating the concept of homeostasis, Cannon concentrated on daily activity. He neglected longer time periods, such as the menstrual cycle. He also overlooked annual rhythms, easily seen in animals that breed at certain times of year and grow thicker, darker coats in winter, changes related to seasonal fluctuations in daylight exposure.

Humans display annual rhythms, too. More babies are born in late summer than at any other time of year in the United States and other countries of similar latitude. In the more than sixty years that U.S. government statisticians have tracked dates of birth, more babies were born in this country in August than in any other month. July and September typically vie for second place and occasionally come in first. In 1998, July topped the chart, with 47,000 more births than February, the least busy month. The birth rates reflect seasonal variations in sexual activity, most likely spurred by heightened secretion of the male sex hormone testosterone in late autumn, possibly triggered by changing amounts of daylight.²

Religious holidays, harvest celebrations, vacation schedules, and personal choices influence the likelihood that people will engage in sexual behavior. But despite the great variety of cultural and individual differences, the yearly biological rhythm persists.

It will be interesting to see if monthly rates shift in 2000, the year this book is published. April 11, 1999, was widely promoted as the ideal date to conceive a millennium baby, which would be born January 1, 2000. The Internet buzzed with strategies to ensure conception. News media around the world provided romantic dinners and hotel rooms to couples attempting to produce the first baby of the year and promised extravagant gifts for the lucky arrival.

Being born in the summer once played a bigger role in enhancing the newborn’s survival than it does today. Plentiful supplies of food meant nursing mothers could eat well. Warm weather eliminated dangers of exposure to frigid air. Fewer viruses float around in summer than in winter. Even today, babies born in the summer and fall tend to be slightly heavier than those born in other seasons, giving them a head start on a healthy life.

Male babies born in the spring, curiously, tend to be a tiny bit taller as adults than those born in the fall. The difference is only one-quarter inch, or 0.6 centimeters, but it’s interesting because it points to yearly variations in hormones critical for growth. The findings come from a study of records collected on more than 500,000 Austrian men at age eighteen, at the time of their compulsory entrance into the army. Spring babies are conceived in summer months, when hours of daylight in Austria are greatest. It is not clear how sunlight might affect height. Increased sunlight simply may bring a more bountiful supply of fresh fruits and vegetables than at other times of year, improving women’s nutrition in the first months of their pregnancy.³

There are seasonal variations in illnesses, too. The risk of developing schizophrenia, for example, is highest for persons born in February and March, and lowest for those born in August and September. Danish researchers reached this conclusion after reviewing records of 1.75 million persons born to Danish mothers between 1935 and 1978, and charting birth dates of the 2,700 who developed schizophrenia. Many factors that affect brain development are believed to play a role in triggering schizophrenia: some, the most critical, are genetic, and thus run in families. But these do not account for all cases of the illness. Other triggers may originate in the environment, including increased exposure to influenza viruses in winter months. There also may be an innate annual rhythm of increased susceptibility to such viruses at that time of year.⁴

A Half-Century of Studies Shows That Body Time Matters

Animal research, starting in the 1950s, showed the importance of timing in treatment. In 1959 Franz Halberg and his colleagues at the University of Minnesota discovered that nearly all the mice given a potential poison at one time of day died. None or only a few of those receiving the same dose of the same chemical twelve hours later did so. Further, the researchers found that almost all of a group of mice exposed to abnormally loud noise at 10 P.M., when they were in their daily activity span, developed seizures. Another group of mice, hearing the same noise at noon, in their rest span, suffered no or minor ill effects. The adverse effects of X rays and other physical and chemical stresses varied across the day in similar fashion.

Time Tells

• Mice and men and women and children prove to be strikingly similar. All respond differently to the same treatment at different times of day. Michael Smolensky learned this lesson as a graduate student in Halberg’s chronobiology laboratories in the 1960s.

"Halberg had embraced with missionary-like fervor the critical, though tedious, task of assessing different medications at different times of day. I decided to study corticosteroids, a synthetic form of the hormone cortisol used to reduce inflammation in severe flare-ups of asthma, arthritis, and other illnesses.

"The body produces cortisol on a regular schedule. Peak secretion occurs around the time we normally awaken, at the start of our daily activity span. I wondered if giving corticosteroids at that time, when the body was prepared for that hormonal surge, would lessen their adverse side effects.

"In one study, I planned to inject groups of young laboratory mice at different times around the clock with either a commonly prescribed corticosteroid medication called methylprednisolone or an inactive saltwater solution. Since graduate students don’t have assistants to help them, I had to camp out in the laboratory. I couldn’t take the chance of missing even one injection time. I collected bread, peanut butter, jelly, apples, Snickers bars, and instant coffee, the staples of a student’s diet, grabbed my sleeping bag, and moved in with my mice.

Each day, I injected methylprednisolone into different groups of mice at midnight, 4 A.M., 8 A.M., noon, 4 P.M., and 8 P.M. In between, I washed and sterilized my instruments, prepared for the next round of injections, and, when I could, grabbed a few minutes of rest. After twenty-one days, I was foggy and cranky from lack of sleep. I was twelve pounds thinner. My clothes had acquired a rodent smell that clung to them through several washings. But the results thrilled me: the mice did well when injected with the medication just after the start of their activity period. They suffered the most side effects when they received the medication just before or in their rest period.⁵

Most Drug Testing Ignores Time of Day

In more recent studies, researchers around the world have seen the same results with methylprednisolone and other medications in numerous human illnesses. But some of their peers regard these findings more as curiosities than as guidelines for standard practice.

About 95 percent of modern drug-development studies use laboratory mice and rats, both nocturnal animals. The humans who conduct the studies work mainly in the daytime. How much time, effort and money have been wasted in this way, we shall probably never know, railed chronobiologist Josephine Arendt of the University of Surrey. It is almost unbelievable that drugs should be first tested in the middle of the rat’s night, she said, when they are mostly destined to be used in the human day.⁶

The implications are unsettling. Can we trust our current drug safety tests? Some chemicals found to be likely carcinogens in these tests may have been considered safe had they been given at the appropriate biological time. Some that looked harmless may prove dangerous if given at a different time.

Even when medications reach the stage in which doctors evaluate their safety and efficacy in humans, time of day often gets little or no attention. Most scientists assume, as the theory of homeostasis claims, that drugs will act the same way and carry the same risk of side effects whenever they are taken. Drug studies typically are conducted in the daytime for the convenience of both scientists and subjects. Tests often begin early in the morning so they can be completed by the end of the normal workday. Ludicrous as it may seem, even some sleeping pills undergo testing this way.

Daily rhythms in the acidity, blood flow, and muscular activity of the stomach alter the rate and even the amount of medication released into the body. Daily rhythms in blood flow to the heart, brain, lungs, and other organs, and in the uptake of drugs by cells and tissues, affect how quickly drugs go to work throughout the body. Daily rhythms in the liver, kidneys, and other organs affect how fast the body uses medications and how long medications stay in the body. All of these rhythms collectively determine how long the medication continues to exert its therapeutic effect. These rhythms also influence interactions between drugs, particularly important in persons with chronic illnesses, who may take two, three, or more medications several times a day.

The only way to find out how a drug will act around the clock is to test it around the clock. Such studies are highly labor intensive. Volunteers must agree to be tested at different times under highly controlled conditions. Subjects sometimes must agree to stay awake for twenty-four hours or longer to avoid the rhythm changes induced by sleep. They may have to sleep at certain times, with periodic awakenings for testing. In medication studies, subjects typically eat standardized meals for breakfast, lunch, and dinner, timed not to interfere with the behavior of the drug they are taking. They must permit frequent blood samples and cooperate in measurements of body temperature, urine output, and other functions. Researchers in turn must assess whether the absorption, metabolism, and other effects of medications differ over the day. Investigators themselves usually have to forgo sleep to follow their