Circadian rhythms help determine when we are most vulnerable to disease
By Melinda Beck-writer for the Wall Street Journal
Heart attacks often occur in the morning. Epileptic seizures peak in the late afternoon. Asthma attacks get worse and more deadly between 11 p.m. and 3 a.m.
Researchers are finding that circadian rhythms, which cycle every 24 hours or so, drive virtually every system in the human body, from circulation and cognition to metabolism, memory and mood. And they play a big role in determining when we are most vulnerable to disease.
Chronobiology—the study of these internal clock mechanisms—has exploded in recent years thanks in part to the discovery of specific genes, to which scientists have given names like Clock, Period and Cryptochrome. Those genes help keep our biological systems in sync with light and darkness, which makes for a rush hour of chemical changes at dawn and dusk.
Understanding biorhythms is helping doctors direct treatments, including the best times to take various medications. It is also suggesting new treatment strategies, such as adjusting the light in nursing homes to help people sleep better.
Of course, people often disrupt their circadian cycles with jet travel, erratic work schedules, watching TV and Web surfing long into the night. That can raise the risk for a variety of health problems, including heart disease and diabetes.
The body’s master time keeper is a group of neurons in the hypothalamus, located behind the eyes, called the suprachiasmatic nucleus, or SCN. In darkness, the SCN prompts the pineal gland to release melatonin, the hormone that facilitates sleep. Other chemical changes reduce body temperature, blood pressure and heart rate, all of which are at their lowest overnight.
Other systems are highly active at night. Stomach-acid production peaks between 10 p.m. and 2 a.m., digesting the evening meal and possibly exacerbating heartburn. The liver dumps glucose into the bloodstream just before dawn. Leptin, a hormone that damps appetite, is high, so people tend to be least hungry when they wake up. And the immune system may be overactive, inflaming airways in asthma sufferers and swelling arthritic joints.
In the morning, light on the retinas signals the SCN to shut off melatonin. Cortisol, a stress hormone, rises instead, preparing the body for the day’s demands. Blood pressure and heart rate start increasing. A substance called PAI-1, which makes blood clot more readily, peaks around 6:30 a.m. Experts think PAI-1 may have protected early humans from bleeding to death from an injury as they set off foraging for food. But in modern humans with plaque-lined arteries, the substance raises the risk of blockages that cause heart attacks and strokes. Those peak around 9 a.m., studies show.
Exposure to bright light at a time the body isn’t used to can advance or delay the circadian cycle. But that doesn’t happen right away, as jet-lag sufferers know. An earlier study that lasted 11 years found that heart attacks among vacationers in Hawaii corresponded more closely to early morning back home than they did to local time.
Eating, sleeping and other behavioral patterns, of course, also affect the body’s daily changes. But various biological systems, including blood pressure, heart rate, blood clotting and adrenaline, rise and fall in circadian rhythms of their own, according to research at the Medical Chronobiology Program at Brigham and Women’s Hospital in Boston and at other centers. If those behavioral patterns and circadian rhythms get out of sync, a variety of health problems can result, as researchers have shown in experiments with lab animals and observed in humans.
For example, when rodents are fed during their usual sleep time, their liver and pancreas adjust to that feeding schedule but their SCN master clock doesn’t. Even if the amount of food is the same, they will gain more weight and fat than rodents fed at the normal time, says Frank Scheer, the chronobiology program’s director.
Shift workers—who make up about 10% of the U.S. workforce—are vulnerable to similar problems when they eat, sleep and work out of sync with their circadian rhythms. Many have higher rates of heart disease, diabetes, obesity, high blood pressure, stroke and other disorders.
Millions of other people develop what experts call “social jet lag” by staying up late and sleeping late a few days each week. “If you do that Friday, Saturday and Sunday, then by Monday morning, when you have to go to work, you are waking up at a much earlier circadian time, which can have consequences for days to come,” says Dr. Scheer. Even the one-hour shift that occurs with setting clocks forward in the spring raises the rate of heart attacks for a week, studies show.
Surveys of tens of thousands of adults by the University of Munich’s Institute of Medical Psychology have found that the greater the difference between sleep time on weekdays and weekends, the more likely people are to be obese.
Many people with depression, bipolar disorder and other mental-health issues have disrupted circadian rhythms and erratic sleep patterns. Patients with bipolar disorder tend to have cycles that are longer than 24 hours, says psychiatrist Michael McCarthy, a member of the University of California, San Diego’s Center for Circadian Biology. There is growing evidence that these problems may be related to defects in clock genes.
Sleep cycles become earlier, shorter and more fragmented as people age. “The studies all show that having disrupted circadian rhythms puts older people at greater risk for cognitive impairment, depression and mortality,” says Sonia Ancoli-Israel, a professor emeritus of psychiatry at the UCSD center.
Such issues are even more pronounced in people with Alzheimer’s disease, whose sleep, core temperature and other biorhythms don’t follow predictable patterns. The increased restlessness, irritability and confusion known as “sundowning” that some Alzheimer’s patients experience in late afternoon isn’t well understood. Another mystery is the so-called witching hour surge in crankiness that babies often demonstrate at the end of the day.
“At the extremes of life, in babies where the brain hasn’t fully developed or in dementia patients, when you are getting degeneration, the time connections in the brain may not be fully coordinated,” Dr. McCarthy suggests. “And fatigue makes everything worse.”
Researchers are starting to develop treatment strategies to take advantage of circadian rhythms or restore them when they are out of sync—a field called chronotherapy.
“It’s a very promising area but the field is very young. More clinical trials need to be done,” says Steven Shea, a professor of public health and preventive medicine at Oregon Health and Science University.
Taking medications at night that help prevent heart blockages, such as long-acting beta-blockers and ACE inhibitors, may lower the risk of early morning heart attacks, experts say. Taking acid-blocking drugs at night might be more effective, given the overnight surge of stomach acid.
Light therapy has been shown to be effective at improving sleep among older people in nursing homes, according to several randomized, controlled trials. “Many older adults are not getting sufficient sunlight,” says Dr. Ancoli-Israel, of UCSD. She says nursing-home patients typically get only a few minutes of bright sunlight a day.
Administering melatonin to aid sleep also has been studied, but with mixed results. And melatonin can worsen glucose tolerance, so it isn’t useful for everybody.
In general, experts say going to bed, getting up and eating meals at the same time every day, getting lots of light in the morning and avoiding it at night can go a long way to improve health and mood. “It’s the same advice we’ve always given,” says Dr. McCarthy. “But now we understand a lot more about why that’s true.”