Circadian medicine’s quest to make the most of our internal clocks


Circadian medicine's quest to make the most of our internal clocks

His observations resonated with circadian scientists struggling to advance in their own institutions. “John managed to bring some discussion or awareness to the discussion that needed to take place,” says Elizabeth Klerman, a professor of neurology at Harvard Medical School who works in the sleep department at Massachusetts General Hospital. Frank Scheer, director of the Medical Chronobiology Program at Brigham and Women’s Hospital, was also impressed. “We’re trying to improve the health of the most vulnerable, we have a responsibility to take care of them, and yet they’re in environments that aren’t conducive to sleep,” he says of hospital patients. “I think his work is beautiful. He’s making great strides in that area.”

Although the PNAS data showed that having hospitals deliver drugs is likely to make more operational than medical sense, they failed to show whether this timing is harmful to patients. If not, why change? Hogenesch’s team and collaborators at other hospitals are now analyzing electronic medical records to see if they can show that the times certain common drugs are given affect their effects. That’s harder than it sounds, because the data hospitals collect is primarily for billing purposes, not research, and when patients receive services and medications aren’t always noted. If the logging of treatment times — of blood draws, vaccines, urine and other samples — were standard in patients’ electronic medical records, it could greatly improve our understanding, Zee notes. “Nowhere on your vaccination card does it say when you got it.” But it should be “that easy,” she adds. “It’s all electronic.”

All data extracted from medical records is still observational data, but the more such data you have from a variety of sources, the more convincing it can be. In the meantime, researchers can create larger and more representative samples by looking at several small studies together in what is called a meta-analysis. Last year, Hogenesch and colleagues published a meta-analysis of previous clinical trials that included the time of day that subjects received one of 48 pharmacological or to argue that drug timing could have a major impact, as a preprint prior to peer review surgical treatments. Unexpectedly, low-dose aspirin, which millions of people take daily to prevent cardiovascular disease, turned out to be the most time-sensitive: Eight out of 10 studies found that it was more effective when given in the evening as opposed to in the morning.

Personalized circadian medicine can be the future. The timing of our clocks varies individually, set by the sun, indoor lighting, genetics, our behavior, our age, each other. Scientists are still struggling to come up with a quick and easy way to determine what stage or stages your organs are in. But right now, absolute precision isn’t required to improve the coordination and strength of your biological rhythms. Circadian researchers generally suggest getting as much sunlight as possible during the day, especially upon waking, dimming the lights before bed, and darkening your bedroom. (Parking during standard time in America, not daylight, would help.) Load up on your calories earlier in the day. Above all, try to keep your schedule comparable throughout the week, including weekends. “Here’s a place to start thinking about optimizing overall health — improving mood, improving overall health,” Helen Burgess, professor of psychiatry and co-director of the Sleep and Circadian Research Laboratory at the University of Michigan, told me. “We all are getting older. A lot of us feel like we’re languishing,” she added. “What are the little things I can do to make me feel better?”

Circadian medicine, in other words, can improve our well-being, but most of us shouldn’t expect it to transform our lives anytime soon. However, there are exceptions to this rule, the unusual circumstances of which may later point to broader applications. As Hogenesch put it to me: “One learns from edge cases.”

Shortly after he arrived in Cincinnati, a colleague from Boston sent him an email from the parents of Jack Groseclose, a teenager with Smith-Kingsmore Syndrome, an extremely rare condition caused by a mutation in a single gene, causing pain and seizures, developmental delays, autism, and a tendency to self-harm. In their letter, Mike and Kristen Groseclose explained that Jack was taking a drug to turn off the gene. It had improved many of his symptoms, but his sleep had taken on a bizarre pattern. For over a week he slept no more than an hour or two, instead pacing constantly. (A Fitbit his parents bought to track his activity showered them with congratulations.) He then slept 14 hours a day for seven to 10 days. “After 10 days of little to no sleep, his body begins to break down,” they wrote. “He gets shaky and unsteady, breaks out with eczema.” Jack’s doctors were amazed. Hoping to find an explanation, the Grosecloses had attached a bar graph of Jack’s sleep cycle and a photo of him to their email. “He looked bad,” Mike told me. Kristen added, “We thought a visual aid might help.”

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