Study exhibits {that a} single blood draw can assess the timing of the circadian rhythm

The answer, according to increasing research, can affect anything from a person’s predisposition to diabetes, heart disease, and depression, to the optimal time to take medication. But unlike routine blood for cholesterol and hormone levels, there is no easy way to accurately measure a person’s individual circadian rhythm.

New CU Boulder research published in the Journal of Biological Rhythms suggests that day may come in the not-too-distant future. The study found that it is possible to determine the timing of a person’s internal circadian or biological clock by analyzing a combination of molecules in a single blood draw.

“If we understand each person’s circadian clock, we may be able to tell them the optimal time of day to eat, exercise, or take medication,” says senior author Christopher Depner, who conducted the study as an assistant professor of integrative physiology at CU Boulder. “It could be groundbreaking from a personalized medicine perspective.”

A central “master clock” in a brain region called the hypothalamus helps regulate the body’s 24-hour cycle, even when people are naturally sleepy at night and feel the urge to wake up in the morning.

Recent studies have shown that almost every tissue or organ in the body also has an internal timing device that is synchronized with this master clock and dictates when we secrete certain hormones, how our heart and lungs function throughout the day, our cadence Fat metabolism and sugar and more.

Up to 82% of the protein-coding genes that are drug targets show 24-hour time patterns, suggesting that many drugs might work better and have fewer side effects if administration were timed appropriately.

When our internal rhythm contradicts our sleep-wake cycle, it can increase the risk of a number of diseases, said Ken Wright, co-author of the study, professor of integrative physiology and director of the sleep and chronobiology laboratory at Boulder CU.

“If we are to be able to pinpoint the timing of a person’s circadian rhythm, we need to know that timing,” he said. “Right now we don’t have an easy way to do that.”

Even in healthy people, the sleep-wake cycles can vary by four to six hours.

Just ask someone, ‘Are you a morning lark, a night owl, or somewhere in between?’ can provide clues about a person’s circadian cycle.

But the only way to accurately measure the timing of an individual’s circadian clock is to do a melatonin rating in low light. This includes holding the person in dim light and drawing blood or saliva every hour for up to 24 hours to measure melatonin – the hormone that naturally increases in the body to indicate bedtime and decreases to wake us up .

In search of a more accurate and practical test, Wright and Depner placed 16 volunteers in a sleep laboratory for 14 days under tightly controlled conditions.

In addition to testing their blood for melatonin every hour, they also used a method called “metabolomics,” which measures the levels of about 4,000 different metabolites (such as amino acids, vitamins, and fatty acids that are byproducts of metabolism) in the blood.

They used a machine learning algorithm to determine which collection of metabolites was linked to the circadian clock – and created a kind of molecular fingerprint for individual circadian phases.

When they tried to predict the circadian phase from that fingerprint from a single blood draw, their results were within about an hour of the more difficult melatonin test, said Depner, now an assistant professor at the of Utah.

The test was significantly more accurate when people were well rested and hadn’t eaten recently – a requirement that could make testing a challenge outside of a laboratory setting. And to be feasible and affordable, a commercial test would likely have to narrow down the number of metabolites it was looking for (their test narrowed it down to 65).

But the study is a critical first step, Wright said.

“We are at the very beginning of developing these circadian rhythm biomarkers, but this promising study shows that it is possible.”

Other research, including some from Wright’s lab, looks at proteomics (looking for proteins in the blood) or transcriptomics (measuring the presence of ribonucleic acid, or RNA) to assess the circadian phase.

Ultimately, researchers envision a day when people can get a blood test during a routine physical exam to pinpoint their circadian phase – so doctors can not only prescribe what to do, but when.

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