Study shows single blood draw potential to assess timing of circadian rhythm

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, according to a new study published in the Journal of Biological Rhythms.

A central ‘master clock’ in a region of the brain called the hypothalamus helps to regulate the body’s 24-hour cycle, including when people naturally feel sleepy at night and have the urge to wake up in the morning. Recent studies have revealed that nearly every tissue or organ in the body also has an internal timing device, synced with that master clock, dictating when we secrete certain hormones, how our heart and lungs function throughout the day, the cadence of our metabolism of fats and sugars, and more.

As many as 82 percent of protein-coding genes that are drug targets show 24-hour time-of-day patterns, suggesting many medications could work better and yield fewer side effects if administration was timed appropriately. When our internal rhythm is at odds with our sleep-wake cycle, that can boost risk of an array of diseases, researchers said.

Even among healthy people, sleep-wake cycles can vary by four to six hours. Simply asking someone, “are you a morning lark, a night owl or somewhere in-between?” can provide hints to what a person’s circadian cycle is.

But the only way to precisely gauge the timing of an individual’s circadian clock is to perform a dim-light melatonin assessment. This involves keeping the person in dim light and drawing blood or saliva hourly for up to 24 hours to measure melatonin, the hormone that naturally increases in the body to signal bedtime and wanes to help wake us up.

In pursuit of a more precise and practical test, researchers brought 16 volunteers to live in a sleep lab for 14 days under tightly controlled conditions. In addition to testing their blood for melatonin hourly, they also used a method called “metabolomics,” assessing levels of about 4,000 different metabolites. Including amino acids, vitamins, and fatty acids that are byproducts of metabolism, in the blood.

The researchers used a machine learning algorithm to determine which collection of metabolites were associated with the circadian clock, creating a sort of molecular fingerprint for individual circadian phases. When they tried to predict circadian phase based on this fingerprint from a single blood draw, their findings were within about one hour of the more arduous melatonin test.

The test was significantly more accurate when people were well rested and hadn’t eaten recently, a requirement that could make the test challenging outside of a laboratory setting. To be feasible and affordable, a commercial test would likely have to narrow down the number of metabolites it’s looking for, whereas their test narrowed it down to 65. However, the study is a crucial first step, the researchers said.

Other research is exploring proteomics, looking for proteins in blood, or transcriptomics, measuring the presence of ribonucleic acid (RNA) to assess circadian phase. Ultimately, the researchers said they can imagine a day when people can, during a routine physical, get a blood test to precisely determine their circadian phase, so doctors can prescribe not only what to do, but when.