BBC – Future – What is the worst time of the day to get sick?

Look at the skin of your forearm. Pinch him if you want. It may not look like it was 12 hours ago, but if you cut it or burn it, the skin would heal more than twice as fast if you hurt it during the day, compared to passed at the time. night.

This variation in our response to insults and injuries extends well beyond the skin. If you are going for a seasonal flu shot, schedule an appointment in the morning: you will produce more than four times as many protective antibodies if you inject it between 9 am and 11 am, as opposed to six hours later. However, if you needed a heart surgery, the opposite is true: your chances of long-term survival are much better if you go under the knife in the afternoon.

People with nocturnal burns take about 11 days more to heal than daytime injuries

Indeed, everywhere you look in the body, from the brain to the immune system, the 24-hour rhythms that regulate the activity of cells and tissues – often called "circadian rhythms" – seem to dictate our physical recovery from infection. or an injury.

"What we are physiologically during the day is different than we are at night," says Tami Martino, director of the Center of Cardiovascular Investigations at the University of Guelph, Ontario, Canada, which seeks to apply these new knowledge on biological synchronization. to human and animal medicine. From cancer to cardiology, from arthritis to allergies, a better understanding of these rhythms could help administer medications and interventions to patients at the times most likely to be effective and least likely to harm. Strengthening these rhythms may also allow patients to recover more quickly and reduce some of the physical symptoms of the disease.

"I personally believe that circadian medicine can forever change the way we manage human health," says Martino. "One of the most promising new technologies to address the global burden of disease is in the areas of gene therapy, stem cells and artificial intelligence.

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The idea that our physiology varies from hour to hour is actually old. The Greek doctor Hippocrates observed 24 hours a day fever severity. Traditional Chinese medicine also describes the vitality of various organs that culminate at different times – the lungs between 3am and 5am, the heart between 11am and 1pm, the kidneys between 5pm and 7pm, and so on. Thanks to a growing number of recent studies, the effects of our internal clocks on disease and modern medicine treatments are arousing renewed interest.

By changing our desires, our behavior and our biochemistry, these rhythms prepare us for regular events in our environment, themselves dictated by the daily cycle of light and darkness. As far as healing is concerned, there is a good reason why it could be increased on the day rather than at night.

"Our cells have evolved to heal wounds more effectively at the biological moment when they are most likely to occur," says John O'Neill, a circadian biologist at the Molecular Biology Laboratory at the Medical Research Council in Cambridge, UK . "If you are a human, it is extremely unlikely that you will sleep in the middle of the night, while during the day, we would be much more likely to hurt ourselves."

His own research has revealed that cells called fibroblasts, which help repair tissue damage by depositing a new collagen on which skin cells attach, migrate more quickly to injured areas during the day.

"We have consistently found a difference of almost two times in wound healing simply by biological time," says O'Neil. And when they analyzed data from the international burn injury database, they found that people with nighttime burns took about 11 days more to heal than daytime injuries.

Our immune system is also subject to biological rhythms that affect the way it responds to infections. It may seem strange at first to vary our ability to respond to pathogens depending on the time of day, says Rachel Edgar, a virologist at Imperial College London. But this feature may have been developed to protect against excessive activation of the immune system.

"If you get a very big inflammatory reaction, you have to be able to control that, otherwise it can cause a lot of damage," says Edgar.

She explored the interaction between circadian rhythms and viral infections such as herpes. In one study, she found that the herpes virus replicated ten times more in infected mice at the beginning of their rest period – which, being nocturnal, fell early in the morning – compared to those who were infected at the beginning of their activity period. Their results suggest that the effect could be due to more than changes in the activity of the immune system. The daily rhythms of infected cells also affect the extent of a viral infection.

This evidence is part of a recent human study, which found improved responses to the seasonal flu vaccine when administered in the morning compared to the afternoon. Still, it's too simplistic to suggest that it's time to get sick, Edgar warns.

"It will be different for different infectious agents," she says.

Take sepsis, an overwhelming and potentially fatal reaction to infection – it can be triggered by the injection into the blood of molecules found on the surface of a bacterium. If you do this to the mice overnight, only 20% of them will survive, compared to more than 90% if they are injected during their active period.

The results open up exciting new perspectives for the treatment of infectious diseases.

"If we know that a virus is spreading to neighboring cells at some point, we could potentially administer antiviral treatments as soon as they are most effective," Edgar says. "This could reduce the amount of antivirals to give, which would also have consequences for patient compliance."

It's not just our response to infections that could benefit from this approach. More than half of the World Health Organization's essential medicines – 250 drugs found in every hospital in the world – seem to affect the molecular pathways regulated by internal cell clocks, which could make them more or less effective depending on the when they are taken. These include aspirin and ibuprofen, common pain relievers, as well as medications for blood pressure, peptic ulcers, asthma and cancer.

In many cases, the drugs in question have a half-life of less than six hours, which means they do not stay in the system long enough to function optimally if they are taken at a suboptimal time . For example, valsartan, a medicine for high blood pressure, is 60% more effective when it is taken in the evening than in the morning. Aspirin has been proven more effective when taken at night, as are some antihistamine tablets for allergies such as hay fever.

A recent human study suggests that radiation therapy may be more effective if it is administered in the afternoon rather than in the morning.

It is not as easy as it may seem to plan drugs and treatments when they are likely to be more effective. The cost of clinical trials is skyrocketing if you have to start systematically looking for the right time of day to administer a treatment. It is also difficult to ask patients to do what they are told. It's hard enough to get them to treatment, but it's even harder to take those medications at some point.

O'Neill and others believe this is one of the main reasons why, despite the interest in so-called chronotherapy, drug manufacturers have not done much.

The circadian rhythms of everyone are not the same either. Some of us are larks and night owls. A significant proportion of the population also works at night, which can impact circadian rhythm and health. And there is currently no quick and easy test for accurately checking where a person's internal clock is.

Then there is the hospital environment itself – many modern hospital buildings have small windows and dimmed interior lighting that stays on day and night. This is problematic because too little daylight and too much artificial light at night disturb our biological rhythms and our sleep.

Poorly aligned or flattened rhythms are a common feature of hospitalized patients. Some medications, including morphine, can also alter the timing of circadian clocks, while patients' sleep – essential to their healing ability – can be disrupted by pain, worry, or noise. This leads us to wonder how seriously this hinders their recovery and survival.

Some of the strongest evidence comes from patients with heart disease. Like other tissues, the cardiovascular system has a high circadian rhythm – our heart rate and blood pressure are lowest when we sleep, but they increase sharply when we wake up; our platelets, small fragments of blood that help the blood clot, are more sticky during the day; while levels of hormones like adrenaline, which contract our blood vessels and make our hearts beat faster, are also higher during the day. These circadian variations affect the timing of serious cardiac events, such as heart attacks.

"If you watch people entering the emergency rooms, you will find that heart attacks are more likely to occur between about 6am and noon, compared to any other time of the day or night," said Martino. However, timing may also affect our ability to recover from a heart injury.

A recent study suggested that in people undergoing cardiac valve replacement surgery, those who underwent surgery in the afternoon were twice as likely to experience a major cardiac event within the next 500 days, compared to those who had had morning surgery. The researchers calculated that if all patients underwent surgery in the afternoon, events could be avoided for a major event on eleven patients. Other studies have shown that for patients recovering from a heart attack or heart surgery, those who were more exposed to daylight had a higher survival rate and left the hospital earlier. .

Animal studies help to understand why this could be. When Martino and his colleagues exposed groups of mice to normal or disturbed light-dark cycles after simulated heart attacks, they found significant differences in the number and type of immune cells that rallied to the heart, the amount of scar tissue and ultimately, survival rate. Mice whose circadian rhythms were disrupted, as could be the case during a hospital stay, were more likely to die from their heart injury. Other studies have revealed differences in the type and number of immune cells that infiltrate the injured heart tissue, depending on the time of injury.

"Some ICUs or cardiac care units will turn down the lights a bit at night, which is a bit helpful, but some are not, at all," says Martino. "For example, if people go to emergency rooms and there are no beds available, they can stay in bright light all night or even in a hallway after having a heart attack or stroke. It is therefore obvious that their sleep and their circadian rhythms will be profoundly disrupted during these first two days, which are of crucial importance for healing. "

So, what to do about it? Planning a surgery when the body is in the best position to deal with it is a solution. For heart surgery, this may be the afternoon, but this may be different for other interventions. For example, O'Neill's study on wound healing suggests that more collagen is deposited when wounds are sustained during the day, which may be associated with greater healing.

"For cosmetic surgery, we could argue a lot later, maybe at night, because the healing would be longer, but could result in fewer scars," he speculates, noting that no one is there. again tested.

Another solution could be to install so-called circadian or human-centered lighting systems, the intensity and color of which vary in 24 hours, trying to reproduce outdoor lighting conditions. At Glostrup Hospital in Copenhagen, Denmark, doctors measure the impact of such a system on the rehabilitation service after a stroke. Until now, the data suggests that patients exhibit more robust circadian rhythms in response to the circadian lighting system and show a reduction in depression and anxiety compared to those in the past. a section of the service with conventional lighting of a hospital.

It may even be possible to design drugs that can stabilize circadian rhythms in hospitalized patients – or block them long enough to allow surgery at the optimal time for healing. Such molecules have already been tested in animals, with promising results.

"In the future, I can imagine a world in which we will use a circadian pill, or the presence or absence of light to cure heart disease," says Martino.

Light, sleep and timing; we often take them for granted, but these three fundamentals can transform health care.

* Linda Geddes is the author of Chasing The Sun: The new science of sunlight and how it shapes our bodies and minds.

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