The SECRETS of your BODY CLOCK can transform your health

Statins at night. Flu jab in the morning. Precise mealtimes. A life-changing new book reveals how...

EVER felt as if you are run by clockwork? That’s because to some extent you are. A biological clock is ticking in every cell of your body. These clocks respond to signals from a patch of your brain which keeps them synchronised with each other, and with the time of day. It’s called the suprachiasmatic nucleus.

Containing 20,000 cells and no bigger than a grain of rice, it is the biological equivalent of the Greenwich Meridian; it’s the reference point used by the billions of other cellular clocks in your body to remain accurate and maintain the circadian rhythm of your body.

The normal working of the brain, immunity, and bodily functions such as heart rate or digestion, are all controlled by this rhythm — disrupt it, and it can damage your health and recovery from illness.

Yet these rhythms can be disrupted by many things: bright light at the wrong time of day; chaotic eating or exercise patterns; certain medications. Even the microbes in our gut have circadian rhythms, which can be disrupted by antibiotics or eating at unusual times. Studies in mice suggest that when this happens, it may further impair the function and rhythm of our organs.

Now, new understanding of how the clocks in our bodies behave is being used to explore how we can recover from illness and make drug treatments work better — with fewer side-effects.

The body clock is so intertwined in the healing process that even the time of day you experience an injury, or an event such as a heart attack, may have an impact on how well and how quickly you recover.

For example, we know that the cardiovascular system has a strong circadian rhythm: blood pressure is lowest when we’re sleeping, but it rises sharply upon waking up; our platelets — small fragments in the blood that help it to form clots — are stickier during the day; and the levels of ‘fight-or-flight’ hormones such as adrenaline, which constrict our blood vessels and make the heart beat faster, are also higher in the daytime.

These circadian variations affect the likelihood of a heart attack: statistically, you’re more likely to have one between 6am and midday than at any other time.

Timing may also affect our ability to recover from heart injury. Studies in mice have revealed differences in the type and number of immune cells that infiltrate injured heart tissue, depending on what time of day the injury occurs. This affects how much scar tissue forms and how well the heart subsequently pumps blood — which ultimately impacts survival.

Human studies have also suggested that patients’ survival prospects are improved if they have heart surgery in the afternoon rather than in the morning.

WHY PAIN IS WORSE AT CERTAIN TIMES OF DAY

IT’S not only the cardiovascular system that shows this variation. A recent study found that skin cells called fibroblasts, which play a key role in wound healing, work more efficiently during the day than at night because of fluctuating levels of proteins, which direct the cells towards injured regions.

Skin wounds that were inflicted during the night (when mice are awake and active) healed faster than those inflicted during the daytime. When the same researchers analysed data from the International Burn Injury Database, they found that people who suffer burns during the night take approximately 11 days longer to heal than those injured during the day.

There are other examples of circadian variations in our physiology: viruses find it easier to replicate and spread between cells at night; allergic reactions are strongest between 10pm and midnight; while joint pain and stiffness are worse in the early morning.

Disruption of these rhythms — which commonly happens in a hospital environment — could impede people’s recovery.

British guidelines for intensive care units recommend natural daylight in every patient’s room, as well as artificial lights which can be turned up or down.

However, even in hospitals that follow this guidance, bedside illuminance during the daytime is well below the levels found even shortly before sunset outdoors.

More generally, modern hospital buildings are often characterised by small windows and dim indoor lighting that remains switched on day and night.

Yet exposure to light at night and an absence of bright light during the day can cause circadian disruption, sending the rhythms in our cells out of sync. This doesn’t only disrupt sleep, which is itself essential for recovery; it has a direct impact on healing too.

For example, a large study of Canadian patients recovering from heart attacks found that the mortality rate among those recuperating in brighter rooms was 7 per cent, compared to 12per cent among patients in gloomier rooms. Compounding the problem, certain drugs, including morphine, can alter the timing of circadian clocks, while patients’ sleep may be further disrupted by pain, worry or noise.

No surprise, then, that critically ill hospital patients often have circadian rhythms that are out of phase with the external time of day. So, stabilising or strengthening these rhythms, by exposing people to bright light during the day and darkness at night, could enhance their recovery.

Some of the strongest evidence for this comes from studies of infants. Although babies are notorious for their fractured sleep, the brain’s master clock seems to be in place from about 18 weeks into a pregnancy. Circadian rhythms mature progressively from that point on, although it’s not until around eight weeks after birth that predictable sleep rhythms emerge.

The developing foetus isn’t exposed to bright light, but its circadian system may latch on to other cues, such as daily fluctuations in its mother’s hormones, heart rate and blood pressure. However, if a baby is born prematurely, these signals are lost. Premature babies are more likely to thrive, it seems, if they are exposed to more natu-

ral light cycles, consisting of 12 hours of light and 12 hours of darkness.

A recent review concluded that such ‘cycled light’ shortened the amount of time they spent in hospital after birth, compared to infants kept in near-darkness or continuous bright light; they also showed a trend towards greater weight gain, reduced eye damage and less crying.

DIMMER LIGHTS SPEED RECOVERY

FEWER studies have investigated the impact of light exposure on adults, but concern about the effects of hospital lighting on our health is prompting action.

The Royal Free Hospital in London is installing circadian lighting (which brightens and dims to simulate dawn and dusk) in its A&E department, and hospitals in other countries have already introduced it.

Evidence to support the use of circadian lighting comes from Glostrup Hospital in Copenhagen, Denmark, where doctors have been measuring the impact of a circadian lighting system in the stroke rehabilitation ward. The lights boost exposure to bright blue light (to which the circadian system is most responsive) during the day, then dim and tune out blue light at night. When checks or procedures are carried out at night, they are performed under amber light.

‘The point is to stabilise circadian rhythms while patients are in hospital, to try to boost their recovery,’ says Anders West, a neurologist at the hospital, who has been leading the project.

The data so far suggests patients exhibit more robust circadian rhythms in response to the circadian lighting, and show reduced fatigue, compared with those on a section of the ward with conventional hospital lighting. They also have reduced depression scores.

PILLS THAT WORK BETTER AT NIGHT

ANOTHER growing area of interest is how the time of day that a medication is administered can dictate how effective it will be.

Almost half of our genes are under the control of our body clocks, and for every major disease investigated so far — including cancer, Alzheimer’s, type 2 diabetes, coronary artery disease, schizophrenia, and obesity — genes strongly associated with the risk of each condition have been found to fluctuate according to the time of day.

This means that hitting them with treatments at times when these controlling genes are more or less active is likely to impact how well they work. In fact, 250 drugs found in every hospital in the world hit molecular pathways that are regulated by internal clocks, which could make them more or less effective depending on when they are taken.

These include aspirin and ibuprofen, as well as drugs for blood pressure, peptic ulcers, asthma and cancer. In many cases, the drugs have a half-life (the time it takes for the amount in the system to reduce by half) of less than six hours. That shows how crucial it is to take them at the optimal time — miss that window and the amount of the drug in your system at the time you want it could be negligible. For instance, the blood pressure drug valsartan is 60per cent more effective when taken in the evening, compared with first thing in the morning. Many cholesterol-lowering statins are also more effective when taken in the evening. Research has also suggested that taking a delayedaction non-steroidal anti-inflammatory drug such as indomethacin before bed may be the most effective way to prevent rheumatoid arthritis pain in the morning.

Such information is rarely shared outside of academic journals. But doctors are beginning to use this understanding to help reduce the side-effects of treatments such as chemotherapy.

Many chemotherapy drugs work by targeting rapidly dividing cells — into which category cancer cells fall. However, they also kill some healthy cells such as those lining the gastrointestinal tract or in the bone marrow. This explains some of the unpleasant side-effects associated with chemotherapy, such as nausea, loss of appetite and a greater risk of infections.

However, healthy cells only divide at certain times of the day, whereas these daily rhythms appear to be absent or disrupted in some cancer cells.

In the Eighties, during tests on mice, French doctor Francis Levi discovered that the chemotherapy drug anthracycline appeared to be more toxic if it was given during the mice’s active period rather than at a time when they would normally be asleep. A subsequent trial in women with ovarian cancer confirmed that the side-effects could be significantly reduced if the drug was given at 6am rather than 6pm.

It’s not just side-effects: chronotherapy, as this area of precision-timed medicine is known, has even been found to increase survival for men with colorectal cancer receiving the chemotherapy drug oxaliplatin by on average three months compared to conventional drug timing. More recently, a study found that the chemotherapy drug irinotecan is better tolerated in the morning if you’re a man, but in the afternoon/early evening if you’re a woman. These time-of-day effects aren’t only confined to cancer.

HAVE FLU JAB IN THE MORNING

FOR instance, the seasonal flu vaccine was recently discovered to generate four times as many protective antibodies if taken between 9am and 11am, compared with when taken six hours later.

Certain medical tests will also give different results depending on when they’re done, which is why many doctors take multiple blood pressure readings over the course of 24 hours, before making a diagnosis of high blood pressure.

Since circadian rhythms exist in every tissue investigated so far, it’s highly likely that similar effects will show up in other diseases, drugs and treatments, as this area is explored further. Challenges remain, though. Besides sex differences, there are differences in the precise timing of our individual rhythms — and there’s currently no quick and simple test to confirm the details of an individual’s internal clock. Having this information could have benefits beyond just optimising the timing of drugs; it could also tell you if someone else’s rhythms were weak or disrupted.

There’s a growing interest in creating drugs that could boost the amplitude of our circadian rhythms, rather than relying on light.

Light, sleep and timing — such basic things, but together they might just have the potential to transform health care.

ADAPTED from Chasing The Sun: The New Science Of Sunlight And How It Shapes Our Bodies And Minds, by Linda Geddes, published by The Wellcome Collection and available from January 10, 2019.