Why taking an aspirin at bedtime (not first thing in the morning) can halve your risk of a stroke 

Our body clock affects everything from when we feel hungry to our sexual compatibility. 

In the first part of our serialisation of his new book, in yesterday’s Daily Mail, one of Britain’s leading experts on our circadian rhythms explained how being aware of these patterns can revolutionise our health. Today, he tells of another of its life-changing powers…

Awareness that we have a body clock — or circadian rhythm – dates from 1729 when the French astronomer Jean-Jacques d’Ortous de Mairan noted how a mimosa plant placed in a room with no light still unfolded and folded its leaves. 

Now, more recent scientific developments on circadian rhythms are helping to improve our lives.

Over the past few decades, the study of human body clocks and how they govern our lives has come on leaps and bounds. I began work in this area 40 years ago and even I am sometimes astonished by the speed of progress in our understanding.

It is deeply frustrating, though, that this knowledge is not being translated into clinical practice even when many of the findings are well-established. This is particularly true regarding the time that medications should be taken to improve their effectiveness and thus transform patient care. That’s why in the second part of this series I want to guide you so you can harness this knowledge for yourself.

The fact is that everything in our bodies is tied to the finely balanced rhythms of our body clock – we are very different people at 12 noon compared to 12 midnight.

And because the hundreds of chemical reactions and physical changes occurring in our bodies vary so much over the day, the symptoms of diseases also change over that time – see below. As a result, there’s an ‘ideal’ time to take many medicines to make them more effective. Much research supports this.

Yet most people don’t take medicines at a time that optimises their impact. Instead, they take them when it is convenient, either for themselves or for the medical staff administering them. Even the timings listed on a prescription – say, ‘two tablets with breakfast’ – are not necessarily up to date with the science, or are vague.

Research has identified body clock-related changes in the action of more than 100 drugs. Yet sadly, this information is not always acted upon by our overworked and time-pressured NHS staff.

But there’s no reason you can’t be guided by this knowledge for your own situation. Of course you must always first discuss what you intend to do with your GP.

Let’s start with two leading causes of premature death – strokes and heart attacks.

Sleep and circadian rhythm disruption (SCRD) – caused by factors such as night shift work, frequent jet lag, the demands of work eroding your sleep and other disruptions to regular routines – can increase the chances of high blood pressure, heart disease and stroke, among other illnesses.

SCRD not only determines whether we’re at risk of health problems, but our circadian rhythms can determine when such events or symptoms might occur.

A stroke happens when a blood vessel in the brain ruptures, or when there’s a blockage in the blood supply to the brain caused by a build-up of fatty plaques in the blood vessels.

Similarly, a heart attack occurs when the supply of blood to the heart is suddenly blocked by plaques in the coronary arteries.

We are most likely to die from a stroke or heart attack first thing in the morning. A major review of studies, based on 11,816 stroke patients, showed a 49 per cent increase in the chance of a stroke between 6am and noon, and similar findings have been repeatedly documented for heart attacks.

But what’s behind this early morning window of danger? This is an important question as it affects the best time to take medications, such as blood pressure drugs (anti-hypertensives) and statins.

A key contributor is the rise in heart rate and blood pressure in the early hours before we wake each day. In effect, this increase – driven by the body clock – gets us up and going. Most significantly, there is also an increase in clotting factors in your blood in the morning, including cells called platelets.

Platelets trigger clot formation and can obstruct blood flow through the creation of a platelet ‘plug’. These normally prevent blood loss following injury – and we are more likely to encounter injury in the day than at night. But platelets can also work against us by producing clots that block blood vessels.

As a result, many people with high blood pressure or otherwise at risk of stroke or heart attack are prescribed antihypertensive drugs or anti-clotting drugs such as aspirin.

Because the hundreds of chemical reactions and physical changes occurring in our bodies vary so much over the day, the symptoms of diseases also change over that time – see below. As a result, there’s an ‘ideal’ time to take many medicines to make them more effective. Much research supports this

Many doctors suggest patients take these pills first thing in the morning as this is when they’re most at risk. Yet the latest research shows that blood pressure medications are more effective when taken before bedtime.

In the most extensive trial, at the University of Vigo in Spain in 2019, more than 20,000 people with high blood pressure were told to take their medication at bedtime or in the morning.

Over the next six years it was found that those who’d taken their pills in the evening had almost half the risk of cardiovascular death, including heart failure and stroke.

This is the result of what’s known as ‘pharmacokinetics’, the way drugs are absorbed and distributed through the body, then broken down and excreted.

These processes all take time. So, taking blood pressure medication at bedtime means that drug levels rise and remain in the body at relatively high levels.

As a result, they can reduce blood pressure to coincide with the time when the sharp rise in blood pressure normally occurs between 6am and noon.

If antihypertensive drugs are taken in the morning, their effectiveness will peak after this surge in blood pressure and long before the next one is due.

A similar effect is seen with aspirin, commonly prescribed to reduce stroke risk as it reduces the ability of platelets to clump and form unwanted blood clots.

Since aspirin levels in the blood rise rapidly, then decline fairly quickly within a few hours, the question is: how does bedtime aspirin reduce platelet ‘stickiness’ in the morning?

The answer is that every evening, 100 billion new platelets are made, so taking aspirin at that time of day, just as they’re being formed, ensures the new platelets are ‘deactivated’ long before the dangerous window for strokes the following morning. The downside is that taking aspirin before bed may increase the chances of damaging the stomach lining, leading to ulcers or reflux – although drugs called proton pump inhibitors (PPIs) can resolve this, see panel below.

Another risk factor for heart attacks or stroke is raised levels of ‘bad’ cholesterol. To address this, many people are prescribed statins which slow down cholesterol production in the liver.

Of course, there’s an optimum time to take statins, too.

Cholesterol levels in the blood follow a circadian rhythm, with cholesterol normally produced between midnight and 6am. The best time to take statins depends on what type you use: some remain effective in the blood for four to six hours, but others work for 20 or even 30 hours. So if you’re on a short-acting statin such as simvastatin, take it around bedtime to ‘hit’ the night-time production in cholesterol.

But if you’re on statins that are effective for 20 to 30 hours, such as atorvastatin) take them any time because their effectiveness will always overlap with higher levels of cholesterol production at night.

Harnessing knowledge of the body clock could make a significant difference to cancer treatment, too.

Increasingly, research is identifying the role of circadian rhythms, and their disruption, in cancer developments and how we can use time to our advantage when treating tumours.

Laboratory studies show that tumours grow much faster if the circadian system is disrupted.

In experiments, mice with simulated jet lag show much faster tumour growth. And similar effects have been demonstrated in humans. Night-shift workers, including nurses, and those with rapidly changing work schedules, such as pilots and air crew, have significantly higher rates of cancer. So sleep and circadian rhythm disruption (SCRD) increases our vulnerability to getting cancer.

In addition, cancer progression is worse in those individuals with SCRD. As a result, one holistic approach often recommended alongside cancer treatments involves trying to stabilise a patient’s circadian rhythms.

This science is relevant to everyone’s attempts to stay healthy.

We should all make sure that our circadian system – specifically, the master clock in our brain – is ‘reset’ daily to be in sync with our 24-hour world. This will enable us to deliver the correct materials to the right organs at the correct concentration at the right time of day to defend ourselves against disease.

Keeping our body clock in sync involves eating at regular times, getting enough exposure to light around both dawn and dusk, and having a consistent sleep/wake routine, getting up and going to bed at the same time each day.

As for cancer treatment, while chemotherapy and radiotherapy both attack fast-growing cancer cells, they also affect healthy cells that are undergoing division, and this can produce traumatising side-effects. But there is normally a circadian time window during the day when healthy cells grow, and this is often very different from that of cancerous cells, which divide and grow much faster. This means that if treatment is given at times of the day when our healthy cells are ‘quietest’ – when they’re dividing and growing the least – the toxicity of the treatment to the healthy cells can be reduced. And so higher doses can be given to ‘blast’ the bad, cancerous cells without having such terrible side-effects.

Studies have shown the benefits of timing drugs to treat ovarian cancer, leukaemia, colorectal cancer and brain tumours, with the optimum delivery window depending on the area affected by cancer.

However, despite all this valuable knowledge, patients are usually given anti-cancer drugs at times convenient for those treating them.

Admittedly, there are important logistical problems delivering toxic drugs in busy hospitals.

Yet modern equipment such as ambulatory medical pumps, which give chemotherapy via a drip at a particular time, could be used at low cost and potentially in patients’ own homes.

Practicalities aside, another major hurdle is a failure to understand the importance of circadian timing.

Most doctors are given very little training in the importance of circadian rhythms, and until this becomes a serious topic for study in medical schools, there will always be a barrier between exciting laboratory findings, medical application and new drug discovery.

This has to change.

© Russell Foster 2022

Adapted from Life Time: The New Science Of The Body Clock And How It Can Revolutionise Your Sleep And Health by Russell Foster, published by Penguin Life on May 19 at £16.99. To order a copy for £15.29 (offer valid to 21/5/22; UK P&P free on orders over £20), visit mailshop.co.uk/books or call 020 3176 2937.

Heart attacks to headaches: when it all happens

From gout to asthma and heart attack, our symptoms – and the likelihood of experiencing an event – alter throughout the day, due to changes driven by our body clock.

Although still an emerging science, this graphic, left, shows what we know about the average peak times for body experiences in the first 12 hours of the day.

Midnight: Eczema and psoriasis: the intense itching of these skin conditions occurs between 8pm and 2am, peaking near midnight when skin is naturally most porous and loses moisture, becoming more dry and itchy.

1am: Gout pain, caused by crystals of uric acid in the joints, tends to strike between 1am and 5am, peaking around 3am to 4am and coinciding with an overnight drop in body temperature, which may encourage the crystals to form.

2am: Cluster headaches. These excruciatingly painful headaches can start at around 2am, possibly due to abnormal messages from the ‘master’ clock in the brain.

3am: Toothache peaks between 3am and 7am due to changes in pain receptors driven by the body clock.

4am: Asthma symptoms tend to be worse around 4am. Lung function is usually at its best around 4pm, with the lowest flow at 4am, which is worse for asthma, probably due to overactive immune responses in the lung.

5am: Babies are usually born between 1am and 7am, peaking around 4am to 5am. This may be a time that was optimal for our ancestors and linked to the night-time release of the hormone melatonin.

6am: Coughing and other symptoms of lung conditions, such as emphysema and chronic bronchitis, tend to worsen in the early hours, often due to the build up of mucus in the lungs overnight. Mucus production is also stimulated as an immune response in preparation for the day.

7am: Joint pain caused by rheumatoid arthritis peaks around 4am to 8am, when more inflammatory chemicals are released in preparation for greater immune protection during the day. 7am is also when osteoarthritis pain and joint stiffness tends to peak. Normally, during the day, joints are cushioned by the elasticity of cartilage which is triggered by circadian rhythm. As we age, this ‘flattens’ and joint-cushioning declines, resulting in pain.

9am: Stroke and heart attack risk peaks between 6am and noon. This is linked to the rise in blood pressure and blood clotting factors in the early morning.

10am: If you’re a ‘lark’ (someone who likes to rise and go to bed early), migraines tend to occur between 8am and midday. However, ‘owls’ (evening types) suffer in the afternoon and early evening. We know the body clock is connected to migraine, but how is not clear.

11am: Our circadian-driven rise in alertness peaks, having prepared us for the new day and increased activity levels.

Significantly, 11pm is when older people tend to start experiencing incontinence, lasting until the early hours. This is because the circadian rhythm in the hormones that regulate urine production – high in the day, low at night – becomes ‘flattened’ as we age, so that urine production isn’t just confined to the day.