Many of us will be used to taking drugs according to a specific timeframe – for instance, certain antibiotics must be taken an hour before food as it can stop the drug being absorbed properly. Others, such as some statins, are meant to be taken in the evening as the liver produces the most cholesterol during sleep.
This relates to the timing of our body clocks to optimise the benefits of treatment – and now there’s a suggestion that this may soon be extended to vaccinations and even cancer care.
Usually, the timing of a cancer treatment depends on when the patient can get to hospital, how busy the clinic is and the availability of medical staff.
But growing evidence suggests giving treatments at certain times of the day could improve life expectancy.
Experts say it’s all down to syncing treatments with our body clock, or circadian rhythm: this regulates just about everything, including the sleep/wake cycle and immunity.
There is a circadian clock in every cell of our bodies – to function effectively, this system must be aligned with day and night, by exposure to light first thing and declining light at dusk.
Now scientists are investigating whether the body clock can be harnessed to improve treatment outcomes and minimise side-effects.
With immunotherapy, for example, which triggers the patient’s immune system to find and destroy cancer cells, emerging evidence suggests that it could be even more effective if doses are timed.
The potential benefits of immunotherapy in the morning may relate to the fact that key parts of the immune system peak early in the day
A study in the journal Nature Medicine last year found that patients with advanced lung cancer who received immunotherapy before 11.30am lived an average of 33 months after their first treatment – those who received treatment later in the day lived an average of about 20 months.
Other studies have shown similar outcomes, including one published earlier this month in the British Journal of Cancer, which found that patients with advanced cancers given ‘early’ immunotherapy sessions lived on average for 21.4 months, compared with 13.1 months in the ‘late’ group.
Russell Foster, a professor of circadian neuroscience at the University of Oxford, told Good Health that the latest findings are ‘very exciting and show, once again, that taking account of the circadian rhythm has an important role to play in improving health outcomes for patients with cancer and other medical issues’.
The potential benefits of immunotherapy in the morning may relate to the fact that key parts of the immune system peak early in the day, he explains.
Immunotherapy needs a strong immune response to trigger the production of antibodies that target cancer cells.
And these immune responses are generally better in the morning, as we evolved to ramp up our natural defences in readiness for being out and about, encountering pathogens and more likely to become infected as a result of injury, says Professor Foster.
Chemotherapy, too, may be more effective if administered according to a schedule, although the best timing seems to depend on the type of cancer, the drugs given and the patient’s gender.
And morning is not always best; research suggests that chemotherapy for women with lymphoma, a type of blood cancer, may be more effective in the afternoon, for example – possibly because in women, the production of white blood cells (a type of immune cell) peaks higher in the morning than it does in men, and chemotherapy given at this time may reduce this, leading to more severe side-effects such as neutropenia (low white blood cell count) and infections.
Russell Foster, a professor of circadian neuroscience at the University of Oxford, told Good Health that the latest findings are ‘very exciting’
Studies have also shown that timing of treatment can reduce side-effects of radiation therapy.
Professor Foster points to studies that found patients who receive radiotherapy in the afternoon for many cancers, including breast and prostate, experience more side-effects than patients who receive it in the morning.
One mechanism driving the difference in outcomes and side-effects could be the daily ebb and flow of a protein, CRY1, which stops the repair of DNA in cells, including cancer cells.
CRY1 levels are low in the morning, so the cancer cells can easily repair their DNA – but when CRY1 levels rise in the afternoon and evening, DNA repair reduces.
Analysis of data from Virgen Macarena University Hospital in Seville, Spain, has found that patients with prostate or breast cancers lived longer if they had treatment in the afternoon and evening: this effect was not seen in lung or brain cancers. Professor Foster says there is, however, ‘a lot we don’t know’.
Indeed, other experts stress more research is needed to ensure such findings aren’t due to other factors, including the fact that people who have treatment in the morning may come from higher economic social groups with better overall health, because they can afford to take time off work, for example.
Dr Robert Dallmann, from the Warwick Chronotherapy Group, which helps establish optimum schedules for drug dosing for cancer, told Good Health: ‘We do need to have more rigorous data before we can be certain, but it is looking extremely promising.’
Far more is known about chronopharmacology, the timing of drug administration to ensure the best response, which has been studied for over 50 years.
Yet, the relationship between drug timing and effectiveness is often ignored by healthcare professionals, says Professor Foster. ‘In view of the fact that many disease symptoms vary across the day, it should also come as no surprise that many of the medicines we take show variable levels of effectiveness across the day/night cycle. Ideally, medications should be delivered at the time of day when they are most needed and most effective.’
‘However, most medicines are not taken at a time that optimises their impact but instead at a time that helps us remember to take them,’ he says.
For example, blood pressure medication is very often taken in the morning because it is a way to remember, but this may miss the maximum risk-window of having a stroke or heart attack, says Professor Foster.
‘Very significantly, there is a circadian driven rise in blood pressure as we approach morning, caused by the release of cortisol and adrenaline – this increases heart rate, combined with an increase in clotting factors.
‘These normally clump together to form blood clots following injury, but they also work against us by producing clots that block blood vessels,’ he adds.
‘The combined effects of a sharp rise in blood pressure between 6am and noon, and peak blood “stickiness” in the morning, corresponds to the greatest chance of having a stroke or heart attack.’
In fact, there’s a 50 per cent greater chance of a stroke between 6am and noon than the rest of the day.
‘Some studies have shown that when blood pressure medication is taken before bedtime, rather than in the morning, it’s more effective at regulating blood pressure and reducing stroke and heart attack risk,’ says Professor Foster.
Studies have also shown that timing of treatments can reduce the side-effects of radiation therapy
‘This is because such drugs have a long “half-life”, remaining at high concentrations for many hours in the body before they are broken down. So, counterintuitively, taking an antihypertensive before bed can reduce your risk of a stroke in the morning.’
An analysis of eight clinical trials, published in the journal Scientific Reports this year, found that the morning blood pressure surge was significantly reduced in patients taking medication before bedtime.
Yet here, too, there is debate. A British Heart Foundation-funded trial in 2022 showed that blood pressure medication worked equally well, whether taken in the morning or evening.
Professor Foster says: ‘Such inconsistencies between studies may be due to the use of different antihypertensives, for instance.’
It’s not just medication timing that might make a difference.
Surgery in the evening or at night is associated with a higher risk of mortality, suggested a review of 20 studies published in the journal Anaesthesia in 2024.
This could be due to many factors, such as night-time surgery more often involving emergency operations, or changes in the patient’s own circadian rhythm, says Professor Foster – who adds that timing treatment is a complex picture.
‘When it comes to surgical outcomes we are still not sure if the benefit is linked to the circadian rhythm of the patient, or the surgeon – who may be more alert and performing optimally in the morning,’ he says.
But experts agree that the potential is exciting.
Dr Dallmann adds: ‘Simple timing changes have the potential to benefit many vulnerable people.’
Do morning jabs offer more protection?
There is growing evidence that the effectiveness of vaccines, such as for flu and Covid, may vary depending on the timing of administration.
A review of 17 studies, published in the journal Frontiers in Public Health in April, found that morning vaccination enhanced antibody responses in adults aged 60 and over.
And the mRNA vaccine for Covid may be more effective at preventing infections if given from 10am until 2pm, with the least favourable time between 4pm and 7pm, said researchers from Washington University’s School of Medicine in 2023.
The timing seemed to make most difference in children and over-50s (as immune systems slow down and produce fewer antibodies with age).
One theory is that the circadian rhythm of the immune system affects its response to outside invaders. The researchers said: ‘It is possible this pattern is reflective of vaccinations in general. We need more research to confirm that.’
