Shift work is on the rise worldwide. New research on mice suggests that a simple lifestyle change – changing mealtimes – could alleviate the negative effects of shift work on the circulatory system. By manipulating the mice’s eating schedules, researchers found that time-restricted feeding helped to prevent inflammation associated with disruption to the circadian rhythm, potentially offering a meaningful intervention for shift workers. Human trials have found similar positive effects.
Just ask any night shift veteran – fighting your internal clock can be brutal on the body.
Shift workers have clearly suffered negative health effects for years, including an increased risk of cardiovascular disease. But with shift work on the rise worldwide, the pressure is mounting to find strategies to help mitigate its effects – without eliminating the graveyard shift.
New research on mice, published in July in eBioMedicine, suggests that a simple lifestyle change could help to ease the burden of shift work on the circulatory system.
Just changing mealtimes could make a meaningful difference to shift workers’ heart health, says lead author Wietse In het Panhuis. “It’s safe, it’s easy, it’s cheap.”
Clocking in
The internal clock is set primarily by light, but there are many other zeitgebers – a German word meaning time-givers – including exercise and eating, says co-author Milena Schönke, a postdoctoral researcher at Leiden University Medical Center.
Shift work is growing in prevalence, accounting for about 15% of the workforce in Europe, says In het Panhuis, who studied the cardiovascular effects of disrupting the circadian rhythm as a PhD student at Leiden University Medical Center in the Netherlands. In addition to an elevated risk of cancer and diabetes, shift workers experience higher rates of atherosclerosis –a cardiovascular condition in which cholesterol and white blood cells form a gooey plaque that clogs up arteries.
Atherosclerosis can lead to heart attack or stroke, and complications arising from atherosclerosis are thought to be the leading cause of death worldwide, according to the World Health Organization.
Researchers think that the disruption to their circadian rhythm is what makes shift workers more likely to develop atherosclerosis.
“Circadian rhythms are the rhythms that drive when you are awake or asleep,” In het Panhuis explains. “But they also drive virtually every process in the body,” from energy metabolism to organ function," says co-author Milena Schönke, a postdoctoral researcher at Leiden University Medical Center.
If you give a mouse a shift schedule
Shift work forces people to defy one of the most powerful zeitgebers – the day-night cycle. That creates a constant discord between what the body expects to happen and the worker’s activity patterns.
Scientists hoping to model shift work in mice learned that convincing a mouse to follow a shift schedule is very difficult. Short of that, the next best thing is simulating another circadian disturbance that is familiar to many human readers – jet lag.
In het Panhuis and his team put mice on a 24-hour day-night cycle. But every 3 days, the light phase arrived 6 hours early. “You can compare this to flying to the east,” he says.
Previous research showed that mice take 5 days to fully recover from this kind of circadian disruption, enabling the researchers to create a state of perpetual jet lag that is physiologically very similar to how shift work affects the human body.
Nocturnal no more
For humans, the zeitgeber of daylight means that it is time to enter our active phase. “For mice, this is the exact opposite. When it is light, they go to sleep.” So in order to defy their natural circadian rhythm, In het Panhuis’s shift-working mice would need to be active during the light phase.
But by manipulating another zeitgeber – eating – In het Panhuis and his team hoped to counteract the effects of light-based disruption of the circadian rhythm. They limited the mice’s access to food to fixed times rather than the round-the-clock buffet most captive mice enjoy. For animals, this is called time-restricted feeding, while for people it is usually called intermittent fasting.
In a previous study, the researchers had tried to restrict the mice’s mealtimes only to the light phase. (Remember, the light is naturally the mouse’s inactive phase, so the equivalent for a human shift worker would be eating only during dark hours.) That enhanced their adaptation, In het Panhuis says.
The next step was to try feeding the mice only during the dark phase – for a human shift worker, that would be equivalent to only eating during daylight hours despite working at night.
To assess whether time-restricted feeding affected atherosclerosis, both in shift-working mice and mice on a normal day-night schedule, the researchers divided 64 mice into crews “working” different “shifts”.
The first group experienced consistent day-night cycles with round-the-clock access to food. The second also had undisturbed day-night cycles but with food access limited to night-time hours. The third and fourth groups experienced that perpetual jet lag designed to simulate shift work – with one group having unrestricted food access and the other time-restricted feeding.
Reducing inflammation
After 100 days, the scientists dissected the mice and inspected the aortic root – an important structure of the heart – for evidence of atherosclerosis.
Curiously, the team could not fully reproduce the cardiac effects of shift work observed in previous studies in this mouse model. Atherosclerotic lesion size and severity did not differ significantly between mice with circadian disruption and mice who had a normal day-night schedule. But between the two groups exposed to “shift work”, the time-restricted feeding group had lower atherosclerotic lesion size than the ad libitum feeding group; indicating that time-restricted feeding is more protective against atherosclerosis than ad libitum feeding in a shift work setting.
But the concentrations of macrophages in the atherosclerotic lesions differed significantly, and these can be an early sign of an atherosclerotic lesion forming. “Monocytes are basically cops patrolling in the blood, eating everything that should not be there,” Schönke says. As plaque begins to form, monocytes flock to the area, munching away at the cholesterol accumulating in the vessel wall and any damaged tissue. Once they take up residence in the tissue, they are called macrophages.
The researchers pivoted to see how mealtimes affected macrophage concentration. Looking at just their simulated shift workers, they compared how mice with time-restricted feeding fared relative to mice who were able to eat whenever they chose.
“Time-restricted feeding at least prevented the increase in macrophage concentration in the atherosclerotic lesions we observed with the circadian rhythm disruption,” Schönke says.
“And that alone, if you want to translate this to humans, is quite meaningful. We know that inflammation is a very strong driver of this and other diseases, even more for people than for mice.”
Mind your zeitgebers
The results from the shift-working mice indicate that intermittent fasting could be a meaningful intervention for people who have to fight their circadian rhythm, the authors say.
In het Panhuis points to another recent study that explored intermittent fasting among humans – that trial found that firefighters who restricted their eating to a 10-hour window for 12 weeks showed improvements in blood pressure, blood glucose and other measures of cardiovascular health.
“If possible, try to eat during the day – during the rhythm that your body naturally wants to stick to,” says Schönke.
Schönke adds that those of us working 9 to 5 should remember our zeitgebers too.
“It is not even just shift workers,” Schönke says. “People who do not work shifts are also pretty good at disturbing our circadian rhythms by staying up really late, looking at a lot of bright screens late at night. All those things are weakening our circadian rhythms as well.”
