That Fascinating Circadian Rhythm

I’m Dr. Michael Greger and this is Nutrition Facts.

There’s one thing we’ve been thinking about a lot lately, and that’s how to stay healthy in the middle of a global pandemic. Especially since we’ve learned that those with underlying health problems like obesity, hypertension, diabetes, and heart disease are more likely to have serious complications if they contract COVID-19. So what do we do? We try to stay healthy – with evidence-based nutrition.

Today, the mighty power of our internal biological circadian clock. Did you know that the same meal eaten at the wrong time of day can double our blood sugars? Here are the facts.

We’ve known for more than a half century now that our “glucose tolerance” declines as the day goes on; meaning, the ability of your body to keep blood sugars under control. If you hook yourself up to an IV, and just drip sugar water into your vein at a steady pace throughout the day, at about 8pm your blood sugars start to go up, even though you haven’t eaten anything and the infusion rate didn’t change. The same amount of sugar is going into your system every minute, but your ability to handle it deteriorates in the evening, but bounces right back in the morning. A meal eaten at 8pm can cause twice the blood sugar response as an identical meal eaten at 8am. It’s as if you ate twice as much!

Your body just isn’t expecting you to be eating when it’s dark outside. Our species may have only discovered how to use fire about a quarter million years ago. We just weren’t built for 24-hour diners.

One of the tests for diabetes is called the glucose tolerance test, to see how fast your body can clear sugar from your bloodstream. You swig down a cup of water with about four and a half tablespoons of regular corn syrup mixed in, and then have your blood sugar measured two hours later. By that point, your blood sugar should be under 140 (mg/dL). Between 140 and 199 is considered prediabetes, and 200 and up is a sign of full-blown diabetes.

The circadian rhythm of glucose tolerance is so powerful that a person can test normal in the morning, but as a prediabetic later in the day. Prediabetics who average 163 at 7am test out as frank diabetics by 7pm, at over 200.

Choosing lower-glycemic foods may help promote weight loss, but timing is critical. Due to this circadian pattern in glucose tolerance, a low-glycemic food at night can cause a higher blood sugar spike than a high-glycemic food eaten in the morning. We’re so metabolically crippled at night: researchers found that eating a bowl of All Bran at 8pm caused as high a blood sugar spike as eating Rice Krispies at 8am. High-glycemic foods at night would seem to be the worst of both worlds. So, if you’re going to eat refined grains and sugary junk, it might be less detrimental in the morning.

The drop in glucose tolerance over the day could therefore help explain the weight-loss benefits of front-loading calories towards the beginning of the day. Even just an earlier versus later lunch may make a difference. People randomized to eat a large lunch at 4:30pm suffered a 46 percent greater blood sugar response compared to an identical meal eaten just a few hours earlier at 1pm. And a meal at 7am can cause 37 percent lower blood sugars than an identical meal at 1pm. Now there doesn’t seem to be any difference between a meal at 8pm and the same meal at midnight. They both seem to be too late. But eating that late, at midnight, or even 11pm can so disrupt your circadian rhythm that it can mess up your metabolism the next morning. resulting in significantly higher blood sugars after breakfast, compared to eating the same supper at 6pm the evening before.

So, these revelations of chronobiology bring the breakfast debate full circle. Breakfast-skipping not only generally fails to cause weight loss, but worsens overall daily blood sugar control in both diabetic  and non-diabetic individuals.

Breakfast skippers also tend to have higher rates of heart disease and atherosclerosis in general. Is this just because breakfast-skipping tends to cluster with other unhealthy choices, such as smoking and sicklier eating habits overall? The link between breakfast skipping and heart disease—even premature death in general—seems to survive attempts to control for these confounding factors. But you don’t know, until you put it to the test.

Does skipping breakfast lead to higher cholesterol, for example? Yes, a significant rise in LDL (bad) cholesterol in those randomized to skip breakfast––about 10 points higher within just two weeks. The Israeli 700/500/200 study found that the triglycerides of the king-prince-pauper group got significantly better—a 60-point drop—while those on the pauper-prince-king group got significantly worse (a 26-point rise). So, consuming more calories in the morning relative to the evening may actually have a triple benefit: more weight loss, better blood sugar control, and lower heart disease risk. So, if you’re going to skip any meal, whether practicing intermittent fasting or time-restricted feeding (where you try to fit all your food into a certain daily time window), it would be safer and more effective perhaps to skip dinner rather than breakfast.

In our next story, we learn how bright light exposure synchronizes the central circadian clock in our brains, whereas proper meal timing helps sync the timing of the clock genes throughout the rest of our body.

One of the most important breakthroughs in recent years has been the discovery of “peripheral clocks.” We’ve known about the central clock, the so-called suprachiasmatic nucleus, for decades. It sits in the middle of your brain, right above where your optic nerves cross, allowing it to respond to night and day. Now we know there are semi-autonomous clocks in nearly every organ of our body. Our heart runs on a clock, our lungs run on a clock, our kidneys run on a clock. Up to 80 percent of the genes in our liver are expressed in a circadian rhythm; our entire digestive tract does too.

The rate at which our stomach empties, the secretion of digestive enzymes, and the expression of transporters in our intestinal lining for absorbing sugar and fat all cycle around the clock. So too does the ability of our body fat to sop up extra calories. The way we know these cycles are driven by local clocks, rather than being controlled by our brain, is that you can take surgical biopsies of fat, put them in a petri dish, and still watch them rhythm away.

All this clock talk is not just biological curiosity. Our health may depend on keeping all these clocks in sync. Think about it like a child playing on a swing. Imagine you’re pushing, but you become distracted by other goings-on in the playground, and stop paying attention to your timing. So, you forget to push, or push too early or too late. What happens? Out of sync, the swinging becomes erratic, slows, or even stops. That is what happens when we travel across multiple time zones or have to work the night shift.

The “pusher” in this case are the light cues falling onto our eyes. Our circadian rhythm is meant to get a bright light push every morning at dawn. But if the sun rises at a different time, or we’re exposed to bright light in the middle of the night, this can push our cycle out of sync and leave us feeling out of sorts. That’s an example of a mismatch between the external environment and our central clock. Problems can also arise from a misalignment between the central clock in our brain and all the other organ clocks throughout our body. An extreme illustration of this is a remarkable set of experiments suggesting even our poop can get jet lag.

Our microbiome seems to have its own circadian rhythm. Even though they’re down where the sun don’t shine, there’s a daily oscillation in both bacterial abundance and activity in our colon. Interesting, but who cares? Check this out: if you put people on a plane and fly them halfway around the world, then feed their poop to mice, they grow fatter than mice fed preflight feces. Though it may have just been bad airline food or something, the researchers suggest the fattening flora was a consequence of circadian misalignment. Indeed, several lines of evidence now implicate “chronodisruption”—the state in which our central and peripheral clocks diverge out of sync—as playing a role in conditions ranging from premature aging and cancer to mood disorders and obesity.

Bright light exposure is the synchronizing swing pusher for our central clock. What drives our internal organ clocks that aren’t exposed to daylight? Food intake. That is why the timing of our meals may be so important. Removing all external timing cues by locking people away under constant dim light, researchers showed you could effectively decouple central from peripheral rhythms just by shifting meal times. They took blood draws every hour, and even took biopsies of their fat every six hours, to demonstrate the resulting metabolic disarray.

Just as morning light can help sync your central clock in your brain, morning meals can help sync your peripheral clocks throughout the rest of your body. Breakfast-skipping disrupts the normal expression and rhythm of these clock genes themselves, which coincides with the adverse metabolic effects. Thankfully, they can be reversed. Take a group of habitual breakfast skippers, and have them eat three meals at 8am, 1pm, and 6pm, and their cholesterol and triglycerides improves compared to taking meals five hours later at 1pm, 6pm, and 11pm. There’s a circadian rhythm to cholesterol synthesis in the body, too which is also strongly influenced by food intake, as evidenced by the 95 percent drop in cholesterol production in response to a single day of fasting. That’s why just a few hours’ shift in meal timing can result in a 20-point drop in LDL cholesterol, thanks to eating earlier meals.

Finally today, we discover the power of chronotherapy. How the same dose of the same drugs taken at a different time of day can have a different effect.

The 2017 Nobel Prize in Medicine was awarded for elucidating the molecular mechanisms of our internal circadian clock. For billions of years, life on Earth evolved to a 24-hour cycle of light and dark, and so, it’s no surprise our bodies are finely tuned to that pattern. But put people in total darkness without any external time cues, and our body still continues to cycle in about a 24-hour “circadian” rhythm. In fact, you can even take tissue biopsies from people and show the cells continue to cycle outside the body in a petri dish. Nearly every tissue and organ in our body has its own internal clock.

An intricate system of intrinsic clocks drives not only some of our behavioral patterns, such as eating, fasting, sleeping, and wakefulness, but our internal physiology; our body temperature, blood pressure, hormone production, digestion, and immune activity. Most of the genes in our body exhibit daily fluctuations in expression, making the circadian rhythm the largest known regulatory system in our body. This cycling is thought to allow for a level of predictability and functional division of labor so that each of our body processes can run at the best time. At night while we’re sleeping, a whole array of internal housekeeping activities can be switched on, for example, and as dawn approaches, our body can shift back into activity mode.

Anyone who’s ever had jet lag knows what throwing our cycle even just a few hours off can do, but now we know our circadian rhythms can literally be the difference between life and death. A study of more than 14,000 self-poisonings found that those who tried committing suicide in the morning were more than twice as likely to die than those who ingested the same dose in the evening. In the same vein, properly timed chemotherapy can not only end up being five times less toxic, but also twice as effective against cancer. The same drugs, at the same dose, but different effects depending on the time that they’re given. Our body absorbs, distributes, metabolizes, and eliminates what we ingest differently depending on when it is during the 24-hour cycle.

We’re just beginning to figure out the optimal timing for different medications. Randomize people suffering from hypertension into taking their blood pressure pills at bedtime instead of in the morning, and not only does the bedtime group achieve better blood pressure control and suffer fewer heart attacks and strokes, but cuts their risk of death in half (yet most physicians and pharmacists tell patients to take them in the morning, potentially doubling their risk of death). If chronotherapy—the optimal timing of drugs—can have such an impact, maybe it should come as no surprise that chrono-prevention—the scheduling of lifestyle interventions like mealtimes—can also make a difference.

In the official Academy of Nutrition and Dietetics position paper on effective treatments for obesity, importance is placed not only on the quantity, but timing of calorie intake, suggesting that consuming more calories “earlier in the day, rather than later in the day can assist with weight management.” Some have gone further and even characterized obesity as a “chronobiological” disease. What evidence do we have to back up these kinds of claims?

Well, the timing of calorie intake may have shifted slightly over the last few decades towards a greater proportion of food later in the day, which raised the question about a possible role in the rise of obesity. Middle-aged men and women who eat a greater share of daily calories in the morning do seem to gain less weight over time, and a study entitled “Timing of food intake predicts weight loss effectiveness” found that dieters eating their main meal earlier in the day seemed to steadily lose more weight than those eating their main meal later.

The obvious explanation for these findings would just be that those who eat later also tend to eat more. And there does seem to be a relationship between when people eat most of their calorie intake and how many calories they end up eating over the entire day, with those eating a greater proportion in the morning eating less overall. Maybe later eaters are overeating junk on the couch watching primetime TV? A tendency has been found for night owls to eat more fast food, soda, and fewer fruits and vegetables. In the field of social psychology, there’s a controversial concept called “ego depletion,” where self-control is viewed as a limited resource like a muscle that can become fatigued from overuse. As the day wears on, the ability to resist unhealthy food choices may decline, leaving one vulnerable to temptation. So, is it just a matter of later eating leading to greater eating?

Remember this study where earlier eaters steadily lost more weight? To their surprise, the early eaters were eating as much as the late eaters despite the difference in weight loss magnitude. The early eaters ended up about five pounds lighter than the late eaters by the end of the 20-week study, even though they were apparently eating the same amount of food.

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Thanks for listening to Nutrition Facts. I’m your host, Dr. Michael Greger.