There are five key elements to weight loss from a circadian point of view: Timing of Meals; Light Exposure; Sleep; What to Eat and When; and Genetic Variants. All of these can come together in our modern world to give you a propensity to gain weight – and all can be hacked to help you lose weight.
Timing is everything when it comes to our bodies.
Midnight snacks, a bowl of cereal before bed, or even ‘saving’ desert until 9 or 10 pm. All of these are fairly normal behaviors these days. Just open up the fridge and pop something in the microwave to heat it up, anytime day or night. Modern convenience at its best; not something our ancestors would have been able to do.
This penchant for eating at any time, day or night, is one factor driving the obesity epidemic.
It is always interesting to look at animal models and agriculture to understand weight gain. Financially it makes the most sense to have animals gain weight quickly for food production, so a lot of research has gone into this topic. For example, farmers have known for decades that low doses of antibiotics increase weight in cattle. When it comes to the timing of eating, it has been known for a long time also that the amount of weight gained for the same quantity of food depends on the time of day that the food is given. For example, a study from 1982 found that catfish gain more weight when fed at a specific time of night.[ref] A more recent example is a mouse study from 2009 that found that mice fed during the time that they normally would be resting gained more fat although they were eating the same number of calories as mice fed during their active period. [ref][ref]
Let’s take a look at the research on people:
A study of a Mediterranean population of 420 looked at weight loss over a 20-week diet. Those who ate earlier in the day (defined here as eating lunch before 3 pm) lost more weight than those who ate later in the day.[ref]
Another study found that “Eating late is associated with decreased resting-energy expenditure, decreased fasting carbohydrate oxidation, decreased glucose tolerance, blunted daily profile in free cortisol concentrations and decreased thermal effect of food..”[ref]
One more example from a 2017 clinical trial that looked at the timing of meals in healthy 18-22-year-olds: “These results provide evidence that the consumption of food during the circadian evening and/or night, independent of more traditional risk factors such as amount or content of food intake and activity level, plays an important role in body composition.”[ref]
Finally, let’s sum this up with the first sentence from a study on circadian misalignment and glucose tolerance. “Glucose tolerance is lower in the evening and at night than in the morning.” Yes, the study goes on to quantify this as being 17% lower glucose tolerance at 8 pm vs 8 am.[ref]
The simple solution is to eat earlier in the day and not snack at night. For some of us, this is easier said than done. So make a plan for your meals for a few days. Yes, actually sit down with a pencil and paper and come up with ideas for shifting your calories to the morning hours. If you are a habitual TV watcher at night (with a subsequent bowl of popcorn and a beer), plan out a couple of evening activities to get you out of the house for a few evenings while you break the snacking habit. Perhaps go for a walk, go see a movie and avoid the overpriced snacks, or dust off your bowling shoes for a quick game.
While this all may sound a bit cut-and-dried, we really are flexible creatures, able to withstand periodically eating at different times without drastic effects. The bigger picture is the chronic effects of eating at the wrong time, rather than just the one-off change up of our daily eating habits. So don’t beat yourself up if you nibble on something at an evening event. Just get back on track for the rest of the week.
Light is also important to weight gain. While it seems strange to think about, again the research on this topic seems to point to an incontrovertible conclusion that light – both bright light exposure in the daytime and no light exposure at night – makes a significant difference to our weight.
In Circadian Rhythm Connections, Part 1: Mood Disorders, I explained how light at a specific wavelength (~480nm, blue light) hits melanopsin containing photoreceptors in our eyes, signaling to our core circadian genes (CLOCK, BMAL1) in the brain that it is daytime.
Our body has both the strong central circadian clock in the suprachiasmatic nucleus in the brain as well as peripheral clocks in our organs. These peripheral clocks include the timing of functions in the liver, pancreas, etc.
The core clock genes are mainly entrained through the cycle of light and darkness, while the peripheral clock in the liver is reset quicker or entrained, by food intake. But the core clock genes do still affect the peripheral clocks.
The location of the core circadian clock resides in a region of the hypothalamus called the suprachiasmatic nucleus (SCN). The SCN signals to the adrenal system to increase adrenal glucocorticoids (e.g. cortisol is a glucocorticoid hormone) production just prior to waking. “This promotes arousal and alertness by enhancing liver gluconeogenesis (from amino acids and fatty acids), promoting the release of liver glucose to the blood, and increasing its uptake in the brain and muscles. Adrenal glucocorticoids have been implicated as a peripheral humoral cue for the entrainment of oscillators such as the liver.” [ref] The SCN also controls the circadian rhythm of the hormones insulin, glucagon, and adrenalin.
That may sound like science mumbo-jumbo, but it has practical implications. For people waking up at 3:30 or 4:00 am every night, this could be caused by the circadian spike in cortisol levels. Personally, I used to see 4:00 am on the clock quite often. Blocking blue light in the evenings, going to be at a reasonable hour, and cutting out snacking after dinner has eliminated the 4 am wake-up for me.
Moreover, animal studies for efficiently producing more meat show us a lot. Chickens have been studied under different lighting conditions for many decades to determine the quickest way to have plump chickens. One study found that chickens exposed to specific wavelengths of light (450-630nm) pack on the pounds better when exposed to the light from 8 am until midnight. The study also notes that poultry workers are adversely affected by blue or green wavelengths of light at night and thus suggests using light in the yellow wavelengths is almost as effective for chicken fattening.[ref]
What does light at night do to people? Shift work seems to be a risk factor for obesity. One study of rotating shift workers (Canadian men) found a 57% increase in the risk of obesity. [ref] Another study of shift workers (Korean women) found a 63% increased risk of obesity. [ref] Numerous other studies have similar results.
You may be thinking that all those shift workers are eating bags of Doritos all night long. Perhaps. But even a dim light at night has been linked to weight gain in animal studies that control for the number of calories eaten.[ref] Another mouse study looked at the effects of dim light at night (5 to 15 lux – similar to a night light) and found that mice fed the same number of calories gained weight when exposed to either dim or bright light at night.[ref]
Dim light at night seems to affect human weight as well. A large study looked at the amount of light in a bedroom at night and correlated higher light amounts to higher BMIs.[ref] Other studies have repeatedly shown the same results.[ref]
Solving this problem is as simple as shutting off that night light, getting some blackout curtains, and eliminating all the glowing LEDs from chargers in your bedroom.
Our modern world of cubicles and working indoors also affect our waistlines. Studies show a link between more light during the day — specifically outdoor light during the morning hours — and weight loss.[ref] One study that tracked people’s light exposure concluded “having a majority of the average daily light exposure above 500 lux (MLiT500) earlier in the day was associated with a lower BMI.”[ref] A study of people in the northern latitudes during the winter found that bright light therapy in the morning increased weight loss and suppressed appetite. [ref]
With this in mind, make getting outside during the morning a priority. Drink your coffee on the porch, walk or bike to work, take a morning break outside, and eat lunch outside if possible.
Sleep is something that every health guru out there puts on their lists of “Top 5 ways to improve blah, blah, blah.” But does it really affect our weight and metabolism that much? Is the benefit worth the trade-off – e.g. is it worth going to bed before 11:00 each night rather than staying up late, having fun with friends or working long hours? Quick answer: Yep. Research shows that it really does make a significant difference.
Fun facts: The average amount of sleep per night has decreased by about 1.5 hours over the last century.[ref] And the recommended amount of sleep for children has decreased by over an hour from 1897 to today.[ref]
Not-so-fun fact: A meta-study of 75,000+ people found that sleeping 5 hours per night or less increased the risk of having metabolic syndrome (e.g. high blood pressure, high blood sugar, overweight) by over 50%. To not have an increased risk of metabolic syndrome, participants had to be sleeping over seven hours a night.[ref]
A 15-day in-patient study looked at the effect of 5 days of insufficient sleep, mimicking the effects of not sleeping enough during the workweek. The study found that insufficient sleep caused greater energy expenditure, but that extra energy expenditure was offset with greater food intake. After the two week trial, participants had gained almost 2 lbs. Women were more likely to be affected by weight gain than men. (Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain) Another larger study had similar findings, with additional results showing that African Americans gained slightly more weight than Caucasians with sleep insufficiency.[ref]
Another study looked at sleep insufficiency (5 hours/night of sleep) and found that insulin sensitivity decreased and inflammatory markers increased.[ref]
Sleep timing also matters. A study looked at the average sleeping time (over a week-long time period) and BMI. The results showed that those who were late sleepers (defined as the midpoint of sleep being after 5:30 am) had an average higher BMI and a greater percentage of calories eaten after 8 pm.[ref]
So that was just three studies; there are hundreds of more studies on this topic showing similar results. The science is clear and unambiguous on this topic.
There are several players involved here, with melatonin being an important one. Melatonin, a hormone that rises and peaks at night while we sleep, is important to our basal metabolism for a couple of reasons that I will go into below. Light at ~480nm (blue wavelength of light) hitting the retina of our eye stops melatonin production. It is surprisingly quick, with 15 seconds of light stopping melatonin production for over 30 minutes and two minutes of blue light suppressing melatonin for more than 45 minutes.[ref] Thus, turning on the bathroom light in the middle of the night means it will take a long time to fall back to sleep.
What is melatonin doing at night while we sleep? Among other things (like acting as an antioxidant), melatonin modulates the secretion of leptin, the hunger hormone. There are also melatonin receptors that regulate the synthesis and secretion of thyroid hormones. “During long photoperiods, higher levels of TSHβ and DIO2 favors the conversion of thyroxine (T4) to triiodothyronine (T3), increasing energy expenditure and basal metabolic rate. Lower, short-photoperiod levels of TSHβ promote dominant DIO3 activity, which converts T4 to both inactive reverse T3 and diiodothyronine T2, increasing food intake and adipose deposits” [ref]
First, let’s take a look at a 2003 study that just kind of makes logical sense. The study looked at medical students who were ‘nocturnal’ – e.g. staying up until 1:30 am and sleeping in until 8:30 am – vs. those who were ‘diurnal’, which would be going to bed well before midnight and getting up when it is light. The nocturnal med students skipped breakfast and ate more of their calories later at night. This caused glucose impairment as well as decreased melatonin and leptin secretion.
It has been known for decades that people are more insulin sensitive in the morning (again why we shouldn’t eat a big meal at night).[ref] Another study states: “Multiple studies have shown that in healthy humans, both insulin sensitivity and beta-cell responsivity to glucose are lower at dinner than at breakfast”. It goes on to explain that mouse models show that deleting one of the core clock genes (BMAL1) in the pancreas causes insulin resistance.[Multiple studies have shown that in healthy humans, both insulin sensitivity and beta-cell responsivity to glucose are lower at dinner than at breakfast] Circadian disruption is intimately coupled with poor glucose metabolism and insulin resistance.
Blue light at night effectively shuts down melatonin production, so you need to block all blue wavelengths for a couple of hours before bed. You may be thinking… “ha! I don’t need to wear silly looking blue-blocking glasses because I have night shift enabled on my phone/tablet.” Well, it turns out that researchers studied the night shift mode at a couple of different settings, and it did very little to prevent melatonin production from being suppressed. So either (shock face!) put away electronic devices a couple of hours before bed or get a pair of blue-blocking glasses.
It takes a couple of weeks to get your body’s melatonin production up to optimal after you start blocking blue light at night. In the meantime, you could increase your consumption of foods that contain melatonin. Foods high in melatonin include tart cherries, grapes, and almonds. Interestingly, melatonin levels fluctuate in plants as well, so the time of harvest, season, and other environmental conditions may affect the levels found in plants.
Why not take a melatonin pill instead of blocking blue light at night? Well, your body’s production of melatonin (without unnatural light) is a bell-shaped curve. Taking a pill gives you a big dose immediately that then gets metabolized and eliminated. Most people are better off with increasing their natural production of melatonin.
The liver coordinates our metabolism through the synthesis of lipids from carbohydrates and the storage of both fats and carbs as glycogen. The liver’s peripheral circadian clock is powered by both the SCN (core clock) and by feeding timing. Also, the CLOCK and BMAL1 genes participate in the rhythm of glucose metabolism and release.
What does this mean? Our body is primed to break things down (metabolize) better at different times of the day. This applies to everything coming into the liver – from foods that we eat to toxins we are exposed to. Here are a couple of studies on food as examples:
A study of 93 overweight women looked at the effects of either a higher calorie breakfast or a higher calorie dinner over a 12-week diet plan. The results showed that those eating the higher calories at breakfast lost 2.5 times the amount of weight as the high dinner group. The higher calorie breakfast group also had a decrease in triglycerides by 33% compared with the high-calorie dinner group which had an increase in triglycerides.
A mouse study found that mice given glucose during their rest period gained more weight than mice given the same amount of glucose during their active period. [ref]
Generally, we can sum it up as glucose metabolism is best in the morning.[ref] It makes sense, then, if you are eating a mixed diet of carbs, proteins, and fats to shift your carb intake towards the morning hours and eat fewer carbs at your evening meal. This is even more evident in studies of people who already have impaired glucose tolerance. One study looked at the differences between high fat in the morning and high carb in the evening or the reverse (high carb morning/high fat dinner). It found that the high-fat morning/high carb dinner “shows an unfavorable effect on glycaemic control” especially in those with already impaired glucose tolerance. “Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism.”[ref]
Time-restricted eating (TRE) is a concept whereby people eat all of their daily calories within a specific window of time. There have been several good animal studies showing that eating the same number of calories during a restricted feeding window (8 hrs to 10 hrs) causes mice to weigh less than the control groups that are eating the same number of calories spread throughout the 24 hour day. It can also reverse the progression of metabolic diseases such as type-2 diabetes.[ref][ref]
What time of the day should you do TRE?
A time-restricted feeding study for an 8 week period had participants eating their normal amount of calories during a 4-hour window in the evening (5 – 9 pm). Participants did lose a little weight, but they also had increased fasting blood glucose levels and impaired glucose tolerance.[ref] This seems to indicate that a time-restricted feeding plan at any time does work to reduce weight, but the feeding window needs to be earlier in the day so as to not impair glucose tolerance.
TRE doesn’t have to be nearly as strict as a four-hour eating window to be effective. A study of overweight individuals who normally had a 14-hour eating window found that reducing their eating window to 10-11 hours caused them to lose about 7lbs over 16 weeks. This was maintained over the next 12 months.[ref]
A cross-over study had participants eat their first meal of the day either a half-hour after waking or 5.5 hours after waking. One of the findings was that PER2 (core circadian rhythm gene) expression was delayed by about an hour when the people shifted their mealtime later in the day. Another finding was that glucose levels remained high in those eating late.[ref]
The research really is good on the effectiveness of a time-restricted eating program. If you are the type of person who likes experimenting and who needs to set some rules for yourself, try a TRE program. Example: eat a good breakfast at 7:30 before heading out the door to work; lunch around noon; and then finish up with a light meal around 6:30 pm. This gives you an 11-hour eating window. Simple. And shown to be effective.
Of course, I have to talk about genetics here. We are all different, and our genes play a role in our natural circadian rhythm. I’ve written other articles on this topic as well, so I won’t go too in-depth here.
The most obvious example of genes affecting our circadian rhythm and our propensity to gain weight is the aptly named CLOCK (Circadian Locomotor Output Cycles Kaput) gene. This is one of our core circadian genes, setting the daily rhythms for the rest of our body.
One well-studied variant of the CLOCK gene is known as 3111T/C or rs1801260. Those who carry the T/T (A/A for 23andMe orientation) genotype have the normal type, while those who carry a C (G for 23andMe orientation) allele (C/C or C/T) are thought to have higher expression of the CLOCK gene and of PER2. Those with C/C or C/T are more likely to be obese, and in a clinical trial, they lost 23% less weight than those with T/T on the same type of diet. [ref]
A small trial with 40 middle-aged women (half were T/T, half were C/T or C/C) found that those who carried the C allele lost less weight (about 7lbs less) and also woke up ~30 minutes later in the morning. They also ate breakfast about an hour later than those with T/T. Additionally, the study looked at heart rate variability and several markers of autonomic nervous system function. It found that “As compared with T/T carriers, risk allele C carriers had a reduction of 34–57% in the daily rhythm amplitude of parasympathetic activity…” The C allele carriers had reduced parasympathetic tone during the night and increased parasympathetic tone during the day. Think of it as an overall flattened sine wave. The study also found that those with higher amplitude (think taller sine wave graph) of parasympathetic tone had greater weight loss during the 30-week study.[ref]
Overall, the CLOCK gene variant leads to an ‘evening’ chronotype. Bipolar patients carrying the C allele are, on average, likely to stay up 79 minutes later at night and sleepless on average as well.[ref] Bariatric surgery patients who carry the variant are more likely to be evening types and also to lose less weight than those without the variant. [ref]
Another study of this variant showed that morning gastric motility may be slower in C allele carriers. Variant carriers also had somewhat lower morning diastolic blood pressure.[ref] This may play a role in timing for breakfast, with C allele carriers perhaps wanting to eat breakfast an hour or two later.
Around 30 – 40 percent of the population carries this CLOCK gene variant. For these people, it may be even more important to watch your blue-light exposure at night so that you aren’t fighting a lack of melatonin alongside your natural propensity for staying up a little later. Get into a good routine for getting to bed at a reasonable hour, and, if possible, shift your morning work schedule a little later to allow you to get enough sleep. Yes, I know that is easier said than done. While you may not be the person who wants to get up at 6:30 am, this variant is more of an hour or two shift rather than an ‘I should sleep in until noon’ excuse.
Circadian Rhythms: Genes at the Core of Our Internal Clocks
Circadian rhythms are the natural biological rhythms that shape our biology. Most people know about the master clock in our brain that keeps us on a wake-sleep cycle over 24 hours. This is driven by our master ‘clock’ genes.
Is intermittent fasting right for you?
There are many internet docs and nutritional gurus promoting fasting as a way to lose weight and get healthy. The recommendations are often for intermittent fasting, for example, a 24-hour fast every week, or sometimes for longer fasts, like a week-long water fast. There are some real, science-based benefits to fasting. But is it right for you? Your genes may hold the answers.
Color TV has made us fat: melatonin, genetics, and light at night
Color TV has made us fat! Nope, not just because of the commercials advertising Taco Bell at night nor the fact that we are laying on our couches watching those commercials. The flickering blue light that can be seen each evening pouring out of almost every window in the neighborhood is fundamentally changing our biology. So my argument goes as follows: obesity started to rise right around 1980 in the US, which coincides with color TV’s being in the majority of homes in the US.