Your Circadian Rhythm
Before you become a time restricted feeding expert, let’s start at the most fundamental topic of this entire subject, your circadian rhythm.
All organisms evolved on a rotating earth, therefore almost every organism on earth has an internal clock that has adjusted to when it is light outside, and when it is dark also known as the light-dark cycle of day and night.
Humans fall under the category of being diurnal, meaning that we are most active during the day and rest during the evening. When we go to bed and after we have been asleep for “X” number of hours without having an alarm set for the next morning, our “internal clock” wakes us up and lets us know “hey it’s morning, time to wake up!” and almost every organ in our body has this same kind of “internal clock” and knows when to be most active, and when it is time to rest and recover. This internal clock is your circadian rhythm.
This is a naturally occurring 24 to 24.5-hour cycle that is at work even in the absence of light fluctuations or a light-dark cycle. This 24-hour oscillation not only governs when you may feel sleepy at night and alert during the day, but it also micromanages our cells and when they are most metabolically active. From the timing of hormone production to when repair processes are activated, all of these processes are temporal and regulated by your circadian rhythm.
The Master Regulator: Suprachiasmatic Nucleus
Before we get into how food and light have significant effect of your circadian rhythm and ultimately your metabolism, i’d like to introduce the organ of your body that runs the show.
Foundational understanding is that different sections of the brain governs different parts of the body, so which part of the brain governs our circadian rhythm?
The suprachiasmatic nucleus (a small pair of nuclei in the hypothalamus situated right above the optic chiasm) which we can call the SCN for short, serves as the master regulator of circadian rhythm. If the SCN in damaged, an organism would then loose normal their normal sense of circadian rhythm.
In one of the earliest examples of brain transplant, researchers removed the SCN of one mouse which first demonstrated to lose its sense of time. Then, after transplanting the SCN of that mouse into another mouse, the mouse who received the SCN exhibited the circadian behaviors of the mouse from which the SCN was removed.  Think of it as getting a brain transplant from Beyoncé and waking up “Like This” which is basically having the schedule to rule the world in a diamond encrusted leotard.
On a serious note, when relating the scenario of the mouse without the SCN who lost its sense of time to neurodegenerative diseases such as Alzheimer’s where we see that in very advanced stages, the SCN becomes affected, we can imply that a damaged SCN would be a major reason for a lost sense of day and night in patients with this disease.
Light’s Effect on Your Circadian Rhythm
We know that our SCN sets our internal clock, with the first sight of bright light received by our eyes. In experiments, blind mice are able to reset their circadian rhythm and in the real world after humans have gone blind they are able to regain their circadian rhythm as well. The hypothesis made after considering these situations was that there must be another light receptor specifically in the eye, and it must be in the eye itself because mice and humans who have been enucleated (have their eye removed) have shown to have lost all circadian rhythm, without the ability to regain it.
Even if someone is blind, they’re circadian rhytm can be reset circadian rhythm unless they are unable to produce a molecule called melanopsin. Melanopsin is a molecule that is sensitive to bright light and found in the retinal ganglion cells of the eye. It is believed to be the visual pigment that synchronizes the circadian cycle to the day and night cycle of our environment. In fact, when melanopsin senses light it inhibits melatonin production. Melatonin is a hormone secreted from the pineal gland that helps to make us feel sleepy when our environment becomes dark. This may serve as an important implication as to why we shouldn’t stare at computer or phone screens close to bed time. If you missed out on Ryan Conley’s article last week on how to achieve a great night’s sleep, click here for some biohacks on how to improve your quality of sleep.
Food’s Effect on Your Circadian Rhythm
The SCN maintains control of peripheral oscillators or “mini clocks”, which exhibit their own near 24-hour rhythm and control circadian phenomena in other tissues and organs. These peripheral clocks may not all be able to receive light cues as our eyes do, but their cues come from food instead. Peripheral oscillators can be found in places like the adrenal gland, esophagus, lungs, liver, pancreas, spleen, and thymus. It has been found that circadian clocks in the liver, specifically regulate metabolism.
These peripheral clocks are important because metabolism does not all happen at once. There are separated times for protein breakdown, DNA replication, etc. You can think about clocks in metabolism as traffic lights in a downtown intersection. Without these stop lights turning on and off at specific times to regulate traffic, there would be accidents and traffic jams. Similarly, in the liver there is a time for separate metabolic processes that if caught in a traffic jam could lead to dysfunction and disease.
Your circadian rhythm is actually the product of a very specific gene conveniently called, CLOCK short for Circadian Locomotor Output Cycles Kaput. CLOCK is a gene that affects both the persistence and period of circadian rhythms. In humans, polymorphisms in the CLOCK gene have been associated with insomnia, weight loss difficulty, and recurrence of major depressive episodes in patients with bipolar disorder. 
One of the most popular studies to show this took 2 groups of mice with the same light-dark cycle, but fed one group during the day and the other group during the evening. Researchers hypothesized that if the liver’s “clock” takes cue from a light, then all clock cycling genes should be identical in both groups. They went on to find that the liver’s clocks did in fact take cue from food and that the cycling genes were not identical across both groups of mice. The day fed animals had a different circadian rhythm than the night fed animals.This shows that the time we eat tells our liver clocks when to turn on and when to turn off. This experiment has been repeated many times and research continues to show that almost every organ outside of the brain responds to the cue of when we eat. After all, 10-15% of the protein-encoding genome is regulated by circadian rhythm and 40-50% of those genes deal with metabolism so food, light, and timing all together have an impact on metabolism that is much more significant than we may think!
Time – Restricted Feeding
Another popular study that shows the benefits of time restricted eating involves 2 groups of mice, who of which both received a high fat diet. 60% of the calories were from lard (~32g), 16g maltodextrin, 8.8g sucrose, 6.5g fiber (cellulose) per serving of chow. One group was restricted to eating within 8-12 hours and the other group could eat ad libitum (whenever they wanted throughout the entire 24-hour time period of each day).
The mice who were restricted to 12-hour feeding showed the following benefits:
- Decreases in fat mass in animals fed an obesogenic (high fat and high carb) diet
- Increases in lean muscle mass in mice fed a normal diet
- Improvements in glucose tolerance and insulin sensitivity
- Reductions in inflammation, improvements in lipid profile, and generally favorable changes in gene expression
- Increases of mitochondrial volume, especially in the liver and brown fat and an increased production of ketone bodies
- Reduced occurrence of fatty liver disease.
- Mice restricted to 9 hours showed an increase in endurance in the context of aerobic exercise.
From this research, Dr. Satchin Panda from the Salk Institute for Biological Studies coined the term Time Restricted Feeding (TRF).TRF has demonstrated health benefits that may include reduction in fat mass, increases in lean muscle mass, lower inflammation, improved heart function with age, increased mitochondrial volume, ketone body production, improved repair processes, and aerobic endurance improvements. Contrarily, in experimental animals who do not have a regulated circadian rhythm had an increased risk of obesity, diabetes, cardiovascular disease, and other metabolic dysfunctions. 
Why We Shouldn’t Eat Too Close to Peak Melatonin Production
While the fitness community loves to tell you that carbs after dark won’t make you fat, it does not necessarily mean that eating a ton of food in bed right before falling asleep is the “healthiest” thing for you. In recent studies, melatonin has been found in the beta islet cells of the pancreas (ever wonder why you felt sleepy after all those carbs after thanksgiving?) The primary function of a beta cell is to store and release insulin. Well, it has been found that the melatonin receptor was present in pancreatic islet cells and that melatonin signals were inhibiting insulin secretion. Therefore, leaving you the least insulin sensitive in the evening.
Applications For You
Research has shown that people who have worked night shifts for 10 years suffer memory loss equal to an additional 6.5 years of age related decline. Which leads to the question of what are the conditions that break down our internal clocks? Obviously, we can imply that not getting enough sleep or eating later than we need might be the culprit, but this is not to say that nutrition does not play a role. Nutrition matters! But when food is not something we cannot always control though, we still have control over time and when we eat. Therefore, TRF may be a good entry point to better living and possibly reaping the benefits seen in mice studies and some small human studies. If you find yourself at a weight loss plateau, try adjusting the time frame in which you eat before reducing calories again, and make sure it is no longer than a 12-hour window. This may be especially important for athletes in a physique sport who are trying to get an edge on the competition, as every little detail down to the timing of your meals matters!
1. Benedetti, F., Serretti, A., Colombo, C., Barbini, B., Lorenzi, C., Campori, E., & Smeraldi, E. (2003). Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 123(1), 23-26.
2. Chaix, A., Zarrinpar, A., Miu, P., & Panda, S. (2014). Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell metabolism, 20(6), 991-1005.
3. DeCoursey, P. J., & Buggy, J. (1989). Circadian rhythmicity after neural transplant to hamster third ventricle: specificity of suprachiasmatic nuclei. Brain research, 500(1-2), 263-275.
4. Dibner, Charma et al (2010) The Mammalian circadian timing system: Organizationand coordination of central and peripheral clocks: annual review of physiology 72/; 512-549
5. Hatori, M., Vollmers, C., Zarrinpar, A., DiTacchio, L., Bushong, E. A., Gill, S., … & Ellisman, M. H. (2012). Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell metabolism, 15(6), 848-860.
6. Lee, H. S., Nelms, J. L., Nguyen, M., Silver, R., & Lehman, M. N. (2003). The eye is necessary for a circadian rhythm in the suprachiasmatic nucleus. Nature neuroscience, 6(2), 111.
7. Masri, S. et al, (2014) Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell 158, 659-672
8. Marquie, J et al (2015) Chronic effects of shift work on cognition, findings from the VISAT longitudinal study. Occup Environ Med 72: 4 258-264
9. Panda, S., Provencio, I., Tu, D. C., Pires, S. S., Rollag, M. D., Castrucci, A. M., … & Kay, S. A. (2003). Melanopsin is required for non-image-forming photic responses in blind mice. Science, 301(5632), 525-527.
10. Peschke, E., Bähr, I., & Mühlbauer, E. (2013). Melatonin and pancreatic islets: interrelationships between melatonin, insulin and glucagon. International journal of molecular sciences, 14(4), 6981-7015.
11. Reiter, R. J., Tan, D. X., & Fuentes-Broto, L. (2010). Melatonin: a multitasking molecule. In Progress in brain research (Vol. 181, pp. 127-151). Elsevier.
12. Reppert, S. M., & Weaver, D. R. (2002). Coordination of circadian timing in mammals. Nature, 418(6901), 935.
13. Schroder, E. A. et al (2013) circadian Ryhtms, skeletal muscle molecular clocks and exercise. Exerc. Sport Sci Rev 41(4)
14. Swaab, D. F., Fliers, E., & Partiman, T. S. (1985). The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain research, 342(1), 37-44.
15. Thaiss, C. A., Zeevi, D., Levy, M., Zilberman-Schapira, G., Suez, J., Tengeler, A. C., … & Kuperman, Y. (2014). Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell, 159(3), 514-529.
16. Zhang, R., Lahens, N. F., Ballance, H. I., Hughes, M. E., & Hogenesch, J. B. (2014). A circadian gene expression atlas in mammals: implications for biology and medicine. Proceedings of the National Academy of Sciences, 111(45), 16219-16224.