I do not want to tell you that you can boost your immune system above its normal capacity through any quick fix or magic pill (because you can’t). What I want to share with you is the importance of your circadian rhythm for your immune system. And how you can boost your immune system through strengthening your circadian rhythm. Or better, by not disrupting your circadian rhythm – which weakens your immune system. I want to help you to boost your immune system to its natural full capacity.
How to use your circadian rhythm to boost your immune system: Your immune system is tightly controlled by your circadian rhythm. Unfortunately, you most likely disrupt your circadian rhythm through your lifestyle, which weakens your immune system and puts it out of balance. You can boost your immune system by taking steps to strengthen your circadian rhythm so that it can work how it should.
Read on to get a full understanding of:
- How your immune system works and why your circadian rhythm plays such a key role for it
- What the difference between a rapid and a specific immune response is and why they both have different circadian rhythms
- Why you are living a shift-work lifestyle that disrupts your circadian rhythm – even without necessarily working any shifts
- Why your lifestyle weakens your immune system and how it makes you more prone to both infectious and non-infectious, chronic diseases
- How you can align with your circadian rhythm to boost your immune system
- How allergies and drug efficiency also follow your circadian rhythm
- My experiences and your key takeaways
First off, your circadian rhythm is the natural, internal rhythm your body goes through every single day. It controls and optimizes all your body functions and allocates a specific time frame to each. This is important because your body cannot do everything at the same time.
You can get a full understanding of your circadian rhythm in this post: “How Does Your Circadian Rhythm Work: All You Need to Know“
Through your circadian rhythm, your body also optimizes the function of your whole immune system. And to boost your immune system, you must not disrupt your circadian rhythm.
Here are the four main ways how you disrupt your circadian rhythm through your lifestyle:
- You don’t receive high enough (natural) light intensities during the day.
- You do receive too much (artificial) light intensity during the evening and at night.
- The (artificial) light you receive during the evening and at night is too high in the blue-light spectrum.
- You eat for too long and/ or too late.
Let’s start with a basic overview of how your immune system works. Then, I will highlight why an un-disrupted circadian rhythm is so vital for your immune system and why a disrupted circadian rhythm weakens your immune system. And finally, we’ll come back to those four main lifestyle problems that disrupt your circadian rhythm and how you can overcome those to boost your immune system.
Your Immune System
How Does Your Immune System Work
To appreciate the role that your circadian rhythm plays for your immune system, let me start with the basics. Let me start with what your immune system needs to cope with.
In a nutshell, your life and life in any form is always under attack. These attacks can be more obvious, like from the predators your ancestors faced – think about saber-toothed tigers or bears. Or they can be more subtle attacks, like the ones that you still face – think about bacteria, viruses, parasites, or cancer. And what these attacks have in common is the daily rise and fall of them occurring. Many of these attackers have their own circadian rhythms. Consequently, your immune system adapted its circadian rhythm in anticipation of this daily rise and fall of attacks.
Your immune system works based on your circadian rhythm. Or, to be more precise, the individual parts of your immune system are timed and organized based in anticipation of when they are most vital. All based on your circadian rhythm. And this is important for your body not only to defend yourself but also to preserve a state of balance.
And what might be counterintuitive is that not all parts of your immune system can be active at the same time. Not even when a threat is detected. If they were, you would actually experience something called a “septic shock,” a state of overwhelm from which your body would not be able to recover. So, what your body instead does is to complete its tasks at different times. Based on your circadian rhythm.
To appreciate the role of your circadian rhythm for your immune system, have a look at what leading researchers Nathalie Labrecque and Nicolas Cermakian stated in their paper about the “Circadian Clocks in the Immune Response”:
“Even if the research to decipher the impacts of circadian clocks on immune cell function is in its infancy, it is clear that this circadian regulation is profound and widespread. All immunocompetent cell types studied so far show some kind of circadian regulation.”Labrecque & Cermakian
With that being said, let’s have a closer look at how your immune system works next.
Your immune system can be divided into two lines of protection: The first line is the rapid but nonspecific line of your immune system. This is called your innate immune system and is sufficient in most cases. But if needed, then it calls on the specific but non-rapid second line of your immune system. This is called your adaptive immune system.
Innate Immune System
How Does Your Rapid but Non-Specific Innate Immune System Work
The first line of protection: your rapid but non-specific innate immune system. From an evolutionary perspective, this is the ancient part. It is a collection of defenses and pathogen (your attackers) recognition.
The initial defense that a pathogen has to overcome are physical barriers that protect potential points of entry to your body. Your skin uses a protein (keratin) to resist physical entry and your body openings are protected by your mucous, hair, or a combination of both. Still, pathogens can enter your body through wounds in your skin like abrasions or punctures or simply by strength in numbers to overcome the protection of your body openings. And also if they are in what you eat or drink. And if the pathogen is a cancer cell, then it doesn’t even need to enter your body in the first place.
Once a pathogen is in your body, your white blood cells (leukocytes) in both your blood and lymph system are there to recognize them as foreign (through pattern-recognition receptors). They can then initiate an inflammatory response. And this local inflammation attracts immune cells to this place.
Now, depending on the recognized pathogen (your attacker), different immune cells participate in the response to it (a simplified overview):
- Against bacteria, you have immune cells that produce antimicrobial agents (called neutrophils) to kill those.
- Against viruses, you have Pac-Man-like immune cells (called mononuclear phagocytes) that eat and destroy those. Besides viruses, they are also effective against bacteria and other foreign substances.
- Against parasites, you have immune cells that secrete vesicular content (called eosinophils) that can damage the parasite membrane.
- Against cancer cells, you have immune cells that recognize cell abnormalities (called natural killer cells) and that can kill tumor cells and certain infected cells.
To recap, this rapid response of your innate immune system depends on many different immune cells. All the way from recognition to destruction. And what do all of these immune cells have in common? Their activity levels all peak based on their circadian rhythm. In anticipation of the daily rise and fall of attacks.
Your innate immune cells follow their circadian rhythm. And most studies found the peak levels in their counts in the daytime or late day.
When your immune system activates these innate immune cells, it also alerts your adaptive immune system. The innate immune system can differentiate among different kinds of pathogens to activate the most effective adaptive immune response. This will further fight those pathogens until those are either completely eliminated or inactivated.
Adaptive Immune System
How Does Your Specific but Non-Rapid Adaptive Immune System Work
The second line of protection: your specific but non-rapid adaptive immune system. From an evolutionary perspective, this is the more recently developed part. It uses an antigen-specific immune response and generates immune memory, allowing for specific long-term protection. However, the adaptive immune system is dependent on the innate immune system to activate it, share information about the kind of pathogen with it, and direct it to the right location.
Now, the immune cells that participate in this adaptive response are a type of white blood cells, called the T and B lymphocyte cells. They have the advantage of responding specifically to that respective pathogen (your attacker). And they can use their immunologic memory when they deal with a known pathogen.
Finally, it is the coordinated response of both T and B cells that destroy the pathogen. And after they are successful, a few of these T and B cells will become long-lived memory cells and become part of the immunologic memory. Ready for long-term protection against that specific pathogen.
Also, your adaptive immune cells follow their circadian rhythm. But their numbers are generally found to peak at night and then decline in the morning and remain low during the day.
It is the two-way communication between your rapid innate immune system and your specific adaptive immune system that makes it so efficient. Also, as you have already seen, they both peak at different times based on their circadian rhythms. And any (circadian) breakdown could lead to flawed communication between these two immune systems. Which, in turn, could result in harmful immunologic responses including autoimmunity, allergy, septic shock, or chronic infection.
A Weakened Immune System
How Living Against Your Circadian Rhythm Weakens Your Immune System
You have seen above that the count of your immune cells from your rapid, innate immune system peaks in the daytime or late day. And that the count of your immune cells from your specific, adaptive immune system peaks at night and declines in the morning and remains low during the day. You have also seen that any miscommunication between those two can result in serious harmful immunologic responses.
And you have also seen that these different immune cells are regulated by your circadian rhythm. Even more so, all immune cell types that have been studied to date show some kind of circadian regulation.
So, what is the effect of your circadian rhythm on your immune system? Let me quote Satchin Panda, one of the leading chronobiologists, here:
“Your immune system has a circadian component, and if you can resync it, you can regulate its response. What’s more, disrupting your circadian code affects your immune system, making you more susceptible to diseases or infections and making it more difficult to recover quickly.”Satchin Panda
Ok, that is a first generic overview of what happens when you disrupt your circadian rhythm: Your immune system is weakened and you become more vulnerable to diseases and infections.
But let’s get more specific now.
The most common way to disrupt your circadian rhythm comes in the form of or modern lifestyles. And one of the most extreme forms to disrupt your circadian rhythm is through shift work. Now, let me introduce why you are (to some extent) a shift worker. At least from the perspective of your circadian rhythm. This is because your lifestyle (again, to some extent) resembles that of a traditional shift worker.
There are many kinds of lifestyles that you can put your body through that have similar effects to shift work. Let’s have a look at two of the most prominent ones and compare them with your lifestyle:
- Shift work through your everyday lifestyle: You fit the definition of shift work if you stay awake for more than three hours between 10:00 pm and 5:00 am for more than 50 days in a year. And, as Satchin Panda puts it, “we are all shift workers simply due to the way we live our lives.”
- Shift work through a social jet lag lifestyle: You fit the definition of social jet lag if your sleep-wake cycles are different (later) on the weekends. And eighty-seven percent of the population suffers from social jet lag.
As you can see, the question here is not if one of these definitions describes your lifestyle. The question rather is to what extent these describe your lifestyle.
Now to the next part: How does shift-work-like lifestyle affect your immune system? It weakens your circadian rhythm and, hence, also the circadian rhythm of your immune system. Your immune system can’t optimize its functions anymore. And that makes you more prone to diseases, both infectious and non-infectious, chronic ones.
How Disrupting Your Circadian Rhythm Makes You More Prone to Infectious Diseases
There is a strong interplay between a disrupted circadian rhythm and being more prone to diseases.
As part of the Maastricht Cohort Study of more than eight thousand workers from forty organizations, Danielle Mohren and colleagues compared shift workers to non-shift workers. What did they find out about their immune systems? Shift workers were more likely to suffer from infectious diseases, ranging from the common cold to stomach infections.
Satchin Panda, professor at the Salk Institute and founding member of the Center for Circadian Biology at the UC, San Diego, summarizes the problem of a weakened circadian rhythm as follows: “Observations show us that when our [circadian] rhythm is off and we come in contact with everyday bugs or viruses that we are typically resistant to, they can cause serious illness.”
Lighting cycles that simulate shift work or jet lag have repeatedly been shown to reduce the lifespan in animals. In one study, mice were put through such a lifestyle by advancing or delaying for a few hours when their lights were turned on and off. The result after a few weeks? For some of these groups, the death rate more than tripled compared to their control groups. And fewer than half of the older mice survived when their light cycle was advanced.
Another mice study had a look at the effect of circadian disruption on viral pneumonia severity. The study group of mice had a disrupted circadian rhythm (in this case through a defective gene) while the control group did not. The result could not have been more different: 100% of the mice with a defective circadian rhythm died from this virus by day eight compared to 0% from the control group even after the end of the experiment at day twenty-one.
Non-Infectious, Chronic Diseases
How Disrupting Your Circadian Rhythm Makes You More Prone to Non-Infectious, Chronic Diseases
The connection between a lifestyle that disrupts your circadian rhythm, such as a shift-work-like lifestyle, and non-infectious, chronic diseases is even further researched and established.
A lifestyle that disrupts your circadian rhythm is associated with an increased risk of immune-related diseases, including:
- Cardiovascular diseases
- Metabolic syndrome (including obesity)
- Gastrointestinal diseases
Let’s have a closer look at a shift-work-like lifestyle and cancer: Many scientific studies have shown how the circadian disruption of a shift-work lifestyle increased the risk of cancer to such an extent that the World Health Organization’s International Agency for Research on Cancer classified shift work as a potential carcinogen in 2007.
And here’s how the disruption of your circadian rhythm increases your risk of cancer: Do you remember that you have immune cells that recognize cell abnormalities (called natural killer cells) and that can kill cancer cells? Well, if you weaken your circadian rhythm then you also disrupt their work. And this reduces how effective they are at eliminating the growth of cancer cells. This, in turn, promotes cancer growth.
In their chapter about the “Circadian Organization of the Immune Response” Daniel Cardinali and colleagues stated the following:
“The circadian clock is one of the most indispensable biological functions”Cardinali et al.
With all the information you have seen above, this probably does not come as a surprise anymore. So, now to the key question: How can you use your circadian rhythm to boost your immune system? Simply, by not disrupting your circadian rhythm and letting it work as it should.
If you are like most people, then there are a few things that can help you to align with your circadian rhythm to get it back on track. And that is what we will look at next.
Boost Your Immune System
How to Get Your Circadian Rhythm Back on Track to Boost Your Immune System
It is really important to state the previous again: Your circadian rhythm plays a vital role for your immune system. And you can boost your immune system by not disrupting your circadian rhythm. Your immune cells are timed and organized based on your circadian rhythm and in anticipation of when they are most vital. In this way, they work in sync and it is important to keep that balance.
So, when you want to boost your immune system, you want to achieve that natural state of balance, where all the parts of your immune system are timed and organized by your circadian rhythm and can work in sync.
The problem with our modern lifestyles is that we are not naturally aligned with our circadian rhythms anymore. You have seen one outcome, your shift-work-like lifestyle (through traditional shift work timings or social jet lag), above. But let’s get a little deeper into what that means for you in your everyday life.
In general, there are four problem areas that most likely prevent you from living aligned with your circadian rhythm. And those are connected to either your light exposure or your eating timings – which are the two most influential factors to set your circadian rhythm(s):
- The first problem is that you don’t receive high enough (natural) light intensities during the day.
- The second problem is that you do receive too much (artificial) light intensity during the evening and at night.
- The third problem is that the (artificial) light you receive during the evening and at night is too high in the blue-light spectrum.
- The fourth problem is that you eat for too long and/ or too late.
You can get a full understanding of each of the four problem areas as well as the tips to overcome these in this post: “How to Get Your Circadian Rhythm Back on Track”
Now you have seen the four biggest problems that disrupt your circadian rhythm and hence weaken your immune system. So let’s have a quick look at what you can do about each of these problem areas
Problem 1: You don’t get enough light during the day
Tip #1 Spend at least two hours outdoors during the first half of every day
Tip #2 Stay as close to windows as possible if you are indoors
Tip #3 Take artificial light showers during the day if needed
Tip #4 Don’t wear sunglasses (if you don’t spend the whole day outside)
Tip #5 Spend a weekend in nature
Problem 2 & 3: You get too much light & blue light during the evening and at night
Tip #6 Adapt your home lighting for the second part of the day
Tip #7 Reduce blue-light emissions from your screens
Tip #8 Use blue-light filtering glasses
Tip #9 Avoid any (blue) lights at night
Problem 4: You eat for too long and/ or too late
Tip #10 Stop eating early enough in the evening
Tip #11 Eat for fewer hours every day
You can get a full understanding of each of the four problem areas as well as the tips to overcome these in this post: “How to Get Your Circadian Rhythm Back on Track”
How Allergies Follow Your Circadian Rhythm
Do you remember that any breakdown in the communication between your innate (the rapid yet non-specific one) and your adaptive immune system (the specific yet non-rapid one) can also lead to allergy?
Now, also allergies do follow your circadian rhythm, meaning that they have a daily pattern of symptoms. For example, the symptoms of most allergies (e.g., asthma or hay fever) are at their worst overnight or early in the morning.
Hopefully, you do not have any allergies. But if you are unfortunate enough to have any, you might want to have a look at when their symptoms normally are at their worst.
Rhythmic Drug Efficiencies
How Drug Efficiency Depends on Timing
It has been long known that the timing of drugs is important for their effectiveness.
Almost every drug target follows a circadian rhythm. Let’s have a look at the biggest gene family in our genome, called the G protein-coupled receptors (GPCRs). Why? Because they are the target of nearly half of the drugs that are on the market. Blood pressure, for example, is regulated by these genes. And medication is most effective following the expression of their circadian rhythm. Which, in the case of blood pressure, would be just before bedtime.
Or let’s take the case of high cholesterol. Imagine that you could use a drug that targets the gene that makes a protein that helps make cholesterol in your liver. Also, this process has a daily rhythm, making more cholesterol in the morning and less at night. Now, at what time would you want a cholesterol drug to be effective? Yes, you would want it to reduce cholesterol production at the time when the genes that produce it are most active.
In general, the potential of using your circadian rhythm to determine the timing of drugs is promising. Especially since nearly all drug targets follow a circadian rhythm. And for some treatments, it has already been shown that the right timing can lead to improved drug efficiency with reduced side effects.
So, the next time you have to take a drug, you might want to double-check when its best timing would be.
My Personal Experiences
I’ve been trying to live aligned with my circadian rhythm for quite a few years now. And with respect to my immune system, there are two changes that I especially want to share with you. One is about catching diseases in general and the other one about a (now past) nut allergy.
Changes with respect to catching diseases. Since I’ve started to strengthen my circadian rhythm, I can’t remember really having been sick. Even more so, there were zero days in the past couple of years that I had to take off work because of sickness. And probably only a handful of days where I did not feel well enough to train.
Changes with respect to allergies. Even more impactful for my daily life is that my body doesn’t react allergically to nuts anymore. Granted, those reactions were never anything serious, more like a really itchy sensation in my mouth that was highly irritating. And that also made me dislike nuts to some extent. But now? I love them and eat them daily. Especially macadamia nuts. And I don’t have any allergic reactions to them anymore.
Now, correlation doesn’t necessarily equal causality and there could have been different factors influencing these changes. Yet, it always feels great to me to achieve similar results than these from promising scientific research. I am more than happy with these changes and hope that you’ll have similarly positive effects.
There are five key takeaways that I want to share with you that all help you boost your immune system through strengthening your circadian rhythm:
- Your circadian rhythm plays a key role for your immune system (and for anything else in your body for that matter).
- Your immune system consists of two parts that both have complementing expressions of your circadian rhythm and that need to be in balance.
- The rapid yet non-specific part of your immune system is called your innate immune system and its immune cells have the highest count during the day and late in the day.
- The specific yet non-rapid part of your immune system is called your adaptive immune system and its immune cells have the highest count during the night.
- Your modern lifestyle most likely has disrupted your circadian rhythm and weakened your immune system.
- You can best boost your immune system by strengthening your circadian rhythm.
- Increase your natural light exposure as much as you can during the day.
- Reduce your artificial light exposure during the evening and at night.
- Don’t eat for too long and/ or too late.
- Almost every drug target follows a circadian rhythm and drugs are more effective and have less severe side effects if taken at the right time.
And now back to you: Have you already identified whether a disrupted circadian rhythm is in the way of boosting your immune system? And if so, what do you plan to do about it?
PS: If you found this information useful, spread the word and help those who would benefit most from it 🙂
- 1.Roenneberg T. Internal Time. Harvard University Press; 2012.
- 2.Panda S. The Circadian Code. Rodale Books; 2018.
- 3.Cermakian N, Lange T, Golombek D, et al. Crosstalk between the circadian clock circuitry and the immune system. Chronobiology International. May 2013:870-888. doi:10.3109/07420528.2013.782315
- 4.Labrecque N, Cermakian N. Circadian Clocks in the Immune System. J Biol Rhythms. April 2015:277-290. doi:10.1177/0748730415577723
- 5.Clark R, Kupper T. Old Meets New: The Interaction Between Innate and Adaptive Immunity. Journal of Investigative Dermatology. October 2005:629-637. doi:10.1111/j.0022-202x.2005.23856.x
- 6.Haus E, Smolensky MH. Biologic Rhythms in the Immune System. Chronobiology International. January 1999:581-622. doi:10.3109/07420529908998730
- 7.Mazzoccoli G, Vendemiale G, La Viola M, et al. Circadian Variations of Cortisol, Melatonin and Lymphocyte Subpopulations in Geriatric Age. Int J Immunopathol Pharmacol. January 2010:289-296. doi:10.1177/039463201002300127
- 8.Ackermann K, Revell VL, Lao O, Rombouts EJ, Skene DJ, Kayser M. Diurnal Rhythms in Blood Cell Populations and the Effect of Acute Sleep Deprivation in Healthy Young Men. Sleep. July 2012:933-940. doi:10.5665/sleep.1954
- 9.Born J, Lange T, Hansen K, Mölle M, Fehm H. Effects of sleep and circadian rhythm on human circulating immune cells. J Immunol. 1997;158(9):4454-4464. https://www.ncbi.nlm.nih.gov/pubmed/9127011.
- 10.Dimitrov S, Benedict C, Heutling D, Westermann J, Born J, Lange T. Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood. May 2009:5134-5143. doi:10.1182/blood-2008-11-190769
- 11.Lange T, Dimitrov S, Born J. Effects of sleep and circadian rhythm on the human immune system. Annals of the New York Academy of Sciences. April 2010:48-59. doi:10.1111/j.1749-6632.2009.05300.x
- 12.Besedovsky L, Born J, Lange T. Endogenous glucocorticoid receptor signaling drives rhythmic changes in human T‐cell subset numbers and the expression of the chemokine receptor CXCR4. FASEB j. September 2013:67-75. doi:10.1096/fj.13-237958
- 13.Abo T, Kawate T, Itoh K, Kumagai K. Studies on the bioperiodicity of the immune response. I. Circadian rhythms of human T, B, and K cell traffic in the peripheral blood. J Immunol. 1981;126(4):1360-1363. https://www.ncbi.nlm.nih.gov/pubmed/6970770.
- 14.Kirsch S, Thijssen S, Alarcon Salvador S, et al. T-cell Numbers and Antigen-specific T-cell Function Follow Different Circadian Rhythms. J Clin Immunol. July 2012:1381-1389. doi:10.1007/s10875-012-9730-z
- 15.Habbal OA, Al-Jabri AA. Circadian Rhythm and the Immune Response: A Review. International Reviews of Immunology. January 2009:93-108. doi:10.1080/08830180802645050
- 16.Merrow M, Roenneberg T. Circadian clocks: how rhythms structure life. Presented at the: coursera; 2019; Ludwig-Maximilians-Universität München (LMU).
- 17.Zhuang X, Rambhatla SB, Lai AG, McKeating JA. Interplay between circadian clock and viral infection. J Mol Med. September 2017:1283-1289. doi:10.1007/s00109-017-1592-7
- 18.Mohren DCL, Jansen NWH, Kant Ij, Galama JMD, van den Brandt PA, Swaen GMH. Prevalence of Common Infections Among Employees in Different Work Schedules. Journal of Occupational and Environmental Medicine. November 2002:1003-1011. doi:10.1097/00043764-200211000-00005
- 19.Davidson AJ, Sellix MT, Daniel J, Yamazaki S, Menaker M, Block GD. Chronic jet-lag increases mortality in aged mice. Current Biology. November 2006:R914-R916. doi:10.1016/j.cub.2006.09.058
- 20.Haspel J, Agapov E, Holtzman MJ. Effects of Circadian Rhythm Disruption on Viral Pneumonia Severity. In: American Journal of Respiratory and Critical Care Medicine; 2015.
- 21.Straif K, Baan R, Grosse Y, et al. Carcinogenicity of shift-work, painting, and fire-fighting. The Lancet Oncology. December 2007:1065-1066. doi:10.1016/s1470-2045(07)70373-x
- 22.Logan RW, Zhang C, Murugan S, et al. Chronic Shift-Lag Alters the Circadian Clock of NK Cells and Promotes Lung Cancer Growth in Rats. JI. February 2012:2583-2591. doi:10.4049/jimmunol.1102715
- 23.Savvidis C, Koutsilieris M. Circadian Rhythm Disruption in Cancer Biology. Mol Med. July 2012:1249-1260. doi:10.2119/molmed.2012.00077
- 24.N. Anisimov V, A. Vinogradova I, V. Panchenko A, G. Popovich I, A. Zabezhinski M. Light-at-Night-Induced Circadian Disruption, Cancer and Aging. Current Aging Science. 2012;5(3):170-177(8).
- 25.Bøggild H, Knutsson A. Shift work, risk factors and cardiovascular disease. Scand J Work Environ Health. 1999;25(2):85-99 (15).
- 26.Scheer FAJL, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proceedings of the National Academy of Sciences. March 2009:4453-4458. doi:10.1073/pnas.0808180106
- 27.Puttonen S, Härmä M, Hublin C. Shift work and cardiovascular disease — pathways from circadian stress to morbidity. Scand J Work Environ Health. 2010;36(2):96-108.
- 28.Sookoian S, Gemma C, Fernández Gianotti T, et al. Effects of rotating shift work on biomarkers of metabolic syndrome and inflammation. J Intern Med. March 2007:285-292. doi:10.1111/j.1365-2796.2007.01766.x
- 29.Karlsson B. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27 485 people. Occupational and Environmental Medicine. November 2001:747-752. doi:10.1136/oem.58.11.747
- 30.Knutsson A. Health disorders of shift workers. Occupational Medicine. March 2003:103-108. doi:10.1093/occmed/kqg048
- 31.Codoñer-Franch P, Gombert M. Circadian rhythms in the pathogenesis of gastrointestinal diseases. WJG. October 2018:4297-4303. doi:10.3748/wjg.v24.i38.4297
- 32.Marcheva B, Ramsey KM, Buhr ED, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. June 2010:627-631. doi:10.1038/nature09253
- 33.Gale JE, Cox HI, Qian J, Block GD, Colwell CS, Matveyenko AV. Disruption of Circadian Rhythms Accelerates Development of Diabetes through Pancreatic Beta-Cell Loss and Dysfunction. J Biol Rhythms. September 2011:423-433. doi:10.1177/0748730411416341
- 34.McAlpine CS, Swirski FK. Circadian Influence on Metabolism and Inflammation in Atherosclerosis. Circ Res. June 2016:131-141. doi:10.1161/circresaha.116.308034
- 35.Haupt CM, Alte D, Dörr M, et al. The relation of exposure to shift work with atherosclerosis and myocardial infarction in a general population. Atherosclerosis. November 2008:205-211. doi:10.1016/j.atherosclerosis.2007.12.059
- 36.Cardinali DP, Esquifino AI, Maestroni GJM, Pandi-Perumal SR. Circadian Organization of the Immune Response. In: Neuroimmunology of Sleep. Springer US; 2007:59-84. doi:10.1007/978-0-387-69146-6_3
- 37.Ede MCM. Circadian rhythms of drug effectiveness and toxicity. Clinical Pharmacology & Therapeutics. November 1973:925-935. doi:10.1002/cpt1973146925
- 38.Wei K, Wang Q, Gan J, et al. Mapping genes for drug chronotherapy. Drug Discovery Today. November 2018:1883-1888. doi:10.1016/j.drudis.2018.06.011
- 39.Winter C, Soehnlein O. The potential of chronopharmacology for treatment of atherosclerosis. Current Opinion in Lipidology. October 2018:368-374. doi:10.1097/mol.0000000000000545