For years, my mom worked night shifts at Vancouver Hospital as an ER respiratory therapist. During the day she was a stay-at-home mom, taking care of my siblings and I, driving us to and from school, and our extracurricular activities. Over time, this lifestyle took a toll on her health and it became quite clear that she only had two choices – quit her job or accept that her body would fail her. Since her retirement, her health has worsened and only after 15 years of making healthier, more balanced dietary choices and exercising more, has her body started to repair itself.
In Canada, approximately 4.1 million of 14.6 million or 28% of employed people do not work a regular day shift.1 It is a well-known fact that working irregular hours causes insomnia and fatigue and burnout. Lesser known is that it also increases the risk of obesity, type 2 diabetes and hypertension.2 In recent years, a much better understanding of the circadian rhythm has developed – explaining how a disrupted circadian rhythm increases the risk of chronic disease, and how a balanced circadian rhythm is key to maintaining a healthier, longer life.
Novel research confirms a complex system of clocks that are intimately synchronized with variations of light and sleep/feeding cycles.2 The body’s master clock, found in the brain, attunes itself to perceived changes in light and sets the time for the whole body.2 Individual organs, such as the heart, thyroid, and liver, also have their own clocks.2 The clocks communicate with each other via a system of nerves and hormones,3 much like the endocrine system, or digestive system.
As the master clock sets the pace and the other clocks follow, activity of every organ and cell is synchronized. Synchronicity ensures that the needs of the body at a particular moment are met. For example, when the body expects a meal, the master clock communicates with organs (especially the liver) and cells to synthesize glucose transporters and enzymes required to metabolize the sudden rush of glucose.4 Individual clocks must work synergistically as the body’s needs change throughout the day. The system also ensures that conflicting metabolic processes occur at different times of the day.5 As the time on the clocks change, each organ can be thought of as a completely different organ.2
Specific genes involved in the regulation of the circadian clocks have now been identified and are being studied in both humans and animal models. We are beginning to understand the function of specific genes, how the genes interact, and how expression of these genes change throughout the day. More importantly, research is striving to understand the process of circadian desynchronization and its potential clinical applications, especially on increasingly number of people who work irregular hours.
The Circadian Rhythm and the Liver
Research shows that the circadian rhythm affects organ function by inducing temporary changes in gene expression. These changes have been most extensively researched in the liver. Genetic analysis shows that 5-20% of the liver’s DNA changes according to the circadian rhythm throughout the day.2 Every aspect of liver function is regulated by the body’s circadian rhythm from the metabolism of cholesterol, detoxification, the conversion of thyroid hormones, and the synthesis of coagulation factors that control bleeding.4
The liver plays an immeasurable role on how our body responds to our surroundings. Suboptimal liver processing of potentially toxic chemicals from daily hygiene products, pesticides, pollution, and food is often the underlying cause of chronic disease. A better understanding of circadian regulation of liver detoxification pathways would strengthen our defence and resilience against various environmental insults. When specific circadian rhythm genes are knocked out, mice show premature aging syndromes as well as widespread deficits in liver detoxification.4
Alcohol undoubtedly stresses the liver’s detoxification pathways and desynchronizes the liver clock from the master clock.2 As the liver’s clock becomes disconnected from the system, liver activity and function no longer addresses the body’s needs at a particular time. Researchers suggest that there may be times during the day when the circadian clock is more vulnerable to the damaging effects of alcohol, times when it’s best to avoid alcohol.2 Unfortunately, (or fortunately), that time is yet to be determined but the its implications are monumental. Laboratory studies also show that alcohol mediates changes to the intestinal clock.2
All health products (supplements, herbs, medications) taken orally are processed by the liver before going to target organs. Since the liver functions as a completely different organ depending on the time of day2, treatments implemented at different times of day could yield better results with fewer side effects. In one study, taking antihypertensives in the evening (compared to morning) showed a greater reduction in cardiovascular events (CVEs) and cardiovascular mortality5.
The Circadian Rhythm and Diabetes
Extreme levels (high or low) of glucose levels are life-threatening medical emergencies. Together, the master clock and liver clock modulate baseline levels of glucose, and its regulating hormones glucagon and insulin.4 This ensures that glucose levels are kept within a safe physiological range, regardless of fluctuations in sleep/wake and feeding cycles. This has tremendous implications on the treatment of type II Diabetes. Diet, poor lifestyle choices and irregular work times are all risk factors for developing type II diabetes.2 Understanding the degree of effect that circadian dysregulation has on insulin and glucose levels would also show the extent that lifestyle choices contribute to the disease process. This would enable naturopathic doctors to better predict the magnitude of benefit of lifestyle and dietary recommendations which are cornerstones of type II Diabetes treatment.
The Circadian Rhythm and Diet
A meal rich in a particular type of nutrient, fat, protein or carbohydrate, has different effects on the body when consumed at different times of the day. People who regularly eat high fat meals at the end of the day are more likely to increase fat synthesis, have elevated cholesterol and fat), and cardiac dysfunction.2 In another study, rodents were forced to eat during times when they should have been sleeping and gene expression in all organ clocks shifted by 12 hours.2 These same mice also showed significant weight gain.2 We might finally have the answer to why that midnight or mid-morning snack might not be the best idea.
What this all means for the future medicine and your health
Furthering our understanding of the circadian system ripples into just about every area of health. It provides insight into and hope for conditions where circadian dysfunction is common that do not yet have a cure, including schizophrenia6, Alzheimer’s, Parkinson’s and Huntingdon disease.7 It means implementing preventative strategies earlier in conditions where circadian dysfunction is a risk factor.4 It’s providing us with more accurate and reliable prognostic factors.
Heart attacks of a certain nature (STEMI) are more likely to happen in the morning.5 Consequently, symptom onset time might be a better prognostic factor than the current prognostic factor used – duration of restricted blood flow.5 This brings to question whether current standards and interventions are to par with research is showing. Further research is necessary.
Novel treatment goals that acknowledge the circadian-induced natural fluctuations of the body could mean better outcomes. Research suggests that normalizing sugar levels before and after breakfast should be the primary treatment goal for diabetes.5 Blood glucose levels in non diabetes remain constant over night whereas diabetic patients have an elevated blood glucose in the morning before breakfast.5 Adrenal gland release of your stress hormone, cortisol, also follows a circadian rhythm.5 In healthy individuals, cortisol levels peak before waking and decrease during sleep.5 Conventional glucocorticoid replacement therapy for adrenal insufficiency often leads to poor outcomes because it does not mimic this natural 24 hour pattern.5
Conclusion
Like a movie director, the circadian rhythm directs everything that happens behind the scenes, coordinating function of all organs and cells. Improving circadian health undoubtedly promotes whole body health.
Our most current understanding of our circadian clocks highlights the risks of working long hours, night shifts or even motherhood. All of which are associated with a higher risk for dyslipidemia, obesity, type 2 diabetes and hypertension.2 The key to living a healthier, longer life is having a regular schedule and for those who are unable to do, understanding the effects of a disrupted circadian rhythm and mitigating these effects. Addressing circadian dysregulation will not only improve your overall health but also slow aging and reduce your risk of developing various chronic disease.
Maintaining a healthy, balanced circadian system can be done by having a regular sleep, eating and activity schedule. A regular schedule allows the body to anticipate and be prepared for varying environmental demands or stresses2, for example, by producing more digestive enzymes in preparation for a meal, so that absorption can follow. Experience a healthier, longer life with a sharper & faster mind, heightened energy levels, and better heart, digestive and reproductive health.
Dr. Olisa Mak is a licensed ND with a general family practice in downtown Vancouver. She has a special interest in bringing awareness to the mind-body connection using homeopathy, botanicals and lifestyle counselling.
She is driven to educate, inspire and empower those around her. Everyone has the potential to achieve their dreams and goals but are often unable to because of their fears, perceptions and circumstances. Dr. Mak strives to work with her patients to remove barriers, empowering patients to seize opportunities and to make the life they want a reality.
References
- “Perspectives On Labour And Income: Work-Life Balance Of Shift Workers”. Statcan.gc.ca. N.p., 2015. Web. 20 May 2016.
- Udoh, Uduak et al. “The Molecular Circadian Clock And Alcohol-Induced Liver Injury”. Biomolecules 5.4 (2015): 2504-2537. Web.
- Okubo, Naoki et al. “Parathyroid Hormone Resets The Cartilage Circadian Clock Of The Organ-Cultured Murine Femur”. Acta Orthopaedica 86.5 (2015): 627-631. Web.
- Reinke, Hans and Gad Asher. “Circadian Clock Control Of Liver Metabolic Functions”. Gastroenterology 150.3 (2016): 574-580. Web.
- Nagy, A. D. and A. B. Reddy. “Time Dictates: Emerging Clinical Analyses Of The Impact Of Circadian Rhythms On Diagnosis, Prognosis And Treatment Of Disease”. Clinical Medicine 15.Suppl_6 (2015): s50-s53. Web.
- Johansson, Anne-Sofie et al. “Altered Circadian Clock Gene Expression In Patients With Schizophrenia”. Schizophrenia Research (2016): n. pag. Web
- Videnovic, Aleksandar and Phyllis C. Zee. “Consequences Of Circadian Disruption On Neurologic Health”. Sleep Medicine Clinics 10.4 (2015): 469-480. Web.