1369802843 © Martin Broz | GettyImages
Getty Images 1369802843

The circadian rhythm and dentistry: Is there a connection?

Nov. 4, 2022
Dentists may encounter a series of physiological and medical issues related to a patient’s circadian rhythm. Understanding these issues can help dentists make better pre- and post-op treatment decisions as well as mitigate risks to patients.

Every human being lives within the constraints of their circadian rhythm. When we wake up in the morning, sunlight shines in our eyes and stimulates the internal master clock in our brains called the suprachiasmatic nucleus (SCN). The SCN then sends signals to the hypothalamus, the pituitary gland, and the pineal gland. The hypothalamus and the pituitary gland govern appetite, thyroid function, temperature, blood pressure (BP), cortisol, growth hormone levels, and the immune system. The pineal gland begins to store the neurotransmitter serotonin, which is converted to melatonin to be released in the early evening to assist us in falling asleep.

How diagnostic technologies impact your practice and ROI

Wake up to OSA

From a medical and physiological perspective, people need to work within their circadian rhythm to maintain health and longevity, and not against it. A person can alter mealtimes, exercise, and regulate the amount of blue light they see from computers and cell phones at night, all of which can alter a person’s circadian rhythm and sleep patterns to the positive or negative. Circadian patterns also regulate physiological issues such as pain, inflammation, and the time when one has the greatest chance of myocardial infarction, which all have distinct maxima and minima at different times of the day.

Relationship to dentistry

So, what role does the circadian rhythm play in dentistry? What should a dentist be aware of concerning this master metabolic clock that governs the physiology of every patient we see?

The circadian rhythm governs virtually all aspects of human physiology. At sunrise, a human being will have a significant elevation in BP, heart rate (HR), and platelet aggregation. The elevated BP and HR occur due to the morning peak in cortisol secreted from the adrenal glands, sensitizing the cardiovascular system to the effects of epinephrine and norepinephrine. By 9:00 a.m., testosterone levels will peak along with insulin sensitivity, followed shortly by the highest level of cognitive capacity and memory lasting until midafternoon. Around 5:30 p.m., a person has their maximum level of muscle efficiency and strength; by 9:00 p.m., the highest body temperature of the day; and by 10:00 p.m., a sharp increase in the level of melatonin from the pineal gland to aid in falling asleep.1-7

Overnight, during slow-wave sleep (SWS), a person will experience their highest levels of thyroid-stimulating hormone and growth hormone (from the pituitary gland), assisting in growth and repair, utilizing metabolic lipolysis for fuel.8,9 Also during the night and overnight, a person’s neutrophil and white blood cell counts will peak at about 8:00 p.m., monocytes will peak at midnight, and basophils and eosinophils between 2:00 a.m., and 4:00 a.m., corresponding to nocturnal asthma and allergic reaction activity.10,11

These functions all occur on a diurnal rhythm every 24 hours in a healthy individual. If the circadian clock of a patient is disrupted, there is great potential for systemic implications for diseases that include diabetes,12,13 cancer,14 osteoporosis,15 and immune-allergic diseases.16

Here, we’ll look at a series of physiological and medical issues related to a patient’s circadian rhythm that dentists may encounter in their patients daily. Gaining a better understanding of these issues will help dentists make better pre- and post-op decisions for treatment and practice risk mitigation to improve the health and safety of their patients.

Part of every dental visit, whether for a simple cleaning or oral surgery, is a physical exam, a comorbidity analysis, and a polypharmacy analysis.17-19 During the exam, a dentist can determine a patient’s general and immediate health, the possibility of a medical issue occurring during a dental procedure, and any potential problems with a post-op prescription.

Morning BP surge in cardiovascular disease (CVD) patients

A patient who presents to the dental office with high BP has a documented risk factor for myocardial infarction and stroke. Many patients will experience a morning surge in BP and cardiac rate related to the morning increase in cortisol. The cortisol sensitizes the cardiovascular system to a parallel rise in epinephrine from the sympathetic nervous system as part of the normal circadian rhythm.20 This morning surge is particularly dangerous for a patient who suffers from CVD.21,22 To mitigate this risk, a dentist may focus on preventive strategies to prevent heart attack and stroke in these patients during dental procedures.

For example, a particularly sharp rise in BP in the morning may be caused by a deficient antihypertensive medication regimen. Most hypertensive patients take their medications in the morning and may, therefore, have insufficient control overnight, as the patient experiences the morning cortisol and epinephrine surge.23 A patient can be questioned about the timing of their medication and asked to keep a five-day journal of evening, afternoon, and morning BP readings to share with the dentist.

Risk mitigation strategies against heart attack or stroke:

  • Discuss medication timing with a patient’s physician to try to improve the BP parameters before a dental procedure.
  • Schedule the procedure for a time when the patient has their lowest BP of the day, based on their existing antihypertensive regimen.
  • Prescribe mild anxiolytics (such as benzodiazepines) before a procedure to prevent an increase in BP and HR before and during the procedure.24-26

Circadian management of diabetic patients

Twenty-four-hour pulsatile insulin secretion occurs in humans, with higher amplitude pulses in obese patients and patients with type 2 diabetes. A patient’s sensitivity to insulin also shows diurnal circadian changes, with abnormal rhythmicity and activity patterns in patients with obesity and diabetes. Insulin sensitivity and blood glucose levels in healthy patients are kept under very careful regulatory controls. In patients with diabetes, the aberrant insulin and glucose metabolism has significant deleterious effects on the patient’s physiology.27

The most common complication in patients with diabetes who are undergoing a dental procedure is a hypoglycemic episode. The highest risk of developing hypoglycemia will occur either during peak insulin activity or when an antidiabetic drug level exceeds the patient’s physiological needs.28

Risk mitigation strategies against hypoglycemic episodes:29

  • Question the patient on the timing of their meals and medication and ask them to keep a five-day journal of the evening, afternoon, and morning blood glucose levels to share with their dentist.
  • Discuss the antidiabetic medication and meal timing with the patient’s physician to try to improve the blood glucose levels before a dental procedure.
  • Schedule the dental procedure for a time when the patient has their most prolonged normalized blood glucose levels during the day, around meals and medication.
  • Recognize the signs and symptoms of low blood glucose levels in a patient, and have an immediate carbohydrate source to administer chairside if necessary.

Circadian management of hypothyroid patients

Hypothyroidism is defined as decreased thyroid hormone production based on aberrant thyroid gland function. It can be caused by pharmacological agents such as lithium and amiodarone, Hashimoto’s disease, surgery, and radioactive iodine. In patients with hypothyroidism, symptoms such as low metabolic rate, obesity, lethargy, and intolerance to cold are prevalent. In healthy patients, the typical circadian pattern of thyroid function shows the highest levels of thyroid hormone secretion and activity overnight between approximately 11:00 p.m. and 4:00 a.m.30,31 Currently, 8–10 million patients in the United States are being treated for thyroid disease.32

Dentists need to employ a risk management strategy to prevent cardiovascular complications resulting from treating dental patients with hypothyroid disorders who are taking thyroid hormone replacement therapy. During a dental procedure, the concurrent use of sympathomimetics (epinephrine or norepinephrine in the local anesthetic) with a patient’s levothyroxine replacement may increase the effects of sympathomimetics or thyroid hormone. This may increase the risk of coronary insufficiency with the administration of local anesthetics.

To prevent potential coronary insufficiency when administering local anesthetics:

  • Ask the patient how long they’ve been on their current thyroid medication regimen to assess if they are euthyroid.
  • Use adrenergic vasoconstrictors cautiously in patients with evidence of excessive thyroid stimulation from levothyroxine replacement.33,34
  • Speak with the patient’s endocrinologist and suggest that the patient take the thyroid hormone in the evening so that hormone levels will be lower in the morning before administration of local anesthesia.35

Circadian management of dental and orofacial pain

It has been clinically determined that a person’s subjective measurement of pain intensity does not stay at a constant level during the day. Therefore, it is reasonable to assume that one of the causes of failed analgesia in the treatment of orofacial pain could be the failure of dentists to observe a patient’s preexisting pain patterns as they relate to their individual circadian rhythms.36

The most common type of pain a dentist encounters in patients is toothache. Pain from a toothache does not occur randomly during the 24-hour period of a day. When the duration of successful local anesthesia was examined, it was found that the midafternoon (approximately 3:00 p.m.) was the time in the circadian day that produced the longest duration of local anesthesia for patients. The shortest duration was found to be in the morning and the evening.37 When the severity of temporomandibular pain was examined on a circadian basis, most patients reported experiencing their peak pain level in the evening.38

Examining data from the discipline of chronopharmacology, it has been found that the highest bioavailability and plasma levels of nonsteroidal anti-inflammatory drugs (NSAIDs) occur in the morning at approximately 7:00 a.m.39,40 Along with these findings, unsurprisingly, the highest level and frequency of side effects encountered with NSAIDs also occur in the morning.41,42

Dental pain and NSAIDs

This is a possible strategy for patients experiencing dental pain with comorbidities or moderate polypharmacy concerns regarding NSAIDs:

For morning pain, Rx 100 mg of extended-release Tramadol (pharmakokinetic efficacy is 16–24 hours) with 500 mg or 1,000 mg of acetaminophen. This will prevent higher morning side effects common with NSAIDs.43

For afternoon and overnight pain (in the same patient), Rx 500 mg acetaminophen, with 200 mg to 400 mg ibuprofen every six hours for two to three days for acute pain. The amount of acetaminophen taken in a 24-hour time period should not exceed 3,000 mg.44 Such personalized analgesic regimens have been successful in patients to maximize pain control and minimize side effects.45,46


The American Heart Association has recently added “sleep” as a measure of cardiovascular health, further informing the public about the necessity of assessing a person’s circadian rhythm in medical therapy.47 Chronopharmacology is also fast becoming a component of medical assessment and treatment.48 It is time for dentistry to get on the bandwagon and implement circadian concepts into daily practice for better patient treatment and safety.  

Editor's note: This article appeared in the November 2022 print edition of Dental Economics magazine. Dentists in North America are eligible for a complimentary print subscription. Sign up here.


1. Gamble KL, Berry R, Frank SJ, Young ME. Circadian clock control of endocrine factors. Nat Rev Endocrinol. 2014;10(8):466-475. doi:10.1038/nrendo.2014.78

2. Garbarino S, Lanteri P, Prada V, Falkenstein M, Sannita WG. Circadian rhythms, sleep, and aging. J Psychophysiol. 2021;35(3):129. doi:10.1027/0269-8803/a000267

3. Zhang D, Colson JC, Jin C, et al. Timing of food intake drives the circadian rhythm of blood pressure. Function (Oxf). 2021;2(1):zqaa034.

4. Azmi NASM, Juliana N, Azmani S, et al. Cortisol on circadian rhythm and its effect on cardiovascular system. Int J Environ Res Public Health. 2021;18(2):676. doi:10.3390/ijerph18020676

5. Bumgarner JR, Walker WH, Nelson RJ. Circadian rhythms and pain. Neurosci Biobehav Rev. 2021;129:296-306. doi:10.1016/j.neubiorev.2021.08.004

6. Hoyle NP, Seinkmane E, Putker M, et al. Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing. Sci Transl Med. 2017;9(415):eaal2774. doi:10.1126/scitranslmed.aal2774

7. Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes. J Appl Physiol. 2005;99(5):2008-2019. doi:10.1152/japplphysiol.00660.2005

8. Bellastella G, Maiorino MI, Scappaticcio L, et al. Chronothyroidology: chronobiological aspects in thyroid function and diseases. Life (Basel). 2021;11(5):426. doi:10.3390/life11050426

9. Czernichow P. Human growth hormone. In: Jacqz-Aigrain E, Choonara I, eds. Paediatric Clinical Pharmacology. CRC Press; 2021:chap 8.7:683-686. doi:10.1201/9780367800666

10. Jacob H, Curtis AM, Kearney CJ. Therapeutics on the clock: circadian medicine in the treatment of chronic inflammatory diseases. Biochem Pharmacol. 2020;182:114254. doi:10.1016/j.bcp.2020.114254

11. Wang C, Lutes LK, Barnoud C, Scheiermann C. The circadian immune system. Sci Immunol. 2022;7(72):eabm2465. doi:10.1126/sciimmunol.abm2465

12. Gamble KL, Berry R, Frank SJ, Young ME. Circadian clock control of endocrine factors. Nat Rev Endocrinol. 2014;10(8):466-475. doi:10.1038/nrendo.2014.78

13. Rakshit K, Thomas AP, Matveyenko AV. Does disruption of circadian rhythms contribute to beta-cell failure in type 2 diabetes? Curr Diab Rep. 2014;14(4):474. doi:10.1007/s11892-014-0474-4

14. Sancar A, Lindsey-Boltz LA, Gaddameedhi S, et al. Circadian clock, cancer, and chemotherapy. Biochem. 2015;54(2):110-123. doi:10.1021/bi5007354

15. Li Y, Zhou J, Wu Y, et al. Association of osteoporosis with genetic variants of circadian genes in Chinese geriatrics. Osteoporos Int. 2016;27(4):1485-1492. doi:10.1007/s00198-015-3391-8

16. Paganelli R, Petrarca C, Di Gioacchino M. Biological clocks: their relevance to immune-allergic diseases. Clin Mol Allergy. 2018;16:1. doi:10.1186/s12948-018-0080-0

17. Terézhalmy GT, Huber MA, Garcia LT, Occhionero RL. Physical Evaluation and Treatment Planning in Dental Practice. 2nd ed. Wiley Blackwell; 2021.

18. Folly P. A practical approach to special care in dentistry. BDJ Student. 2022;29(7). doi:10.1038/s41406-022-0279-x

19. Khaitovych MV. Polypharmacy: definition, risks, management. Oral Gen Health. 2021;2(3):7-12. doi:10.22141/ogh.2.3.2021.240720

20. Dodt C, Breckling U, Derad I, Fehm HL, Born J. Plasma epinephrine and norepinephrine concentrations of healthy humans associated with nighttime sleep and morning arousal. Hypertension. 1997;30(1 Pt 1):71-76. doi:10.1161/01.hyp.30.1.71

21. Bilo G, Grillo A, Guida V, Parati G. Morning blood pressure surge: pathophysiology, clinical relevance and therapeutic aspects. Integr Blood Press Control. 2018;11:47-56. doi:10.2147/IBPC.S130277

22. Fodor DM, Marta MM, Perju-Dumbrava L. Implications of circadian rhythm in stroke occurrence: certainties and possibilities. Brain Sci. 2021;11(7):865. doi:10.3390/brainsci11070865

23. Smolensky MH, Hermida RC, Ayala DE, Tiseo R, Portaluppi F. Administration–time-dependent effects of blood pressure-lowering medications: basis for the chronotherapy of hypertension. Blood Press Monit. 2010;15(4):173-180. doi:10.1097/MBP.0b013e32833c7308

24. Morgan TO. Should blood pressure medication be taken in the morning or evening? J Hypertens. 2015;33(2):263-265. doi:10.1097/HJH.0000000000000471

25. Silvestre FJ, Miralles-Jorda L, Tamarit C, Gascon R. Dental management of the patient with ischemic heart disease: an update. Med Oral. 2002;7(3):222-230.

26. Syed M. Dental management of cardiovascular compromised patient: a review. J Adv Med Dent Sci Res. 2021;9(6):60-63. doi:10.21276/jamdsr

27. Kurose T, Hyo T, Yabe D, Seino Y. The role of chronobiology and circadian rhythms in type 2 diabetes mellitus: implications for management of diabetes. ChronoPhysiology Therap. 2014;4:41-49. doi:10.2147/CPT.S44804

28. Zammitt NN, Frier BM. Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care. 2005;28(12):2948-2961. doi:10.2337/diacare.28.12.2948

29. Lamster IB. Diabetes Mellitus and Oral Health: An Interprofessional Approach. John Wiley & Sons; 2014. doi:10.1002/9781118887837

30. Russell W, Harrison RF, Smith N, et al. Free triiodothyronine has a distinct circadian rhythm that is delayed but parallels thyrotropin levels. J Clin Endocrinol Metab. 2008;93(6):2300-2306. doi:10.1210/jc.2007-2674

31. Ikegami K, Refetoff S, Van Cauter E, Yoshimura T. Interconnection between circadian clocks and thyroid function. Nat Rev Endocrinol. 2019;15(10):590-600. doi:10.1038/s41574-019-0237-z

32. General information/press room. American Thyroid Association. https://www.thyroid.org/media-main/press-room/

33. FDA package insert for Synthroid.

34. Yagiela JA. Adverse drug interactions in dental practice: interactions associated with vasoconstrictors. Part V of a series. J Am Dent Assoc. 1999;130(5):701-709. doi:10.14219/jada.archive.1999.0280

35. Bolk N, Visser TJ, Nijman J, Jongste IJ, Tijssen JGP, Berghout A. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial. Arch Intern Med. 2010;170(22):1996-2003. doi:10.1001/archinternmed.2010.436

36. Bruguerolle B, Labrecque G. Rhythmic pattern in pain and their chronotherapy. Adv Drug Deliv Rev. 2007;59(9-10):883-895. doi:10.1016/j.addr.2006.06.001

37. Pöllmann L. Circadian changes in the duration of local anaesthesia. Int J Oral Surg. 1982;11(1):36-39. doi:10.1016/s0300-9785(82)80046-x

38. van Grootel RJ, van der Glas HW, Buchner R, de Leeuw JRJ. Patterns of pain variation related to myogenous temporomandibular disorders. Clin J Pain. 2005;21(2):154-165. doi:10.1097/00002508-200503000-00007

39. Clench J, Reinberg A, Dziewanowska Z, Ghata J, Smolensky M. Circadian changes in the bioavailability and effects of indomethacin in healthy subjects. Eur J Clin Pharmacol. 1981;20(5):359-369. doi:10.1007/BF00615406

40. Ollagnier M, Decousus H, Cherrah Y, et al. Circadian changes in the pharmacokinetics of oral ketoprofen. Clin Pharmacokinet. 1987;12(5):367-378. doi:10.2165/00003088-198712050-00003

41. Perpoint B, Mismetti P, Simitsidis S, et al. Dosing time optimizes sustained-release ketoprofen treatment of osteoarthritis. Chronobiol Int. 1994;11(2):119-125. doi:10.3109/07420529409055898

42. Moore JG, Goo RH. Day and night aspirin-induced gastric mucosal damage and protection by ranitidine in man. Chronobiol Int. 1987;4(1):111-116. doi:10.1080/07420528709078514

43. Ultram ER FDA package insert for once-daily dosing.

44. Bauerlein DK, Williams AP, John PR. Optimizing acetaminophen use in patients with risk factors for hepatotoxicity: reviewing dosing recommendations in adults. Pain Med. 2021;22(7):1469-1472. doi:10.1093/pm/pnaa274

45. Von Korff M, Merrill JO, Rutter CM, Sullivan M, Campbell CI, Weisner C. Time-scheduled vs. pain-contingent opioid dosing in chronic opioid therapy. Pain. 2011;152(6):1256-1262. doi:10.1016/j.pain.2011.01.005

46. Kim MJ, Chung JW, Kho HS, Park JW. The circadian rhythm variation of pain in the orofacial region. J Oral Med Pain. 2015;40(3):89-95. doi:10.14476/jomp.2015.40.3.89

47. American Heart Association adds sleep to cardiovascular health checklist. American Heart Association. June 29, 2022. https://newsroom.heart.org/news/american-heart-association-adds-sleep-to-cardiovascular-health-checklist

48. Zhang N, Zhao Y, Tang M, Zhang Y, Ning S, Cui Z. Application of chronopharmacology in the hypertension treatment. Chin J Clin Pharmacol Ther. 2022;27(4):418-422. doi:10.12092/j.issn.1009-2501.2022.04.010

Sponsored Recommendations

Clinical Study: OraCare Reduced Probing Depths 4450% Better than Brushing Alone

Good oral hygiene is essential to preserving gum health. In this study the improvements seen were statistically superior at reducing pocket depth than brushing alone (control ...

Clincial Study: OraCare Proven to Improve Gingival Health by 604% in just a 6 Week Period

A new clinical study reveals how OraCare showed improvement in the whole mouth as bleeding, plaque reduction, interproximal sites, and probing depths were all evaluated. All areas...

Chlorine Dioxide Efficacy Against Pathogens and How it Compares to Chlorhexidine

Explore our library of studies to learn about the historical application of chlorine dioxide, efficacy against pathogens, how it compares to chlorhexidine and more.

Whitepaper: The Blueprint for Practice Growth

With just a few changes, you can significantly boost revenue and grow your practice. In this white paper, Dr. Katz covers: Establishing consistent diagnosis protocols, Addressing...