While our literature survey has emphasized circadian factors that affect psychological and sleep disturbances, and non-drug treatment approaches that normalize the daily cycle, there is an explosion of research on medical applications that very possibly will transform how doctors diagnose illness and manage treatment, with less reliance on conventional medication, or with significant dose reduction and minimization of adverse effects.  Again, it boils down to determination of the effects of disrupted or displaced circadian rhythms as a major pathogenic agent.

The immune system itself is modulated by the inner clock, and is compromised when clockwork goes awry. Cancer cells proliferate on a circadian cycle, and interventions can be optimized with appropriately timed treatment. Circadian misalignment is a distinct precursor to diabetes.  The list goes on and on, as you will see by checking (and reading) our references.

Our underlying message is that the armamentarium of chronotherapy—light therapy, light protection, wake therapy, melatonin administration (all of these time-anchored to an individual’s chronotype, rather than the clock on the wall)—is in the cards for supplementation or even substitution for conventional medical therapeutics.

REFERENCES

Books

Turek F, Zee P (eds.).  Regulation of Sleep and Circadian Rhythms. Boca Raton, Florida, CRC Press, 1999
Smolensky M, Lamberg L. The Body Clock Guide to Better Health: How to Use your Body’s Natural Clock to Fight Illness and Achieve Maximum Health. New York, Holt, 2001

 

Reviews

Lévi F, Canon C, Dipalma M, Florentin I, Misset JL. When should the immune clock be reset? From circadian pharmacodynamics to temporally optimized drug delivery. Annals of the New York Academy of Sciences 1991;618:312-329.
Schwartz WJ. A clinician’s primer on the circadian clock: Its localization, function, and resetting. Advances in Internal Medicine 1993;38:81-106.
Lemmer B. Relevance for chronopharmacology in practical medicine. Seminiars in Perinatology 2000;24:280-290.
Bass J, Takahashi SJ. Circadian integration of metabolism and energetics. Sciece 2010;330:1349-1354.
Reutrakul S, Van Cauter E. Interactions between sleep, circadian function, and glucose metabolism: Implications for risk and severity of diabetes. Annals of the New York Academy of Sciences 2014;1311:151–173.

Studies

Jan JE, Espezel, H, Appleton RE. The treatment of sleep disorders with melatonin. Developmental Medicine and Child Neurology 1994;36:97-107.
Blei AT, Zee P. Abnormalities of circadian rhythmicity in liver disease. Journal of Hepatology 1998;29:832-835.
Scheer FA, van Doornen LJ, Buijs RM. Light and diurnal cycle affect human heart rate: possible role for the circadian pacemaker. Journal of Biological Rhythms 1999;14:202-212.
Zeitzer JM, Ayas NT, Shea SA, Brown R, Czeisler CA. Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia. Journal of Clinical Endocrinology and Metaolism 2000;85:2189-2196.
Scheer FA, Van Montfrans GA, van Someren EJ, Mairuhu G, Buijs RM. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43:192-197.
Staels B. When the Clock stops ticking, metabolic syndrome explodes. Nature Medicine 2006;12:54-55.
Scheer FA, Zeitzer JM, Ayas NT, Brown R, Czeisler CA, Shea SA. Reduced sleep efficiency in cervical spinal cord injury: association with abolished night time melatonin secretion. Spinal Cord 2006;44:78-81.
Moser M, Schaumberger K, Schernhammer E, Stevens RG. Cancer and rhythm. Cancer Causes Control 2006;17:483-487.
Koch BC, Nagtegaal JE, Hagen EC, van der Westerlaken MM, Boringa JB, Kerkhof GA, Ter Wee PM. The effects of melatonin on sleep-wake rhythm of daytime haemodialysis patients: a randomized, placebo-controlled, cross-over study (EMSCAP study). British Journal of Clinical Pharmacology. 2009;67:68-75.
Goel N, Stunkard AJ, Rogers NL, Van Dongen HP, Allison KC, O’Reardon JP, Ahima RS, Cummings DE, Heo M, Dinges DF. Circadian rhythm profiles in women with night eating syndrome. Journal of Biological Rhythms 2009;24:85-94.
Forman JP, Curhan GC, Schernhammer ES. Urinary melatonin and risk of incident hypertension among young women.  Journal of Hypertension 2010;28:446-451.
Yang MY, Yang WC, Lin PM, Hsu JF, Hsiao HH, Liu YC, Tsai HJ, Chang CS, Lin SF. Altered expression of circadian clock genes in human chronic myeloid leukemia. Journal of Biological Rhythms 2011;26:136-148.
Kripke DF, Langer RD, Kline LE. Hypnotics’ association with mortality or cancer: a matched cohort study. British Medical Journal Open 2012;2:e000850.
Monk TH, Buysse DJ. Exposure to shift work as a risk factor for diabetes. Journal of Biological Rhythms 2013;28:356-359.