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. La melatonina nocturna diaria reduce la presión arterial en pacientes masculinos con hipertensión esencial. Hipertensión 2004;43:192-197.
Staels B. Cuando el reloj deja de funcionar, estalla el síndrome metabólico. Medicina Natural 2006;12:54-55.
Scheer FA, Zeitzer JM, Ayas NT, Brown R, Czeisler CA, Shea SA. Reducción de la eficiencia del sueño en la lesión de la médula espinal cervical: asociación con la secreción nocturna de melatonina abolida. Médula Espinal 2006;44:78-81.
Moser M, Schaumberger K, Schernhammer E, Stevens RG. Cáncer y ritmo. Control de causas de cáncer 2006;17:483-487.
Koch BC, Nagtegaal JE, Hagen EC, van der Westerlaken MM, Boringa JB, Kerkhof GA, Ter Wee PM. Los efectos de la melatonina en el ritmo de sueño y vigilia de los pacientes en hemodiálisis diurna: un estudio cruzado, aleatorizado, controlado con placebo (estudio EMSCAP). Revista británica de farmacología clínica. 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. Perfiles de ritmo circadiano en mujeres con síndrome de alimentación nocturna. Revista de Ritmos Biológicos 2009;24:85-94.
Forman JP, Curhan GC, Schernhammer ES. La melatonina urinaria y el riesgo de hipertensión incidente entre las mujeres jóvenes. Revista de Hipertensión 2010;28:446-451.
Yang MY, Yang WC, Lin PM, Hsu JF, Hsiao HH, Liu YC, Tsai HJ, Chang CS, Lin SF. Expresión alterada de los genes del reloj circadiano en la leucemia mieloide crónica humana. Revista de Ritmos Biológicos 2011;26:136-148.
Kripke DF, Langer RD, Kline LE. Asociación de los hipnóticos con la mortalidad o el cáncer: un estudio de cohorte emparejado. Revista médica británica abierta 2012; 2: e000850.
Monje TH, Buysse DJ. La exposición al trabajo por turnos como factor de riesgo para la diabetes. Revista de Ritmos Biológicos 2013;28:356-359.