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Chronotherapeutics: Untapped Potential in Patient Care by Dr David W Lescheid, ND, PhD

Chronotherapeutics: Untapped Potential in Patient Care

Recent systems science approaches confirm that human physiology follows different circadian rhythms, dynamically changing throughout 24-hour cycles of sunlight and darkness (1). Different clocks within the body control these rhythms. For example, the ‘central’ clock, which resides in the suprachiasmatic nucleus of the brain, regulates communication pathways between sunlight, specific photoreceptors in the retina, the brain, the pineal gland, and hormones such as melatonin and the orexins (1). Peripheral clocks also exist in the heart, lung, adipose tissue, pancreas, liver, stomach, cochlea, intervertebral discs, red blood cells, adrenal gland, thyroid gland, muscle, skin, ovary, uterus, breast, lymph nodes, testes, and eyes (2). Hormones, neurotransmitters, immune cells and cytokines, and platelets of the endocrine, nervous, immune, and cardiovascular systems (2), as well as levels of some of the specialized pro-resolving lipid mediators controlling inflammation resolution, also rise and fall within a 24-hour cycle (3). Circadian rhythms are found even in mitochondrial biology, including levels of their enzymes, metabolites, and oxidative/reductive intermediates (4), as well as in gut microbiota (5).

Our body’s central and peripheral clocks evolved to be in tune with the rhythms of the natural environment that our ancestors lived in. Hours of sunlight have overarching effects; when we sleep, eat our meals, and exercise also influences our rhythms (2). Moreover, temperature, signals from the hypothalamus-pituitary-adrenal axis, including glucocorticoids (6), and cycles of the moon (7), adjust bodily rhythms to keep them harmonious and in sync with the outside world.

Diseases, including cardiovascular disease, cancer, obesity, migraine, and various mental health conditions, are associated with disruption of normal physiological rhythms in various ways, including working night shifts or repeated jet lag (8). Even social jet lag, defined as a misalignment of sleep timing between weekdays and weekends, contributes to disease (9). Altered health is also associated with exposure to artificial light at night, particularly blue light from computer screens or other hand-held devices at inappropriate times, such as close to bedtime (10). Aging, persistent or overwhelming psychological stress, excess intake of caffeine and alcohol, as well as exposure to certain environmental pollutants and some pharmaceutical drugs also contribute to disrupted circadian rhythms and disease (11).

An increased understanding of the health costs of interfering with normal bodily rhythms assists naturopathic doctors in recommending fundamental lifestyle changes and therapeutics that can profoundly influence patient care. Moreover, the relatively new but growing scientific field named chronotherapeutics indicates that maximal treatment benefits are achieved if various treatments are given in alignment with body rhythms. For example, dramatic reduction in the risk of cardiovascular events such as death, heart attack, heart failure, and stroke is achieved if antihypertensive medications are taken before going to bed, compared to if the same medications are taken in the morning when waking up (12). Furthermore, in an animal model of bone fracture, dexamethasone impaired healing and caused a marked shift in gene expression if it was administered during the resting period compared to the active period (13). The difference in gene expression was so profound depending on the timing of administration that the authors conclude, “it’s almost as if morning anti-inflammatories and evening anti-inflammatories were two different drugs” (13). The therapeutic effect of other pharmaceutical drugs including acetaminophen, simvastatin, low-dose aspirin, and anticancer drugs also is improved if the optimal timing of administration is included in patient care (14).

It is possible that the effectiveness of natural anti-inflammatories, probiotics, as well as other natural health products, could be enhanced if they are taken at certain times of the day, although further scientific evidence is needed.  Moreover, increasing evidence also suggests that human health is influenced not only by what we eat but also by when we eat, suggesting regulated eating times (i.e. chrononutrition) would also benefit patients seeking weight loss and/or support for general health improvement (15). Different types of physical exercise may also be more beneficial when completed during unique times of the day (16), adding regulated times for different physical activities (i.e. chronoexercise) as part of comprehensive patient care.

Current scientific evidence firmly supports the healing power of nature; increasing scientific evidence suggests that this healing power is amplified when the activities that we do, the rest that we have, and the food, drinks, and medicines that we take, are in harmony with the timing of the rhythms of nature and our individual physiology. Adding chronotherapeutics and providing medicine in the 4th dimension (17), including timing of administration and individual chronotype (18) as part of prevention and treatment plans, is an exciting medical development and provides naturopathic doctors with additional strategies with untapped potential for improved patient care.


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  13. Al-Waeli H, Nicolau B, Stone L, et al. Chronotherapy of Non-Steroidal Anti-Inflammatory Drugs May Enhance Postoperative Recovery. Sci Rep. 2020;10(1):468
  14. Kaur G, Phillips C, Wong K, Saini B. Timing is important in medication administration: a timely review of chronotherapy research. Int J Clin Pharm. 2013;35(3):344–358
  15. Adafer R, Messaadi W, Meddahi M, Patey A, Haderbache A, Bayen S, Messaadi N. Food Timing, Circadian Rhythm and Chrononutrition: A Systematic Review of Time-Restricted Eating’s Effects on Human Health. Nutrients. 2020 Dec 8;12(12):3770. 
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  17. Cederroth CR, Albrecht U, Bass J, et al. Medicine in the Fourth Dimension. Cell Metab. 2019;30(2):238–250
  18. Montaruli A, Castelli L, Mulè A, Scurati R, Esposito F, Galasso L, Roveda E. Biological Rhythm and Chronotype: New Perspectives in Health. Biomolecules. 2021 Mar 24;11(4):487

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