A White Paper April 2018
Introduction / Background
Environmental temperature is a universal entraining cue for circadian cycles for all mammals. Thermal regulation is a major factor for life as it influences most biochemical reactions. Temperature has become less of an influence in our day to day lives as behavioral adaptation including well-heated houses, good thermal insulation of clothing, warm vehicles and short exposures to cold has created an artificial single temperature climate. Modern mattresses and bedding focus on comfort but have added foams and materials that create a warm to hot microclimate under the sheets. Passive thermal regulation using gels, fans, moisture wicking, etc. are not sufficient to influence thermal triggers in the body. The trend to keep humans constantly comfortable in thermally regulated environments is preventing and in the case of insomnia, delaying or stopping the natural physiological thermal regulation at night.
Disease, hormone imbalance, age, high metabolism, diet, weight, are all contributing to making this disconnection from our natural thermal pathway even more exaggerated. Sleep deprivation is an epidemic. The Rand Institute estimates yearly productivity loss in the US at $411 billion annually (9). It is a mandate for modern society to put aside the day and look closely at what we do during sleep. If sleep duration, sleep hygiene, and sleep quality can all be improved and changed without drugs and chemicals but with cold therapy then as a society we can reverse the sleep deprivation productivity deficit. When modern humans use cold therapy nightly, it will help treat diseases due to mismatches in circadian biology and allow the human body to heal, learn and manage itself during sleep as our biology demands.
Abstract / Business Case
Studies done on the Sherpa’s and NASA astronauts clearly show a major metabolic benefit of cold environment adaption and cold exposure therapy that has been under served by modern science and medicine. Sherpas and astronauts can sustain themselves well on a lowered caloric intake yet with superior ability to handle physical and emotional stress when cold adapted. Applying this cold exposure time each day allows higher circulation.
Cold Therapy has had increased popularity and with that documented results. Spending time each 24-cycle using cold exposure, shortens healing and recovery times. Athletes have been using ice baths and Cryotherapy chambers for recovery with amazing results. Core body temperature remains stable while the extreme temperatures outside cause the body to release anti-inflammatory proteins and endorphins. It allows athletes almost instant muscle recovery, reduces chronic pain and inflammatory conditions, aids weight loss and skin rejuvenation. Cryotherapy is used post-surgery to accelerate healing and reduce pain without the side effects of pain medications.
The key question then should be how can we get these benefits to everyone. How can we use the time we sleep to recover more and be more productive during the day? Time is relative for all of us. A large percentage of the population gets less than 6 hours of sleep. We need to realize that the thermal coefficient of the sleep environment makes this biochemistry work against their efforts during the day of diet and exercise to live better. If they changed only the thermal sleep environment to cold and kept everything else the same the quality of the recovery during each 24-hour cycle is measurably different.
Current wearables, sleep apps, sleep trackers are confirming what we as a society are measuring in productivity loss; modern humans are sleeping horribly. Despite advances in technology, and perhaps because of the added technology we are less healthy, sleeping poorly and struggling with chronic, inflammation, stress, and mental and physical health issues. The mandate to use sleep efficiently and effectively must be applied to the country as a whole. No drugs, no habit changes are required to stop the sleep deprivation epidemic; but we must allow the thermal regulation adaptions that ruled our biological clocks to do what they are meant to do during sleep-rest, recover, manage emotional and physical stress so we can do it all again the next day.
Problem Statement / Introduction
Cold exposure and cold therapy are documented to affect recovery and health. By delving deeper, and taking cold therapy into sleep and applying it to the current thermogenesis crisis happening nightly and preventing optimal sleep. Research proves the role that temperature has on the sleep-wake cycles and proves that cold therapy can influence and improve sleep quality and quantity.
In the past two decades, research has been carried out on animals and humans to clarify the influence of ambient temperatures on sleep. This research focuses on the structure of various parts of the sleep cycle at ambient or near ambient temperatures.
Thermoneutrality, is defined as the range of ambient temperatures within which the metabolic process and natural thermoregulation is actuated by the body naturally.(23) The current microclimate created during sleep in the microclimate under the covers, exceeds thermoneutrality for significant numbers of people. Several factors such as body size, age, sexual cycle, season, disease, etc. all exacerbate the extent to which the sleeping body is out of thermoneutrality. Present experimental evidence shows that this thermal load outside of thermoneutrality elicits not only an increase in waking time but also an alteration of sleep structure, causes total or selective sleep deprivation.
Sleep deprivation causes adverse health effects and even mortality. It is now an established fact that sleep is strongly related the thermoregulation. Core body temperature cycles in conjunction with the sleep-wake rhythm. During a baseline of normal sleep cycles, core body temperature decreases during the nocturnal or sleep onset phase and increases during the wake phase. Without thermoneutrality, sleep onset with a required body core decrease doesn’t happen or is delayed. 98% of insomnia sufferers exhibit a delayed or non-existent core body drop. Parasomnia occurs often as a result of an increase in core body temperature during REM sleep. In a normal cycle the core temperature doesn’t start to increase until much later and close to the wake onset. The changes in thermal load over time can lead to the evolution of a ultradian waking-sleep cycle.
Heavy positive thermal loads exert arousing episodes and often start the body to respond by movement, sweating and poor sleep structure. Night sweats often occur during slow wave sleep or deep sleep. In contrast, a normal deep sleep cycle has a lower core body temperature. In a warmer thermal environment, body movement increases which is contrary to the sleep paralysis state that exists during normal sleep cycles. All of these thermal environmental conflicts can be mitigated and prevented by using cold therapy throughout the night.
Thermal stimuli in the form of cold therapy, and in the range of influence from providing thermoneutrality to pushing the limits of cold exposure just before sleep arousal, causes specific and non-specific changes in the waking-sleep cycle. For the purpose of this paper, we will look at cold therapy as an actively maintained sleep environment with a thermal coefficient of more than 5F from the thermally maintained environment in a modern household. A coefficient of more than 5 (to the edge of individual comfort) is preferred. The state of comfort, being objective since the individual sleeping may not be able to register discomfort even at a lower temperature environment than the ambient temperature that existed at the start of sleep. Although passive cooling such as fans, gel or moisture wicking can contribute to a more comfortable environment, the amount of cooling has to be defined as significant enough to change and influence core body temperature. .
Introduction of Solution
Water is a unique molecule. The specific heat capacity of water is far superior to air. The fluidity of water allows it to circulate and be thermally regulated in a manner that a gel, although derived from water, doesn’t have. In order for cold therapy at night to be significant and therefore measurable it has to cause a change in the biological stages allowing for a healthy sleep onset and wake timing cycle. Cold therapy would then use water as the thermal delivery device to effect thermal regulation during the thermogenesis that happens in the body at night and in modern bedroom scenarios.
In 2007, Todd and Tara Youngblood, invented the Cube; thermal regulated, thermostat controlled, mattress pad. Using water, to circulate under a body and regulate the effect of the thermogenesis that occurs in that microclimate, the Cube was able to have profound effects on insomnia and thermoregulation symptoms. Thousands of real life testimonies, support the research evidence that in studies such as Kumar et al, that body temperature and sleep are controlled by the same mechanism, and by controlling body temperature we can control sleep.
Application of Solution
Daily cycles of light and temperature are perhaps the two most reliable environmental timing cues for living systems on Earth. The neurobiological mechanisms of both sleep and circadian regulation have been unraveled partly in the last decade. By using cold therapy in relation to body temperature, arousal state, and the circadian timing system as the signaling pathway for the circadian modulation of sleep and wakefulness. Although mammals do not normally entrain to external environmental temperature cycles (19), cold therapy is ideal as an internal entraining cue in mammals because of the existence of circadian rhythms of body temperature driven by the suprachiasmatic nucleus SCN. Indeed, externally applied temperature cycles can sustain rhythmic clock. In the mammalian brain, a “master clock” located in the SCN of the hypothalamus keeps in sync the many independent clocks located in tissues and organs throughout the body (62). The coherence of these peripheral clocks is achieved through a cold therapy system in which the thermal regulation, in this case, the Cube, mimics natural temperature and sleep cycles by removing modern thermal statis in the bed microclimate. This temporal shift is converted to nonphotic cues that permeate the rest of the body, coordinating the oscillation of peripheral clocks, improving quality and quantity of sleep.
Buhr et al. also make inroads into the molecular pathways involved in temperature entrainment by building on an old idea that the temperature shock response plays a role in circadian systems ( 58). Cold therapy and cold exposure can evoke slight variations in core body temperature ( 60). The roles of temperature and cold therapy in the circadian system are part of an emerging realization of the deep interconnections between metabolism and peripheral clock function ( 62). Thus, despite the thermal 4/13/2018 Page 5 dynamics of a modern bed environment, seemingly slight fluctuations in core body temperature—if occurring at regular intervals—appear to be a major modality to enhance, deepen, and lengthen sleep cycles. It will be important to continue research into the extent that cold therapy modulates core body temperature rhythms in people of all states of health, diet, gender, age, stress level, etc. but the real possibly now exists to help biological clocks undergo life changing adjustments.
The Cube, as a cold therapy device is designed for and effectively thermal regulates the body throughout the night. By circulating water through the mattress pad, activity testing and maintaining the desired temperature throughout the night, sleep quality and quantity is improved. The application of this one device has the potential to be the first to dramatically affect the sleep deprivation epidemic and the productivity of millions of people without drug side effects and without a significant commitment of energy on behalf of the user. The simplicity of using cold therapy to manage and mitigate body thermogenesis throughout the night makes this an ideal solution. There has to be a significant and measurable change in temperature to affect the core body temperature.
Results / Conclusion
The circadian timing system in humans governs the wake-sleep cycle and synchronizes biological processes but it is, to epidemic levels, being forced into a state of dysfunction through the modern sleep environment. The results of the research and antidotal user experience as well as, performance improvements, demonstrate that changes in core body temperature rhythms are capable of entraining and enhancing the amplitude of the circadian rhythms of sleep even though the SCN remains resistant. By allowing the body to achieve thermoneutrality, or even aid the body in the temperature drop required for sleep onset and healthy sleep cycles, thermal stimuli and cold therapy creates consistent waking-sleep cycles. This reveals the critical role of chiliIPAD in the resetting of circadian and sleep wake cycles to prevent sleep deprivation its productivity and life costs.
Appendices Appendix A – Author Tara Youngblood, co-founder of Kryo, Inc.; sleep researcher and scientist 4/13/2018 Page 6 Appendix B – Websites of Interest
References 1.Heller HC, Edgar DM, Grahn DA, Glotzbach SF. Sleep, thermoregulation, and circadian rhythms. In: FMJ, editor. Handbook of Physiology, sect 4: environmental physiology. New York: Oxford University Press; 1996. pp. 1361–1374. 2. Thermoregulation as a sleep signalling systemGilbert, Saul S et al.Sleep Medicine Reviews , Volume 8 , Issue 2 , 81 - 93 3. Kräuchi, K. and Wirz-Justice, A. Circadian rhythm of heat production, heart rate, and skin and core temperature under unmasking conditions in men. Am J Physiol. 1994;267: R819–R829 4. Parsons K: Human Thermal Environments. 1993, Taylor & Francis, Oxford 5. Lushington, K, Dawson, D, and Lack, L. Core body temperature is elevated during constant wakefulness in elderly poor sleepers. Sleep. 2000; 23: 504–510 6. Welsh DK, Logothetis DE, Meister M, Reppert SM. Neuron. 1995;14:697. 4/13/2018 Page 7 7. Van Someren EJ: Mechanisms and functions of coupling between sleep and temperature rhythms. Prog Brain Res. 2006, 153: 309-324. 8. Barrett J, Lack L, Morris M: The sleep-evoked decrease of body temperature. Sleep. 1993, 16: 93-99. 9. Hafner, Marco, Martin Stepanek, Jirka Taylor, Wendy M. Troxel, and Christian Van Stolk. Why sleep matters — the economic costs of insufficient sleep: A cross-country comparative analysis. Santa Monica, CA: RAND Corporation, 2016. https://www.rand.org/pubs/research_reports/RR1791.html.. 10. Welsh DK, Yoo SH, Liu AC, Takahashi JS, Kay SA. Curr Biol. 2004;14:2289. 11. Stratmann M, Schibler U. J Biol Rhythms. 2006;21:494. 12. Brown SA, Zumbrunn G, Fleury-Olela F, Preitner N, Schibler U. Curr Biol. 2002;12:1574. 13. Kornmann B, Schaad O, Bujard H, Takahashi JS, Schibler U. PLoS Biol. 2007;5:e34. 14. Glaser FT, Stanewsky R. Curr Biol. 2005;15:1352. 15. Lahiri K, et al. PLoS Biol. 2005;3:e351. 16. Liu Y, Merrow M, Loros JJ, Dunlap JC. Science. 1998;281:825. 17. Sewitch, D.E. Slow wave sleep deficiency insomnia: a problem in thermoregulation at sleep onset. Psychophysiology. 1987; 24: 200–215 18. Aschoff, J.J. Circadian control of body temperature. in: J.D. Hardy, A.P. Gagge, A.J. Stowijk (Eds.) Physiological and behavioral temperature regulation. Charles C Thomas,Springfield; 1970: 905–919 . 19. ( * )Lack, L.C. and Lushington, K. The rhythms of human sleep propensity and core body temperature.J Sleep Res. 1996; 5: 1–11 4/13/2018 Page 8 20. Prolo LM, Takahashi JS, Herzog ED. J Neurosci. 2005;25:404. 21. Herzog ED, Huckfeldt RM. J Neurophysiol. 2003;90:763. 22. Lack, L. and Gradisar, M. Acute finger temperature changes preceding sleep onsets over a 45-h period. J Sleep Res. 2002; 11: 275–282 23. Parmeggiani PL: Interaction between sleep and thermoregulation: an aspect of the control of behavioral states. Sleep. 1987, 10: 426-435. 24. Pennartz C, de Jeu M, Bos N, Schaap J, Geurtsen A. Nature. 2002;416:286. 25. Kleitman, R., Ramsaroop, A., and Engelmann, T. Variations in skin temperatures of the feet and hands and the onset of sleep. Fed Proc. 1948; 7: 66 26. Kräuchi, K., Cajochen, C., Werth, E., and Wirz-Justice, A. Functional link between distal vasodilation and sleep-onset latency?. Am J Physiol. 2000; 278: R741–R748 27. Kubo, H., Yanase, T., and Akagi, H. Sleep stage and skin temperature regulation during night-sleep in winter. Psychiatry Clin Neurosci. 1999; 53: 121–123 28. Temperature, thermoregulation, and sleep In Principles and Practice of Sleep Medicine (2005), pp. 292-304 by Craig H. Heller edited by Meir H. Kryger, Thomas Roth, William C. Dement, John Orem 29. Dijk, D.-J. and Czeisler, C.A. Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J Neurosci. 1995; 15: 3526–3538 30. Honma S, Honma K, Shirakawa T, Hiroshige T. Physiol Behav. 1988;44:247. 31. Honma S, Yasuda T, Yasui A, van der Horst GT, Honma K. J Biol Rhythms. 2008;23:91. 32. Tataroglu O, Davidson AJ, Benvenuto LJ, Menaker M. J Biol Rhythms. 2006;21:185. 4/13/2018 Page 9 33. Lack, L. C., Gradisar, M., Van Someren, E. J. W., Wright, H. R., & Lushington, K. (2008). The relationship between insomnia and body temperatures. Sleep Medicine Reviews, 12(4), 307-317. 34. Wadekar S, Li D, Sánchez E. Mol Endocrinol. 2004;18:500. 35. Rutter J, Reick M, McKnight SL. Annu Rev Biochem. 2002;71:307. 36. (*)Lushington, K., Dawson, D., and Lack, L. Core body temperature is elevated during constant wakefulness in elderly sleepers. Sleep. 2000; 23: 1–7 37. Balsalobre A, Marcacci L, Schibler U. Curr Biol. 2000;10:1291. 38. O’Neill JS, Maywood ES, Chesham JE, Takahashi JS, Hastings MH. Science. 2008;320:949. 39. Murphy, P.J. and Campbell, S.S. Nighttime drop in body temperature: a physiological trigger for sleep onset?. Sleep. 1997; 20: 505–511 40. Mosser DD, Kotzbauer PT, Sarge KD, Morimoto RI. Proc Natl Acad Sci U S A. 1990;87:3748. 41. Boulant, J.A and Bignall, K.E. Hypothalamic neuronal responses to peripheral and deep-body temperatures. Am J Physiol. 1973; 225: 1371–1374 42. Diernfellner AC, Schafmeier T, Merrow MW, Brunner M. Genes Dev. 2005;19:1968. 43. Van Someren, E.J.W. More than a marker: interaction between the circadian regulation of temperature and sleep, age-related changes, and treatment possibilities. Chronobiol Int. 2000; 17: 313–354 44. Kaushik R, et al. PLoS Biol. 2007;5:e146. 45. Charkoudian, N. Skin blood flow in adult human thermoregulation: how it works, when it does not, and why. Mayo Clin Proc. 2003; 78: 603–612 46. Low KH, Lim C, Ko HW, Edery I. Neuron. 2008;60:1054. 47. Majercak J, Sidote D, Hardin PE, Edery I. Neuron. 1999;24:219. 4/13/2018 Page 10 48. Sehadova H, et al. Neuron. 2009;64:251. 49. de la Iglesia HO, Cambras T, Schwartz WJ, Diez-Noguera A. Curr Biol. 2004;14:796. 50. Buhr, Ethan, Seung-Hee Yoo, Joseph S Takahashi Science. 2010, Oct 15;330(6002): 379-285. 51.D. K. Welsh et al., Annu. Rev. Physiol. 72, 551 (2010). 52. C. Dibner et al., Annu. Rev. Physiol. 72, 517 (2010). 53. Van Someren, E.J.W. Sleep propensity is modulated by circadian and behaviorinduced changes in cutaneous temperature. J Thermal Biol. 2004; 29: 437–444 54. Fronczek, R., Raymann, R.J.E.M., Romeijn, N., Overeem, S., Fischer, M., Van Dijk, J.G. et al.Manipulation of core body and skin temperature improves vigilance and maintenance of wakefulness in narcolepsy. Sleep. 2008; 31: 233–240 55. Van Someren, E.J.W. Mechanisms and functions of coupling between sleep and temperature rhythms. Prog Brain Res. 2006; 153: 309–324 56.H. van Marken Lichtenbelt, W.D., Daanen, H.A., Wouters, L., Fronczek, R., Raymann, R.J., Severens, N.M. et al. Evaluation of wireless determination of skin temperature using iButtons. Physiol Behav. 2006; 88: 489–497 57.A. Busza et al., J. Neurosci. 27, 10722 (2007). 58.L. Rensing et al., Chronobiol. Int. 4, 543 (1987). 59. Leon C. Lack, Michael Gradisar, Eus J.W. Van Someren, Helen R. Wright, Kurt Lushington. Sleep Medicine Reviews, Vol. 12, Issue 4, p307–317August 2008 60.M. E. Sandström et al., Amino Acids 37, 279 (2009). 61.M. Stratmann, U. Schibler, J. Biol. Rhythms 21, 494 (2006). 4/13/2018 Page 11 62. D. K. Welsh et al., Annu. Rev. Physiol. 72, 551 (2010). 63. Raymann, R.J.E.M. Mild skin warming, a non-Pharmacological way to modulate sleep and vigilance. RJEM, 2013. 64. Angilletta, Michael J. Thermal adaptation: a theoretical and empirical synthesis. Oxford University Press, 2009.