Zzzzzz… Circadian Clocks in the Classics

I was recently alerted to the 2017 Nobel prize for medicine going to Jeffrey C Hall, Michael Rosbash and Michael W Young for their discovery of the internal clock of living organisms and it seemed like the perfect opportunity to write a confluent essay about circadian rhythms in the classics of Chinese medicine. While Hall, Rosbash and Young discovered the genes which govern our internal clock, the proteins they encode and the feedback loop by which they form a daily cycle, the observations for which they demonstrated a material mechanism were recorded in the earliest medical classics in China.

Time is measurable only through the passage of some regular events. This makes all measurements essentially arbitrary depending on the events which are chosen to be the basis of the measurement and the divisions that are applied to it. This exemplifies the principle that was inherent in Chinese medicine and science in general that searched for meaningful categories and patterns instead of trying to find objective and absolute truths. There was also a fundamental belief that the human body was a microcosm of the universe which led to two natural measurements of time: the movements of celestial bodies which measured the passage of days, months and years, and the cycles inherent in the human body such as the breath, the sleep-wake cycle and seasonal variations. It was a matter of principle that the human should live in harmony with the environment by keeping these cycles synchronised or disease would result. The character used to represent chronic disease is 病 Bing which consists of the radical 疒, which is a pictographic representation of a person on a stretcher or a sickbed, and  丙, a Heavenly Stem, a term for the element connected with each year in the Chinese calendar. The human body was also seen as a mirror of society and civilisation whose prosperity would depend on preparing for the seasons and acting appropriately. Therefore time can be seen as the principle that connected mankind to culture and the heavens and is an important aspect of that elusive, incorporeal concept that is said to compose all things in the universe and be the basis of life, 氣 Qi.

Since tracking time was vital for ancient people to prosper, so it was essential for ancient medicine too. Intervention was rarely a single procedure like surgery is today and the timing, frequency and duration of treatment were key to their success. The classics of Chinese medicine provided several quite detailed models, almost all of which have been neglected in the modern age in favour of the “Chinese Organ Clock”.

organ-clock

The Modern Chinese Organ Clock

In this model the 12 meridians are neatly assigned to two hour segments of the day and while it is so popular that barely any other model appears on a search for Chinese medical clocks, a search for its source finds no original description or reference to a classic text (although as we shall see there may be hints that this model or something like it was known to the authors of some of the texts). It certainly has its merits and many of the modern discoveries about circadian rhythms do fit quite well into functions of the organ assigned to those hours (bearing in mind they may not have the same function as their western translation) but there are plenty of articles about that already.

Today I want to look at some of the older models of internal time that are actually described in the classics and see if they can tell us anything about the ancient mindset towards our daily cycle. I will begin by describing the Twelve Earthly Branches on which all cycles of time were based and is of relevance to all the models that follow before turning to the specific sections of the medical classics that discuss time. First I will look at some chapters in the Su Wen which give advice on the importance of connecting our sleep-wake cycle with the daylight hours of the season before looking at some more technical descriptions of our biological clock in the Ling Shu and asking what they might have been trying to tell us. Next I will describe the model extracted from the Shang Han Lun which seems to have anticipated much of our current knowledge of our daily peaks and troughs in performance. Finally I will consider practical implications these insights may give us for clinical practice.

The Twelve Earthly Branches

Each of these models of time are based upon an even older system, that of the 12 Earthly Branches which were originally used as a method to calculate the passage of days since the Shang dynasty. By plotting the growing and shrinking of daylight hours, or the length of a shadow from a post in the ground, the following chart is obtained.

Taiji-and-daylight

Taiji Diagram Derived from Daylight

This can then be recorded using the hexagrams of the I Ching to produce the 12 Growing and Declining Hexagrams to explain the rising and setting of the sun. This basic model of the ebb and flow of time was then applied to other cycles and has been designated to the hours of the day since at least 100-200 B.C. (Liu, 2005).  When applied to the day these equate to:

䷗ : 復 Fu, governs the hours between 11am – 1am, known as 子 Zi.
䷒ : 臨 Lin, governs the hours between 1am – 3am, known as 丑 Chou.
䷊ : 泰 Tai, governs the hours between 3am – 5am, known as 寅 Yin.
䷡ : 大壯 Da Zhuang, governs the hours between 5am – 7am, known as 卯 Mao.
䷪ : 夬 Guai, governs the hours between 7am – 9am, known as 辰 Chen.
䷀ : 乾 Qian, governs the hours between 9am – 11am, known as 巳 Si.
䷫ : 姤 Gou, governs the hours between 11am – 1pm, known as 午 Wu.
䷠ : 遯 Dun, governs the hours between 1pm – 3pm, known as 未 Wei.
䷋ : 否 Pi, governs the hours between 3pm – 5pm, known as 申 Shen.
䷓ : 觀 Guan, governs the hours between 5pm – 7pm, known as 酉 You.
䷖ : 剝 Bo, governs the hours between 7pm – 9pm, known as 戌 Xu.
䷁ : 坤 Kun, governs the hours between 9pm – 11pm, known as 亥 Hai.

For an in-depth discussion of these I would refer the reader to Wu and Wu (2014) or Golding (2013). For the purpose of this essay it is worth noting that since each period refers to a point in the cycle of hexagrams, the same name is used for the passage of hours, days, months and years in each cycle which draws our attention to the fractal nature of ancient Chinese time. My previous post on Strange Loopy Time in Ancient China has discussed this concept already while this post is aimed at looking at just one of those cycles, the diurnal one, in greater detail. No cycle can ever be entirely isolated though and has to be seen in relation to both the smaller cycles of which it is comprised and the larger ones which determine its context.

The current Organ Clock is obtained by assigning one of the 12 Zangfu organs to each period. It is probably the simplest to divorce from any wider context and overlay onto our own 24 hour clock which has almost certainly contributed to its popularity. Other methods of dividing up the day can also be used drawing on the five phase model (as a cross with Earth in the centre as the earlier models were represented) or by using the Six Divisions as we shall see later.

five-phase-cross

Wuxing or Five-Phases represented as cross with Earth in the centre surrounded by Wood/Expansion, Fire/Opulence, Metal/Contraction and Water/Storage

Whatever explanatory model is overlaid to highlight a particular pattern, all temporal cycles in ancient China are derived from this basic model of Growing and Declining Hexagrams and every following one is just a means of dividing or classifying the periods differently depending on the context and the phenomena it wishes to explain.

Nei Jing Su Wen

The earliest mention of the importance of keeping a regular cycle is in the first part of the Huang Di Nei Jing, The Yellow Emperor’s Internal Classic, known as the Su Wen, Simple Questions, estimated to have been written around the Warring States period 400-300 B.C. and connects the diurnal cycle to the yearly cycle of seasons from which others are derived. This shows the inseparability of any of these cycles in the Chinese medical model since one (the diurnal) is intimately connected to and influenced by another (the yearly seasonal one). In the first chapter the author gives an account of how an idealised ancient people were able to live long and healthy lives, in part due to the fact that “Their rising and resting had regularity” while lamenting that for people of today “rising and resting miss their terms”. Chapter 2 then elaborates upon this:

“The three months of spring, they denote effusion and spreading…
Go to rest late at night and rise early…
This is correspondence with the qi of spring and it is the Way to nourish life.
Opposing it harms the liver…

The three months of summer, they denote opulence and blossoming…
Go to rest late at night and rise early.
Never get enough of the sun…
This is correspondence with the qi of summer and it is the Way to nourish growth.
Opposing it harms the heart…

The three months of autumn, they denote taking in and balance…
Go to rest early and rise early, get up together with the chicken…
This is correspondence with the qi of autumn and it is the Way to nourish gathering.
Opposing it harms the lung…

The three months of winter, they denote securing and storing…
Go to rest early and rise late.
You must wait for the sun to shine…
This is correspondence with the qi of winter and it is the Way of nourishing storage.
Opposing it harms the kidneys.” (trans. Unschuld & Tessenow, 2011)

The chapter also gives some specific advice on how to act during each of the seasons which has been omitted in order to clarify the most important points about the circadian rhythm: first, that each season demands a different waking and sleep cycle; second, that this cycle is dependent upon the sun and daylight hours; and third, that refusing to obey this cycle results in harm to the body’s associated system. The text goes on to state that this damage will become apparent in the next season. This is important because it states that the damage done to our bodies by disobeying the circadian rhythm only becomes apparent over time which is one of the big problems of a sleep deprived society: once manifest the phase for easy resolution has passed.

The organs given here need not be dogmatically ascribed their TCM definitions or syndromes. In fact the symptoms given in the chapter are closer to the elemental natures of the organs and are better translated in this instance to being the internal reflection of the season (e.g. if one harms the Lung in autumn then the ability to “gather in” is harmed resulting in the “outflow of food” in winter). Whether the symptoms given turn out to be accurate prognoses or symbolic descriptions of the disrupted principle must be left to epidemiological studies of broken sleep cycles and their resulting disease patterns to establish. To my knowledge no such study has been conducted but it certainly has plausibility that if we are deprived of sleep during the autumn then by winter our immune system may be in a poorer state than usual to resist the regular winter outbreaks of norovirus.

Several other chapters in the Nei Jing Su Wen deal with time, especially chapters 66-71 but they are largely thought to be a later addition and deal with the “Qi of Heaven”, astrology and cycles of time measured in years and more. These are all topics that cannot be covered here.

Nei Jing Ling Shu

The second part of the Nei Jing, the Ling Shu, Divine Axis, has several chapters that deal explicitly with diurnal cycles of Qi in the body. Of these chapter 15 explains the method of measuring time in ancient China using a water clock called a clepsydra which divided the day into 100 sections. Chapter 16 deals with the movement of Ying Qi (Nutritive Qi, or literally the Camp as opposed to the Guard) which is clear and travels inside the channels while chapter 76 deals with the movement of Wei Qi (Defensive, or literally the Guard) that is described as turbid, aggressive and travels outside the main channels providing functions such as movement of the sinews and bodily defences. Chapter 18 deals with both, providing further details into their generation and meeting. Some of these details are repeated in the Nan Jing ch. 1 but provide no new information. The speed at which they circulate is too rapid to map onto a daily cycle but they provide some interesting insights into other smaller cycles of which the diurnal cycle is composed and rests upon.

Ying Qi

The Ying Qi is the Qi most commonly talked about when discussing meridians and points. Chapter 16 of the Ling Shu is presumably the inspiration for the popular Organ Clock because it follows the same order as described in this chapter, also the same one as is laid out in chapter 10 when describing the channels in detail. In this instance there is also an additional circuit through the extraordinary Du vessel and the abdomen (presumably the Ren and also maybe the two Qiao Mai that are included in the measurements of the vessels in ch. 17). However the main departure from the Organ Clock is the timing, both its starting point and the speed at which it completes a circuit.

In the Ling Shu ch. 16 the cycle begins with the “the intake of grain… The grain enter the stomach. The Qi are forwarded to the Lung. They flow into the centre, and they disperse toward the outside.” The suggestion here is that the circuit begins after food has entered the stomach which would contradict the modern Organ Clock unless you tend to eat just before 3am. However the next line says that “The pure essence … always circulates, without cease” which suggests that there is a continuous cycle and that it is circulating even when we do not eat. The most likely solution is that there is a continuous circuit but some is lost performing functions during the day and this then gets topped up with fresh Qi from the digestion of food which enters the Lung channel at every mealtime or shortly after.

The speed is described in Ch 15 where it is calculated from the length of the vessels and the distance the Qi moves with each breath. One complete circuit is made every two marks on the water clock or 50 complete circuits in 24 hours. This means the Qi moves at a rate averaging one channel every couple of minutes or one complete circuit every 28 minutes and 48 seconds. The use of the breath to calculate the movement in the vessels is interesting because it ties the circulation to an even shorter bodily cycle which also has its own phases of inhalation and exhalation that are also represented by the Growing and Declining Hexagrams in meditation practices. Variation in the speed of the breath does not appear to have occurred to them as a confounding variable in this model.

04-waxing-waning-qian-kun

The Growing and Declining Hexagrams in relation to the breath and the Microcosmic Orbit meditation

The two sets of 25 circuits is significant since it would put each two hour division on the regular Organ Clock at 4⅙ complete circuits of Qi making these cycles synchronise only once every every 12 hours after 25 cycles and six sections of the Organ Clock. Midnight is described as a “grand meeting” although it never explains why and why the point at midday when the cycles also connect is not. If this chapter was written with another larger cycle in mind, like the Organ Clock, then it would be natural for the point when all the cycles connected and started again to be considered somehow “grand”, like the point in a clockwork pocket watch where the many different rotations of the gears eventually bring all the hands back to point to 12 at the same time.

The term for “midnight” used is 夜半, Yeban, which literally means “halfway through the night” and is not referencing any specific hour so it need not be referring to 12 am.  The most likely time is probably 3 am which seems to be a more popular starting point for the diurnal clocks in Chinese medicine. This would be the exact moment the Organ Clock’s Lung hour would be starting and if the cycle of the Ying Qi through the channels was also starting over then it would also be entering the Lung at this time too. Other lines such as “When the the sun goes down the Yang Qi are exhausted” would support this suggesting that it is based upon the Twelve Earthly Branches where the last Yang line departs from the ䷖ Bo hexagram at 9pm and moves into ䷁ Kun, pure Yin. The midpoint between 9pm and 9am would then be 3am governed by the ䷊ Tai hexagram whose name can be translated as “great” or “grand” and is when Yin and Yang become balanced again. This “grand meeting” is also described as occurring at a time when “All the people are asleep” making a later hour than midnight seem appropriate since a few night owls might still be awake by torchlight even in an ancient world.

Despite being an interesting mathematical exercise the use of this system is not really discussed and no evidences for observing its course in daily life are given. It seems to be a description of how the energy from our food is extracted and distributed than a circadian rhythm per se. If there is to be another important cycle to our daily routine it is probably the times we receive our energy and how it is managed. The problem with that as an explanation is that half an hour is far too quick if we overlay this model over that of blood glucose levels and insulin release after a meal which generally takes around 2 hours to complete.

normal-blood-sugars

Normal Blood Sugars Chart. Source: Diabetesdaily.com

While it is not much of a stretch to group four of these half hour cycles together to make a 2 hour cycle, one for each of the four points of the five phase cross revolving around Earth at the centre, and keep within the recurring theme of cycles within cycles common to classical Chinese timekeeping, this is not directly stated in the text.

Other explanations for the speed and frequency of the cycles of Ying Qi described in the Ling Shu could be possible. The authors may have observed there was some individual variance in any particular diurnal peak or trough that was considered normal. The circulation of the Qi in the channels every half hour and its relation to meals may have explained that each person’s peak will depend on when the latest cycle is passing through the meridian required for that function.

In a similar vein it may be showing how long a change takes to filter through the entire system and so be a guide for how long treatments should last. This would explain why most treatments on the Ying level retain the needles for around 20 minutes while Extraordinary Vessel treatments take longer in order to complete the final circuit (technically it takes 24 minutes 32 seconds to complete the regular circuit and 4 minutes 16 seconds to pass through the Extraordinaries based on the calculations given).

It could also explain how long it takes our Zangfu to adjust to physical or mental activity. When exercising the circuit completes the Lung (breath), Spleen (flesh/muscle) and Stomach/Large Intestine (suppressing appetite and bowels, generating heat) in around 8 minutes before moving into the Heart/Kidney and Taiyang section where the Heart sends Blood to supply the movement of the sinews, we reach peak temperature and initiate sweating. After 20-25 minutes the Liver Qi may be said to be unbound and coursing freely and then the body is ready for more intense exercise such as deep stretching (tendons coming under the Liver). In a little under half an hour a circuit is complete meaning the benefits of exercise to have reached the entire system. Incidentally, half an hour of exercise a day is what is currently recommended to achieve the physical and mental benefits exercise (NHS, 2015; Harveston et al., 2016). In meditation a similar duration and pattern is observed: first one “sets up the forge and crucible” (Yangming is Earth and Metal but also characterised by Heat) by settling the breath and bodily desires of the Po (Lung) and focusing the Yi (intention, housed in the Spleen), then inverting Fire and Water by sending the Shen into the lower Dan Tian (Heart and Kidneys) before experiencing the flights of spirit attributed to the Hun. Approximately 20 minutes would cover a standard meditation session with periods over 25 minutes facilitating work on the Extraordinary realms.

None of these are not stated explicitly in the chapters on the Ying Qi which are discussions of theoretical physiology only so we can only speculate but claims to be able to predict the course of diseases and use the clocks to influence treatment are made for the movement of the Wei Qi making it likely that there was a similar reason for describing the other circulations in such detail too. It seems less probable that they were meant to dictate where to put the needles in a given treatment session though since they change channel every couple of minutes so the practitioner would have to race to keep up.

Wei Qi

The movement of the Wei Qi has more relevance to circadian rhythms and is given in much more detail in the Ling Shu Chapter 76 detailing exactly which channels it travels to and when. It begins during the period of 3-5am, “at dawn … when the eyes widen” and from here ascends into the head and along the foot Taiyang to the toe. Another branch comes from the corner of the eye and travels along the hand Taiyang to the little finger. This pattern continues through the Shaoyang and Yangming circuits, each time starting from the eyes and descending to the feet and hands before it “continues into the Yin section and once again links up with the eyes”. The Yin section referred to appears to be the Shaoyin Kidney channel. After 25 circuits through the Yang conduits the Qi passes from the Shaoyin channel to the Kidneys during the period between 5-7pm and into the interior where it circulates another 25 times through the Zang organs in the order of Kidneys, Heart, Lung, Liver and then Spleen following the order of the Ke controlling cycle of the five phases. When the eyes open in the morning then the clock is reset and the cycle begins again meaning that the exact starting point of this cycle and speed it travels is variable depending on the season.

The chapter then goes on describe precise times for where the Qi should be according to each mark on the ancient water clock although it actually confuses the matter by contradicting its earlier statements. It says that each time the water descends by a mark it moves to a different division with the 25th section seeing a return to Taiyang where it starts a second set of 25 in the second half of the day. Since there are 100 marks in a day this means that 50 divisions are traversed during the daylight hours making 12.5 completed circuits. This directly opposes the earlier statement that a complete cycle takes 2 marks on the clock making 25 circuits during the daytime and that the cycles are variable according to the season. This can either be seen as an error or we have to assume that one circuit is two divisions and the circuits alternate between relatively Yang and Yin subdivisions with its own Yang and Yin cycle (Shaoyang being a relatively Yin division of Yang as it is “half internal and half external”). This exemplifies the principle of time as fractal cycles within cycles.

I would have preferred to use a sun dial to measure a cycle that begins at first light and ends at dusk. It feels like the use of the clepsydra is complicating things unnecessarily. It may have simply been that it was more practical to have a water clock in a treatment room, making adjustments according to the time of year, than it was to go outside and check the time on a sun dial for each patient which might not even be working on a cloudy day. For the modern practitioner who wants to use this system a calculator has been provided at https://chronopuncture.com.

Ganzhi

An Example of the Wei Qi daily cycle. Source: chronopuncture.com

They appear to have adopted the approach of there being 50 division in a day and also divided the 25 yin cycles into a similar four part circuit by merging the Shaoyin organs together making a complete circuit Kidney/Heart → Lung → Liver → Spleen → Kidney/Heart rather than the more obvious approach of assigning each Zang organ five periods each to make 25. I presume this is justified by the fact that no other two organs are next to their own Six Division pair in the cycle. This makes 12 complete Yin circuits to match the 12 complete Yang circuits adding a return to the Shaoyin organs where it passes into the Shaoyin channel ready to begin in Taiyang again. If the earlier statement on 25 nightly circuits is to be believed then each complete Yin cycle must also divided into two smaller circuits with presumably the Heart and Lung being a relatively Yang circuit through the Upper Jiao, the Spleen and Kidneys being the Yin circuit while the Liver, which is Yin in structure and Yang in function, straddles both like a second horizontal axis to the Shaoyin vertical one.

The purpose of this cycle is explicitly stated as assisting in treatment:

“When the time sections are carefully observed, the course of a disease can be predicted. If one neglects the time sections and acts contrary to the observations, none of the hundred diseases will be curable…

When a disease is in repletion, pierce those [qi that are] arriving.
When a disease is in depletion, pierce those [qi that are] leaving…

To carefully observe where the qi are and then to pierce them, that is called ‘meeting the time’.” (trans. Unschuld, 2016)

Personally I am not convinced. Those who make Stems and Branches a major feature of their practice will always claim that their methods are superior, just as those who practice Tung, Tan, TCM, Five Element and Western styles also claim that theirs are better than the others too. It should be simple enough to put such claims to the test but they rarely ever do. I suspect that what it did for practitioners who used this system was provide a very technical context for the treatment, improving the non-specific effects with a lot of bold rhetoric backed up by complex charts, mathematical calculations and specialist knowledge. If your patients enjoy such things then it might help but it might equally have the opposite effect for a lot of patients who do not want “astrology with needles”. I will discuss some potentially useful timings for treatment later but the main interest I have in these cycles is what they tell us about the insights ancient people had into our circadian rhythm.

Despite whatever contradictions or confusion appears to exist in the text of this chapter, it seems to be discussing a circadian rhythm and suggests that it is our seeing the daylight and moving that is the driving force behind it. Together with the description of movement of the Ying Qi inside the channels it suggests that our internal cycles are driven by two main stimuli: daylight entering our eyes that triggers movement in our bodies and the times we eat which relate to metabolic cycles. The modern science of chronobiology suggests much the same thing (Ballesta et al., 2017). The Nei Jing‘s descriptions contain implicit warnings about doing either of these things too late at night which would trigger a new waking cycle and a surge of Qi through the conduits or Yang sinews when the Yin phase of body should be occurring. Perhaps this explains the meticulous way that the cycles are calculated with a water clock: the water clock always completes its 100 marks per day and the body should match it but if, through our actions, we lose sync with the passage of day and night that is being measured objectively then harm can occur. Recent studies are finding the damaging effects screen lights have on our sleeping patterns (e.g. Kayaba et al., 2014; Green et al., 2017) so its quite impressive that a model as old as this may have predicted the harm they would cause thousands of years before the first screen was invented!

Shang Han Lun

The second classic that mentions circadian rhythms and provides the best map of our 24 hour bodily cycle is the Shang Han Lun, Discussion of Cold Damage, c. 200 A.D. This model requires some explanation due to being under appreciated in modern practice with greater preference given to the Organ Clock. Zhang Zhong-Jing provides certain times when certain diseases attributed to his system of Six Divisions are supposed to resolve themselves. I am not concerned so much with the nature of these diseases which can be read about in one of the many translations and commentaries to the Shang Han Lun (e.g. Mitchell, Ye and Wiseman, 1999) but rather in the model of the day that Zhang Zhong-Jing uses. The diseases which are supposed to resolve themselves at these time do so because that particular time of day is when that division governs and the regular function, once free of the pathogen, will now assert itself. It is the normal functions of those divisions which are of relevance to this discussion but due to the text’s focus on pathology rather than physiology and the terse nature of Zhang Zhong-Jing’s writing style, they have to be inferred.

The time periods he described are:

Shaoyang : 3am – 9am
Taiyang : 9am – 3pm
Yangming : 3pm – 9pm
Taiyin : 9pm – 3am
Shaoyin : 11pm – 5am
Jueyin : 1am – 7am

The first thing to notice about this clock is that the Yang divisions command a far greater proportion of the day (18 hours) than the Yin whose 6 hour periods are made to overlap during the night in order to condense them all into a 10 hour zone and yet it corresponds roughly with the way the day is divided in human nature, to approximately two-thirds to three-quarters waking and one-third to a quarter sleeping. Just as the Su Wen ch. 2 placed a special emphasis on the sun to guide our circadian rhythms, so Zhang Zhong-Jing made Yang and the presence of light the focal point for his biological clock. However, Yin is not placed into a subordinate or second place. Each Yin section is just as long as the Yang sections, they are merely condensed into overlapping periods, suggesting that the Yin period of night is every bit as important as the daytime but true to its Yin nature it is densely compressed while the daytime is diffused across a longer period. This might seem obvious but compare this to our current system where the day is divided into exactly equal am and pm blocks with no emphasis on daylight or night-time implicit beyond the fact that the sun should be at its meridian point at precisely 12 noon. This might go some way to explaining why it has taken three scientists winning a Nobel prize for our culture to finally take circadian rhythms seriously again although it may be some way before businesses consider adjusting their work hours according to the levels of daylight.

It is also worth noting that this model shares roughly the same proportions as the shorter cycle described for the Wei Qi in the Ling Shu ch. 76, moving through three Yang divisions (albeit with Taiyang and Shaoyang reversed) before returning through the Yin realm for one quarter of their time. The Shang Han Lun was primarily concerned with infectious diseases and so it is reasonable to assume that the diurnal cycle it described was the daily rhythm of the Wei Qi. This also means it does not have to exist in opposition to the standard Organ Clock whose order follows that of the Ying Qi described in Ling Shu ch. 16 and may be referring to circadian clock of the Zangfu and regular channels instead.

The next thing to notice is the order of the cycles. As mentioned before Shaoyang appears before Taiyang in this model. Shaoyang is the “lesser Yang”, its nature, defined in the Su Wen ch. 6, is to pivot and is located in the early morning, as night turns to day and light emerges from darkness so is naturally a “lesser Yang” compared to the brightness of midday. This period when the sun is at its peak is ruled by Taiyang, the “greater Yang”, whose nature is to open. Yangming is the “Yang brilliance”, its nature is to close and it governs the period of time when the sun sets. We see a similar pattern with the Yin periods but here the Taiyin which opens is at the start of the evening, the Jueyin which closes at the end of the night and the point at which they cross over is Shaoyin, the pivot. It seems to be following the sleep cycle where the night opens to allow us to rest in Yin, corresponding with the initial and most essential phases of the sleep cycle that we need to recharge, it then pivots during the midnight hours and as Yin closes on us we enter into the lighter phases, gradually crossing over into the Shaoyang from 3am onwards where we may even be partially awake, or actually wake up if our Yin is insufficient, and are likely to have dreams that we remember. This 4 hour overlapping time also corresponds to our individual variation in sleep requirements, from 6-10 hours, averaging at 8. To look at these in more detail it is necessary to compare them to the Twelve Earthly Branches and the Growing and Declining Hexagrams upon which Liu (2015) says this system is based.

The most significant hours upon which each division is decided appears to be the one when it begins. Taiyang, meaning “Greater Yang”, starts at 9 am, governed by the ䷀ Qian hexagram of all Yang lines. It’s opposite, Taiyin, “Greater Yin” division, starts at the opposite time, 9 pm, governed by the ䷁ Kun hexagram of all Yin lines. The afternoon period between these is the Yangming division, starting at 3 pm and governed by the ䷋ Pi hexagram, when the dominance of Yang starts to wane, coming to a close, as is the nature of Yangming, with ䷖ Bo when the last Yang line disappears.

The period of midnight and the early morning are more interesting. The two ‘pivoting’ moments of the Shaoyin and Shaoyang occur during this time and are also placed at key points in the progression of Yang: at midnight, governed by the ䷗ Fu hexagram, when the progression towards total Yin is complete and we begin to see the return of Yang, and in the morning from 3 am, governed by the ䷊ Tai hexagram, when Yin loses it dominance to become equal with Yang but with Yang on the ascent and dawn soon to break. Recall also that 3 am is also the “grand meeting” when all the cycles of the Ying Qi meet up together and also the very centre of the Shaoyin period which is the division that covers the central axis of the Heart and Kidney making this a special pivot indeed. The Jueyin period starts at 1 am and is the the last Yin period to start, at the deepest level of Yin where all three Yin phases dominate before reverting back to Yang through the relationship of Jueyin to Shaoyang. The hexagram which governs this period is ䷒ Lin translated as “nearing” implying anticipation of the return of Yang. The return of Yang through the Jueyin/Shaoyang relationship also explains why the order is different from cycle of the Wei Qi in Ling Shu ch. 76. This cycle only travels through the Shaoyin system during the day and so reverts back to Yang through its own Taiyang pairing.

Zhang Zhong-Jing could just have easily have placed his periods in equal 4 hour slots or followed the rise and fall of Yin but as a medical clock his emphasis was on the body and he clearly saw that it was most attuned to the sun. The discrepancy from the order of Ling Shu ch. 76 is most likely simply due a different a different phenomena being observed. The shorter cycle explains the physiological process of a bright light perceived externally (Taiyang) becoming interiorised and translating into hormone functions which mostly come under the heading of Shaoyin Kidney function (Wang and Robertson, 2008) whereas the sun does not burst into the sky but pivots out of darkness and reaches its brightest at midday. In any case, the simplicity and elegance the Shang Han Lun clock makes it uniquely comparable to the modern understanding of the circadian rhythms and easy to apply to clinical practice.

Comparison to the Modern Circadian Clock

Zhang Zhong-Jing’s system is perhaps a little more technical than the conventional Organ Clock with overlapping Six Division phases and corresponding Growing and Declining Hexagrams but it actually has a much greater descriptive power and fits modern circadian chart mappings surprisingly well. The simplest comparison is with serotonin and melatonin which respond directly to daylight. Melatonin is generated from serotonin through a process that is inhibited by exposure to daylight. This means that as daylight dims serotonin is converted to melatonin while during the day melatonin production ceases and serotonin levels rise again. This makes the serotonin/melatonin connection to the cycle of the sun pretty obvious and not in need of much explanation suffice to say that it is described in both the advice of Su Wen Ch. 2 to rise and rest with the lengthening and shortening of the days and the description of Wei Qi circulation Ling Shu Ch. 76 starting at dawn with the opening of the eyes.

Cortisol also engages in a circadian cycle that we can compare to the classical models:

cortisol

Circadian rhythm of cortisol. Spikes during the day are meal related cortisol release. Source: Chan & Debono (2010)

Cortisol levels reach their lowest point, pivoting from decline to ascent between 11 pm and 1 am, during the Shaoyin phase of night and the Zi hours governed by ䷗ Fu where the central pivoting of Yang’s return occurs. It then accelerates sharply, seeing another pivot from below to above the MESOR line (the mean average throughout the day) during the hours of Yin (3-5 am) governed by ䷊ Tai as the advance of Yang matches and overtakes Yin and the Shaoyang phase begins. It peaks during the Si hour at 9 am, governed by ䷀ Qian as the Taiyang phase begins, staying high throughout the day only dipping back below the MESOR line during the final Yangming hour, Xu (7-9 pm) governed by ䷖ Bo when Yang departs and Yin takes over. Hence we can see that cortisol’s relation to MESOR line correlates with uncanny prescision to Zhang Zhong-Jing’s Yang phases of the day.

Testosterone levels also fluctuate throughout the day but follow an interesting pattern when considered next to classical Chinese models of time:

testosterone

Predicted and mean (SD) observed serum testosterone concentration profiles for healthy young men. Source: Gupta et al. (2000)

The most striking thing to notice is that its ascent occurs mostly at night, during the Yin phases of the Shang Han Lun whereas we would expect it to follow Yang, being the male sex hormone. On closer inspection we find that it does in fact follow Yang according to the progression of the Growing and Declining Hexagrams. Its deepest dip occurs at 10 pm, during Hai time (9 pm – 11 pm), governed by ䷁ Kun, pure Yin. It then climbs as Yang ascends, peaking around 10 am during the Si time (9 am – 11 am) governed by ䷀ Qian, pure Yang, and then declines as Yang departs. This means that testosterone does actually follow Yang, correlating to the number of Yang lines in each hexagram.

Since serotonin, melatonin, cortisol and testosterone all match some aspect of the classical circadian model it is no surprise that the charts detailing the peaks and troughs of our physical and mental abilities also fit quite closely, especially since these would be things that Zhang Zhong-Jing and his contemporaries would have been able to observe.

CircadianRythm

Circadian Clock Chart. Source: Onnit.com

Around 3 am the pure Yin phase comes to end with our deepest sleep coming just before this time at the period between 1 am – 3 am when all three Yin divisions are in control. From this point we enter into the Shaoyang pivoting phase and see our body temperature reach its lowest just as the Shaoyin phase comes to an end. Shaoyin diseases are characterised by Yin and Yang imbalances resulting in abnormal body temperatures while Shaoyang disorders are also characterised with alternating sensations of Heat and Cold making this hour an appropriate time to experience to experience an extreme of temperature, especially cold in normal conditions as the Shaoyin stores the Ming Men Fire, or heat when this function is compromised and this Fire escapes (night sweats being a classic Yin deficiency sign).

As Yang increases our body temperature starts to rise again along with our blood pressure and testosterone while at 7.30 am, immediately after the hours of Jueyin terminate and the Yin phases cease, melatonin secretion stops. At 9 am, when Taiyang begins and we are in the hour of ䷀ Qian, the most Yang hour, our testosterone reaches its height and by 10 am we have our highest levels of alertness. Then around 3 pm, during the change from Taiyang to Yangming, we have our best co-ordination and reaction times, followed by our peak cardiovascular efficiency and muscle strength at 5 pm, while our highest blood pressure and body temperature occurs at 6.30 pm and 7 pm respectively. The Yangming channels are the only pair that are described in Su Wen ch. 24 and Ling Shu ch. 65 as abounding in both Qi and Blood making this the most suitable period for our physical abilities and blood pressure to peak. This would also explain the recent discovery that the risks from heart surgery are halved in the afternoon compared to morning (Montaigne et al., 2017), the afternoon being the time governed by the Shaoyin and Taiyang organs (the Heart/Kidney axis and their external pairs) of the regular Organ Clock and the Yangming phase of the Wei allowing maximum Qi an Blood to be available to actually endure the surgery. Yangming is also characterised by Heat making highest body temperature an appropriate physiological state for this phase. Yin may be starting to dominate at this moment but the remaining Yang lines are at the top of the of the hexagram meaning that Yang and Heat will most likely be seen as the outward expression despite an advancing Yin on the interior. The time when our body temperature is hottest will also be the time when our Yang will be escaping most rapidly.

Finally, at 9 pm as Yangming ends and the Yin cycles begin melatonin secretion starts and bowel movements are suppressed. Taiyin pathology is primarily characterised by diarrhoea-type disorders due to deficiency which would make suppression of bowel movements an appropriate assumption for the normal physiological activity of the Taiyin. This the first Yin phase to take control and is the only one in command at this time. Soon after it is also joined by Shaoyin at 11 pm which also controls the lower orifices and whose disturbance is often characterised by the need to urinate at night. Finally the Jueyin period also starts at 1 am taking us back to the moment of deepest sleep when all three Yin phases are in control before Taiyin terminates and Yang starts to return. Shaoyang overlaps with the remaining two Yin at 3 am, only Jueyin at 5 am and finally Shaoyang alone ruling from 7 am until its termination at 9 am.

The main difference between Zhang Zhong-Jing’s model and the circadian rhythm diagrams like the ones above is the level at which researchers operate. Western science uncovers the biological mechanisms going on at the chemical and cellular level while Chinese medicine makes observations based on the whole organism and sought find the patterns that unified us with the environment we live in. These suit their different modalities since western drugs are usually monotherapies making the precise time of a particular metabolic process of importance to how a specific drug will work. Chinese medicine works with imprecise and complex processes, formulas which contain hundreds if not thousands of potentially active ingredients working in synergy and seeks to find patterns when things are likely to happen in order to ascertain the best period in which to generate a general shift.

Practical Implications

Theoretical models aside what are practical applications for this model? In relation to sleep disorders, whether a simple jet lag, a more complex form of insomnia, or one of the many maladies for which disrupted sleep is a component, the answer is simple: attempt to treat as late as possible, preferably during the evening when Yin is advancing and the Taiyin period approaches. For the treatment itself I will not go into any specific protocols and points as everyone has their own style but as a general rule you cannot go far wrong with the advice of the Su Wen ch. 24 to “remove that from which they suffer and pay attention to what they long for… drain what is present in surplus and supplement what is insufficient” (I will leave “first remove their blood” to the therapist’s discretion). Divergent channels might also be appropriate due to their linking the Exterior and Interior with a tendency to gather around the eyes but since so little is written on them in the classics there are no universally agreed protocols for them and they remain just a suggestion (although watch this space for the next post as I have been thinking about these and the other secondary meridians lately). Whatever the particulars, if they go home with the relaxed and sleepy feeling that is a common effect of most treatments then the result has been achieved. They should avoid screens, stimulating activities and eating late at night to maintain the effect. After a good night’s sleep they should wake the next morning back in the present cycle. For a more chronic problem the aim should be to do that repeatedly until a new habit is formed. This seems a whole lot simpler and more practical that some protocols such as stimulating the Horary point of each channel as its hour comes on the Organ Clock according to your destination time zone (Micleu, 2015) which seem so complicated for a non-acupuncturist to calculate and learn that I suspect they are designed more to get the acupuncturist invited on better holidays than to be an effective treatment protocol for the patient.

Another suggestion could be to treat musculoskeletal problems during the day and perhaps ideally in the early afternoon. 1-3 pm is the Taiyang phase of both cycles whose corresponding division is the most superficial of the six, governs the Wei Qi of the sinews and is the most likely to be attacked by pathogenic forces first. This is also in anticipation of the Yangming phase when reactions, coordination and muscle strength reach their peak, preparing the patient for the best time to practice rehabilitative exercises. Musculoskeletal disorders should be treated with a fairly active, movement and mobilisation based treatment accompanied by exercises at a time when the patient will move most easily afterwards, while a treatment designed to induce rest should be done at a time when rest will be possible afterwards.

Other disorders could be treated according to time but it would probably be advisable to take advantage of the Internal-External pairings to avoid treating all the Yin patients in the middle of the night. Having broader 6 hour periods makes it easier to fit patients into these bands making this more practical than other chronological systems that often demand quite specific and anti-social hours to be met and often something of a astrological chart to be drawn up to decide exactly where their different energies are at any particular time in order to select a specific point. Personally I prefer a system that simply points me in the right direction and allow palpation to guide me towards the specifics with the aim being to obtain an observable or palpable return to balance. Whatever your method, acupuncture or any therapy should be aimed at facilitating a change rather than being the change in itself and if timing can help with that then it should be used. Other cycles should also be considered such as times of year (more warming treatments in the autumn and winter months) as well as the cycles of patient’s diseases. Teaching them to notice cues that indicate a condition will develop and using treatment to stop it in its tracks is far better than treating it once it is manifest, as declared in several of the classics (Jin Gui Yao Lue, ch. 1, Su Wen ch. 2, Ling Shu chs. 4 & 55, Nan Jing ch. 77), or giving treatments at arbitrary fixed intervals.

These cycles could also potentially be used to maximise the benefits of herbal remedies. Formulas aimed at helping sleep should probably all take at least one dose during the Yin phase of the day, from 5pm-5am. Those aimed at clearing Heat could take one dose around 7-9pm when Pericardium rules over the hour, the Shang Han Lun declares it to be in the Yangming phase and body temperature is peaking. For Blood or Yin deficiency perhaps the next hour, 9-11pm is better, when the Shang Han Lun considers the first Yin phase to have begun and the hexagram ䷁ Kun controls the hour. Similar patterns can be devised for most disorders which may be more practical to apply to herbs by telling them the optimal hours to take their medicine than it is to be calling them in for treatment at awkward times. This idea is becoming popular in western medicine too where the optimum times for drug delivery is known to increase tolerability up to five-fold and efficacy by up to double (Ballesta et al., 2017) but the current evidence supporting the timings of drugs (e.g. glucocorticoids tolerated better in the morning, anti H1 and H2 antihistamines more effective in the evening) would be difficult to translate to herbal remedies since herbs are not monotherapies and are likely to be acting on more than one mechanism. Traditional logic may turn out to be better although testing it would be as problematic as testing other areas of traditional medicine has proved to be.

It might also be possible to use some of these theories to develop testable hypotheses and novel treatment strategies. Bright light exposure at midday is already being used to treat depression, both the seasonal kind for which it is well established and also potentially non-seasonal (Al-Karawi and Jubair, 2016; Penders et al., 2016) and bipolar varieties (Sit et al., 2017). The midday period is during the Heart section of the Organ Clock and the Taiyang phase of the Shang Han Lun meaning that it supports Chinese chronobiological theory and could easily be viewed as a high tech rediscovery of the Chinese therapeutic principle of sun exposure. This could be another example of how to use circadian timing in the treatment of depression with appointments at midday complemented with a sun lamp in addition to regular treatment although the patient should also use it as a daily self help treatment at home too. It may be possible to condition the response to treatment to the exposure to midday light and make it more even effective. Certainly treatment of depression should not take place at midday if it involves a darkened room or lying face down. They should also not be used in the morning by bipolar patients as researchers discovered that morning light therapy induced hypomania in some cases (Sit et al., 2015). In Chinese medical theory this this is the time of the Yangming organs whose excess can often lead to psychiatric symptoms of Heat and mania and the Shaoyang period of the Wei which is also associated with psychological disturbances (and may confirm what many night owls like myself always suspected of “morning people” too). There must be more associations and ideas for treatment that could be developed using the Chinese model as a basis too. For example, the early morning should be the best time to treat Yang-type conditions and harmonise digestive disorders since the Yang is increasing in the Hexagrams while the Yangming organs and Shaoyang phase are governing the hours until 9 am but this is pure conjecture unless some evidence can be generated to support or refute it.

Conclusions

Hall, Rosbash and Young’s award has brought the importance of circadian rhythms to the attention of the scientific and medical community. In recent times sleep has become an increasingly scarce resource in a productivity obsessed society that views sleep as unproductive time. I hope that their discoveries lead to us taking our down-time more seriously and not towards using the interventions being developed for treating broken circadian cycles to support the drive to reduce sleep even more like some companies are trying to do with food (Cadwalladr, 2016). I am quite sure that if they do there will be unforeseen (or foreseen but ignored) consequences. New advancements in chronobiology need not be all bad though. In recent years there have been a number of advances made in measuring the various circadian rhythms through wearable devices (Ballesta et al., 2017) which could be translated into useful information for Chinese medical practitioners who could map the information onto the traditional cycles and use them to assess the progress of treatments instead of their intended purposes to optimise drug delivery and reduce toxicity for each patient. Given the emphasis on harmonising the human cycle with the celestial ones in classical Chinese medicine it would make sense that the objective of many treatments is to return the circadian rhythms to their natural state. Being able to objectively measure these cycles could pave the way for a revolution in assessment and treatment options if they can demonstrate an influence. A search on pubmed for “circadian” and “acupuncture” or “Chinese medicine” produced only three studies specifically investigating this in English (Spence et al., 2004; Zhong et al., 2011; Kim et al., 2012).

Classical Chinese models of the circadian clock seem to be surprisingly accurate when compared to modern charts but it is important that we do not only take the simplest and apply it to everything as often happens with the Organ Clock in popular sources. Just as modern researchers use multiple readings such as temperature, serum cortisol, testosterone and melatonin levels to measure a person’s circadian rhythm, so too in order to properly apply Chinese chronology we have to understand there are multiple cycles at work, of the Wei and and Ying, initiated by light and the consumption of food, each with its own sub-cycles and operating as part of greater yearly cycles and the individuals life cycle before its true explanatory power can be achieved. Then it attains something that is a close approximation to the modern literature and perhaps more practical for the average clinician. Ancient descriptions aimed to record observable patterns with mnemonic devices that would be pragmatic for clinical use and they still serve this function providing a useful framework on which we can pin the modern diurnal fluctuation of various hormones and their associated behaviours.

Sleep scientist Matthew Walker described the current situation as a “catastrophic sleep-loss epidemic” (Cooke, 2017) which could make this the second time in modern history that Chinese medicine has a significant role to play in curbing an epidemic disease after the discovery of Artemesinin by Youyou Tu. The fact that two Nobel prizes for medicine have gone to people whose research involved finding the mechanisms behind Chinese medical observations (whether stated as the researchers objective or not), it suggests that we could be entering a time when traditional knowledge enjoys the benefits of modern scrutiny and not just the criticisms.

References:

Al-Karawi, D. and Jubair, L. (2016). Bright light therapy for nonseasonal depression: Meta-analysis of clinical trials. Journal of Affective Disorders 198:64-71. Available from: http://dx.doi.org/10.1016/j.jad.2016.03.016 [Accessed 10-10-17].

Ballesta, A., Innominato, P.F., Dallmann, R., Rand, D.A. and Lévi, F.A. (2017). Systems Chronotherapy. In: Pharmacological Reviews 

Cadwalladr, C. (2016). Could You Stomach Huel, the Food of the Future? In The Guardian 31st July 2016. Available from: https://www.theguardian.com/science/2016/jul/31/huel-human-fuel-hi-tech-food-powder [Accessed 12-10-17].

Chan, S. and Debono, M. (2010). Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy. In Therapeutic Advances in Endocrinology and Metabolism 1(3): 129–138. Available from: http://dx.doi.org/10.1177/2042018810380214 [Accessed 1-11-17].

Chronopuncture.com (2004). Qi Calculator. Available from: https://chronopuncture.com/qi.htm [Accessed 5-10-17].

Cooke, R. (2017). The shorter your sleep, the shorter your life: the new sleep science. The Guardian, 24th Sept 2017. Available from: https://www.theguardian.com/lifeandstyle/2017/sep/24/why-lack-of-sleep-health-worst-enemy-matthew-walker-why-we-sleep [Accessed 04-10-17].

Golding, R. (2013). The Complete Stems and Branches. Moondance Publishers.

Green, A. Cohen-Zion, M., Haim, A and Dayan, Y. (2017). Evening light exposure to computer screens disrupts human sleep, biological rhythms, and attention abilities. In Chronobiology International 34 (7). Available from: http://dx.doi.org/10.1080/07420528.2017.1324878 [Accessed 7-10-17].

Gupta, S.K., Lindemulder, E.A. and Sathyan, G. (2000). Modeling of circadian testosterone in healthy men and hypogonadal men. Journal of Clinical Pharmacology 40:731–8. Available from http://dx.doi.org/10.1177/00912700022009486 [Accessed 2-11-17].

Harveston, A.T., Hannon, J.C., Brusseau T.A., Podlog, L., Papadopoulos, C., Durrant, L.H., Hall, M.S., Kang, K.D. (2016). Acute Effects of 30 Minutes Resistance and Aerobic Exercise on Cognition in a High School Sample. Research Quarterly for Exercise and Sport 87(2):214-20. Available from http://dx.doi.org/10.1080/02701367.2016.1146943 [Accessed 15-10-17].

Kayaba, M., Iwayama, K., Ogata, H., Seya, Y, Kiyono, K., Satoh, M. and Tokuyama, K. (2014). The effect of nocturnal blue light exposure from light-emitting diodes on wakefulness and energy metabolism the following morning. In Environmental Health and Preventive Medicine 19(5): 354-361. Available from: http://dx.doi.org/10.1007/s12199-014-0402-x [Accessed 7-10-17].

Kim, H.M., Cho, S.Y., Park, S.U., Sohn, I.S., Jung, W.S., Moon, S.K., Park, J.M., Ko, C.N. and Cho, K.H. (2012). Can acupuncture affect the circadian rhythm of blood pressure? A randomized, double-blind, controlled trial. In Journal of Alternative and Complementary Therapy 18(10):918-23. Available from: https://doi.org/10.1089/acm.2011.0508 [Accessed 2-11-17].

Liu, G. (2015). Foundations of Theory for Ancient Chinese Medicine. Singing Dragon. London and Philadelphia.

Micleu, C. (2015). Using Acupuncture Points to Eliminate Jet Lag. The Jade Institute. Available from: https://www.jadeinstitute.com/jade/acupuncture-to-eliminate-jet-lag.php [Accessed 05-10-17].

Mitchell, C., Ye, F. and Wiseman, N. (1999). Shang Han Lun: On Cold Damage, Translation & Commentaries. Paradigm Publications. Brookline, MA.

Montaigne, D., Marechal, X., Modine, T., Coisne, A., Mouton, S., Fayad, G., Ninni, S., Klein, C., Ortmans, S., Seunes, C., Potelle, C., Berthier, A., Gheeraert, C., Piveteau, C., Deprez, R., Eeckhoute, J., Duez, H., Lacroix, D., Deprez, B., Jegou, B., Koussa, M., Edme, J-L., Lefebvre, P., Staels, B. (2017). Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study. In The Lancet. Available from: http://dx.doi.org/10.1016/S0140-6736(17)32132-3http://dx.doi.org/10.1016/S0140-6736(17)32132-3 [Accessed 1-11-2017].

NHS (2015). Physical activity guidelines for adults. Available from: http://www.nhs.uk/Livewell/fitness/Pages/physical-activity-guidelines-for-adults.aspx [Accessed 15-10-17].

Nobel Foundation (2017). The Nobel Prize in Physiology or Medicine 2017: Jeffrey C. Hall, Michael Rosbash, Michael W. Young: Press Release 2017-10-02. Available from: https://www.nobelprize.org/nobel_prizes/medicine/laureates/2017/press.html [Accessed 04-10-17].

Penders, T.M., Stanciu, C.N., Shoemann, A.M., Ninan, P.T., Bloch, R., Saeed, S.A. (2016). Bright Light Therapy as Augmentation of Pharmacotherapy for Treatment of Depression: A Systematic Review and Meta-Analysis. Primary Care Companion for CNS Disorders 18(5). Available from: http://dx.doi.org/10.4088/PCC.15r01906 [Accessed 10-10-17].

Sit, D, Wisner, K.L., Hanusa, B.H., Stull, S. and Turman, M. (2015). Light therapy for bipolar disorder: a case series in women. Bipolar Disorders 9(8): 918-27. Available from: http://dx.doi.org/10.1111/j.1399-5618.2007.00451.x [Accessed 10-10-17].

Sit, D.K., McGowan, J., Wiltrout, C., Diler, R.S., Dills, J.J., Luther, J.L., Yang, A., Ciolino, J.D., Seltman, H., Wisniewski, S.R., Terman, M. and Wisner, K.L. (2017). Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial. American Journal of Psychiatry. Available from: http://dx.doi.org/10.1176/appi.ajp.2017.16101200 [Accessed 10-10-17].

Spence, W.D., Kayumov, L., Chen, A., Lowe, A., Jain, U., Katzman, M.A., Shen, J., Perelman, B. and Shapiro, C.M. (2004). Acupuncture Increases Nocturnal Melatonin Secretion and Reduces Insomnia and Anxiety: A Preliminary Report. In Journal of Neuropsychiatry and Clinical Neurosciences 16(1):19-28. Available from: http://dx.doi.org/10.1176/jnp.16.1.19 [Accessed 3-11-17].

Sung, Y-M. (2010). Understanding the Jin Gui Yao Lue: A Practical Textbook. People’s Medical Publishing House. Beijing.

Wu, Z-X. and Wu, K.T. (2014). Heavenly Stems and Earthly Branches – Tian Gan Di Zhi: The Heart of Chinese Wisdom Traditions. Singing Dragon. London and Philadelphia.

Unschuld, P.U. (1986). Nan Ching: The Classic of Difficult Issues. University of California Press. Berkeley, Los Angeles.

Unschuld, P.U. and Tessenow, H. (2011). Huang Di Nei Jing Su Wen: An Annotated Translation of Huang Di’s Inner Classic – Basic Questions. University of California Press. Berkeley, Los Angeles.

Unschuld, P.U. (2016). Huang Di Nei Jing Ling Shu: The Ancient Classic on Needle Therapy. University of California Press. Berkeley, Los Angeles.

Wang, J-Y. and Roberston, J.D. (2008). Applied Channel Theory in Chinese Medicine. Wang Ju-Yi’s Lectures on Channel Therapeutics. Eastland Press. Seattle.

Zhong, G.W., Chen, M.J., Luo, Y.H., Xiang, L.L., Xie, Q.Y., Li, Y.H., Zhang, C. and Gao, F. (2011). Effect of Chinese herbal medicine for calming Gan (肝) and suppressing hyperactive yang on arterial elasticity function and circadian rhythm of blood pressure in patients with essential hypertension. In Chinese Journal of Integrated Medicine 17(6):414-20. Available from: https://doi.org/10.1007/s11655-011-0761-6 [Accessed 2-11-17].

Advertisements