Poor sleep is a common complaint, population-based studies across multiple countries indicate that approximately 30% of people report one or more insomnia symptoms. Insomnia and sleep problems are not only an inconvenience but can have a significant effect on wellbeing and overall health. Chronic sleep disturbance is associated with an increased risk of a multitude of diseases including Alzheimer’s, cardiovascular disease, diabetes as well as depression and anxiety.
Sleep is characterised in most organisms as a behavioural state of diminished responsiveness to external stimuli coincident with changes in cortical brain activity and muscle tone. The exact mechanisms involved during sleep are still being understood however one prevailing theory with strong supportive evidence is that sleep serves a restorative function for the brain and body. Although the amount and timing of sleep varies greatly among species, the occurrence and biological need for sleep is evolutionarily conserved1.
Normal sleep requirements
The major factor involved in sleep initiation is the neurotransmitter melatonin, which is produced from serotonin, and synthesis of the latter is stimulated by daylight. When in darkness the pineal gland detects the lack of light and initiates the conversion of serotonin to melatonin; magnesium and B6 are cofactors. Melatonin is involved in the inducement of sleep by many mechanisms including binding to receptors in the body to help relaxation and reducing dopamine levels, a neurotransmitter that helps wakefulness2.
Circadian rhythms also play an essential role in the initiation of sleep. We have evolved to rise and sleep with the pattern of the sun, waking around dawn and sleeping after sunset. Our natural circadian rhythm is beginning to become overridden by creation of “cities that never sleep” with exposure to unnatural light and shift work being major players in sleep disruption.
Whilst light exposure does effect circadian rhythm it is not the sole factor – otherwise we might expect populations (e.g. some Scandinavians) who experience polar nights (24 hours of darkness in mid-winter) to spend 24 hours a day sleeping and vice versa in summer. Clearly this is not the case although they may sleep a little longer in winter3.
The development of our circadian rhythm is also hard wired into our DNA, each cell possesses its own biological clock and we are designed to function on a 24 hour cycle, even in the absence of sunlight. We have an innate body clock programmed within our cells to maintain a balance of our circadian rhythm. Many genes, hormones and neurotransmitters are involved in this delicate regulation and disruption to genetic, hormonal or neural signalling may have a significant effect on sleep quantity and quality. This was discovered in 1729, a French astronomer called Jean Jacques d’Ortous de Marian took plants that displayed daily leaf movements and put them in the dark for several days. He noted that the leaves of the plants continued to open during the day and close at night despite the absence of sunlight. Based on this seminal experiment, he concluded that the observed rhythm was not passively driven by a cyclic environment but was an innate property of the plant. So we are designed to live our day in a twenty four hour cycle which is in tune with the cycle of the Earth’s rotation upon its axis3.
The other factor that controls when we sleep is ‘sleep pressure’ which is directly related to the amount of time we have been awake. In other words, the longer we are awake, the greater the pressure to sleep.
Sleep pressure is related to levels of adenosine in the brain – during periods of wakefulness the brain’s level of adenosine increases; conversely during sleep adenosine levels decrease. Adenosine is thus a sleep-promoting molecule. Incidentally, caffeine helps with wakefulness by blocking the attachment of adenosine to its receptors; however adenosine continues to build-up so when the effects of caffeine wear off sleep pressure will return.
Hormones affecting sleep
The endocrine control over the circadian pacemaker is reflected in changes in serum levels of cortisol, melatonin and other neurotransmitters. Melatonin, noradrenaline, and acetylcholine decrease with light activation, whereas cortisol, serotonin, GABA, and dopamine levels increase.
Cortisol, the hormone that is secreted during periods of stress, has an effect on both the circadian rhythm and melatonin production. Firstly cortisol works antagonistically to melatonin, as it is involved in stimulating alertness. The secretion of cortisol begins in the morning to stimulate wakefulness; it rises, then falls throughout the day dropping to its lowest levels in the late evening when it is time to sleep.
In healthy individuals, we expect a peak melatonin level at approximately 3 am, whereas cortisol peaks at approximately 9 am. The transition from low light to bright light in the morning results in a surge in cortisol levels and a decline in melatonin levels4,5.
During periods of stress large amounts of cortisol are produced and there is an increased activation of the hypothalamic-pituitary-adrenal (HPA) axis. This excess cortisol can interfere with melatonin production and also the normal circadian rhythm and thus have a negative effect on sleep.
A study in older adults found that evening cortisol was higher in those reporting short sleep duration and more sleep disturbances the night before. Chronic insomnia symptoms and shorter sleep duration on at least three occasions were also associated with a steeper rise in the cortisol awakening response and higher levels of cortisol later in the day, respectively6.
In vivo study data indicate that stress negatively influences the synthesis of melatonin in the pineal gland, thus attenuating the day-night variations of circulating melatonin. The effect might be mediated by increased cortisol, which binds to pineal organ-specific glucocorticoid receptors to modulate melatonin rhythm7.
Indeed there is a bi-directional relationship, any awakening from sleep will be associated with a burst of cortisol, and cortisol levels are increased in insomnia.
Impaired insulin sensitivity or insulin resistance is known to have an effect on many aspects of health such as increasing inflammation, weight gain and driving type 2 diabetes (T2D). However poor blood sugar regulation and impaired insulin signalling can also affect sleep quality. Side effects of T2D which can impair sleep include nocturia, nocturnal hypoglycaemia, peripheral neuropathy, restless leg syndrome and sleep disordered breathing. These conditions, when associated with diabetes, can cause fragmented sleep and poor quality of life8.
Studies using continuous blood glucose monitoring have shown that patients with type 1 diabetes mellitus spent an average of 2.3 h per day with glucose levels below 70 mg/dL (3.9 mmol/L), and most of the hypoglycaemic values occurred at night. These findings were corroborated by another study, also using continuous blood glucose monitoring, showing that in more than half of the nights studied, nocturnal hypoglycaemia occurred9.
Not only can insulin resistance trigger insomnia but chronic poor sleep may also be a risk factor for the development of T2D. A 2015 meta-analysis of prospective studies showed that both individuals who sleep for short periods and those who sleep for long periods are at increased risk of developing T2DM, with a proposed ‘optimal’ sleep duration of 7–8 h per night8.
Oestrogen and Progesterone
Current research has demonstrated that women and girls are twice as likely to experience sleep disruption and insomnia throughout their lifespan as men and boys. And the consequences of poor sleep may also be more significant in females as well. The exact mechanisms for this are not well understood but sleep disturbance seems to be influenced by hormonal changes during menstruation, pregnancy, post-partum and menopause. Women tend to have increased deep or slow wave sleep but report more sleep problems. Studies suggest that differences in sleep patterns between sexes are removed in the absence of sex steroid hormones, suggesting they play a role in sleep quality10.
It is well known that sleep quality diminishes during menopause, this could suggest that oestrogen and or progesterone play a role in supporting sleep. Other symptoms of menopause such as night sweats and hot flushes may independently disrupt sleep and therefore sleep disturbance during menopause may be mostly secondary to other menopausal symptoms. However disturbed sleep during perimenopause can occur independently of hot flashes11.
It may have more to do with progesterone, which is known as the relaxing hormone; progesterone has a mildly sedative effect by increasing the production of GABA, the calming neurotransmitter10,12. During the reproductive years, sleep has been observed to be of better quality during the follicular phase and peaking during the luteal phase of menstruation. During menses, progesterone (and oestrogen levels) drop off which may have a negative effect on sleep quality. In a randomised double blind control trial, progesterone had no effect on undisturbed sleep but restored normal sleep when sleep was disturbed acting as a “physiologic” regulator rather than as a hypnotic drug. Use of progesterone might provide a therapeutic strategy for the treatment of sleep disturbances, in particular in ageing where sleep is fragmented and of lower quality13.
A human epidemiological study showed that neither subclinical hypothyroidism nor hyperthyroidism is significantly associated with decreased sleep quality. However, this study did not look at clinical hypothyroidism and there is limited evidence of sleep disturbances in hypothyroidism. This could be via hypothyroidism increasing sleep apnoea and therefore affecting sleep indirectly (sleep apnoea may trigger waking and disrupt slow wave sleep)15,16.
Sleep is essential for normal testosterone levels, which peak during sleep and it has been demonstrated that sleep loss suppresses testosterone secretion. Experimental data suggest that testosterone may have an effect on subjective sleep quality and quantity. Low testosterone may affect overall sleep quality and studies have shown that when testosterone is replaced there is an improvement in sleep quality. On the other hand, large doses of exogenous testosterone and anabolic/androgenic steroid abuse are associated with abnormalities in sleep duration and architecture. Therefore, the importance of appropriate testosterone levels for maintaining adequate sleep and conversely the importance of sleep for supporting healthy testosterone production has been recognised17.
Supporting healthy sleep
When clients present with sleep disturbances it is therefore important to consider the role of hormonal regulation. So conditions including insulin resistance, oestrogen dominance, reduced testosterone, adrenal and thyroid dysfunction should be considered, as well as factors independent of hormone balance.
Healthy sleep: good habits and tips
Creating a sleep ritual – a set of little things before bed to help prepare physically and psychologically for sleep – can guide the body into a deep, healing sleep. It may take weeks or months, but using these tools in a coordinated way, along with addressing any relevant hormone imbalances, will eventually reset biological rhythms.
Naturally regulate the sleep/wake cycle
- Ensure daytime full light exposure.
- Have time before bed in natural dimming light away from bright screens.
- Sleep in darkness and quiet – consider using a sleep mask or earplugs.
- Consider using a low wattage incandescent bulb.
Keep a regular sleep cycle
- Set a regular bedtime routine – go to bed at the same time each night. Choose a time when generally feeling tired each night. Try not to break the routine.
- Wake up at the same time each day, even at weekends. If you are getting enough sleep you should wake naturally without an alarm. If you need an alarm clock then you should go to bed earlier.
- Nap to make up for lost sleep during the day if possible, rather than disturb the normal sleep/wake cycle.
- Fight after dinner drowsiness otherwise napping at this time could result in waking through the night. Consider an earlier meal and a walk after eating before bed.
Create a relaxing bedtime ritual
- Making a consistent effort to relax and unwind before bed will allow easier and more deep sleep. A peaceful bedtime routine sends a powerful signal to the brain that it is time to wind down and let go of the day’s stresses.
- Keep noises down (earplugs might help).
- Keep the room cool. Most people sleep best at around 18oC with adequate ventilation.
- Make sure the bed is comfortable. Waking often with a sore back or neck suggests the mattress or pillow may need changing.
- Create an aesthetic environment that encourages sleep – use serene and restful colours and eliminate clutter and distraction.
- Avoid work or watching television in bed.
- Consider using a relaxation, meditation or guided imagery CD, any of these may help with getting to sleep and will certainly help with relaxation.
Eat right and get regular exercise/physical activity
- Eat at least 3 hours before bedtime. Try to make dinnertime early in the evening. Fatty and spicy or rich, heavy foods are best avoided in the evening.
- Avoid alcohol before bedtime, it helps initiate sleep but causes interruptions and poor quality sleep.
- Cut down on caffeine. Ideally no caffeine after midday – some people take 12 hours to metabolise caffeine. Make sure this includes any medication that contains caffeine e.g. headache tablets (if prescription medication contains caffeine, discuss with the G.P. before stopping any medication).
- Avoid too many liquids in the evening, this will cause middle of the night wakings to eliminate.
- Quit Smoking. Smoking causes sleep problems in numerous ways. Nicotine is a stimulant, plus smokers experience nicotine withdrawal during the night, making it harder to sleep.
- Avoid high intensity exercise after dinner.
- 5-hydroxytryptophan (5HTP) is a precursor to serotonin and can be useful for initiating sleep for some people, particularly if melatonin or serotonin levels are low.
- Montmorency cherry is a natural source of melatonin, the neurotransmitter responsible for the induction of sleep.
- L-theanine has been shown to aid relaxation and reduce anxiety by increasing alpha brain waves and GABA levels (the calming brain neurotransmitter).
- Magnesium – a cofactor for melatonin production; it also supports muscle relaxation.
- Sleep is under tight regulation via our innate circadian rhythm, this is initiated from an evolutionary perspective by a balance of our relationship with the Earth’s 24 hour cycle and our own cell cycles controlled by DNA. Our lifestyles today mean that we have overridden the natural cycle of the Earth, for example, by exposure to artificial light late in the evening.
- Our sleep neurotransmitter melatonin is produced during darkness and is responsible for the induction of sleep (artificial lights can affect melatonin production). The stress hormone cortisol works in opposition to melatonin and can inhibit melatonin production, therefore excess stress can affect sleep quality.
- Risk of insulin resistance increases with poor sleep but it also may affect sleep by exacerbating symptoms such as nocturia (frequent urination at night), nocturnal hypoglycaemia (low blood sugar), peripheral neuropathy, restless leg syndrome and sleep disordered breathing. Type 2 diabetes is associated with poor sleep.
- Progesterone is associated with improved sleep quality through its relationship with the calming neurotransmitter GABA. Dysregulation of oestrogen and progesterone may reduce sleep quality. Also menopausal women may have disturbed sleep due to symptoms such as night sweats and hot flushes which disturb sleep quality.
- There is some evidence that hypothyroidism may affect slow wave sleep (which is particularly restorative). However research is limited and more studies are needed to confirm this.
- Testosterone production is increased during sleep and low levels of testosterone are associated with reduced sleep quality.
- Hormonal imbalances should therefore be considered in clients with reduced sleep quality and/or quantity.
- Lifestyle factors and good ‘sleep hygiene’ are also important for supporting healthy sleep.
If you have questions regarding the topics that have been raised, or any other health matters, please do contact me (Helen) by phone or email at any time.
email@example.com, 01684 310099
Helen Drake and the Cytoplan Editorial Team
Relevant Cytoplan Products
5HTP Plus– 5-hydroxytryptophan (precursor to serotonin) with cofactors B6 and magnesium. This supplement is not suitable for those on antidepressant medication.
Cyto-Night – contains montmorency cherry (natural source of melatonin), glycine, hops and magnesium
Biofood Magnesium – 100mg of elemental magnesium per tablet
L-Theanine – amino acid found in green tea
Thyroid Support – contains tyrosine, selenium and kelp
Blood Glucose Support – contains chromium, cinnamon, magnesium, zinc and molybdenum
Adrenal Support – Botanical and mineral complex with B5
Phyto-Flavone – source of phyto-oestrogens from soy isoflavones
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- Martyn-Nemeth P, Phillips SA, Mihailescu D, et al. Poor sleep quality is associated with nocturnal glycaemic variability and fear of hypoglycaemia in adults with type 1 diabetes. J Adv Nurs. 2018;74(10):2373-2380. doi:10.1111/jan.13765
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- Baker FC, Lee KA. Menstrual Cycle Effects on Sleep. Sleep Med Clin. 2018;13(3):283-294. doi:10.1016/j.jsmc.2018.04.002
- Caufriez A, Leproult R, L’hermite-Balé M, Kerkhofs M, Copinschi G. Progesterone Prevents Sleep Disturbances and Modulates GH, TSH, and Melatonin Secretion in Postmenopausal Women. E614 jcem.endojournals.org J Clin Endocrinol Metab. 2011;(4):96. doi:10.1210/jc.2010-2558
- Carpenter AC, Timiras PS. Sleep organization in hypo- and hyperthyroid rats. Neuroendocrinology. 1982;34(6):438-443. doi:10.1159/000123342
- Akatsu H, Ewing SK, Stefanick ML, et al. Association between thyroid function and objective and subjective sleep quality in older men: The osteoporotic fractures in men (MrOS) study. Endocr Pract. 2014;20(6):576-586. doi:10.4158/EP13282.OR
- Kuczyński W, Gabryelska A, Mokros Ł, Białasiewicz P. Obstructive sleep apnea syndrome and hypothyroidism – merely concurrence or causal association? Pneumonol Alergol Pol. 2016;84(5):302-306. doi:10.5603/PiAP.2016.0038
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