Introduction

Did you get enough sleep this past week? Can you remember the last time you woke up without an alarm and feeling refreshed? If the answer to any of these questions is “no,” you are not alone. In fact, two-thirds of adults throughout all developed nations fail to obtain the recommended eight hours of sleep per night.

Did you know that routinely sleeping less than six or seven hours a night devastates your immune system, and more than doubles your risk of cancer? A lack of sleep is a key lifestyle determiner of whether or not you will develop Alzheimer’s disease. It also increases the likelihood of your coronary arteries becoming blocked and brittle, resulting in cardiovascular disease, stroke and congestive heart failure. Sleep disruption also further contributes to all major psychiatric conditions including depression, anxiety and suicidality. 

Why is it Important? 

As you can see, getting enough sleep is absolutely, mind-blowingly essential for mental and physical well-being. But why does sleep matter? Besides stealing our time, what does sleep really do for us?  

Important for Brain Function  

Sleep plays a vital role in brain function. A lack of sleep affects memory, learning abilities, mental clarity and emotional intelligence. Sleep deprivation has been linked to numerous neurological and psychiatric conditions including Alzheimer’s disease, anxiety, depression, bipolar disorder, suicide, stroke, and chronic pain. A prevailing view in psychiatry has been that mental disorders cause sleep disruption. However, studies have demonstrated that it’s not just a one-way street, that otherwise healthy people can experience a neurological pattern of brain activity similar to that observed in many of these psychiatric conditions simply by having their sleep disrupted.1 In fact, many of the brain regions commonly impacted by psychiatric mood disorders are the same regions that are involved in sleep regulation and impacted by sleep loss. By improving sleep quantity, quality and regularity, it is possible to significantly improve symptoms in psychiatric populations.

When it comes to Alzheimer’s disease for example, it’s interesting to note that sleep disturbance precedes the onset of Alzheimer’s disease by several years, suggesting that it may be an early warning sign of the condition, or perhaps even a contributing factor.2 Following diagnosis, the severity of sleep deprivation will then progress in linear fashion to the neurological symptoms of the Alzheimer’s patient. And finally, over 60% of Alzheimer patients have at least one clinical sleep disorder, insomnia being the most common.  

Helps to Reduce your risk of Type 2 Diabetes  

The link between sleep loss and abnormal blood sugar levels first emerged in a series of large epidemiological studies spanning several continents.3 Independent of one another, the researchers found far higher rates of type 2 diabetes among individuals that reported sleeping less than six hours a night routinely. Even when adjusting for other contributing factors such as body weight, alcohol consumption, smoking, age, gender, race and caffeine use, the association remained significant.4  

The less you sleep, the more you are likely to eat. In addition, your body becomes unable to manage those calories effectively, especially the build up of sugar in your bloodstream. This is because in a sleep-deprived state, the cells of the body become far less receptive to insulin. The cells begin to repel rather than absorb the dangerously high levels of glucose. Sleeping less than 7 or 8 hours a night significantly increases your likelihood of developing type 2 diabetes. 

Helps to Regulate your Appetite  

Research has shown that inadequate sleep decreases the concentrations of the satiety-signalling hormone, leptin and increases levels of the hunger-instigating hormone, ghrelin.5 So lack of sleep mutes the chemical message that tells us to stop eating and increases the urge to keep eating.

Another recent discovery is that sleep loss increases levels of circulating endocannabinoids which are chemicals produced by the body which, like cannabis, stimulate appetite and increase your desire to snack. This increase in endocannabinoids combined with the changes in leptin and ghrelin levels caused by inadequate sleep form a potent storm, driving you in one direction: overeating. This sets up the potential for metabolic syndrome and obesity.6

Reduces your Risk of Cardiovascular Issues 

Recent research shows that lack of sleep can increase your risk of cardiovascular issues via its impact on the sympathetic nervous system. In a 2004 Japanese study of 2,282 male workers, those sleeping less than six hours over a 14 year period were 300 to 400% more likely to suffer one or more cardiac arrests than those sleeping between 7-8 hours.7 In 2011, another study was done which tracked just less than half a million men and women of varied ages, race and ethnicities across eight different countries. Progressively shorter sleep was associated with 45% increased risk of developing and/or dying from coronary heart disease within 7 to 25 years from the start of the study.8 Both these studies took into account other cardiac risk factors such as smoking, physical activity and body mass.

A study has shown that you don’t need a full night of total sleep deprivation to inflict a significant impact on your cardiovascular system. Even just one night of losing 1 to 2 hours of sleep will quicken the contracting rate of a person’s heart and significantly increase their systolic blood pressure.9 Beyond accelerating your heart rate and increasing your blood pressure, a lack of sleep can also mean you are more likely to suffer calcification of your coronary arteries, significantly increasing your risk of a coronary heart attack.  

Balances your Hormones  

Sleep also supports the optimal functioning of your reproductive system and hormones. In a study done at the University of Chicago, a group of young males were allowed to sleep for only five hours for one week.10 The researchers found a significant drop in their testosterone relative to their own baseline levels of testosterone when fully rested. In fact, the researchers concluded that the hormonal blunting effect is so large that it effectively “ages” a man by ten to fifteen years! Men suffering from sleep disorders, especially sleep apnoea associated with snoring, have markedly lower levels of testosterone than those of similar age and backgrounds who do not suffer from a sleep condition. Lack of sleep also affects sperm count and quality.

Inadequate sleep also affects the reproductive system of women. Routinely sleeping less than six hours a night results in a 20% drop in follicular-releasing hormone in women which is a hormone that peaks just prior to ovulation and is necessary for conception.11 In a report that brought together findings from studies over the past forty years of more than 100,000 employed women, those working irregular night-time hours who had poor-quality sleep, had a 33% higher rate of abnormal menstrual cycles than those working regular daytime hours.12 Moreover, the women working erratic hours were 80% more likely to suffer from issues of sub-fertility and reduced ability to get pregnant. Women who do become pregnant and routinely sleep less than 8 hours a night are also significantly more likely to suffer a miscarriage in the first trimester relative to those consistently sleeping eight hours or more a night. 

Supports your Immune System and Reduces Your Risk of Cancer  

Poor quality sleep can also suppress your immune function, negatively affecting the balance of bacteria in the gut and increasing inflammation. In fact, studies have shown that not enough sleep and poor sleep quality can leave your immune system more susceptible to infectious illnesses like the common cold.13 During sleep, your body releases more cytokines which are proteins needed to fight an infection or to reduce inflammation. If you don’t get enough sleep, your body produces less cytokines, making you more susceptible to infection. In addition, infection-fighting antibodies and cells are reduced during these periods when you don’t get enough sleep.

A study done at the University of California showed just how rapidly and comprehensively a brief dose of short sleep can affect your cancer fighting immune cells. The researchers found that a single night of four hours sleep in a cohort of healthy young men, swept away 70% of the natural killer cells circulating in the immune system, relative to a full eight-hour seep.14 It has also been discovered that night-time shift work, and the disruption to circadian rhythms and sleep that it causes, considerably increases the risk of developing numerous different forms of cancer. In fact, Denmark recently became the first country to pay worker compensation to women who had developed breast cancer after years of night shift work in government-sponsored jobs such as nurses or air cabin crew.

Helps You Live Longer  

Last but not least, sleep also helps you live longer. A 2014 study published in Frontiers in Aging Neuroscience concluded that getting routine good quality sleep is a significant factor in achieving longer life spans. The researchers found that human longevity is associated with regular sleep patterns, maintenance of slow wave sleep and favourable lipid profile which was also impacted by sleep.15 By also increasing your risk of developing many chronic diseases, sleep deprivation has the ability to shorten your life expectancy.

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How Does it Work? 

Sleep is a very complex process inside your body. It is regulated by the body’s circadian rhythm where your body thrives on exposure to light during the day and darkness at night. In the morning, your body, releases cortisol which helps wake you up and at night-time, when it gets dark, it releases melatonin, which helps you relax and go to sleep. Melatonin is released by the pineal gland. The release of these two hormones are governed by the suprachiasmatic nucleus (SCN), located in the hypothalamus, which is commonly referred to as the ‘master clock.’ The SCN receives communication from melanopsin (a photo pigment of the eye) which contains cells that respond to either the natural light or darkness.16

How Much Sleep Should You Get? 

As we have seen, research shows that getting too little and too much sleep can increase your risk of cardiovascular disease and reduce your life span. In fact, a 2017 study found that a “sweet spot” of approximately seven hours per night is optimal for the health and functioning of most adults. However, there may be differences based on your age, gender, health, activity level and genetic makeup.18  

You may have noticed that as you got older, you needed less sleep than when you were a child. Newborn babies for example, typically need 14-17 hours of sleep per day and pre-schoolers need 10-13 hours. Teens typically require 8-10 hours per day. 

Sleep Disruptors  

There are various dietary and lifestyle factors that can increase the risk of getting inadequate sleep or poor sleep quality. These include:

• Caffeine and sugar
  

Especially if consumed later in the day, can keep you awake at night and make it difficult to fall asleep in the first place. Caffeine is an adenosine antagonist which means that it prevents adenosine from doing its job of getting you to fall asleep.

• Alcohol
  

While alcohol in small amounts may help you get to sleep, research has shown that a high alcohol intake results in increased sleep disruption, lower quality of sleep and shorter sleep duration.

• Spicy and acidic foods
  

For some people, spicy foods like citrus and tomatoes can cause indigestion and reflux, making it difficult to get comfortable. This is especially true if you’ve eaten late right before you go to bed. It can also make you more likely to wake up at night.

• Poor sleep routines and exposure to blue light
  

Exposure to blue light can increase the risk of getting inadequate sleep or poor sleep quality.

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Other Ways to Improve your Sleep  

Sleep Hygiene

Paying attention to sleep hygiene is one of the most straightforward ways that you can set yourself up for a good sleep. Strong sleep hygiene means having both a bedroom environment and daily routine that promotes consistent, uninterrupted sleep. It’s all about making positive habits that make it easier to sleep soundly throughout the night and wake up refreshed.

• Set your sleep schedule
  

Having a set schedule normalises sleep as an essential part of your daily routine and gets your brain and body accustomed to getting the full amount of sleep that you need. Make sure you have a fixed wake-up time regardless of whether it’s a weekday or weekend. If you want to shift your sleep times, don’t try to do it all at once. It’s better to make small, step-by-step adjustments of up to an hour or two so you can slowly get adjusted to a new schedule. Also, try not to overdo it with naps as it can throw out sleep at night. If you have to nap, keep them relatively short and limited to the early afternoon.  

• Follow a nightly routine
  

How you prepare for bed can determine how easily you’ll be able to fall asleep. Give yourself 30 minutes to wind down before you sleep and take advantage of whatever puts you in a state of calm such as soft music, light stretching, reading or meditation exercises.  

• Make sure your room is dark and at the right temperature.
  

Make sure your room is dark and at the right temperature. It’s best to have a window open so that you have good air flow.

• Turn off any blue lights
  

Turn off any blue lights and don’t give in to the temptation to look at your screens before you close your eyes. Light can hinder the production of melatonin and cell phones, tablets and laptops cause mental stimulation that is hard to shut off.  

• Be comfortable
  

Make sure your mattress is comfortable and you have the right amount of blankets for body warmth.

• Don’t toss and turn
  

It helps to have a healthy mental connection between being in bed and actually being asleep. For that reason, if after twenty minutes, you haven’t gotten to sleep, get up and stretch, read or do something else that is calming in low light before trying to fall asleep again.

• Protein
  

Have protein at night in combination with essential fatty acids (EFAs) to enable sufficient relaxation (protein is made up of amino acids including L-tryptophan which plays an important role in serotonin and melatonin synthesis). Protein may also stabilise blood sugars and prevent hypoglycaemia at night and EFAs are required structurally for neuronal membrane health as well as for production and regulation of prostaglandins that promote and suppress sleep

• Ensure that night-time meals are light and easily digestible
  

Ensure that night-time meals are light and easily digestible. If you’ve ever eaten a heavy meal near bedtime, you may have noticed that it can make it harder to fall asleep. It also might wake you up during the night.

• Avoid all stimulants
  

Avoid all stimulants especially in the hours before bedtime such as caffeine, alcohol, sugar and artificial sweeteners.

Exercise

Exercise is also very important for a good night’s sleep. Being physically active during the day can help expend excess energy which will make it easier for your body to relax in the evening. Exercise also reduces stress, boosts endorphins, increases blood flow which will all help to get a better night’s rest. Aim to do 30 minutes of exercise per day with a combination of more high intensity exercise, resistance training as well as stretching or yoga exercises which will also help to combat stress.

Top Natural Remedies 

If you’ve incorporated all the sleep hygiene tips into your routine and you’re still struggling to sleep, then it may be worth trying a natural sleep aid supplement. There are many herbal remedies that have been scientifically proven to be helpful in not only getting to sleep but staying asleep. Some of these include:

• Chamomile
  

Chamomile is a well-known herb that has been used for centuries to help one relax and put one to sleep. One review found that the herb acts as a mild sedative helping to calm the mind, reduce anxiety and ease insomnia.21 It is also a digestive herb which means it can help to calm any stomach upset which may also be preventing you from getting a good night’s rest. It can be taken in a variety of forms but is has been shown to be effective even as a tea.

• Lemon Balm
  

Lemon Balm is regarded highly for its ability to help with insomnia as well as reduce stress and anxiety. Clinical research shows that taking a standardised lemon balm extract twice daily for 15 days reduces insomnia by 42% in patients with sleep disorders.22 It helps to reduce sleep disturbance, sleep latency and daytime dysfunction compared to placebo. Other clinical research suggests that a single dose of lemon balm extract 600 mg increases calmness and alertness in healthy adults undergoing laboratory-induced psychological stress.23

• Passionflower
  

Passionflower is a very common herb used in sleep supplements as it not only works as a sedative by stimulating increased GABA production, it also has been shown to be equally as effective as some anti-anxiety medications. For example, one clinical study showed that taking passionflower extract 45 drops per day reduces symptoms of non-specific anxiety comparable to oxazepam.24 It’s a great herb to take as a tea before bed-time to improve sleep onset and quality.

• Valerian
  

Valerian is perhaps the most famous sleep herb of all. A 2006 meta-analysis shows that taking valerian significantly increases the chance of having improved sleep quality compared to a placebo group.25 Other research shows valerian extract 600mg daily for 3.5 months has similar effects to oxazepam 10mg for improving sleep quality, sleep duration and feelings of refreshment after sleeping.26

• Skullcap
  

Skullcap has traditionally been used for centuries as a nerve relaxant. Baicalin is the main bioactive constituent that exhibits considerable anxiolytic-like and antidepressant effects. In studies, it has shown a strong protective activity against neurotoxicity-mediated disorders by regulating different cell signalling pathways and by binding to GABA receptors.27 It also has strong antioxidant, anti-inflammatory and anti-excitotoxicity properties, making it a great natural sleep aid especially where there is hyperactivity of the brain.  

• Ashwagandha
  

Ashwagandha is known as an adaptogen, which are a class of herbs that assist with the stress response and energy. It is also the only adaptogen that can be taken at bedtime as it has been shown to improve sleep quality and reduce the time it takes to fall asleep. The constituent in Ashwagandha which is known to have a beneficial effect for sleep is called triethylene glycol (TEG). It has the ability to induce significant amounts of non-rapid eye movement sleep with little change in rapid eye movement sleep, making it a great herb to be used in insomnia therapy. Ashwagandha also works on sleep as it reduces stress. Clinical research shows that taking ashwagandha root extracts 240-600 mg daily for 60 days reduces perceived stress levels by 30% to 44% and decreases cortisol levels by 22% to 28% when compared with baseline in adults with chronic stress.28 These changes were also significant when compared with the changes seen for patients treated with placebo.

• Hops
  

Humulus lupulus, commonly known as Hops, is used as a sedative due to its calming, sleep inducing properties. It is also a spasmolytic and is used as a digestive aid which may also contribute to its use for insomnia. It has the ability to increase GABA activity and thereby inhibiting the central nervous system as well as being able to bind to melatonin and serotonin receptors that are involved in circadian rhythm and sleep regulation.29 These findings have been confirmed in a clinical trial where, in combination with valerian, sleep quality and sleep onset were improved.30

• St Johns Wort  
  

St Johns Wort has a long history of use as an herbal treatment for a variety of ailments but is perhaps most well known for its use in depression. In fact, in the past twenty years, it has become a mainstream alternative treatment for depression which brings with it a series of symptoms such as strong feelings of sadness and guilt, a loss of interest or pleasure and irregular sleeping patterns to name a few. Ample research including meta-analyses points to the efficacy of St Johns Wort in treating all forms of depression and its symptoms similarly to conventional antidepressants.31

Make Sleep a Priority 

Some would say that sleep deprivation is one of the greatest public health challenges in the 21st century in the developed world due to its having a catastrophic impact on our health, our life expectancy and our quality of life. Sleep is essential for life, and your diet and lifestyle can have a significant impact on how refreshing your sleep is. Eating the right foods, avoiding stimulants and creating lifestyle habits that encourage a good night’s rest will go a long way to improving your quality of life as a whole.  

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References

1 Krause, A. J., Simon, E. B., Mander, B. A., Greer, S. M., Saletin, J. M., Goldstein-Piekarski, A. N., & Walker, M. P. (2017). The sleep-deprived human brain. Nature reviews. Neuroscience, 18(7), 404–418. https://doi.org/10.1038/nrn.2017.55

2 Lloret, M. A., Cervera-Ferri, A., Nepomuceno, M., Monllor, P., Esteve, D., & Lloret, A. (2020). Is Sleep Disruption a Cause or Consequence of Alzheimer's Disease? Reviewing Its Possible Role as a Biomarker. International journal of molecular sciences, 21(3), 1168. https://doi.org/10.3390/ijms21031168

3 Knutson K. L. (2007). Impact of sleep and sleep loss on glucose homeostasis and appetite regulation. Sleep medicine clinics, 2(2), 187–197. https://doi.org/10.1016/j.jsmc.2007.03.004 

4 Gottlieb, D. J., Punjabi, N. M., Newman, A. B., Resnick, H. E., Redline, S., Baldwin, C. M., & Nieto, F. J. (2005). Association of sleep time with diabetes mellitus and impaired glucose tolerance. Archives of internal medicine, 165(8), 863–867. https://doi.org/10.1001/archinte.165.8.863

5 Taheri, S., Lin, L., Austin, D., Young, T., & Mignot, E. (2004). Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS medicine, 1(3), e62. https://doi.org/10.1371/journal.pmed.0010062

6 Hanlon, E. C., Tasali, E., Leproult, R., Stuhr, K. L., Doncheck, E., de Wit, H., Hillard, C. J., & Van Cauter, E. (2016). Sleep Restriction Enhances the Daily Rhythm of Circulating Levels of Endocannabinoid 2-Arachidonoylglycerol. Sleep, 39(3), 653–664. https://doi.org/10.5665/sleep.5546

7 Hamazaki, Y., Morikawa, Y., Nakamura, K., Sakurai, M., Miura, K., Ishizaki, M., Kido, T., Naruse, Y., Suwazono, Y., & Nakagawa, H. (2011). The effects of sleep duration on the incidence of cardiovascular events among middle-aged male workers in Japan. Scandinavian journal of work, environment & health, 37(5), 411–417. https://doi.org/10.5271/sjweh.3168

8 Cappuccio, F. P., Cooper, D., D'Elia, L., Strazzullo, P., & Miller, M. A. (2011). Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. European heart journal, 32(12), 1484–1492. https://doi.org/10.1093/eurheartj/ehr007

9 Tochikubo, O., Ikeda, A., Miyajima, E. & Ishii, M. (1996). Effects of Insufficient sleep on blood pressure monitored by a new multibiomedical recorder, Hypertension, 27(6):1318-24.

10 Leproult, R., & Van Cauter, E. (2011). Effect of 1 week of sleep restriction on testosterone levels in young healthy men. JAMA, 305(21), 2173–2174. https://doi.org/10.1001/jama.2011.710

11 Touzet, S., Rabilloud, M., Boehringer, H., Barranco, E., & Ecochard, R. (2002). Relationship between sleep and secretion of gonadotropin and ovarian hormones in women with normal cycles. Fertility and sterility, 77(4), 738–744. https://doi.org/10.1016/s0015-0282(01)03254-x

12 Walker, M. (2017). Why We Sleep. Penguin Books, pp. 180.

13 Cohen, S., Doyle, W. J., Alper, C. M., Janicki-Deverts, D., & Turner, R. B. (2009). Sleep habits and susceptibility to the common cold. Archives of internal medicine, 169(1), 62–67. https://doi.org/10.1001/archinternmed.2008.505

14 Irwin, M., McClintick, J., Costlow, C., Fortner, M., White, J., & Gillin, J. C. (1996). Partial night sleep deprivation reduces natural killer and cellular immune responses in humans. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 10(5), 643–653. https://doi.org/10.1096/fasebj.10.5.8621064

15 Mazzotti, D. R., Guindalini, C., Moraes, W. A., Andersen, M. L., Cendoroglo, M. S., Ramos, L. R., & Tufik, S. (2014). Human longevity is associated with regular sleep patterns, maintenance of slow wave sleep, and favorable lipid profile. Frontiers in aging neuroscience, 6, 134. https://doi.org/10.3389/fnagi.2014.00134

16 Moore R. Y. (2007). Suprachiasmatic nucleus in sleep-wake regulation. Sleep medicine, 8 Suppl 3, 27–33. https://doi.org/10.1016/j.sleep.2007.10.003

17 Watson, C. J., Baghdoyan, H. A., & Lydic, R. (2010). Neuropharmacology of Sleep and Wakefulness. Sleep medicine clinics, 5(4), 513–528. https://doi.org/10.1016/j.jsmc.2010.08.003

18 Yin, J., Jin, X., Shan, Z., Li, S., Huang, H., Li, P., Peng, X., Peng, Z., Yu, K., Bao, W., Yang, W., Chen, X., & Liu, L. (2017). Relationship of Sleep Duration With All-Cause Mortality and Cardiovascular Events: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. Journal of the American Heart Association, 6(9), e005947. https://doi.org/10.1161/JAHA.117.005947

19 St-Onge, M. P., Roberts, A., Shechter, A., & Choudhury, A. R. (2016). Fiber and Saturated Fat Are Associated with Sleep Arousals and Slow Wave Sleep. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 12(1), 19–24. https://doi.org/10.5664/jcsm.5384

20 Lin, H. H., Tsai, P. S., Fang, S. C., & Liu, J. F. (2011). Effect of kiwifruit consumption on sleep quality in adults with sleep problems. Asia Pacific journal of clinical nutrition, 20(2), 169–174.

21 Srivastava, J. K., Shankar, E., & Gupta, S. (2010). Chamomile: A herbal medicine of the past with bright future. Molecular medicine reports, 3(6), 895–901. https://doi.org/10.3892/mmr.2010.377

22 Cases, J., Ibarra, A., Feuillère, N., Roller, M., & Sukkar, S. G. (2011). Pilot trial of Melissa officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Mediterranean journal of nutrition and metabolism, 4(3), 211–218. https://doi.org/10.1007/s12349-010-0045-4

23 Kennedy, D. O., Little, W., & Scholey, A. B. (2004). Attenuation of laboratory-induced stress in humans after acute administration of Melissa officinalis (Lemon Balm). Psychosomatic medicine, 66(4), 607–613. https://doi.org/10.1097/01.psy.0000132877.72833.71

24 Akhondzadeh, S., Naghavi, H. R., Vazirian, M., Shayeganpour, A., Rashidi, H., & Khani, M. (2001). Passionflower in the treatment of generalized anxiety: a pilot double-blind randomized controlled trial with oxazepam. Journal of clinical pharmacy and therapeutics, 26(5), 363–367. https://doi.org/10.1046/j.1365-2710.2001.00367.x

25 Bent, S., Padula, A., Moore, D., Patterson, M., & Mehling, W. (2006). Valerian for sleep: a systematic review and meta-analysis. The American journal of medicine, 119(12), 1005–1012. https://doi.org/10.1016/j.amjmed.2006.02.026

26 Ziegler, G., Ploch, M., Miettinen-Baumann, A., & Collet, W. (2002). Efficacy and tolerability of valerian extract LI 156 compared with oxazepam in the treatment of non-organic insomnia--a randomized, double-blind, comparative clinical study. European journal of medical research, 7(11), 480–486.

27 Awad, R., Arnason, J. T. & Trudeau, V. (2003). Phytochemical and biological analysis of skullcap (Scutellaria lateriflora L.): A medicinal plant with anxiolytic properties. Phytomedicine, 10: 640-649.

28 Chandrasekhar, K., Kapoor, J., & Anishetty, S. (2012). A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian journal of psychological medicine, 34(3), 255–262. https://doi.org/10.4103/0253-7176.106022

29 Abourashed ,E.A., Koetter, U., & Brattström, A. (2004). In vitro binding experiments with a valerian, hops and their fixed combination extract (ze91019) to selected central nervous system receptors. Phytomedicine, 11(7–8):633–638

30 Morin, C. M., Koetter, U., Bastien, C., Ware, J. C., & Wooten, V. (2005). Valerian-hops combination and diphenhydramine for treating insomnia: a randomized placebo-controlled clinical trial. Sleep, 28(11), 1465–1471. https://doi.org/10.1093/sleep/28.11.1465

31 Klemow, K.M., Bartlow, A., Crawford, J., et al. (2011). Medical Attributes of St. John’s Wort (Hypericum perforatum) In: Benzie IFF, Wachtel-Galor S, editors. Herbal Medicine: Biomolecular and Clinical Aspects. 2nd edition. Boca Raton (FL): CRC Press/Taylor & Francis. Chapter 11. Available from: https://www.ncbi.nlm.nih.gov/books/NBK92750/

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