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Achieving Restorative Sleep

November 2016

By Brian Cortez

If you’re having trouble falling asleep, you’re not alone. An estimated 50 to 70 million American adults suffer from chronic sleep deprivation—a problem that only worsens with advancing age.1-3

The situation is so significant that the Institute of Medicine referred to insufficient sleep as “an unmet public health problem.”1 That was a decade ago. With current estimates claiming that half the US population will suffer from a sleep disorder during their lifetime,4 the situation isn’t much better today.

Research shows that insufficient sleep increases the risk for numerous deadly conditions—such as heart attack, stroke, diabetes, and hypertension—and can even lead to shorter lifespans.1,2,5

There is a high demand for drugs that provide relief. But while prescription sleep aids can work for a while, they come with a long list of side effects that impact quality of life—and many are highly addictive.6 Adding to the list of concerns are the findings of a recent study on the increased risk of premature mortality associated with use of these drugs.7

There are natural compounds that have been shown to help enhance sleep and alleviate the anxiety that can be an underlying cause.

Causes and Impact of Poor Sleep

Poor sleep quality has a far greater impact on our bodies than simply making us feel fatigued. It can affect endurance,8 contribute to weight gain,9 and lead to an increase in fine lines and wrinkles.10 Sleep disorders also have profound physiological consequences that contribute to long-term health risks, and even to shorter lifespans.

And sleep deprivation has been associated with accelerated aging. This was seen in a study showing that middle-aged men that sleep 5 hours or less had on average 6% shorter telomeres compared to those sleeping more than 7 hours.11 Telomeres are the “caps” on chromosomes that gradually shorten with time, and may represent a kind of “fuse” that indicates biological aging.

Stress, anxiety, and depression are common symptoms present in individuals experiencing chronic insomnia, because they negatively affect circadian rhythms and modify both sleep duration and sleep quality.12-17 Virtually everyone who suffers from sleep disorders reports increased stress and anxiety in their lives.18,19 Stress can set in motion a host of biochemical changes that culminate in a vicious cycle which leads to poor sleep, which leads to greater stress.20

Because of the tremendous impact stress has on sleep, any remedy for poor sleep should include components that also help to lower anxiety and relieve stress. There are non-drug approaches that have been found to promote sleep, while helping alleviate anxiety and stress. Let’s examine each compound individually.

Bioactive Milk Peptides

Nutrients found in milk called bioactive milk peptides (chains of amino acids) have been found to enhance sleep quality, shorten the time to get to sleep, and reduce daytime dysfunction.21 Importantly, they have also been shown to simultaneously produce a calming, sedative effect that helps combat anxiety. Researchers discovered that bioactive milk peptides activate brain cell receptors for neurotransmitters that reduce anxiety, such as GABA, serotonin, and dopamine.22,23

The ability to activate GABA receptors in the brain is one reason the anti-anxiety drugs in the benzodiazepine class (think Valium, Ativan, and others) are so effective.22 The advantage of milk peptides is that unlike benzodiazepine drugs, which can become habit forming, bioactive milk peptides induce relaxation and sleep without the side effects.24 Animal studies show that, while bioactive milk peptides produce the same anti-anxiety effects as Valium, they don’t produce the “disinhibition” that can lead to risk-taking behavior associated with such drugs.24

These encouraging results have been seen in human studies as well. For example, a group of women experiencing stress-related symptoms such as anxiety, sleep problems, and general fatigue were given bioactive milk peptides (150 mg a day) or a placebo.25 After 30 days, the supplemented women experienced significant improvements compared to the placebo in symptoms related to digestion (65.6% improvement), cardiovascular function (48.9% improvement), cognitive function (62.5% improvement), and social difficulty (40.2% improvement).

In addition to improving sleep and reducing stress, bioactive milk peptides reduce many of the underlying biomarkers associated with the stress response, including elevated blood pressure, heart rate, and cortisol.26,27

Ashwagandha

Ashwagandha  

Anxiety is a common cause of insomnia, and insomnia can lead to further anxiety. Ashwagandha (Withania somnifera), a medicinal herb with long-standing, widespread use in ancient medical systems, can play an important role in breaking up this vicious cycle.

Ashwagandha is an adaptogen, a compound that induces physiological balance in the body and reduces the impacts of stress. Its uses have included targets such as cancer, infection, immunomodulation, and neurodegenerative disorders.28,29 Studies also show that it has a beneficial impact on anxiety, stress, and insomnia.29-32 In fact, “somnifera” from its scientific name in Latin means “sleep-inducer.”33

Ashwagandha has numerous constituents that are showing anti-anxiety properties.28,29 In a human study of adults with a history of chronic stress, taking 300 mg of ashwagandha twice daily for 60 days led to a significant reduction in scores on stress-assessment scales. Impressively, those taking ashwagandha also had a highly significant reduction in blood levels of the stress hormone cortisol during the treatment period.32

In addition to combating chronic stress itself, ashwagandha combats some of its side effects. In a study of people facing chronic stress, supplementation with ashwagandha led to significant improvements in perceived stress, food cravings, and happiness. The subjects also experienced significant reductions in serum cortisol, body weight, and body mass index.30 These findings are especially important in light of the known weight-gain effects of stress and anxiety—particularly in those who use food to “self-medicate.”

As an added benefit, animal studies show that ashwagandha protects the brain from some of the harmful behavioral and biochemical effects of sleep deprivation, such as impaired locomotor activity, and impaired learning and memory.34-36

A key reason why ashwagandha has such a powerful impact on stress is because it activates nerve cell receptors for the calming neurotransmitter GABA.31 These are the same receptors that are the target for the benzodiazepine drugs, which are used to treat anxiety and sleep problems.

As a result, numerous animal studies have suggested that extracts from ashwagandha have anxiety-reducing effects comparable to those produced by such common prescription drugs as diazepam (Valium) and lorazepam (Ativan). They also have antidepressant effects comparable to those produced by imipramine (Tofranil) and fluoxetine (Prozac).37-41

By combating anxiety, stress, and even depression, ashwagandha addresses some of the primary causes of chronic insomnia.

What You Need to Know
SIDEBAR IMAGE ALT TEXT

Restoring Youthful Sleep

  • Chronic poor sleep affects more than 70 million Americans.
  • Stress is both a cause and a consequence of poor sleep, and is a major long-term health threat.
  • Mainstream medicine’s anti-stress and sleep-inducing drugs are effective but carry an appalling array of side effects.
  • The natural substances melatonin, bioactive milk peptides, and ashwagandha extracts all contribute in different ways to enhancing sleep and relieving stress.
  • Together, these nutrients work to normalize disrupted day/night cycles, relieve anxiety, and help our bodies cope with stress.
  • Those with sleep difficulties should add these soothing, anxiety-relieving, and sleep-promoting nutrients to their bedtime regimens.

Individual Responses to Melatonin

Life Extension® was the first to introduce melatonin back in 1992. While it has helped numerous people improve their overall sleep, its efficacy varies significantly based on individual variability.

Melatonin is produced by the pineal gland in response to darkness and it helps control the body’s sleep/wake cycles.42

Melatonin levels fall with age, which results in impaired sleep and also contributes to some of the consequences associated with disordered sleep, such as accelerated cognitive decline, cardiovascular disease, and metabolic disorders.43 Many of these effects are now thought to be related to melatonin’s impact on specific brain cells and regions of the brain involved in controlling our day/night cycles.44 Some chronic conditions, such as elevated blood sugar, can suppress normal melatonin production, perhaps accounting for poor sleep in diabetics.45

Replacing or boosting deficient melatonin has been shown to help normalize sleep/wake patterns and enhance good sleep.44,46 Studies show that raising melatonin levels can counteract the impaired activity/rest cycles common in older animals.47 And a human study has now shown that raising melatonin levels can improve sleep patterns, quality, and duration.48

Melatonin and Prescription Drugs

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There’s no doubt that melatonin is effective in helping otherwise healthy people fall asleep, sleep better, and awake refreshed.49,50 But the real test of melatonin’s sleep-improving properties is to determine its effectiveness in people who have chronic sleep-impairing conditions, or in those taking drugs that impair sleep. Melatonin has passed that test.

For example, drugs known as beta blockers are used for cardiovascular disease by more than 22 million people in the US. One of the problems with these drugs is that they suppress natural nighttime melatonin secretion, which produces the common side effect of insomnia.51 Researchers decided to put supplemental melatonin to the test in this challenging group of subjects.

For the study, middle-aged men and women taking beta blockers received either 2.5 mg of melatonin or a placebo nightly for three weeks. Researchers found that the supplemented subjects had significantly greater total sleep time (+36 minutes), a shorter time to fall asleep (-14 minutes), and they increased their sleep efficiency by 7.6%, compared with placebo recipients.51

Similarly, people who have survived cancer or other potentially fatal disorders often have sleep disturbances that last for years. Melatonin has been found to be useful in this group of people as well. In a study of postmenopausal breast cancer survivors, 52% reported poor sleep in the month before the study. But those taking 3 mg of melatonin daily had significant improvements in overall sleep quality and daytime dysfunction, compared with placebo recipients.52

Melatonin is also beneficial in postmenopausal women, a group known for suffering from sleep problems. A study showed that a daily 5 mg dose of melatonin significantly improved sleep quality in healthy menopausal women, and produced significant reductions in body weight, which is an important contributor not only to insomnia, but to other health risks as well.53

For many people who rely on anti-anxiety medication such as Valium or Xanax to fall asleep, it is important to note that the use of these medications can suppress melatonin levels.54 According to one study, a single dose of alprazolam (Xanax) dramatically suppressed the body’s natural nocturnal melatonin rise, thereby making it more difficult to achieve natural sleep and making individuals more dependent on the medication for sleep.55

Recently, scientists have begun studying the use of melatonin as a way to reduce dependence on benzodiazepine drugs by people suffering from insomnia.56 This points up the importance of avoiding the use of commonly available, highly addictive sleep medications in favor of melatonin for preserving our natural sleep cycles.

Summary

Summary  

Stress leads to insomnia, and poor sleep induces yet more stress in a vicious circle of misery. Sleep problems worsen as we age, are exacerbated by many chronic and acute diseases, and raise our risk for long-term serious illness. There’s even evidence that poor sleep has an effect on our chromosomal telomeres, shortening them (and thus our lives) prematurely.

Prescription and over-the-counter sleep aids can be effective, but the majority of them have side effects, including the potential for dependence and tolerance (where they stop working).

Fortunately, long-revered natural products continue to demonstrate the ability to enhance sleep and alleviate stress, while also protecting against the harmful effects of stress and sleep deprivation.

Melatonin helps reset our sleep-wake cycles and promotes better, more effective sleep. Bioactive milk peptides and ashwagandha both help relieve the stress that can impair sleep, and they also contribute directly to sleep quality and quantity.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Institute of Medicine Committee on Sleep M, Research. The National Academies Collection: Reports funded by National Institutes of Health. In: Colten HR, Altevogt BM, eds. Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem. Washington (DC): National Academies Press (US); National Academy of Sciences.; 2006.
  2. Cirelli C. Brain plasticity, sleep and aging. Gerontology. 2012;58(5):441-5.
  3. Robertson M, Keene AC. Molecular mechanisms of age-related sleep loss in the fruit fly - a mini-review. Gerontology. 2013;59(4):334-9.
  4. Yurcheshen M, Seehuus M, Pigeon W. Updates on Nutraceutical Sleep Therapeutics and Investigational Research. Evid Based Complement Alternat Med. 2015;2015:105256.
  5. The effects of sleep deprivation on sleepiness, performance, stress and immune system. Glas Srp Akad Nauka Med. 2009(50):111-23.
  6. Pagel JF, Parnes BL. Medications for the Treatment of Sleep Disorders: An Overview. Prim Care Companion J Clin Psychiatry. 2001;3(3):118-25.
  7. Weich S, Pearce HL, Croft P, et al. Effect of anxiolytic and hypnotic drug prescriptions on mortality hazards: retrospective cohort study. BMJ. 2014;348.
  8. Oliver SJ, Costa RJ, Laing SJ, et al. One night of sleep deprivation decreases treadmill endurance performance. Eur J Appl Physiol. 2009;107(2):155-61.
  9. Spivey A. Lose sleep, gain weight: another piece of the obesity puzzle. Environ Health Perspect. 2010;118(1):A28-33.
  10. Sundelin T, Lekander M, Kecklund G, et al. Cues of fatigue: effects of sleep deprivation on facial appearance. Sleep. 2013;36(9):1355-60.
  11. Jackowska M, Hamer M, Carvalho LA, et al. Short sleep duration is associated with shorter telomere length in healthy men: findings from the Whitehall II cohort study. PLoS One. 2012;7(10):e47292.
  12. Perlis ML, Giles DE, Mendelson WB, et al. Psychophysiological insomnia: the behavioural model and a neurocognitive perspective. J Sleep Res. 1997;6(3):179-88.
  13. Sukegawa T, Itoga M, Seno H, et al. Sleep disturbances and depression in the elderly in Japan. Psychiatry Clin Neurosci. 2003;57(3):265-70.
  14. Hall M, Buysse DJ, Nowell PD, et al. Symptoms of stress and depression as correlates of sleep in primary insomnia. Psychosom Med. 2000;62(2):227-30.
  15. de Saint Hilaire Z, Straub J, Pelissolo A. Temperament and character in primary insomnia. Eur Psychiatry. 2005;20(2):188-92.
  16. Vollrath M, Wicki W, Angst J. The Zurich study. VIII. Insomnia: association with depression, anxiety, somatic syndromes, and course of insomnia. Eur Arch Psychiatry Neurol Sci. 1989;239(2):113-24.
  17. Bonnet MH, Arand DL. Hyperarousal and insomnia. Sleep Med Rev. 1997;1(2):97-108.
  18. Boland EM, Ross RJ. Recent Advances in the Study of Sleep in the Anxiety Disorders, Obsessive-Compulsive Disorder, and Posttraumatic Stress Disorder. Psychiatr Clin North Am. 2015;38(4):761-76.
  19. McEwen BS, Karatsoreos IN. Sleep Deprivation and Circadian Disruption: Stress, Allostasis, and Allostatic Load. Sleep Med Clin. 2015;10(1):1-10.
  20. Sanford LD, Suchecki D, Meerlo P. Stress, arousal, and sleep. Curr Top Behav Neurosci. 2015;25:379-410.
  21. de Saint-Hilaire Z, Messaoudi M, Desor D, et al. Effects of a bovine alpha S1-Casein tryptic hydrolysate (CTH) on sleep disorder in Japanese general population. Open Sleep Journal. 2009;2:26-32.
  22. Miclo L, Perrin E, Driou A, et al. Characterization of alpha-casozepine, a tryptic peptide from bovine alpha(s1)-casein with benzodiazepine-like activity. Faseb j. 2001;15(10):1780-2.
  23. Mizushige T, Sawashi Y, Yamada A, et al. Characterization of Tyr-Leu-Gly, a novel anxiolytic-like peptide released from bovine alphaS-casein. Faseb j. 2013;27(7):2911-7.
  24. Messaoudi M, Lalonde R, Schroeder H, et al. Anxiolytic-like effects and safety profile of a tryptic hydrolysate from bovine alpha s1-casein in rats. Fundam Clin Pharmacol. 2009;23(3):323-30.
  25. Kim JH, Desor D, Kim YT, et al. Efficacy of alphas1-casein hydrolysate on stress-related symptoms in women. Eur J Clin Nutr. 2007;61(4):536-41.
  26. Messaoudi M, Lefranc-Millot C, Desor D, et al. Effects of a tryptic hydrolysate from bovine milk alphaS1-casein on hemodynamic responses in healthy human volunteers facing successive mental and physical stress situations. Eur J Nutr. 2005;44(2):128-32.
  27. Cicero AF, Rosticci M, Gerocarni B, et al. Lactotripeptides effect on office and 24-h ambulatory blood pressure, blood pressure stress response, pulse wave velocity and cardiac output in patients with high-normal blood pressure or first-degree hypertension: a randomized double-blind clinical trial. Hypertens Res. 2011;34(9):1035-40.
  28. Singh N, Bhalla M, de Jager P, et al. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-13.
  29. Dar PA, Singh LR, Kamal MA, et al. Unique Medicinal Properties of Withania somnifera: Phytochemical Constituents and Protein Component. Curr Pharm Des. 2016;22(5):535-40.
  30. Choudhary D, Bhattacharyya S, Joshi K. Body Weight Management in Adults Under Chronic Stress Through Treatment With Ashwagandha Root Extract: A Double-Blind, Randomized, Placebo-Controlled Trial. J Evid Based Complementary Altern Med. 2016.
  31. Candelario M, Cuellar E, Reyes-Ruiz JM, et al. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABArho receptors. J Ethnopharmacol. 2015;171:264-72.
  32. Chandrasekhar K, Kapoor J, Anishetty S. 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 J Psychol Med. 2012;34(3):255-62.
  33. Agarwal NK, Agarwal SK. Ayurvedic Naturoceuticals: Evidence Based Data and Clinical Implications. Part I. Medical Science. 2016;20(77):5-9.
  34. Kumar A, Kalonia H. Protective effect of Withania somnifera Dunal on the behavioral and biochemical alterations in sleep-disturbed mice (Grid over water suspended method). Indian J Exp Biol. 2007;45(6):524-8.
  35. Kumar A, Kalonia H. Effect of Withania somnifera on Sleep-Wake Cycle in Sleep-Disturbed Rats: Possible GABAergic Mechanism. Indian J Pharm Sci. 2008;70(6):806-10.
  36. Manchanda S, Mishra R, Singh R, et al. Aqueous Leaf Extract of Withania somnifera as a Potential Neuroprotective Agent in Sleep-deprived Rats: a Mechanistic Study. Mol Neurobiol. 2016.
  37. Bhattacharya SK, Bhattacharya A, Sairam K, et al. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000;7(6):463-9.
  38. Gupta GL, Rana AC. Protective effect of Withania somnifera dunal root extract against protracted social isolation induced behavior in rats. Indian J Physiol Pharmacol. 2007;51(4):345-53.
  39. Gupta GL, Rana AC. Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. Indian J Exp Biol. 2008;46(6):470-5.
  40. Kulkarni SK, Singh K, Bishnoi M. Comparative behavioural profile of newer antianxiety drugs on different mazes. Indian J Exp Biol. 2008;46(9):633-8.
  41. Kaurav BP, Wanjari MM, Chandekar A, et al. Influence of Withania somnifera on obsessive compulsive disorder in mice. Asian Pac J Trop Med. 2012;5(5):380-4.
  42. Germain A, Kupfer DJ. Circadian rhythm disturbances in depression. Hum Psychopharmacol. 2008;23(7):571-85.
  43. Hardeland R. Melatonin in aging and disease -multiple consequences of reduced secretion, options and limits of treatment. Aging Dis. 2012;3(2):194-225.
  44. Hablitz LM, Molzof HE, Abrahamsson KE, et al. GIRK Channels Mediate the Nonphotic Effects of Exogenous Melatonin. J Neurosci. 2015;35(45):14957-65.
  45. Amaral FG, Turati AO, Barone M, et al. Melatonin synthesis impairment as a new deleterious outcome of diabetes-derived hyperglycemia. J Pineal Res. 2014;57(1):67-79.
  46. John TM, Brown MC, Brown GM. An oral melatonin replacement regimen that re-establishes the normal circadian levels of urinary 6-sulphatoxymelatonin in functionally pinealectomized rats. J Pineal Res. 1992;13(4):145-50.
  47. Delgado J, Terron MP, Garrido M, et al. Diets enriched with a Jerte Valley cherry-based nutraceutical product reinforce nocturnal behaviour in young and old animals of nocturnal (Rattus norvegicus) and diurnal (Streptopelia risoria) chronotypes. J Anim Physiol Anim Nutr (Berl). 2013;97(1):137-45.
  48. Howatson G, Bell PG, Tallent J, et al. Effect of tart cherry juice (Prunus cerasus) on melatonin levels and enhanced sleep quality. Eur J Nutr. 2012;51(8):909-16.
  49. Nagtegaal JE, Kerkhof GA, Smits MG, et al. Delayed sleep phase syndrome: A placebo-controlled cross-over study on the effects of melatonin administered five hours before the individual dim light melatonin onset. J Sleep Res. 1998;7(2):135-43.
  50. Zisapel N. Drugs for insomnia. Expert Opin Emerg Drugs. 2012;17(3):299-317.
  51. Scheer FA, Morris CJ, Garcia JI, et al. Repeated melatonin supplementation improves sleep in hypertensive patients treated with beta-blockers: a randomized controlled trial. Sleep. 2012;35(10):1395-402.
  52. Chen WY, Giobbie-Hurder A, Gantman K, et al. A randomized, placebo-controlled trial of melatonin on breast cancer survivors: impact on sleep, mood, and hot flashes. Breast Cancer Res Treat. 2014;145(2):381-8.
  53. Walecka-Kapica E, Klupinska G, Chojnacki J, et al. The effect of melatonin supplementation on the quality of sleep and weight status in postmenopausal women. Prz Menopauzalny. 2014;13(6):334-8.
  54. Atsmon J, Oaknin S, Laudon M, et al. Reciprocal effects of chronic diazepam and melatonin on brain melatonin and benzodiazepine binding sites. J Pineal Res. 1996;20(2):65-71.
  55. McIntyre IM, Burrows GD, Norman TR. Suppression of plasma melatonin by a single dose of the benzodiazepine alprazolam in humans. Biol Psychiatry. 1988;24(1):108-12.
  56. Cardinali DP, Golombek DA, Rosenstein RE, et al. Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse. Pharmacol Res. 2016;109:12-23.