Proprietary formula of Valerian extract (root, 0.07%), White Willow Bark extract (15% salicin), Chamomile extract (flower, 4:1), and Melatonin

Research Summary

Preparations of Valerian root has been used worldwide to promote relaxation and restful sleep. Both animal and human studies have indicated valerian’s positive effects on sleep; while in vitro studies suggest that Valerian may work as the GABA receptor agonist.

Animal experiments indicate that chamomile extract can decrease sleep latency (Shinomya et al. 2005) and inhibit locomotor activity. As suggested by both in vitro and animal experiments, these effects can be attributed to the impact of the key constituents in Matricaria chamomilla extract on other than GABA(A)-benzodiazepine receptor neurotransmission systems (Viola H et al. 1995).

Exogenous melatonin reportedly increases sleepiness, decreases core temperature, and increases peripheral temperature. The research also suggests that melatonin may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age in humans, probably, by activating peripheral receptors or altering autonomic activity (Burgess et al. 2001; Geoffriau M et al. 1998).

Willow bark has been used known for its discomfort alleviation properties since the ancient times. Animal studies indicate that the active ingredients in the herb may have an impact on cyclooxygenase-mediated prostaglandin release as well as the herb may possess antioxidant and lipooxygenase-inhibiting effects (Fiebich B.L. & S. Chrubasik. 2004).

LunaSom PM is the dietary supplement to specifically combine these ingredients to promote restful sleep, calm away tensions of the everyday life, and alleviate minor discomforts.

History and Modern Research

Valerian

The root of valerian has been a popular calming and sleep-promoting agent for centuries. The earliest documented use of Valerian for insomnia is found in the writings of Galen in the second century A.D. The sedative properties of valerian became known in several European countries in the 18th century. Since then, the herb has been used to abate daytime excitement and sleep disturbances (Blumenthal 1998; Houghton P.J. 1998).

The substances (currently known) that may contribute to the valerian root (Valeriana officianalis L.) activity are terpenoid in nature: sesquiterpenes and iridoids. The most important valerian sesquiterpenes are valerenic acid and acetoxyvalerenic acids. Other ingredients that were isolated from the herb are alkaloids, furanofuran lignans, and free amino acids such as -aminobutyric acid (GABA), tyrosine, arginine, and glutamine (Bruneton 1999: 596-597; Hadley & Petry 2003).

Numerous small-scale studies conducted on Valerian and its constituents have shown that administration of the Valerian extract and/or its compounds resulted in an improvement in perceived sleep latency and wake time after sleep onset as was indicated from questionnaires, self-rating scales and night-time motor activity (Leathwood et al. 1982; Leathwood et al. 1985; Balderer & Borbely 1985; Lindahl & Lindwall 1989; Schulz et al. 1994; Donath et al. 2000; Poyares et al. 2002; Zeigler et al. 2002); reduction of nighttime awakening and increase in REM sleep (Herrera-Arellano et al 2001) and a reduction in physiological stress reactivity during stressful situations (Wheatley 2001; Cropley et al. 2002).

Chamomile

Chamomile was used by early Egyptian physicians for fevers and by ancient Greeks, Romans and Indians for headaches and disorders of the kidneys, liver, and bladder. Anglo-Saxons believed it was 1 of the 9 sacred herbs given to humans by god Woden. Chamomile is cultivated worldwide for use as a sedative, spasmolytic, anti-inflammatory, and vulnerary agent.

Chamomile, consisting of fresh or dried flower heads of Matricaria recutita L. (syn. Chamomilla recutita (L.) Rauschert), contains an acidic mucilage, coumarins, phenolic acids, and sesquiterpenoid lactones, the drug contains an essential oil (3-15 ml/kg) and flavonoids. It is also contains luteolin glucosides, quercetin glycosides, and isorhamnetin (Bruneton 1999: 520).

Melatonin

Melatonin, also known as N-acetyl-5-methoxytryptamine and N-[2-(5-Methoxy-1H-indol-3-yl)ethyl] acetamide is a solid, lipophilic, and hydrophobic substance. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. In this synthesis, L-tryptophan is first metabolized into 5-hydroxytryptophan and then into 5-hydroxytryptamine, also known as serotonin. 5-hydroxytryptamine is hydrolyzed into melatonin in two-step process in the pinealocytes of the pineal gland (PDR for Nutritional Supplements 2001).

Multiple studies conducted on melatonin have shown that administration of melatonin had a significant impact on sleep onset latency, sleep efficiency, and total sleep duration (MacFarlane et al. 1991; Zhdasnova et al. 1995; Peck et al. 2004; Brzezinski et al. 2005; Busceni et al. 2005).

Willow Bark

The analgesic and antipyretic properties of Willow bark have been known since the ancient Egyptian, Greek, Indian, and Roman civilizations. The first record of its use was found in the Ebers’ papyrus, which is said to be written over 3500 years ago. Recommendations for use of willow bark for alleviation of bone-joint discomfort are found in the writings of Hippocrates, Dioscorides, and Pliny the Elder (Vane J.R. 2000; Setty & Sigal, 2005).

White willow bark (Salix alba L.) is rich in phenolic compounds such as proanthocyanidin dimmers and trimers, flavonoids (104% flavanones), and glycosides of phenols and of phenolic acids (Bruneton 1999: 252-253.) Preliminary evidence suggests that administration of herbal extract of White Willow Bark containing salicin can be beneficial to people with bone-related discomfort (Chrubasik et al. 2001; Schmidt et al. 2001).

Safety

The Botanical Safety Handbook (American Herbal Products Association, 1997) offers a rating for Valerian officinalis L. as class 1 (herbs that can be safely consumed when used appropriately). The Commission E lists no contraindications or interactions of valerian with other drugs (Blumenthal 1998: 226-227). However, the WHO states that it should not be used during pregnancy or lactation (WHO 1999). The Commission E lists no known side effects. However, the WHO states that headaches, excitability, uneasiness, and insomnia have been associated with chronic use of valerian (WHO 1999). The American Herbal Pharmacopoeia also cautions that valerian can cause nervousness and heart palpitations in sensitive individuals and occasional headache and gastrointestinal distress (Upton et al. 1999).

According to Commission E monographs, there are no contraindications, interactions with other drugs, or side effects to Chamomile flower (Blumenthal 1998: 107). The Botanical Safety Handbook (American Herbal Products Association, 1997) offers a rating for Matricaria recutita L. as class 1 (herbs that can be safely consumed when used appropriately.

Melatonin is generally regarded as safe. Psychomotor disturbances, increased seizure risk, and blood clotting abnormalities have been reported in isolated cases. Pregnant women, people with elevated blood sugar, those on blood pressure lowering medications, as well as taking blood-thinning agents should consult their health care professional prior to use melatonin-containing supplements (Melatonin. Monograph. 2005).

The Botanical Safety Handbook (American Herbal Products Association, 1997) offers a rating for Salix alba L. as class 1 (herbs that can be safely consumed when used appropriately). “Because of white willow bark’s active constituents, interactions like those encountered with salicylates may arise. However, in reviewing the scientific literature available so far, there are no definite indications for this.” (Blumenthal 1998: 230). Although the anti-platelet effect of willow bark is less pronounced than that of aspirin, concomitant use of the herb with anti-coagulant/anti-platelet drugs theoretically might increase the risk of bleeding. People with compromised kidney function and those with aspirin hypersensitivity and asthma should consult their health care professional prior to use of products containing willow bark.

References

1. American Herbal Product Association. 1997. Botanical Safety Handbook. M. McGuffin, C. Hobbs, R. Upton, and A. Goldberg (eds) CRC Press: Boca Raton.

2. Balderer. G and A.A. Borbely. 1985. Effect of valerian on human sleep. Psychopharmacology. 87: 406-409.

3. Blumenthal, M. (ed.) 1998. The Complete German Commission E Monographs. Therapeutic Guide to Herbal Medicine. Integrative Medicine Communications: Boston.

4. Bruneton, Jean. 1999. Pharmacognosy. Phytochemistry of Medicinal Plants. 2nd edition. Lavoisier Publishing: Londres, Paris, New York.

5. Brzezinski, A et al. 2005. Effects of exogenous melatonin on sleep: A meta-analysis. Sleep Medicine Reviews. 9: 41-50.

6. Burgess H.J. et al. 2001. Effects of bright light and melatonin on sleep propensity, temperature, and cardiac activity at night. J Appl Physiol. 91: 1214-1222.

7. Buscerni N et al. 2005. The efficacy and safety of exogenous melatonin for primary sleep disorders. A meta-analysis. J Gen Intern Med. 20: 1151-1158.

8. Chrubasik S et al. 2001. Treatment of low back pain with a herbal or synthetic anti-rheumatic: A randomized controlled study. Willow bark extract for low back pain. Rheumatology. 40: 1388-1393.

9. Cropley M et al. 2002. Effect of kava and valerian on human physiological and psychological responses to mental stress assessed under laboratory conditions. Phytotherapy Research. 16: 23-27.

10. Donath F et al. 2000. Critical evaluation of the effect of valerian extract on sleep structure and sleep quality. Pharmacopsychiatry. 33: 47-53.

11. Fiebich B.L. & S. Chrubasik. 2004. Effects of an ethanolic Salix extract on the release of selected inflammatory mediators in vitro. 11: 136-138.

12. Geoffriau M et al. 1998. The physiology and pharmacology of melatonin in humans. Hormone Research. 49: 136-141.

13. Hadley S. and J.J. Petry. 2003. Valerian. American Family Physician. 67(8): 1755-1758.

14. Hendler SS et al (eds.) 2001. PDR for Nutritional Supplements. Thomson Healthcare: Montvale.

15. Houghton P.J. 1998. The scientific basis for the reputed activity of valerian. J. Pharm Pharmacol. 51: 505-512.

16. Leathwood P.D. et al. 1982. Aqueous extract of valerian root (Valeriana officinalis L.) improves sleep quality in man. Pharmacology Biochemistry & Behavior. 17: 65-71.

17. Leathwood P.D. & f. Chauffard. 1985. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Medica.

18. Lindahl O. & L. Lindwall. 1989. Double-blind study of a valerian preparation. Pharmacology Biochemistry & Behavior. 32: 1065-1066.

19. MacFarlane J.G. et al. 1991. The effects of exogenous melatonin on the total sleep time and daytime alertness of chronic insomniacs: A preliminary study. Biol Psychiatry. 30: 371-376.

20. No Author. 2005. Melatonin. Monograph. Alternative Medicine Review. 10(4): 326-336.

21. Peck J.S. et al. 2004. Cognitive effects of exogenous melatonin administration in elderly persons. Am J Geriatr Psychiatry. 12: 432-436.

22. Poyares D.R et al. 2002. Can valerian improve the sleep of insomniacs alter benzodiazepine withdrawal? Progress in Neuro-Psychopharmacology & Biological Psychiatry. 26: 539-545.

23. Schmid B et al. 2001. Efficacy and tolerability of a standardized willow bark extract in patients with osteoarthritis: Randomized placebo-controlled, double blind clinical trial. Phytotherapy research. 15: 344-350.

24. Schulz H et al. 1994. The effect of valerian extract on sleep polygraphy in poor sleepers: A pilot study. Pharmacopsychiatry. 27: 147-151.

25. Setty A.R. & L.H. Sigal. 2005. Herbal medications commonly used in the practice of rheumatology: Mechanisms of action, efficacy, and side effects. Seminars in Arthritis and Rheumatism. 34: 773-784.

26. Vane J.R. 2000. The Fight Against Rheumatism: from Willow Bark to COX-1 Sparing Drugs. Journal of Physiology and Pharmacology. 51(4): 573-586.

27. Viola H et al. 1995. Apigenin, a component of Matricaria recutita flowers is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med. 61: 213-216.

28. Wheatley D. 2001. Stress-induced insomnia treated with kava and valerian: Singly and in combination. Human Psychopharmacology Clin Exp. 16: 353-356.

29. Zhdanova IV et al. 1995. Sleep-inducing effects of low doses of melatonin ingested in the evening. Clinical Pharmacol Ther. 57: 552-558.