Supplements for Sleep and Stress

(originally published 10/21/2008)

Perhaps one of the best-known supplements in the category is melatonin, which is often taken to promote a healthy sleep cycle. “Your natural cycle of sleeping and waking hours [the circadian rhythm] is controlled by your melatonin levels,” Amanda Steele, co-founder and CEO, Dreamerz, noted. “Typically, melatonin levels rise in the evening as a cue for sleep, remain high for most of the night and decline as dawn nears. Natural melatonin levels do decline gradually as you age; some older adults produce very small amounts or none at all.”

Accumulating evidence suggests melatonin supplementation may regulate the circadian clock and be a beneficial in the treatment of certain insomnias, according to a 2004 study review from University, Ill.6 Unfortunately, the review also found the therapeutic potential of melatonin has been difficult to realize in clinical trials, possibly owing to non-specific actions of the agent and its unfavorable pharmacokinetic properties when administered orally.

However, the amount of melatonin being taken might inadvertently skew study results, a 2005 study review from HadassahMedicalCenter, Jerusalem stated.7 Only a small dose of melatonin is necessary for a restful effect; typical melatonin pills contain many times the effective amount. According to the researchers, when the melatonin receptors in the brain are exposed to too much of the hormone, they become unresponsive, leading many to mistakenly believe melatonin supplementation does not work. Conversely, as Ken Halvorsrude, president of Doctor’s Best, pointed out, the dosage might be inconsequential; some individuals simply won’t respond to melatonin supplementation, for whatever reason.

Tryptic bovine alphaS1-casein hydrolysate (milk protein), branded as ingredient Lactium® by Pharmachem Laboratories Inc., aids in sleep and relaxation. It was discovered by examining the science behind the old wives’ cure of drinking a glass of warm milk before bed to induce sleepiness. “Observing the calm and relaxed state of babies after drinking milk, scientists sought to identify a relationship between milk consumption and any resulting calming effect. Scientists were able to isolate this relaxation protein from dairy milk and concentrate it,” said Steele.

Scientists from National Agronomique Paris-Grignon, Paris, researched the putative effects of tryptic bovine alphaS1-casein hydrolysate on stress-induced sleep disorders.8 Rats were subjected to chronic stress in the form of environmental disturbances, while receiving an oral administration of the alphaS1-casein hydrolysate (CH). Chronic stress significantly reduced sleep duration in control rats during the first two days of the stress period, but stress-induced sleep disturbance was prevented in CH-treated rats. CH administration allowed the maintenance of slow wave sleep (deep sleep) duration and even a slight increase in paradoxical sleep (REM sleep) duration in treated rats.

A similar study examined the effects of CH on females with stress-related symptoms.9 Sixty-three female volunteers, suffering from at least one stress-related disorder such as anxiety, sleep problems and general fatigue, randomly received either CH tablets or a placebo for 30 days. Results showed the 30-day treatment by CH reduced their symptoms, particularly in digestion, cardiovascular, intellectual, emotional and social problems.

Another natural calming agent, gamma-aminobutyric acid (GABA), “helps prevent neurotransmitters from overfiring,” Jayson Kroner, C.S.N., editor for NOW Foods Health and Fitness, said. “It appears to be most appealing to those who struggle with stress-related sleep disturbances.” This amino acid, which is produced in the brain, acts as a neurotransmitter, suppressing nerve impulses related to stress and anxiety. Normally, the brain produces sufficient amounts of GABA, but for those with insufficient levels, they may experience a range of health problems, including irritability, depression and insomnia. In fact, a study from University of Bergen, Norway, found evidence that suggests depression may be modulated by GABA.10 Results showed  animals exposed to chronic mild stress (CMS) had lower GABA levels compared to controls. In addition, after CMS there was a lack of 5-HT (the main excitatory receptor for serotonin) stage-dependency, which the researchers believe may represent a link between depression-like behavior and sleep abnormalities.

Two human studies on the effect of orally administrated GABA on relaxation and immunity during stress were conducted by Pharma Foods International Co. Ltd., Kyoto, Japan.11 The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after three tests on each volunteer as follows: intake only water, GABA or L-theanine. After 60 minutes of administration, GABA significantly increased alpha waves and decreased beta waves compared to water or L-theanine, showing GABA not only induces relaxation, but also reduces anxiety.

The second study was conducted to see the role of the relaxant and anti-anxiety effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into two groups, placebo and GABA. All subjects crossed a suspended bridge as a stressful stimulus, and immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. It was concluded GABA could work effectively as a natural relaxant and its effects could be seen within one hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.

L-theanine, another unique amino acid, has been recently been receiving increased attention and is the star of many studies, according to Beeta Little, director of product development and technical services, Bluebonnet Nutrition Corp. “Over time, L-theanine allows for increased focus and concentration, improving the ability to remember and learn, in conjunction with promoting a sense of relaxation and well being without interfering with cognitive abilities,” she said.

Indeed, researchers from Unilever Food and Health Research Institute, The Netherlands, discovered tea contains L-theanine, and hypothesized it may modulate aspects of brain function in humans.12 Evidence from EEG studies showed L-theanine significantly increased activity in the alpha frequency band, which indicates it relaxes the mind without inducing drowsiness, even at doses as small as 20 mg, the amount typically found in a cup of black tea. A similar study examined the possibility that L-theanine may influence psychological and physiological states under stress.13 The study examined these possible effects in a laboratory setting using a mental arithmetic task as an acute stressor. Twelve participants underwent four separate trials: one in which they took L-theanine at the start of an experimental procedure, one in which they took L-theanine midway, and two control trials in which they either took a placebo or nothing. The results showed that L-theanine intake resulted in a reduction in the heart rate (HR) and s-IgA responses to an acute stress task relative to the placebo control condition.

Surprisingly, sleeplessness and stress can be caused simply by poor diet. “There are certainly a number of factors which can cause stress and lack of sleep, but one fundamental factor in both stress and insomnia is the mineral magnesium (Mg),” said Ken Whitman, president, Peter Gillham’s Natural Valley. “Everybody needs nutritional magnesium every day; at least 80 percent of us don’t get our minimum daily requirement of magnesium from our diets.” A study on 14 full-term newborns revealed sleep behavior was correlated to the serum Mg level.14 After administering an injection of serum Mg, quiet sleep increased, whereas active sleep decreased.
Of course, dietary supplements are only the tip of the iceberg; there are lifestyle changes that need to be made if customers want to be free of stress. Retailers should encourage their customers to have a healthy, active lifestyle. “Inner peace is vitally important so that one can more fully enjoy life and live in the moment as much as possible,” advised James Donovan, president and CEO, NuTru. Daily exercise, a nutritious diet and adequate sleep are all good habits that must be practiced to ensure a balanced life.


1. Turek FW, et al. “Melatonin, sleep, and circadian rhythms: rationale for development of specific melatonin agonists.” Sleep Med. 2004 Nov;5(6):523-32.

2. Brzezinski A, et al. “Effects of exogenous melatonin on sleep: a meta-analysis.” Sleep Med Rev. 2005 Feb;9(1):41-50.

3. Guesdon B, et al. “A tryptic hydrolysate from bovine milk alphaS1-casein improves sleep in rats subjected to chronic mild stress.” Peptides. 2006 Jun;27(6):1476-82. Epub 2005 Nov 21.

4. Kim JH, et al. “Efficacy of alphas1-casein hydrolysate on stress-related symptoms in women.” Eur J Clin Nutr. 2007 Apr;61(4):536-41. Epub 2006 Nov 29.
5. Grønli J, et al. “Extracellular levels of serotonin and GABA in the hippocampus after chronic mild stress in rats. A microdialysis study in an animal model of depression.” Behav Brain Res. 2007 Jul 19;181(1):42-51. Epub 2007 Mar 19.

6. Abdou AM, “Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans.” Biofactors. 2006;26(3):201-8.

7. Nobre AC, et al. “L-theanine, a natural constituent in tea, and its effect on mental state.” Asia Pac J Clin Nutr. 2008;17 Suppl 1:167-8.
8. Kimura K, et al. “L-Theanine reduces psychological and physiological stress responses.” Biol Psychol. 2007 Jan;74(1):39-45. Epub 2006 Aug 22.

9. Dralle D, et al. “Serum magnesium level and sleep behavior of newborn infants.” Eur J Pediatr. 1980 Sep;134(3):239-43.

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