Scientific Research & Evidence




Calcium

Brain Calcium Controls How Long We Sleep
We know calcium is good for our bones, but it might also be the key to a good night sleep. Researchers at the RIKEN Quantitative Biology Center (QBiC) and the University of Tokyo in Japan have unveiled a new theory for how sleep works. Published in the journal Neuron, the work shows how slow-wave sleep depends on the activity of calcium inside neurons.
https://www.eurekalert.org/pub_releases/2016-03/r-bcc031416.php

Diet and Sleep Physiology: Public Health and Clinical Implications
Micronutrients intake have also been suggested to affect sleep patterns. For example, associations have been reported for deficiencies in vitamin B1, folate, phosphorus, magnesium, iron, zinc, and selenium with shorter sleep duration, lack of alpha-carotene, selenium, and calcium with difficulty falling asleep, low intake of vitamin D and lycopene with sleep maintenance, and low intake of calcium and vitamin C with non-restorative sleep.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554513/


Vitamin B6

Natural Treatments for Insomnia
Impaired brain serotonin production – may be related to cofactor insufficiency (Vitamin B6 and zinc) or magnesium deficiency (magnesium is required for phosphorylation of pyridoxine into its active form pyridoxal-5-phosphate). Impaired ability to relax – often related to chronic stress, which is associated with increased need for Vitamin B3 and Vitamin B6.
http://nutritionmedicine.org/what-is/what-is-insomnia/natural-treatments-for-insomnia/

Vitamins and Sleep: These Vitamins Deficiencies Can Cause Sleep Trouble
Vitamin B6 helps your body take tryptophan and turn it into serotonin, a key hormone that helps with everything from feeling happy to getting good rest. It can help you sleep better and wake up feeling more rested. Fish is a great source of B6, but you can also get it from spinach, bananas, whole grains, chickpeas, and carrots if you’re vegetarian or vegan.
https://www.venturacwc.org/vitamins-and-sleep/


Magnesium

Magnesium Intake and Sleep Disorder Symptoms
In clinical trials, dietary magnesium use can improve insomnia symptoms. However, little is known about the association between dietary magnesium consumption and sleep disorder symptoms including daytime falling asleep, sleepiness and snoring at the population level.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6212970/

The Effects of Magnesium – Melatonin - Vit B Complex Supplementation in Treatment of Insomnia
The results of this study demonstrate that supplementation with Magnesium-melatonin-vitamin B complex for 3 months has a significant positive effect on sleep disturbances and is highly effective for the treatment of patients with insomnia. Regardless of the insomnia aetiology, Magnesium-melatonin-vitamin B complex supplementation reduces insomnia symptoms, as well as its consequences, thus improving the patients’ quality of life and preventing potential unwanted clinical, social, economic, or emotional repercussions.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910806/


Melatonin

The effectiveness of melatonin for promoting healthy sleep: a rapid evidence assessment of the literature
Exogenous melatonin, as both prescription and over the counter pills/tablets, has become one of the most frequently requested non-prescription sleep aids due to its regulator role in the internal timing of biological rhythms, including promotion/regulation of sleep. Melatonin is marketed to help promote total sleep time, aid with fatigue from jet lag, or balance circadian rhythms from jet lag and rotating shift work. Evidence suggests melatonin may reduce the time it takes for people with delayed sleep phase syndrome (i.e., sleep is delayed by two or more hours beyond the conventional bedtime, causing difficulty in waking at a desired time) to fall asleep; melatonin may also help reset the body’s sleep-wake cycle. Importantly, melatonin has been shown to serve as a mediator between the thermoregulatory and arousal system in humans, such that exogenous administration of melatonin during the day can result in sleepiness in association with reduced core temperature.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273450/

Melatonin: What to Do and How to Take It
Melatonin is an important physiological sleep regulator in diurnal species including humans. The sharp increase in sleep propensity at night usually occurs 2 h after the onset of endogenous melatonin production in humans; in addition, the duration of nocturnal melatonin relays night length information to the brain and various organs, including the SCN itself. The circadian melatonin rhythm is closely associated with the sleep rhythm in both normal and blind subjects. Ageing, the presence of certain diseases [e.g. primary degeneration of the autonomic nervous system and diabetic neuropathy, some types of neoplasms and Alzheimer's disease (AD)] and certain drugs (e.g. β‐blockers, clonidine, naloxone and non‐steroidal anti‐inflammatory drugs) abolish the nocturnal production of melatonin and are associated with impaired sleep.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057895/


L-tryptophan

Analysis, Nutrition, and Health Benefits of Tryptophan
Lieberman used available data for 29 687 US adults to determine the effect of the average daily intake of 826 mg/d of tryptophan on liver and kidney function, depression, and sleep outcomes. The authors conclude that the high intake of tryptophan does not seem to affect liver and kidney function or carbohydrate metabolism but was inversely associated with the self-reported level of depression and positively associated with sleep duration. In a related investigation, Bravo analyzed whether consumption of cereals enriched with tryptophan might facilitate the reconsolidation of the sleep/wake cycle and counteract depression and anxiety. In the study by Wenefrida, middle-aged/elderly individuals consumed standard cereals with a tryptophan content of 22.5 mg/30 g at breakfast and dinner in the control and cereals with a tryptophan content of 60 mg/30 g in the treatment week. The results show that consumption of the higher tryptophan cereals increased sleep efficiency and sleep time and improved anxiety and depression symptoms.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158605/

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis
Tryptophan has been shown to have direct effects on sleep, producing an increase in rated subjective sleepiness, and decrease in total wakefulness. This improved quality of sleep is associated with an improvement in hedonic and cognitive measures, improved morning alertness and brain measures of attention.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728667/


Goji

A randomized, double-blind, placebo-controlled, clinical study of the general effects of a standardized Lycium barbarum (Goji) Juice, GoChi
This randomized, double-blind, placebo-controlled clinical trial is the first study reported from outside China that has examined the general effects of the orally consumed goji berry, Lycium barbarum, as a standardized juice (GoChi; FreeLife International LLC, Phoenix, AZ) to healthy adults for 14 days. Significant differences between day 1 and day 15 were found in the GoChi group (N = 16) in increased ratings for energy level, athletic performance, quality of sleep, ease of awakening, ability to focus on activities, mental acuity, calmness, and feelings of health, contentment, and happiness.
https://pubmed.ncbi.nlm.nih.gov/18447631/

Insomnia
In one study where subjects had eaten two kiwis an hour before bed, every night, for four weeks, subjects demonstrated significantly better onset, duration, and efficiency of their sleep. Tart cherries have been associated with improved sleep, as well as almonds, raspberries, goji berries, tomatoes and fenugreek seeds, which have all been found to contain natural levels of melatonin.
https://nutritionfacts.org/topics/insomnia/


Chamomile

An Herbal Medicine of the Past With a Bright Future
Traditionally, chamomile preparations such as tea and essential oil aromatherapy have been used to treat insomnia and to induce sedation (calming effects). Chamomile is widely regarded as a mild tranquilizer and sleep-inducer. Sedative effects may be due to the flavonoid, apigenin that binds to benzodiazepine receptors in the brain.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995283/

The effects of chamomile extract on sleep quality among elderly people: A clinical trial
The use of chamomile extract can significantly improve sleep quality among elderly people. Thus, it can be used as a safe modality for promoting elderly people's sleep.
https://pubmed.ncbi.nlm.nih.gov/29154054/


Lemon Balm

Sleep Promoting Effects of IQP-AO-101: A Double-Blind, Randomized, Placebo-Controlled Exploratory Trial
The history of plant-derived sleep aids goes back as far as ancient times. Plants such as valerian (Valeriana officinalis L.), hops (Humulus lupulus L.), passion flower (Passiflora incarnata L.), lavender (Lavandula officinalis L.) or lemon balm (Melissa officinalis L.) have been used by healers to reduce anxiety, induce calmness, and promote sleep. Since medicinal plants are made up of a variety of constituents that exert different beneficial properties that may help to combat sleep problems, different herbs are often combined to achieve synergistic effects. However, solid evidence of their efficacy is lacking for many natural products available on the market. To date, clinical trials in humans provide preliminary evidence for only a few herbal sleep aids, such as valerian, passion flower or lemon balm.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521387/

Lemon Balm
Several studies show that lemon balm combined with other calming herbs (such as valerian, hops, and chamomile) helps reduce anxiety and promote sleep. Few studies have examined lemon balm by itself, except for topical use. For example, in one study of people with minor sleep problems, 81% of those who took an herbal combination of valerian and lemon balm reported sleeping much better than those who took a placebo.
https://www.mountsinai.org/health-library/herb/lemon-balm


Passionflower

Effect of a medicinal plant (Passiflora incarnata L) on sleep
In research, Passiflora incarnata induced a significant increment in the total sleep time (p<0.05). Concomitantly, a significant decrement in wakefulness (W) was observed (p<0.05). In contrast, time spent in rapid eye movement (REM) sleep showed a decreasing tendency, since both its frequency and mean duration were reduced.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699852/

A double-blind, placebo-controlled investigation of the effects of Passiflora incarnata (passionflower) herbal tea on subjective sleep quality
Passiflora incarnata is a traditional herbal sedative, anxiolytic and a popular sleep aid used for the treatment of sleep disturbance. The aim of the present study was to investigate the efficacy of Passiflora incarnata herbal tea on human sleep, as measured using sleep diaries validated by polysomnography (PSG). This study featured a double-blind, placebo-controlled, repeated-measures design with a counterbalanced order of treatments (passionflower vs placebo tea), separated by a 1 week 'washout' period. Of six sleep-diary measures analysed, sleep quality showed a significantly better rating for passionflower compared with placebo (t(40) = 2.70, p < 0.01). These initial findings suggest that the consumption of a low dose of Passiflora incarnata, in the form of tea, yields short-term subjective sleep benefits for healthy adults with mild fluctuations in sleep quality.
https://pubmed.ncbi.nlm.nih.gov/21294203/


L-Taurine

Effect of Taurine and Caffeine on Sleep-Wake Activity in Drosophila Melanogaster
Treatment with taurine at 0.1% to 1.5% reduces locomotor activity by 28% to 86% and shifts it from diurnal to nocturnal. At 0.75%, taurine also increases total sleep by 50%. Our results show that taurine increases sleep, while caffeine, as previously reported, attenuates sleep.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630960/

Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms
The role of caffeine and taurine in sleep-wake activity has been studied in a model utilizing Drosophila melanogaster. Taurine treatment elevated sleeping duration, but caffeine attenuated sleep. A high ratio between taurine and caffeine promoted sleep, whereas a low ratio prevented sleep to a larger extent in comparison with an equal amount of caffeine treatment alone. The low doses of taurine-mediated enhancing action of caffeine may provide a justification for the occurrence of both components in energy-enhancing drinks, including Monster® and Red Bull®.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536745/


Hops

Sleep improving effects of a single dose administration of a valerian/hops fluid extract - a double blind, randomized, placebo-controlled sleep-EEG study in a parallel design using electro hypnograms
Repetitive administrations of valerian/hops combinations have been widely used for self-administered therapy of sleep disturbances.
https://pubmed.ncbi.nlm.nih.gov/18559301/

The Sedative Effects of Hops
The concentration of 2 mg of hop extract effectively decreased nocturnal activity in the circadian activity rhythm. On the basis of this investigation, administration of non-alcoholic beer would be recommended due to its hop content and consequent sedative action, which would be an aid to nocturnal sleep.
https://pubmed.ncbi.nlm.nih.gov/22849837/


St. John’s Wort

St. John’s Wort
St. John’s wort is a plant with yellow flowers that has been used in traditional European medicine as far back as the ancient Greeks. The name St. John’s wort apparently refers to John the Baptist, as the plant blooms around the time of the feast of St. John the Baptist in late June. Historically, St. John’s wort has been used for a variety of conditions, including kidney and lung ailments, insomnia, and depression, and to aid wound healing.
https://www.nccih.nih.gov/health/st-johns-wort

St. John’s Wort
St. John's wort has been used in alternative medicine as a likely effective aid in treating mild to moderate depression and related symptoms such as anxiety or insomnia.
https://www.uofmhealth.org/health-library/d04408a1


GABA

GABA and l-theanine mixture decreases sleep latency and improves NREM sleep
GABA/l-theanine mixture has a positive synergistic effect on sleep quality and duration as compared to the GABA or l-theanine alone. The increase in GABA receptor and GluN1 expression is attributed to the potential neuromodulatory properties of the GABA/l-theanine combination, which seems to affect sleep behavior.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366437/

Safety and Efficacy of Gamma-Aminobutyric Acid from Fermented Rice Germ in Patients with Insomnia Symptoms: A Randomized, Double-Blind Trial
RFE-GABA can be used to reduce sleep latency and improve subjective sleep quality without serious adverse effects. Because it is a naturally extracted substance without severe adverse events, RFE-GABA may be widely administered as a supplement to improve sleep health in the general population.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031986/


Skullcap

Skullcap
Skullcap was used formerly for nervous disorders, including hysteria, nervous tension, epilepsy and chorea. It is now used largely as a sedative and sleeping pill, often in combination with other herbs.
https://www.ncbi.nlm.nih.gov/books/NBK548757/

Skullcap Herb: A Restorative Relaxing Nervine
As a relaxing nervine, skullcap herb is commonly used to relax a busy mind at night to promote sleep. Another insomnia indication is for someone who has tense muscles and can’t relax enough naturally to fall asleep. Restless legs at night could also be calmed with skullcap (though I would also consider magnesium in these cases).
https://www.herbalremediesadvice.org/skullcap-herb.html


L-theanine

Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial
Stress-related symptom (i.e., depression, anxiety-trait, and sleep) scores decreased and cognitive function (i.e., verbal fluency and executive function) scores improved after four weeks of L-theanine administration. The reduction in sleep quality problems (disturbances in sleep latency, sleep disturbance, and use of sleep medication) was greater in the L-theanine administration compared to the placebo administration.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6836118/

The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial
Actigraph watch data findings indicated that [those] who consumed L-theanine obtained significantly higher sleep percentage and sleep efficiency scores, along with a non-significant trend for less activity during sleep (defined as less time awake after sleep onset) compared to those in the placebo group. L-theanine at relatively high doses was well tolerated with no significant adverse events.
https://pubmed.ncbi.nlm.nih.gov/22214254/


Ashwagandha

Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: A double-blind, randomized, parallel-group, placebo-controlled study
The present study confirms that Ashwagandha root extract can improve sleep quality and can help in managing insomnia. Ashwagandha root extract was well tolerated by all the participants irrespective of their health condition and age. Additional clinical trials are required to generalize the outcome.
https://pubmed.ncbi.nlm.nih.gov/32818573/

Can ashwagandha improve your sleep?
Pharmacological treatments for insomnia often encourage habituation or even dependency. The soporific effect of ashwagandha poses no such risk and thus offers significant hope to insomniacs. Withania Somnifera, as its name suggests, has genuine soporific qualities, which have long been thought to originate from its roots. Yet scientists (2) have shown that the plant’s leaves contain triethylene glycol (TEG) and that it is this component which is actually responsible for its soporific effects. The effects of TEG alone have indeed been shown to have a sleep-inducing effect.
https://www.nutranews.org/en--stress-sleep--can-ashwagandha-improve-your-sleep--1566


Inositol

Myo-Inositol and Its Derivatives: Their Emerging Role in the Treatment of Human Diseases
Inositol is a very promising treatment for depression and panic disorder. It is promising for bipolar disorder, anxiety, obsession, compulsion, eating disorders, hostility, sadness, tension and fatigue. It is quite safe.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6798087/

Inositol: UMB Digital Archive
Inositol is used orally for diabetic neuropathy, conditions associated with disorders of fat transport and metabolism, panic disorder, high cholesterol, insomnia, cancer, depression, schizophrenia, Alzheimer's disease, attention deficit-hyperactivity disorder (ADHD), autism, treating lithium-induced side effects, psoriasis, promoting hair growth, and treating conditions associated with polycystic ovary syndrome, including anovulation, hypertension, hypertriglyceridemia, and elevated serum concentrations of testosterone.
https://archive.hshsl.umaryland.edu/bitstream/handle/10713/12153/Inositol_Final_2020_02.pdf?sequence=6


5-HTP

5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology
L-5-hydroxytryptophan (5-HTP) is produced from tryptophan by tryptophan hydroxylase (TPH) and its decarboxylation yields serotonin (5-hydroxytryptamine, 5-HT), a monoamine neurotransmitter involved in the modulation of mood, cognition, reward, learning, memory, sleep and numerous other physiological processes. 5-HT is further transformed to melatonin (N-acetyl-5-methoxytryptamine), the hormone primarily released by the pineal gland that regulates the sleep–wake cycle.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796270/

Sleep-promoting effects of the GABA/5-HTP mixture in vertebrate models
Our available evidence suggests that the GABA/5-HTP mixture modulates both GABAergic and serotonergic signaling. Moreover, the sleep architecture can be controlled by the regulation of GABAA receptor and GABA content with 5-HTP.
https://pubmed.ncbi.nlm.nih.gov/27150227/


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