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The Effects of Magnesium -Melatonin -Vit B Complex Supplementation in Treatment of Insomnia

August 2019
Macedonian Journal of Medical Sciences 7(18)

DOI:10.3889/oamjms.2019.771

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Authors:

Petar Vojvodić

Specijalisticka lekarska ordinacija iz oblasti psihijatrije Psihocentrala Beograd

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Insomnia means difficulty in falling asleep and/or stays asleep. Insomnia commonly leads to daytime sleepiness, lethargy, and a general feeling of being unwell. The most common treatment of insomnia includes GABAA receptor positive allosteric modulators or Melatonin agonists. Our study aimed to evaluate the efficacy of Magnesium-melatonin-vitamin B complex supplement in the treatment of insomnia. The study included 60 patients diagnosed with insomnia. The patients were randomly divided into study group (N = 30), and control group (N = 30), and study group was treated with Magnesium-melatonin-vitamin B complex (one dose contains 175 mg liposomal magnesium oxide, 10 mg Vit B6, 16 μg vit B12, melatonin 1 mg, Extrafolate-S 600 μg) once a day 1 hour before sleep, during the 3 months. The severity of insomnia symptoms was measured by self-reported Athens insomnia scale (AIS), with a cutoff score by Soldatos (AIS score ≥ 6). Mean AIS score at zero points was 14.93 ± 3.778 in the study group and 14.37 ± 4.081 in the control group (p = 0.476), indicating the compatibility of the groups, and both scores correspond to mild to moderate insomnia. Mean AIS score after 3 months of the Magnesium-melatonin-vitamin B complex supplementation was 10.50 ± 4.21 corresponding to mild insomnia, while median AIS score in the control group was 15.13 ± 3.76 which is referred to moderate insomnia, and difference among groups was significant (p = 0.000). Our founding's indicating that 3 months of the Magnesium-melatonin-vitamin B complex supplementation has a beneficial effect in the treatment of insomnia regardless of cause.

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Open Access Maced J Med Sci. 2019 Sep 30; 7(18):3101-3105. 3101

ID Design Press, Skopje, Republic of Macedonia

Open Access Macedonian Journal of Medical Sciences. 2019 Sep 30; 7(18):3101-3105.

https://doi.org/10.3889/oamjms.2019.771

eISSN: 1857-9655

Global Dermatology

The Effects of Magnesium – Melatonin - Vit B Complex

Supplementation in Treatment of Insomnia

Gorica Djokic1, Petar Vojvodić1, Davor Korcok2, Anita Agic2, Anica Rankovic1, Vladan Djordjevic1, Aleksandra Vojvodic3,

Tatjana Vlaskovic-Jovicevic1, Zorica Peric-Hajzler4, Dusica Matovic4, Jovana Vojvodic1, Goran Sijan5, Uwe Wollina6, Michael

Tirant7, Nguyen Van Thuong8, Massimo Fioranelli9*, Torello Lotti10

1Clinic for Mental Disorders “Dr. Laza Lazarevic”, Belgrade, Serbia; 2Abela Pharm, Belgrade, Serbia; 3Department of

Dermatology and Venereology, Military Medical Academy, Belgrade, Serbia; 4Military Medical Academy, Belgrade, Serbia;

5Clinic for Plastic Surgery and Burns, Military Medical Academy, Belgrade, Serbia; 6Department of Dermatology and

Allergology, Städtisches Klinikum Dresden, Dresden, Germany; 7Guglielmo Marconi University, Rome, Italy; 8Vietnam

National Hospital of Dermatology and Venereology, Hanoi, Vietnam; 9Department of Nuclear Physics, Sub-nuclear and

Radiation, G. Marconi University, Rome, Italy; 10Department of Dermatology, G. Marconi University, Rome, Italy

Citation: Vojvodić P, Korcok D, Agic A, Rankovic A,

Djordjevic V, Vojvodic A, Vlaskovic-Jovicevic T, Peric-

Hajzler Z, Matovic D, Vojvodic J, Sijan G, Wollina U,

Tirant M, Van Thuong N, Fioranelli M, Lotti T. The Effects

of Magnesium – Melatonin - Vit B Complex

Supplementation in Treatment of Insomnia. Open Access

Maced J Med Sci. 2019 Sep 30; 7(18):3101-3105.

https://doi.org/10.3889/oamjms.2019.771

Keywords: Insomnia; Magnesium; Melatonin; Athens

insomnia scale; Supplement

*Correspondence: Massimo F ioranelli. Department of

Nuclear Physics, Sub-nuclear, and Radiation, G. Marconi

University, Rome, Italy. E-mail:

massimo.fioranelli@gmail.com

Received: 13-Jun-2019; Revised: 04-Jul-2019;

Accepted: 05-Jul-2019; Online first: 30-Aug-2019

Korcok, Anita Agic, Anica Rankovic, Vladan Djordjevic,

Aleksandra Vojvodic, Tatjana Vlaskovic-Jovicevic, Zorica

Peric-Hajzler, Dusica Matovic, Jovana Vojvodic, Goran

Sijan, Uwe W ollina, Michael Tirant, Nguyen Van Thuong,

Massimo Fioranelli, Torello Lotti. This is an open-access

article distributed under the terms of the Creative

Commons Attribution-NonCommercial 4.0 International

License (CC BY-NC 4.0)

Funding: This research did not receive any fi nancial

support

Competing Interests: The authors have declared that no

competing interests exist

Abbreviations: APA- American Psychiatric Association;

DSM-5- Diagnostic Criteria from Diagnostic and Statistical

Manual of Mental Disorders, 5th edition; ACP- The

American College of Physicians; CBT- Cognitive

behavioral therapy; 5-HT2- Serotoninergic receptors type

2; GABA-A- Gamma-aminobutyric acid receptors type A;

H1- Histamine receptors type 1; D2- dopamine receptors

type 2; OR1- orexin receptors type 1; OR2- orexin

receptors type 2; Mel 1- melatonin receptors type 1; Mel

2- melatonin receptors type 2; 5-HT- Serotonin receptor

system; DA- Dopamine receptor system

Abstract

Insomnia means difficulty in falling asleep and/or stays asleep. Insomnia commonly leads to daytime sleepiness,

lethargy, and a general feeling of being unwell. The most common treatment of insomnia includes GABAA

receptor positive allosteric modulators or Melatonin agonists. Our study aimed to evaluate the efficacy of

Magnesium- melatonin-vitamin B complex supplement in the treatment of insomnia. The study included 60

patients diagnosed with insomnia. The patients were randomly divided into study group (N = 30), and control

group (N = 30), and study group was treated with Magnesium-melatonin-vitamin B complex (one dose contains

175 mg liposomal magnesium oxide, 10 mg Vit B6, 16 μg vit B12, melatonin 1 mg, Extrafolate-S 600 μg) once a

day 1 hour before sleep, during the 3 months. The severity of insomnia symptoms was measured by self-reported

Athens insomnia scale (AIS), with a cut-off score by Soldatos (AIS score ≥ 6). Mean AIS score at zero points was

14.93 ± 3.778 in the study group and 14.37 ± 4.081 in the control group (p = 0.476), indicating the compatibility of

the groups, and both scores correspond to mild to moderate insomnia. Mean AIS score after 3 months of the

Magnesium- melatonin- vitamin B complex supplementation was 10.50 ± 4.21 corresponding to mild insomnia,

while median AIS score in the control group was 15.13 ± 3.76 which is referred to moderate insomnia, and

difference among groups was significant (p = 0.000). Our founding’s indicating that 3 months of the Magnesium-

melatonin-vitamin B complex supplementation has a beneficial effect in the treatment of insomnia regardless of

cause.

Introduction

Insomnia is a sleep disorder with difficulties to

fall asleep or stay asleep or both. It is the most

common sleep disorder, according to the American

Psychiatric Association (APA), with approximately

30% of all adults and 6-10% of those who have

severe symptoms diagnosed as insomnia disorder [1].

Diagnostic Criteria from the Diagnostic and

Statistical Manual of Mental Disorders, 5th edition

(DSM-5) include:

- Difficulty in initialisation or maintaining sleep

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or early-morning awakening that leads to low quantity

or quality of sleep.

- Sleep disturbance that leads to impairment

in social, occupational, educational, academic,

behavioural, or other important areas of functioning.

- Patients experience this even with adequate

opportunity to sleep, at least 3 nights per week, and

for at least 3 months.

- Insomnia is not explained by the presence of

mental disorders or medical conditions and is not

associated with another sleep disorder [2].

Pharmaceutical and nonpharmaceutical

treatments are recognisable for insomnia. The

American College of Physicians (ACP) advised

cognitive-behavioural therapy (CBT) as a first-line

treatment for chronic insomnia in adults. Sleep

hygiene training (avoiding caffeine, exercise near

bedtime, watching TV or surfing the internet from the

bed) can help you change some of these disruptive

behaviours [1].

Medications that have insomnia as an

approved indication are:

- Benzodiazepine receptor agonist (non-

selective GABA-A receptor positive allosteric

modulator)-estazolam, eszopiclone, flunitrazepam,

flurazepam, lormetazepam, nitrazepam, quazepam,

temazepam, triazolam, zaleplon, zolpidem (alpha 1

subunit selective benzodiazepine receptor agonist).

- Norepinephrine and serotonin reuptake

inhibitor and 5-HT2 receptor antagonistdoxepine in

very low doses 3mg and 6mg for insomnia in the USA

- H1 and D2 receptor antagonist

promethazine

- OR1 and OR2 receptor antagonist

suvorexant

- Mel1 and Mel2 receptor agonist ramelteon

and melatonin [3].

The hormone melatonin is produced during

the sleep cycle. Studies are inconclusive regarding

whether melatonin can help treat insomnia in adults,

but melatonin could promote sleep by helping to

regulate the body’s bio clock and sleep-wake cycles

and to adhere to more healthful sleep patterns.

Research indicates that melatonin may shorten the

time it takes to fall asleep, increase overall sleep

amounts, and may increase REM sleep [4], [5], [6].

Few sleep-promoting nutrients enhance sleep

and relaxation. Magnesium is a muscle relaxant and

inducer of the deeper sleep. Circadian rhythms

dysregulation and compromised lifestyle also increase

magnesium excretion, leading to deficiency [7].

Magnesium supplementation improves sleep

efficiency, sleep time and sleep onset latency, early

morning awakening, and insomnia objective measures

such as the concentration of serum renin, melatonin,

and serum cortisol, in older adults [8]. Dietary

magnesium intake may have long-term benefits in

reducing the likelihood of daytime falling asleep in

women [9]. Anxiety can cause insomnia, and vice

versa which can result in a self-perpetuating cycle,

which leads to chronic insomnia. According to

Australia’s Sleep Health Foundation, anxiety and

worrying are leading causes of insomnia [1]. Existing

evidence is suggestive of a beneficial effect of Mg on

subjective anxiety in anxiety vulnerable samples, and

for mild-to-moderate depression in adults within 2

weeks [10], [11]. According to the National Sleep

Foundation, insomnia promotes depression and

depression-induced insomnia. A meta-analysis of 34

studies concluded that insomnia is significantly

associated with an increased risk of depression, which

has implications for the prevention of depression in

non-depressed individuals with insomnia symptoms

[12]. Melatonin and the nonselective MT1 /

MT2 receptor agonist agomelatine have displayed

anxiolytic-like action and have been used in the

elderly, but exact mechanisms of action are still

unknown [13], [14]. Recent studies suggest that the

MT2 receptor is implicated in the antidepressant-like

effects of melatonin [15], [16].

The recent results showed mixed effects of

vitamin B12 on sleep patterns [17] and promoting an

effect of vitamin B6 on the reduction of psychological

distress, which could induce sleep disturbance [18].

Contrary to that, there is clear evidence on the

antidepressant effect of vitamin B12 [19] and vitamin

B6 for therapy of hormone-related depression in

women [20].

Our study aimed to evaluate the efficacy of

Magnesium-melatonin-vitamin B complex supplement

in the treatment of insomnia.

Material and Methods

The study included 60 patients diagnosed

with insomnia who refused to take drugs for insomnia

and have a positive attitude towards the supplements.

The patients were randomly divided (bias coin

randomization) into study group (N = 30), and control

group (N = 30), and study group was treated with

Magnesium-melatonin-vitamin B complex (one dose

contains175 mg liposomal magnesium oxide, 10 mg

Vit B6, 16 μg vit B12, melatonin 1mg, Extrafolate-S

600 μg) once a day 1 hour before sleep, during the 3

months. The manufacturer advertises it as mild rapid-

acting natural sleep medicine containing magnesium,

melatonin, and vitamin B complex. It is recommended

to use one capsule daily, evening dose, an hour

before sleep. We followed the manufacturer’s

recommendation regarding the supplement intake.

The severity of insomnia symptoms was measured by

self-reported Athens insomnia scale (AIS), with

Djokic et al. The Effects of Magnesium - Melatonin-Vit B Complex Supplementation in Treatment of Insomnia

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Open Access Maced J Med Sci. 2019 Sep 30; 7(18):3101-3105. 3103

Gamma-aminobutyric off score by Soldatos (AIS

score ≥ 6). The severity of insomnia measured by AIS

was graded according to Morin’s criteria: AIS score 7-

14- mild insomnia; AIS score 15-21- moderate

insomnia; AIS score 22-28- severe insomnia. AIS and

CGI-S scores were evaluated at zero points and after

3 months of supplement consumption.

Statistical analysis

All collected data were analysed using the

IBM SPSS Statistics for Windows (IBM SPSS, IBM

Corp., Armonk, NY, USA) software, version 22.0. The

descriptive statistics are presented as a central

tendency (means) and variability (standard deviation

and variation interval). Means were compared with the

independent samples t-test, while for testing data of

different categories, we used Pearson’s χ2 test and

Mann-Whitney test. We used repeated-measures

analysis of covariance (RM ANCOVA) for the

assessment on t0 and t90 between and within the

groups. The level of statistical significance was set at

p < 0.05.

Results

Gender distribution was 67% male and 33%

female in the study group and 77% male and 23%

female in the control group. The average age in the

study group was 51.40 ± 14.61 years, and 44.93 ±

14.40 years in the control group, the age distribution

of subjects indicating the comparability of the studied

groups (p = 0.090). Mean AIS score at zero points

was 14.93 ± 3.778 in the study group and 14.37 ±

4.081 in the control group (p = 0.476), indicating the

compatibility of the groups, and both scores

correspond to mild to moderate insomnia. Mean AIS

score after 3 months of the Magnesium-melatonin-

vitamin B complex supplementation was 10.50 ± 4.21,

corresponding to mild insomnia, while the median AIS

score in the control group was 15.13 ± 3.76 which

refers to moderate insomnia, and difference among

groups was significant (p = 0.000) (Table 1).

Table 1: AIS score at zero and endpoint

T90

X ± SD; Med

(min-max)

X ± SD; Med

(min-max)

p**

Study group

14.93 ± 3.78; 15

(9-24)

0.476

10.50 ± 4.21; 9

(3-20)

0.000

Control group

14.37 ± 4.08;

13.5 (9-24)

15.13 ± 3.76; 14

(10-24)

*Mann-Whitney test; **Wilcoxon test.

Mean CGI-S at zero point was 3.57 ± 0.568 in

study group, and 3.43 ± 0.58 in control group (p =

0.328). Difference become significant at the end point

visit (p = 0.05) with mean CGI-S score 2.97 ± 0.77 in

the study group, and 3.53 ± 0.63 in control group

(Table 2).

Table 2: CGI-S at zero and endpoint

T90

X ± SD; Med (min - max)

p**

Study group

3.57 ± 0.57; 4 (3-5)

0.328

2.97 ± 0.77; 3 (1-4)

0.005

Control group

3.43 ± 0.57; 3 (3-5)

3.53 ± 0.63; 3 (3-5)

*Mann-Whitney test; **Wilcoxon test.

Mean CGI-I score after 3 months was 3.23 ±

0.73 (minimally improved), which is significantly

different in comparison with mean CGI-I score in

control group 4.07 ± 0.25 (no change) (p = 0.000)

(Table 3).

Table 3: CGI-I at the endpoint

T90

X ± SD; Med (min - max)

Study group

3.23 ± 0.73; 3 (2-4)

0.000

Control group

4.07 ± 0.25; 4 (4-5)

*Mann-Whitney test.

Discussion

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.

Magnesium is one of the most important

minerals in the human body. It is involved in more

than 300 enzyme systems responsible for the

maintenance of normal homeostasis [9]. One of the

more recently discovered functions of magnesium is

its effect on cellular timekeeping and regulation of

circadian rhythm. Studies that back up this theory

have shown that inadequately low levels of serum

magnesium are associated with low quality sleep and

insomnia [17]. Lack of magnesium intake seems to be

involved in the development of depression, which

increases the risk of insomnia [12].

A study performed by Abbasi et al. [8]

examined the independent role of magnesium in the

treatment of insomnia. After 8 weeks of magnesium

supplementation, the patients had increased sleep

time, as well as sleep efficiency. The results

demonstrate that magnesium supplementation brings

significant improvement, both subjective and

objective, to the patients who have insomnia. These

results are consistent with the results of our study,

which demonstrates that magnesium, isolated or as a

part of a combination supplement, is successful in

treating insomnia. Interestingly, a statistically

significant increase in serum melatonin concentration

was recorded in the experimental group that received

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dietary magnesium supplementation compared to the

placebo group. This finding suggests the complicated

interaction between these two elements that are both

important for the regulation of sleep and the day-night

cycle.

Melatonin is a hormone produced and

secreted by the pineal gland. It has an important role

in the maintenance of the organism circadian rhythm,

which is being expressed through a wide range of

different physiologic, neuroendocrine, and behavioural

functions. Its plasma concentrations reach a peak

during nighttime, while during the daytime, they are

barely measurable [15]. Animal and human studies

have demonstrated that melatonin binds to the

receptors in the central nervous system, producing an

effect on sleep promotion and sleeping phase shifts

[13], [16].

Pharmacological agents that are prescribed

for insomnia cannot reproduce the properties of

physiological sleep and are associated with adverse

effects like sedation, anxiety, tremor, tolerance to the

drug or dependence [13]. The research conducted by

Ochoa-Sanchez et al., [21] revealed that melatonin

receptor agonists had much more favourable

pharmacological properties in terms of sleep

promotion and regulation when compared to

prescribed benzodiazepines. Also, melatonin and its

agonists did not produce adverse effects commonly

attributable to benzodiazepines.

The study of Grima et al. [5], which dealt with

melatonin administration for sleep disturbances after

traumatic brain injury, reported a significant

improvement in sleep quality and sleep efficiency, as

well as a reduction in fatigue and anxiety symptoms,

after only 4 weeks of melatonin treatment. This result

is consistent with our study, although patients in our

experimental group did not receive isolated melatonin,

as a part of the Magnesium-melatonin-vitamin B

complex supplement, and they received it for a

substantially longer period as well.

From the B vitamins group, the best examined

in terms of sleeping interactions is vitamin B12. The

direct relationship between insomnia and vitamin B12

levels is yet to be established. However, vitamin B12

deficiency is known to be involved in the

pathophysiology of depression, which can commonly

be associated with insomnia [19].

Lichstein et al. [18] examined the influence of

different vitamin supplementation on sleep quality and

duration. The results suggest that the use of

combined multivitamin supplements, as well as single

vitamins, including vitamin B complex, hurts sleep

maintenance, causes a higher rate of insomnia, and

requires greater use of sleep medicine. In contrast to

this study, our results show that vitamin B complex, in

combination with magnesium and melatonin, has a

positive effect on sleep regulation and can be used to

treat insomnia. This could be attributed to the

combined additive effect of the three components of

the prescribed supplement, in contrast to the single

effects of isolated molecules that were previously

tested.

Although there are studies that investigated

the effect of different combined supplements for the

treatment of insomnia, to the best of our knowledge,

this is the first study that investigated the particular

combination of Magnesium-melatonin-vitamin B

complex supplement. The research conducted by

Rondanelli et al. [22] investigated the influence of the

supplement consisting of melatonin, magnesium, and

zinc on insomnia in the elderly.

Their results showed that these elements

were effective in managing sleep disorders after 2

months of treatment. This finding is consistent with

our study, which shows that common elements from

both studies – magnesium, and melatonin have a

significant effect on sleep regulation.

Our findings indicate that 3 months of the

Magnesium-melatonin-vitamin B complex

supplementation has a beneficial effect in the

treatment of insomnia regardless of cause. According

to our results, Magnesium-melatonin-vitamin B

complex augmentation improves AIS and CGI-S score

with statistical significance relative to the control

group. The global improvement according to the CGI-I

score, was minimal but significant different compared

with the control group where there was no change.

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Dec 2023

Introduction B vitamins help generate energy within cells. A significant portion of populations in developed countries suffer a deficiency in one or more B vitamins. This study assesses the use of vitamin B supplements and their effects. Methodology This cross-sectional study was conducted using public participants in Saudi Arabia. Participants from all over Saudi Arabia were recruited through self-conducted surveys to study the effects of using vitamin B supplements on appetite, BMI, energy, and sleep, and to identify any side effects in participants. Inclusion criteria included age (18 years or older) and use of vitamin B supplements. Children, pregnant women, adults who had never used vitamin B, and those not willing to participate in the study were excluded. Results In total, 1,521 adults were recruited. Most of the participants were young Saudi Females. While taking vitamin B supplements, a minority of participants complained of mild gastrointestinal upset, but a significant proportion experienced no side effects. In this study, a significant proportion of participants experienced an increase in appetite, which was associated with a significant increase in BMI after taking vitamin B supplements. This study also explored increases in energy, which were significant and associated with significant increases in sleeping time. Male participants in the present study noticed a significant increase in erectile dysfunction (ED). Conclusions This study found significant effects of vitamin B supplements on BMI, appetite, energy, and sleep, as well as an increase in ED in male participants. More studies are needed to further explore these findings.

Network Pharmacology Analysis of the Potential Pharmacological Mechanism of a Sleep Cocktail

Article

Full-text available

May 2024

Insomnia, also known as sleeplessness, is a sleep disorder due to which people have trouble sleeping, followed by daytime sleepiness, low energy, irritability, and a depressed mood. It may result in an increased risk of accidents of all kinds as well as problems focusing and learning. Dietary supplements have become popular products for alleviating insomnia, while the lenient requirements for pre-market research result in unintelligible mechanisms of different combinations of dietary supplements. In this study, we aim to systematically identify the molecular mechanisms of a sleep cocktail’s pharmacological effects based on findings from network pharmacology and molecular docking. A total of 249 targets of the sleep cocktail for the treatment of insomnia were identified and enrichment analysis revealed multiple pathways involved in the nervous system and inflammation. Protein–protein interaction (PPI) network analysis and molecular complex detection (MCODE) analysis yielded 10 hub genes, including AKT1, ADORA1, BCL2, CREB1, IL6, JUN, RELA, STAT3, TNF, and TP53. Results from weighted correlation network analysis (WGCNA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of insomnia-related transcriptome data from peripheral blood mononuclear cells (PBMCs) showed that a sleep cocktail may also ease insomnia via regulating the inflammatory response. Molecular docking results reveal good affinity of Sleep Cocktail to 9 selected key targets. It is noteworthy that the crucial target HSP90AA1 binds to melatonin most stably, which was further validated by MD simulation.

Melatonin in sleep disorders. comparison of different products and literature review

Article

Full-text available

Feb 2024

Introduction: sleep disorders in paediatrics are a growing problem. Melatonin is the drug of choice and it is common to receive advertising for multiple products containing melatonin in primary care. In this paper, a comparative analysis of these products is carried out, examining the most recent scientific evidence, in order to determine whether their use is justified or not. Methods: a descriptive study was conducted on melatonin-containing products sold in pharmacies in Spain and aimed at the paediatric population. Subsequently, a systematic review of documents on the use of melatonin in children and on each extra component present in the products collected was carried out. Results: fifty-three products were analysed. The most common form of administration was drops or millilitres. The usual recommended dose of melatonin was 1 mg per day. The most frequently reported added component was vitamin B6, and lemon balm and passionflower were the most frequently used herbs. None of the products were specifically listed in the Spanish Agency for Medicines and Health Products, and no bibliographical references were found in the advertising of any of the products. Conclusions: although the efficacy of melatonin in sleep disorders is well known, there is currently no consensus on its effective dose in children. The substances most frequently associated with melatonin have little literature to support their results in sleep, and there are no standardised doses for them either, or doses lower than these are used due to a lack of studies in the paediatric population.

Homeostasis of Circadian Rhythm and Therapeutic Approaches to Manage its Related-Disorders: The Case of Medicinal Mushrooms Rich in Melatonin

Article

Full-text available

Sep 2023

Circadian rhythm consists of complicated molecular mechanisms to orchestrate environmental stimuli to intrinsic molecular clocks. However, circadian rhythm is frequently deregulated in modern society by both extrinsic and biological factors leading to Circadian Rhythm Sleep Disorders (CRSD).

Efficacy and safety of Dimdazenil in the adult insomnia patients: A phase II randomized, multicenter, double-blind, placebo-controlled, parallel-group study

Article

Full-text available

Oct 2023
SLEEP

Objective: To evaluate the efficacy and safety of Dimdazenil, a positive allosteric modulator with selectivity for α1, α5 subunit-containing GABAA receptors, on sleep variables in patients with insomnia disorder. Methods: In this randomized, double-blind, placebo-controlled trial, adults (18-65 years) with insomnia disorder were randomized (1:1:1:1 to receive daily oral placebo, Dimdazenil (1.5, 2.5, or 5 mg) for 14 days. The primary efficacy outcome was the total sleep time (TST) on Day 1/2 and Day 13/14, measured by polysomnography. The secondary outcome measures included 1) latency to persistent sleep (LPS), sleep efficiency (SE), wake after sleep onset (WASO) and number of awakenings (NAW) on Days 1/2 and Day 13/14; 2) the average subjective sleep latency (sSL), total sleep time (sTST), wake after sleep onset (sWASO) and number of awakenings (sNAW) recorded in sleep diary and sleep questionnaire, and the evaluation of insomnia severity index (ISI). Rebound insomnia, withdrawal and treatment-emergent adverse events (TEAE) were also assessed. Results: Of 569 patients screened, 288 (76.4% female) were randomized and received one dose. For the primary outcomes, TST was significantly improved in the Dimdazenil 1.5, 2.5 and 5 mg group compared with the placebo group at Day 1/2, and significantly improved in the Dimdazenil 2.5 and 5 mg groups compared with the placebo group at Day 13/14. The Least Squares Means (standard errors) and 95% Confidence Intervals for the three active doses compared to placebo are 25.5 (8.31), (9.16, 41.89) for the 1.5 mg dose; 17.4 (8.19), (1.29, 33.55) for the 2.5 mg dose; 22.8 (8.15), (6.72, 38.80) for the 5 mg dose on Day 1/2. Corresponding data on Day 13/14 are 7.6 (8.07), (-8.24, 23.53) and 19.3 (8.06), (3.43, 35.17) and 18.2 (7.95), (2.49, 33.80). LPS was significantly reduced in the Dimdazenil 5 mg group compared with the placebo group on Day 1/2. SE was significantly improved in the Dimdazenil 1.5 and 5 mg group compared with the placebo group at Day 1/2. In the subjective sleep parameters, sSL on average was significantly lower in the Dimdazenil 1.5, 2.5 and 5 mg groups compared with the placebo group. sTST on average was significantly higher in the Dimdazenil 1.5, 2.5 and 5 mg groups compared with the placebo group. The most common TEAEs were dizziness, vertigo and weakness with no clinically-relevant treatment-related serious adverse events. Conclusion: Dimdazenil of 1.5, 2.5 and 5 mg improved certain objective and subjective sleep outcomes in people with insomnia disorder, with a favorable safety profile. These findings suggested that Dimdazenil may represent a promising new treatment for insomnia disorder, a prevalent condition with limited effective and safe treatments available.

Mediating effects of DNA methylation in the association between sleep quality and infertility among women of childbearing age

Article

Full-text available

Sep 2023
BMC PUBLIC HEALTH

Background This study aims to investigate the association between sleep quality and infertility among women and to explore the mediating effects of DNA methylation in this association. Methods This study is a population-based case–control study. The relationship between sleep quality and infertility was investigated in women with anovulatory infertility (n = 43) and healthy controls (n = 43). Genome-wide DNA methylation was profiled from peripheral blood samples using the Illumina Infinium Human Methylation 850k BeadChip. Differentially methylated CpGs between cases and controls were identified using the ChAMP R package. The mediating effect of DNA methylation between sleep quality and infertility among women was investigated using the Bayesian estimation method provided by the R package “mediation”. Results The survey included 86 women of reproductive age, with 43 participants each in the case and control groups. The average age of the women was 27.6 ± 2.8 years (case group: 27.8 ± 3.0 years, control group: 27.4 ± 2.7 years). A total of 262 differentially methylated CpGs corresponding to 185 genes were identified. Difficulty falling asleep was a risk factor for infertility in women (OR = 3.69, 95%CI = 1.14, 11.99), and a causal mediation effect of DNA methylation CpGs was found. The mediating effect coefficient for cg08298632 was 0.10 (95%CI = 0.01–0.22), and the proportion of the total effect mediated by this methylation site increased to 64.3%. Conclusion These results suggest that DNA methylation CpGs (cg08298632) play a significant role in the relationship between difficulty falling asleep and infertility in females. These findings contribute to our understanding of the underlying mechanisms that connect difficulty falling asleep and infertility in women. Further studies are necessary to fully understand the biological significance and potential therapeutic applications of these findings. The identified DNA methylation sites provide new and valuable insights and potential targets for future studies aiming to prevent and treat female infertility.

Prevalence of Sleep Disturbance Potential–Associated Factors among Undergraduate Pharmacy Students in Saudi Arabia

Article

Jul 2024

A BSTRACT Background Many studies across the globe have observed the significant effect of sleep disturbance on the academic achievement of medical students. Objective: This research was conducted to define the prevalence of sleep disturbance and to discover the consequences and management of this condition among undergraduate pharmacy students of Mohammed Al-Mana College for Medical Sciences (MACHS). Methods We conducted a questionnaire-based online survey among different levels of MACHS pharmacy students. Results A total of 165 students participated in the study, of whom 132 (80%) were females and 33 (20%) were males. Most of the participants, 142 (86.06%), were staying with their parents, whereas few of them were staying alone (23; 13.94%). While a handful of them, 29 (17.58%), did not have their bedrooms, most of them had their bedrooms (136; 82.42%). When asked about drinking caffeine-rich products in the afternoon or at night, most of them responded “sometimes” (78; 47.27%), followed by the category “always” (61; 36.97%), “rarely” (15; 9.09%), and then the category of students who responded “not at all” (11; 6.67%). Overall, 35 (21.21%) of the study participants had a smoking habit, 72 (43.63%) tried to treat their sleep disturbance, whereas 42 (25.45%) were getting treatment for insomnia. Conclusion Most pharmacy students at MACH College, especially females, have sleep problems. Mostly, the prevalence is common during exam periods, and it mildly affects their grade point average.

The effects of melatonin and magnesium in a novel supplement delivery system on sleep scores, body composition and metabolism in otherwise healthy individuals with sleep disturbances

Article

May 2024
CHRONOBIOL INT

The purpose of this study was to investigate the effects of a novel dietary supplement, including melatonin and magnesium, delivered via coffee pods on sleep quality, resting metabolic rate (RMR), and body composition in individuals with poor sleep quality disturbances. Using a double-blinded, randomized, crossover trial, we recruited 35 participants to a 4-week intervention with both supplements (1.9 mg melatonin + 200 mg elemental magnesium before sleep) and placebo conditions, considering a 7d washout period between treatments. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was applied, RMR (kcal) was measured using indirect calorimetry (canopy ventilated open-circuit system) and body composition was assessed using dual-energy X-ray absorptiometry. Decreases in PSQI and anger - hostility scores, as well as in energy intake and fat mass, were observed (p < 0.05) for both conditions, from baseline to the end of each 4-week intervention. Differences between conditions were also observed for these parameters along with energy spent in activity, number of sedentary breaks, sleep efficiency, latency time, time in bed, total sleep time, awakening time, and movement index (p < 0.05) favouring the supplement condition. However, the final PSQI questionnaire scores still indicated poor sleep quality on average (PSQI > 5), in both conditions, with no changes regarding RMR. A melatonin-magnesium supplement, in a coffee pod format, showed improvements in sleep quality in otherwise healthy individuals with sleep disturbances, however PSQI questionnaire scores still indicated poor quality on average (PSQI > 5).

Effectiveness of Magnesium Supplementation on Sleep Quality and Related Health Outcomes for Adults with Poor Sleep Quality: A Randomized Double-Blind Placebo-Controlled Crossover Trial

Preprint

Full-text available

Feb 2024

Objectives: Conduct a randomized double-blind placebo-controlled crossover trial on adults with nonclinical insomnia symptoms to examine the effectiveness of magnesium supplementation on sleep quality and mood. Methods: Participants (N = 31 adults, M age = 45.49) were randomized to either the Magnesium (1 g/d) or Placebo Condition for 2 weeks. Following a two-week washout, participants engaged in the alternative condition. Standardized self-reports (i.e., Insomnia Severity Index, Pittsburgh Sleep Quality Index, Berlin Questionnaire, Pittsburgh Sleep Quality Index, Restorative Sleep Questionnaire, Pain and Sleep Questionnaire, Flinders Fatigue Scale, Trait Anxiety Inventory, Perceived Stress Scale, Profile of Mood States) were completed at Baseline and Post Conditions along with daily objective measures of sleep/activity (i.e., Oura Ring). ISRCTN registry is ISRCTN70584524. Results: Magnesium supplementation resulted in significant improvements compared to Placebo for sleep quality, mood, and activity outcomes (e.g., sleep duration, deep sleep, sleep efficiency, readiness, activity balance, and HRV Readiness), p’s < .05. Nonsignificant improvements for the magnesium condition compared to the placebo condition were evidenced for the Restorative Sleep Questionnaire, Anxiety, Perceived Stress, and Flinder’s Fatigue Scale, p’s > .05. No adverse events were reported and adherence was 100%. Conclusion: Magnesium may be an effective nonpharmacological intervention to promote sleep and mental health. Longer term clinical trials conducted in a variety of populations and settings are encouraged.

A practical guide to improve sleep and performance in athletes

Article

Full-text available

Oct 2023

Sleep is vital for optimal mental and physical health. For athletes, optimizing sleep is becoming a popular strategy to enhance athletic performance. Athletes often complain of sleep problems including insufficient sleep and insomnia symptoms and are also at a higher risk for sleep disordered breathing. Sleep disorders and insufficient sleep can contribute to excessive sleepiness, daytime dysfunction, and performance problems. In contrast, better sleep provides benefits for physical health and athletic performance. For athletes, multiple factors can contribute to insufficient sleep. Sport-specific factors include frequent travel across time zones, competition and training schedules, high training loads, and sleeping in an unfamiliar environment. Non-sport-related factors include work, social, and family commitments; attitudes and sleeping beliefs; individual characteristics, such as chronotype or preference for morning or evening; and lifestyle choices. Fortunately, there are strategies that can be implemented to improve sleep in athletes including (a) education and emphasis on the importance of sleep; (b) sleep screening; providing extra sleep opportunities like (c) banking sleep and (d) napping; improving sleep hygiene like (e) proper light exposure; (f) a good pre-sleep routine; (g) a conducive sleep environment; (h) a strategy for supplementation; (i) utilizing circadian timing adjustments; and (j) jet lag management. Increased recognition of the importance of sleep from sport professionals and screening for sleep disorders and disturbances will be key for future athlete health, well-being, and performance.

Magnesium Intake and Sleep Disorder Symptoms: Findings from the Jiangsu Nutrition Study of Chinese Adults at Five-Year Follow-Up

Article

Full-text available

Sep 2018

(1) Background: 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. (2) Methods: We used data from 1487 adults aged 20 and above attending the Jiangsu Nutrition Study. At baseline in 2002, dietary magnesium was assessed by 3-day weighed food records. At follow-up in 2007, sleep disorder symptoms, including daytime falling asleep, sleepiness and snoring at night, were gathered using a sleep questionnaire. (3) Results: The mean intake of magnesium was 332.5 mg/day. In total, 5.3%, 13.2% and 35.7% of the subjects reported daytime falling asleep, daytime sleepiness, and snoring during sleep, respectively. Compared with the lowest quartile of magnesium intake, the highest quartile was associated with decreased likelihood of falling asleep (odds ratio (OR) 0.12 (0.02, 0.57)) in women but not in men after adjusting for demographic, anthropometric, lifestyle factors, hypertension, and overall dietary patterns. No associations were found between dietary magnesium intake and daytime sleepiness nor night snoring in either gender. (4) Conclusions: Dietary magnesium intake may have long-term benefits in reducing the likelihood of daytime falling asleep in women.

Efficacy of melatonin for sleep disturbance following traumatic brain injury: A randomised controlled trial

Article

Full-text available

Jan 2018
BMC MED

Background: The study aimed to determine the efficacy of melatonin supplementation for sleep disturbances in patients with traumatic brain injury (TBI). Methods: This is a randomised double-blind placebo-controlled two-period two-treatment (melatonin and placebo) crossover study. Outpatients were recruited from Epworth and Austin Hospitals Melbourne, Australia. They had mild to severe TBI (n = 33) reporting sleep disturbances post-injury (mean age 37 years, standard deviation 11 years; 67% men). They were given prolonged-release melatonin formulation (2 mg; Circadin®) and placebo capsules for 4 weeks each in a counterbalanced fashion separated by a 48-hour washout period. Treatment was taken nightly 2 hours before bedtime. Serious adverse events and side-effects were monitored. Results: Melatonin supplementation significantly reduced global Pittsburgh Sleep Quality Index scores relative to placebo, indicating improved sleep quality [melatonin 7.68 vs. placebo 9.47, original score units; difference -1.79; 95% confidence interval (CI), -2.70 to -0.88; p ≤ 0.0001]. Melatonin had no effect on sleep onset latency (melatonin 1.37 vs. placebo 1.42, log units; difference -0.05; 95% CI, -0.14 to 0.03; p = 0.23). With respect to the secondary outcomes, melatonin supplementation increased sleep efficiency on actigraphy, and vitality and mental health on the SF-36 v1 questionnaire (p ≤ 0.05 for each). Melatonin decreased anxiety on the Hospital Anxiety Depression Scale and fatigue on the Fatigue Severity Scale (p ≤ 0.05 for both), but had no significant effect on daytime sleepiness on the Epworth Sleepiness Scale (p = 0.15). No serious adverse events were reported. Conclusions: Melatonin supplementation over a 4-week period is effective and safe in improving subjective sleep quality as well as some aspects of objective sleep quality in patients with TBI. Trial registration: Identifier: 12611000734965; Prospectively registered on 13 July 2011.

Role of magnesium supplementation in the treatment of depression: A randomized clinical trial

Article

Full-text available

Jun 2017
PLOS ONE

Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. Several studies have looked at the association between magnesium and depression, yet its role in symptom management is unclear. The objective of this trial was to test whether supplementation with over-the-counter magnesium chloride improves symptoms of depression. An open-label, blocked, randomized, cross-over trial was carried out in outpatient primary care clinics on 126 adults (mean age 52; 38% male) diagnosed with and currently experiencing mild-to-moderate symptoms with Patient Health Questionnaire-9 (PHQ-9) scores of 5–19. The intervention was 6 weeks of active treatment (248 mg of elemental magnesium per day) compared to 6 weeks of control (no treatment). Assessments of depression symptoms were completed at bi-weekly phone calls. The primary outcome was the net difference in the change in depression symptoms from baseline to the end of each treatment period. Secondary outcomes included changes in anxiety symptoms as well as adherence to the supplement regimen, appearance of adverse effects, and intention to use magnesium supplements in the future. Between June 2015 and May 2016, 112 participants provided analyzable data. Consumption of magnesium chloride for 6 weeks resulted in a clinically significant net improvement in PHQ-9 scores of -6.0 points (CI -7.9, -4.2; P<0.001) and net improvement in Generalized Anxiety Disorders-7 scores of -4.5 points (CI -6.6, -2.4; P<0.001). Average adherence was 83% by pill count. The supplements were well tolerated and 61% of participants reported they would use magnesium in the future. Similar effects were observed regardless of age, gender, baseline severity of depression, baseline magnesium level, or use of antidepressant treatments. Effects were observed within two weeks. Magnesium is effective for mild-to-moderate depression in adults. It works quickly and is well tolerated without the need for close monitoring for toxicity.

The Effects of Magnesium Supplementation on Subjective Anxiety and Stress—A Systematic Review

Article

Full-text available

Apr 2017

Background: Anxiety related conditions are the most common affective disorders present in the general population with a lifetime prevalence of over 15%. Magnesium (Mg) status is associated with subjective anxiety, leading to the proposition that Mg supplementation may attenuate anxiety symptoms. This systematic review examines the available evidence for the efficacy of Mg supplementation in the alleviation of subjective measures of anxiety and stress. Methods: A systematic search of interventions with Mg alone or in combination (up to 5 additional ingredients) was performed in May 2016. Ovid Medline, PsychInfo, Embase, CINAHL and Cochrane databases were searched using equivalent search terms. A grey literature review of relevant sources was also undertaken. Results: 18 studies were included in the review. All reviewed studies recruited samples based upon an existing vulnerability to anxiety: mildly anxious, premenstrual syndrome (PMS), postpartum status, and hypertension. Four/eight studies in anxious samples, four/seven studies in PMS samples, and one/two studies in hypertensive samples reported positive effects of Mg on subjective anxiety outcomes. Mg had no effect on postpartum anxiety. No study administered a validated measure of subjective stress as an outcome. Conclusions: Existing evidence is suggestive of a beneficial effect of Mg on subjective anxiety in anxiety vulnerable samples. However, the quality of the existing evidence is poor. Well-designed randomised controlled trials are required to further confirm the efficacy of Mg supplementation.

Insomnia and the risk of depression: A meta-analysis of prospective cohort studies

Article

Full-text available

Nov 2016
BMC PSYCHIATRY

Background Observational studies suggest that insomnia might be associated with an increased risk of depression with inconsistent results. This study aimed at conducting a meta-analysis of prospective cohort studies to evaluate the association between insomnia and the risk of depression. Methods Relevant cohort studies were comprehensively searched from the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases (up to October 2014) and from the reference lists of retrieved articles. A random-effects model was used to calculate the pooled risk estimates and 95 % confidence intervals (CIs). The I² statistic was used to assess the heterogeneity and potential sources of heterogeneity were assessed with meta-regression. The potential publication bias was explored by using funnel plots, Egger’s test, and Duval and Tweedie trim-and-fill methods. Results Thirty-four cohort studies involving 172,077 participants were included in this meta-analysis with an average follow-up period of 60.4 months (ranging from 3.5 to 408). Statistical analysis suggested a positive relationship between insomnia and depression, the pooled RR was 2.27 (95 % CI: 1.89–2.71), and a high heterogeneity was observed (I² = 92.6 %, P < 0.001). Visual inspection of the funnel plot revealed some asymmetry. The Egger’s test identified evidence of substantial publication bias (P <0.05), but correction for this bias using trim-and-fill method did not alter the combined risk estimates. Conclusions This meta-analysis indicates that insomnia is significantly associated with an increased risk of depression, which has implications for the prevention of depression in non-depressed individuals with insomnia symptoms.

Vitamin B12 Supplementation in Treating Major Depressive Disorder: A Randomized Controlled Trial

Article

Full-text available

Nov 2013
Open Neurol J

Recent literature has identified links between vitamin B12 deficiency and depression.We compared the clinical response of SSRI-monotherapy with that of B12-augmentation in a sample of depressed patients with low normal B12 levels who responded inadequately to the first trial with the SSRIs. Patients with depression and low normal B12 levels were randomized to a control arm (antidepressant only) or treatment arm (antidepressants and injectable vitamin B12 supplementation). A total of 199 depressed patients were screened. Out of 73 patients with low normal B12 levels 34 (47%) were randomized to the treatment group while 39 (53%) were randomized to the control arm. At three months follow up 100% of the treatment group showed at least a 20% reduction in HAM-D score, while only 69% in the control arm showed at least a 20% reduction in HAM-D score (p<0.001). The findings remained significant after adjusting for baseline HAM-D score (p=0.001). Vitamin B12 supplementation with antidepressants significantly improved depressive symptoms in our cohort.

Unveiling the role of melatonin MT2 receptors in sleep, anxiety and other neuropsychiatric diseases: A novel target in psychopharmacology

Article

Full-text available

Aug 2013
J PSYCHIATR NEUROSCI

Melatonin (MLT) is a pleiotropic neurohormone controlling many physiological processes and whose dysfunction may contribute to several different diseases, such as neurodegenerative diseases, circadian and mood disorders, insomnia, type 2 diabetes and pain. Melatonin is synthesized by the pineal gland during the night and acts through 2 G-protein coupled receptors (GPCRs), MT1 (MEL1a) and MT2 (MEL1b). Although a bulk of research has examined the physiopathological effects of MLT, few studies have investigated the selective role played by MT1 and MT2 receptors. Here we have reviewed current knowledge about the implications of MT2 receptors in brain functions. We searched PubMed, Web of Science, Scopus, Google Scholar and articles reference lists for studies on MT2 receptor ligands in sleep, anxiety, neuropsychiatric diseases and psychopharmacology, including genetic studies on the MTNR1B gene, which encodes the melatonin MT2 receptor. These studies demonstrate that MT2 receptors are involved in the pathophysiology and pharmacology of sleep disorders, anxiety, depression, Alzheimer disease and pain and that selective MT2 receptor agonists show hypnotic and anxiolytic properties. Studies examining the role of MT2 receptors in psychopharmacology are still limited. The development of novel selective MT2 receptor ligands, together with further preclinical in vivo studies, may clarify the role of this receptor in brain function and psychopharmacology. The superfamily of GPCRs has proven to be among the most successful drug targets and, consequently, MT2 receptors have great potential for pioneer drug discovery in the treatment of mental diseases for which limited therapeutic targets are currently available.

The effect of magnesium supplementation on primary insomnia in elderly: A double-blind placebo-controlled clinical trial

Article

Full-text available

Dec 2012
J Res Med Sci

Nearly 50% of older adults have insomnia, with difficulty in getting to sleep, early awakening, or feeling unrefreshed on waking. With aging, several changes occur that can place one at risk for insomnia, including age-related changes in various circadian rhythms, environmental and lifestyle changes, and decreased nutrients intake, absorption, retention, and utilization. The natural N-methyl-D-aspartic acid (NMDA) antagonist and GABA agonist, Mg(2+), seems to play a key role in the regulation of sleep. The objective of this study was to determine the efficacy of magnesium supplementation to improve insomnia in elderly. A double-blind randomized clinical trial was conducted in 46 elderly subjects, randomly allocated into the magnesium or the placebo group and received 500 mg magnesium or placebo daily for 8 weeks. Questionnaires of insomnia severity index (ISI), physical activity, and sleep log were completed at baseline and after the intervention period. Anthropometric confounding factors, daily intake of magnesium, calcium, potassium, caffeine, calories form carbohydrates, and total calorie intake, were obtained using 24-h recall for 3 days. Blood samples were taken at baseline and after the intervention period for analysis of serum magnesium, renin, melatonin, and cortisol. Statistical analyses were performed using SPSS19 and P values < 0.05 were considered as statistically significant. No significant differences were observed in assessed variables between the two groups at the baseline. As compared to the placebo group, in the experimental group, dietary magnesium supplementation brought about statistically significant increases in sleep time (P = 0.002), sleep efficiency (P = 0.03), concentration of serum renin (P < 0.001), and melatonin (P = 0.007), and also resulted in significant decrease of ISI score (P = 0.006), sleep onset latency (P = 0.02) and serum cortisol concentration (P = 0.008). Supplementation also resulted in marginally between-group significant reduction in early morning awakening (P = 0.08) and serum magnesium concentration (P = 0.06). Although total sleep time (P = 0.37) did not show any significant between-group differences. Supplementation of magnesium appears to improve subjective measures of insomnia such as ISI score, sleep efficiency, sleep time and sleep onset latency, early morning awakening, and likewise, insomnia objective measures such as concentration of serum renin, melatonin, and serum cortisol, in elderly people.

The relationship between micronutrient status and sleep patterns: a systematic review

Article

Oct 2016

Objective To review articles on the relationship of dietary and circulating micronutrients with sleep patterns, and to identify issues surrounding implications for future research and public health practice. Design A systematic review was conducted. PubMed, Embase and Scopus were searched through January 2016. Setting Both experimental and observational studies were included. However, studies that focused on secondary sleep impairment due to comorbidities were excluded. Subjects Individuals in different age groups, from infants to older adults. Results A total of twenty-six articles were selected. In the articles reviewed, researchers generally supported a potential role of micronutrients, particularly Fe and Mg, in the development of sleep stages among infants and in reversing age-related alterations in sleep architecture in older adults. Micronutrient status has also been linked to sleep duration, with sleep duration positively associated with Fe, Zn and Mg levels, and negatively associated with Cu, K and vitamin B12 levels. The mechanisms underlying these relationships include the impact of micronutrients on excitatory/inhibitory neurotransmitters and the expression of circadian genes. Conclusions Although the number of studies on the relationship between micronutrient status and sleep remains low, evidence has emerged that suggests a link between dietary/circulating micronutrients and sleep. Future research is needed to investigate the dose-dependent as well as the longitudinal relationships between micronutrient levels and human sleep across populations, test the interactions among micronutrients on sleep outcomes, and ultimately examine the clinical relevance of micronutrients on sleep health.

Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation

Article

Jun 2015
MOL NEUROBIOL

Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P < 0.05). Use of melatonin prevented memory impairment induced by SD. Furthermore, melatonin normalized SD-induced reduction in the hippocampus activity of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, melatonin enhanced the ratio of reduced to oxidized glutathione GSH/GSSG in sleep-deprived rats (P < 0.05) without affecting thiobarbituric acid reactive substance (TBARS) levels (P > 0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD.

The Effects of Magnesium -Melatonin -Vit B Complex Supplementation in Treatment of Insomnia

Abstract

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