The Role of Supplements and Over-the-Counter Products to Improve Sleep in Children: A Systematic Review.
Alice Innocenti,
Giuliana Lentini,
Serena Rapacchietta,
Paola Cinnirella,
Maurizio Elia
et al.
Systematic Review
International journal of molecular sciences
2023
14 اقتباسات
PubMed
DOI
CC-BY
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Study Design
- نوع الدراسة
- systematic_review
- التدخل
- The Role of Supplements and Over-the-Counter Products to Improve Sleep in Children: A Systematic Review. iron, 5-hydroxytryptophan (5-HTP), theanine, antihistamines (OTC supplements)
- المقارن
- Placebo
- اتجاه التأثير
- Mixed
- خطر التحيز
- Moderate
Abstract
The sleep-wake cycle is a complex multifactorial process involving several neurotransmitters, including acetylcholine, norepinephrine, serotonin, histamine, dopamine, orexin and GABA, that can be, in turn, regulated by different nutrients involved in their metabolic pathways. Although good sleep quality in children has been proven to be a key factor for optimal cognitive, physical and psychological development, a significant and ever-increasing percentage of the pediatric population suffers from sleep disorders. In children, behavioral interventions along with supplements are recommended as the first line treatment. This systematic review was conducted, according to the PRISMA guidelines, with the purpose of assessing the principal nutrients involved in the pathways of sleep-regulating neurotransmitters in children and adolescents. Our focus was the utilization of over the counter (OTC) products, specifically iron, hydroxytryptophan, theanine and antihistamines in the management of different pediatric sleep disorders with the intention of providing a practical guide for the clinician.
Full Text
Figures
Tables
Table 3
| Study | Design | Objective | Subjects (Age) | Methods | Results |
|---|---|---|---|---|---|
| Bruni et al., | open trial | assess L-5-HTP effects on sleep terrors | 45 children | EEG and sleep | at 6 months follow-up 83.9% of children treated with L-5-HTP were sleep terror-free, while 71.4% of children in the comparison group continued to show sleep terrors |
| Aparicio et al., | double blind | effects of day/night | 18 infants | TRP-enriched milk. Sleep daily agenda, actigraphy and urine catecholamine and serotonin metabolites | TRP-enriched milk induces an increase in sleep quality and duration, probably due to an increase in serotonin levels |
| Harada et al., | cohort study | evaluate the association between morning TRP intake and circadian typology | 2279 children | TRP index, M-E questionnaire | significant positive correlation between TRP index and M-E questionnaire in infants and young elementary school students aged 0–8 yrs. Lower TRP indices correlated with difficulty in both falling asleep and in waking up in the morning, and with tendency to anger and depression |
| Cubero et al., | double blind | influence of TRP-enriched | 30 infants | actigraphy | TRP-enriched cereals improve sleep quality in terms of sleep onset latency and decrease in the awakenings |
| Nakade et al., | cohort study | correlation between TRP | 744 children | M-E questionnaire | children with nutritionally well-balanced breakfasts tended to be more morning-typed, and woke up and fell asleep at earlier times |
| Nakade et al., | cohort study | evaluate the integrated effects of tryptophan and vitamin B6 intake at breakfast and following sunlight exposure on the circadian typology and sleep habits | 816 children | TRP index, | positive correlation between M-E index and TRP index only in children exposed to sunlight for longer than 10 min after breakfast |
| Van zyl et al., | retrospective | L-TRP as a treatment for | 165 children | PSG and | 84% of children taking L-TRP experienced improvements in their parasomnia vs. 47% of non-treated |
Table 1
| Study | Design | Objective | Subjects (Age) | Methods | Results |
|---|---|---|---|---|---|
| Peirano et al., 2007 [ | retrospective | association of IDA in infancy with long term alteration of the sleep cycle organization | 55 children | PSG | IDA in early infancy is associated with long-term changes in the temporal organization of the sleep stages |
| Simakajornboon et al. 2003 [ | prospective study | assess relationship between serum iron and ferritin levels and PLMS, and response to supplemental iron therapy | 39 children | PSG, serum iron and ferritin levels | positive correlation between PLMS index and iron levels; 76% of patients improved PLMS index after 3 months of iron supplementation with an increase in ferritin levels |
| Dosman et al., 2007 [ | open label | effect of iron supplementation on sleep and serum ferritin levels in children with ASD | 33 ASD children | clinical evaluation, serum ferritin levels, SDSC, PLMS scale | restless sleep score showed improved after iron supplementation |
| Kordas et al., | Randomized | effect of iron supplementation on infant’s sleep as reported by the mothers in Nepali and | 877 Pembans | maternal reports | longer sleep duration in iron supplemented infants vs. placebo |
| Grim et al., | retrospective study | efficacy and safety of IV iron sucrose in children with RLS/PLMD | 16 children | PSG, serum | IV iron sucrose can be considered a valid and rather safe alternative to oral iron supplementation |
| Tilma et al., | cohort study | define pediatric RLS symptoms and iron supplementation efficacy | 22 children | clinical evaluation, serum iron and ferritin | high PLMS index correlated with serum ferritin levels, iron treatment positively correlated with a ferritin-concentration-dependent clinical effect |
| Dye et al., | retrospective study | assessment of long-term effects of iron treatment in pediatric RLS and PLMD | 105 children | iron, ferritin, and PLMS index at baseline and at 3, 6, 12 and 24 months after iron therapy | improvement in PLMS index and ferritin levels >2 years after iron treatment |
| Gurbani et al., 2019 [ | retrospective study | impact of iron treatment on | 226 children | ferritin level and PSG before and after iron treatment | iron therapy correlated with improvement in PLMS index, RLS symptoms and resolution of NREM sleep parasomnias |
| Reynolds et al., 2019 [ | randomized | oral ferrous sulphate as treatment for insomnia in children with ASD and low ferritin levels | 20 children | serum iron and ferritin levels, actigraphy and Sleep CGI-S at baseline and after 3 months of iron supplementation | amelioration in Sleep CGI-S |
| Ryan et al., | retrospective study | to evaluate the risk of iron deficiency in AS and the efficacy of iron supplementation on correlated sleep disorders | 19 AS children | sleep history, PSG, serum ferritin levels before and after oral, IV or combined iron supplementation | AS patients with increased prevalence of iron deficiency and sleep disturbances (vs. age-matched controls), treatable with iron supplementation |
| DelRosso et al., 2020 [ | retrospective study | understanding the causative factors in the treatment response variability of PLMD in children | 77 children | clinical | increase in serum ferritin levels in response to oral iron supplementation best predicting factor in evaluating PLMD symptoms alleviation |
| DelRosso et al., 2021 [ | retrospective study | appraise efficacy and safety of IV FCM in RLS and PLMD | 39 patients | serum iron and ferritin levels and CGI | IV FCM valid and safe alternative in PLMD non-responders to oral iron supplementation |
| DelRosso et al., 2021 [ | retrospective study | compare oral FS and IV FCM | 30 children | serum ferritin, iron profile, video-PSG at baseline and at 3- month follow-up after treatment with either oral FS or IV FCM | IV FCM with greater beneficial effect on pediatric RSD vs. oral FS supplementation |
| Mikami et al., 2021 [ | prospective study | determine effects of iron supplementation on psychological status of iron deficient children and adolescents, including sleep difficulties | 19 children | PSQI, CGI-S, POMS and CES-d | after iron treatment, contextually to increase in serum ferritin, significant improvement in PSQI, CGI-S, CES-d scores and in POMS subscales at week 12 |
| Al-shawwa et al., 2022 [ | case report | effectiveness of iron infusion therapy in an RLS patient with related sleep disturbances | 2-year-old child | IV iron | complete resolution of RLS and sleep-related disorder |
Table 2
| Study | Design | Objective | Subjects (Age) | Methods | Results |
|---|---|---|---|---|---|
| Merenstein et al., 2006 [ | double-blind, | to evaluate the efficacy of diphenhydramine hydrochloride therapy in children with frequent nocturnal awakenings | 44 infants | parental reports | diphenhydramine no more effective than placebo |
| Ghanizadeh et al., 2013 [ | randomized | to investigate the efficacy of | 30 children | VAS and CGI-S at baseline and | significant reduction in bruxism severity with hydroxyzine treatment, with respect to placebo |
| Wesselhoeft et al., 2021 [ | descriptive study | to investigate the use of melatonin, z-drugs and sedating antihistamines among Scandinavian children and young adults | all Scandinavian children | public databases from Sweden, Norway, and Denmark | annual prevalence of sedating antihistamine use was highest in Sweden, 13/1000 in 2018; 7.5/1000 in Norway and 2.5/1000 in Denmark. Melatonin the most commonly used hypnotic. |
Table 4
| Study | Design | Objective | Subjects (Age) | Methods | Results |
|---|---|---|---|---|---|
| Lyon et al., | randomized, double-blind | L-theanine efficacy on sleep quality of ADHD children | 98 children | actigraphy and PSQI | L-theanine increased sleep time and efficiency in ADHD patients |
| Unno et al., | double-blind crossover | low caffeine green tea effect on sleep quality and stress levels of middle-aged individuals | 20 adults | EEG, | low caffeine green tea |
| Unno et al., | open trial | low caffeine green tea effect on sleep quality in the | 10 elderly | EEG, | low caffeine green tea improved sleep quality |
| Hidese et al., | randomized control trial | effects of L-theanine on stress-related symptoms and cognitive functions in healthy adults | 30 adults | self-rating depression scale, state-trait anxiety inventory-trait, PSQI | significant improvement in sleep onset latency, sleep disturbances and use of sleep medication |
| Halson et al., | randomized control trial | validate nutritional | 18 adult males (20- 33 years) | PSG, cognitive tests, postural sway, subjective sleep | nutritional interventions can induce a significant improvement in sleep onset latency |
| Ross et al., | case report | nutrients efficacy on mood disorders and sleep | 26-year-old | self-report | nutritional supplements can |
| Noah et al., | randomized control trial | effect of Mg-Teadiola on stress | 100 adults | PSQI | better scores at PSQI on day 56 |
| Langan-Evans et al., | randomized, double- blind, cross-over trial | effects of a nutritional blend, including L-theanine, on sleep quality | 16 adults | actigraphy, PSQI, | the nutritional blend increased total sleep duration and sleep efficiency |
| Thiagarajah et al., | randomized, double- blind, cross-over trial | evaluate effects of alpha-s1-casein tryptic hydrolysate and L-theanine on sleep quality | 39 adults | PSQI, heart rate, blood pressure, salivary cortisol, EEG | improvement in PSQI total score, sleep latency, sleep duration, sleep habitual efficiency, daytime dysfunction, and increased total and frontal alpha power significantly |
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