|
Markus et al. (2005) [40]
Netherlands
|
Adults without sleep complaints
(n = 14)
Age (22 ± 3 years)
Adults with mild sleep complaint
(n = 14)
Age (22 ± 2 years)
|
20 g L-TRP-enriched
A-LAC protein
(4.8 g L-TRP/100 g amino acids w/w)
1 night
|
Double-blind
Placebo-controlled
|
Subjective Sleep Quality Measures:
Stanford Sleepiness Scale
|
Improved morning alertness
(p = 0.013) and increased attention (p = 0.002) in both groups.
Improved performance in participants with sleep complaints only (p = 0.05).
|
L-Tryptophan
|
Ong et al. (2017) [41]
Australia
|
Healthy males without sleep complaint
(n = 10)
Age (26.9 ± 5.3 years)
|
20 g L-TRP-enriched
A-LAC protein
(4.8 g L-TRP/100 g amino acids w/w) of A-LAC protein
2 nights
|
Double-blind
Placebo-controlled
Randomized
Crossover
|
Objective Sleep Quality Measures (Actigraphy):
Total sleep time
Sleep onset latency
Sleep efficiency (%)
Wake time after sleep onset
Subjective Sleep Measures (Sleep Log):
Bedtime
Time taken to fall asleep
Frequency of awakenings
Time taken to return to sleep
Waking time
Rising time
Total sleep time
|
Increased objective and subjective total sleep time by 12.8% (p = 0.037) and 10.8%
(p = 0.013), respectively; increased objective sleep efficiency by 7.0%
(p = 0.028).
|
|
Cubero et al. (2007) [42]
Spain
|
Pre-weaning infants
(n = 30)
Age (4–20 weeks)
|
Diet A: Standard formula Diet B: Standard formula during the day and night formula (3.4 g L-TRP/100 g protein)
Diet C: Day formula during the day (1.5 g L-TRP/100 g protein) + night formula (3.4 g L-TRP/100 g protein) in the evening
1 week per formula
|
Double-blind
Randomized
|
Objective Sleep Quality Measures (Actigraphy):
Time of nocturnal sleep
Minutes of immobility
Sleep latency
Nocturnal awakenings
Sleep efficiency (%)
Sleep Diary:
Sleep over 24 h
Number of bottle feeds
Observations or incidences that would influence the infants rest
|
Diet C improved objective total sleep time (p < 0.05) and subjective (parent) sleep improvement; Diet B and Diet C reduced objective sleep onset latency; Diet B improved objective sleep efficiency.
(All p’s < 0.05)
|
|
Bravo et al. (2013) [43]
Spain
|
Older adults with sleep difficulties
(n = 35)
Age (55–75 years)
|
L-TRP (60 mg) enriched cereal for breakfast and dinner
1 week
|
Blind assay
|
Objective Sleep Quality Measures (Actigraphy):
Time in bed
Assumed sleep
Actual sleep time
Sleep onset latency
Sleep efficiency (%)
Number of awakenings
Immobile time
Total activity
Fragmentation index (indicator of quality of rest)
|
Improvements in objective sleep measures including increase in actual sleep time (p < 0.01); increase in sleep efficiency (p < 0.001); increase in immobile time (p < 0.01); reduction in sleep latency (p < 0.01); wake bouts
(p < 0.05); total activity (p < 0.01); fragmentation index (p < 0.001).
|
5-HTP
|
Bruni et al. (2004) [44]
Italy
|
Children with sleep terrors
(n = 45)
Age (3.2–10.6 years)
|
2 mg/kg
(Daily)
20 days
|
Randomized, controlled
|
Frequency of sleep terrors
|
After 1-month:
Sleep terrors reduced > 50% from
baseline in 93.5% of children treated with 5-HTP (p < 0.00001).
After 6 months:
51.6% were sleep-terror free
(p < 0.001).
|
Melatonin
|
Scheer et al. (2012) [45]
USA
|
Hypertensive adults on beta blockers
(n = 16)
Age (45–64 years)
|
2.5 mg
(nightly, 1 h before bedtime)
3 weeks
|
Randomized,
Double-blind
Placebo-controlled
Parallel-group design
|
Objective Sleep Quality Measures
(Polysomnography):
Sleep stages
Total sleep time
Time in bed
Sleep efficiency (%)
Objective Sleep Quality Measures (Actigraphy):
Sleep onset latency
Total sleep time
Sleep efficiency (%)
|
Increased total sleep time by 32 min
(p = 0.046); increased sleep efficiency by 7.6% (p = 0.046). Decreased sleep onset latency to stage 2 NREM sleep by 14 min (p = 0.001) and increased the duration of stage 2 NREM sleep by 42 min (p = 0.037).
|
|
Grima et al. (2018) [46]
Australia
|
Adults with sleep disturbance post onset of traumatic brain injury
(n = 33)
Age (37 ± 11 years)
|
2 mg
(nightly 2 h before bedtime)
4 weeks
|
Randomized,
Double-blind
Placebo-controlled
Two-period
Two-treatment
Crossover study
|
Objective Sleep Quality Measures (Actigraphy)
Sleep onset latency
Total sleep time
Sleep duration
Sleep efficiency (%)
Sleep Diary:
Sleep onset/offset
Sleep duration
Subjective Sleep Quality Measures:
PSQI
ESS
FSS
|
Improved subjective sleep quality
(p < 0.0001) and objective sleep efficiency (p < 0.04).
|
|
Xu et al. (2020) [47]
China
|
Adults with primary insomnia (n = 97)
Age (45–60 years)
|
3 mg
(nightly 1 h before bedtime)
4 weeks
|
Randomized,
Double-blind
Placebo-controlled
Parallel study
|
Objective Sleep Quality Measures
(Polysomnography):
Sleep stages
Total sleep time
Sleep onset latency
Wake after sleep onset
Sleep efficiency (%)
Subjective Sleep Quality Measures:
PSQI
ESS
ISI
|
Decreased objective sleep measures including early morning wake (p = 0.001) and decreased percentage of Stage 2 NREM sleep (p = 0.031).
|
L-Cysteine
|
Sadasivam et al. (2011) [48]
India
|
Adults with obstructive sleep apnea
(n = 20)
Age (53.1 ± 2.3 years)
|
600 mg (Mucinac,
Cipla), three times per day
30 days
|
Randomized,
Placebo-controlled
|
Objective Sleep Quality Measures
(Polysomnography):
Sleep stages
Total sleep time
Sleep onset latency
Wake after sleep onset
Sleep efficiency (%)
Sleep apnea
Snoring
Subjective Sleep Quality Measures:
ESS
|
Improvements in objective slow wave sleep as sleep percent time (p < 0.001) and sleep efficiency.
(p < 0.05).
Reduction in subjective Epworth Sleepiness Score (p < 0.001).
|
|
Rao et al. (2019) [49]
Japan
|
Healthy adult males
(n = 22)
Age (27.5 ± 0.9 years)
|
4 × 50 mg
(nightly, 1 h before bedtime)
6 days
|
Randomized,
Double-blind
Placebo-controlled
Crossover trial
|
Objective Sleep Quality Measures (Actigraphy):
Time in bed
Wake after sleep onset
Sleep onset latency
Sleep length
Sleep efficiency (%)
Subjective Sleep Quality Measures:
Obstructive Sleep Apnea
Inventory questionnaire
|
Improvements in objective sleep measures including an increase in objective sleep efficiency (p < 0.047) and reduction in intermittent
wakening (p < 0.044).
Improvements in subjective sleep measures including feeling of recovery from exhaustion or fatigue scores (p < 0.042) and improvement in refreshed upon awakening scores
(p < 0.014).
|
L-Theanine
|
Lyon et al. (2011) [50]
Canada
|
Boys with ADHD
(n = 98)
Age (8–12 years)
|
2 × 100 mg
(twice per day,
morning and evening)
6 weeks
|
Randomized,
Double-blind
Placebo-controlled
Parallel trial
|
Objective Sleep Quality Measures (Actigraphy):
Wake after sleep onset
Sleep onset latency
Sleep length
Nocturnal activity
Sleep efficiency (%)
Subjective Sleep Quality Measures:
Pediatric Sleep Questionnaire
|
Improved objective measures including sleep efficiency (p < 0.05), and reduced nocturnal activity (p < 0.05).
|
|
Sarris et al. (2019) [51]
Australia
|
Adults with GAD
(n = 46)
Age (40.7 ± 15 years in TG; 32.2 ± 9.29 years in PG)
|
225 mg (twice daily); increased to 450 mg (twice daily) if anxiety score did not reduce by ≥35% after 4 weeks
8 weeks
|
Randomized,
Double-blind
Placebo-controlled
Multi-center pilot study
|
Subjective Sleep Quality Measures:
ISI
|
Improved subjective sleep
satisfaction
(p < 0.015); improvements in ISI scores for “difficulty in falling asleep”
(p < 0.049); “Problems waking up too early” (p < 0.017); and “interference with daily functioning” (p = 0.030) in control.
|
|
Hidese et al. (2019) [52]
Japan
|
Healthy Adults
(n = 30)
Age (48.3 ± 11.9 years)
|
200 mg tablet daily before sleep
4 weeks
|
Randomized,
Double-blind
Placebo-controlled
Crossover trial
|
Subjective Sleep Quality Measures:
PSQI
|
Improved subjective sleep quality (p < 0.013), reduced sleep onset latency, sleep disturbance and use of sleep medication (All p’s < 0.05).
|
Vitamin B12
|
Mayer et al. (1996) [53]
|
Healthy Adults
(n = 20)
Age (CB12 = 36.6 ± 5.2 years.
MB12 = 36.2 ± 5.2 years)
|
3 mg
(cyano-(CB12) or methylcobalamin (MB12))
14 days
|
Randomized
Single-blind
Between subject’s design
|
Objective Sleep Quality Measures (Actigraphy):
Wake after sleep onset
Sleep onset latency
Sleep length
Nocturnal activity
Sleep efficiency (%)
Subjective Sleep Quality Measures:
Morning and Evening VAS
|
Reduction in objective sleep time
(p = 0.036) in MB12 group improvements in sleep quality and daytime alertness (All p’s < 0.05).
|
|
Luboshitzky et al. (2002) [54]
Israel
|
Healthy Adult Males
(n = 12)
Age (22–26 years)
|
100 mg
(5.00 PM)
Once
|
Randomized
Placebo-controlled
Parallel trial
|
Objective Sleep Quality Measures (EEG):
Sleep stages (%)
Total recording time
Sleep latency
Actual sleep time
Sleep efficiency (%)
REM latency
|
No effect.
|
Vitamin B6
|
Ebben et al. (2002) [55]
USA
|
Healthy Adults
(n = 12)
Age (18–28 years)
|
100 mg
250 mg
Placebo
(All nightly before bed)
5 days per treatment
|
Placebo-controlled
Double-blind
Crossover trial
|
Subjective Sleep Quality Measures:
Sleep questionnaire
Dream Salience Scale
|
Increase in dream salient scores in
250 mg B6 treatment compared to placebo (p = 0.05).
|
|
Aspy et al. (2018) [56]
Australia
|
Healthy Adults
(n = 100)
Age (mean = 27.5)
|
120 mg
(pyridoxine hydrochloride)
Vitamin B Complex
(120 mg pyridoxine hydrochloride + other B vitamins)
Placebo
(All nightly before bed)
5 days
|
Randomized
Double-blind
Placebo-controlled trial
|
Subjective Sleep Quality Measures:
Sleep log
|
Increased the amount of dream content recalled (p = 0.032) and decrease in sleep quality (p = 0.014) in B complex group.
|
Vitamin D
|
Ghaderi et al. (2017) [57]
Iran
|
Adults undergoing Methadone Treatment.
(n = 68)
Age (25–70 years)
|
50,000 IU
(once per fortnight)
12 weeks
|
Randomized
Double-blind
Placebo-controlled trial
|
Subjective Sleep Quality Measures:
PSQI
|
Improvement in subjective sleep score
(p = 0.02).
|
|
Mason et al. (2016) [58]
USA
|
Overweight menopausal females with low VitD
(n = 218)
Age (50–75 years)
|
2000 IU vitamin D3
(daily)
12 months
|
Randomized
Double-blind
Placebo-controlled trial
|
Subjective Sleep Quality Measures:
PSQI
|
Increase in PSQI score (p = 0.01) and increase in need to take sleep medication (p < 0.01).
|
Vitamin C
|
Dadashpour et al. (2018) [59]
Iran
|
Adults on hemodialysis with sleep disorder
(n = 90)
Age (18–70 years)
|
500 mg /5 cc intravenously–3 times per week
8 weeks
|
Randomized
Double-blind
Trial
|
Subjective Sleep Quality Measures:
PSQI
VAS
|
Reductions in subjective sleep quality, sleep latency, daytime dysfunction
(All p’s = 0.001).
|
|
Yeom et al. (2007) [60]
Korea
|
Adults with Stage IV cancer
(n = 39)
Age (53.5 ± 10.5 years)
|
10 g vitamin C intravenously twice with 3-day interval, then
4 g oral supplement daily
1 week
|
Prospective study
|
Subjective Sleep Quality Measures:
European Organization for
Research and Treatment of Cancer Core Quality-of-Life questionnaire (EORTC QLQ-C30)-Korean Version
|
Lower subjective scores for sleep disturbance and fatigue (p < 0.005).
|
|
Murck et al. (2000) [61]
Germany
|
Older adults without sleep disturbances (n = 12)
Age (60–80 years)
|
10 mmol for 3 days, then
20 mmol for 3 days, then
30 mmol daily for 14 days
|
Randomized
Placebo-controlled
Crossover design
|
Objective Sleep Quality Measures (EEG):
Sleep stages (%)
Total recording time
Sleep latency
Actual sleep time
Sleep efficiency (%)
REM latency
|
Increase in slow wave sleep (p < 0.05), delta and sigma waves (p < 0.05 for both).
|
Magnesium
|
Abbasi et al. (2012) [62]
Iran
|
Older adults
(n = 43)
Age (65 ± 4.6 years)
|
414 mg magnesium oxide (250 mg Mg)
Twice per day
8 weeks
|
Double-blind
Placebo-controlled trial
|
Subjective Sleep Quality Measures:
ISI
Sleep Log
|
Increase in subjective sleep time
(p = 0.002) and subjective sleep efficiency (p = 0.03); decrease in subjective sleep onset latency (p = 0.04), and insomnia severity index (p = 0.006).
|
|
Hornyak et al. (2004) [63]
Germany
|
Alcohol dependent adults in subacute withdrawal with sleep disturbance
(n = 11)
|
30 mmol Magnesium
L-aspartate hydrochloride (10 mmol morning and 20 mmol evening) daily
4 weeks
|
Open Pilot Study
|
Objective Sleep Quality Measures (Polysomnography):
Sleep stages
Total sleep time
Sleep onset latency
Wake after sleep onset
Sleep efficiency (%)
Periodic leg movements in sleep (PLMS)
Subjective Sleep Quality Measures:
PSQI
|
Decrease in objective sleep latency
(p = 0.03), improvement in subjective sleep quality (p = 0.05).
|
Zinc
|
Saito et al. (2017) [64]
Japan
|
Healthy Adults
(n = 94)
Age (20–84 years)
|
Group A: Placebo
Group B: 15 mg
Group C: 15 mg + Astx
Group D: Placebo + 16 mg + Astx
12 weeks
|
Randomized
Double-blind
Placebo-controlled
Parallel group trial
|
Objective Sleep Quality Measures (Actigraphy):
Wake after sleep onset
Sleep onset latency
Sleep length
Frequency
Nocturnal activity
Sleep efficiency (%)
Subjective Sleep Quality Measures:
PSQI
|
Improvements in objective sleep efficiency in group B (p = 0.025); objective sleep onset latency in Group B and D (p < 0.032) and (p = 0.004), respectively.
|
|
Gholipour et al. (2018) [65]
Iran
|
ICU nurses
(n = 54)
Age (31.2 ± 5.42 years)
|
1 × 220 mg
(every 72 h)
1 month
|
Multi-center
Randomized
Two parallel group
Placebo-controlled trial
|
Subjective Sleep Quality Measures:
PSQI
|
Improvements in subjective total sleep quality (p < 0.002); sleep onset latency
(p < 0.003), sleep duration (p < 0.02) and total sleep quality score (p < 0.008).
|