Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study.

Su Eun Lim, Ho Seok Kim, Siwoo Lee, Eun Young Kang, Jong-Hyun Lim et al.

Other Frontiers in nutrition 2024 5 цитирований

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Study Design

Тип исследования: RCT
Размер выборки: 40
Длительность: 8 weeks

Вмешательство: Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study. None
Препарат сравнения: Placebo
Направление эффекта: Positive
Риск систематической ошибки: Moderate

Abstract

INTRODUCTION: The use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover, recent studies have shown a significant correlation between sleep quality and gut microbiota composition. This study aimed to assess the impact of LTC-022, a commercially available dietary supplement containing Lactium and L-theanine, on enhancing sleep quality. METHODS: Forty participants experiencing sleep discomfort were enrolled in a double-blind randomized controlled trial, wherein they received LTC-022 or a placebo orally for 8 weeks. The effects of treatment on sleep quality were assessed using the Pittsburgh Sleep Quality Index and Insomnia Severity Index. To comprehensively evaluate changes in sleep patterns, various parameters were evaluated, including the time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO) counts, and bedtime. These parameters were derived from daily sleep logs recorded over the 8-week study period, categorized into weekdays and weekends. Stool samples were analyzed for microbiome composition. The V4 region of bacterial 16S rRNA genes was amplified using specific primers (515F and 806R) and targeted for analysis. Microbial diversity, including operational taxonomic units, the Shannon and Chao indices, the Firmicutes/Bacteroidetes (F/B) ratio, and the variety of bacterial taxa, was assessed. RESULTS: No significant differences were observed in sleep quality and insomnia scale characteristics between the two groups. In-depth analysis using sleep diaries showed that WASO counts after 8 weeks and bedtime after 4 weeks showed significant differences between the LTC-022 and control groups. In the LTC-022 group, significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts, and earlier bedtime. Microbiome analysis revealed that the abundance of the genera Blautia and Ruminococcus increased in fecal samples from the LTC-022 group. CONCLUSION: These results suggest that continuous LTC-022 intake has a beneficial effect on maintaining sleep duration and an appropriate bedtime. Additionally, changes in the gut microbiota may be linked to changes in sleep patterns resulting from the consumption of Lactium and L-theanine. CLINICAL TRIAL REGISTRATION: https://cris.nih.go.kr/cris/search/detailSearch.do/22841, KCT0007750.

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Figure 1

Participant flow and allocation in a double-blind, randomized, placebo-controlled trial investigating Lactium and L-theanine supplementation for sleep disturbance in adults.

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Figure 2

Outcomes of sleep quality measures comparing the Lactium and L-theanine supplementation group with placebo, indicating potential improvements in sleep disturbance parameters among treated participants.

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Tables

Table 1

Characteristic	Total	LTC-022 (n = 20)	Control (n = 20)	p-value
Sex, n (%)
Male	2 (5.0)	1 (5.0)	1 (5.0)	1.000
Female	38 (95.0)	19 (95.0)	19 (95.0)	1.000
Age, yr. (SD)	47.8 (6.8)	48.2 (6.7)	47.4 (7.1)	0.176
BMI, kg/m² (SD)	23.3 (2.5)	23.3 (2.6)	23.3 (2.4)	0.954
Drinking, n (%)
Yes	18 (45.0)	10 (50.0)	8 (40.0)	0.751
No	22 (55.0)	10 (50.0)	12 (60.0)	0.751
Smoking, n (%)
Yes	3 (7.5)	2 (10.0)	1 (5.0)	1.000
No	37 (92.5)	18 (90.0)	19 (95.0)	1.000
Safety indices
AST, U/L (SD)	20.60 (6.69)	22.20 (7.56)	19.00 (5.42)	0.132
ALT, U/L (SD)	16.78 (8.14)	18.45 (8.91)	15.10 (7.12)	0.197

Table 2

Variables	LTC-022	Control	p-value	p-interaction^†
Sleep quality
Baseline	9.7 (2.43)	10.8 (2.86)	0.198^a	0.621
Week 4	6.75 (2.34)^*	7.9 (2.83)^*	0.340^b
Week 8	6.55 (2.48)^*	6.95 (2.96)^*	0.847^b
Insomnia severity
Baseline	13.0 (4.30)	14.2 (3.16)	0.322^a	0.676
Week 4	8.60 (3.78)^*	10.75 (4.61)^*	0.211^b
Week 8	7.25 (3.68)^*	9.4 (5.71)^*	0.282^b

Table 3

Variables	Weekday				Weekend
Variables	LTC-022	Control	p-value	p-interaction^†	LTC-022	Control	p-value	p-interaction^†
TIB (min)
Baseline	456.70 (57.70)	455.35 (72.05)	0.949^a	0.864	453.88 (57.50)	453.33 (73.77)	0.980^a	0.656
Week 4	458.28 (47.64)	450.09 (76.19)	0.744^b		476.27 (74.51)	474.72 (116.3)	0.839^b
Week 8	465.09 (55.82)	457.17 (112.63)	0.767^b		482.88 (65.18)	462.29 (81.43)	0.345^b
TST (min)
Baseline	392.40 (58.04)	400.39 (49.73)	0.648^a	0.367	401.13 (52.49)	412.38 (56.38)	0.523^a	0.300
Week 4	412.45 (45.41)^*	397.70 (53.69)	0.143^b		428.94 (82.58)	421.71 (86.08)	0.444^b
Week 8	419.75 (53.98)^*	407.86 (80.42)	0.404^b		443.25 (65.26)^*	414.50 (59.31)	0.123^b
SOL (min)
Baseline	64.30 (40.53)	54.96 (59.80)	0.570^a	0.355	52.75 (41.97)	40.96 (52.29)	0.441^a	0.359
Week 4	45.83 (31.84)^*	52.39 (66.08)	0.135^b		47.33 (41.30)	53.01 (69.36)	0.280^b
Week 8	45.34 (41.67)	49.30 (58.81)	0.499^b		39.63 (34.78)	47.79 (58.65)	0.273^b
SE (%)
Baseline	86.04 (8.58)	88.93 (10.27)	0.346^a	0.222	88.75 (8.46)	91.72 (8.49)	0.281^a	0.349
Week 4	90.14 (6.17)^*	89.34 (10.32)	0.124^b		89.91 (8.23)	90.21 (10.17)	0.528^b
Week 8	90.50 (8.06)^*	90.56 (8.97)	0.527^b		91.81 (6.51)	90.65 (10.09)	0.253^b
WASO (counts)
Baseline	2.42 (1.49)	1.66 (0.74)	0.053^a	0.007	1.95 (0.97)	1.89 (0.80)	0.824^a	0.601
Week 4	1.62 (1.68)^*	1.55 (0.71)	0.119^b		1.50 (1.67)	1.79 (0.94)	0.499^b
Week 8	1.31 (1.83)^*	1.63 (0.96)	0.010^b		1.60 (2.55)	1.53 (0.99)	0.926^b
Bedtime (hh:mm)
Baseline	24:33 (59.66)	24:22 (67.06)	0.605^a	0.083	24:43 (53.01)	24:28 (85.43)	0.524^a	0.193
Week 4	24:06 (48.32)^*	24:25 (66.72)	0.021^b		24:20 (66.33)	24:25 (84.43)	0.503^b
Week 8	24:01 (56.44)^*	24:25 (68.58)	0.090^b		24:01 (62.02)^*	24:29 (66.34)	0.055^b

Table 4

Genus	LTC-022	Control	p-value
Bifidobacterium	5.13 (4.79)	9.74 (6.62)	0.041
Prevotella	13.23 (12.45)	3.09 (6.53)	0.027
Erysipelatoclostridium	0.18 (0.62)	0.29 (0.41)	0.024
Megamonas	1.96 (4.08)	0.62 (2.50)	0.018

Table 5

LTC-022
Genus	Baseline	Week 8	p-value
Bilophila	0.17 (0.18)	0.10 (0.06)	0.046
Blautia	6.59 (3.40)	7.43 (2.94)	0.031
Clostridium	0.47 (0.86)	0.22 (0.55)	0.027
Holdemania	0.02 (0.02)	0.01 (0.01)	0.045
Hungatella	0.27 (0.24)	0.60 (0.79)	0.027
Ruminococcoides	0.02 (0.09)	1.08 (2.44)	0.037
Ruminococcus	2.01 (2.12)	3.54 (3.37)	0.003
Sutterella	1.73 (1.74)	0.99 (0.77)	0.017

Table 6

Control
Genus	Baseline	Week 8	p-value
Anaerobutyricum	1.07 (0.81)	1.50 (2.05)	0.039
Bifidobacterium	5.34 (3.39)	9.71 (6.59)	0.003
Collinsella	1.96 (1.88)	2.93 (2.71)	0.045
Eubacterium	0.13 (0.17)	0.29 (0.45)	0.049
Faecalibacterium	15.91 (8.56)	11.95 (6.88)	0.008
Odoribacter	0.15 (0.13)	0.26 (0.28)	0.044
Parasutterella	0.65 (1.06)	0.31 (0.49)	0.026
Prevotella	6.52 (9.91)	3.09 (6.53)	0.049
Ruminococcus	2.13 (2.36)	2.97 (3.33)	0.047
Sutterella	1.01 (1.13)	0.70 (0.84)	0.017

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Dietary supplementation with Lactium and L-theanine alleviates sleep disturbance in adults: a double-blind, randomized, placebo-controlled clinical study.

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