Calambres (menstruales)

5-HTP is a direct precursor to serotonin, which converts to melatonin, giving it a mechanistic basis for sleep maintenance. Clinical studies show 5-HTP reduces REM sleep fragmentation and augments overall sleep quality. In combination clinical formulas, 5-HTP has been shown to increase total sleep time and reduce nocturnal awakenings. Evidence is promising but most robust for combination formulas rather than isolated 5-HTP RCTs.

Ashwagandha (Withania somnifera) root extract has been specifically shown to reduce wake after sleep onset (WASO) in multiple RCTs. A 2020 double-blind RCT (n=144, 600 mg/day, 6 weeks) found significant improvements in WASO (p<0.05), sleep efficiency (p<0.01), and total sleep time (p<0.001) versus placebo. A 2021 meta-analysis of 5 RCTs (n=400) confirmed a significant overall sleep benefit (SMD −0.59, 95% CI −0.75 to −0.42).

Preclinical data demonstrate that essential oil and saponin fractions of Semen Platycladi prolong total sleep duration in PCPA-induced insomnia mice, in addition to shortening sleep onset. The dual action on serotonergic and GABAergic targets suggests a broad sleep-maintenance effect beyond mere sedation. No human trials have been conducted.

The same open-label combination study (Abdellah et al. 2019) showed a significant reduction in nighttime awakenings (p<0.0001) in insomnia patients alongside increased total sleep duration. The EMA herbal monograph recognizes E. californica for traditional use in minor sleep disorders including disturbed sleep. Preclinical data in rodents support extended sleep duration in a dose-dependent manner.

Chamomile contains apigenin, which binds to GABA-A receptor benzodiazepine sites to produce mild anxiolytic and sedative effects supporting sleep maintenance. A 2017 RCT in 80 postpartum women found chamomile tea for 2 weeks significantly improved sleep quality versus controls. A 2024 Nutrition Reviews meta-analysis identifies apigenin-containing chamomile among a small group with converging objective and subjective evidence for improving multiple sleep parameters.

The Nutrients 2023 clinical study (n=21) using polysomnography demonstrated that 800 mg nightly Poria cocos ethanol extract significantly reduced sleep arousal, a direct measure of sleep maintenance. Animal studies also show reduced wake frequency during the sleep period following P. cocos administration.

Oral GABA has been shown in a randomized, double-blind trial to improve sleep parameters including nighttime awakenings and overall sleep quality in insomnia patients. GABA increases alpha-wave brain activity (relaxation) and reduces beta-wave activity (arousal), supporting sleep maintenance. It is the principal inhibitory neurotransmitter and a mechanistic backbone for sleep continuity regulation.

Preclinical studies show Ganoderma extract prolongs total sleep time and increases non-REM sleep in rodent models through GABAergic potentiation and serotonergic pathway upregulation. A rat Alzheimer's model study demonstrated significant improvements in both NREM and REM sleep duration.

Glycine has robust polysomnographic clinical evidence for reducing wakefulness after sleep onset (WASO) and improving sleep maintenance. A randomized, placebo-controlled crossover trial using 3 g at bedtime showed significantly decreased WASO on PSG and reduced next-day fatigue. Its mechanism involves NMDA receptor-mediated core body temperature reduction in the suprachiasmatic nucleus, a critical physiological requirement for sustained deep sleep.

Honokiol is the primary sleep-active neolignan in Magnolia bark, acting as a potent positive allosteric modulator of GABA-A receptors (α1β2γ2 subunits) to dose-dependently increase NREM sleep and suppress wakefulness in controlled animal studies. Effects are partially reversed by flumazenil, confirming benzodiazepine-site GABAergic mechanism. Honokiol is the pharmacologically characterized compound responsible for Magnolia bark's sleep-maintenance properties.

Hops (Humulus lupulus) strobiles contain 2-methyl-3-buten-2-ol and alpha/beta acids that act on GABA-A receptors to promote sedation and sleep continuity. Commission E (Germany) approves hops for restlessness and sleep disorders. Combined valerian-hops RCTs demonstrate improved sleep consolidation and reduced nighttime awakenings. A study in nursing students found nightly non-alcoholic hops beer improved actigraphy-measured sleep quality.

Kava (Piper methysticum) kavalactones modulate GABA-A receptors, voltage-gated ion channels, and limbic activity to produce anxiolytic and sedative effects addressing hyperarousal-driven sleep maintenance insomnia. Peer-reviewed reviews confirm kava reduced sleep onset time and promoted deeper sleep in controlled studies. Hepatotoxicity risk — for which FDA has issued an advisory — significantly moderates its clinical use.

L-Theanine promotes relaxation and reduces nocturnal arousal via GABA modulation, serotonin elevation, and alpha-wave promotion, without causing daytime sedation. Clinical studies show improved subjective sleep quality and reduced nighttime awakenings, particularly in anxiety-driven sleep disruption. A 2024 Nutrition Reviews meta-analysis identified L-theanine as having promising sleep-promoting properties as a subsidiary sleep aid.

L-Tryptophan is an essential amino acid and upstream precursor to serotonin and melatonin. A 2021 systematic review and meta-analysis of 18 studies found tryptophan supplementation significantly reduced wake after sleep onset (WASO, SMD −1.08 min, p=0.017), the primary objective marker of sleep maintenance difficulty. Doses of ≥1 g were particularly effective versus lower doses, and a 2025 meta-analysis confirmed these findings.

Multiple randomized controlled trials demonstrate that lavender essential oil inhalation improves sleep quality, reduces sleep latency, and decreases nocturnal awakenings. A 2015 RCT in coronary ICU patients found lavender inhalation significantly improved Pittsburgh Sleep Quality Index scores. A 2025 RCT in post-craniotomy patients showed significantly reduced awakenings and lower apnea-hypopnea index.

Lemon balm (Melissa officinalis) inhibits GABA transaminase, increasing synaptic GABA availability and reducing neuronal arousal relevant to sleep maintenance. Commission E approves lemon balm for nervousness and insomnia. A study (600 mg/day, 15 days) reduced insomnia symptoms by 42% with 85% of participants reporting improved sleep. Evidence is strongest in combination with valerian and other herbs.

Lotus seed extract increases NREM and total sleep time in animal models, indicating sleep maintenance benefits. The human pilot trial showed significant improvements in WASO (wake after sleep onset), a direct measure of sleep maintenance.

Magnesium acts as an NMDA receptor antagonist and GABA-A agonist, mechanistically supporting sustained sleep continuity. A double-blind, placebo-controlled RCT in elderly insomniacs (500 mg/day, 8 weeks) found significant improvements in sleep efficiency, total sleep time, and early morning awakening alongside increased melatonin and reduced cortisol. Animal models show magnesium deficiency specifically increases wakefulness and reduces slow-wave sleep, reversed by reintroduction of the mineral.

Magnolia bark (Magnolia officinalis) contains honokiol and magnolol, which act as positive allosteric modulators of GABA-A receptors. Animal studies demonstrate dose-dependent increases in NREM sleep duration and suppression of wakefulness with honokiol, partially reversed by flumazenil, confirming the GABAergic mechanism. Traditional use in TCM (Hou Po) for anxiety and sleep disorders spans over 2,000 years.

Melatonin is an endogenous pineal hormone with the most robust scientific evidence among natural compounds for improving sleep maintenance. Multiple meta-analyses of RCTs demonstrate significant increases in sleep efficiency and total sleep time. A 2005 meta-analysis of 17 RCTs found melatonin increased sleep efficiency by 2.2% and total sleep duration by 12.8 minutes versus placebo. A 2013 meta-analysis of 19 RCTs confirmed improvements in total sleep time and overall sleep quality; effects do not dissipate with continued use.

Passionflower (Passiflora incarnata) contains flavonoids that modulate GABA-A receptors, producing anxiolytic and mild sedative effects relevant to sleep maintenance in anxiety-driven insomnia. A randomized crossover trial found passionflower tea significantly improved subjective sleep quality versus placebo. Commission E (Germany) approves passionflower for nervous restlessness and sleep disorders. Evidence for isolated WASO-specific sleep maintenance effects is preliminary.

P. tenuifolia saponin fractions consistently extend pentobarbital-induced sleep duration in multiple preclinical insomnia models, indicating that the herb prolongs total sleep time and supports maintenance of sleep. Mechanistic targets include GABA-A receptor subunits and serotonergic pathways.

Low progesterone—particularly in perimenopause and postmenopause—is a primary driver of sleep maintenance insomnia (early-morning awakening and fragmented sleep). Oral micronized progesterone taken at night generates allopregnanolone via hepatic metabolism, promoting sleep continuity. RCT and clinical cohort evidence supports this effect in menopausal women.

The 2026 SLEEP conference RCT (n=218) found reishi extract reduced Insomnia Severity Index scores more than melatonin, an index that captures both sleep initiation and maintenance. The Wang & Wang 2022 study showed increased total sleep duration in chronic insomnia patients, consistent with maintained sleep. Mechanistically, GABAergic modulation and HPA-axis cortisol dampening support sleep consolidation.

Saffron (Crocus sativus) active compounds crocin, crocetin, and safranal modulate serotonin reuptake and GABA receptors to improve sleep quality and maintenance. A meta-analysis of 8 clinical trials confirmed significant sleep quality improvement with minimal adverse effects. An RCT (n=63, 14 mg twice daily) significantly improved multiple validated sleep quality measures within one week, with sustained effects at 28 days.

The 2025 double-blind crossover RCT reported that S. lateriflora extract improved overall sleep quality scores in primary insomnia patients, with participants in the active group maintaining or improving total sleep time while the placebo group worsened. Baseline average total sleep time was 4–5 hours in both groups, suggesting a maintenance problem as well as onset problem.

The Restorative Sleep Questionnaire used in the Hausenblas et al. (2024) RCT captures sleep continuity and restorative aspects; MgT showed benefits for staying asleep in adults with sleep problems. Preclinical evidence links higher brain Mg²⁺ to improved sleep architecture, including deeper sleep stages.

Valerenic acid is the primary bioactive marker compound in Valeriana officinalis root, responsible for its sleep-maintenance effects via partial GABA-A receptor allosteric modulation (beta-subunit) and 5-HT5A receptor partial agonism. It is the compound measured for valerian extract standardization. Multiple meta-analyses of valerian RCTs show significantly improved subjective sleep quality and sleep efficiency relevant to maintenance insomnia.

Multiple RCTs and systematic reviews document valerian's effects on sleep maintenance outcomes including reduced wake-after-sleep-onset (WASO) and fewer nocturnal awakenings, though evidence is inconsistent across studies. A 2006 meta-analysis of 16 RCTs (n=1,093) showed a statistically significant relative risk of improved sleep of 1.8 (95% CI 1.2–2.9). The 2020 Shinjyo et al. systematic review (60 studies, n=6,894) found improvements in subjective sleep quality and NREM stage 3 time, with GABAergic sedation proposed as the underlying mechanism.

Jujube seed (Suan Zao Ren, Ziziphus spinosa/jujuba) is the principal herb in Traditional Chinese Medicine specifically indicated for sleep-maintenance insomnia characterized by frequent nocturnal awakening, vivid dreaming, and palpitations. Use is documented since the Shennong Bencao Jing (c. 200 CE). Active jujubosides modulate GABA-A receptors and suppress orexin neuron excitability; spinosin shows 5-HT1A agonism. Preliminary clinical and preclinical data support these traditional sleep-maintenance effects.