There is that moment in the evening when we turn off the light. Our brain, however, does not do the same.

Sleep is not a passive "shutdown." The transition from wakefulness to nighttime rest is actively controlled by networks in the brain. Wakefulness-promoting and sleep-promoting systems change their activity, neurotransmitters take on different roles, the internal clock sends temporal signals, and body temperature also shifts.

Many neurochemical systems work together simultaneously. These include GABA, glutamate, serotonin, histamine, orexin, and acetylcholine.^[1]

The central idea of this edition is therefore: No single substance "makes sleep." It arises from a finely tuned neurological interplay.

While we are awake, several ascending nerve systems keep the cerebral cortex active. When we fall asleep, sleep-promoting networks in the anterior hypothalamus gain influence and inhibit parts of these wakefulness systems. The switch is thus actively organized – not simply the result of exhaustion.

Our circadian clock in the suprachiasmatic nucleus of the hypothalamus also contributes to when our organism is set for wakefulness or sleep.^[1]

For end consumers, this can be simplified as follows: Falling asleep is a shift in neurological balance.

Because the study better reflects the biology of sleep than the idea of a single "sleep substance." Several of the substances examined act at different points in the nervous system or sleep physiology.

L-tryptophan is an essential amino acid. In the body, serotonin can be produced from it via 5-hydroxytryptophan; serotonin in turn is the starting material for the production of melatonin.

A meta-analysis of tryptophan and sleep found mainly evidence for less wakefulness after falling asleep. More pronounced effects were observed at examined amounts of 1 g or more; other sleep parameters did not change consistently.^[3]

The correct interpretation is therefore: Tryptophan belongs to a biologically relevant signaling pathway. But this does not automatically mean that more tryptophan necessarily produces more melatonin or better sleep.

L-theanine is a non-proteinogenic amino acid from tea leaves. It is being studied in connection with neuronal excitability, stress, and relaxation.

A systematic review and meta-analysis published in 2025 included 19 studies with a total of 897 participants. In the pooled data, some subjective sleep parameters improved, including time to fall asleep, daytime impairment, and subjective overall sleep quality. For objective sleep measurements, the results were much less clear.^[4]

This is a good example of why SCIENCE PROOF distinguishes between perception and objective measurement.

GABA – gamma-aminobutyric acid – is one of the most important inhibitory neurotransmitters of the central nervous system. GABAergic nerve cells are essential in the regulation of sleep and wakefulness.

In a small randomized, placebo-controlled crossover study, orally administered GABA shortened sleep latency and increased total non-REM sleep time.^[5]

Nevertheless, an important distinction is necessary: The fact that the body's own GABA system is central to sleep does not automatically prove that orally administered GABA works in the brain in the same way. The clinical evidence for supplemented GABA is significantly more limited than the neurobiological evidence for GABA itself.

Glycine is not only an amino acid, but also a neurotransmitter. Depending on the receptor and region of the nervous system, it can have different functions.

Small human studies with 3 g of glycine before bedtime reported improvements in subjective sleep quality as well as changes in polysomnographic parameters. Other work discusses a lowering of core body temperature as a possible mechanism – a process naturally associated with falling asleep.^[6]

Here too, the dosage question is important: The classic glycine sleep studies usually worked in the gram range.

Magnesium is involved in numerous processes of the nervous system. Among other things, it influences the electrical excitability of nerve cells and interacts with glutamatergic signaling pathways.

In 2025, a randomized, double-blind, placebo-controlled study was published specifically with magnesium bisglycinate. 155 adults with subjectively poor sleep quality received 250 mg of elemental magnesium from magnesium bisglycinate or placebo for four weeks.^[7]

The Insomnia Severity Index improved significantly compared to placebo – however, the effect size was small at Cohen's d = 0.2.^[7]

This differentiation is exactly what is important: A statistically measurable effect does not automatically have to be a large effect.

Ashwagandha (Withania somnifera) is studied particularly in connection with stress, tension, and sleep. Since sustained alertness and stress reactions can make the transition to sleep more difficult, this intersection is biologically plausible.

A meta-analysis of five randomized controlled trials with a total of 400 adults found a small but significant effect of ashwagandha extracts on sleep. Stronger effects were seen in subgroups with insomnia as well as with longer duration of use and higher examined dosages.^[8]

Important: Ashwagandha extracts differ in extraction and standardization. Results from one specific extract cannot automatically be transferred to every other extract.

Vitamin B6 is not a classic sleep substance. However, its active form pyridoxal-5'-phosphate acts as a cofactor in numerous enzymatic reactions – including in the production of neurotransmitters.

The metabolic pathway from tryptophan to serotonin requires vitamin B6 as a cofactor in the step from 5-hydroxytryptophan to serotonin.^[9]

This is biologically relevant, but does not mean that additional vitamin B6 automatically improves sleep. In a randomized study, a high dose of B6 did change dream recall, but did not significantly change other measured sleep variables.^[10]

The appropriate role in the overall picture is therefore: Cofactor of a neurological network – not a sleep aid.

Vitamin B12 should also not be presented as a classic sleep substance. More interesting is the research on circadian rhythms.

In a small crossover study with nine healthy individuals, methylcobalamin shifted the 24-hour melatonin rhythm compared to placebo by about 1.1 hours forward, without changing the timing of sleep.^[11]

The data are old and small. However, they show why B12 is discussed more in connection with biological time control than with a direct sedating effect.

The studies examined different substances, dosages, extracts, groups of people, and time periods. Some work was small; some used combinations instead of individual substances.

Most importantly, the specific combination of the ingredients discussed here was not tested as a complete formulation in a clinical study.

From the data, it is scientifically reasonable to derive why individual components are interesting for sleep biology. What cannot be derived from it is a blanket proof of efficacy for another specific formulation.

Perhaps we should think of sleep less like a light switch – and more like a sunset.

The nervous system changes its state step by step. Wakefulness networks, inhibitory signals, internal clock, temperature, and numerous neurotransmitters interlock.

Research on nutrients is at different stages: For some substances, there are already multiple controlled human studies; for others, mainly evidence of biological mechanisms or small clinical investigations.

That is exactly why it's worth taking a closer look at Science – not to turn every study into a promise, but to better understand how fascinating our body's functioning is.