The mechanism of L-Arginine on sleep quality

The sleep quality improvement effect of L-Arginine does not stem from direct sleep induction; instead, it indirectly optimizes sleep structure, prolongs deep sleep duration, and reduces nighttime awakenings by regulating four core pathways: nitric oxide (NO) synthesis, neurotransmitter balance, hormone secretion rhythm, and physiological microenvironment stability. Its mechanism of action can be elaborated in the following four dimensions:

Mediating NO Production to Improve Cerebral Blood Flow and Thermoregulation, Optimizing Conditions for Sleep Onset

L-Arginine is the sole substrate for endothelial nitric oxide synthase (eNOS). The NO produced through its metabolism can dilate cerebral blood vessels and enhance the efficiency of cerebral oxygen and nutrient supply. Middle-aged and elderly populations often experience cerebral microcirculatory dysfunction due to decreased vascular elasticity, which leads to problems such as difficulty falling asleep and light sleep. The NO-mediated improvement in cerebral blood flow can alleviate hypoxic excitation of neurons, laying a stable physiological foundation for sleep onset.

Meanwhile, NO can dilate cutaneous blood vessels, promote heat dissipation from the body surface, and help the human core temperature drop steadily—a rhythmic reduction in core temperature is a key physiological signal for falling asleep, and this effect is particularly significant for insomniac populations with thermoregulatory disorders.

Regulating Neurotransmitter Balance to Inhibit Central Excitation and Promote Sleep Maintenance

Sleep maintenance relies on the dynamic balance between inhibitory and excitatory neurotransmitters. L-Arginine indirectly regulates this balance through the NO pathway:

It activates the activity of γ-aminobutyric acid (GABA)-ergic neurons in the brain and promotes GABA release. As the main inhibitory neurotransmitter in the central nervous system, GABA can reduce the firing frequency of cerebral cortical neurons, inhibit excessive sympathetic nerve activation, relieve nighttime anxiety and physical tension, and decrease the number of awakenings during sleep.

It suppresses the excessive release of excitatory neurotransmitters such as glutamate, preventing the central nervous system from remaining in a state of sustained excitation, thereby shortening sleep onset latency and extending the continuity of sleep cycles.

Modulating the Secretion of Sleep-Related Hormones to Optimize Sleep Rhythm and Repair Function

By improving blood supply to target organs and upregulating the activity of key enzymes, L-Arginine regulates the secretion of two core sleep-related hormones:

Promoting melatonin synthesis: NO can improve blood perfusion of the pineal gland and simultaneously upregulate the activity of arylalkylamine N-acetyltransferase—the rate-limiting enzyme for melatonin synthesis—accelerating the conversion of tryptophan to melatonin. As the core hormone regulating circadian rhythms, increased melatonin secretion can correct disrupted sleep-wake cycles, and is particularly suitable for populations with shift work, jet lag syndrome, or insufficient melatonin secretion in middle and old age.

Stimulating growth hormone secretion: Growth hormone is primarily secreted during deep sleep and has a body repair function. NO generated from L-Arginine can directly stimulate the pituitary gland to secrete growth hormone, while prolonging the duration of deep sleep, enhancing the "repair efficiency" of sleep, and alleviating daytime fatigue caused by insufficient deep sleep.

Alleviating Physical Stress States to Reduce Sleep-Disturbing Factors

Physical stress states such as excessive sympathetic nerve activation and blood pressure fluctuations are important triggers for nighttime awakenings. NO derived from L-Arginine can inhibit sympathetic nerve activity, reduce the fluctuation amplitude of nighttime heart rate and blood pressure, and decrease awakenings caused by cardiovascular stress. Meanwhile, the anti-inflammatory and antioxidant effects of NO can mitigate chronic low-grade inflammation in the body, relieve the stimulation of inflammatory factors on the sleep center, and further improve sleep stability.

It should be noted that the effects of L-Arginine are dose-dependent: a moderate dosage (3–6 g per day) can preferentially activate eNOS to generate protective NO. Excessive supplementation (more than 10 g per day) may activate inducible nitric oxide synthase (iNOS), leading to the production of large amounts of toxic NO, which triggers side effects such as headaches and nocturia, and instead disrupts sleep.