Phosphatidylserine improves sleep quality

I. Regulation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Stress Response

The hypothalamic-pituitary-adrenal axis is the core regulatory system for the human body to cope with stress. Chronic stress or anxiety leads to excessive activation of the HPA axis, manifested by increased secretion of cortisol (stress hormone), thereby interfering with the sleep cycle. Phosphatidylserine (PS) inhibits excessive HPA axis excitation through the following pathways:

Reducing Cortisol Levels: Studies show that phosphatidylserine directly acts on the pituitary and adrenal glands to inhibit the release of adrenocorticotropic hormone (ACTH), thereby reducing cortisol synthesis and secretion. Lower cortisol levels alleviate wakefulness, promote falling asleep, and reduce nighttime awakenings.

Regulating Glucocorticoid Receptor Sensitivity: Phosphatidylserine may enhance the body's stress tolerance by improving the feedback regulation function of hypothalamic glucocorticoid receptors, avoiding sleep fragmentation caused by stress (such as increased light sleep and decreased deep sleep).

II. Influence on the Inhibitory Effect of the γ-Aminobutyric Acid (GABA)ergic Nervous System

GABA is the main inhibitory neurotransmitter in the central nervous system, and its functional deficiency leads to excessive neuronal excitation, causing insomnia or difficulty maintaining sleep. The regulation of the GABAergic system by phosphatidylserine is reflected in:

Enhancing GABA Receptor Activity: As a component of cell membrane phospholipids, phosphatidylserine optimizes the binding efficiency of GABA receptors (such as GABAA receptors) with ligands by regulating neuronal cell membrane fluidity, promotes chloride ion influx, enhances neuronal inhibitory conduction, and thus induces a sedative effect.

Promoting GABA Synthesis and Release: Some studies have found that phosphatidylserine may indirectly promote GABA synthesis by affecting the activity of glutamic acid decarboxylase (a key enzyme for GABA synthesis). At the same time, its regulatory effect on the stability of the presynaptic membrane may promote the synaptic release of GABA, prolonging the duration of inhibitory signals.

III. Improving Neuronal Energy Metabolism and Sleep-Wake Cycle Regulation

Sleep quality is closely related to the energy state of neurons, and phosphatidylserine plays an important role in cellular energy metabolism and circadian rhythm regulation:

Optimizing Mitochondrial Function: As a component of the mitochondrial membrane, phosphatidylserine maintains the structural integrity of mitochondria and promotes ATP synthesis efficiency. When neurons have sufficient energy supply, it can reduce wakefulness signal transmission caused by energy depletion and support the brain's "metabolic cleaning" process during sleep (such as cerebrospinal fluid clearing waste products like β-amyloid).

Regulating Circadian Gene Expression: Phosphatidylserine may affect the gene expression of the hypothalamic suprachiasmatic nucleus (SCN, the circadian center), such as regulating the rhythmic expression of circadian genes like Period (Per) and Cryptochrome (Cry), making the sleep-wake cycle more synchronized with the circadian rhythm, thereby improving sleep onset time and sleep continuity.

IV. Indirect Improvement of Sleep through Antioxidant and Neuroprotective Effects

Oxidative stress and neuroinflammation are potential causes of insomnia and sleep disorders. The antioxidant properties of phosphatidylserine can indirectly optimize sleep through the following mechanisms:

Scavenging Free Radicals and Inhibiting Lipid Peroxidation: The fatty acid chains of phosphatidylserine (such as polyunsaturated fatty acids) can act as endogenous antioxidants to neutralize hydroxyl radicals, superoxide anions, etc., reduce neuronal membrane lipid peroxidation damage, and avoid sleep structure damage caused by oxidative stress (such as shortened rapid eye movement sleep period).

Inhibiting Neuroinflammatory Signals: Phosphatidylserine can down-regulate the activation of inflammatory pathways such as nuclear factor κB (NF-κB), reduce the release of pro-inflammatory factors such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and thus alleviate inflammation-related sleep disorders (such as reduced risk of sleep apnea).

V. Regulating Melatonin Secretion and Sleep-Wake Transition

Melatonin is a key hormone regulating the circadian rhythm, and its secretion disorder leads to difficulty falling asleep or early awakening. The regulatory effect of phosphatidylserine on melatonin is reflected in:

Promoting Melatonin Synthesis: Phosphatidylserine may promote the nighttime secretion peak of melatonin by enhancing the activity of tryptophan hydroxylase (a precursor enzyme for melatonin synthesis) or improving the membrane function of pineal cells, shortening the sleep latency (the time from wakefulness to falling asleep).

Enhancing Melatonin Receptor Sensitivity: Phosphatidylserine can optimize the distribution and conformation of melatonin receptors (MT1 and MT2) on the cell membrane, improve the binding affinity of receptors to melatonin, and thus enhance its sleep-inducing effect, especially for the improvement of melatonin receptor function decline caused by aging.

VI. Clinical Evidence and Mechanistic Synergistic Effects

Multiple clinical studies have shown that supplementing phosphatidylserine (especially PS extracted from soybeans or krill) can significantly shorten the sleep onset time of insomniacs, increase deep sleep time, and reduce nighttime awakenings. Its mechanism is not the effect of a single pathway but a virtuous cycle (benign cycle) of "stress relief-neural inhibition-rhythm synchronization" through the synergism of multiple pathways such as HPA axis inhibition, GABAergic enhancement, energy metabolism optimization, and melatonin regulation, ultimately achieving the improvement of sleep quality.

It should be noted that the physiological effects of phosphatidylserine are related to dosage, source (such as plant-based vs. animal-based), and individual differences, and its mechanism research is still in-depth. However, existing evidence has supported its potential value as a functional food or dietary supplement to improve sleep.