Phosphatidylserine

Phosphatidylserine (PS) is a phospholipid component of cell membranes, most abundant in the phospholipid bilayer of neuronal cells. It functions primarily as a structural element that maintains membrane fluidity and participates in signal transduction, particularly in the brain where it supports the integrity of synaptic membranes and facilitates neurotransmitter activity.

• Cognitive function: Randomized controlled trials (RCTs) in older adults show that 300 mg/day of PS for 12–16 weeks improves working memory, episodic recall, and attention, especially under stress.
• Stress‑induced cortisol reduction: Meta‑analysis of 7 trials (n ≈ 500) reported a 30 % decrease in cortisol after 10 days of 400 mg/day PS, suggesting benefit for stress‑related mood disturbances.
• Exercise performance: Small crossover studies (n = 20–30) have shown that 400–800 mg/day of PS can blunt exercise‑induced cortisol spikes and modestly improve endurance capacity in trained athletes.
• Metabolic health: Preliminary data indicate that PS may modestly improve insulin sensitivity and lipid profiles in overweight adults, likely via membrane‑mediated insulin receptor signaling.
• Overall: The strongest evidence supports cognitive and stress‑modulation benefits, with emerging data in physical performance and metabolic regulation.

• Location: Phosphatidylserine resides primarily in the inner leaflet of the plasma membrane, where its negatively charged head group interacts with intracellular proteins.
• Co-factor and Modulation: It serves as a co-factor for protein kinases (e.g., PKC, Akt) and modulates the activity of phosphatidylinositol‑3‑kinase (PI3K) pathways, influencing synaptic plasticity.
• Enhancement: PS also enhances the activity of the Na⁺/K⁺‑ATPase and supports calcium‑dependent neurotransmitter release by stabilizing membrane microdomains (lipid rafts).
• Brain Function: In the brain, PS facilitates the synthesis of acetylcholine and dopamine by providing a substrate for phospholipase-A2, which liberates arachidonic acid and downstream eicosanoids that regulate neuronal signaling.
• Systemic Effects: Systemically, PS integrates into peripheral cell membranes, improving insulin receptor conformation and thereby enhancing glucose uptake via the PI3K/Akt pathway.
• Cortisol Regulation: Its capacity to modulate cortisol release is thought to involve regulation of the hypothalamic‑pituitary‑adrenal (HPA) axis through membrane‑bound glucocorticoid receptors.

• Molecular Formula & Name: Phosphatidylserine is a glycerophospholipid with the molecular formula C₁₃H₂₆NO₁₀P. Its IUPAC name is (2‑S‑(3‑hydroxy‑2‑methyl‑propyl)‑1‑(2‑hydroxy‑3‑(2‑hydroxy‑1‑oxo‑2‑p‑hydroxy‑2‑methyl‑propyl)‑? (the full IUPAC name is extensive and typically abbreviated as PS).
• Structure: The molecule consists of a glycerol backbone esterified at the sn‑1 and sn‑2 positions with fatty acid chains (commonly 16:0/18:1 or 18:0/20:4) and a phospho‑serine headgroup at the sn‑3 position.
• Charge & Function: The headgroup carries a net negative charge at physiological pH, facilitating interactions with positively charged protein domains.
• Properties: Its amphiphilic nature enables incorporation into bilayer membranes, influencing fluidity and curvature.
• Melting Point & Solubility: PS has a melting point around 55 °C (depending on fatty acid composition) and is soluble in organic solvents (chloroform, methanol) but poorly soluble in water, necessitating lipid‑based delivery systems for oral supplements.

• Natural Sources: Natural sources of phosphatidylserine include bovine brain tissue (historically) and soy, sunflower, or rapeseed phospholipid extracts.
• Commercial Production: Modern commercial PS is primarily derived from soy lecithin or sunflower seed phospholipids through enzymatic de‑acylation and re‑esterification processes that enrich the serine headgroup.
• Purification: High‑purity (>95 %) PS is obtained by chromatographic purification to remove phosphatidylcholine and other contaminants.
• Consumer Considerations: For vegan or allergen‑sensitive consumers, non‑animal, non‑genetically‑modified (non‑GMO) soy or sunflower-derived PS is preferred.
• Quality Control: Quality considerations include verifying the phosphatidylserine content by HPLC, absence of heavy metals, and compliance with Good Manufacturing Practices (GMP). The presence of residual phosphatidic acid or phosphatidylinositol should be minimal (<1 %) to ensure product potency and safety.