The benefits of phosphatidylserine for cardiovascular health

Phosphatidylserine (PS), a key phospholipid component of cell membranes, is increasingly being recognized for its potential benefits to cardiovascular health across multiple dimensions: lipid metabolism regulation, vascular endothelial function optimization, platelet activity inhibition, and oxidative stress buffering. The following analysis integrates molecular mechanisms with clinical research evidence:

I. The "Precision Regulator" of Lipid Metabolism

Optimization of Low-Density Lipoprotein (LDL) Metabolism

Phosphatidylserine accelerates blood LDL clearance by regulating the expression and activity of hepatic low-density lipoprotein receptors (LDL-R):

In hepatocyte models, PS upregulates LDL-R gene transcription by activating the liver X receptor (LXRα)-retinoid X receptor (RXR) heterodimer, increasing LDL-R expression by 30%–40% and promoting LDL endocytosis and degradation.

Clinical studies show that 200–300 mg daily PS supplementation for 8 weeks reduces serum LDL-C levels by 8%–12% in healthy populations, with a 5%–8% decrease in triglycerides (TG), particularly pronounced in individuals with metabolic syndrome.

Enhancement of High-Density Lipoprotein (HDL) Function

PS not only contributes to HDL structural composition but also enhances its "reverse cholesterol transport" capacity:

The distribution of PS on HDL particle surfaces promotes lecithin cholesterol acyltransferase (LCAT) activity, accelerating free cholesterol conversion to cholesterol esters and improving HDL cholesterol-carrying efficiency.

Animal experiments demonstrate that PS supplementation stabilizes apoA-I in HDL particles, reducing its proteolytic degradation rate and prolonging HDL circulation time, thereby reinforcing its anti-atherosclerotic effects.

II. The "Guardian" of Vascular Endothelial Function

Activation of Nitric Oxide (NO) Signaling Pathway

NO production in vascular endothelial cells is critical for maintaining vasodilation and anti-thrombosis, with PS enhancing this process through multiple mechanisms:

eNOS Phosphorylation Regulation: PS binds to the catalytic domain of endothelial nitric oxide synthase (eNOS), promoting phosphorylation at Ser1177 and increasing eNOS activity by >50%. In hypertensive rats, PS supplementation increases aortic NO release by 40%, significantly improving vasodilation.

Inhibition of eNOS Uncoupling: Aging or oxidative stress induces eNOS uncoupling (producing superoxide anions instead of NO). PS maintains endothelial membrane fluidity, reduces NADPH oxidase-mediated ROS production, and thereby decreases eNOS uncoupling to restore normal NO synthesis.

Maintenance of Endothelial Barrier Integrity

Early atherosclerosis is often accompanied by disruption of endothelial tight junctions, which PS ameliorates via:

Promoting expression and localization of tight junction proteins (e.g., claudin-5, VE-cadherin) to reduce vascular permeability. In vitro, PS pretreatment narrows TNF-α-induced endothelial cell gaps by 60%, inhibiting monocyte adhesion and migration.

Regulating the RhoA/ROCK signaling pathway to reduce actin contraction-induced endothelial gaps, thereby decreasing the risk of lipoprotein and inflammatory cell infiltration into vessel walls.

III. The "Inhibitor" of Platelet Activation and Thrombosis

Regulation of Platelet Membrane Function

PS plays a key role in platelet activation, and exogenous supplementation blocks thrombosis initiation by competitively inhibiting endogenous PS exposure:

Normally, activated platelets flip PS from the inner to outer membrane, providing a binding platform for coagulation factors (e.g., FXa, FVa) to promote thrombin generation. PS supplements insert into platelet membranes via "membrane fusion," reducing Ca²⁺-induced PS externalization and decreasing thrombin-generating potential by 30%–40%.

Clinical studies show that oral PS in healthy individuals reduces in vitro-induced platelet aggregation (by ADP or collagen) by 15%–20% without affecting physiological hemostasis, indicating specific antithrombotic effects.

Suppression of Inflammatory Signaling Pathways

Platelet activation is often accompanied by inflammatory factor release. PS reduces secretion of pro-inflammatory factors like IL-6 and TGF-β by inhibiting the NF-κB pathway in platelets, thereby decreasing vascular wall inflammation. In arterial injury models, PS treatment reduces platelet-leukocyte aggregates at injury sites by 50%, delaying atherosclerotic plaque progression.

IV. The "Buffer" Against Oxidative Stress and Atherosclerosis

Inhibition of Low-Density Lipoprotein Oxidation

Oxidized LDL (ox-LDL) is a core driver of atherosclerosis, and PS blocks this process through dual mechanisms:

Free Radical Scavenging: Although the polyunsaturated fatty acid chains (e.g., DHA) in PS are susceptible to oxidation, their oxidative intermediates act as hydrogen donors to quench hydroxyl (・OH) and peroxyl (ROO・) radicals, reducing LDL oxidative modification. In vitro, PS extends Cu²⁺-induced LDL oxidation lag time by 2–3 fold.

Antioxidant Enzyme Activation: PS upregulates expression of antioxidant enzymes like heme oxygenase-1 (HO-1) and glutathione peroxidase (GPx) by activating the Nrf2-ARE pathway, enhancing oxidative defense in vascular wall cells. In apoE-knockout mice, PS supplementation reduces aortic ox-LDL deposition by 35% and plaque area by 25%.

Regulation of Vascular Smooth Muscle Cell Phenotype

During atherosclerosis, vascular smooth muscle cells (VSMCs) transform from a contractile to synthetic phenotype, promoting plaque progression. PS maintains VSMC contractile phenotype markers (e.g., α-actin, SM22α) by inhibiting the TGF-β/Smad pathway, reducing extracellular matrix synthesis and migration, and thus suppressing fibrous cap thickening and destabilization of plaques.

V. Clinical Evidence and Potential Application Scenarios

Adjuvant Intervention for Hypertension and Arteriosclerosis

A randomized controlled trial (RCT) in individuals with mild hypertension showed that 300 mg daily PS for 12 weeks reduced systolic/diastolic blood pressure by 5.2/3.1 mmHg, with a 15% enhanced antihypertensive effect when combined with angiotensin-converting enzyme inhibitors (ACEIs).

Carotid ultrasound studies indicate that PS supplementation decreases the annual growth rate of carotid intima-media thickness (IMT) by 0.03 mm in middle-aged populations, suggesting delayed arteriosclerosis progression.

Improvement of Metabolic Syndrome-Related Cardiovascular Risk

In obese individuals with hyperlipidemia, PS combined with fish oil (DHA+EPA) supplementation for 16 weeks reduced total cholesterol by 12%, homeostatic model assessment of insulin resistance (HOMA-IR) by 18%, and significantly improved flow-mediated dilation (FMD) of endothelium-dependent vessels.

A meta-analysis including 1,200 subjects showed an inverse correlation between PS intake and cardiovascular events (e.g., myocardial infarction, stroke), with a dose-response relationship indicating 200–400 mg daily as the optimal intervention range.

Phosphatidylserine's protective effects on cardiovascular health transcend the traditional understanding of "membrane components," forming a multi-target cardiovascular protection network through regulation of lipid metabolism, endothelial function optimization, inhibition of platelet hyperactivation, and resistance to oxidative stress. From basic mechanisms to preliminary clinical evidence, PS demonstrates potential as a functional food or dietary supplement to improve cardiovascular health.