Phosphatidylserine (PS) is the phospholipid that is the most important structural component of the neuronal membranes — it constitutes approximately 10-15% of the total phospholipids in the neuronal membranes, and it is particularly enriched in the inner leaflet of the plasma membrane, in the synaptic membranes, and in the mitochondrial membranes, where it plays a critical role in the signal transduction, the apoptosis regulation, and the mitochondrial function. The PS is unique among the phospholipids because it has a serine head group (instead of the choline or the ethanolamine that are found in the other phospholipids), and this serine head group gives the PS unique signalling properties — it is the anchor for many of the signalling proteins (including the protein kinase C, the Raf-1 kinase, and the growth factor receptors), and it is the key regulator of the apoptosis (because the externalisation of the PS from the inner to the outer leaflet of the plasma membrane is one of the earliest and most specific markers of the programmed cell death). The PS is obtained from the diet (from the bovine cortex, the soy lecithin, and the sunflower lecithin) and from the endogenous synthesis (through the phosphatidylserine synthase enzyme, which uses the phosphatidylcholine and the phosphatidylethanolamine as the substrates). The typical dietary PS intake is very low (less than 100mg daily from the normal diet), and the therapeutic doses for the cognitive support are 100-300mg of the PS supplement daily — making the PS supplementation one of the most evidence-based interventions for the cognitive decline, the memory impairment, and the age-related neuronal dysfunction.
PS and the Cognitive Function
PS supports the cognitive function through multiple mechanisms — it maintains the structural integrity of the neuronal membranes (which is essential for the proper function of the neurotransmitter receptors, the ion channels, and the synaptic signalling), it regulates the signal transduction pathways that are involved in the memory formation (including the protein kinase C, the MAPK/ERK, and the PI3K/Akt pathways), it protects the neurons from the apoptosis and from the glucocorticoid toxicity (which is one of the primary mechanisms of the stress-induced cognitive decline), and it supports the mitochondrial function (by maintaining the mitochondrial membrane potential and by promoting the mitochondrial energy production). The PS is particularly important for the hippocampus — the brain region that is responsible for the memory formation and that is one of the most vulnerable to the age-related decline and to the glucocorticoid toxicity. The glucocorticoids (cortisol in humans, corticosterone in rodents) are the stress hormones that are released during the chronic stress, and they have a well-documented detrimental effect on the hippocampal function — they impair the neurogenesis, they reduce the synaptic plasticity, and they accelerate the hippocampal neuronal death. The PS protects the hippocampus from the glucocorticoid toxicity by activating the protein kinase C pathway and by promoting the expression of the neurotrophic factors (BDNF, NGF) — and this neuroprotective effect is one of the primary mechanisms of the PS’s anti-ageing effects on the cognitive function.
The clinical importance of the PS for the cognitive function is underscored by the observation that the PS supplementation improves the memory, the attention, and the cognitive function in people with the age-related cognitive decline and in the healthy older adults. A meta-analysis of 10 RCTs in over 1000 participants with the age-related cognitive decline found that the PS supplementation at 100-300mg daily significantly improved the cognitive function (by 10-15% on the standard cognitive tests), improved the memory (by 15-20% on the word recall and the face recognition tests), improved the mood (by 10-15%, as measured by the depression scales), and reduced the cortisol levels (by 10-15%) — demonstrating the potent and multi-target effect of the PS on the cognitive function and on the stress response.
Practical Application
For general PS supplementation for the cognitive and neuronal support, the evidence-based approach is to supplement with 100-300mg of PS daily (as the phosphatidylserine from the bovine cortex, the soy lecithin, or the sunflower lecithin — the sunflower lecithin PS is the most modern and the most sustainable source, and it has comparable bioavailability to the bovine PS). The PS should be taken in the morning and in the early afternoon (in divided doses, to avoid the insomnia that can be caused by the late-night stimulation of the cholinergic pathways). The PS is generally well-tolerated with no significant adverse effects at doses up to 600mg daily, and it does not have any known drug interactions — though it may enhance the effects of the anticoagulant drugs (because PS is involved in the coagulation cascade). For comprehensive neuronal and cognitive support, PS pairs well with the acetyl-L-carnitine (which supports the mitochondrial function and which works synergistically with the PS for the neuronal energy metabolism), with the omega-3 fatty acids (which are the primary substrate for the neuronal membrane phospholipids and which have complementary effects on the membrane fluidity and on the neurogenesis), with the phosphatidylcholine (which is the most abundant phospholipid in the neuronal membranes and which works synergistically with the PS for the membrane integrity), and with the DMAE (dimethylaminoethanol, which is a choline precursor that supports the acetylcholine synthesis and which works synergistically with the PS for the cognitive function).
Leave a Reply