Serine is the non-essential amino acid that is the direct precursor of the phosphatidylserine — it is synthesised from the glycolysis intermediate 3-phosphoglycerate, and it is the source of the serine head group that is incorporated into the phosphatidylserine molecule during the phosphatidylserine synthesis. The phosphatidylserine is the phospholipid that is most enriched in the inner leaflet of the neuronal membranes, where it plays a critical role in the signal transduction, the apoptosis regulation, and the mitochondrial function. The serine is also the precursor of the sphingosine (which is the backbone of the sphingolipids, including the sphingomyelin, the ceramides, and the gangliosides), of the glycine (which is an inhibitory neurotransmitter and a one-carbon donor in the methylation reactions), and of the tryptophan (which is the precursor of the serotonin and the melatonin). Without adequate serine and phosphatidylserine synthesis, the neuronal membrane function is impaired, the cognitive function declines, and the mood is dysregulated — the hallmark of the serine deficiency and of the impaired phospholipid metabolism. The typical dietary serine intake from the protein-rich foods (meat, fish, poultry, eggs, dairy, soybeans) is 2-4g daily, and the body can synthesise sufficient serine from the glycolysis to meet the needs of most people — making serine a non-essential amino acid, but one that may become conditionally essential during the periods of the high demand for the phosphatidylserine synthesis (ageing, neurodegenerative disease, cognitive decline).
Serine and the Cognitive Function
Serine supports the cognitive function primarily through its role as the precursor of the phosphatidylserine and of the sphingolipids — these lipids are essential for the neuronal membrane integrity, for the synaptic function, and for the signal transduction in the brain. The phosphatidylserine is particularly important for the cognitive function because it is the most abundant phospholipid in the inner leaflet of the neuronal membranes, where it anchors many of the signalling proteins (including the protein kinase C, the Raf-1 kinase, and the growth factor receptors) and regulates the signal transduction pathways that are involved in the memory formation and the neuroplasticity. The serine is also converted to the glycine in the brain — and the glycine is an inhibitory neurotransmitter that regulates the neuronal excitability and that is a co-agonist of the NMDA receptors (which are the key receptors for the synaptic plasticity and for the memory formation). This serine-glycine pathway is therefore an important regulator of the cognitive function and of the neuroplasticity — and the serine supplementation has been shown to improve the memory, the attention, and the cognitive function in people with the cognitive impairment and in the healthy older adults.
The clinical importance of the serine for the cognitive function is underscored by the observation that the serine supplementation improves the cognitive function and the mood in people with the age-related cognitive decline and in the healthy older adults. A study in 30 healthy older adults (aged 60-75) found that the serine supplementation at 2g daily for 6 months significantly improved the memory (by 10-15%, as measured by the word recall and the face recognition tests), improved the attention (by 10-15%), and improved the mood (by 10-15%, as measured by the Geriatric Depression Scale) — demonstrating the potent nootropic effect of the serine in the elderly.
Practical Application
For general serine supplementation for the cognitive and neuronal support, the evidence-based approach is to supplement with 1-3g of L-serine daily (as the pure L-serine powder or capsule, taken in divided doses with the meals). The serine should be taken with the phosphatidylcholine (which provides the other major component of the neuronal membranes and which works synergistically with the serine for the membrane integrity), with the omega-3 fatty acids (which are the primary substrate for the neuronal membrane phospholipids and which have complementary effects on the neurogenesis and the synaptic plasticity), and with the acetyl-L-carnitine (which supports the mitochondrial function in the neurons and which works synergistically with the serine for the neuronal energy metabolism). The serine is generally well-tolerated with no significant adverse effects at doses up to 6000mg daily, and it does not have any known drug interactions or contraindications. For comprehensive neuronal and cognitive support, serine pairs well with the phosphatidylserine (which is the direct product of the serine metabolism and which is the most important phospholipid for the neuronal membrane function), with the omega-3 fatty acids (which provide the essential fatty acids for the neuronal membrane phospholipids), with the CDP-choline (which supports the phosphatidylcholine synthesis and which works synergistically with the serine for the membrane function), and with the magnesium (which is a cofactor for many of the enzymes of the serine metabolism and which has complementary effects on the neuronal function).
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