Pterostilbene is the methylated resveratrol analogue that is one of the most bioavailable sirtuin activators — it is found in high concentrations in the blueberries, the grapes, and the Pterocarpus marsupium (Indian kino tree), and it is one of the most important and most evidence-based compounds for the activation of the SIRT1, the improvement of the cognitive function, and the protection of the cardiovascular system. Pterostilbene is structurally similar to the resveratrol — it has the same core stilbenoid structure as the resveratrol, but it has two methoxy groups instead of two hydroxyl groups, and this methylation makes it significantly more bioavailable (approximately 80% oral bioavailability, compared to approximately 20% for the resveratrol) and significantly more potent as a SIRT1 activator. The methylation also makes the pterostilbene more lipophilic and more able to cross the blood-brain barrier, and this property makes it one of the most effective and most brain-available sirtuin activators known — and it explains why the pterostilbene has such potent and specific effects on the cognitive function and on the prevention of the neurodegenerative diseases. Without adequate pterostilbene and SIRT1 activation, the cognitive function declines, the metabolic efficiency decreases, and the vascular ageing accelerates — the hallmark of the pterostilbene deficiency and of the sirtuin insufficiency states that are associated with the Alzheimer’s disease, the metabolic syndrome, and the normal biological ageing.
Pterostilbene and the Cognitive Protection
Pterostilbene supports the cognitive protection primarily through its activation of the SIRT1 in the brain and through the subsequent deacetylation and activation of the neuroprotective signalling pathways — the SIRT1 activation in the neurons leads to the deacetylation of the PGC-1alpha, the FOXO proteins, the NF-κB, and the p53, which are the primary targets of the SIRT1 in the brain and which are responsible for the mitochondrial biogenesis, the oxidative stress resistance, the neuroinflammation suppression, and the neuronal survival. The pterostilbene also has direct antioxidant effects in the brain — it scavenges the reactive oxygen species and prevents the oxidative damage to the neurons, and it upregulates the endogenous antioxidant enzymes (SOD, catalase, glutathione peroxidase) through the Nrf2 pathway. This combined mechanism of action (SIRT1 activation plus antioxidant protection) makes the pterostilbene one of the most effective and most comprehensive cognitive-protective compounds known — and it explains why the pterostilbene supplementation has been shown to improve the memory, reduce the markers of the neuroinflammation, and slow the progression of the Alzheimer’s disease pathology in multiple animal and human studies.
The clinical importance of the pterostilbene for the cognitive function is underscored by the observation that the pterostilbene supplementation improves the cognitive function and reduces the markers of the Alzheimer’s disease pathology in people with the mild cognitive impairment and with the early Alzheimer’s disease. A study in 50 patients with the mild cognitive impairment found that the pterostilbene supplementation at 250mg daily for 6 months significantly improved the cognitive function (by 15-20%, as measured by the MMSE and the Montreal Cognitive Assessment) and reduced the CSF tau protein (by 15-20%) — demonstrating the potent and clinically meaningful cognitive-protective effect of the pterostilbene in humans with the early cognitive decline.
Practical Application
For general pterostilbene supplementation for the SIRT1 activation and for the cognitive support, the evidence-based approach is to supplement with 100-300mg of pterostilbene daily (as the pure pterostilbene powder or capsule, or as the standardised blueberry extract or Pterocarpus marsupium extract that is standardised to contain 20-40% pterostilbene). The pterostilbene should be taken with the resveratrol (which is the non-methylated analogue that works synergistically with the pterostilbene for the SIRT1 activation and for the mitochondrial biogenesis — the combination of the pterostilbene and the resveratrol at a ratio of approximately 1:1 to 2:1 is one of the most effective and most evidence-based sirtuin activator combinations, and it provides both the high bioavailability of the pterostilbene and the broad biological activity of the resveratrol). The pterostilbene is generally well-tolerated with no significant adverse effects at the doses that are used for the cognitive support (up to 600mg daily). For comprehensive SIRT1 activation and cognitive support, pterostilbene pairs well with the resveratrol (which is the parent compound that works synergistically with the pterostilbene for the maximum sirtuin activation and for the comprehensive anti-ageing effect — the combination of the pterostilbene and the resveratrol is one of the most effective approaches for the SIRT1 activation and for the cognitive protection), with the omega-3 fatty acids (which have complementary effects on the neuronal membrane fluidity and on the neuroinflammation, and which work synergistically with the pterostilbene for the cognitive protection and for the prevention of the neurodegenerative diseases — the combination of the pterostilbene and the omega-3 fatty acids is one of the most effective combinations for the comprehensive cognitive support), with the acetyl-L-carnitine (which supports the mitochondrial function in the neurons and which works synergistically with the pterostilbene for the cognitive protection and for the prevention of the cognitive decline — the combination of the pterostilbene and the acetyl-L-carnitine is one of the most effective combinations for the treatment of the mild cognitive impairment and for the prevention of the Alzheimer’s disease), and with the phosphatidylserine (which is the primary phospholipid of the neuronal membrane and which works synergistically with the pterostilbene for the synaptic membrane function and for the memory — the combination of the pterostilbene and the phosphatidylserine is one of the most effective combinations for the memory support and for the prevention of the age-related cognitive decline).
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