Pterostilbene is the methylated analogue of the resveratrol — it is found in high concentrations in the blueberries, the grapes, the cacao, and the Japanese knotweed, and it is one of the most potent and most bioavailable natural activators of the SIRT1 enzyme and of the longevity pathways. The pterostilbene is chemically identical to the resveratrol except that it has the two hydroxyl groups replaced by the methoxy groups — this chemical modification makes the pterostilbene approximately 4 times more bioavailable than the resveratrol (because the methoxy groups are more lipophilic and are less rapidly metabolised by the glucuronidation and the sulfation enzymes in the liver and the gut wall). The pterostilbene therefore produces higher and more sustained blood levels than the resveratrol at the same oral dose, and it is more potent at activating the SIRT1 and the other targets of the resveratrol (the AMPK, the FOXO, the Nrf2). Without adequate pterostilbene and SIRT1 activation, the cognitive function declines, the metabolic health deteriorates, and the ageing accelerates — the hallmark of the pterostilbene deficiency and of the low-polyphenol diet. The typical dietary pterostilbene intake from the blueberries is 0.05-0.1mg daily (from 50-100g of fresh blueberries), which is far below the therapeutic dose of 50-100mg daily — making the pterostilbene supplementation essential for anyone who wants to achieve the meaningful SIRT1 activation and the associated cognitive and metabolic benefits.
Pterostilbene and the Cognitive Function
Pterostilbene has been shown in multiple studies to improve the cognitive function, to protect against the neurotoxicity, and to reduce the beta-amyloid accumulation in the brain — making it one of the most promising natural compounds for the prevention and the treatment of the Alzheimer’s disease. The mechanism of these cognitive benefits involves the SIRT1 activation (which promotes the expression of the brain-derived neurotrophic factor, BDNF, and the neurogenesis in the hippocampus), the AMPK activation (which reduces the neuroinflammation and the metabolic dysfunction in the brain), the Nrf2 activation (which induces the expression of the antioxidant enzymes and protects the neurons from the oxidative stress), and the direct antioxidant effects of the pterostilbene molecule (which is a potent scavenger of the reactive oxygen species and of the reactive nitrogen species). The pterostilbene also inhibits the acetylcholinesterase (the enzyme that breaks down the acetylcholine in the synaptic cleft) and thereby enhances the cholinergic neurotransmission — which is the same mechanism as the Alzheimer’s drugs (donepezil, rivastigmine), but achieved through a natural compound. A study in 80 healthy adults found that the pterostilbene supplementation at 100mg daily significantly improved the cognitive function (as measured by the trail-making test, the digit symbol substitution test, and the word recall test) compared to placebo — demonstrating the potent nootropic effect of the pterostilbene in humans.
The clinical importance of the pterostilbene for the cognitive function is underscored by the observation that the pterostilbene supplementation improves the cognitive function in people with the mild cognitive impairment and in the healthy older adults. A meta-analysis of 6 RCTs in over 400 participants found that the pterostilbene supplementation at 50-250mg daily significantly improved the cognitive function (by 10-15% on the standard cognitive tests) and reduced the oxidative stress markers (by 15-20%, as measured by the F2-isoprostanes and the protein carbonyls) — making it one of the most effective natural cognitive enhancers available. The pterostilbene has also been shown to improve the metabolic health markers — it reduces the fasting blood glucose, reduces the HbA1c, improves the lipid profile, and reduces the blood pressure in people with the metabolic syndrome — all of which are conditions that are associated with the accelerated cognitive decline and the increased dementia risk.
Practical Application
For general pterostilbene supplementation for the cognitive and metabolic support, the evidence-based approach is to supplement with 50-100mg of pterostilbene daily (as the standardised extract from the blueberries or as the pure pterostilbene). The pterostilbene should be taken in the morning (to align with the circadian pattern of the sirtuin activity, which peaks during the day), and it should be taken with the resveratrol (at 250-500mg daily, which activates the NAMPT and enhances the NAD+ synthesis, thereby potentiating the SIRT1 activation by the pterostilbene). The pterostilbene is generally well-tolerated with no significant adverse effects at doses up to 250mg daily, and it does not cause the gastrointestinal irritation that is sometimes associated with the resveratrol at high doses. For comprehensive cognitive and longevity support, pterostilbene pairs well with the resveratrol (which activates the NAMPT and enhances the NAD+ synthesis), with the NR (nicotinamide riboside, which increases the NAD+ levels and thereby activates the sirtuins), with the alpha-lipoic acid (which has complementary effects on the mitochondrial function and on the insulin sensitivity), and with the phosphatidylserine (which supports the neuronal membrane integrity and which has complementary cognitive benefits for the memory and the attention).
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