Vinpocetine is the periwinkle derivative that is one of the most effective natural compounds for the enhancement of the cerebral blood flow — it is synthesised from the vincamine (the major alkaloid of the periwinkle, Vinca minor), and it is used as the cognitive enhancer and as the neuroprotective agent in Europe, Japan, and other countries (but not in the United States, where it is classified as a dietary supplement). The vinpocetine is unique among the nootropics because it has multiple and complementary mechanisms of action — it is a potent inhibitor of the phosphodiesterase type 1 (PDE1), it is a vasodilator of the cerebral blood vessels, it is an antioxidant, and it is a neuroprotective agent that reduces the calcium influx and the excitotoxicity in the neurons. The primary mechanism of the vinpocetine’s cognitive enhancement is the inhibition of the PDE1 — this enzyme normally breaks down the cyclic GMP (cGMP), which is the second messenger that mediates the vasodilatory effect of the nitric oxide (NO) on the cerebral blood vessels. By inhibiting the PDE1, the vinpocetine increases the cGMP levels in the vascular smooth muscle cells of the cerebral blood vessels, thereby causing the vasodilation and the increase in the cerebral blood flow. This increased cerebral blood flow delivers more oxygen, more glucose, and more nutrients to the brain — and it removes the metabolic waste products (CO2, lactate, reactive oxygen species) more efficiently — thereby improving the cognitive function, the attention, and the memory. Without adequate vinpocetine and cerebral perfusion, the brain is underperfused, the cognitive function declines, and the neuronal ageing accelerates — the hallmark of the vinpocetine deficiency and of the cerebral hypoperfusion that is associated with the normal ageing, the stroke, and the vascular cognitive impairment.
Vinpocetine and the Cognitive Function
Vinpocetine supports the cognitive function primarily through the increase in the cerebral blood flow — by inhibiting the PDE1 and increasing the cGMP in the cerebral vasculature, the vinpocetine causes the vasodilation of the cerebral blood vessels and the increase in the cerebral blood flow (by 20-30% in some studies, as measured by the Xenon-133 clearance technique and by the functional MRI). This increased blood flow delivers more oxygen and glucose to the brain (the two primary substrates for the cerebral energy metabolism), thereby improving the neuronal function, the synaptic transmission, and the cognitive processing — particularly in the areas that are involved in the memory and the attention (the hippocampus, the prefrontal cortex, the parietal cortex). The vinpocetine also has direct effects on the neurons — it reduces the calcium influx through the voltage-gated calcium channels, thereby reducing the excitotoxicity and the calcium-induced neuronal death; it scavenges the reactive oxygen species, thereby protecting the neurons from the oxidative damage; and it modulates the NMDA and the GABA receptors, thereby regulating the excitatory and the inhibitory neurotransmission in the brain. These multiple mechanisms of the vinpocetine (enhanced cerebral blood flow, reduced excitotoxicity, antioxidant, neuromodulation) make it one of the most comprehensive and most effective nootropics for the cognitive enhancement and for the neuroprotection.
The clinical importance of the vinpocetine for the cognitive function is underscored by the observation that the vinpocetine 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 6 RCTs in over 400 participants with the age-related cognitive decline found that the vinpocetine supplementation at 10-40mg daily significantly improved the cognitive function (by 10-15% on the standard cognitive tests), improved the memory (by 10-15%), and improved the attention (by 10-15%) — demonstrating the potent and consistent effect of the vinpocetine on the cognitive function in humans.
Practical Application
For general vinpocetine supplementation for the cerebral blood flow and for the cognitive support, the evidence-based approach is to supplement with 10-40mg of vinpocetine daily (as the pure vinpocetine powder or capsule, taken 2-3 times per day with the meals). The vinpocetine should be started at the low dose (10mg daily) and titrated gradually to the therapeutic dose (20-40mg daily) to minimise the side effects (which can include the headache, the flushing, the gastrointestinal symptoms, and the dizziness). The vinpocetine is generally well-tolerated with no significant adverse effects at doses up to 60mg daily, and it does not have any significant drug interactions — though it may enhance the effects of the anticoagulant and the antiplatelet drugs (because it has mild antiplatelet effects). For comprehensive cerebral blood flow and cognitive support, vinpocetine pairs well with the Ginkgo biloba (which is another natural compound that enhances the cerebral blood flow through a complementary mechanism involving the inhibition of the platelet activating factor and the increase in the nitric oxide production), with the phosphatidylserine (which supports the neuronal membrane integrity and which works synergistically with the vinpocetine for the cognitive function), with the acetyl-L-carnitine (which supports the mitochondrial function and which works synergistically with the vinpocetine for the neuronal energy metabolism and the cognitive function), and with the alpha-GPC (which provides the choline precursor for the acetylcholine synthesis and which works synergistically with the vinpocetine for the cholinergic enhancement).
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