on September 18, 2026
The brain and the need for an adequate supply of oxygen
Nervous tissue has a high energy demand and depends continuously on the supply of oxygen and glucose through the cerebrovascular system. Alterations in perfusion can therefore have important consequences on neuronal function, especially when associated with aging, cerebrovascular diseases, or other cardiovascular risk factors.
However, it is important to distinguish true cerebral hypoxia from a more subtle condition of reduced neurovascular efficiency. Clinically significant cerebral hypoxia can occur, for example, in the presence of a severe reduction in blood oxygenation, cerebral ischemia, stroke, or other acute conditions, and requires specific medical evaluation. A Ginkgo-based supplement cannot replace the diagnosis and treatment of these conditions.
The nutraceutical interest in Ginkgo arises instead from the possibility of intervening on some of the processes that can accompany brain aging: microcirculation, oxidative stress, neuronal energy metabolism, neuroinflammation, and vulnerability of nerve cells.
Brain aging is also a neurovascular problem
With advancing age, the brain is exposed to a progressive modification of vascular and metabolic function. The reduction in the microcirculation's adaptive capacity can be associated with reduced efficiency in the distribution of oxygen and nutrients, while oxidative stress and mitochondrial dysfunction can make neurons more vulnerable.
To this is added low-grade chronic neuroinflammation, in which glial cells and inflammatory mediators can contribute over time to the alteration of the neuronal environment.
For this reason, cognitive function cannot be considered exclusively as a property of neurons: it also depends on the integration between neurons, endothelium, microcirculation, glial cells, and energy metabolism.
In this context, Ginkgo biloba is particularly interesting because its pharmacological profile does not depend on a single molecule or a single target.
Ginkgo biloba: a multi-target phytocomplex
The leaves of Ginkgo biloba contain several classes of bioactive substances. Among the most studied are flavonoids, ginkgolides, and bilobalide.
Flavonoids contribute to the antioxidant profile of the phytocomplex and can counteract some processes associated with the production of reactive oxygen species.
Ginkgolides, on the other hand, are characterized, among other pharmacological activities, by the ability to antagonize platelet activating factor, or PAF, a mediator involved in platelet activation and inflammatory processes.
Bilobalide, a component of the terpene fraction, has been studied mainly for its neuroprotective and mitochondrial effects. Experimental studies indicate that it can help preserve mitochondrial respiratory function in ischemic conditions and reduce some mechanisms associated with neuronal damage.
The complexity of the phytocomplex is therefore consistent with a model in which different components act simultaneously on multiple levels of cerebral pathophysiology.
Cerebral microcirculation and oxygen availability
One of the most interesting aspects of Ginkgo concerns the neurovascular component.
The EMA reports pharmacodynamic data in humans related to changes in cerebral perfusion, blood viscosity, and platelet aggregation, although the extent and clinical relevance of these effects depend on the preparation and the population studied.
This allows for the formulation of a precise pathophysiological rationale: promoting vascular conditions compatible with improved perfusion can help maintain brain function, especially when there is a vascular component in cognitive decline.
Cerebral oxygenation depends on many variables: arterial saturation, hemoglobin, cardiac output, pressure, cerebrovascular autoregulation, regional perfusion, and neuronal metabolism.
Ginkgo can be studied as a modulator of the neurovascular environment when there is a real reduction in cerebral oxygenation.
Bilobalide and mitochondrial protection
The mitochondrion represents a particularly important point because the neuron has a high energy demand.
During ischemia and hypoxia, alterations occur in oxidative phosphorylation, ATP production, calcium homeostasis, and the production of reactive oxygen species. Mitochondrial impairment can therefore turn a transient reduction in energy supply into a cascade of cellular damage.
Experimental studies have shown that bilobalide can preserve some functions of the mitochondrial respiratory chain during ischemic conditions and reduce neuronal excitotoxicity. In animal models of cerebral ischemia, treatment with bilobalide has also shown effects on mitochondrial respiration and glutamate release.
These data are biologically interesting because they suggest a possible mechanism through which Ginkgo could increase neuronal resilience when energy availability is compromised.
However, it is essential to distinguish these results from clinical practice: much of the evidence on the anti-ischemic mechanisms of bilobalide comes from cellular and animal studies and does not demonstrate that taking Ginkgo prevents or treats cerebral ischemia in humans.
Oxidative stress and neuroinflammation
The brain is particularly vulnerable to oxidative stress due to its high metabolic activity and the lipid composition of neuronal membranes.
Standardized Ginkgo extract has been studied for its antioxidant properties and the ability of its components to interfere with cellular processes involved in inflammation and oxidative damage. The terpene fraction has also been studied in models of cerebral ischemia, in which anti-apoptotic, antioxidant, and anti-excitotoxicity effects have been observed.
This set of activities is particularly relevant in brain aging, because oxidative stress and inflammation can feed each other and progressively compromise the adaptive capacity of neurons.
Neuroprotection must therefore be understood as the protection of the cellular systems that maintain neuronal functionality, not as a generic "stimulating" action on the brain.
What do clinical studies show about cognitive function?
The most consistent clinical evidence does not concern young and healthy people who simply want to improve their cognitive abilities, but subjects with cognitive impairment or dementia, particularly when neuropsychiatric manifestations are present.
A systematic review and meta-analysis of randomized controlled trials on the standardized extract EGb 761 included 2,684 patients treated for approximately 22-26 weeks. The analyses found statistically significant differences in favor of the extract compared to placebo for cognition, activities of daily living, and global assessment. The studied doses were 120 or 240 mg/day, with generally more consistent results at the dose of 240 mg/day.
Another meta-analysis comprising nine studies and over 2,500 patients highlighted benefits especially with 240 mg/day in the domains of cognition, daily activities, and global clinical assessment.
Particularly interesting is a 24-week randomized study conducted on 410 people with mild-to-moderate dementia and neuropsychiatric symptoms. The standardized extract at the dose of 240 mg/day produced improvements compared to placebo in both cognitive tests and neuropsychiatric symptoms, with a similar overall frequency of adverse events between the groups.
A systematic review specifically dedicated to mild neurocognitive disorder identified nine clinical studies involving a total of 946 participants. Most studies reported favorable signals in neuropsychological tests, while methodological heterogeneity calls for caution in interpreting the results.
And in healthy people?
The situation is different in healthy adults.
The EMA reports that the cognitive effects observed in clinical studies are primarily documented in elderly populations with deficits, while the results are less consistent in young and healthy subjects.
Even studies conducted in cognitively intact elderly people have not provided uniform evidence of clinically relevant cognitive improvement. In a four-month randomized trial conducted on 90 healthy elderly people, a supplement containing Ginkgo along with other nutritional components did not provide overall evidence of cognitive improvement sufficient to attribute the effect exclusively to Ginkgo.
This distinction is important: clinical evidence on Ginkgo does not authorize it to be considered a universal cognitive enhancer.
Its rationale appears more compelling when there is neurovascular vulnerability or pre-existing cognitive decline, always within the context of a clinical assessment.
Ginkgo and "brain oxygen deficiency": what can we really say?
The concept of "brain oxygen deficiency" can refer to very different situations.
True cerebral hypoxia or ischemia can be an acute and potentially serious condition. In the presence of sudden neurological symptoms, alterations in consciousness, difficulty speaking, loss of strength or sensation, sudden changes in vision, severe dizziness associated with neurological deficits, or other signs consistent with a cerebrovascular event, urgent medical evaluation is necessary.
In other cases, however, a person may describe mental fatigue, difficulty concentrating, cognitive slowing, or a "blank mind" without true cerebral hypoxia. These symptoms can have numerous causes: sleep disorders, anemia, nutritional deficiencies, medications, metabolic disorders, stress, depression, cardiovascular diseases, nocturnal respiratory disorders, or neurological problems.
In this second scenario, Ginkgo can be considered, when appropriate, as nutraceutical support for the neurovascular system.
From the microcirculation to brain longevity
Longevity does not simply coincide with an increase in years of life. An essential part of healthy aging involves maintaining autonomy, memory, attention, and the ability to interact with the environment.
The aging brain must therefore be considered as a system in which the following converge:
- perfusion and microcirculation;
- energy metabolism;
- mitochondrial function;
- oxidative balance;
- neuroinflammatory response;
- neuronal integrity;
- synaptic plasticity;
- cardiovascular and metabolic health.
Ginkgo is therefore of particular interest because its constituents interact with more than one of these levels simultaneously. This characteristic helps explain why its rationale differs from that of a simple cognitive stimulant.
Standardization of the extract is essential
Not all products containing "Ginkgo" are necessarily equivalent.
The main clinical evidence available concerns primarily standardized extracts, in particular preparations characterized by a precise flavonoid and terpenoid lactone content. Consequently, it is not correct to automatically transfer the results obtained with a specific standardized extract to any Ginkgo leaf preparation or to any supplement containing non-comparable amounts of extract.
The dose, phytochemical standardization, quality of the raw material, and overall composition are therefore determining factors in interpreting the evidence.
Safety and interactions
The fact that a substance is of plant origin does not mean that it is free from pharmacological interactions.
The EMA reports a possible increased susceptibility to bleeding associated with Ginkgo leaf medicines and recommends particular caution in subjects taking anticoagulants or antiplatelet agents. Precautions are also reported around surgical procedures and in patients with a predisposition to seizures.
The presence of anticoagulant, antiplatelet, nonsteroidal anti-inflammatory drug, or other medication therapy must therefore be communicated to the doctor or pharmacist before use.
This aspect is particularly important in elderly people, in whom polypharmacy is frequent.
An integrated perspective on brain health
Interest in Ginkgo is therefore part of a broader strategy to protect brain function.
The maintenance of microcirculation and cognitive function also depends on controlling the main cardiovascular and metabolic risk factors, regular physical activity, sleep quality, diet, abstinence from smoking, and maintaining adequate mental and social activity.
In this context, Ginkgo can represent a phytotherapeutic support with a neurovascular and neuroprotective rationale, especially when the goal is to support cognitive function in the presence of conditions for which clinical evidence exists.
Experimental research also suggests interesting mechanisms related to mitochondrial protection and the response to ischemic damage. However, these data must not be turned into the assertion that Ginkgo can prevent or treat true cerebral hypoxia, a stroke, or acute ischemia.
The central point is therefore to distinguish support of neurovascular physiology and treatment of a cerebrovascular disease. In the first case, Ginkgo represents a phytocomplex of considerable scientific interest; in the second, a medical diagnostic and therapeutic pathway is essential.
Bibliographic references
- Efficacy and tolerability of Ginkgo biloba extract EGb 761 in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials. Clinical Interventions in Aging. 2014;9:2065-2077.
- Efficacy and adverse effects of ginkgo biloba for cognitive impairment and dementia: a systematic review and meta-analysis. Journal of Alzheimer's Disease. 2014.
- Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomised, placebo-controlled trial to confirm the efficacy and safety of a daily dose of 240 mg. Journal of Psychiatric Research. 2012;46:716-723.
- Efficacy and safety of a once-daily formulation of Ginkgo biloba extract EGb 761 in dementia with neuropsychiatric features: a randomized controlled trial. International Journal of Geriatric Psychiatry. 2011.
- Ginkgo biloba Extract EGb 761 in the Treatment of Patients with Mild Neurocognitive Impairment: A Systematic Review. 2023.
- The neuroprotective mechanisms of ginkgolides and bilobalide in cerebral ischemic injury: a literature review. Molecular Medicine. 2019;25:57.
- Neuroprotection by bilobalide in ischemia: improvement of mitochondrial function. Pharmazie. 2013;68:584-589.
- Bilobalide and neuroprotection. Pharmacological Research. 2002;46:565-568.
- Ginkgo biloba on focal cerebral ischemia: a systematic review and meta-analysis. 2014.
- European Medicines Agency, European Union herbal monograph on Ginkgo biloba L., folium. EMA/HMPC/321097/2012.
