Brain-derived neurotrophic factor (BDNF) can be considered a natural "brain antidepressant," as low levels of BDNF in the brain have been linked to mood disorders. BDNF is important for various physiological processes, including neuronal development, synaptic plasticity, neurogenesis, neuroprotection, and mood regulation. The connection between the BDNF signaling pathway and major depressive disorder is widely studied and is of great importance for advancing our understanding and treatment of this alarming disorder. However, much remains to be discovered, as research in this field is very active. Despite the existence of effective treatments, relapses after treatment and resistance to standard therapeutic options are common, underscoring the need for ongoing research. Studies have found that reduced BDNF levels are associated with a higher frequency of depressive symptoms, suggesting that BDNF plays a significant role in the underlying mechanisms of this illness, in addition to other important mechanisms such as oxidative stress, HPA axis imbalances, and altered neurotransmission.
The interaction of oxidative stress, HPA axis imbalance, serotonergic pathways, and BDNF plays a significant role in the development and progression of depression and other neuropsychiatric disorders. These interconnected mechanisms lead to advances in the diagnosis and treatment of depressive disorders, ultimately improving the lives of people with depression.
Blood levels of BDNF were lower in humans with obesity and type 2 diabetes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents beta-cell depletion. Reduced BDNF levels are associated with neurodegenerative diseases involving neuronal loss, such as mental and neurodegenerative disorders. Obesity is associated with an increased risk of depression, possibly due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management.
Short-chain fatty acids, such as butyrate, contribute to the upregulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis leads to reduced BDNF levels, which could affect neuronal development and synaptic plasticity. Increased intestinal permeability leads to an influx of gut microbial components such as lipopolysaccharides, and the resulting systemic inflammation can lead to neuroinflammation in the central nervous system.
BDNF is a marker of the effectiveness of exercise/physical activity in managing symptoms such as fatigue, pain, depression, and sleep disorders. Studies have reported increases in BDNF levels, but less than half showed significant increases in BDNF after exercise or physical activity programs.
Food-medicine homology is a traditional concept in which certain natural materials act as both food and medicine, offering both nutritional value and therapeutic benefits. Several classes of bioactive compounds exist in the brain that could be stimulated by natural compounds. Natural compounds can influence the levels and activity of neurotransmitters in the brain, which are essential for proper neuronal communication. Certain phytonutrients influence the production and regulation of neurotransmitters, such as serotonin and dopamine, which are key chemicals involved in regulating mood and emotional well-being. Other bioactive molecules involved in the brain include neurotrophic factors and growth regulators, such as brain-derived neurotrophic factor (BDNF), hormones, and neurosteroids, such as vitamin D. Recent technological and imaging advances are increasingly highlighting their important role in brain health as well. Thus, epigallocatechin-3-gallate (EGCG) from green tea and curcumin are polyphenols with evidence supporting their positive impacts on the symptomatology of mood disorders and possible mood-associated biomarkers such as brain-derived neurotrophic factor (BDNF).
Dr. Paul Marik, you are the best. Love your articles which are not only insightful and thorough but easy to comprehend. The graphics are very helpful. Always enjoy getting your email in my inbox! Thank you.
I would also add that continuous intellectual learning stimulates neuroplasticity and likely participates, among other mechanisms, through pathways related to BDNF.
Continuous intellectual learning—reading, studying, learning languages, music, new skills, analyzing—"continuous intellectual learning stimulates neuroplasticity and likely participates, among other mechanisms, through pathways related to BDNF."
THE EVIDENCE ON LEARNING → NEUROPLASTICITY/COGNITIVE RESERVE IS CONSIDERABLY BETTER THAN THE DIRECT EVIDENCE OF LEARNING → INCREASED BLOOD BDNF.
Therefore, rather than simply trying to "raise BDNF," I find it more interesting to maintain a neuroplastic environment throughout life:
🏃 Exercise. Aerobic exercise acutely increases BDNF, and intensity seems to matter a great deal. In a human study, 6 minutes of high-intensity interval training produced significantly greater increases in circulating BDNF than 90 minutes of light exercise.
😴 Good sleep. Sleep isn't just "something you can't do without": it's essential for synaptic plasticity, memory, and brain function. Sleep deprivation disrupts brain processes related to plasticity.
A 2025 meta-analysis on cognitive training and aging found changes in brain networks associated with cognitive improvements resulting from training. This is fairly direct evidence that the aging brain retains adaptive capacity.
Studies also indicate that executive function training promotes cognitive and neural improvements in old age. Cognitive improvements were generally limited to trained tasks or those with almost complete transfer. Structural improvements were evidenced by increases in gray matter and cerebral cortex. Overall, there was an increase in subcortical activation and a decrease in frontal activation after training.
This systematic review summarizes existing studies on cognitive interventions and rehabilitation for treating long COVID symptoms and analyzes their potential use in occupational therapy. Nineteen articles met the inclusion criteria and were classified into five intervention types: (a) cognitive training, (b) cognitive-behavioral therapy, (c) neurostimulation, (d) neurostimulation combined with cognitive training, and (e) multicomponent rehabilitation programs. There is strong evidence supporting cognitive training, moderate evidence supporting cognitive-behavioral training, and weak evidence supporting other interventions provided by occupational therapists to address the cognitive symptoms of long COVID in adults.
Intensive learning/use of a new skill was associated with experience-dependent structural changes in the hippocampus, a region essential for learning and memory. Furthermore, the era of artificial intelligence, in which technological advances are transforming the dynamics of employment and education, has led to the idea that lifelong learning systems have become a fundamental necessity. Through an individualized, adaptable, and effective method, artificial intelligence significantly contributes to skills development. Its application in vocational training facilitates the creation of personalized learning experiences, improves access to a wide range of educational resources, and enhances the quality of training through comprehensive data analysis. Furthermore, artificial intelligence optimizes adult education by providing a platform that adapts to diverse learning styles and paces, streamlines the process, and increases student engagement throughout.
A review/meta-analysis on cognitive reserve across the lifespan links greater reserve with a lower risk of dementia. Cognitive reserve (CR) plays a crucial role in delaying the onset and progression of Alzheimer's disease (AD). Lifestyle choices and experiences contribute to CR and influence cognitive aging. However, practical challenges remain for its application in clinical settings, especially in individuals with advanced cognitive impairment. Education, while commonly used as a proxy for CR, may not fully reflect its complexity. Alternatives such as occupational complexity could offer more practical measures, but their application is still under development. Addressing these limitations is essential for advancing dementia prevention strategies.
I am, again, a poster-child for this lifestyle, but neuroplasticity and brain remodeling are lately observed to be much stimulated by hallucinogens such as psylocibin, and there is much experimental interest,
This is wonderful Paul! Thanks for highlighting the role of BDNF in improving neuropsychiatric disorders. I would like to add that ketamine is a powerful inducer of BDNF and we are seeing significant improvement in neuropsychiatric disorders following treatment low doses of sublingual ketamine in many people. Other neuroplastogens (i.e. medicines that stimulate BDNF) include psilocybin mushrooms, ayahuasca (a tea made in the South American Amazon), Ibogaine (a plant from Central Africa) and others. Hopefully we can continue exploring these medicines for their therapeutic benefits.
Brain-derived neurotrophic factor (BDNF) can be considered a natural "brain antidepressant," as low levels of BDNF in the brain have been linked to mood disorders. BDNF is important for various physiological processes, including neuronal development, synaptic plasticity, neurogenesis, neuroprotection, and mood regulation. The connection between the BDNF signaling pathway and major depressive disorder is widely studied and is of great importance for advancing our understanding and treatment of this alarming disorder. However, much remains to be discovered, as research in this field is very active. Despite the existence of effective treatments, relapses after treatment and resistance to standard therapeutic options are common, underscoring the need for ongoing research. Studies have found that reduced BDNF levels are associated with a higher frequency of depressive symptoms, suggesting that BDNF plays a significant role in the underlying mechanisms of this illness, in addition to other important mechanisms such as oxidative stress, HPA axis imbalances, and altered neurotransmission.
The interaction of oxidative stress, HPA axis imbalance, serotonergic pathways, and BDNF plays a significant role in the development and progression of depression and other neuropsychiatric disorders. These interconnected mechanisms lead to advances in the diagnosis and treatment of depressive disorders, ultimately improving the lives of people with depression.
Blood levels of BDNF were lower in humans with obesity and type 2 diabetes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents beta-cell depletion. Reduced BDNF levels are associated with neurodegenerative diseases involving neuronal loss, such as mental and neurodegenerative disorders. Obesity is associated with an increased risk of depression, possibly due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management.
Short-chain fatty acids, such as butyrate, contribute to the upregulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis leads to reduced BDNF levels, which could affect neuronal development and synaptic plasticity. Increased intestinal permeability leads to an influx of gut microbial components such as lipopolysaccharides, and the resulting systemic inflammation can lead to neuroinflammation in the central nervous system.
BDNF is a marker of the effectiveness of exercise/physical activity in managing symptoms such as fatigue, pain, depression, and sleep disorders. Studies have reported increases in BDNF levels, but less than half showed significant increases in BDNF after exercise or physical activity programs. Food-medicine homology is a traditional concept in which certain natural materials act as both food and medicine, offering both nutritional value and therapeutic benefits. Several classes of bioactive compounds exist in the brain that could be stimulated by natural compounds. Natural compounds can influence the levels and activity of neurotransmitters in the brain, which are essential for proper neuronal communication. Certain phytonutrients influence the production and regulation of neurotransmitters, such as serotonin and dopamine, which are key chemicals involved in regulating mood and emotional well-being. Other bioactive molecules involved in the brain include neurotrophic factors and growth regulators, such as brain-derived neurotrophic factor (BDNF), hormones, and neurosteroids, such as vitamin D. Recent technological and imaging advances are increasingly highlighting their important role in brain health as well.
The increase in BDNF is linked to a diet rich in polyphenols, physical exercise, fasting/intermittent fasting, and control of inflammation and glucose. Plant-based foods likely to increase BDNF in humans include:
1) Blueberries, blackberries, and strawberries are rich in anthocyanins, a type of flavonoid associated with increased BDNF and improved cognitive function.
2) Human studies show improved memory and a parallel increase in BDNF with diets rich in fruit and vegetable flavonoids.
3) Anthocyanins appear to activate neuronal plasticity pathways (CREB–BDNF).
4) Pure cocoa (high in flavanols). Interventions with flavanol-rich cocoa increase BDNF and improve cognition in adults.
5) Olives and extra virgin olive oil (along with the Mediterranean diet). Diets rich in polyphenols are associated with higher BDNF levels in population studies.
6) Cruciferous vegetables. They reduce inflammation and oxidative stress, two factors that suppress BDNF.
7) Green tea and catechins. Recent reviews show effects on cognition, although the direct impact on BDNF is inconsistent in humans.
8) Turmeric. Experimental evidence suggests increased BDNF via reduced inflammation and CREB activation.
9) Black grapes. Resveratrol and other polyphenols may modulate neuroplasticity pathways.
You left out one of the most important factors, estradiol. From Gemini: Hormone Replacement Therapy (HRT)—specifically 17$\beta$-estradiol supplementation—exerts a dynamic influence on BDNF expression and cognitive function in perimenopausal women. However, clinical outcome data reveal a nuanced picture: while HRT reliably upregulates BDNF at the molecular level, its functional effect on cognition depends heavily on timing, formulation, and pre-existing neuronal health.
That last sentence refers to the timing hypothesis with female hormone replacement therapy.
An excellent overview. BDNF sits at the intersection of neuroplasticity, metabolism, and recovery, making it an important area of research across multiple neurological conditions. As the field evolves, it will be interesting to see which strategies demonstrate not only increases in BDNF, but meaningful improvements in long-term clinical outcomes.
Please check your AI. This statement, “Many antidepressants—including SSRIs—as well as ketamine and electroconvulsive therapy appear to exert part of their therapeutic effect by increasing BDNF signaling,” is highly misleading. None of these interventions have any significant “therapeutic effect,” and all produce harm.
This is not something that a patient can do.
This is being investigated by researchers. .. its role is unclear.
Thanks for this. Most informative.
Thanks for the feedback.
Thanks. Good chatting.
Okay. Thanks.
Yes... you right
Brain-derived neurotrophic factor (BDNF) can be considered a natural "brain antidepressant," as low levels of BDNF in the brain have been linked to mood disorders. BDNF is important for various physiological processes, including neuronal development, synaptic plasticity, neurogenesis, neuroprotection, and mood regulation. The connection between the BDNF signaling pathway and major depressive disorder is widely studied and is of great importance for advancing our understanding and treatment of this alarming disorder. However, much remains to be discovered, as research in this field is very active. Despite the existence of effective treatments, relapses after treatment and resistance to standard therapeutic options are common, underscoring the need for ongoing research. Studies have found that reduced BDNF levels are associated with a higher frequency of depressive symptoms, suggesting that BDNF plays a significant role in the underlying mechanisms of this illness, in addition to other important mechanisms such as oxidative stress, HPA axis imbalances, and altered neurotransmission.
The interaction of oxidative stress, HPA axis imbalance, serotonergic pathways, and BDNF plays a significant role in the development and progression of depression and other neuropsychiatric disorders. These interconnected mechanisms lead to advances in the diagnosis and treatment of depressive disorders, ultimately improving the lives of people with depression.
Blood levels of BDNF were lower in humans with obesity and type 2 diabetes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents beta-cell depletion. Reduced BDNF levels are associated with neurodegenerative diseases involving neuronal loss, such as mental and neurodegenerative disorders. Obesity is associated with an increased risk of depression, possibly due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management.
Short-chain fatty acids, such as butyrate, contribute to the upregulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis leads to reduced BDNF levels, which could affect neuronal development and synaptic plasticity. Increased intestinal permeability leads to an influx of gut microbial components such as lipopolysaccharides, and the resulting systemic inflammation can lead to neuroinflammation in the central nervous system.
BDNF is a marker of the effectiveness of exercise/physical activity in managing symptoms such as fatigue, pain, depression, and sleep disorders. Studies have reported increases in BDNF levels, but less than half showed significant increases in BDNF after exercise or physical activity programs.
Food-medicine homology is a traditional concept in which certain natural materials act as both food and medicine, offering both nutritional value and therapeutic benefits. Several classes of bioactive compounds exist in the brain that could be stimulated by natural compounds. Natural compounds can influence the levels and activity of neurotransmitters in the brain, which are essential for proper neuronal communication. Certain phytonutrients influence the production and regulation of neurotransmitters, such as serotonin and dopamine, which are key chemicals involved in regulating mood and emotional well-being. Other bioactive molecules involved in the brain include neurotrophic factors and growth regulators, such as brain-derived neurotrophic factor (BDNF), hormones, and neurosteroids, such as vitamin D. Recent technological and imaging advances are increasingly highlighting their important role in brain health as well. Thus, epigallocatechin-3-gallate (EGCG) from green tea and curcumin are polyphenols with evidence supporting their positive impacts on the symptomatology of mood disorders and possible mood-associated biomarkers such as brain-derived neurotrophic factor (BDNF).
https://pubmed.ncbi.nlm.nih.gov/25568448/ (2012).--
https://pubmed.ncbi.nlm.nih.gov/17173978/ (2015).---
https://www.mdpi.com/1999-4923/15/8/2081 (2023)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/ (2015).---
https://www.mdpi.com/1422-0067/23/12/6827 (2022).---
https://www.mdpi.com/1422-0067/23/3/1172 (2022).----
https://www.mdpi.com/2227-9059/12/9/1994 (2024)..
https://www.mdpi.com/1420-3049/30/4/848 (2025)
https://www.mdpi.com/2075-1729/15/7/1147 (2025)
https://www.mdpi.com/2075-4663/13/8/253 (2025)
https://www.mdpi.com/2072-6643/17/19/3069 (2025)
https://www.mdpi.com/2072-6643/18/5/855 (2026)
https://www.mdpi.com/1422-0067/27/4/1788 (2026)
https://www.mdpi.com/2413-4155/8/4/84 (2026)
https://www.mdpi.com/journal/ijms/special_issues/6DM0S41G7R (2026)
Dr. Paul Marik, you are the best. Love your articles which are not only insightful and thorough but easy to comprehend. The graphics are very helpful. Always enjoy getting your email in my inbox! Thank you.
I would also add that continuous intellectual learning stimulates neuroplasticity and likely participates, among other mechanisms, through pathways related to BDNF.
Continuous intellectual learning—reading, studying, learning languages, music, new skills, analyzing—"continuous intellectual learning stimulates neuroplasticity and likely participates, among other mechanisms, through pathways related to BDNF."
THE EVIDENCE ON LEARNING → NEUROPLASTICITY/COGNITIVE RESERVE IS CONSIDERABLY BETTER THAN THE DIRECT EVIDENCE OF LEARNING → INCREASED BLOOD BDNF.
Therefore, rather than simply trying to "raise BDNF," I find it more interesting to maintain a neuroplastic environment throughout life:
🏃 Exercise. Aerobic exercise acutely increases BDNF, and intensity seems to matter a great deal. In a human study, 6 minutes of high-intensity interval training produced significantly greater increases in circulating BDNF than 90 minutes of light exercise.
https://pubmed.ncbi.nlm.nih.gov/36631068/ (2023)
🧠 Continuous learning
😴 Good sleep. Sleep isn't just "something you can't do without": it's essential for synaptic plasticity, memory, and brain function. Sleep deprivation disrupts brain processes related to plasticity.
https://arxiv.org/abs/1706.03835?utm_source=chatgpt.com (2017)
🌱 Intellectual and social activity
A 2025 meta-analysis on cognitive training and aging found changes in brain networks associated with cognitive improvements resulting from training. This is fairly direct evidence that the aging brain retains adaptive capacity.
Studies also indicate that executive function training promotes cognitive and neural improvements in old age. Cognitive improvements were generally limited to trained tasks or those with almost complete transfer. Structural improvements were evidenced by increases in gray matter and cerebral cortex. Overall, there was an increase in subcortical activation and a decrease in frontal activation after training.
https://www.nature.com/articles/s41514-025-00290-5?utm_source=chatgpt.com (2025)
https://www.sciencedirect.com/science/article/abs/pii/S1568163718303118 (2019)
https://www.sciencedirect.com/science/article/abs/pii/S1568163722001660 (2022)
This systematic review summarizes existing studies on cognitive interventions and rehabilitation for treating long COVID symptoms and analyzes their potential use in occupational therapy. Nineteen articles met the inclusion criteria and were classified into five intervention types: (a) cognitive training, (b) cognitive-behavioral therapy, (c) neurostimulation, (d) neurostimulation combined with cognitive training, and (e) multicomponent rehabilitation programs. There is strong evidence supporting cognitive training, moderate evidence supporting cognitive-behavioral training, and weak evidence supporting other interventions provided by occupational therapists to address the cognitive symptoms of long COVID in adults.
https://journals.sagepub.com/doi/full/10.1177/15394492251328310 (2026)
Tomato Intake Improves Cognitive Performance and Modulates Functional Brain Networks in Healthy Adults: A Randomized Crossover Clinical Trial
https://www.mdpi.com/2076-3921/15/5/644 (2026)
Intensive learning/use of a new skill was associated with experience-dependent structural changes in the hippocampus, a region essential for learning and memory. Furthermore, the era of artificial intelligence, in which technological advances are transforming the dynamics of employment and education, has led to the idea that lifelong learning systems have become a fundamental necessity. Through an individualized, adaptable, and effective method, artificial intelligence significantly contributes to skills development. Its application in vocational training facilitates the creation of personalized learning experiences, improves access to a wide range of educational resources, and enhances the quality of training through comprehensive data analysis. Furthermore, artificial intelligence optimizes adult education by providing a platform that adapts to diverse learning styles and paces, streamlines the process, and increases student engagement throughout.
https://www.eneuro.org/content/12/6/ENEURO.0128-25.2025?utm_source=chatgpt.com (2025)
https://www.igi-global.com/chapter/lifelong-learning-systems-in-the-age-of-ai/386005 (2026)
https://api.taylorfrancis.com/content/chapters/edit/download?identifierName=doi&identifierValue=10.1201/9781003655190-22&type=chapterpdf (2027)
A review/meta-analysis on cognitive reserve across the lifespan links greater reserve with a lower risk of dementia. Cognitive reserve (CR) plays a crucial role in delaying the onset and progression of Alzheimer's disease (AD). Lifestyle choices and experiences contribute to CR and influence cognitive aging. However, practical challenges remain for its application in clinical settings, especially in individuals with advanced cognitive impairment. Education, while commonly used as a proxy for CR, may not fully reflect its complexity. Alternatives such as occupational complexity could offer more practical measures, but their application is still under development. Addressing these limitations is essential for advancing dementia prevention strategies.
https://pubmed.ncbi.nlm.nih.gov/38681665/ (2024)
https://www.tandfonline.com/doi/abs/10.1080/14737175.2024.2445015 (2025)
"Strategies That Increase BDNF . . ."
What about Remote Ischemic Conditioning (RIC)? You don't mention it.
I asked his reason but he wouldn't give an answer. Oh well.
I am, again, a poster-child for this lifestyle, but neuroplasticity and brain remodeling are lately observed to be much stimulated by hallucinogens such as psylocibin, and there is much experimental interest,
https://www.nature.com/articles/s41386-022-01389-z
https://pmc.ncbi.nlm.nih.gov/articles/PMC9665925/
This is wonderful Paul! Thanks for highlighting the role of BDNF in improving neuropsychiatric disorders. I would like to add that ketamine is a powerful inducer of BDNF and we are seeing significant improvement in neuropsychiatric disorders following treatment low doses of sublingual ketamine in many people. Other neuroplastogens (i.e. medicines that stimulate BDNF) include psilocybin mushrooms, ayahuasca (a tea made in the South American Amazon), Ibogaine (a plant from Central Africa) and others. Hopefully we can continue exploring these medicines for their therapeutic benefits.
Brain-derived neurotrophic factor (BDNF) can be considered a natural "brain antidepressant," as low levels of BDNF in the brain have been linked to mood disorders. BDNF is important for various physiological processes, including neuronal development, synaptic plasticity, neurogenesis, neuroprotection, and mood regulation. The connection between the BDNF signaling pathway and major depressive disorder is widely studied and is of great importance for advancing our understanding and treatment of this alarming disorder. However, much remains to be discovered, as research in this field is very active. Despite the existence of effective treatments, relapses after treatment and resistance to standard therapeutic options are common, underscoring the need for ongoing research. Studies have found that reduced BDNF levels are associated with a higher frequency of depressive symptoms, suggesting that BDNF plays a significant role in the underlying mechanisms of this illness, in addition to other important mechanisms such as oxidative stress, HPA axis imbalances, and altered neurotransmission.
The interaction of oxidative stress, HPA axis imbalance, serotonergic pathways, and BDNF plays a significant role in the development and progression of depression and other neuropsychiatric disorders. These interconnected mechanisms lead to advances in the diagnosis and treatment of depressive disorders, ultimately improving the lives of people with depression.
Blood levels of BDNF were lower in humans with obesity and type 2 diabetes. Brain-derived neurotrophic factor regulates glucose and energy metabolism and prevents beta-cell depletion. Reduced BDNF levels are associated with neurodegenerative diseases involving neuronal loss, such as mental and neurodegenerative disorders. Obesity is associated with an increased risk of depression, possibly due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management.
Short-chain fatty acids, such as butyrate, contribute to the upregulation of brain-derived neurotrophic factor (BDNF), and gut dysbiosis leads to reduced BDNF levels, which could affect neuronal development and synaptic plasticity. Increased intestinal permeability leads to an influx of gut microbial components such as lipopolysaccharides, and the resulting systemic inflammation can lead to neuroinflammation in the central nervous system.
BDNF is a marker of the effectiveness of exercise/physical activity in managing symptoms such as fatigue, pain, depression, and sleep disorders. Studies have reported increases in BDNF levels, but less than half showed significant increases in BDNF after exercise or physical activity programs. Food-medicine homology is a traditional concept in which certain natural materials act as both food and medicine, offering both nutritional value and therapeutic benefits. Several classes of bioactive compounds exist in the brain that could be stimulated by natural compounds. Natural compounds can influence the levels and activity of neurotransmitters in the brain, which are essential for proper neuronal communication. Certain phytonutrients influence the production and regulation of neurotransmitters, such as serotonin and dopamine, which are key chemicals involved in regulating mood and emotional well-being. Other bioactive molecules involved in the brain include neurotrophic factors and growth regulators, such as brain-derived neurotrophic factor (BDNF), hormones, and neurosteroids, such as vitamin D. Recent technological and imaging advances are increasingly highlighting their important role in brain health as well.
The increase in BDNF is linked to a diet rich in polyphenols, physical exercise, fasting/intermittent fasting, and control of inflammation and glucose. Plant-based foods likely to increase BDNF in humans include:
1) Blueberries, blackberries, and strawberries are rich in anthocyanins, a type of flavonoid associated with increased BDNF and improved cognitive function.
2) Human studies show improved memory and a parallel increase in BDNF with diets rich in fruit and vegetable flavonoids.
3) Anthocyanins appear to activate neuronal plasticity pathways (CREB–BDNF).
4) Pure cocoa (high in flavanols). Interventions with flavanol-rich cocoa increase BDNF and improve cognition in adults.
5) Olives and extra virgin olive oil (along with the Mediterranean diet). Diets rich in polyphenols are associated with higher BDNF levels in population studies.
6) Cruciferous vegetables. They reduce inflammation and oxidative stress, two factors that suppress BDNF.
7) Green tea and catechins. Recent reviews show effects on cognition, although the direct impact on BDNF is inconsistent in humans.
8) Turmeric. Experimental evidence suggests increased BDNF via reduced inflammation and CREB activation.
9) Black grapes. Resveratrol and other polyphenols may modulate neuroplasticity pathways.
https://pubmed.ncbi.nlm.nih.gov/25568448/ (2012).--
https://pubmed.ncbi.nlm.nih.gov/17173978/ (2015).---
https://pmc.ncbi.nlm.nih.gov/articles/PMC5166520/?utm_source=chatgpt.com (2016)
https://pmc.ncbi.nlm.nih.gov/articles/PMC5166520/?utm_source=chatgpt.com (2016)
https://www.mdpi.com/1999-4923/15/8/2081 (2023)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4697050/ (2015).---
https://www.mdpi.com/1422-0067/23/12/6827 (2022).---
https://www.mdpi.com/1422-0067/23/3/1172 (2022).----
https://www.mdpi.com/2227-9059/12/9/1994 (2024)..
https://www.sciencedirect.com/science/article/pii/S2475299124000295?utm_source=chatgpt.com (2024)
https://www.mdpi.com/1420-3049/30/4/848 (2025)
https://www.mdpi.com/2075-1729/15/7/1147 (2025)
https://www.mdpi.com/2075-4663/13/8/253 (2025)
https://www.mdpi.com/2072-6643/17/19/3069 (2025)
https://pmc.ncbi.nlm.nih.gov/articles/PMC12292568/?utm_source=chatgpt.com (2025)
https://www.mdpi.com/2072-6643/18/5/855 (2026)
https://www.mdpi.com/1422-0067/27/4/1788 (2026)
https://www.mdpi.com/2413-4155/8/4/84 (2026)
https://www.mdpi.com/journal/ijms/special_issues/6DM0S41G7R (2026)
You left out one of the most important factors, estradiol. From Gemini: Hormone Replacement Therapy (HRT)—specifically 17$\beta$-estradiol supplementation—exerts a dynamic influence on BDNF expression and cognitive function in perimenopausal women. However, clinical outcome data reveal a nuanced picture: while HRT reliably upregulates BDNF at the molecular level, its functional effect on cognition depends heavily on timing, formulation, and pre-existing neuronal health.
That last sentence refers to the timing hypothesis with female hormone replacement therapy.
An excellent overview. BDNF sits at the intersection of neuroplasticity, metabolism, and recovery, making it an important area of research across multiple neurological conditions. As the field evolves, it will be interesting to see which strategies demonstrate not only increases in BDNF, but meaningful improvements in long-term clinical outcomes.
Hi Paul,
Please check your AI. This statement, “Many antidepressants—including SSRIs—as well as ketamine and electroconvulsive therapy appear to exert part of their therapeutic effect by increasing BDNF signaling,” is highly misleading. None of these interventions have any significant “therapeutic effect,” and all produce harm.
Cheers!
Richard