Neuroplasticity and BDNF

1. What This Mechanism Is

Neuroplasticity describes the brain's ability to adapt structurally and functionally. BDNF (Brain-Derived Neurotrophic Factor) is a key marker: it promotes neuronal survival, synapse formation, and neuronal networking. Changes in BDNF levels correlate with learning ability, memory, and mood regulation. Other markers, such as synaptic proteins (e.g., synaptophysin) or inflammatory mediators (e.g., IL-6), complete the picture. Regulation occurs via signalling pathways like MAPK/ERK or PI3K/Akt, which are influenced by external factors such as diet, exercise, or stress.

Neuroplasticity in humans can be measured indirectly through cognitive tests, imaging (e.g., fMRI, DTI), or biomarkers in the blood (BDNF, inflammatory parameters). Direct measurements in brain tissue are rarely possible. Controlled studies often use combined endpoints (e.g., memory performance + BDNF levels) to capture effects. Animal experiments and cell studies provide insights into mechanisms but are not always transferable. Variability between individuals complicates clear conclusions.

2. Which Substances Influence This Mechanism

All substances in the database for which this mechanism is described—ordered by the extent of human testing. The numbers represent studies per type of investigation.

3. How Robust This Evidence Is

Substances with multiple controlled human studies are well established: omega-3 fatty acids, vitamin D, magnesium, probiotics, and adaptogens (e.g., Bacopa monnieri). These consistently demonstrate effects on BDNF or cognitive parameters. Chronic inflammation and the gut microbiome are also well researched but more complex to interpret. Evidence is weaker for substances such as humic acid complexes, turmeric, or melatonin—here, laboratory or animal studies predominate, while human data are lacking or merely observational.

Many substances act via shared pathways: anti-inflammatory effects, antioxidant activity, or modulation of the gut microbiome. For example, both omega-3 fatty acids and vitamin D influence BDNF expression, potentially through anti-inflammatory mechanisms. While combining substances with complementary effects (e.g., probiotics + omega-3) seems plausible, this remains untested. The role of humic acid complexes in neuroplasticity is theoretically credible (e.g., via detoxification or microbiome modulation) but scarcely investigated.

4. Key Human Studies

• 1 Plasticity Biomarkers, Interleukin 6, and Motor Performance Responses to Trans-auricular Vagus Nerve Stimulation Post-Stroke: A Randomised Controlled Trial (2026) — Chronic inflammation
• 2 The effect of MIND diet on sleep status, anxiety, depression, and cardiometabolic indices in obese diabetic women with insomnia: study protocol for a randomised controlled trial (2024) — Chronic inflammation
• 3 Dietary anthocyanins and the MAPK signalling pathway: from food sources to molecular mechanisms (2026) — Chronic inflammation
• 4 Gut-Brain Axis and Perioperative Gut Microbiome in Postoperative Cognitive Dysfunction: Implications for Neurosurgical Patients (2025) — Gut microbiome
• 5 Multi-dimensional dynamic monitoring of the gut microbiota-emotion axis and precision exercise intervention in compulsory drug rehabilitation: A 24-week randomised controlled trial (2026) — Gut microbiome
• 6 Potential synergistic effects of exercise and gut microbiota on post-stroke recovery: mechanistic insights and a proposed stage-specific research framework (2026) — Gut microbiome
• 7 Bacopa monnieri as augmentation therapy in the treatment of anhedonia: preclinical and clinical evaluation (2020) — Adaptogens
• 8 Potential clinical applications of Ashwagandha (Withania somnifera) in medicine and neuropsychiatry (2022) — Adaptogens
• 9 The neurocognitive effects of Bacopa monnieri and cognitive training on markers of brain microstructure in healthy older adults (2021) — Adaptogens
• 10 Long-chain omega-3 fatty acids improve brain function and structure in older adults (2014) — Omega-3 fatty acids
• 11 N-3 polyunsaturated fatty acids promote astrocyte differentiation and neurotrophin production independent of cAMP in patient-derived neural stem cells (2021) — Omega-3 fatty acids
• 12 Nutritional interventions in depression: the role of vitamin D and omega-3 fatty acids in neuropsychiatric health (2025) — Omega-3 fatty acids
• 13 Effect of synbiotic and probiotic supplementation on serum brain-derived neurotrophic factor level, depression and anxiety symptoms in haemodialysis patients: a randomised controlled trial (2021) — Probiotics
• 14 Effect of short-term, high-dose probiotic supplementation on cognition, related brain functions and BDNF in patients with depression: a secondary analysis of a randomised controlled trial (2023) — Probiotics
• 15 Randomised controlled trial evaluating synbiotic supplementation as an adjuvant therapy in the treatment of Parkinson’s disease (2025) — Probiotics
• 16 Effects of cholecalciferol supplementation on depressive symptoms, C-peptide, serotonin, and neurotrophin-3 in type 2 diabetes mellitus: a double-blind (2024) — Vitamin D
• 17 The role of stress-related biomarkers, immune-inflammatory pathways, and genetic polymorphisms in cognitive-behavioural therapies for chronic low back pain (2026) — Vitamin D
• 18 Vitamin D and omega-3 supplementation for emotional and behavioural dysregulation in autism spectrum disorders: a systematic review (2026) — Vitamin D
• 19 Effects of vitamin D and/or magnesium supplementation on mood, serum levels of BDNF, inflammatory biomarkers, and SIRT1 in obese women: a study protocol (2020) — Magnesium
• 20 The effects of magnesium supplementation on serum levels of brain-derived neurotrophic factor (BDNF) and depression status in patients with depression (2021) — Magnesium
• 21 Modulating progression: combined effects of magnesium supplementation and intermittent fasting on tau hyperphosphorylation in Alzheimer’s disease (2025) — Magnesium
• 22 A randomised controlled trial to determine the effects of curcumin and epigallocatechin-3-gallate supplementation on serum brain-derived neurotrophic factor (2026) — Turmeric and curcumin
• 23 The role of nutraceuticals as a complementary therapy against various neurodegenerative diseases: a mini-review (2020) — Turmeric and curcumin
• 24 Therapeutic role of curcumin in adult neurogenesis for the management of psychiatric and neurological disorders: a scientometric study leading to an in-depth review (2023) — Turmeric and curcumin

5. Open Questions

• Humic acid complexes: Are there direct effects on BDNF or neuroplasticity in humans, or only indirect effects via anti-inflammatory mechanisms?
• Combination therapies: Do substances such as omega-3 and probiotics enhance each other’s effects on neuroplasticity, or are there antagonistic effects?
• Long-term effects: How stable are changes in BDNF or cognitive parameters after discontinuation of substances (e.g., adaptogens or vitamin D)?
• Individual factors: What role do genetics or pre-existing conditions (e.g., depression) play in the efficacy of substances on neuroplasticity?
• Dose-response relationship: Are there optimal dosages for substances such as magnesium or turmeric to influence BDNF?

See also the gap list covering all substances. This page is recalculated with each update.