In order to investigate ways to increase BDNF, I conducted a literature search on PubMed. I saved abstracts that mentioned nootropics or habits that increase BDNF or prevent a decrease in BDNF. Scroll down to see the complete list of 54 ways to increase BDNF.
I've classified each entry as one of the following:
- research chemical
- endogenous substance, e.g., already present in your body
- intervention, e.g., electroconvulsive therapy
- supplement
- food
- drug
- lifestyle, e.g., diet and exercise
These categories are not particularly neat and there's often overlap. For example, melatonin is both a supplement, an endogenous substance, and is also found in food (like walnuts).
Caveats
- Not everything on this list is safe.
- Not all the entries directly increase BDNF, some entries prevent a decrease in BDNF.
- Some entries activate the Trk B receptor without necessarily affecting BDNF.
Stepping Back - What's BDNF?
Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor that regulates plasticity and cell survival in the brain. It's of tremendous interest to researchers because abnormal BDNF signaling plays a role in everything from depression to Alzheimer's disease.
Specifically, BDNF is a *pro-survival signal *in the central nervous system.
This means that the local expression of BDNF signals the brain to maintain synapses. BDNF also provides trophic support for neurons. Some researchers think that BDNF is the common endpoint of most antidepressant drugs. For example, most SSRIs ultimately converge on increased BDNF and neurogenesis despite individual differences at the neurotransmitter level.
Sometimes I need to remind myself that just because a substance increases BDNF does not necessarily imply that its effects are beneficial.
Low-dose methamphetamine likely increases BDNF but that does not mean you should start using crystal.
1. 7, 8-dihydroxyflavone
Type: research chemical
7,8-dihydroxylfavone is a BDNF mimetic, and may not increase BDNF itself. It binds the Trk B receptor in the brain.
Further reading:
- Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the TrkB receptor.
2. Ampakines
Type: research chemical
Ampakines are potentially high-risk research compounds. More research is needed to assess the risk of neurotoxicity. See this discussion on Sunifiram.
Further reading:
- Combined ampakine and BDNF treatments enhance poststroke functional recovery in aged mice via AKT-CREB signaling.
3. LM22A-4
Type: research chemical
LM22A-4 is a partial agonist of TrkB, the primary receptor for BDNF. LM22A-4 fails to cross the blood-brain-barrier when administered systemically, so LM22A-4 has been given to animals instead via intranasally, which results in TrkB activation. The compound produces neurogenic and neuroprotective effects in animals.
Further reading:
- BDNF mimetic compound LM22A-4 regulates cementoblast differentiation via the TrkB-ERK/Akt signaling cascade.
4. Thyroid hormone
Type: endogenous
Thyroid hormone regulates the metabolism of every cell in the body. Thyroid increases neurogenesis and BDNF.
Further reading:
- Developmental thyroid hormone insufficiency reduces expression of brain-derived neurotrophic factor (BDNF) in adults but not in neonates.
5. Melatonin
Type: endogenous
Even if you don't suffer from insomnia, the neuroprotective effects of melatonin cannot be dismissed. Melatonin is among the most potent antioxidants.
Further reading:
- Effect of Melatonin on Glutamate: BDNF Signaling in the Cerebral Cortex of Polychlorinated Biphenyls (PCBs)-Exposed Adult Male Rats.
6. Intranasal insulin
Type: endogenous
Further reading:
- Intranasal insulin exerts beneficial effects by improving cerebral blood flow, Nrf-2 expression and BDNF in STZ (ICV) induced memory-impaired rats.
7. Intranasal oxytocin
Type: endogenous
Further reading:
- The effects of oxytocin on cognitive defect caused by chronic restraint stress applied to adolescent rats and on hippocampal VEGF and BDNF levels.
8. Testosterone
Type: endogenous
Further reading:
- Adolescent testosterone influences BDNF and TrkB mRNA and neurotrophin-interneuron marker relationships in mammalian frontal cortex.
9. Progesterone
Type: endogenous
Further reading:
- Progesterone Changes VEGF and BDNF Expression and Promotes Neurogenesis After Ischemic Stroke.
10. 17β-estradiol
Type: endogenous
Further reading:
- 17β-estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas.
11. Adenosine
Type: endogenous
Since coffee is an adenosine antagonist, should we therefore drink less coffee? This result seems to imply that caffeine could inhibit BDNF expression via adenosine blockade.
Further reading:
- Activation of adenosine A2A receptor up-regulates BDNF expression in rat primary cortical neurons.
12. High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS)
Type: intervention
Further reading:
- High-Frequency Repetitive Transcranial Magnetic Stimulation (rTMS) Improves Functional Recovery by Enhancing Neurogenesis and Activating BDNF/TrkB Signaling in Ischemic Rats.
13. Electroconvulsive therapy
Type: intervention
Not recommended unless you have severe, treatment-resistant depression.
Further reading:
- Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder.
14. Acupuncture
Type: intervention
Further reading:
- The neuroprotective role of acupuncture and activation of the BDNF signaling pathway.
15. Deep brain stimulation
Type: intervention
Further reading:
- Deep brain stimulation of the ventral striatum increases BDNF in the fear extinction circuit.
16. Physical therapy
Type: intervention
Further reading:
- Physical therapy intervention (PTI) increases plasma brain-derived neurotrophic factor (BDNF) levels in non-frail and pre-frail elderly women.
17. Vitamin D
Type: supplement
Vitamin D is the one supplement I think everyone should take.
Further reading:
- Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial.
18. Resveratrol
Type: supplement
Further reading:
- Resveratrol Increases Serum BDNF Concentrations and Reduces Vascular Smooth Muscle Cells Contractility via a NOS-3-Independent Mechanism.
19. Schisandra chinensis
Type: supplement
Further reading:
- Schisandra chinensis produces the antidepressant-like effects in repeated corticosterone-induced mice via the BDNF/TrkB/CREB signaling pathway.
20. Folic acid
Type: supplement
Further reading:
- Folic acid prevented cognitive impairment in experimental pneumococcal meningitis.
21. Piperine
Type: supplement
Piperine also enhances the bioavailability of curcumin.
Further reading:
- Piperine reverses the effects of corticosterone on behavior and hippocampal BDNF expression in mice.
22. Panax ginseng
Type: supplement
Further reading:
- Effects of ginsenoside Rb1 on the stress-induced changes of BDNF and HSP70 expression in rat hippocampus.
23. Omega-3
Type: supplement
Studies on omega-3 have been equivocal. At the very least, omega-3 polyunsattured fatty acids are unlikely to be harmful, provided that they're not contaminated with mercury.
Further reading:
- Omega-3 deficiency and neurodegeneration in the substantia nigra: involvement of increased nitric oxide production and reduced BDNF expression.
24. Nobiletin
Type: supplement
Nobiletin is a very promising cognitive enhancer that does not receive the attention that it should.
Further reading:
- Nobiletin Ameliorates the Deficits in Hippocampal BDNF, TrkB, and Synapsin I Induced by Chronic Unpredictable Mild Stress.
25. Fingolimod
Type: supplement
Further reading:
- Fingolimod, a sphingosine-1 phosphate receptor modulator, increases BDNF levels and improves symptoms of a mouse model of Rett syndrome.
26. Quercetin
Type: supplement
I'd avoid quercetin supplementation.
Instead, here are some quercetin-rich foods: apples; peppers; red wine; dark cherries and berries (blueberries, bilberries, blackberries and others); tomatoes; cruciferous veggies, including broccoli, cabbage and sprouts; leafy green veggies, including spinach, kale; citrus fruits.
Further reading:
- Quercetin attenuates cell apoptosis in focal cerebral ischemia rat brain via activation of BDNF-TrkB-PI3K/Akt signaling pathway.
27. Magnolol
Type: supplement
Further reading:
- Antidepressant-like effect of magnolol on BDNF up-regulation and serotonergic system activity in unpredictable chronic mild stress treated rats.
28. Zinc
Type: supplement
Zinc is a double-edged sword. See [Zinc: the brain's dark horse](https://www.ncbi.nlm.nih.gov/pubmed/19623531
).
Further reading:
- Dietary zinc supplementation of 3xTg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction.
29. Oroxylin A
Type: supplement
Further reading:
- Oroxylin A Induces BDNF Expression on Cortical Neurons through Adenosine A2A Receptor Stimulation: A Possible Role in Neuroprotection.
30. Bright light therapy
Type: lifestyle
Bright light therapy in the morning is beneficial on multiple levels. It entrains your biological clock, improves mood, and enhances sleep quality.
Further reading:
- Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain.
31. Exercise
Type: lifestyle
If there's a "magic bullet" then it's exercise.
Further reading:
- The effect of acute exercise on serum brain-derived neurotrophic factor levels and cognitive function.
32. Sunlight
Type: lifestyle
Even if sunlight doesn't increase BDNF you should get some sun and fresh air.
Further reading:
- Serum BDNF concentrations show strong seasonal variation and correlations with the amount of ambient sunlight.
33. Sex
Type: lifestyle
Sex is an environmental novelty that increases BDNF.
Further reading:
- Sex and stress hormone influences on the expression and activity of brain-derived neurotrophic factor.
34. Calorie restriction
Type: lifestyle
Eating less and more than needed on alternate days prolongs life.
Further reading:
- Effect of Food Deprivation or Short-term Western Diet Feeding on BDNF Protein Expression in the Hypothalamic Arcuate, Paraventricular, and Ventromedial Nuclei.
35. Meditation
Type: lifestyle
Further reading:
- The Pilot Study of the Effect of Meditation to the Serum Brain-Derived Neurotrophic Factor (BDNF) of Medical Students, Srinakharinvirot University.
36. Ketone bodies
Type: lifestyle
Both exercise and a high-fat diet will stimulate ketone bodies Beta-hydroxybutyrate and acetoacetate are produced by the liver in periods of carbohydrate restriction. Under usual conditions, the brain exclusively uses glucose for energy. But ketone bodies can provide an alternative energy source.
Further reading:
- Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate.
37. Socialization
Type: lifestyle
Just in case you needed an excuse to go talk to some people.
Further reading:
- Social isolation after stroke leads to depressive-like behavior and decreased BDNF levels in mice.
38. "Enriched housing"
Type: lifestyle
Further reading:
- Enriched housing reverses age-associated impairment of cognitive functions and tPA-dependent maturation of BDNF.
39. Blueberries
Type: food
Double-blind, randomized, placebo-controlled trials have demonstrated that blueberries improve cognitive ability in older adults.
Further reading:
- Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels.
40. Cacao or dark chocolate
Type: food
Cacao also increases cerebral blood flow, neurogenesis, and improves cognitive ability in older adults.
Further reading:
41. Curcumin
Type: food
Curcumin is a promiscuous ligand; it binds a lot of protein targets. This can make it difficult to pin down its true mechanism due to off-target effects.
Further reading:
- Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.
42. Agomelatine
Type: drug
Agomelatine is a melatonergic antidepressant developed by Servier. Rarely, agomelatine can impair liver function and is contraindicated in patients with hepatic impairment.
Further reading:
- Agomelatine Increases BDNF Serum Levels in Depressed Patients in Correlation with the Improvement of Depressive Symptoms.
43. Fluoxetine
Type: drug
Further reading:
- Effects of fluoxetine on brain-derived neurotrophic factor serum concentration and cognition in patients with vascular dementia.
44. Citalopram
Type: drug
Further reading:
- Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise.
45. Reboxetine
Type: drug
Further reading:
- Hippocampal brain-derived neurotrophic factor expression following treatment with reboxetine, citalopram, and physical exercise.
46. Sertraline
Type: drug
Further reading:
- Changes in BDNF serum levels in patients with major depression disorder (MDD) after 6 months treatment with sertraline, escitalopram, or venlafaxine.
47. Mirtazepine
Type: drug
Mirtazapine is an atypical antidepressant with serotonergic and noradrenergic activity. It's highly sedating, which can improve sleep quality but result in an undesirable hangover effect.
Mirtazepine increases both BDNF and neurogenesis.
Mirtazepine is an ingredient in Californian rocket fuel.
Further reading:
- Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-α in Patients of Major Depressive Disorder with Severe Depression.
48. Duloxetine
Type: drug
Further reading:
- Effects of Duloxetine Treatment on Cognitive Flexibility and BDNF Expression in the mPFC of Adult Male Mice Exposed to Social Stress during Adolescence.
49. Nicotine
Type: drug
Nicotine has also been reported to impair hippocampal neuroplasticity, so tread lightly.
Further reading:
- Acute nicotine treatment attenuates lipopolysaccharide-induced cognitive dysfunction by increasing BDNF expression and inhibiting neuroinflammation in the rat hippocampus.
50. Sodium butyrate
Type: drug
Sodium butyrate (GHB) is an interesting drug. One the one hand, it's one of the most powerful sleep aids in existence. It increases slow wave sleep while concomitantly increasing growth hormone secretion; most other sedatives knock you out while actually impairing sleep quality.
However, GHB is likely neurotoxic.
Further reading:
- Sodium butyrate and mood stabilizers block ouabain-induced hyperlocomotion and increase BDNF, NGF and GDNF levels in brain of Wistar rats.
51. Ketamine
Type: drug
It's interesting that the biomedical establishment changes their tenor about ketamine in the last decade. Pre-2000, there are studies suggesting that ketamine suppresses BDNF expression. But after the recognition that ketamine may be a useful antidepressant, you find more and more studies suggesting that ketamine promotes BDNF expression. Hm...
Further reading:
- Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test.
52. Venlafaxine
Type: drug
Further reading:
- Changes of serum concentrations of brain-derived neurotrophic factor (BDNF) during treatment with venlafaxine and mirtazapine: role of medication and response to treatment.
53. Memantine
Type: drug
Memantine behaves similarly to magnesium by blocking NMDA-type glutamate receptors in a voltage-gated manner.
Further reading:
- Memantine treatment reverses anhedonia, normalizes corticosterone levels and increases BDNF levels in the prefrontal cortex induced by chronic mild stress in rats.
54. GABA(A) receptor blockade
Type: drug
The downside risk of GABAergic blockade is increased anxiety and seizures. Always be walkin' the line.
Further reading:
- GABA(A) receptor blockade enhances memory consolidation by increasing hippocampal BDNF levels.