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All About BDNF + Natural Factors that Increase It

Written by Puya Yazdi, MD | Last updated:
Medically reviewed by
Matt Carland, PhD (Neuroscience) | Written by Puya Yazdi, MD | Last updated:

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What You Need To Know About BDNF

Researchers now recognize that the brain continues to reorganize itself by forming new neural connections throughout life. The birth of new neurons in the brain is referred to as neurogenesis [1].

Neurotrophins are chemicals that help to stimulate and control neurogenesis. Scientists believe BDNF is among the most active neurotrophins [1].

In the brain, BDNF is active in the hippocampus, cortex, and forebrain – areas vital to learning, memory, and higher thinking. Hence, researchers concluded that BDNF is important for long-term memory [1].

It is also expressed in the retina, motor neurons, the kidneys, saliva, and the prostate [1].

BDNF has been shown to play a role in neuroplasticity, which allows nerve cells in the brain to compensate for injury and adapt to new situations or changes in the environment [2].

BDNF helps to support the survival of existing neurons and encourages the growth, regeneration, and creation of new neurons and synapses [1].

BDNF has been shown both to facilitate glutamate release at the presynapse and to increase postsynaptic glutamate receptor synthesis [3].

One study found that blood BDNF decreases significantly with age [4].

It’s important to realize that BDNF levels can be different in different places. So the following measures exist: blood BDNF levels, CSF BDNF levels, and BDNF levels in various brain locations. Scientists suggest that, in healthy people, there’s likely no correlation between BDNF in the blood and CSF [4].

However, a different study suggested that BDNF in the blood is thought to be a reliable and sensitive marker of its variations occurring in the brain. The researchers posited that this would be a sensible conclusion since BDNF can cross the brain barrier. Nonetheless, this link has yet to be confirmed [5, 6].

BDNF and Health

This section explores associations between BDNF and aspects of health.

The majority of studies covered in this article deal with associations only, which means that a cause-and-effect relationship hasn’t been established.

For example, just because sleep problems have been linked with low BDNF in certain brain areas doesn’t mean that insomnia is caused by low BDNF. Nor does it mean that increasing BDNF will improve symptoms of insomnia, unless clinical data about a direct link are available. However, data are lacking to make such claims.

Additionally, even if a study did find that low brain BDNF contributes to insomnia, BDNF levels are highly unlikely to be the only causative factor. Complex disorders like insomnia always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.

Weight

Scientists think that BDNF may affect weight. No data suggests that BDNF causes weight loss, though. In animals, BDNF suppresses food intake through hippocampal signaling [7].

BDNF infusion into the rat brain has been shown to lower body weight and to suppress appetite [8].

BDNF increases energy metabolism in obese diabetic animals, partly through activating the stress response and inducing UCP1 – an uncoupling protein that creates brown fat, which is easily burned for fuel [9].

In healthy women, the more overweight women are the lower their blood BDNF [4].

In some studies, blood levels of BDNF were lower in humans with obesity and type-2 diabetes [7]. BDNF was also lower in the blood of obese children in one study [8].

Decreased levels of blood BDNF have been found in underweight women with anorexia [10].

Sleep

BDNF in rats is higher after wakefulness than after sleep, and BDNF increases after sleep deprivation [11].

BDNF triggers slow-wave sleep by promoting “synaptic potentiation” [11].

In mice, the level of exploratory behavior – that points to mental and physical stimulation or novelty – induces BDNF [12]. BDNF, in turn, is the signaling molecule that causes an increase in slow-wave sleep [11, 12].

All in all, scientists think that the more stimulated or sleep-deprived animals are, the more they need slow-wave sleep, and the molecular link is BDNF. These theories have yet to be explored in humans.

Wellness

Scientists hypothesize that higher BDNF levels may be critical when it comes to acquiring new knowledge, retaining memories, and promoting overall feelings of happiness. Some even say BDNF can be viewed as a natural “antidepressant of the brain” [13] since low brain BDNF levels have been linked with mood problems [14].

Limited studies found a link between lower BDNF brain levels and Huntington’s disease. The authors hypothesized that low BDNF might influence the neuro-degenerative symptoms of the disorder, though this hasn’t been fully confirmed [2].

Mice that are engineered to have hearts that don’t produce any BDNF quickly develop heart failure [15].

Some researchers have even suggested that low BDNF might be among the possible links between depression and heart disease, though their theory remains unproven [16].

BDNF prevents exhaustion of the pancreas in diabetic mice by restoring the level of insulin-secreting granules in beta cells [17].

BDNF also improved insulin resistance in the oral glucose tolerance test in mice [18].

When BDNF is injected in the rostral ventrolateral medulla (mice), blood pressure increases [19].

Additionally, people who are genetically lower BDNF producers have lower systolic blood pressure [20].

One of the mechanisms by which salt increases blood pressure is by increasing vasopressin, which is mediated by an increase in BDNF [21].

Animal studies suggest that brain size is correlated with lifespan — and that BDNF may play a role in this link, since it affects neurogenesis [22].

However, when it comes to supporting optimal cognitive function, it’s not quite as simple as “more BDNF = better”. For example, multiple studies in rats have reported that low BDNF in the forebrain can cause deficits in learning and memory — but so can BDNF levels that are too high [23]! Therefore, there is probably a “sweet spot” (or “optimal range”) for BDNF.

The Circadian Rhythm

Scientists discovered that BDNF follows a circadian rhythm and decreases as the day goes on (24).

When light hits the retina, it gets transmitted to the hypothalamus — in particular the suprachiasmatic nucleus (SCN). This causes the SCN neurons to fire, via the neurotransmitter glutamate [25].

The SCN is the central clock and is the conductor of the circadian rhythm. When the SCN fires, that’s when the circadian rhythm starts and causes wakefulness [25].

BDNF can enhance glutamate neurotransmission in SCN neurons and potentiates glutamate-induced shifts of the circadian rhythm [26].

BDNF secreted at night is probably required for light-induced shifts in the circadian rhythm [26].

In mice, BDNF injection at 4 PM caused the circadian rhythm to be pushed off by 2.3 hours (so if an animal wakes up at 8 AM, it’d wake up at ~ 10 AM)… BDNF treatment during 10 PM caused the circadian rhythm to be pushed back 2.3 hours (so if they wake up at 8 AM, they’d wake up at ~ 6 AM). No phase shift occurred when BDNF was applied during the day at 7 AM [27].

BDNF-induced circadian shifts were dependent on Glutamate/NMDA receptor stimulation of the SCN [28].

Theoretically, it’s plausible to say that if a person has low BDNF, they may find it harder to set their circadian rhythm. On the other hand, high BDNF could cause the SCN to be over-active, which could also lead to circadian rhythm problems. However, this theory has not been confirmed in humans.

Socializing and Love

In one small study, BDNF blood levels were correlated with romantic attachment, but only in women. The higher the BDNF, the lower the women scored on an avoidance test (ie, they were more friendly and likely to form bonds) [29].

Therefore, BDNF may play a role in promoting social relationships through a specific decrease of avoidance and fear of the stranger and unfamiliar individuals [29].

In experimental animals, estrogens induce BDNF synthesis in several brain regions [29].

Scientists are exploring if this is linked to the fact that women score higher on anxiety scales than men [29].

Brain Disorders

Some researchers are investigating whether increasing BDNF can potentially help a number of devastating brain disorders, including Alzheimer’s disease, Parkinson’s disease, Lou Gehrig’s disease, and Huntington’s Disease (HD) [2].

Factors that Increase BDNF

Most importantly, always work with your doctor to treat any underlying conditions causing your symptoms. You may try the additional strategies listed below if you and your doctor determine that they could be appropriate. None of these strategies should ever be done in place of what your doctor recommends or prescribes.

Lifestyle

Exercise

Exercise is certainly one of the best ways to boost BDNF levels [30, 31].

In sedentary male college students, high-intensity exercise boosted both the BDNF levels and memories [31].

The changes in BDNF levels were found in nerve cells within days after exercise in both male and female rats and were sustained even several weeks after exercise [2].

In rats, low-intensity exercise is actually better than high-intensity exercise at increasing BDNF levels [32].

This accords with evidence in normal rats that show low-intensity exercise can improve synaptic plasticity better than high-intensity exercise. These effects have not yet been researched in humans [32].

Sleep

People suffering from insomnia had lower BDNF levels compared with sleep-healthy controls. Scientists consider that this is one method by which stress may decrease BDNF – by ruining sleep. According to some unverified theories, whether stress causes mental disorders depends on if sleep is maintained or disturbed [33].

In rats, chronic sleep deprivation led to increased IL-1b and TNF and reduced BDNF [34]

In antidepressant therapy, elevated BDNF is a possible predictor of whether antidepressants are working, though an unreliable one. BDNF doesn’t actually coincide with a decrease in depression, and for this reason, it’s thought that much of the predictive effect might be based on sleep. This means that BDNF may be a marker of how well people are sleeping, though large-scale studies are needed to confirm this theory [35].

Stress Reduction

Chronic or acute stress and cortisol decrease BDNF in the rat hippocampus [36] and prefrontal cortex [37, 38].

Acute stress more significantly decreases BDNF [36].

People who are under a lot of stress show less BDNF [39].

Sun

In an analysis of 2,851 individuals in the Netherlands, it was found that blood BDNF increased in the spring and summer and decreased in the fall and winter. BDNF levels correlated to the number of hours a person was exposed to the sunshine [40].

However, vitamin D supplements are likely ineffective.

Supplemental vitamin D in a human trial does not increase BDNF [41].

Supplemental vitamin D in postmenopausal women actually decreases BDNF [42].

The VDR doesn’t regulate BDNF [43], so scientists consider the effects might not be from vitamin D3.

Sunlight has high energy photons/blue light, infrared, UVB, and UVA — all four of which have unique properties.

Cognitive Stimulation

A highly stimulating early social environment in animals increases BDNF [44].

In mice, the level of exploratory behavior induces BDNF [12] – in humans, this would equate to mental and physical stimulation or novelty.

When you learn things or challenge your brain, the brain increases BDNF because of its important role in learning and memory [45].

Various mental games may be useful if you aren’t getting in a flow state in the day. You know you’re in flow if:

  • You’re consumed with a task
  • You’re not thinking about the future or the past
  • You’re not questioning if you like what you’re doing
  • You’re not bored
  • You’re not stressed

Intermittent Fasting

In mice, alternate-day fasting, with a single meal of about 600 calories on a fast day, increased the production of BDNF by 50 to 400 percent, depending on the brain region. The effects of fasting on BDNF in humans are unknown [46, 47].

Additionally, calorie restriction increases BDNF in rodents, but not in humans in this study. Therefore, it’s likely not effective [48].

Keep to a Circadian Rhythm

Some scientists have hypothesized that circadian rhythm dysregulation is linked with low BDNF. For example, people with traumatic brain injuries, who have a dysregulated circadian rhythm also have lower BDNF production [49] – even though other theories suggest BDNF should go up to heal the brain injury.

Diet/Foods

Scientists are investigating whether the following dietary factors can increase or decrease BDNF levels:

  • The Ketogenic Diet [50]
  • The so-called “Standard American Diet” (“SAD”) — i.e. a diet high in sugar and saturated fat — may decrease BDNF production [51]
  • Fish oil / DHA [52, 53]
  • Hi-maize/Resistant starch – converts to butyrate, which causes an increase in BDNF [54]
  • Honey: FOS, GOS (Prebiotics) [55]
  • Blueberries [56]
  • Cocoa (flavonoids) [57]
  • Soy – Both estradiol and soy phytoestrogens significantly increased BDNF in the frontal cortex of female rats [58].

However, no clinical evidence supports the approaches listed above to increase BDNF. The above-mentioned factors refer to animal and cell-based research, which should guide further investigational efforts. Findings from these studies should not be interpreted as supportive of any health benefit.

Hormones/Neurotransmitters

Scientists found links between the following hormones and BDNF levels in animals:

Human data are lacking.

There are no studies to suggest that increasing these hormones raises BDNF in humans.

Do not take any hormones without seeing a doctor. Taking hormones without medical supervision can be extremely dangerous.

Devices

  • PEMF (Pulsed Electromagnetic Field Therapy) [64]
  • Bright Light Device [65]
  • tDCS [66]

Supplements

Make sure to speak with your doctor before taking any supplements. Make sure to let them know about any prescription or over-the-counter medication you may be taking, including vitamins and herbal supplements.

If you and your doctor agree that supplementing is a good idea, choose products made by a trusted and reliable manufacturer.

Remember that dietary supplements have not been approved by the FDA for medical use. Supplements generally lack solid clinical research. Regulations set manufacturing standards for them but don’t guarantee that they’re safe or effective.

Some research suggests these supplements may help increase BDNF and support mental health:

  • Butyrate [54]
  • Quercetin [67] and kaempferol
  • Caffeine [68]
  • Curcumin produces neuroprotective effects via activating BDNF/TrkB-dependent MAPK and PI-3K cascades in rodent cortical neurons [69].
  • Niacin [70]
  • Magnesium [71] (in the prefrontal cortex, hippocampus)
  • Lactate – Researchers injected people with lactate and found BDNF levels rose after [72].
  • Magnesium L-Threonate – Elevation of brain magnesium increased NMDA receptors (NMDARs) signaling, BDNF expression, the density of presynaptic puncta, and synaptic plasticity in the prefrontal cortex [73].
  • Inosine [74]
  • L plantarum [75]
  • Gynostemma [76]
  • EGCG [77]
  • Lithium – Elevates BDNF by inhibition of GSK-3, which also increases skeletal muscle growth [78].
  • Olive leaf
  • NAC [79]
  • Theanine [80] – Increases BDNF and attenuates cortisol-to-DHEA, also has low affinity for AMPA, kainate, and NMDA receptors [81]. (unrelated, but did you know it’s an NMDA agonist?)
  • Rhodiola / Salidroside [82]
  • Resveratrol [83]
  • Rehmannia [84]
  • Ginseng – When pretreated orally, GRb1 significantly inhibited the stress-mediated decline of BDNF levels whereas it further increased the stress-mediated elevation of HSP70 levels [85].
  • Baicalin [86]
  • Bacopa – In rats, bacopa increased BDNF when the animals were exposed to chronic unpredictable stress [87].
  • Fo-ti (He-Shou-wu) [88]

Other supplements:

  • Beta-alanine [89]
  • Euphoria longan [90]
  • Phytoceramides [91]
  • 2-Deoxy-Glucose [92]

Drugs

Caution: Selfhacked does not support taking these or any drugs. Do not take this post as promoting the use of these medications. It is for informational purposes alone. These are popular drugs, and people should know their uses, the evidence behind them, and their drawbacks.

No drug has ever been approved by the FDA for the purpose of increasing BDNF levels; the studies below are investigational and not powerful enough to be considered sufficient evidence for use. Do not take any drug without a doctor’s recommendation.

Joe does not use any drugs from this list because he likes to increase BDNF naturally.

  • Semax (ACTH analog) [93]
  • Citalopram (Celexa, SSRI) [2]
  • Tianeptine (Tricyclic) [94, 95]
  • Ladostigil (experimental drug) – A reversible acetylcholinesterase and butyrylcholinesterase inhibitor, and an irreversible monoamine oxidase B inhibitor. Enhances expression of GDNF and BDNF [96].
  • Rasagiline [97]

Some illegal drugs also increase BDNF but affect the brain in an overall detrimental way and cause serious harm. They are classified as Schedule I drugs, which means that they are illegal, have a high potential for harm and abuse, and no valid medical uses.

Many of these drugs – including MDMA, cocaine, LSD, and ketamine – can hijack the brain’s reward system, causing addiction. Their use can also lead to life-threatening conditions and should be avoided at all costs [98, 99, 100101].

Effects of Genes on BDNF Production

If you got your DNA sequenced and have a SelfDecode account, you can find out if your SNPs have been associated with higher or lower BDNF production.

Here is Joe’s version of BDNF SNPs:

  1. RS11030101 (BDNF) AT
  2. RS11030104 (BDNF) AA
  3. RS12273363 (BDNF) TT
  4. RS12273539 (BDNF) CC
  5. RS2049046 (BDNF) AA
  6. RS56164415 (BDNF) GG
  7. RS6265 (BDNF) CT
  8. RS7103411 (BDNF) TT
  9. RS8192466 (BDNF) GG

For more information on the genetics of BDNF, see the comprehensive SelfHacked post on the BDNF gene.

Want More Targeted Ways to Enhance Brain Function?

If you’re interested in improving your cognitive function, we recommend checking out SelfDecode’s Cognitive Function DNA Wellness Report. It gives gene-based diet, lifestyle, and supplement tips that can help improve your cognitive function. The recommendations are personalized based on your genes.

SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thanks for your support!

About the Author

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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