There has been a fair amount of buzz about brain-derived neurotropic factor of late – commonly referred to as BDNF. If you think BDNF has something to do with the brain, then you are correct. It’s a protein in the brain and nerves that has a big job. It’s involved in preserving already-existing nerve cells and encouraging the growth of new nerve cells and synapses – the structures that support signal transmission from one nerve cell to the next. Growth of new nerve cells – called brain plasticity – helps the brain heal after an injury from trauma, a stroke, or other adverse health conditions. Maintaining brain plasticity supports healthy brain function as we age.

BDNF plays an important role in learning, memory, and behavior. As a result, BDNF has broad influence on mood, sleep patterns, eating habits, and appetite. Some of these effects are within the brain and central nervous system, while some occur in other parts of the body.

In addition to the brain and nerves, BDNF is found in the pancreas, retinas, kidneys, prostate, uterus, muscles, GI tract, lungs, heart, and salivary glands. Therefore, some of BDNF’s effects occur outside the brain. It plays a factor in regulating glucose metabolism by enhancing the uptake of glucose by the muscles and protecting the sensitive insulin-producing beta cells in the pancreas. BDNF also increases cardiac muscle contractions and improves circulation by promoting endothelial nitric oxide synthase (eNOS) – an enzyme that causes the smooth muscles in the artery walls to relax.

Factors associated with low BDNF

Age: Our level of BDNF decreases naturally as we age. It is at its highest level during the developmental phases of the brain and nervous system, with a higher level early in life helping to facilitate learning and motor skill development.

Chronic conditions: A low level of BDNF is associated with chronic neurological conditions, such as multiple sclerosis, Parkinson’s disease, and Huntington’s disease; depression; chronic stress; Alzheimer’s disease and other dementias; insulin resistance associated with type 2 diabetes and metabolic syndrome; and increased mortality rates in general.

Sedentary lifestyle: A sedentary lifestyle is associated with a lower level of BDNF, regardless of whether a person is overweight or not.

Tobacco smoking: Although the effect of tobacco smoke on BDNF is somewhat contradictory, most evidence points to heavy smoking decreasing the serum level of BDNF, while moderate tobacco smoking might not.

Air pollution: Exposure to a significant amount of air pollution can affect BDNF. A Chinese study looked at women’s exposure to air pollution during pregnancy, their levels of BDNF, and developmental scores in their offspring. The closure of a nearby coal power plant was concurrent with the study. Babies born prior to the closure of the plant had significantly lower BDNF levels and lower developmental quotient scores than those babies born after the plant’s closure.1

History of trauma and stress: A history of childhood trauma and recent multiple stressors is associated with lower BDNF levels. This decrease appears to be caused by at least two factors: inflammation and an increased level of cortisol.

High-fat, high-sugar diet: A poor diet can also have a detrimental effect. In an animal study, individuals fed a high-fat, high-sugar diet – to simulate a typical Western diet – for two months experienced decreased BDNF in the hippocampus, the area of the brain that plays a major role in memory and learning. This decrease was accompanied by decreased learning performance.2

Lifestyle and other factors that increase BDNF

If you engage in less than desirable lifestyle habits, don’t despair. There are also lifestyle habits that can increase BDNF.

Exercise: Although a sedentary lifestyle can negatively impact BDNF and brain function, exercise helps to reverse it. One effect of exercise is to simply increase circulation to the brain. But evidence also suggests exercise increases BDNF. In addition, exercise increases the size of the hippocampus. High-intensity interval training – HIIT – is a way of exercising that alternates short periods of intense anaerobic exercise with less intense recovery periods. HIIT is particularly effective at modulating cortisol, preventing high blood sugar and increasing BDNF. And, according to a Mayo Clinic study, HIIT might slow the aging process. But be sure to exercise in a clean environment because it is thought that vigorous exercise in a polluted environment could negate the positive effects of exercise.

Physical activity: Even beyond purposeful exercise, merely engaging in some form of physical activity can benefit BDNF levels. A study on type 2 diabetes found that avoiding sedentary periods for longer than 15 minutes resulted in increased BDNF. This effect was more pronounced in participants who didn’t normally engage in moderate-to-vigorous exercise.3 So, if your job involves sitting for long periods of time, then stand up and move, bounce in your chair, or move your arms and legs several times an hour.

Mental and physical exercise combined: Games that incorporate both mental and physical activity can increase BDNF. For example, one study of individuals in a long-term care facility found that two 40-minute sessions of “exergame” activities using an Xbox 360 Kinect twice a week for six weeks significantly increased their BDNF levels.4

Calorie restriction/intermittent fasting: As noted above, the typical high-fat, high-sugar Western diet can contribute to low BDNF levels. On the flipside, numerous studies (mainly in animals) have shown that general calorie restriction or intermittent fasting can lead to increased BDNF and improved cognitive function. Interestingly, a higher level of BDNF also contributes to decreased food intake, while a lower level contributes to obesity.

Treating depression: A low BDNF level is well established as a contributing factor to depression. Studies show that one way anti-depressant medications work to improve depression is by increasing the level of BDNF.5

Sunlight exposure: Similar to vitamin D, exposure to sunlight increases BDNF. Its level tends to be higher in the spring/summer months than the fall/winter months. One study looked at the number of sunlight hours in the 10 weeks prior to having BDNF levels checked and found a positive correlation. In other words, the more sunshine you’re in, the higher your BDNF level.6 This could be one of the mechanisms associated with seasonal affective disorder (SAD).

Specific foods: The following are some specific foods or food groups that have been shown to increase BDNF:

  • A high-protein diet
  • Pomegranate
  • Fish and fish oil
  • Olive oil
  • Blueberries and other berries
  • Dark chocolate

Nutrients and plant extracts: The following are nutrients and botanicals, or plant-based extracts, that have been shown to enhance BDNF levels:

  • Curcumin/turmeric
  • Acetyl-L-carnitine
  • Alpha-lipoic acid
  • Melatonin
  • Glutathione
  • Sulforaphane (broccoli seed extract)
  • Grape seed polyphenols
  • Green tea
  • Quercetin
  • Ginkgo biloba
  • Hypericum perforatum
  • Bacopa monnieri
  • Rhodiola rosea
  • Ashwagandha
  • Whole coffee fruit extract

It appears that many of the botanicals and nutrients that provide cognitive or mood support do so by enhancing BDNF levels. Because many of the BDNF studies have been conducted on animals, more human clinical studies are warranted.

Coffee: Is it the caffeine or the polyphenols?

In the case of coffee, although caffeine itself can modulate BDNF, the polyphenols appear to be the star of the show.

In a small pilot study, 25 healthy adults ages 18 to 55 were randomly divided into five groups with each taking one 100-mg dose of: (1) whole coffee fruit extract, (2) green coffee caffeine powder, (3) grape seed extract, (4) green coffee bean powder, or (5) a silicon dioxide placebo. A sixth group took nothing, giving the study two control groups. Plasma BDNF was tested before taking the supplements and at 30-minute intervals for two hours.

The study found a significant 137-percent increase in BDNF in the whole coffee fruit extract group. By contrast, participants taking green coffee caffeine powder had a 43-percent increase in BDNF, while those taking grape seed powder had a 30-percent increase. Caffeine was ruled out as a major contributing factor because the coffee fruit extract is at most only 2-percent caffeine, while the green coffee caffeine powder is 72.8-percent caffeine and grape seed extract has no caffeine. The placebo, no treatment, and the green coffee bean extract (2% caffeine) groups did not have an increase in serum BDNF.7

In another study, whole coffee fruit extract increased BDNF by 91 percent after one hour, while a cup of brewed coffee increased it by only 21 percent.8 The authors conclude the polyphenol content of the whole coffee fruit extract is the primary contributing factor to increased BDNF levels in these studies.

To learn more about whole coffee fruit extract’s support for brain health, explore Thorne’s Brain Factors, which contains 100 mg of whole coffee fruit extract per capsule.


  1. Tang D, Lee J, Muirhead L, et al. Molecular and neurodevelopmental benefits to children of closure of a coal burning power plant in China. PLoS One 2014;9(3):e91966. doi: 10.1371/journal.pone.0091966.
  2. Molteni R, Barnard RJ, Ying Z, et al. A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience 2002;112(4):803-814. doi: 10.1016/s0306-4522(02)00123-9.
  3. Júdice PB, Magalhães JP, Hetherington-Rauth M, et al. Sedentary patterns are associated with BDNF in patients with type 2 diabetes mellitus. Eur J Appl Physiol 2021;121(3):871-879. doi: 10.1007/s00421-020-04568-2.
  4. Monteblanco-Cavalcante M, Fraga I, Dalbosco B, et al. Exergame training-induced neuroplasticity and cognitive improvement in institutionalized older adults: A preliminary investigation. Physiol Behav 2021;241:113589. doi: 10.1016/j.physbeh.2021.113589.
  5. Rana T, Behl T, Sehgal A, et al. Unfolding the role of BDNF as a biomarker for treatment of depression. J Mol Neurosci 2021;71(10):2008-2021. doi: 10.1007/s12031-020-01754-x.
  6. Molendijk ML, Haffmans JP, Bus BA, et al. Serum BDNF concentrations show strong seasonal variation and correlations with the amount of ambient sunlight PLoS One. 2012;7(11):e48046. doi: 10.1371/journal.pone.0048046.
  7. Reyes-Izquierdo T, Nemzer B, Shu C, et al. Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects. Br J Nutr 2013;110(3):420-425.
  8. Reyes-Izquierdo T. Argumedo R, Shu C, et al.Stimulatory effect of whole coffee fruit concentrate powder on plasma levels of total and exosomal brain-derived neurotrophic factor in healthy subjects: an acute within-subject clinical study. Food Nutr Sci 2013;4:984-990.