Depression and BDNF

How to Naturally Alleviate Depression

Depression is a mental state characterized by psychological symptoms such as low mood and self-esteem, irritability and intolerance to others, difficulty in making decisions, anxiety, and suicidal thoughts.

Physically, it is manifested by slow movement and speech, lack of energy, unexplained aches and pains, lack of energy, and sleep disturbance.

Depression can be caused by life events such as grief, bipolar disorder, post-natal depression, and seasonal affective disorder. At the molecular level, depression has been proposed to be associated with the reduced brain levels of the Brain-derived neurotrophic factor (BDNF) that plays an essential in activity-dependent neuronal plasticity such as learning and memory [1] [2].

Tackling Depression by Rising BDNF Levels

BDNF is a neurotrophin that is vital to the survival, growth, and maintenance of neurons in key brain circuits involved in emotional and cognitive function. The neurotrophic hypothesis of depression proposes that depression is associated with reduced brain BDNF levels and that antidepressant treatments relieve depressive behavior and increase BDNF levels [3].

However, other studies have shown that BDNF levels can be increased independently of anti-depression treatments. For instance, a study showed that chronic REM (rapid eye movement) sleep loss impairs hippocampal BDNF expression, which decreased memory and cognition [4]. 

Exercise is another natural promoter of BDNF expression and studies have shown that voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity [5].

Other studies have shown that sunlight exposure promotes BDNF expression as BDNF levels correlated with seasonal variations in the amount of ambient sunlight [6]. Finally, intermittent, and regular fasting, low carbohydrate diet, and magnesium intake have also been shown to increase BDNF levels [7][8][9].


BDNF plays an essential in activity-dependent neuronal plasticity such as learning, and memory and its low levels are associated with depression. Although the neurotrophic hypothesis of depression proposes the use of antidepressant treatments to increase BDNF levels, other non-chemical approaches can be used such as exercise, deep sleep, outdoor activities for sunlight, and an appropriate diet and fasting.


[1] Castrén, E., Võikar, V. and Rantamäki, T., 2007. Role of neurotrophic factors in depression. Current opinion in pharmacology7(1), pp.18-21.

[2] Lee, B.H. and Kim, Y.K., 2010. The roles of BDNF in the pathophysiology of major depression and in antidepressant treatment. Psychiatry investigation7(4), p.231.

[3] Duman, R.S., 2002. Pathophysiology of depression: the concept of synaptic plasticity. European psychiatry17, pp.306-310.

[4] Rahmani, M., Rahmani, F. and Rezaei, N., 2020. The brain-derived neurotrophic factor: missing link between sleep deprivation, insomnia, and depression. Neurochemical research45(2), pp.221-231.

[5] Gómez-Pinilla, F., Ying, Z., Roy, R.R., Molteni, R. and Edgerton, V.R., 2002. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. Journal of neurophysiology88(5), pp.2187-2195.

[6] Molendijk, M.L., Haffmans, J.P., Bus, B.A., Spinhoven, P., Penninx, B.W., Prickaerts, J., Voshaar, R.C.O. and Elzinga, B.M., 2012. Serum BDNF concentrations show strong seasonal variation and correlations with the amount of ambient sunlight. PloS one7(11), p.e48046.

[7] Katare, R.G., Kakinuma, Y., Arikawa, M., Yamasaki, F. and Sato, T., 2009. Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway. Journal of molecular and cellular cardiology46(3), pp.405-412.

[8] Gyorkos, A., Baker, M.H., Miutz, L.N., Lown, D.A., Jones, M.A. and Houghton-Rahrig, L.D., 2019. Carbohydrate-restricted diet and exercise increase brain-derived neurotrophic factor and cognitive function: a randomized crossover trial. Cureus11(9).

[9] Afsharfar, M., Shahraki, M., Shakiba, M., Asbaghi, O. and Dashipour, A., 2021. The effects of magnesium supplementation on serum level of brain derived neurotrophic factor (BDNF) and depression status in patients with depression. Clinical nutrition ESPEN42, pp.381-386.

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