Brain-derived neurotrophic factor, or BDNF, is a nerve growth protein (neurotrophin) crucial to the development and maintenance of the human brain. When we explore and learn, BDNF is at work, restructuring the brain, growing new dendrite branches (Horch & Katz, 2002), and in turn, these activities themselves promote BDNF expression, enhancing mood and subsequent learning.

BDNF and mitochondria have a reciprocal relationship. The activity of mitochondrial complex 1-initiated oxidative phosphorylation corresponds to BDNF activity, and BDNF in turn interacts with ATPase to enhance mitochondrial respiratory coupling, increasing ATP production (Markham, et al., 2012). At the same time, ATP increases BDNF expression (Klein, et al., 2012). This reciprocity aligns with Ray Peat’s idea that “energy and structure are interdependent, at every level.”

BDNF ‘donor’ neurons (green) increasing branching in neighboring neurons (red). BDNF is a fertilizer for brain cell connections.

In stress and aging, including in Alzheimer's, Parkinson's, and Huntington's disease, BDNF expression is markedly decreased, impairing neural adaptability and function.

Chronic stress induces mitochondrial dysfunction in the brain, leading to a reduction in BDNF expression (Liu & Zhou, 2012). Thus, in the stressed, traumatized, and inflamed, there is an impaired ability to learn and rigid psychospiritual functioning.

However, there are many simple strategies by which we can promote and preserve BDNF, protecting our clarity and sanity, which are discussed further down.

BDNF is largely, if not primarily, the mechanism by which antidepressants work. Antidepressant drugs increase the transcription factor CREB, leading to a delayed increase in BDNF (Conti, et al., 2002; Casarotto, et al., 2022). By halting mitochondria at presynaptic sites so that they accumulate, BDNF increases neurotransmitter release and synaptic plasticity, improving cognition and mood (Su, et al., 2013).

BDNF is produced in the muscles, promoting mitochondrial quality via enhancing mitofission (the separation of one mitochondria into two) and mitophagy (the recycling of damaged mitochondria) (Ahuja, et al., 2022). This helps to explain exercise’s ability to enhance resilience to stress and oppose aging. The BDNF protein is small, so it’s able to cross the blood brain barrier and exert, for example, positive effects on the brain in response to muscular secretion from exercise (Pan, et al., 1998).

BDNF raises cellular antioxidant capacity by upregulating the enzyme superoxide dismutase 2 (He & Katusic, 2012). In oxidative stress, BDNF activity drops, indicating both its depletion in response to increased demand and disrupted expression presumably due to oxidative stress impairing cellular resilience.

BDNF facilitates glucose transport (by inducing GLUT3) and increases insulin sensitivity (via insulin receptor tyrosine phosphorylation and phosphatidylinositol 3-kinase) and parasympathetic tone (via brainstem cholinergic neurons), assisting adaptivity of the organism in confronting challenging activities (Tsuchida, et al., 2001; Marosi & Mattson, 2015).

By acting on hypothalamic neurons, BDNF suppresses appetite, and has been shown to induce weight loss by reducing food intake and increasing the resting metabolic rate, with more energy burned as heat (Pelleymounter, et al., 1995; Urabe, et al., 2013; Wu & Xu, 2022).

Cancer cells use BDNF to their own benefit, which sparked temporary concern over BDNF overexpression being involved in cancer, but it was more recently shown that the body responds to cancer by overexpressing BDNF in the hypothalamus, amplifying anti-tumor immune system activity and decreasing proteins that protect cancer cells (Radin & Patel, 2017).

Replenishing antioxidant stores, for example nutritionally (exogenous antioxidants) or through environmental enrichment (which increases endogenous antioxidants), restores and maintains BDNF (Fahnestock, et al., 2012; Lee, et al., 2019).

The hours of sunshine a person gets positively correlates to serum BDNF concentrations, helping to explain the seasonal affective disorder phenomenon (Molendijk, et al., 2012).

Serum BDNF concentrations by month of sampling.

Strategies to increase BDNF:

• Intellectual challenge (Nicastri, et al., 2022)
• Meditation & mindfulness (Gomutbutra, et al., 2020)
• Yoga & tai chi (Naveen, et al., 2013; Lee, et al., 2014)
• Laughter (Cheng, et al., 2020)
• Exercise (Canton-Martínez, et al., 2022)
• Red light therapy, as transcranial photobiomodulation/low-level laser therapy (Meng, et al., 2013; Hamblin, 2016; Heo, et al., 2019)
• Sauna (Kojima, et al., 2018)
• Aspirin (Patel, et al., 2018)
• Black seed oil (Nigella sativa) (Zadeh, et al., 2022)
• Virgin coconut oil (Mansouri, et al., 2023)
• Progesterone (Kaur, et al., 2007; Su, et al., 2012)
• Magnesium (Pochwat, et al., 2015; Abiri, et al., 2022)
• Vitamin B3, niacinamide form (Hathorn, et al., 2011)
• Caffeine (Lao‐Peregrín, et al., 2017)
• Green tea, via its catechin polyphenols (Gundimeda, et al., 2014)
• Theanine (Wakabayashi, et al., 2012)
• Rhodiola rosea (Gao, et al., 2021)
• Monoamine oxidase inhibitors (Assareh, et al., 2012)
• Acute sleep deprivation (Ma, et al., 2020)
• Ketosis, via beta-hydroxybutyrate (Marosi, et al., 2016)

Factors that impair BDNF:

• Chronic inflammation (Porter & O’Connor, 2022)
• Chronic sleep deprivation (Rahmani, et al., 2020)
• Stress & trauma (Kundakovic, et al., 2015)
• Blue light at night reduces BDNF by 18.4% (Liu, et al., 2022)
• Lack of movement (Júdice, et al., 2021)
• Boredom, isolation, & loneliness (Berry, et al., 2012)
• Overtraining (Aguiar Jr., et al., 2008)
• Acute nicotine usage (Kenny, et al., 2000)
• Junk food diets (Molteni, etal., 2002)
• Aspartame (Kamel, 2015/recentissues_pdf/2015/October/October_2015_1492521278_232.pdf))