aging

How Micronutrients & Exercise Ameliorate Aging | Dr. Rhonda Patrick

Posted on February 21st 2024 (over 1 year)

In my keynote at LongevityFest 2023, I share powerful habits to delay aging and improve healthspan, presented at the American Academy of Anti-Aging Medicine.

exercise

Why vigorous exercise improves cognitive function | Dr. Martin Gibala

Posted on October 4th 2023 (over 1 year)

In this clip, Dr. Martin Gibala examines the cognitive benefits of HIIT and the emerging insights on lactate's role in brain health.

• How Micronutrients & Exercise Ameliorate Aging | Dr. Rhonda Patrick
  Aging Vitamin D Exercise Omega-3 Micronutrients Magnesium BDNF
  In my keynote at LongevityFest 2023, I share powerful habits to delay aging and improve healthspan, presented at the American Academy of Anti-Aging Medicine.
• Why vigorous exercise improves cognitive function | Dr. Martin Gibala
  Exercise Brain Muscle BDNF Lactate
  In this clip, Dr. Martin Gibala examines the cognitive benefits of HIIT and the emerging insights on lactate's role in brain health.

News & Publications

• Ketogenic diet raises brain blood flow by 22% and increases brain-derived neurotrophic factor by 47%, highlighting its potential to support cognitive function even in people without cognitive impairment. pubmed.ncbi.nlm.nih.gov
  Brain Diet Ketosis Memory BDNF Ketogenic Diet

  Glucose has long been considered the brain’s primary fuel, but ketone bodies may offer critical support, especially during periods of low carbohydrate availability. A recent study found that a ketogenic diet boosted levels of brain-derived neurotrophic factor (BDNF)—a key protein that supports brain health—by 47%, highlighting the diet’s potential to support brain health even in people without cognitive impairment.

  Researchers recruited 11 healthy but overweight adults to participate in a randomized, crossover study. Each participant followed two different diets: a ketogenic diet high in fat and low in carbohydrates, and a standard balanced diet. Each diet lasted three weeks and ended with brain imaging scans (using MRI and PET) and blood tests to measure brain blood flow and BDNF levels.

  They found that the ketogenic diet markedly increased ketone levels in the blood compared to the standard diet. Brain blood flow rose by 22% after eating the ketogenic diet, and BDNF levels increased by 47%. Researchers also found a strong link between ketone levels in the blood and higher brain blood flow.

  This was a small study, but the findings suggest that a ketogenic diet enhances brain blood flow and boosts vital brain-supporting proteins, even in people without memory loss. This opens up new possibilities for using ketogenic nutrition as a strategy to preserve cognitive function and support long-term brain health. Learn how to plan the optimal ketogenic diet in this clip featuring Dr. Dominic D'Agostino.

  Read more
• Uphill walking, even at a slow pace, provides cognitive benefits by increasing brain lactate and stimulating BDNF production—a protein critical for memory and learning. www.sciencedirect.com
  Exercise Brain Memory BDNF Lactate

  If you’re struggling to remember things, a robust workout might help. Scientists have discovered that exercise can increase levels of brain-derived neurotrophic factor (BDNF), a protein that supports learning and memory. A recent study in rats found that low-speed uphill exercise raises blood lactate levels, increasing lactate and BDNF in key brain regions involved in cognition.

  Researchers divided rats into three groups: One remained inactive, another walked on a flat treadmill, and a third walked uphill at a 40% incline. The exercise sessions lasted either 30 or 90 minutes. To see if lactate from the blood contributed to brain changes, some rats also received a direct lactate injection.

  Uphill exercise increased lactate levels in the animals' blood and brains, while flat treadmill walking did not. After 90 minutes, uphill exercise also raised BDNF levels in brain regions linked to memory and learning. The lactate injection showed that blood lactate passed into the brain, reinforcing that exercise-induced increases in blood lactate can influence brain chemistry.

  These findings suggest that walking uphill—even slowly—provides cognitive benefits by raising brain lactate and stimulating BDNF production. This type of exercise could be a practical and safe way to support brain health, especially for older adults or those looking to enhance memory and learning. To learn more strategies to boost brain health, check out the Cognitive Enhancement Blueprint, a member-only perk.

  Read more
• BDNF emerges as a critical marker of omega-3 fatty acid levels in the brain. www.nature.com
  Brain Omega-3 BDNF

  The Omega-3 Index measures omega-3 fatty acid concentrations in red blood cells. It provides a reliable assessment of long-term intake and is highly reflective of fatty acid composition in most tissues, with one notable exception – the brain. A recent study suggests that brain-derived neurotrophic factor (BDNF), a protein involved in learning and memory, is a more reliable measure of brain omega-3 concentrations than the Omega-3 Index.

  Researchers gave rats and mice different types and amounts of supplemental omega-3 fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and dietary fish and krill oils. Then, they measured the fatty acids in the animals' red blood cells (Omega-3 Index) and the BDNF concentrations in their plasma and brain tissues.

  They found that increased brain omega-3 levels were positively associated with elevated plasma BDNF but inversely associated with red blood cell concentrations, suggesting that plasma BDNF is a more dependable biomarker than the Omega-3 Index for evaluating the effectiveness of omega-3 supplementation and dietary intake in enhancing brain function.

  BDNF is critical for brain function, neurogenesis, neuronal survival, memory, and body weight regulation. Low BDNF concentrations are typical in psychiatric disorders but typically rise after antidepressant treatment and high omega-3 fatty acid doses. Exercise and DHA-rich diets also elevate BDNF, and some evidence suggests that BDNF mediates DHA’s beneficial brain effects.

  • Learn more about the Omega-3 Index in our stub article.
  Read more
• Whole-body hyperthermia activates muscle hormone irisin and increases neuroprotective factors. www.sciencedirect.com
  Exercise Brain Muscle Sauna BDNF Neurodegeneration

  Exposure to high heat while sauna bathing causes mild hyperthermia – an increase in the body’s core temperature – that induces a thermoregulatory response to restore homeostasis and condition the body for future heat stressors. These adaptations to high temperatures involve increased production of brain derived neurotrophic factor (BDNF), a promoter of neuroplasticity, and irisin, a biomarker of exercise. Findings of a new report demonstrate that whole-body hyperthermia increases BDNF and irisin in healthy young adults.

  Whole-body hyperthermia is a therapeutic strategy used to treat various diseases, including cancer and depression. Previous research has shown that use of a hyperthermia chamber increases BDNF to a greater extent than light intensity exercise. Some research has suggested that BDNF production is stimulated by irisin, a hormone secreted from muscle in response to exercise. Irisin may mediate some of the beneficial effects of exercise and sauna use in humans, but additional research is needed.

  The authors recruited 20 male participants (average age, 22 years) and assessed their baseline heat tolerance using a hyperthermia protocol. Participants reclined in a hyperthermia chamber while the researchers increased the temperature of the chamber by 50 degrees F every ten minutes until the participant reached their personal heat threshold. Next, participants completed ten hyperthermia sessions tailored to their baseline conditioning, during which the hyperthermia chamber was set to a temperature of 150 to 175 degrees F. Following a three-week wash-out period, they completed ten sham treatments over two weeks, during which the hyperthermia chamber was set to a temperature of 75 to 77 degrees F.

  Participants had an average core body temperature of 102 degrees F at the end of each whole-body hyperthermia treatment. Following ten whole-body hyperthermia treatments, participants had a significant increase in circulating irisin levels (6.3 micrograms per milliliter) compared to their baseline levels (5.0 micrograms per milliliter) and compared to their irisin levels following the sham treatment (5.4 micrograms per milliliter). Whole-body hyperthermia treatment also significantly increased BDNF levels (28.3 picograms per liter) compared to baseline (25.9 picograms per liter).

  In healthy young adults, ten whole-body hyperthermia significantly increased irisin and BDNF levels. The authors noted that future studies should explore the effects of whole-body hyperthermia on adipose tissue, which also produces irisin.

  • Link to full publication.
  • To learn more about the connections between whole-body hyperthermia, BDNF, and brain health, visit our topic page on whole-body hyperthermia here
  Read more
• Decreased brain derived neurotrophic factor, physical activity, and brain volume are associated with greater memory impairment. www.nature.com
  Brain Aging BDNF

  Brain derived neurotrophic factor (BDNF) is a growth factor associated with decreased risk of dementia and improved cognitive function in humans. While BDNF promotes brain cell growth plasticity, its precursor form, called proBDNF, has the opposite effect, promoting cell death. The authors of a recent report investigated the relationship between blood levels of pro-BDNF and memory loss.

  The effects of Alzheimer’s disease on the brain can be observed 10 to15 years before the onset of dementia, which presents the opportunity for early detection. Even though BDNF is known to cross the blood-brain barrier, whether blood levels of BDNF are reflective of BDNF activity in the brain is unclear. Establishing blood biomarkers of dementia risk provides the ability for early intervention.

  The authors recruited 256 older adults (average age, 68 years) without dementia. They analyzed magnetic resonance imaging (MRI) scans of the participants’ brains and measured blood levels of BDNF and proBDNF. Participants completed questionnaires to measure memory and physical activity habits.

  The investigators reported that increased age and decreased physical activity were associated with poorer memory performance. MRI findings showed decreased volume in the hippocampus, the region of the brain associated with memory, in those with worse memory scores. Finally, the authors reported that decreased blood levels of BDNF, but not pro-BDNF, were associated with worse memory performance.

  These results echo earlier findings that exercise is associated with greater BDNF activity and better memory performance. The authors conclude the measuring blood levels of BDNF may be an effective strategy for early detection of dementia.

  • Link to full report.

  • Learn more about BDNF and brain health in our overview article.

  Read more
• BDNF variant may mediate degree of brain benefits from exercise. www.sciencedaily.com
  Exercise Brain Memory ADHD BDNF

  Exercise improves cognitive function and reduces the risk neurodegenerative diseases such as Alzheimer’s disease. Some of these benefits are mediated by brain-derived neurotrophic factor (BDNF). Findings from a 2012 study showed that regular exercise improved cognitive function and increased BDNF levels, but a genetic variant in BDNF influenced the degree of these effects.

  BDNF is a protein that acts on neurons in the central and peripheral nervous systems. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. This genetic variant, known as Val66Met, alters exercise-driven release of BDNF and affects learning, memory, and emotion.

  The intervention study involved 75 sedentary, healthy, young adults between the ages of 18 and 35 years. The participants took memory tests and mental health surveys before and after engaging in their randomly assigned respective activities: no exercise; four weeks of exercise with exercise and a test on the last day; four weeks of exercise, without exercise on the final test day; or a single bout of exercise on the last test day.

  The participants who engaged in exercise showed improvements in memory and experienced lower levels of perceived stress, but only if they exercised for four weeks including the final day of testing. Participants who engaged in a single bout of exercise showed no changes in memory performance and demonstrated higher perceived stress levels. The authors of the study noted improvements in the participants' memory only if they did not carry the Val66Met variant, suggesting that the associated reduction in BDNF release attenuated some of the cognitive benefits of exercise. They also noted that the improvements in cognitive function were not correlated to improvements in mental health.

  These findings suggest that the variable effects of exercise on brain function are related to a genetic variant that influences the production of BDNF.

  • Link to full study.
  Read more
• Carriers of a common BDNF genetic variant demonstrate more rapid decline from Alzheimer's disease. www.sciencedaily.com
  Brain Alzheimer's Genetics BDNF Neurodegeneration

  BDNF plays critical roles in many aspects of cognitive function, including learning and memory formation. A single-nucleotide polymorphism (SNP) in the gene that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in a specific region of the DNA where the gene is located. Evidence suggests that carrying the Met allele (Met/Met or Val/Met genotype) is associated with lower BDNF expression.. A 2017 study found that amyloid-beta burden impaired BDNF-related learning and memory.

  Amyloid-beta is a toxic 42-amino acid peptide that aggregates and forms plaques in the brain with age. Amyloid-beta is associated with Alzheimer’s disease, a progressive neurodegenerative disease that can occur in middle or old age and is the most common cause of dementia.

  The study involved more than 1,000 adults (approximately 55 years at the beginning of the study) who were enrolled in a larger study of Alzheimer’s disease. Nearly 65 percent of the participants were at high risk for developing Alzheimer’s disease, having at least one parent diagnosed with the condition. Each of the participants underwent cognitive assessment and BDNF genotyping five times over a period of four to 11 years. In addition, a small cohort of participants underwent imaging studies to assess amyloid-beta burden.

  The genotyping revealed that approximately one-third of the participants were carriers of the Met-66 allele. Compared to Val/Val carriers, Met-66 carriers showed steeper declines in cognitive function. In addition, Met-66 carriers with greater amyloid-beta burden showed an even greater cognitive decline, likely due to lower BDNF expression. These findings suggest that a SNP in the gene for BDNF influences cognitive health and could serve as a therapeutic target against Alzheimer’s disease.

  • Link to full study.
  Read more
• BDNF delivery via hydrogel improves respiratory function in rats with spinal cord injury. www.sciencedaily.com
  Tissue Repair BDNF

  Approximately 17,000 people living in the United States will experience traumatic spinal cord injury in any given year. A severe complication associated with spinal cord injury is the loss of respiratory function, which often occurs due to paralysis of the diaphragm muscle. A 2018 study showed that BDNF delivery to the injured spinal cord improved respiratory function in rats.

  Previous research has demonstrated that systemic delivery of neurotrophic factors is associated with many undesirable side effects, such as muscle spasms and chronic pain, and exerts reduced efficacy. The authors of the current study used a water-based gel to deliver a solution of polysaccharide-BDNF particles to spinal cord-injured female rats. This delivery mode keeps the BDNF at the site of injury instead of allowing it to become more widely distributed. Then they measured the action potential in the rats' diaphragm muscle.

  They found that the BDNF hydrogel improved diaphragm muscle contractility by more than 60 percent, likely due to BDNF-mediated protection and/or restoration of neurons that innervate the diaphragm.

  These findings suggest that targeted delivery of BDNF is a viable strategy for preserving respiratory function following traumatic spinal cord injury.

  • Link to full study.
  Read more
• From the blood to the brain: BDNF-producing blood cells travels to the hypothalamus in adults, regulating and suppressing appetite [animal research] www.sciencedaily.com
  Brain Obesity BDNF

  From the article:

  We knew that blood cells produced BDNF,“[…] "We didn’t know why it was produced in blood cells.”

  Dr. Hiroshi Urabe and Dr. Hideto Kojima, current and former postdoctoral fellows in Chan’s laboratory respectively, looked for BDNF in the brains of mice who had not been fed for about 24 hours. The bone marrow-derived cells had been marked with a fluorescent protein that showed up on microscopy. To their surprise, they found cells producing BDNF in a part of the brain’s hypothalamus called the paraventricular nucleus.

  “We knew that in embryonic development, some blood cells do go to the brain and become microglial cells,” said Chan. […]“This is the first time we have shown that this happens in adulthood. Blood cells can go to one part of the brain and become physically changed to become microglial-like cells.”

  A new way to affect appetite and obesity?

  When normal bone marrow cells that produce BDNF are injected into the third ventricle (a fluid-filled cavity in the brain) of mice that lack BDNF, they no longer have the urge to overeat, said Chan.

  All in all, the studies represent a new mechanism by which these bone-marrow derived cells control feeding through BDNF and could provide a new avenue to attack obesity, said Chan.

  He and his colleagues hypothesize that the bone marrow cells that produce BDNF fine tune the appetite response, although a host of different appetite-controlling hormones produced by the regular nerve cells in the hypothalamus do the lion’s share of the work.

  • Publication
  Read more
• BDNF mimetic 7,8-dihydroxyflavone protects neurons against cell death. www.sciencedaily.com
  Brain Parkinson's BDNF Stroke

  BDNF’s neuroprotective capacity suggests that it could be useful in preventing or treating neurodegenerative diseases. Circumventing problems with BDNF’s delivery, half-life, and other limitations has proven challenging. A 2010 study found that 7,8-dihydroxyflavone, a BDNF mimetic, exerted neuroprotective qualities similar to those of BDNF.

  7,8-dihydroxyflavone is a type of flavonoid compound present in a variety of plants. Flavonoids exert antioxidant and anti-inflammatory effects, among others. Some evidence indicates that 7,8-dihydroxyflavone might be useful in reversing the damage associated with lead poisoning in children.

  The authors of the study screened 2,000 bioactive compounds to gauge their ability to protect rodent and human neurons from apoptosis and identified five compounds, including 7,8-dihydroxyflavone, that showed potential in protecting the cells. Then they treated the cells with BDNF and the various compounds and deprived the cells of oxygen and glucose.

  They found that none of the compounds was as effective as 7,8-dihydroxyflavone in protecting the cells from apoptosis. In fact, 7,8-dihydroxyflavone was even more protective than BDNF. They also found that 7,8-dihydroxyflavone exerted its protective qualities by activating a receptor called TrkB, to which BDNF binds. They replicated their findings in an in vivo study of mice, indicating that 7,8-dihydroxyflavone enhances neuronal survival.

  These findings demonstrate that flavonoid compounds that mimic the effects of BDNF show potential as therapeutics against neurodegenerative diseases.

  • Link to full study.
  Read more
• Plasma levels of BDNF lower in women with history of suicide attempts. www.sciencedaily.com
  Brain Depression BDNF

  Suicide is a major public health concern, claiming the lives of nearly 800,000 people worldwide each year. A history of a suicide attempt is a robust predictor of a future attempt. Findings from a 2017 study suggest that plasma levels of BDNF are a marker for suicidality.

  BDNF is a protein that plays critical roles in the creation and functioning of neurons and the ability of synapses to strengthen or weaken over time. Low BDNF levels are associated with an increased risk for depression.

  The participants in the study included 34 women with a history of suicide attempt and 39 without (average age, 33 years). The women were matched based on age, ethnicity, family income, body mass index, and cigarette smoking history. The authors of the study assessed the women’s mental health history and current status and took blood samples to determine BDNF levels.

  Thirty (88 percent) of the women who had attempted suicide had a lifetime history of major depressive disorder. Of these, 14 (40 percent) met the criteria for current major depressive disorder. The women with a history of suicide attempt had lower levels of BDNF than women without a history of suicide – a difference that was maintained even after taking into account other potential psychiatric or demographic factors. The authors of the study posited that lower BDNF levels represent a trait-like biochemical indicator of suicide risk and might be relevant for suicide prevention.

  Other biochemical indicators of suicide have been identified, as well. For example, markers of accelerated extrinsic aging have been observed in the blood of suicide completers. Age acceleration is a phenomenon that occurs when an individual’s epigenetic age exceeds their chronological age. Learn more about epigenetic aging in this overview article.

  • Link to study abstract.
  Read more
• BDNF genetic variant predicts success in alcohol dependence treatment. www.sciencedaily.com
  Brain Alcohol Genetics Addiction BDNF

  Alcohol dependence is a complex disorder that increases a person’s risk of death from all causes. Findings from a 2009 study suggest that variations in certain genes can impact the likelihood of relapsing following treatment.

  BDNF is involved in neuronal growth and survival, as well as influencing neurotransmitters – chemical signals from the nervous system. Low BDNF levels have been linked to the development of depression, anxiety, and alcohol dependence.

  Previous research has demonstrated that alcohol dependence has a genetic component. The current study investigated whether common variations in certain genes would have an effect on post-treatment relapse.

  The prospective study involved 154 participants who met the criteria for alcohol dependence and were admitted to a treatment facility. The patients provided blood samples for genetic analysis and completed self-assessment questionnaires about depression, hopelessness, impulsivity, and the severity of their alcohol use. The authors followed up with participants for approximately one year to assess whether they had relapsed. Relapse was defined as any drinking during the observation period, with heavy drinking considered as more than four drinks per day for more than four consecutive days. During the follow-up period, 59 (48 percent) participants relapsed, with 48 returning to heavy drinking. The average time to relapse was 218 days.

  The authors tested a genetic variant that resides in the BDNF gene, known as Val66Met. They observed that participants with the Val form of this gene were more likely to relapse compared to those with the Met version. Participants with two copies of the Val allele – one from each parent – had higher rates of relapse and shorter times to relapse when compared to carriers of at least one Met allele.

  These findings suggest that BDNF influences a person’s ability to remain abstinent following treatment for alcohol dependence. With further evaluation, these findings may help clinicians to identify people at increased risk for post-treatment relapse and tailor their care plans.

  • Link to study abstract.
  Read more
• Bipolar disorder patients experience generalized impaired cellular resilience and broad reductions in BDNF that may contribute to the disease www.sciencedaily.com
  Brain Depression Stress BDNF

  From the article:

  Effective neuronal plasticity also depends on neurotrophins, which are regulatory factors that promote development and survival of brain cells. Brain-derived neurotrophic factor (BDNF) is the neurotrophin mostly found in the brain. It has been extensively investigated in bipolar disorder patients and has been suggested as a hallmark of bipolar disorder. Indeed, some studies have shown that the levels of BDNF in the serum of bipolar disorder patients are reduced whenever patients undergo a period of depression, hypomania, or mania. Other studies have shown that regardless of mood state, bipolar disorder patients present reduced levels of BDNF. Overall, changes in BDNF levels seem to be a characteristic found in bipolar disorder patients that may contribute to the pathophysiology of the disease.

  Immediate early genes:

  Immediate early genes (IEGs) are a class of genes that respond very rapidly to environmental stimuli, and that includes stress. IEGs respond to a stressor by activating other genes that lead to neuronal plasticity, the ability of brain cells to change in form and function in response to changes in the environment. Ultimately, it is the process of neuronal plasticity that gives the brain the ability to learn from and adapt to new experiences.

  One type of protein produced by IEGs is the so-called Early Growth Response (EGR) proteins, which translate environmental influence into long-term changes in the brain. These proteins are found throughout the brain and are highly produced in response to environmental changes such as stressful stimuli and sleep deprivation. Without the action played out by these proteins, brain cells and the brain itself cannot appropriately respond to the many stimuli that are constantly received from the environment.

  […]

  in a previous study done by the group in 2016, one type of IEG gene known as EGR3, that normally responds to environmental events and stressful stimuli, was found repressed in the brain of bipolar disorder patients, suggesting that when facing a stressor, the EGR3 in bipolar disorder patients does not respond to the stimulus appropriately. Indeed, bipolar disorder patients are highly prone to stress and have more difficulties dealing with stress or adapting to it if compared to healthy individuals. What the research group is now suggesting is that both EGR3 and BDNF may each play a critical role in the impaired cellular resilience seen in bipolar disorder, and that each of these two genes may affect each other’s expression in the cell. “We believe that the reduced level of BDNF that has been extensively observed in bipolar disorder patients is caused by the fact that EGR3 is repressed in the brain of bipolar disorder patients. The two molecules are interconnected in a regulatory pathway that is disrupted in bipolar disorder patients,”

  • Publication
  Read more
• Decreased exposure to air pollution associated with improved cognitive development and increases BDNF levels in children. www.sciencedaily.com
  Brain Development Pollution BDNF

  Exposure to air pollutants is associated with an increased risk of developing many health disorders, including heart disease, stroke, chronic obstructive pulmonary disease, lung cancer, and acute respiratory infections. Some evidence suggests that exposure to air pollution can impair neurological development in children. A 2014 study showed that reducing exposure to polycyclic aromatic hydrocarbons (PAHs) was associated with improved cognitive development and increased BDNF levels in children.

  Polycyclic aromatic hydrocarbons are produced during the combustion of coal, oil, gasoline, trash, tobacco, and wood. High-temperature cooking, such as grilling, promotes the formation of PAHs in meat and other foods. PAHs promote the formation of DNA adducts – covalent modifications of DNA that can drive carcinogenesis.

  The study involved two cohorts of mother-child pairs who lived near a coal plant in China. One cohort of pairs was made up of 150 women who were pregnant while the coal power plant was operational and the other was made up of 158 women who were pregnant after it closed. None of the women smoked, and they all lived within 2.5 kilometers (about 1.5 miles) from the coal plant.

  The authors of the study analyzed BDNF levels and their relationship to adduct formation and developmental outcomes in the two cohorts. They collected umbilical cord blood and maternal blood samples and measured the amount of DNA adducts in the samples. They also measured plasma levels of BDNF. When the children reached the age of two years, they underwent standardized testing that assessed motor, adaptive, language, and social development.

  The children who were born to women who were pregnant after the plant closed had lower levels of PAH-DNA adducts, higher concentrations of BDNF, and higher developmental scores than those who were born to women who were pregnant when the plant was operational. Higher BDNF levels were associated with developmental scores. The findings suggest that reducing exposure to air pollutants during pregnancy lowers levels of PAH-DNA adducts and increases BDNF levels in infants.

  Interestingly, clinical trials have demonstrated that sulforaphane, a compound derived from cruciferous vegetables (especially broccoli sprouts), can reduce the harmful effects of exposure to air pollutants (including PAHs) in humans. Sulforaphane works by switching on the activity of the body’s in-house detoxication pathways. Learn more about sulforaphane in this podcast featuring Dr. Jed Fahey.

  • Link to full study.
  Read more
• Restoration of BDNF-mediated signaling as a potential therapeutic strategy against Huntington's disease. www.sciencedaily.com
  Brain BDNF Neurodegeneration

  Huntington’s disease is a progressive neurodegenerative disorder characterized by uncontrolled movements, speech problems, personality changes, and dementia. The disease is caused by a single genetic mutation, called a CAG repeat, that drives abnormal protein folding and aggregation of the huntingtin protein and subsequent death of striatal neurons. Findings from a 2010 study demonstrate that modulating pathways involved in BDNF-mediated signaling shows promise as a therapeutic against Huntington’s disease.

  Evidence suggests that normal huntingtin promotes the expression of BDNF, but mutated huntingtin impairs it. Striatal neurons need BDNF for their normal function and survival. A critical component in BDNF’s actions on striatal cells is a receptor called TrkB, to which BDNF binds. Levels of TrkB are diminished in Huntington’s disease.

  The authors of the in vitro cell study investigated the effects of BDNF administration on mutant huntingtin. They found that altered cell-signaling in the Ras/MAPK/ERK1/2 pathway in cells expressing mutant huntingtin drove the loss of TrkB receptors, increased striatal cells' sensitivity to oxidative damage, and promoted cell death. These findings suggest that identifying ways to modulate the Ras/MAPK/ERK1/2 pathway and restore BDNF-related signaling shows promise as a therapeutic strategy against Huntington’s disease.

  • Link to full study.
  Read more
• BDNF genetic variant influences response to exposure therapy among people with PTSD. www.sciencedaily.com
  Brain Behavior Anxiety BDNF

  Exposure therapy is a type of cognitive behavioral therapy commonly used to treat people with posttraumatic stress disorder (PTSD). Some evidence suggests that BDNF mediates the response to exposure therapy, which can vary among people. A 2013 study demonstrated that genetic differences in BDNF expression influences how well a person responds to exposure therapy.

  A single-nucleotide polymorphism (SNP) in the region of the DNA that encodes BDNF causes a substitution of the amino acid valine (Val) by methionine (Met) in the BDNF protein. Evidence suggests that carriers of the Met allele (Met/Met or Val/Met genotype) have reduced hippocampal function, poor episodic memory, and decreased exercise-induced secretion of BDNF.

  The study involved 55 people between the ages of 18 and 65 years who had previously participated in an eight-week exposure therapy program. The participants provided DNA (via saliva samples) for BDNF genotyping.

  The genotyping revealed that 30 participants carried the Val/Val BDNF allele, and 25 participants carried the Met-66 allele. Carriers of the Met-66 allele showed a poorer response to exposure therapy than carriers of the Val/Val allele, suggesting that the SNP influenced BDNF expression and subsequent response to cognitive behavioral therapy.

  • Link to full study.
  Read more
• Low BDNF during pregnancy is associated with depression during pregnancy and subsequent low fetal birth weight. www.sciencedaily.com
  Brain Pregnancy Development BDNF

  Depression is the most common form of mental health condition worldwide, affecting more than 322 million people. The disorder affects women disproportionately and is particularly common during pregnancy. Findings from a 2017 study demonstrated that serum levels of BDNF drop considerably during pregnancy, potentially increasing a woman’s risk for depression.

  BDNF modulates synaptic plasticity and long-term potentiation – critical aspects of memory storage and brain function. Low BDNF levels are associated with increased risk for depression00181-1/fulltext?cc=y=).

  The study involved 139 healthy pregnant women (77 Blacks and 62 whites) who were assessed three times during their pregnancies (once during each trimester) and again at four to 11 weeks postpartum. The authors of the study measured the participants' BDNF and cortisol levels via blood samples, gathered demographic data, and conducted psychosocial assessments. They reviewed the women’s medical records to determine their infants' birth weights.

  The results of their assessments indicated that the women’s BDNF levels dropped considerably over the course of their pregnancies but rebounded during the postpartum period. In general, Black women had higher BDNF levels and lower cortisol levels than white women during pregnancy and postpartum. Lower levels of BDNF during the second and third trimesters were associated with higher risk for depression and lower birthweight babies, regardless of race.

  Interestingly, these findings contradict those of an earlier study in rats and humans. However, the authors of the current study suggested that the conflicting findings may have been due to differences in assays used to measure BDNF.

  Evidence indicates that exercise increases BDNF. Exercise is generally considered safe for pregnant women and may be a way to prevent some of the changes in mood that occur during pregnancy.

  • Link to study abstract.

  • Watch this video in which Dr. Rhonda Patrick describes some of the mental health benefits associated with exercise.

  • Learn more about depression in our overview article.

  Read more
• Preclinical evidence suggests BDNF may be a potent interventional tool in Alzheimer's and brain aging by directly improving learning and memory www.sciencedaily.com
  Exercise Brain Alzheimer's Aging Memory BDNF

  From the article:

  For these experiments, the researchers injected the BDNF gene or protein in a series of cell culture and animal models, including transgenic mouse models of Alzheimer’s disease; aged rats; rats with induced damage to the entorhinal cortex; aged rhesus monkeys, and monkeys with entorhinal cortex damage.

  In each case, when compared with control groups not treated with BDNF, the treated animals demonstrated significant improvement in the performance of a variety of learning and memory tests. Notably, the brains of the treated animals also exhibited restored BDNF gene expression, enhanced cell size, improved cell signaling, and activation of function in neurons that would otherwise have degenerated, compared to untreated animals. These benefits extended to the degenerating hippocampus where short-term memory is processed, one of the first regions of the brain to suffer damage in Alzheimer’s disease.

  […]

  “In this series of studies, we have shown that BDNF targets the cortical cells themselves, preventing their death, stimulating their function, and improving learning and memory. Thus, BDNF treatment can potentially provide long-lasting protection by slowing, or even stopping disease progression in the cortical regions that receive treatment.”

  Read more
• Brain-derived neurotrophic factor may be able to disrupt cocaine-seeking when applied directly to the nucleus accumbens in the brain [animal research] www.sciencedaily.com
  Brain Behavior Addiction BDNF

  From the article:

  Cocaine relapse was significantly reduced in a preclinical model when brain-derived neurotropic factor (BDNF) was applied to the nucleus accumbens deep in the brain immediately before cocaine-seeking behavior, report investigators at the Medical University of South Carolina (MUSC) in an article published online in June 2018 by Addiction Biology.

  […]

  While other research groups have studied how BDNF administration affects drug self-administration and relapse, no one has looked at what happens if BDNF is given immediately before relapse.

  Since low serum BDNF levels are seen in cocaine-dependent patients compared to non-addicts, the MUSC researchers sought to better understand the connection between BDNF and cocaine relapse. The nucleus accumbens was selected as the focal point for BDNF administration since it is a central component of the brain reward circuit.

  “An important aspect of this study is that while others have shown that BDNF is important for establishing the state of addiction, we find that can also be used to reverse addiction,” says Peter Kalivas, Ph.D., professor and chair in the Department of Neuroscience. “This exemplifies that the primary effect of BDNF is to promote changes in the brain, and that this capacity to change the brain contributes to how people get addicted, but also can be harnessed to remove brain pathologies such as drug addiction.”

  The findings reported in Addiction Biology are the first to show that applying BDNF to the nucleus accumbens immediately before the reinstatement phase, when the rats are once again seeking cocaine due to cue exposure, greatly reduces relapse.

  Read more
• Beta-hydroxybutyrate, a ketone, increases brain-derived neurotrophic factor expression: relevance for neurodegenerative disease www.sciencedaily.com
  Exercise Brain Alzheimer's Diet Ketosis BDNF HDAC Inhibitor

  β-hydroxybutyrate production consequent to exercise induces within the muscle the activities of a key promoter involved in the production of brain-derived neurotrophic factor.

  From the article:

  Studies have shown that BDNF levels in the brains of people with Alzheimer’s or Huntington’s disease are, on average, half that of people without either brain-damaging disease.

  Among the key findings of the current study was that a ketone, a chemical naturally produced in the liver called beta-hydroxybutyrate (DBHB), triggers biological reactions that activate the BDNF gene to produce more of its protein. DBHB has long been known to build up in the body and brain with exercise. Ketones are “by-product” chemicals made when animals break down fat as an alternative energy source after having drained more readily available sugar stores during exercise.

  Specifically, Chao says, the researchers found that DBHB prevents other proteins in the brain known as histone deacetylase complexes, or HDACs, from suppressing BDNF production by altering the environment of the BDNF gene.

  • Publication
  Read more
• Environmental enrichment alone produces browning of fat and enhanced weight control not accountable by exercise alone [animal study]
  Brain Obesity Memory Fat BDNF Thermogenesis

  From the article:

  “Up to now the only known approach to inducing brown fat has been through exposure to chronic cold. Our research reveals a novel way of doing this without cold exposure. We show that animals living in an enriched environment become lean and resistant to diet-induced obesity, even in the presence of unlimited food.”

  […]

  The current study used a similarly designed environment, with 15-20 mice housed in large containers equipped with running wheels, tunnels, huts, wood toys, a maze, and nesting material, in addition to unlimited food and water.

  Key findings include the following:

  • Enriched animals showed a significant reduction in abdominal white fat mass (49 percent less than controls).

  • Exercise (running in a wheel) alone did not account for the changes in body composition and metabolism of enriched animals.

  • Fed a high fat diet (45 percent fat), enriched animals gained 29 percent less weight than control mice and remained lean, with no change in food intake. Enriched animals also had a higher body temperature, suggesting that greater energy output, not suppressed appetite, led to the resistance to obesity.

  Read more
• Increases in brain-derived neurotrophic factor from aerobic exercise associated with appetite suppression, weight loss, and improved blood pressure www.sciencedaily.com
  Exercise Brain Obesity Blood Pressure Aerobic Weight Loss BDNF

  From the article:

  The team evaluated blood levels of BDNF before and after a three-month program of aerobic exercise in 15 overweight or obese men and women. The seven men and eight women, ages 26 to 51, worked out on a treadmill and bicycle. They were asked about their calorie intake and told to continue eating their usual number of calories. The participants were unaware that one of the study’s objectives was to evaluate changes in food intake.

  At the end of the study, the subjects had decreased BMI, waist circumference, and blood pressure, the data showed. They also reported consuming fewer calories than at the beginning of the study. Over the three months, BDNF levels greatly increased. This higher the concentration of BDNF, the less the subject’s intake of calories and the greater the weight loss, Araya said.

  Thus, it is possible that increases in BDNF suppress appetite, she said. They did not test appetite suppression directly, but some past studies have shown that aerobic exercise suppresses appetite.

  Read more
• Greater BDNF expression in brain tied to up to 50% slower decline in memory in older people (for those in top decile of expression) www.sciencedaily.com
  Brain Alzheimer's Memory Dementia BDNF

  A study of BDNF gene expression in post-mortem brain tissue found that BDNF may provide a buffer against dementia, particularly when higher expression is found in the context of the classical Alzheimer’s brain pathology of amyloid-beta plaques and tau tangles.

  From the article:

  For the study, 535 people with an average age of 81 were followed until death, for an average of six years. They took yearly tests of their thinking and memory skills, and after death, a neurologist reviewed their records and determined whether they had dementia, some memory and thinking problems called mild cognitive impairment or no thinking and memory problems. Autopsies were conducted on their brains after death, and the amount of protein from BDNF gene expression in the brain was then measured.

  […]

  The rate of cognitive decline was about 50 percent slower for those in the highest 10 percent of protein from BDNF gene expression compared to the lowest 10 percent. The effect of plaques and tangles in the brain on cognitive decline was reduced for people with high levels of BDNF. In the people with the highest amount of Alzheimer’s disease hallmarks in their brains, cognitive decline was about 40 percent slower for people with the highest amount of protein from BDNF gene expression compared to those with the lowest amount.

  Read more