In a collaboration between researchers1 from the University of Queensland and the German Center for Neurodegenerative Diseases, scientists discovered quercetin has proneurogenic effects in the hippocampus of the brain.
The hippocampus is located within the temporal lobe and is part of the limbic system.2 This is a part of the brain where behavioral and emotional responses are generated. These responses are central to survival and include reproduction, caring for babies, feeding and the fight-or-flight response. Other parts of the limbic system include the thalamus, hypothalamus, basal ganglia and amygdala.
The hippocampus is a well-studied part of the brain, which takes its name from the shape that resembles a seahorse. This area plays a crucial role in memory consolidation, coding and learning.3 Another of its major functions is forming a cognitive map, which is related to your ability to acquire new knowledge, store it and recall it.
Your behavior is dependent on your ability to acquire new knowledge and represent the information accurately. Damage to this area can produce maladaptive behaviors. “Evidence supports the role the hippocampus plays in decision-making as it relates to memory deficits that result from an Alzheimer’s type of dementia.”4
According to the Alzheimer’s Association,5 the number of people living in the U.S. who have Alzheimer’s disease is growing. There were an estimated 5.8 million people diagnosed with Alzheimer’s in 2020. Nearly two-thirds are women. Experts estimate that as the population of people over 65 continues to grow, the number with Alzheimer’s will also rapidly increase.
By 2050, it is projected 13.8 million will have Alzheimer’s disease. This new data offer more information about caring for the health of your memory and learning centers that are often hardest hit by Alzheimer’s disease. As I discuss below, there are also other strategies you can use to protect your brain health.
Quercetin Stimulates Proneurogenic Activity
The research design of the featured study in Stem Cell Reports6 was built on past studies that have demonstrated the benefits of phytochemicals found in plant foods. As the researchers wrote, one of the interesting processes is the brain’s plasticity, which is necessary for structural and functional modifications to happen when exposed to internal and external stimuli.
The researchers said they chose apples as they are widely consumed across the globe resulting in a generalized exposure.7 The study began with an in vitro examination of quercetin, which is an abundant flavonoid found in apple peel.
The second half of the study was an in vivo study using an animal model. After their data analysis, the researchers ultimately found that apples contained compounds in the peel and the flesh that helped promote neurogenesis.
Quercetin from the peel and another active compound from the apple flesh, 3,5-Dihydroxybenzoic acid (DHBA), demonstrated the ability to increase precursor cell proliferation and neurogenesis.
The researchers measured the effect on neural precursor cells, which are stem cells that can generate neural cell types within the brain. They found the effect was like that reported in past studies for other compounds such as resveratrol and epigallocatechin-3-gallate (EGCG), which is found in green tea.8
During the lab portion of the study, the researchers found that stem cells generated from a mouse brain were protected and exhibited more neurogenesis when quercetin and DHBA were added to the cell cultures.9 During the animal study, they found structures in the brain that were associated with learning and memory had more neurons when the mice were given doses of quercetin or DHBA.
Exercise Also Stimulates Brain Growth
Another stimulus that promotes neurogenesis is exercise. One study10 from the University of British Columbia discovered that aerobic training could increase the volume of the hippocampus in older women who had mild cognitive impairment.
The scientists engaged 86 women ages 70 to 80 years and assigned them to a twice-weekly program over six months. The women engaged in aerobic activity, resistance training or balance and tone training. Those enrolled in the aerobic training showed significant improvement in hippocampal volume.
As reported in Science magazine,11 neurogenesis without exercise may not be enough to protect memory and learning. One animal model demonstrated that increasing levels of brain-derived neurotrophic factor (BDNF) were required before the animals could outperform the control mice on testing.
BDNF is a key molecule produced in the brain with exercise and may help to explain the neuroprotective and cognitive benefits people experience with exercise.12 Much less is known about the interaction between exercise, BDNF and neurogenesis in the human brain as the inaccessibility of human brain tissue is the limiting factor.
More is known about the benefits from animal models, while indirect measurements of neurogenesis are used in human participants. Senior author of the paper published in Science, Rudolph Tanzi, Ph.D., commented on the results of chemically induced neurogenesis with exercise:13
“In our study we showed that exercise is one of the best ways to turn on neurogenesis and then, by figuring out the molecular and genetic events involved, we determined how to mimic the beneficial effects of exercise through gene therapy and pharmacological agents.
Although exercise-induced AHN [adult hippocampal neurogenesis] improved cognition in Alzheimer’s mice by turning on neurogenesis, trying to achieve that result by using gene therapy and drugs did not help.
That was because newly born neurons, induced by drugs and gene therapy, were not able to survive in brain regions already ravaged by Alzheimer’s pathology, particularly neuroinflammation. So, we asked how neurogenesis induced by exercise differs.
The lesson learned was that it is not enough just to turn on the birth of new nerve cells, you must simultaneously ‘clean up’ the neighborhood in which they are being born to make sure the new cells survive and thrive. Exercise can achieve that …”
More Strategies to Protect Brain Health
There are additional strategies you can use to help promote brain health. Astaxanthin is one. This powerful antioxidant is a naturally occurring carotenoid responsible for the pink or red color found in salmon, trout, lobster and other seafood.14
It’s often referred to as the “king of antioxidants”15 and is derived from haematococcus microalgae that produce it as a protective mechanism to shield it from ultraviolet light.16 In your body, it helps protect against reactive oxygen species and oxidation that play a role in heart disease, Alzheimer’s disease, Parkinson’s disease and aging.
In one review of the literature,17 scientists identified several pathways astaxanthin may take to help slow brain aging. They also found it increases BDNF levels and attenuates oxidative damage to DNA, lipids and proteins. Another nutrient found in fatty fish that helps protect your brain health is omega-3 fatty acids. Omega-3 fats are long-chain polyunsaturated fatty acids that include EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid).
They are crucial for cell membranes and play an anti-inflammatory role in the body.18 DHA is especially crucial for brain health as it is an essential structural component that is found in high levels in the neurons.
As I have written before, and covered in my book “Superfuel,” co-written with James DiNicolantonio, Pharm.D., when there is an inadequate amount of omega-3, the nerve cells become stiff and are prone to inflammation. This reduces proper neurotransmission from cell to cell and the cells become compromised.
Low levels of DHA have been linked to both memory loss and Alzheimer’s disease, and some studies have suggested degenerative brain diseases may potentially be reversible when sufficient DHA is provided.19,20 However, it is important to choose wild-caught Alaskan salmon, krill oil or other sources of safe fish, such as sardines, to meet these nutritional requirements. I discuss why in “The High Cost of Salmon Farming.”
There are also many benefits to nutritional ketosis, only one of which is providing adequate fuel to your brain for optimal functioning. You’ll find more information about the metabolic and antiaging benefits, as well as the importance of cyclical ketosis, in the article “Ketones: The Fourth Fuel.”
Strategies to Slow Brain Aging
There are strategies you can use to improve brain function and others you should avoid as they have a negative impact on brain health. To protect your brain health, processed foods and sugar are two dietary culprits to avoid.
Regular consumption of foods high in sugar is also linked to a higher risk of Type 2 diabetes21 and Type 2 diabetes is associated with a 60% higher risk for any type of dementia.22 One study found people who were recently diagnosed with Type 2 diabetes also had a 16% increased risk for dementia, indicating even after having diabetes for a short time you are still at increased risk for dementia.
An increased risk for dementia may also be present with higher levels of glucose without Type 2 diabetes. In one study,23 researchers found that even without a diagnosis of Type 2 diabetes, people with higher hemoglobin A1c and glucose measurements had significantly lower scores on memory testing. Also, participants with higher blood sugar levels had lower hippocampal volume.
Another source of carbohydrates and blood glucose is alcohol. Chronic excessive alcohol consumption is known to cause neuronal dysfunction and brain damage.24 Yet, even moderate alcohol consumption can reduce brain volume and is associated with neuronal changes.25
In a large study evaluating brain aging and alcohol,26 researchers from the University of Southern California examined 17,308 brain scans of cognitively normal participants.
They found that for every gram of alcohol consumed each day, the participants’ brain aged 0.02 years, which is equivalent to 7.3 days. To put this in perspective, 12 ounces of regular beer have approximately 14 grams of alcohol.27
Chronic sleep deprivation is another lifestyle component that can trigger poor brain health. When you don’t get enough sleep, your brain cannot do the necessary housekeeping.
Researchers from Marche Polytechnic University in Italy28 show that astrocytes, which are a type of glial cells in the brain that normally get rid of unnecessary nerve connections, start to break down healthy nerve synapses when you are chronically sleep-deprived.
The researchers looked at astrocyte activity in four groups of mice and found that chronically sleep-deprived mice had more than double the activity of the well-rested mice and instead of targeting only damaged cells, astrocytes were beginning to destroy healthy synopsis, an activity that could lead to neurodegenerative diseases.
Quercetin and Exercise Serve Important Roles in Immunity
Together, exercise and quercetin help to support your immune system. The interaction of lifestyle choices with your immune system has become even more important in 2020 after the release of SARS-CoV-2. In one review of the literature,29 researchers describe a “remarkable increase in the number of descriptive studies on exercise and immune system” than occurred in the 1990s.
The preponderance of the evidence demonstrates exercise has an important positive and complex effect on the immune system. The compelling link between physical activity and a strong immune defense system continues to be supported by research data.30
There is a clear inverse relationship between your risk of illness and moderate exercise. While athletes can experience an increased risk after intense training, habitual moderate exercise delays the onset of age-related immune dysfunction and reduces your risk of illness.
In 2020, scientists also began calling for regular exercise, even in isolation without access to gyms or sports clubs, as it can play an important role in supporting the immune system.31 Regular exercise of adequate intensity has been suggested as an auxiliary tool for preparing the immune system,32 even in the elderly.33
Quercetin has also been highlighted in the medical literature as it acts as a zinc ionophore, helping move zinc into the cells where it can halt viral replication, and as a synergistic partner with vitamin C. Yet, on its own, quercetin acts as a natural antihistamine and anti-inflammatory that can also lower your risk for viral illnesses.
Researchers have also found that quercetin can inhibit the expression of casein kinase II (CK2),34 which down-regulates the ability of the cell to generate type 1 interferon when it is attacked by a virus. By inhibiting the expression of CK2, quercetin may help slow the replication of RNA viruses.
In addition to apple peel, you can find quercetin in foods such as plums, red grapes, green tea, elder flower and onions.35 Considering its wide-ranging benefits, quercetin may also be a useful supplement for many, either acutely, for times you feel you’re coming down with something, or more long-term for metabolic health and, potentially, brain health.
If you choose to supplement, I believe that quercetin is best taken at night (with zinc) before you go to bed, and you haven’t eaten for at least three to four hours. You will sleep for eight hours, and if you are metabolically flexible, this is the time that you will dive into nutritional ketosis.
The other benefit of taking quercetin at night is to take advantage of its senolytic action. This helps to remove senescent cells, which are similar to nonreplicating cancer cells that secrete powerful proinflammatory cytokines. You can optimize quercetin’s senolytic properties if you take it while you are fasting. I talk more about quercetin in “Another Reason to Add Quercetin to Your Daily Supplements.”
