Our brain is subject to aging, just like the rest of our body. It is also subject to disease, which is unique in the sense that it can change the very essence of who we think we are.
Alzheimer’s can turn a loved one into a stranger. It can claim memories, personality, and relationships, leaving family members of the afflicted with a haunting echo of someone that once knew them.
Fortunately, even as the disease grows in prevalence, researchers are also learning more about factors that put us at risk, and habits we can cultivate to keep our brain healthy.
One recent example comes out of a collaboration between researchers1 from the University of Queensland and the German Center for Neurodegenerative Diseases. They discovered that a phytochemical in apple peels can stimulate the growth of new neurons (neurogenesis).
This phytochemical is called quercetin. While the researchers found this compound did not help the brain grow neurons when used at high concentrations, it was pro-neurogenic at low concentrations, which means it led to the creation of new neurons, specifically in the hippocampus region of the brain.
The brain has a hippocampus within each of the temporal lobes (which are just above the ears). The hippocampus 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 later.
Your behavior is affected by this constant accumulation of knowledge and damage to the thalamus can produce maladaptive behaviors because of its broad effects on emotion and cognition.
The hippocampus is also the area that takes the initial damage when the plaques and tangled fibers of Alzheimer’s start to destroy brain function.
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 of people with Alzheimer’s will also rapidly increase.
By 2050, it is projected 13.8 million Americans will have Alzheimer’s disease.
Quercetin Stimulates Proneurogenic Activity
The new study looked at how quercetin, a plant flavonol found in the apple peel, spurred neuron growth. Flavonols are a type of flavonoid, a compound with many functions in plants, including being an essential pigment for bright colors in fruit and vegetables.
Flavonoids are also powerful antioxidants, which help the immune system work better by neutralizing free radicals.
The study was published in Stem Cell Reports 6, and was built on past studies that have demonstrated the benefits of phytochemicals found in plant foods.
The researchers noted that plant compounds were vital for maintaining cognitive function by growing new neurons (neurogenesis). That’s what makes the new findings encouraging. This ability of the brain to reshape and grow itself is critical to our cognitive agility. The fact that a compound in apple peel—and another in its flesh—can help the brain do that is a testament to the benefits we receive from natural food.
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 (within glass) examination of quercetin, which is the most abundant flavonoid in the apple’s peel.
The second half of the study was an in vivo (within the living) 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 plant 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 thing we can do 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 it is all but impossible to study living human brain tissue.
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 the microscopic algae haematococcus 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 reduces 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).
These nutrients 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. There are also many benefits to nutritional ketosis, only one of which is providing adequate fuel to your brain for optimal functioning. That’s an article all on its own. Strategies to Slow Brain Aging
There are strategies you can use to improve brain function and others you should avoid as they can harm your brain.
Avoid Processed Food
To protect your brain, you should avoid processed foods and sugar.
Regular consumption of high-sugar foods is linked to a higher risk of Type 2 diabetes21 and Type 2 diabetes is associated with a 60 percent higher risk for any type of dementia.22
One study23 found that even without a diagnosis of Type 2 diabetes, participants with higher blood sugar levels had lower hippocampal volume and people with higher hemoglobin A1c and glucose measurements had significantly lower scores on memory testing.
That memory finding could be significant.
In two separate studies, researchers at the Alzheimer’s Disease Research Center at the Mayo Clinic and the Center for Demographic and Aging Research, found poor memory performance predicted a higher risk of dementia.
Drink Less Alcohol
Chronic excessive alcohol consumption causes dysfunction of 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.
One small 2018 study by the National Institutes of Health found even going one night without sleep increased the amount of beta-amyloid protein in the brain. This is the protein that creates the plaque linked to cognitive decline among Alzheimer’s patients.
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. Their study of sleep-deprived mice suggests that these astrocytes start to break down healthy nerve synapses when you are chronically sleep-deprived.
Quercetin’s Other Job
While the new study highlights quercetin’s role in neurogenesis, the medical literature has highlighted its capacity as a zinc ionophore, helping move zinc into the cells where it can halt viral replication. Research has also found it is a synergistic partner with vitamin C. On its own, quercetin acts as a natural antihistamine and anti-inflammatory that can also lower your risk for viral illnesses.
The body is an ever-unfolding chain reaction and researchers have found that quercetin can improve one of them by inhibiting 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. This means that 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, elderflower, and onions.35 Considering its wide-ranging benefits, quercetin may also be a useful supplement, 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.
Another 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.