The ‘Big 3’ Supplements Everyone Needs to Preserve for Optimal Brain Integrity
Bridging the Gap Between the Brain and Nutrition
The pancreas is commonly known as the ‘powerhouse’ of digestive enzymes. This flat-spongy-pear-shaped organ just behind your stomach produces digestive juices containing these digestive enzymes. These juices created by the exocrine tissue of your pancreas leave via the bile duct of the pancreas and flow into the duodenum (the first part of the small intestine), where they break down food and macromolecules that enter through the stomach. But before then, digestion begins in the mouth when you chew.
Like the pancreas, the mouth has exocrine glands known as… drum-roll… salivary glands. Yup! Salivary glands produce saliva, which is about 98% water and 2% electrolytes, mucus, hormones, antibodies, and of course, a small relative proportion of enzymes.
These digestive enzymes (amylase, protease, and lipase) found in the mouth begin and facilitate the process of digestion by breaking down larger food, such as a burrito, into smaller food, such as a smaller burrito. This is partly why you may develop digestive problems if you omit to chew but swallow (thus omitting/degrading the first part of digestion).
After swallowing this smaller burrito, it then travels down the esophagus into the stomach, where it sits between 2-4 hours while the stomach grinds and churns your burrito in a bed of thick mucus produced by the cells in the gastric glands lining your stomach. In this stage, the cells found in the gastric glands concoct a gastric juice containing water, hydrochloric acid (basically Hydrogen and Chloride bonded), electrolytes, mucus, and… digestive enzymes, where the burrito is further broken down into a micro-burrito.
Then the food enters the small intestine, where more enzymes break down the macromolecules (carbs, protein, and lipids) into smaller molecules (glucose, amino acids, fatty acids, and glycerol). Once the micro-burrito is broken down into its smaller components (carbohydrates, proteins, lipids, minerals, and vitamins), it moves down to the jejunum and ileum (the second and third parts of the small intestine), where most of the nutrient absorption occurs. Nutrient absorption is made possible by tiny hair-like projections called villi that increase the surface area lining the small intestine allowing nutrients to get trapped and absorbed by enterocytes of the villi into capillaries of the circulatory system and lacteals of the lymphatic system.
Without villi, the surface area of the small intestine would be much smaller, allowing many essential micro-nutrients to pass through undetected. A relatively common disease that causes malnutrition by degrading the villi lining of the intestine is Celiac Disease.
Bridging the Gap Between the Brain and Nutrition Continued
Most nutrient absorption takes place in the capillaries. However, larger fatty acids and fat-soluble nutrients get packaged by chylomicrons and shipped through lymph due to their sheer size and attraction towards one another. Fat-soluble vitamins (A, D, E, and K) dissolve into fat (cholesterol, phospholipids, and fatty acids) because non-polar molecules tend to mix with non-polar solvents and, therefore, like micro-lovers, are inseparable. Once in the lymph, this milky-white substance of fluid and fat called chyle hitch a ride to the thoracic duct where it goes ‘drip-drip’ into the heart and then ‘lub dub’ into the bloodstream where the lovers are introduced back into society while the rest of the blood components (amino acids, glucose, water-soluble vitamins, minerals) go about their business regulating chemical processes by activating enzymes that release hormones, repair cells, provide energy and growth that the brain could use for its benefit.
But for nutrients to directly move from the blood into the brain's neurons, they must first travel through small blood vessels leading to the brain called carotid and vertebral arteries. A weakening or swelling of these arteries is called a cerebral aneurysm, and an obstruction could cause bleeding in the brain. However, the brain has a defensive wall made of endothelial cells, astrocytes, and pericytes… not parasites but pericytes called a Blood-Brain Barrier. This multicellular structure is the wall between the bloodstream and the brain, and an unorthodox mode of entry is by breaking down this wall.
Neurotoxicants found in alcohol (Ethanol) can gain access easily and, if consumed in excess, increase the BBB’s permeability over time, allowing cells to attack the myelin around your nerves leading to neurological diseases such as Alzheimer's and Parkinson’s.
On the contrary, “Low to moderate drinking (<8 drinks per week for women and <15 drinks per week for men) was associated with a consistently higher cognitive function trajectory and a lower rate of cognitive decline compared to non-drinkers in older adults” (Ruiyuan Zhang, MD, MS). The dose may be what makes the poison.
Setting the digression aside, if a nutrient was to pass through the BBB, there are four ways through which it can:
Transmembrane diffusion
Saturable transporters
Adsorptive endocytosis
Extracellular pathways
An easy way to remember these 4 is by remembering the word SEAT or EATS.
I will omit the last two and instead provide two examples of transmembrane diffusion and saturable transporters:
1) Ethanol can pass because it is both somewhat polar (mixes in water) and partially lipophilic (mixes in fat), using its characteristics to its advantage (T).
1.2) Water can fit through the tight junctions of the wall since it is small enough (T).
2) Glucose needs a transporter such as Glut3 (S).
2.) DHA (an omega-3 fatty acid) needs a cell membrane protein Mfsd2a (S) to pass and enter the Central Nervous System (CNS), where it could build brain and nerve cells or activate neurons and the communication between them by electrical and chemical means, where one neuron sends a message (neurotransmitters) to another neuron to complete a task such as memory storage.
As shown above, what we eat not only enters the blood and affects the tissues and organs of our body but also can enter the arteries of our brain, which directly communicate with the different brain regions.
But why is that important? The brain controls the very fact that you can read this article and retain the information. The fact that you can consciously reason through a problem to form methods and convictions is also governed by the brain. This 3-pound organ contains an average of 86 billion neurons that enable and control thoughts, memories, emotions, touch, motor skills, vision, and much more. And now more than ever, science is validating the role of nutrition in upholding the integrity of the brain, and dare-I-say nutrition is unlocking a greater capacity for the brain to do more, understand better, and learn quicker. In the following, I will discuss the ‘3 big’ supplements everyone needs to preserve for optimal brain integrity and reach a higher potential— a genius you.
Omega-3 Fatty Acids
Cytokines affecting neurotransmitters
The two principal omega 3’s (EPA & DHA) found abundantly in sardines, anchovies, salmon, algae, salmon roe, and omega-3 supplements have already been well established in many studies to support the brain through their involvement in many biochemical reactions. Some of these include synthesizing proteins and gases called SPMs, which hamper inflammation by suppressing pro-inflammatory cytokines and resolving infection.
Cytokines have been shown to affect the metabolism of multiple neurotransmitters, such as dopamine, serotonin, and glutamate, by negatively impacting their synthesis, release, and uptake. Other biological networks, such as pleasure, mood, learning, memory, and appetite suppression, are negatively impacted by disrupting the neurotransmitter system.
Studies on depression and Cognitive performance
A small study among young adults who showed a depressive inventory score of mild to moderate depression and did not take antidepressants found that those who took two fish oil capsules totaling 1000 mg EPA and 400 mg of DHA considerably improved their depressive symptoms after 21 days. At the end of the study, 67% of participants no longer met the criteria for depression. These results and many similar outcomes can be partly explained by the increase in white matter myelination around the neuronal axons implicated in depression.
Such effects are not only exclusive to individuals with depression or mild cognitive impairment. For instance, a study recruiting over 300 healthy adults between the age of 25-49 showed that after six months, participants who took 360 mg DHA and 900 mg EPA a day had marked improvement in accuracy, speed, and memory scores across all cognitive tasks compared to placebo and DHA rich group. As was stated in the study, these results may be attributed to strengthened communication between brain regions. This is partly due to increased brain-derived neurotrophic factors, developing new connections, and repairing damaged brain cells even in healthy adults.
The recommended dose and where to get it
Most studies with significant results typically use about 2000 mg of EPA and DHA combined. This can be achieved with two cans of sardines, a fillet of salmon, 3 oz of salmon roe a day, or by investing in a quality omega-3 supplement.
It is important to note that many manufacturers omit re-adding the triglyceride backbone back to the omega-3 fatty acid because it is cheaper. This, unfortunately, makes the end product the least bioavailable form of Omega-3.
The Brand I use is KION, and I take double the dose to reach the 2-gram mark daily. Other brands, such as Nordic Naturals (which has vegan options), Thorne, and Pure Encapsulation are also committed to the quality of their supplements.
Lions Mane
Compounds in lions mane
Lion's mane, also known as Hericium Erinaceus, has been touted in the 21st century as one of the leading brain foods. For example, a world-renowned American mycologist and advocate of adaptogenic mushrooms, Paul Stamets, say’s, “Lions Mane may be our first smart Mushroom,” and he goes on to say that “It confers cognitive benefits on our aging population.”
Lion's mane contains compounds called hericenones and erinacines found in the fruiting body (hericium) and mycelia (erinaceus) of the lion's mane mushroom. During digestion, these natural products separate from the mushroom, travel through the bloodstream and cross the Blood-Brain Barrier easily into the vessels where they stimulate Nerve growth factors (NGF) and Brain-derived neurotrophic factors (BDNF) in areas such as the hippocampus.
Understanding NGF and BDNF
Brain-derived neurotrophic factors and Nerve growth factors are members of the neurotrophic family. NGF is a protein that binds to the TrkA and p75 receptor, and BDNF is a protein that attaches to the TrkB and p75 receptor, where it stimulates the growth, maintenance, survival, and proliferation of new neurons called neurogenesis. Although NGF and BDNF are structurally related, expressed in the brain, and both have a part in neurogenesis, there are distinctions.
The most crucial distinction between the two neurotrophins is that they bind to receptors in different brain regions. And although different areas of the brain can communicate with one another by sending signals, each region of the brain has a specific purpose. For example, You can send your package to UPS, and UPS can carry that package to a different destination. However, You, UPS, and the destination all have different purposes.
The purpose of NGF can be summed up as promoting growth and survival in peripheral, sensory, and sympathetic nerve cells, such as information relayed between the body and brain.
And the purpose of BDNF, specifically for cognition, is to promote short, and long-term memory and alleviate symptoms of depression and anxiety.
Studies on cognition and anxiety
A small double-blind study of elderly Japanese men and women diagnosed with mild cognitive impairment taking 3 grams of Lions Mane tablets daily showed significant improvement compared to the placebo group throughout weeks 8, 12, and 16. And the scores reversed four weeks later when the group stopped taking the lion’s mane tablets.
Another study found that after two months, the mice given lions mane took over 2x less time to approach a novel object and 2x more time exploring it than the other mice suggesting an increase in novelty-seeking behavior. Like humans, mice exhibit a remarkably identical anxious response to novel stimuli, even at the molecular level. Mice and humans with “similar alternations in the BDNF gene took significantly longer to get over the innocuous stimuli and stop having a conditioned fear response” (Dr. Fatima Soliman). The anxious response that holds mice and humans back from the unknown can be ameliorated by expressing the BDNF gene.
The recommended dose and where to get it
There isn’t much research on the recommended dose; instead, do what works best for you. Start with 1 gram for the first week by mixing it in coffee, tea, or any shake, unless you’re taking capsules, and adjust accordingly to how you feel. Fortunately, Lion's mane doesn’t typically have side effects. However, if you experience adverse side effects such as stomach discomfort, swelling, or anything more serious, then, by all means, don’t take lions mane or look for another brand.
The product that I’ve consistently used and liked is called Real Mushrooms. Another brand produced by Paul Stamets called Host Defense is also one I recommend. Whatever lion’s mane you choose, keep in mind that the end product should be low in starch and high in beta-glucans (which are polysaccharides found in the cell wall of functional mushrooms).
Creatine
It is commonly understood that creatine has the potential to increase lean muscle mass, improve strength, and expedite recovery during exercise by creating changes within the muscle cell. However, creatine, a compound found in muscle cells, has also been shown to play an essential role in brain energy homeostasis and positively affects working memory and intelligence.
Creatine supplies the brain with energy much faster than any other energy-producing system (glycolytic and oxidative) by binding to phosphate to make phosphocreatine and donating the phosphate to ADP to make ATP. Additionally, creatine ingestion can increase phosphocreatine stores in the brain and increase ATP production during exercise and cognitive tasks.
Studies also show brain-boosting effects independent of ATP production. One study found that creatine supplementation and physical activity increased all mitochondrial biogenesis factors, a cellular process that produces new mitochondria as an adaptive response to stress.
Studies on mood and cognition
A study on sleep-deprived mice showed that the mice who took creatine and drugs increased their plasma dopamine and reduced cortisol levels more than the drug-alone group. These mood-enhancing effects suggest that creatine may activate dopamine receptors independent of the drug used.
Another study testing working memory and intelligence on 45 young adult vegetarian subjects found that the group who took 5 grams of creatine orally improved both measures after six weeks compared to the placebo. It is important to note that vegetarians are much more likely to be deficient in creatine since it is naturally found in animal tissue, and the body can only make about 1 gram per day. Therefore, the significant effect could be a bi-factor of creatine deficiency.
But what about omnivores? Could they benefit as well? Yes, absolutely. However, the more creatine you have in your body, the less likely there will be a cognitive benefit. Studies show that cognitive performance won’t be as notable as a non-meat eater if you regularly eat meat. Nonetheless, if you want to optimize and perform at your best, taking a creatine supplement might be the sail that keeps you moving more efficiently through a task.
The recommended dose and where to get it
To maximize creatine storage quickly, taking 20 grams for 7-14 days is common, followed by a maintenance dose of 3-6 grams. I started with 6 grams for two months but now take 3-4 grams daily, 5-7 days a week.
Fortunately, creatine quality is easy to come by. Whenever purchasing creatine, look for a creatine monohydrate without any fillers (shown next to the ingredients on the nutrition label). The creatine I use is called Thorne Creatine. It's more pricy and blends well into beverages. Nutricost Creatine Monohydrate is my choice when I’m on a budget.
Bottom Line
Many wish to be a better version of their current self. To not be stagnant and regress but to move beyond our current frame of reference into a new space. To be able to hold, cherish, and understand what we have so that we can build and grow from it. Perhaps you’re a college student who needs that subsidiary reserve for a test. Maybe you’re a doctor, lawyer, or entrepreneur looking for a way to get ahead of your comrades. And you wonder whether there is a supplement you could take that would noticeably affect your emotional and/or intellectual cognition. The reality is yes. Although the research is promising, you’re an individual, and what might be advantageous for someone could be less so for you.
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