The Mechanisms of Optimal Brain Health

Volume 1, Part 1


Breakthroughs in brain research have skyrocketed during the past several decades. A new perception of the brain has emerged, which accounts for the interaction between the cranial brain and a «second brain», which resides within the gut. Scientists now explain the brain in terms of the microbiome-Gut Brain Axis (GBA), a bidirectional communication system between the microbiome, the central nervous system (CNS), the autonomic nervous system (ANS), the enteric nervous system (ENS), and the hypothalamus pituitary adrenal (HPA) axis.1

The HPA axis coordinates adaptive responses to all stressors (stress-inducing agents), including those that are physical, mental, and emotional.2 In fact, the HPA axis is part of the limbic system, which is the region of the brain that governs emotion, behavior, motivation, long-term memory, and olfaction.3 When we encounter stress, the hypothalamus secrets corticotropin-releasing factor (CRF), which stimulates adrenocorticotropic hormone (ACTH) secretion from the pituitary gland, which then causes the adrenal glands to produce and release cortisol. Stress hormones like cortisol are one of the primary mechanisms by which the brain and gut communicate with each other.

Neurotransmitters are another major mechanism by which the brain and gut communicate. In fact, the ENS includes between 200 and 600 million neurons, which are embedded in the walls of the alimentary canal from the esophagus to the anus.4 This is more neurons than are contained by either the spinal cord or the peripheral nervous system. The ENS produces over 30 different neurotransmitters, including GABA, serotonin, melatonin, histamine, and acetylcholine. Around 95% of the body’s serotonin is located within the gut.5 Most of these neurotransmitters are produced by or regulated by the gut microbiome, thus demonstrating its profound importance and influence.6

The Gut Microbiome and the Brain

Besides playing a direct and substantial role in digestion, the microbiome also affects the CNS via neural, neuroendocrine, neuroimmune, and humoral links.7 Significantly, our mood and emotions can be regulated, or at least influenced by the microbiome. In 2013, Dr. Ted Dinan and his colleagues at University College Cork coined the term «psychobiotics» to describe an emerging class of probiotics that are capable of altering mood. «Such “mind-altering” probiotics», they explained, «may act via their ability to produce various biologically active compounds, such as peptides and mediators normally associated with mammalian neurotransmission».8

In terms of behavior, the microbiome is also believed to play a critical role in anxiety, motivation, and even socialization. In one study, scientists administered Lactobacillus probiotics to mice, which resulted in the mice behaving less anxiously and being more willing to explore open, exposed areas of their environments. Moreover, the mice exhibited increased levels of GABA, which is associated with decreased anxiety and depression.9 For another study, when scientists transported microbes from the guts of one strain of mice to another, the receiving group began exhibiting behavioral traits of the donating group. For example, the receiving group, which had previously been hesitant to explore unchartered areas, became far less inhibited.10 Regarding socialization, germ-free mice that are raised in sterile environments, thereby preventing the proper development of the microbiome, demonstrate abnormal social behavior and clear autistic-like traits.11

Glutathione and Brain Health

Glutathione, also known as «the master antioxidant», is one of the body’s most important detoxification molecules. Antioxidants are the body’s defense against free radicals (dangerous molecules that cause inflammation and other damage, including accelerated ageing, DNA strand denaturing, and mitochondrial damage).12 Free radicals arise from many external influences, including environmental pollution, emotional stress, physical stress, pharmaceutical drugs, cigarette smoke, electromagnetic pollution, denatured foods, artificial preservatives, herbicides, pesticides, and common household chemicals. On the other hand, free radicals also arise from normal biological processes, particularly the metabolizing of oxygen. Despite only constituting about 2% of body weight, the brain consumes about 20% of the body’s oxygen, which means it generates a considerable amount of reactive oxygen species (free radicals formed the oxygen metabolism).13 The brain’s glutathione needs, therefore are high. Insufficient brain glutathione uptake, over time, can contribute to cognitive decline. For a breakthrough study in 2015, scientists made the novel discovery that glutathione levels constitute a clinically relevant biomarker for both mild cognitive impairment and for Alzheimer’s disease.14

Omega-3 and Brain Health

Omega-3 fatty acids are one of the most widely studied molecules with respect to brain health and are unambiguously one of the most beneficial molecules for preventing inflammation and cognitive decline, while mitigating the consequences of brain ageing.15, 16 As we grow older, the brain becomes increasingly susceptible to inflammation, which underlies declined learning and memory function. One way scientists quantify these declines is by measuring long-term potentiation (LTP) — an electrophysiological property of certain neuronal circuits, which is used as a model to investigate the pathways involving synaptic plasticity, learning, and memory.17 Dietary supplementation of long-chain omega-3 (EPA and DHA) has been shown to reverse age-related impairments in LTP.18

It’s important to clarify that omega-3 fatty acids appear in short-chain, as well as long-chain versions. The short-chain version is alpha-linolenic acid (ALA), whereas the long-chain versions are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). ALA is found in various nuts and seeds, particularly flax seeds and chia seeds. DHA and EPA, on the other hand, can only be obtained from animal-food sources, most notably oily fish. Broadly speaking, the health benefits of omega-3 come from the long-chain molecules, DHA and EPA.19 The body can convert ALA into the beneficial DHA and EPA forms, but this conversion is inefficient.20 Therefore, it’s always preferable to consume omega-3 in its DHA and EPA forms, whether from supplements or food sources. Besides the aforementioned benefits, other brain-related benefits of long-chain omega-3 include:

  • EPA has been shown to be as effective as Prozac in treating depression.21
  • For infants and young children, DHA supplementation is associated with increased IQ, improved communication and social skills, less behavioral problems, decreased risk of developmental delay, and decreased risk of ADHD and autism.22, 23, 24
  • Fish consumption and omega-3 supplementation are linked to decreased age-related mental decline and a reduced risk of Alzheimer’s disease.25, 26
  • DHA supplementation is linked to improved quality of sleep.27, 28

Leaky Brain Syndrome and its Prevention

The blood brain barrier (BBB) is a highly selective, semipermeable membrane barrier that keeps circulating blood from the brain separate from extracellular fluid in the central nervous system (CNS), thereby protecting the brain by denying access to any potentially harmful molecules. «Leaky brain» is a colloquial term for BBB hyper-permeability, a condition whereby the BBB becomes increasingly permeable, thereby setting the stage for various degenerative brain conditions.

A multitude of factors contribute to leaky brain, including inflammation, excessive stress (resulting in an overactive HPA axis), leaky gut, elevated homocystein, and many other factors.29, 30, 31, 32 There are many tests that practitioners utilize to help determine whether or not a patient has or is prone to leaky brain. These tests include the GABA-EEG test, the Evans Blue-dyed albumin test, and the elevated MMP9 test. If allowed to progress, leaky brain can contribute to many serious conditions, including:

  • Brain fog.33
  • Alzheimer’s disease.34
  • Depression.35
  • Cognitive decline.36

Neurogenesis and Brain Plasticity

With age, the brains of most people decline, but this need not be the case. Exciting new research demonstrates that adult brains are capable of neurogenesis (the birth of new neurons) and neuroplasticity (the malleability of neural circuits).37 In early 2017, scientists at the University of Alabama at Birmingham, found that newly born granule cell neurons in the dentate gyrus wire themselves into neural networks by forming synapses via neuroplasticity. The dentate gyrus is the region of the hippocampus that deals with new episodic memories, the spontaneous exploration of novel environments, and various other functions.38 One of the best ways to stimulate neurogenesis is through regular exercise. Exercise directly increases synaptic plasticity by affecting synaptic structure and strength, while simultaneously strengthening the systems that underlie plasticity including neurogenesis, metabolism and vascular function.39

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