Evaluating the impact of toxins on metabolic, immune, and brain health
In my course Cognitive Decline: Solving the Puzzle, I discuss four steps to address the impact of toxic chemicals on brain health. In this guide, I go over the steps in more detail.
This material is pulled from my book, Why Isn’t My Brain Working? A Revolutionary Understanding of Brain Decline and Effective Strategies to Recover Your Brain's Health
I highly recommend you have this book on hand as a reference companion to the course as it goes into much more detail on addressing various underlying mechanisms. You can also find more information on my YouTube videos, podcasts, and website articles at drknews.com.
Remove or limit your dependence on toxic home, body, and lawn products as much as possible. For additional reading, see this article.
Brain Inflammation
One of the reasons your brain may not be working is because of inflammation in the brain, also referred to as “neuroinflammation.” Do you have any of these symptoms?
Symptoms of neuroinflammation
• Brain fog
• Unclear thoughts
• Low brain endurance
• Slow and varied mental speeds
• Loss of brain function after trauma
• Brain fatigue and poor mental focus after meals
• Brain fatigue promoted by systemic inflammation
• Brain fatigue promoted by chemicals, scents, and pollutants
Inflammation in the body chronic joint pain, infections, inflammatory bowel disease, or an unmanaged autoimmune condition releases immune messengers called cytokines. These cytokines send messages across the blood-brain barrier that activate inflammation in the brain, which alters brain function and destroys brain tissue. Likewise, inflammation or degeneration in the brain can activate the body’s
immune system and trigger systemic inflammation.
For example, researchers are studying this model as a major cause of chronic depression, which in some cases is the result of brain inflammation decreasing the firing rate of neurons in the frontal lobe. In these cases, people typically don’t respond to antidepressants since the medications do not address the underlying inflammation.
It is always important to consider this inflammatory cytokine model of depression when someone complains of brain fog, chronic pain, swelling, and inflammation. Addressing the causes of inflammation and providing natural compounds to dampen neuroinflammation can produce very promising results.
The brain’s immune system
Microglia cells, the brain’s immune soldiers are at the root of brain inflammation. They determine whether your brain is inflamed and aging too quickly.
Microglia cells are either in a resting state or an active state. In normal conditions, the microglia perform many functions vital for healthy brain function. They dispose of dead neurons, beta-amyloid plaque, and other cellular debris that may interfere with healthy communication between neurons. However, in a heightened state of activation, they create an overzealous inflammatory immune response that causes brain inflammation, or neuroinflammation.
A long-term consequence of chronic neuroinflammation is neuron death and the development of neurodegenerative disorders.
Many things can activate the microglia and inflame the brain
Mechanisms that increase the risk of activating brain microglia
• Diabetes and high-carbohydrate diets lead to the production of glycosylated end products, which activate the microglial cells
• Lack of oxygen from poor circulation, lack of exercise, chronic stress response, heart failure, lung disorder, anemia
• Previous head trauma
• Autoimmune reaction to neurological tissue
• Dietary gluten for those who are gluten intolerant
• Low brain antioxidant status
• Alcohol and drug abuse
• Environmental pollutants
• Systemic inflammation
• Inflammatory bowel conditions
• Compromised blood-brain barrier
Microglia have no off switch
The body’s immune system can turn off the immune response when necessary. Otherwise, a splinter might continue to produce swelling and pus long after it has been removed.
Unfortunately, the brain is quite simplistic when it comes to inflammation. Once microglia become overstimulated, they are like fierce little Chihuahuas with AK-47s. They startle at anything that comes by, firing off their machine gun in a 360-degree circle, including at healthy brain tissue.
When microglia are overactivated, neurons die. With no built-in off switch, the microglia can continue on their rampage for their entire lifespan, destroying healthy brain tissue and speeding up brain degeneration in the process. That there are 10 microglia cells for every neuron doesn’t help, nor does it help that they recruit other microglia cells during the inflammatory process.
Microglia activation induces a domino effect in which one microglia activates another, and so on. These activated cells perpetuate an ongoing vicious cycle that can lead to chronic and persistent neuroinflammation that may last for weeks, months, or years.
Microglia cells are not all bad. The problem is that they don’t operate well in an environment that includes processed, genetically modified, and inflammatory foods, heavy metals, bacteria, environmental pollutants, or other harmful substances all heightening their activation.
Key concepts related to brain inflammation
• Your brain is saturated with immune cells called microglia cells.
• The microglia cells perform many important functions under normal conditions to help transmission between neurons, such as the removal of dead neurons and plaques.
• In a heightened state of activation, microglia create a persistent, self-perpetuating state of neuroinflammation.
• Microglia cells can activate and promote neuroinflammation in response to inflammatory diets, head trauma, lack of oxygen, diabetes, environmental toxins, autoimmunity, and systemic inflammation.
• Neuroinflammation decreases the speed of neuron responses and leads to symptoms such as brain fog and depression. Chronic neuroinflammation leads to neuron death and neurodegenerative changes.
One of the biggest risks of activating the microglia is a leaky blood-brain barrier. The blood-brain barrier is a finely woven mesh of astroglial cells and blood vessels surrounding and protecting the brain. It is designed to allow only nano-sized particles in or out as needed and keep unhealthy things out. However, like the gut, it can become damaged and “leaky,” allowing dangerous intruders to slip in and potentially trigger the ultra-sensitive microglia. The blood-brain barrier is extremely vulnerable to various aspects of modern life, such as inflammation and high cortisol from chronic stress. The most common symptom of a leaky blood-brain barrier is brain fog or reduced brain function after exposure to environmental insults such as gasoline fumes, chemical cleaning products, or inflammatory foods. The good news is that even though the blood-brain barrier degrades easily, it also has the potential to regenerate quickly. Simply stabilizing your blood glucose and cortisol levels, reducing inflammatory
triggers such as gluten, clearing up a gut infection or chronic virus, boosting your antioxidant system, and supporting anti-inflammatory mechanisms can help restore the blood-brain barrier and better protect your brain.
Causes for the breakdown of the blood-brain barrier
• Chronic stress
• Alcohol
• Elevated glucose and diabetes
• Chronic environmental toxic exposure
• Elevated homocysteine from B vitamin deficiency
• Poor diet and antioxidant status
• Systemic inflammation
The pharmaceutical industry appears to be focused on developing drugs to shut down microglia cells, which would be therapeutic in Alzheimer’s and Parkinson’s diseases, head trauma, stroke, and other conditions that cause rapid inflammation and degeneration. However, their success has yet to match the performance of many natural compounds that have demonstrated in peer-reviewed literature excellent microglia-quenching abilities. They are flavonoids that include apigenin, baicalein, resveratrol, catechin, rutin, and curcumin. These flavonoids cross the blood-brain barrier and have powerful anti-inflammatory effects in the brain.
One might also want to use these flavonoids preventively, considering the many stressors we endure these days. I personally take a combination of all these flavonoids daily to decrease brain-based inflammation because I know, like anyone else with a stressful lifestyle, that I have some degree of brainbased inflammation that I want to dampen. You may not notice their effects if you don’t have a major inflammatory process, but they can still be protective.
The effects of these flavonoids can be profound for those suffering from brain fog, a condition in which it’s hard to think clearly, and one feels disconnected or fuzzy-headed. Inflammation in the body, whether in the joints or the skin, is often painful. However, the brain has no pain fibers, so inflammation doesn’t hurt. It presents instead as brain fog.
Brain fog can be secondary to a food intolerance, lack of sleep, gut infections, hypothyroidism, extreme stress, autoimmunity, systemic inflammation, and other factors. Brain inflammation distorts healthy neurotransmission, leading to fuzzy and incomplete synapses and symptoms of brain fog. If your brain fog clears up with the flavonoids, that indicates brain inflammation is an issue. These flavonoids are useful for patients with brain fog, depression, and slow mental speed associated with chronic pain, swelling, or autoimmunity.
Although these flavonoids can address brain inflammation, they do not necessarily address the underlying cause of inflammation. That should always be dealt with as well.
In addition to dampening neuroinflammation, these compounds have also been suggested as nutritional support for neurodegenerative conditions, such as brain trauma, stroke, peripheral neuropathy, and overall brain antioxidant protection. I use them in my practice with all cases of head trauma and degenerative brain conditions. I find that using the flavonoids in combination creates a synergistic effect; however, using any of them in isolation is also effective.
The biggest clinical issue with these flavonoids is using an amount large enough to dampen neuroinflammation. Supporting neuroinflammation is not a simple, linear model in which dosage can be based on a patient’s body size or symptom severity. It is like asking how much water you need to put out a fire it depends on the extent of the inflammation. It is not uncommon for a person with neuroinflammation to require several hundred to a couple thousand milligrams of each compound to dampen their inflammation. The biggest mistake clinicians and individuals make is not using doses significant enough to dampen neuroinflammation.
The best way to use these compounds is to start with a small dose and increase it slowly until the desired outcome is reached. The more symptomatic you are, the easier it will be to identify the correct dosage. For example, if you take 200 mg daily of curcumin and do not notice any impact on your inflammationbased depression, brain fog, or poor mental endurance, you may notice significant improvement at 2,000 mg daily.
There is no way to determine the correct dosage for those with no noticeable symptoms, but 100–500 mg of each flavonoid may be good as a preventive strategy. It is a brain-protection strategy I use for myself.
In addition to using flavonoids to dampen neuroinflammation, you must address pro-inflammatory factors in your diet and environment and neurological autoimmunity.
Compounds that dampen microglial neuroinflammation
• Apigenin
• Luteolin
• Baicalein
• Resveratrol
• Rutin
• Catechin
• Curcumin
Testing for blood-brain barrier permeability
• Cyrex Labs Array 20 Blood-Brain Barrier Permeability™ screen
• S100B test
The role of the liver in loss of chemical tolerance
Symptoms of poor liver detoxification
• Acne and unhealthy skin
• Bloating
• Swelling
• Hormone imbalances
• Weight gain
• Poor bowel function
If liver function becomes compromised, it can increase your toxic load and chemical intolerance. Likewise, toxic exposures and inflammation can hinder liver metabolic function.
The common term for how the liver works is “liver detoxification.” However, I want you to know that this is not the term researchers use. If you decide to research the subject yourself on PubMed, an online repository of peer-reviewed studies, you should instead use the terms “hepatic biotransformation,” “detoxication,” or “metabolomics.”
Liver detoxification basics
In a nutshell, liver detoxification involves making fat-soluble compounds water-soluble to eliminate them in the urine, feces, or sweat.
When a fat-soluble compound enters the liver, it enters the “Phase I pathway.” The Phase I pathway changes the structure of the compound for the sole purpose of having molecules attach to it in the Phase II pathway to prepare it for elimination.
Phase II has several pathways that metabolize the compounds in different ways: methylation, glucuronidation, sulfation, acetylation, and glutathione conjugation. Once molecules are added to the compound in Phase II, it is heavy and stable enough to be eliminated from the body safely.
In Phase III, the metabolized compounds are end products ready for elimination. This phase depends on a sufficiently alkaline diet (a diet rich in produce with little to no processed foods) and healthy bile synthesis and gallbladder function, especially for fecal elimination. Naturally, healthy bowel function and lack of constipation are important for this phase as well.
When liver detox pathways don’t work
When a compound goes through Phase I, it becomes more immune-reactive and pro-inflammatory.
Theoretically, this is not a problem as Phase II is there to sweep in and stabilize these immune reactive compounds.
However, inherited genetic traits may cause variations or defects in how these pathways work, one reason medications affect people differently. Just because you have a genetic predisposition does not
necessarily mean that gene will express itself, but factors such as diet or lifestyle can trigger these genes. The detoxification pathways have also been shown to gradually lose integrity as we age.
Two possibilities exist when a person’s liver Phase II pathway is hindered. One is that an already inflammatory compound, such as an environmental toxin, is made more inflammatory in Phase I. Because a hindered Phase II pathway cannot complete the job, this more toxic compound goes back into circulation, which may activate the immune system and inflammation.
Because the liver cannot metabolize it, this new toxic metabolite is now officially a toxicant, increasing your chemical load and risk of developing inflammatory conditions such as loss of chemical tolerance and autoimmunity.
The second possibility is that formerly inactive compounds are metabolized into immune-reactive compounds. For instance, if the liver fails to detoxify a xenoestrogen, which resembles natural hormones, it can attach to hormone receptor sites and disrupt metabolism. Even the body’s own estrogen can be transformed into a more toxic version that competes with healthy forms of estrogen for receptor sites.
Researchers have linked these detoxification breakdowns with serious neurological diseases such as Alzheimer’s or Parkinson’s. For instance, in one case study, researchers investigated why a man developed a sudden onset of late-stage Parkinson’s symptoms after exposure to a particular pesticide. A genetic profile of his liver detoxification pathways revealed a defect in the pathways that metabolized this pesticide. Because aging also impacts liver detoxification, older people taking multiple drugs may react to their medications.
Our world overlooks the effect of environmental compounds on health, but it is very real. It’s like when people refused to believe the connection between germs and infection because they couldn’t see them. We cannot see these environmental compounds, but the research shows that, without question, they negatively impact our health. Although we are all coping with exposure, the integrity of our body’s defense system is an important factor in health.
Nutrients to support healthy liver detoxification
Different nutritional and botanical compounds support the liver’s detoxification pathways. I use all of these as they work well together, and we can’t be sure which pathway is compromised.
Phase I and Phase II support
The compounds that support these pathways are milk thistle seed extract, dandelion root extract, gotu kola extract, panax ginseng, L-glutathione, glycine, N-acetylcysteine, and DL-methionine. In addition to supporting Phase I and II, these compounds also support blood flow and cell growth in the liver.
Methylation is a Phase II detox pathway also important for healthy brain function. Nutrients that support methylation include choline, trimethylglycine, MSM, beetroot, and betaine HCl. These nutrients also support homocysteine metabolism (for an anti-inflammatory effect) and healthy bile synthesis and metabolism.
These nutrients support healthy bile synthesis and elimination to help remove metabolized toxins from the body. They include dandelion root extract, milk thistle seed extract, ginger root, phosphatidylcholine, and taurine.
Detoxification and glutathione support
These nutrients support liver detoxification, glutathione levels, and recycling. They include Nacetylcysteine, cordyceps extract, Gotu kola extract, milk thistle seed extract, L-glutamine, and alphalipoic acid.
How the brain affects liver detoxification
Poor brain function can affect liver detoxification. In my brain book, I discuss how brain degeneration and declining brain function can impact autonomic function and cause symptoms such as poor digestion, dry eyes, incontinence, high blood pressure, etc. Poor brain function can also impact the liver and its ability to detoxify the body.
In some cases, exercises that stimulate the vagus nerve, which relays communication between the brain and the organs, can help neurologically activate or reboot liver function. This includes vigorous gargling, singing loudly, engaging the gag reflex, and coffee enemas. Symptoms of insufficient vagal tone include poor intestinal motility (constipation), poor digestive enzyme production (bloating, indigestion), floating stool or undigested food in stool and symptoms of poor liver detoxification.
To learn more about vagus nerve activation, link to this article on my site.
The Phase I pathway of liver detoxification uses a diverse family of enzymes called cytochrome P450 (CYP450). As it turns out, the brain also contains CYP450 enzymes for its own detoxification. These enzymes are responsible for breaking down toxins in the brain for elimination. Unfortunately, brain inflammation and poor brain health can hinder the function of these CYP450 enzymes. Poor brain detoxification has been linked with various neurological and psychiatric disorders.
The compounds we use to support liver detoxification are ineffective for brain detoxification because they cannot cross the blood-brain barrier. The key to supporting healthy brain detoxification is to prevent and manage inflammation in the brain.
Supporting the liver to manage the loss of chemical tolerance
The most effective compounds we’ve seen for dampening inflammation from toxins and their impact on the liver are high doses of emulsified resveratrol and curcumin given in combination. Although each is a powerful anti-inflammatory compound alone, given together, their effect is four-fold greater, and when emulsified, they are even more powerful. Studies show that both compounds effectively protect the body from damage due to environmental toxins and dampen inflammation.
You must take high enough amounts of each of these to notice an effect. In studies, subjects were given up to 400 mg of resveratrol and 800 mg of curcumin daily. However, the necessary dose is different for everyone, so don’t assume that is the correct dose for you.
Refer to the recommended nutraceuticals in Step Two.
Additionally, glutathione is powerful and considered the body’s master antioxidant. Use as much as you need to quench inflammation. My preferred source is an oral liposomal glutathione called Trizomal Glutathione, which I formulated for Apex Energetics. Some patients need as many as three full syringes (more than 1,500 mg) daily
Other options are S-acetyl-glutathione or compounds that are precursors to glutathione and support glutathione recycling: N-acetyl L-cysteine, cordyceps extract, Gotu kola, milk thistle, L-glutamine, and alpha-lipoic acid. I formulated a product for Apex Energetics called Glutathione Recycler.
Most people tolerate glutathione supplementation. However, some do not. Start with a small dose to test your tolerance.
More and more people today show up in their practitioners’ offices with health problems triggered by environmental compounds. What do many of these practitioners do? They test for heavy metals and environmental chemicals, which always come back positive, and then chelate the patient using chemicals such as DMSA, DMPS, or EDTA.
Or they put the patient on an intense liver detoxification program. If a patient has adverse reactions, this is simply dismissed as a detox reaction. But the truth is that chelating someone with neurological autoimmunity and loss of chemical tolerance can be devastating and permanently destroy brain and nerve tissue.
Why? Because research has found that chelation pulls heavy metals out of body tissue and redistributes them, so they make their way into the brain, promoting toxicity, inflammation, neurodegeneration, and sometimes serious side effects.17 18 19 In these cases, chelation promotes immune activation from chemical intolerance it’s like giving a person with celiac disease gluten. Studies since 1999 have repeatedly shown that chelation pushes toxins into the brain, yet it continues as a popular practice.
Does this mean I’m anti-chelation? No, I am not anti-chelation. Chelation is unsafe for people with a loss of chemical tolerance who have exaggerated immune responses to chemicals.
However, there are times when chelation is appropriate, such as in the case of acute exposure to toxic chemicals or heavy toxicity. A serum heavy metal test, which most chelation enthusiasts disdain, can help determine toxicity levels in the case of acute exposure.
Also, in some cases, when a neurodegenerative disease is severe and progressed, it is assumed these toxic metals have already reached the brain and removing them might be advantageous. However, for a relatively healthy person who isn’t suspected of having heavy metal toxicity in the brain yet who shows blood-brain barrier permeability, chelation can unnecessarily expose the brain to heavy metals.
Chelation must not be undertaken until the person demonstrates the immune barrier integrity and glutathione status is restored.
A person must be healthy enough to tolerate the adverse reactions chelation may produce and always calculate the clinical risk-to-benefit ratio. Make no mistake, there are associated risks and reactions with chelation therapy, such as redistribution of the metals into the brain.
How do you know if you suffer from a loss of chemical tolerance? We can test for loss of chemical tolerance by measuring antibodies to environmental chemicals. Positive antibodies indicate an overzealous immune reaction to environmental chemicals and, thus loss of chemical tolerance.
Do not confuse testing for antibodies with tests that measure the quantity of chemicals and heavy metals as shown in urine, hair, stool, or with a DMPS challenge. When it comes to loss of chemical tolerance, the immune system’s tolerance to these compounds is the key factor, not the quantities of the compounds in the body. This explains why some people cannot tolerate even trace exposures without reacting.
Standard lab tests for heavy metals
Most labs measure levels of environmental chemicals in the body using serum, urine, hair, or stool, and each type of testing has its limitations. Blood serum testing for acute toxic exposures is conventional toxicology's most commonly accepted test. However, this test is criticized for being inaccurate for nonacute exposures or for its inability to measure levels of toxins stored in tissues.
The reproducibility and accuracy of hair testing are controversial and inaccurate when samples are submitted to various laboratories. I do not find hair testing accurate or reliable enough for clinical use. Urine and stool tests also raise concerns in terms of reliability and reproducibility.
Other tests involve a “challenge” with a chelating agent such as dimercaptosuccinic acid (DMSA), 2-3 dimercapto-1-propanesulfonic acid (DMPS), or ethylenediaminetetraacetic acid (EDTA). A challenge test typically involves a baseline urine measurement for heavy metals and then a second urine test after a challenge with a chelating agent. If the challenge test shows higher levels of heavy metals, it is theorized the individual has high amounts of toxins in their tissues.
Which test you’re given depends on your healthcare provider’s bias and training, and there is much controversy in this field. Regardless of the test, I personally find that measuring the quantity of an isolated heavy metal or environmental toxin is a limited diagnostic marker compared to assessing an individual’s immune tolerance to environmental chemicals.
We can screen for elevated antibodies to environmental compounds with the Chemical Immune Reactivity Screen from Cyrex Laboratories. Elevated chemical antibodies indicate an exaggerated immune response to the chemicals, which can trigger neurological autoimmunity or degeneration of the brain because of systemic inflammation.
Ideally, we should not have high antibodies to common environmental chemicals found in plastic bottles, upholstery, carpeting, dry cleaning, cosmetics, etc. Elevated antibodies indicate loss of chemical tolerance and risk for abnormal immune reactions to everyday environmental chemicals.30
Cyrex Array 11 Chemical Immune Reactivity Screen
Aflatoxin antibodies
These antibodies indicate immune reactivity to a toxic metabolite from fungi called mycotoxins. These toxins tend to be found on stored grains and are a common source of exposure in the U.S. food supply.
Formaldehyde antibodies
These antibodies indicate immune reactivity to chemicals in commonly used plastic products such as kitchen utensils, toys, adhesives, etc.
Trimellitic and phthalic anhydride antibodies
These antibodies indicate immune reactivity to chemicals used in the production of plasticizers and are found in PVC pipes, fiberglass products, paint resins, perfumes, insect repellents, etc.
Isocyanate antibodies
These antibodies indicate immune reactivity to chemicals in polymers and polyurethane products used in various foams and insulators in bedding, window frames, shoe padding, etc.
Benzene antibodies
These antibodies indicate immune reactivity to petrochemicals from gasoline, with exposure typically coming from burning gasoline.
Bisphenol-A antibodies
These antibodies indicate immune reactivity to chemicals in commonly used plastic products such as plastic bottles and bags.
Tetrabromobisphenol-A antibodies
These antibodies indicate immune reactivity to chemicals in fire retardants used on most new furniture, mattresses, and carpets.
Tetrachloroethylene antibodies
These antibodies indicate immune reactivity to a chemical found typically in dry cleaning and upholstery products.
Mercury and heavy metals antibodies
These antibodies indicate immune reactivity to metal compounds found in lead pipes, paints, and dental amalgams.
Glutathione is a safe chelator
Glutathione doesn’t just protect cells by acting as an antioxidant. It is also a safe chelator, meaning it can bind to environmental compounds and help remove them from the body. Nutrients that support glutathione levels and recycling have been shown to chelate and excrete heavy metals from the body without displacing them into other tissues, such as the brain.
Although glutathione does not have the same chelating and binding ability as commonly used chelating agents such as DMSA, DMPS, and EDTA, it is a very attractive form of therapy because it chelates without redistributing metals into other tissues.
Glutathione also binds to metals to form complex structures that are less toxic and immune-reactive than unbound metals. These factors make glutathione a preferred source of support for those that have lost their chemical tolerance. Also, glutathione support is available as a dietary supplement over the counter, unlike DMSA, DMPS, and EDTA, which require a prescription.
Additional Resources from Dr. Kharrazian
This material is pulled from my book, Why Isn’t My Brain Working? A Revolutionary Understanding of Brain Decline and Effective Strategies to Recover Your Brain's Health
I highly recommend you have this book on hand as a reference companion to the course as it goes into much more detail on addressing various underlying mechanisms. You can also find more information on my YouTube videos, podcasts, and website articles at drknews.com.
For more guided support, you may also be interested in my courses: Save Your Brain: The Six-Week Brain Rescue Program or Cognitive Decline: Solving the Puzzle.
