My seven-year-old son was actively regressing. After being told there was "no medical reason" for his worsening autistic symptoms, I went searching for answers. After scouring the internet, I finally came across something that made sense – something that could explain how my son's autism and my tendency toward autoimmunity might be linked. It was logical, scientific and actionable. It was a series of podcasts by Dr. Kendal Stewart, otolaryngologist, neurotologist, skull-base surgeon and neuroimmune specialist. This man was putting together more pieces of this puzzle than anything else I could find. Soon, I understood autism and many other common conditions as neuroimmune syndromes.
Dr. Stewart treats what he calls neuroimmune syndromes, conditions in which the underlying problem involves both the nervous and immune systems, typically in a combined state. These conditions are often described for their symptoms. Since the cause is not fully understood, treatment for these conditions is typically aimed at managing symptoms. Dr. Stewart takes it a step further by attempting to address the body's underlying weaknesses and deficiencies in order to restore function.
At the root of most of these problems is a methylation deficiency. Methylation is a really important process in the body which I am neither qualified nor motivated enough to try to explain the intricacies of. You nerds can google it if you want. Let's just say that a methylation deficiency can cause all kinds of things in your body to get all jacked up. Yes, "all jacked up" is some pretty fancy medical terminology. Stay with me, here.
I'll do my best to explain just what you need to know and spare you the boring details. In a nutshell, methylation has to do with the body's ability to process and deliver certain nutritional elements where they are needed in the body. It is responsible for at least 250 processes in the body, including the process of turning genes on and off. Many nutrients are involved, but B vitamins are the major players here. Since they are water-soluble, they need to be methylated in order to reach the fatty environments of the nervous system, immune system and mitochondria where they are vital for proper functioning of the body.
This is accomplished with the help of certain enzymes. You may have heard of methylenetetrahydrofolate reductase, or MTHFR. This is the enzyme that catalyzes the seventh and final step of folate (vitamin B9) metabolism. Mutations of the gene that codes for this enzyme (also called MTHFR) are quite common. If you have such a mutation, the amount of bioactive folate or methyl folate (also called L-5-methyltetrahydrofolate or 5-MTHF) that is available within your cells will be less than optimal. Besides MTHFR mutations, you can also have deficiencies at any of the preceding steps in the folate cycle. Or you may have weaknesses in the processing of one of folate's co-factor vitamins, B-12. Poor diet and nutrient malabsorption problems won't help either, of course. And if you have folate receptor autoantibodies on top of all that, you'll be in pretty sad shape.
Folate is necessary for energy production in the body. It's essential for making DNA and RNA, our genetic material. It's needed for making new cells of all types, so it's especially important during times of rapid cell division, such as early childhood, adolescence and pregnancy. Since new blood cells are constantly being made in our bodies, folate deficiency is a major cause of anemia. Deficiency of this essential nutrient is also linked to conditions such as heart disease, stroke and cancer. Suffice it to say that folate is pretty darn important.
The word folate comes from the Latin folium, meaning "leaf." This is because the main source of folate is green leafy veggies. Ya'll get enough of those, right? And of course your kids do, right? Riiight. Well if you don't, you probably get a lot of your folate in the form of folic acid, a synthetic version of the nutrient that's been added to cereal grains (in the U.S. and many industrialized countries) since the 90s. This was done to reduce the incidence of severe birth defects called neural tube defects.
If you're part of the estimated 40-60% of the population with MTHFR genetic mutations, your ability to convert folic acid (synthetic folate) to 5-MTHF (the active form) is impaired. This impairment can range from mild to severe, depending on the type and number of mutations you have that affect folate metabolism.
If your genetic weaknesses are bad enough, you're going to run into problems sooner or later. Recall that folate is particularly important to the nervous and immune systems. Now I'll explain how we get into the neuroimmune syndromes.
Consequences of Methylation Deficiency
Impaired Production of Neurotransmitters
B vitamins are needed to make neurotransmitters (chemical messengers), especially serotonin and dopamine. Serotonin is our "happiness hormone," so an insufficiency may cause anxiety and depression. We typically associate dopamine with pleasure, reward and motivation, so it's easy to see how dopamine insufficiency is involved in things like addiction and gambling problems. But dopamine is involved in so much more. Dopamine is a biggie.
Dopamine also affects such things as short-term memory, concentration, focus, organization skills, eye tracking, eye movement and focusing, sleep patterns, mood stability, hormonal regulation, bowel motility, fine motor skills, seizure threshold, pain threshold and more. Dopamine insufficiency causes poor delivery of information to the brain and poor processing of that information as well as anxiety, irritability, cognitive difficulties, and slow reflex responses. Anyone have ADD/ADHD, learning disorders or processing problems? Chances are you've got a dopamine issue.
Immune System Imbalance
Ok, so how does a methylation deficiency affect the immune system? Wouldn't it cause immune deficiency? No, not exactly. It causes immune imbalance.
An imbalance develops between two important types of immune cells: T-cells and B-cells. T-cells are responsible for going after the bad guys: harmful bacteria, viruses and cancerous cells. When T-cells become deficient, the body compensates with another type of immune cell: the B-cell. These are your antibody producers. Too much B-cell activity means lots of inflammation manifested by such things as allergies, food sensitivities, asthma, gastrointestinal inflammation and atopic rashes such as eczema.
Science has hinted at immune system abnormalities in autism for decades. A small study published in 1990 was the first to observe reduced numbers of T-cells in autistic subjects. Although this immune system involvement has been debated since the 1990s, research in this area has been surprisingly (or perhaps not-so-surprisingly) slow. Dr. Stewart tests T-cells in his autistic patients and their results routinely come back abnormal. Each time an abnormal result is recorded, someone from the State of Texas calls his clinic to inquire whether the patient with the abnormal result has HIV/AIDS. No, they do not have HIV/AIDS – they have autism, a neuroimmune syndrome!
Pathogens and Viral Activation
When T-cells are deficient, the body has a hard time keeping pathogens at bay. One may suffer from chronic or recurring infections, such as bacterial, yeast or parasitic. An imbalance of organisms in the gut, known as dysbiosis, is a likely consequence, altering the all-important gut-brain connection that everyone's talking about these days. Yes, the gut is so important that it's even being called our "second brain." For an interesting discussion of this, read Dr. Perlmutter's book, Brain Maker (includes a chapter about autism) or listen to Dr. Stewart's podcast:
Viruses stay with us after the active infection is over. Normally, they are kept dormant by the healthy immune system. But when the immune system is not healthy, they can sometimes reactivate and cause problems. A well-known example of this would be the chickenpox (varicella-zoster) virus coming back years later as shingles. A handful of these neurotropic viruses – viruses that infect the nervous system – are known to stick around and cause problems. For example, the Epstein–Barr virus (of mononucleosis fame) is associated with certain cancers and autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and lupus.
Healthy T-cells are needed to keep the viruses suppressed. So, while the T-cells are slacking off, the B-cells are working overtime trying to fight these pathogens the best way they know how: with chronic inflammation.
Impaired Detoxification and Oxidative Stress
Methylation deficiency leads to decreased production of glutathione, the body's chemical cleanser and master antioxidant. Insufficient glutathione leads to buildup of toxins and cell damage due to oxidative stress. This, in turn, leads to further depletion of glutathione and even more toxic buildup and oxidative stress. And the vicious cycle continues. Glutathione also plays an important role in immune system function and inflammation control.
In addition, decreased production of metalloproteins that clear heavy metals from the body leads to buildup of these highly toxic substances.
Decreased Production of Nitric Oxide
Nitric oxide is a gas (not to be confused with nitrous oxide, "laughing gas") that, among other things, plays an important role in circulation, brain health, immune cell function, digestion and the health of muscle cells and mitochondria. Working alongside our hormones, it is involved in communication between cells to maintain normal bodily functions. It's produced naturally in the body from arginine, an amino acid obtained from protein-rich plant and animal sources such as beef, pork, poultry, seafood, nuts, seeds and legumes. A downstream effect of poor methylation is decreased production of nitric oxide. Named Molecule of the Year in 1992, nitric oxide plays a very important role in our overall health.
Decreased Steroid Hormone Production
Another consequence of methylation deficiency is decreased production of steroid hormones. Insufficient steroid hormones leads to poor inflammation control.
Hmm . . . there's that word again – inflammation. That seems to be a theme here. Inflammation is an appropriate and important immune response, but there's such thing as too much of a good thing. The majority of Dr. Stewart's patients with neuroimmune syndromes have a genetic tendency toward aggressive inflammation.
These are just some of the effects of poor methylation. Clearly, proper methylation is a cornerstone of good health!
Methylation Deficiency and Autism
So all of this can't be good for a developing child, right? Of course not! The child may struggle until they eventually just run out of gas, as my son did. Or, when faced with a big enough stressor (a "triggering event") they will be sent down a rabbit hole without the resources to get themselves out. If the triggering event happens in infancy, before language has developed, the child will have nonverbal autism. If it happens later on, the child will be higher functioning on the autism spectrum. A triggering event during the school-age years and beyond may lead to a diagnosis of ADHD, chronic fatigue syndrome, fibromyalgia or any of the neuroimmune syndromes.
It makes so much sense. We now know that chronic inflammation of the brain is a hallmark of autism. And so many of the things we see in autism, such as allergies, food sensitivities, gastrointestinal inflammation, dysbiosis, high viral titers, high levels of heavy metals and several signs of dopamine and serotonin insufficiency can all be explained.
Give the child the resources to get out of that rabbit hole!
Dr. Stewart treats neuroimmune syndromes using a three-prong approach. Treatment may look a little different from person to person because everyone has a unique set of genetics. But whether the problem is autism, ADHD, migraines, vertigo, dizziness, rheumatoid arthritis, lupus, dementia or Alzheimer's, all three of these elements are important to healing:
1. Inflammation Control
This is accomplished through diet and a variety of natural and pharmaceutical interventions. Dr. Stewart recommends what he calls a "low inflammatory diet," which typically eliminates gluten, casein (milk protein), soy, eggs and yeast. He also stresses "clean" eating, avoiding chemical food additives and eating organic as much as possible, as well as limiting environmental exposure to chemicals and allergens.
He frequently prescribes low-dose naltrexone and recommends CBD oil (purchased from a reputable supplier) and a variety of other natural supplements with anti-inflammatory properties. He occasionally uses a mild steroid medication, but also supplements with natural hormones when indicated.
Listen to Dr. Stewart's podcast about inflammation for a further explanation.
2. Mitochondrial Energy
The mitochondria are the "batteries of the cells," responsible for energy production in each and every cell in our body. Well, that sounds important.
It totally is! If our mitochondria are weak, we are weak. If we are weak, we don't heal well and we experience things like fatigue, low muscle tone and poor recovery from exercise. You can imagine how important these little batteries must be to the biggest energy consumer of the body: the brain. Many people have mitochondrial weakness without having actual mitochondrial disease (which is quite rare).
Can you guess what form of folate the mitochondria need? If you guessed 5-MTHF, give yourself 10 points. Methyl folate is a must, but some people may need some additional support. Through genetic testing (and interpretation by a qualified professional) you can learn whether supplementation to support mitochondrial energy may benefit you.
Dr. Stewart speaks extensively about mitochondria in the following two podcasts:
The game plan here is to supply all the nutritional elements that are required for the type of cell you're trying to heal. The basic "recipe" for methylation support includes folate and vitamins B-12 and B-6 in the proper forms, amounts and ratio. A product we love and use daily is Neurobiologix Neuro-immune Stabilizer Topical Cream. This product or Methylation Complete may be a good starting place for many people.
For more information about choosing supplements, including a discussion about the two products I just mentioned, listen to this podcast:
Neurobiologix also offers a whole range of unique supplements that have been specifically designed to address the concerns of those with neuroimmune syndromes, including neurotransmitter support, immune support, inflammation, pathogens, detoxification, hormonal support, and mitochondrial energy. Several of their formulas are available as kid-friendly topical creams. I knew I hit the jackpot when I found this company. These supplements are truly changing our lives!
I'm a Believer
Dr. Stewart has made a believer out of me. That's because he's healing my son. He would disagree with me, though. He would say that he's just putting back into his body what was missing so his body can heal itself.
Either way, it's beautiful.