What I want someone to take away from this is, one, the importance of molybdenum and B2 as two vitamins that you’re most likely deficient in if you’re autistic; two, that supporting the MTHFR gene requires more than folate, B6 & B12, which is the current standard (there is a full list in the MTHFR section); three, that a disrupted gut microbiome has an impact on your physical health, mental health, and have been shown to cause brain damage; four, the importance of methylated B vitamins and choline.
Molybdenum & B2 – Molybdenum (huge detox mineral and one of the 21 essential nutrients) was found to be down regulated in 80% of autistic subjects in a small study, but in the bigger picture, a molybdenum deficiency creates a B2 deficiency (which a study of 600 autistic children found a 100% functional B2 deficiency). Both deficiencies have consequences, but B2 in particular is needed for: promoting butyrate production in the gut (preventing hyperabsorption of oxalate), modulates certain gut bacteria (helps gut dysbiosis), helps convert cholesterol to bile (remember we have a cholesterol issue), helps generate H2O2 to kill pathogens (helping gut dysbiosis), and is needed to utilize B12, B6, and iron. B12 and B6 are needed for the MTHFR gene, so following it back, B2 and molybdenum potentially are also necessary to support that gene if you’re autistic. B2 is also needed to process vitamin D. Vitamin D also helps regulate the gut.
MTHFR – 98% of autistic people have a MTHFR mutation. It has both mental and physical health consequences, both long term and short term, if not addressed. It can be checked using homocysteine levels by your doctor. Supporting the MTHFR gene helps things like high histamine levels, emotional rigidity, anxiety, cardiovascular health, blood clotting disorders, psychological health, and neurotransmitter function.
ADDRESSING MTHFR GENE MUTATIONS IN DEPTH & ITS IMPACT
According to Masterjohn, the MTHFR gene is profoundly important to mental and physical health and things like anxiety, mental flexibility/mental rigidity, getting stuck on negative thoughts, inflammation from allergic reactions or histamine in food, healthy digestion, the liver clearing toxins and stable blood sugar and muscles working optimally. It does this because it makes methyfolate, which is part of the methylation cycle. What’s important to note is it’s extremely diet dependent, which doesn’t bode well if you have a limited diet, like a lot of us do.
I’m going to summarize Chris Masterjohn’s protocol because it worked for me, but please listen to his podcasts or subscribe to him to learn more information. So the highlights are:
–5 mg of B2 to improve the ability of MTHFR to make methylfolate. Masterjohn doesn’t say this, but since we’re all autistic, molybdenum is important here because if we’re molybdenum deficient, which the only study done showed very conclusively we probably are, then we need molybdenum to handle B2
–500 mg TMG 2x a day. This acts as an alternative to methyfolate and helps you get around a poorly-functioning MTHFR.
–5 grams of creatine. This is a pathway that breaks down with MTHFR mutations, and it also helps reduce the need for methylfolate.
–400-600 mcg of methyfolate from food with an option 400 mcg of supplement
–3 grams of glycine per meal. Glycine helps stabilize the methylation system helping to prevent swings in mood, mental state, and energy. Low methyfolate levels lead to glycine loss, so the glycine is to replace what is lost.
If methylfolate makes you angry or depressed, add glycine and start with a lower amount of folate. And if you’re like me, who has symptoms of low acetylcholine levels (poor learning & memory, an inability to perform under sustained focus or muscular power), try alpha-GPC for at least half of your choline needs. Alpha-GPC is only 40% choline, so multiply by .4 to figure how much choline you are getting from it. He goes into specifics on his podcast and website on how to replace these with food, so please reference that for more specifics. I’m trying to keep this simple here. He has a choline calculator and other tips for personalizing the protocol (like when folinic acid is better instead of methylfolate based on genetics).
It’s important to keep in mind that the studies I have seen used B12, B6, and folate only when they reference how to correct MTHFR. They certainly didn’t bring into account B2 or molybdenum, which are necessary for B6 and B12 to function, and deficient in autism.
Cronometer is an easy app to track your intake so you know what you may get when it comes to other vitamins.
You can have normal homocysteine levels and have MTHFR mutations because the gene’s ability to function is highly dependent on diet plus, depending on genetics, the extent to which the mutation affects you is different for everyone. But in autism, we tend to have high levels, potentially because of the B2 and molybdenum deficiencies interfering with our body’s ability to use B6 and B12. As another study points out, “study designs should take into consideration even the other B vitamin status (such as B1 and B6)…blood sample for homocysteine should be taken and lowering it with vitamin implementation should be done due to low cost and fast application.” cite
And then here’s a quote from a study referencing MTHFR’s impact on neurotransmitters and neuropsyciatric symptoms, to expand on what I already covered: “Observations on the antidepressant effects of folate supplementation may suggest the effect of these nutrients in psychopathology. Folate also considerably influences the rate of synthesis of tetrahydrobiopterin, a cofactor in the hydroxylation of phenylalanine and tryptophan, rate-limiting steps in the biosynthesis of dopamine, norepinephrine, and serotonin, neurotransmitters postulated to impact the monoamine hypothesis of affective disorders. In addition, there is a study supporting that genetic modifications affecting the MTFHR level or function decreases the 5-methyltetrahydrofolate level further results in increased homocysteine. There are many meta-analyses in the literature that reveal the correlation between psychiatric diseases and MTHFR gene polymorphisms. It is also a non-negligible reason for OCD. SAM3 and methyl folate have been shown to exert stronger antidepressant effects than placebos when administered in parenteral and certain oral forms, and are even more effective than tricyclic antidepressants. Total plasma homocysteine can be as a sensitive marker of functional deficiency of folate and vitamin B12. Total homocysteine level changes have also been suggested to be correlated with numerous psychiatric disorders (e.g., schizophrenia and affective disorders). Also, some literature reported neuropsychiatric symptoms in patients with vitamin B12 deficiency, including ataxia, mania, hallucinations, memory loss, depression, paresthesias, proprioception loss, delirium, dementia, personality change, and abnormal behavior. As mentioned earlier, folate and vitamin B12 deficiencies inhibit the methylation reactions, as well as elevate homocysteine levels, which results in a drop in neurotransmitter levels and affects other biochemical pathways in the cell to varying adversely degrees.”cite
Glycine acts as an inhibitory neurotransmitter in the brain, which means it can have a calming effect on neural activity. Glycine can also inhibit the effects of excitatory neurotransmitters like glutamate, which are known to be involved in the pathophysiology of some neurological and psychiatric disorders, including ASD. Researchers have explored whether glycine supplementation or medications that modulate glycine receptors might have a therapeutic role in ASD by reducing excitatory neurotransmission.
GUT DYSBIOSIS OVERVIEW
“LPS also renders toxins from Candida Albicans more damaging. The poisonous effects of LPS are so potent that they produce symptoms of autism even without the help of Candida Albicans and heavy metals. All collected experiments on the following website involve laboratory mice injected with only LPS and exhibiting the same symptoms as those in ASD.
LPS induces a depressive syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. This result has been replicated so many times by different research studies that the names, “Sickness Behavior” and “Endotoxemia” are now applied to this condition.  The mission of this website is to collect and display links to some of the available research articles from PubMed, a service from the National Library of Medicine and the National Institute of Health, that link LPS to the varied and diverse symptoms of ASD. We were able to find and collect experiments for almost every possible neurological and biological symptom of ASD in order to prove that most symptoms of ASD, have a corresponding experiment on Medline that proves each is a symptom of LPS toxicity.
The articles on this website are just a tiny fraction of the available research The amount of evidence is overwhelming. For example, performing a search for “hippocampus lps”, in PubMed will retrieve 222 citations.”
The number of similarities between ASD and LPS toxicity is sufficiently impressive to demand attention and cannot be ignored. The following are symptoms of LPS poisoning; these symptoms are also found in children with autism:
-Reductions in oligodendrocyte or myelin markers
-A marked cerebral cytokine response
-White matter injury
-Changes in amygdala
-Change in dopamine and serotonin levels
-Reduction of blood flow to the brain
-Changes in blood-brain barrier permeability for large (protein) molecules
-Increased the number of pyramidal and granular cells in the hippo-campus
EMOTIONS AND BEHAVIOR
-Reduction in social behavior
-Lack of social interaction
-Increase in addiction
-Lack of exploratory behavior
-Breakage and depletion of microvilli
-The tight junctions widen and become disrupted.
IBS and IBD
-Disrupted Intestinal Transit
-LPS is linked to the problems of gluten,soy and dairy in ASD children
-Increase in TNF alpha.
-Increases in certain NK cells and monocytes
-Increases in lymphocytes
-Low Levels of Thyroid
-Low Levels of Glutathione
-Low Levels of Amino Acids
-Impairment of Bile Flow
-Increasing the Number of Viable Candida Albicans
-An increase in pain sensitivity
This page also gives a thorough summary, all cited, for additional treatment options. Here’s the page in a quick glance:
What LPS impacts:
-Fatigue: LPS-induced “sickness behavior” causing fatigue.
-Poor Memory: Impaired memory due to LPS administration.
-Anxiety and Low Empathy: Decreased empathy and increased anxiety with LPS.
-Depression and Social Disconnection: LPS-induced depression and social disconnection.
-Inability to Experience Pleasure: Reduced ability to feel pleasure due to LPS.
-Disturbed Sleep: LPS disrupts sleep patterns.
-Fever: Elevated LPS levels lead to fever.
-Poor Reproductive Health in Women: LPS linked to reproductive health issues.
-Reduced Appetite: LPS reduces appetite.
-Low Pain Tolerance: Decreased pain tolerance with LPS.
-Diabetes: LPS associated with an increased risk of diabetes.
-Obesity: LPS linked to obesity.
-Metabolic Syndrome: LPS associated with metabolic syndrome.
-Heart Disease: LPS levels are increased in heart disease.
-Non-Alcoholic Fatty Liver Disease: Elevated LPS in non-alcoholic fatty liver disease.
-Inflammatory Bowel Disease: Consistently high LPS levels in IBD patients.
-Cancer: Higher LPS levels associated with colorectal tumors.
-Alzheimer’s Disease: LPS linked to Alzheimer’s disease.
-Parkinson’s Disease: Elevated LPS in Parkinson’s disease.
-Autism: Higher LPS levels in individuals with autism.
-HIV: LPS transport accelerates HIV progression.
-Retinal Disease: LPS-induced inflammation affects the retina.
Prebiotics: Inulin, oligofructose, and resistant starch reduce LPS and inflammation while promoting beneficial gut bacteria.
Probiotics: Lactobacillus GG, Bifidobacterium, and Saccharomyces boulardii lower LPS levels and systemic inflammation.
Polyphenols: Grape extract, resveratrol, and cranberry polyphenols combat LPS-induced inflammation.
Red Wine: Red wine consumption increases beneficial gut bacteria and decreases LPS-producing bacteria but should be consumed in moderation.
Omega-3 Fatty Acids: High-dose omega-3 supplementation reduces fever and inflammatory cytokines, positively affecting gut bacteria.
Olive Oil: High-phenol olive oil limits LPS and inflammatory cytokines, while high-oleic acid diets reduce LPS-induced inflammation.
Orange Juice: Consuming orange juice with a high-fat meal prevents LPS-related oxidative stress and inflammation.
Peanuts: Peanuts, especially those high in oleic acid, reduce LPS levels in overweight individuals.
Bilberries: Bilberries consumption reduces LPS and inflammatory markers.
Exercise: Regular exercise lowers blood LPS levels, but short-term exercise may temporarily increase intestinal permeability.
Vagus Nerve Stimulation: Noninvasive vagus nerve stimulation and acetylcholine reduce the release of inflammatory cytokines in response to LPS.
Meditation, Breathing, and Cold Exposure: Activation of the sympathetic nervous system through meditation, breathing exercises, and cold exposure reduces LPS-induced inflammation.
Lactoferrin: Lactoferrin, found in milk and saliva, binds to LPS and prevents inflammation.
Activated Charcoal: Activated charcoal removes LPS from the intestine but not elsewhere in the body
It is highly studied including in elderly populations, athletes, pregnancy, schizophrenia, diabetes, liver issues, and deemed generally safe. In studies of autistic children, in lowered irritability and hyperactivity significantly. Where I used it was to help clean up my gut. It is a potent destroyer of bacterial biofilms. Bacteria create biofilms, which can be hard to disrupt. The most obvious example of this is the bacterial plaques on your teeth the dentist scrapes off. Studies in mice also showed restructuring of the gut including promoting the growth of akkermansia, bifidobacterium, lactobacillus, and allobaculum when given NAC.
Where NAC is also important is that it’s a precursor to glutathione, which is a molecule that the liver needs to detox (thinking smoking, alcohol, acetaminophen, etc.) and is part of a system of enzymes within all cells that helps reduce oxidative damage. As a short history, glutathione was first proposed in autism when there were signs of oxidative stress in children’s peripheral blood. Glutathione also donates sulfur groups and was suggested for use due to a deficiency in sulfur availability. However, supplementing is poorly absorbed by mouth, cannot survive the intestinal tract, and doesn’t raise blood or tissue levels of glutathione. It has to be in what’s called a “reduced” form to work, which is *expensive.* Studies of glutathione supplementation in ASD showed a reduction in self-harm and improved sensory integration.
Studies of NAC taken with glycine improved glutathione deficiencies, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfinction, genotoxicity, muscle strength, and cognition in elderly populations. I’m bringing this up because to support your MTHFR gene, you should consider taking glycine, which pairs well with NAC.
THINGS THAT ARE HELPFUL TO KNOW/LESS KNOWN SUPPLEMENTS:MOLYBDENUM
Sulfite oxidase: Converts sulfite to sulfate, preventing the dangerous buildup of sulfites in the body
Aldehyde oxidase: Breaks down aldehydes, which can be toxic to the body. Also, it helps the liver break down alcohol and some drugs, such as those used in cancer therapy
Xanthine oxidase: Converts xanthine to uric acid. This reaction helps break down nucleotides, the building blocks of DNA, when they’re no longer needed. They can then be excreted in the urine
Mitochondrial amidoxime reducing component (mARC): This enzyme’s function isn’t fully understood, but it’s thought to remove toxic byproducts of metabolism
Having a molybdenum deficiency interferes with our ability to handle B2 (as does an iodine or selenium deficiency), which then impacts B6, B12, MTHFR, and vitamin D status. Another huge reason is handling toxins in the body. Molybdenum is one of the 21 essential nutrients that our bodies cannot survive without. So keeping in mind that above I pointed out that bacteria gives off toxins like aldehydes, an important nutrient that handles the aldehydes is molybdenum. There’s a small study that effectively showed 80% of 13 autistic participants had a down regulation of the vitamin. What we don’t know is what amount should be supplemented if you’re autistic and why there’s a down regulation. Molybdenum is also closely tied with B6, which is heavily studied and very helpful in ASD.
For those of you with low ferritin levels, molybdenum, via the xanthine oxidase component, helps reduce cellular ferric to ferrous ferritin. Meaning that if your ferritin levels are low, molybdenum could be the cause (as could B2). Both copper and molybdenum influence the transport and release of iron.
Taking too much molybdenum is toxic for the brain. Most supplements I see are between 175 and 500 mcg. I did have my levels tested before I supplemented to make sure they were sufficiently low to warrant supplementation. I did this because the general knowledge is that molybdenum deficiencies are rare, but the studies on us show that we have a down regulation in it. I wanted to know if I potentially followed the pattern of the very small study that was done, and I feel like I did. Keep in mind that the molybdenum tests at your doctor’s office are designed to test for high levels as high levels are more known to be the issue, usually from workplace exposure. My test results came back “below detectable levels.” Based on the lab’s key, I’m either at the very lowest end of acceptable or deficient, which very likely follows the trend of the study. Molybdenum levels are also higher in people who smoke cigarettes, as an important note.
B2 – Functional vitamin B2 levels were assessed in 600 children with autism aged between two and 30 years old. Every child assessed was found to have functional vitamin B2 deficiency. All of them. “This deficiency then affects the metabolism of fatty acids, glucose and amino acids. Functional B2 deficiency also affects the activity of succinate dehydrogenase – the linking enzyme between energy production in Krebs cycle and electron transfer in the Electron Transport Chain. In addition, functional B2 (as FMN) is also required for the activation of vitamin B6. Given that it is known that vitamin B2, in its active forms, FMN and FAD, is involved as a co-factor in over 100 enzymes, these findings have profound implications for energy production in the brain of the children and for the activation and control of neurotransmitters, amongst other reactions.” cite
B2 in particular is needed for promoting butyrate production in the gut (preventing hyperabsorption of oxalate), modulates certain gut bacteria (helps gut dysbiosis), helps convert cholesterol to bile (remember we have a cholesterol issue and reduced bile), helps generate H2O2 to kill pathogens (helping gut dysbiosis), and is needed to utilize B12, B6, and iron.
B6 – B6 is a highly studied nutrient in autism. It’s often paired with magnesium and has been used successfully to help reduce irritability, improve communication, and lower oxidative stress, to name just a few. Inadequate B6 is linked to depression and mental health. It’s essential for over 140 processes in the body, from metabolism to protein utilization to amino acids to nervous system to immune system to brain function. That’s basically everything. Once ingested, the body turns B6 into P5P, the more bioavailable form, via the liver. ASD tends to be deficient in usable P5P and considering how much it’s used for, including methylation, that has numerous downstream effects.
The reason I’m highlighting it here is because the standard form in supplements is pyridoxine hydrochloride. Meaning, in most multivitamins you pick up, you’ll see pyridoxine HCL as the form. Recent studies are showing that pyridoxine is not as effective as we thought it was. In summation, “the inactive form pyridoxine competitively inhibits the active pyridoxal-5′-phosphate. Consequently, symptoms of vitamin B6 supplementation are similar to those of vitamin B6 deficiency.” Unfortunately, there’s no real RDA for P5P. It’s not as widely studied as the other forms, but it is known to be more efficiently taken into the body and does not require being synthesized by the liver, unlike pyridoxine.
Another important thing to note is that ASD tends to have high plasma B6 but low P5P, meaning that the B6 is not being converted to P5P and is, therefore, unusable. Pulling blood for B6, which would be the default to check B6 levels, will not give you an accurate level of usable B6 in the body. You have to pull plasma P5P, and many doctors don’t realize this.
There is also a link between cholesterol and glycine, which primarily involves the synthesis of bile acids in the liver. Both cholesterol and glycine play essential roles in this process, which is crucial for the digestion and absorption of dietary fats. This process helps in the digestion and absorption of dietary fats and fat-soluble vitamins (like A, D, E, and K). I bring this up here, but if you read in the MTHFR section, we need glycine to support the MTHFR mutations.
Important things to know to raise vitamin D levels:
-You need enough magnesium in your system or supplementing is worthless because magnesium is a cofactor to vitamin D
-If you take vitamin D, you should always take vitamin K2 with it also. There are several forms of vitamin K, with MK-7 and MK-4 being the most common. I have never been able to get my vitamin D levels up, but there’s new research showing that taking D3 and K2 at 8-12 hours apart may be more effective (D3 in morning and K2 at night). Since my levels have never raised much even on 10,000 IUs of D3/K2 in MK-7 form, I’ll update this as soon as I get tested again to see if it works. I’m finding references to research from Japan showing that taking the MK-4 version of K2 has impressive results helping to clear amyloid from the brain, improve stomach juices, pancreatic secretions, bile from the liver, intestinal wall integrity, all of which have an impact on how vitamin D is absorbed. I’m still hunting down those studies, though, but I’ll post them when I find them.
-B2 is needed to process D3, so we’re back to B2 again. More specifically, B2 stimulates liver enzymes, which is important for the production of the active form of D3.
DIETS TO KNOW ABOUTOxalates
Oxalates are an ion used by microbes for communication between fungus and bacteria, but they’re also found in foods at varying levels. In plants, it binds with calcium in the plant, which lowers the overall available calcium (look up spinach and oxalate for the most common example). Everybody produces some oxalate in their body, but our bodies manufacture more during stress responses…and being autistic is partially defined as being perpetually stressed. Humans lack an oxalate-degrading gene in our genome so we’re reliant upon our gut bacteria to handle it. Some people do have proper bacteria in their gut to handle oxalates specifically, but autism often doesn’t have that bacteria as part of the gut dysbiosis. When oxalate in the body gets too high, it interferes with mineral metabolism, changes mitochondrial function, and adds to oxidative stress. It can settle in tissues and joints where it causes havoc if there’s enough of it. Where you’re familiar with oxalates and don’t realize it is kidney stones. Kidney stones are oxalates. There’s a Facebook group called TLO: Trying Low Oxalates that has more information if you think this might be something you want to look into more.
Chris Masterjohn also has a podcast episode where he explains that, theoretically, with enough biotin, we might have a system that can handle oxalates outside of the gut bacteria.
I wish doctors had a better understanding of oxalate in regards to autism. As a real life example, I had an autistic friend whose doctor told him to eat spinach daily to help detox heavy metals, attempting to help his autoimmune issues that weren’t responding well to any treatment. Unfortunately, this is probably one of the worst things to suggest if you’re autistic, and I’m sure the doctor had no idea that he was adding to the damage. It’s a good example of why this knowledge is so important for treating issues and improving quality of life, and why I wish doctors would educate themselves on why autism is different than the general population. Garlic would have been a much better option.
There’s evidence that being deficient in B6 is a cause of endogenous oxalate production. It’s been found in another study that possibly what was interpreted as a B6 deficiency might have been misinterpreted and is actually a B2 deficiency. But considering B2 is required to change B6 into a usable form, B2 is still important in this either way. It’s another place where a molybdenum deficiency could be wrecking havoc.
I’ve known some ASD and ADHD people who find low-dose lithium orotate help them, and this could be part of the reason.