I think molybdenum cofactor is the reason that I was able to recoup from burnout so well.  There are other pieces that needed to be addressed because those deficiencies also deserve respect in their own right, but the molybdenum cofactor was at the top of the list for me. The molybdenum cofactor isn’t just one nutrient.  The molybdenum cofactor requires molybdenum, sulfur, and copper together.  Rosemary Waring was the first to realize there could be an issue with the sulfur pathway in autism, and since then, more studies have shown we have a sulfur deficit. Two studies have also shown we have a molybdenum issue.  Combined, we theoretically  have a molybdenum cofactor deficiency. When I looked up the diagnostic criteria for a genetic molybdenum cofactor deficiency and then cross-referenced if I could find that criteria in autistic studies, I realized that I could, which is why I think this should generate a lot more attention.  What happens with this deficiency is you become sulfite toxic, which is also supported in autism, which one study showing some ASD children had 50 times the levels of sulfites as neurotypicals.

 

What’s not being recognized is the damage this deficiency can cause and how widespread the effects of a molybdenum cofactor deficiency can reach.  A environmental, meaning lacking in our diet, molybdenum cofactor deficiency has not been studied.  The information currently known is based off of the very rare genetic condition where either sulfur or molybdenum cannot be utilized by the body at all, which is often diagnosed by 28 days of age (a baby) and has a one-year mortality.  Late diagnosis is rare at 2 years old.  There is one study of a Crohn’s patient who didn’t have any molybdenum in his TPN, and he went into a coma.  300 mcg corrected it.  He showed the same diagnostic criteria I’m referencing. What’s really important about molybdenum is that the RDA does not take into consideration a population that is known to be sulfite toxic, which would raise molybdenum requirements, and has a limited diet, which would lower our intake of the nutrients.  We’ve also been found to have a downregulation of molybdenum, meaning a little may not be enough.

 

I also believe that Navauix’s work shows that the molybdenum cofactor is very much worth addressing in the autistic population.  Navauix does an amazing job of presenting the complex deterioration that happens with the body is chronically stuck in fight or flight, or what he calls the cell danger response.  Part of this process involves the body changing how ATP is released from energy to more of a danger signal, which is where I think Navauix explains burnout without probably even knowing it exists.  This change in ATP also activates inflammasomes, which increases inflammation. Navauix did a small study on ASD children using Suramin, a West African sleeping sickness medication that’s no longer in production, to shut down the 19 purine receptors.  He addresses purine receptors specifically because purinergic signaling releases endogenous ATP and sustains the cell danger response.  In other words, turning off the purine receptors turns off the “danger switch” in the body and stops the cell danger response.  This took some of the ASD kids from nonverbal to verbal in a few hours.  When the medication wore off, the symptoms returned.

 

So here’s the important thing: low molybdenum produces excess purines!  This is why I say the most important thing I did to address my burnout was actively work to fix my low molybdenum levels.  What I did was unintentionally reduce the danger signal that my body was sending out and also gave my body the ability to handle its toxic load again and start to return to homeostasis. It took over 2 milligrams for me to be on the low end of normal for molybdenum when I tested plasma levels.  I’ll be testing what 3 milligrams of molyb puts me at soon because I’m still having symptom relief as I increase the dose.  This is the first time in decades I’m at least sometimes dreaming pleasant dreams where I wake up happy.  Our system is very much based on using the pieces of science that can produce a profit and ignoring the science that isn’t profitable.  In this scenario, I 100% believe that there’s science showing that we desperately need molybdenum and sulfur, and then fix other deficiencies on a per-person basis, and that could have a huge symptom reduction in autism.  Everyone has different genetics and a different gut biome and will need to address different nutrients individually, but the molybdenum cofactor seems to be the foundation of the pattern.  I would love to see a study that addresses if correcting our molybdenum and sulfur levels, especially in the Level 1 population, which is what I am, can improve quality of life.

 

That being said, even if sulfite toxicity was taken more seriously in autism, there is already a pharmaceutical and an amino acid that will chelate sulfites that may be applicable to us.  There are pharmaceuticals already in existence that could be applied.

 

Other important pieces of the cell danger response (CDR):

Evolutionarily conserved metabolic response that protects cells and hosts from harm.  It’s triggered by encounters with chemical, physical, psychological, or biological threats that exceed the cellular capacity for homeostasis.

When danger is detected, mitochondria alter cellular metabolism by downregulation to shield the cell from further injury. This involves decreasing oxygen consumption, cell stiffen membranes, changes take place in DNA methylation, ATP is released from the cell as a warning, host behavior alters (activity/procreation take a back seat). Electron flow changes, redox, lipid dynamics, carbon and sulfur resource allocation, protein folding, vitamin availability, metal homeostasis are all also changed. The gut microbiome is also disturbed.

Vitamin D metabolism is altered because D, 24alpha-hydroxalase is increased to support cell inflammation, which actually inactivates vitamin D.  It also increases the risk of developing autoantibodies that may include anti-thyroid antibodies. When functional vitamin D is decreased, renal wasting of magnesium can occur.

The ratio of of formyl-tetrahydrofolate to methyltetrahydrofolate is changed, which increases nucleotides like IMP and dTMP that require 1-carbon donation. The resulting increase in IMP synthesis is used to make purine nucleotides like ATP (which is then used as a danger signal).

The entire danger response is sustained by purinergic signaling. Purinergic signaling is involved in every fundamental cell communication, stress response, autonomic, vestibular, and sensory integration pathway known.

Acute activation of the cell danger response stimulated the B6-dependent enzyme histidine decarboxylase to yield histamine because it’s a vasodilator that facilitates the delivery of increased oxyygen to sites of inflammation.

Low plasma levels of B6 are a common feature of inflammation and CDR, which has the effect of increasing the kynurenine/tryptophan ratio and increasing S1P in flamed tissues, sustaining the CDR response.

When the CDR response is active, intracellular conditions favor sequestration of trace and heavy metals, which are not easily mobilized.

Metabolic features of the cell danger response – ScienceDirect

Cell-Danger-Response-IHCAN.pdf (aonm.org)

 

 

Function of molybdenum – Handles four enzyme pathways, but I’m only going to talk about three here:
Sulfite to sulfur: without sufficient molybdenum, sulfites accumulate, causing brain damage
Aldehyde oxidase: Needed to handle aldehydes in the body. Some vitamins, like B6,  are aldehydes and require molybdenum to be utilized. Other pathogens, like candida, produce toxic aldehydes as a byproduct and without molyb, they cannot be handled effectively
Xanthine oxidase: needed to break down purines, which is a known pathway that can cause autistic symptoms.

 

Urinary Essential Elements of Young Children with Autism Spectrum Disorder and their Mothers – PMC (nih.gov) –  found the participants had a functional deficiency of autism, meaning their body wasn’t using the molybdenum effectively

Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders – PubMed (nih.gov) – – found a down regulation in molybdenum in the majority of partipants

 

The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation – PMC (nih.gov) – This study goes so far as to say the mechanism of autism is aldehyde toxicity. Considering a large portion of us weren’t born from parents that consumed alcohol, it feels very limited.  But it is worth taking into consideration that candida, which is common in autism, puts off toxic aldehydes, which would require extra molybdenum to handle.  Basically, the aldehydes could potentially be from other sources other than alcohol.

 

B6 study – B6 is a aldehyde B vitamin, meaning it needs molybdenum to be handled by the body.  Specifically, molybdenum, iodine, and selenium. There are also connections with candida because low B6 sets up an environment for candida to thrive.

Why is vitamin B6 effective in alleviating the symptoms of autism? – ScienceDirect

Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements – PubMed (nih.gov)

Megavitamin B6 and Magnesium in the Treatment of Autistic Children and Adults | SpringerLink

 

 

Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data (nih.gov) – shows purine dysfunction is connected to autism

 

High sulfites can inhibit the glutamate to glutamine conversion, leading to glutamate toxicity, which is also a known issue in autism
A Mechanism of Sulfite Neurotoxicity – Journal of Biological Chemistry (jbc.org)

Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders – untitled (psu.edu)

 

Sulfur studies:

Sulfate Deficiency as a Risk Factor for Autism | Journal of Autism and Developmental Disorders (springer.com) – concludes that more maternal sulfur intake is connected with milder autistic symptoms
(PDF) Sulphur Metabolism in Autism (researchgate.net) – one of the early studies
Sulfur amino acid metabolism and related metabotypes of autism spectrum disorder: A review of biochemical evidence for a hypothesis – PubMed (nih.gov)
Impaired Sulfate Metabolism and Epigenetics: Is There a Link in Autism? (mdpi.com)

Why are we deficient?: Sulfur was historically present in water, now less common due to cleaner city water removing the sulfur. A restricted diet or ARFID would exacerbate a deficiency. Potential issues with the sulfur pathway. A high oxalate diet would lower sulfur levels because oxalates and sulfur share the same pathway.

 

There is a big connection between candida and autism.  What’s interesting about candida and molybdenum involves two areas: one is that a low B6 environment allows candida to thrive; and two is that fungus loves purines, and low molybdenum levels produce excessive purines.  Studies of Suramin, which stops all purine production in the body, show that it is also incredibly effective on candida.  Low molybdenum interferes with B6 being used in the body because molybdenum is a cofactor of B6.

Anti-Candida albicans IgG Antibodies in Children With Autism Spectrum Disorders – PMC (nih.gov)

 

Diagnostic criteria I’ve found for the genetic molybdenum cofactor deficiency: accumulation of sulfite, S-sulfocysteine, thiosulfate, taurine.  There’s a reduction in cystine/cysteine, homocysteine, and PLP (what B6 gets converted to in the body).  Speech delay and dystonia are common in MCD.

Found in autism:  Speech delay is one of the core symptoms of autism, and dystonia has been observed in all levels of autism.  We have all the other diagnostic criteria except taurine and homocysteine are different because we’re usually high homocysteine and low taurine. In the case I’m presenting here, we don’t have an inability to handle the molybdenum cofactor enzyme.  Since we have a deficiency, the taurine pathway wouldn’t be blocked; and issues with methylation lead to high homocysteine, whereas in the genetic condition, the body doesn’t have the ability to handle the nutrients needed for homocysteine and present with a complete lack of homocysteine.

Description I’ve found for brain damage for the genetic molybdenum cofactor deficiency:  “Neuroimaging usually demonstrates severe abnormalities. An early stage of generalized edema is quickly followed by features mimicking severe generalized hypoxic–ischemic encephalopathy, which evolves within a few weeks to a characteristic appearance, including cortical atrophy and loss of white matter with cyst formation, hypoplastic corpus callosum, abnormal basal ganglia, hydrocephalus ex vacuo, dilated ventricles, cerebellar and brainstem hypoplasia, and mega cisterna magna.”

Damage found in autism: I can find studies showing the same brain damage except for hydrocephalus ex vacuo and cyst formation.

Considering autism has been known to have sulfite levels 50x what is found in controls and that the damage in the genetic molybdenum cofactor deficiency is from sulfite toxicity, this isn’t really surprising that we have similar diagnostic criteria.

 

One of the issues I see with the way we look at autistic diets is we continue the assumption that having a limited diet and deficiencies is a symptom of autism instead of looking for the symptoms those deficiencies cause.  It’s known that we don’t get enough nutrients.   The levels of nutrients I needed for some nutrients in particular was far more than I would get from a multivitamin.  Molybdenum, zinc, thiamine, magnesium, iodine, tryptophan and glycine all required higher doses initially.  Glycine in particular.  I took 9 grams a day and still tested as having low levels, which makes sense because being folate deficient causes glycine loss, and glycine is needed for detoxing also.  In particular, glycine, B6, molybdenum, and iodine all had results that I could really feel were beneficial.  The others I supplemented off of needs I found after testing.  With molybdenum, 500 mcgs helped, but I still tested as borderline deficient. I bumped it up to 1.5 mg, and still tested as the low end of normal.  It wasn’t until I bumped it up to 1.5 mgs, though, that I could really feel the difference in clarity of thought and comfort in my own body.  The best way I have to explain it is it really grounded me and made the world a lot more light.

 

Symptoms that resolved with me:

It feels like molyb started taking me out of fight or flight.  This is the first time I’m having the occasional happy dream in decades.  My body started moving again comfortably.  My triggers lessened dramatically.  I’m more comfortable being in close proximity to people.  I don’t always want to be touched, but more likely to want to hug and show affection to those I care about. Moving through emotional states faster (not getting “stuck”) and my internal resistance to changing activities decreased.  My body moved – not with frantic energy, but with expression.  It breathed again.  My time spent zoning out decreased dramatically.   I went from sleeping 4 hours a night to 7 or 8.  I was diagnosed with congenital adrenal hyperplasia in 2013, and my hormones have normalized more and more each year since addressing nutrient deficiencies.  Now they are in the normal range with no steroids.  My thoughts stopped throwing themselves against my skull.  I don’t repeat music in my head near as much and my music is varied, although I still stim with some songs. I’m more comfortable taking up space and stating my needs because my nervous system is a lot calmer.  I still have to “do the work,”but the work is easier when I’m not fried.

 

Mitochondrial Nutrients What it is: Autism is known as a disorder that includes mitochondrial dysfunction and damage.   Mitochondrial nutrients refer to the nutrients vital for the optimal functioning of mitochondria. Mitochondria are pivotal to generating ATP, which is our energy or “spoons.”. Mitochondrial nutrients include, generally, omega fatty acids, antioxidants (like melatonin and zinc), the vitamin B family, and magnesium. These nutrients participate in various mitochondrial processes, including the Krebs cycle, electron transport chain reactions, and oxidative stress management. The interplay of these nutrients supports mitochondrial efficiency, cellular energy production, and overall cellular resilience. The importance of maintaining a balance of mitochondrial nutrients lies in their role in preventing oxidative damage, optimizing energy production, and influencing cellular functions critical for health and longevity.

Here’s the important part and why I bring this up. When I started this research, I assumed that basic B vitamin deficiencies weren’t my problem because I ate well and was always told we got enough in our diet. Those vitamins were too basic and autism had to be something more complicated, right? As I dug deeper and deeper, I realized that the basics were a huge part of the problem, and that as complicated as the symptoms were, the relief I got from molybdenum, sulfur/NAC, B2, B6, and zinc was absolutely tangible.  The idea that we get enough from our diet feels like a blind eye is being turned when you take into consideration that we’re also defined by a restricted diet, intestinal problems including gastroparesis, and gut dysbiosis.  We don’t come even close to having a normal diet or normal ability to take in nutrients properly.

Cofactors are important and worth chasing down. For example, molybdenum is needed for B2, and once B2 starts back up, B6 can work properly. B6 is needed to reduce producing endogenous oxalates and lowers cortisol, so my sleep improved and stress levels lowered when my body finally had enough of it to use. Zinc is needed for over 200 reactions in the body, from DNA to repairing tissue to the immune system; and lipopolysaccharides and heavy metals will deplete it. Low zinc levels are related to altered mental states like psychosis and depression, which below I link to the burnout to psychosis cycle. Zinc is incredibly important. On a personal note, I was able to express myself better verbally when I addressed zinc.

Links:
An energetic view of stress: Focus on mitochondria – https://www.sciencedirect.com/science/article/pii/S0091302218300062
The Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332922/
The Role of Nutrients in Protecting Mitochondrial Function and Neurotransmitter Signaling: Implications for the Treatment of Depression, PTSD, and Suicidal Behaviors https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417658/#:~:text=These%20nutrients%20include%20%CF%893%20fatty,for%20depression%20and%20suicidal%20behaviors.
Oxidative Stress in Autism Spectrum Disorder—Current Progress of Mechanisms and Biomarkers https://www.frontiersin.org/articles/10.3389/fpsyt.2022.813304/full#:~:text=ASD%20is%20caused%20by%20oxidative,have%20been%20developed%20and%20employed.
Mitochondrial function in the brain links anxiety with social subordination – https://www.pnas.org/doi/10.1073/pnas.1512653112
Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study – https://pubmed.ncbi.nlm.nih.gov/12195231/
Amino Acids, B Vitamins, and Choline May Independently and Collaboratively Influence the Incidence and Core Symptoms of Autism Spectrum Disorder – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9318435/

What it is: A reduced ability to convert folate into a usable form in the body because of a genetic mutation. Mutations in the MTHFR gene are found in 98% of the autistic population. Folate is one of the mitochondrial nutrients, and problems here show up downstream in other ways.
What’s interesting about this gene is that the level it affects you largely depends on the number of mutations you have and your diet. So if you have heavy mutations and a poor diet, it’s going to have a larger impact on you than if you eat a wide variety of healthy food, fruits, and vegetables and have a small mutation. If not supported, it has the potential to have both mental and physical health consequences, not to mention create further vitamin deficiencies. Supporting the MTHFR gene has the potential to help high histamine levels, anxiety, cardiovascular health, blood clotting disorders, psychological health (including emotional rigidity), and neurotransmitter function. That’s a lot of possible benefit. Folate independently supports mental health so much that there’s a prescription methylfolate called Deplin prescribed for depression.

Supporting the MTHFR gene has a lot less to do with folate than we’re led to believe.  A riboflavin (B2) deficiency will also interfere with MTHFR enzyme’s ability to function.  I use a lot of information from Chris Masterjohn PhD because few people have put that thorough of information out there regarding MTHFR and other nutrients and the microbiome.  Masterjohn believes the research shows that a folate deficiency depletes glycine.  This becomes important when you realize how important glycine is for calming the nervous system and detoxing, along with buffering extra methyl groups.
Your “MTHFR” Is Just a Riboflavin Deficiency

Treatment: One way to check if your MTHFR needs support is getting homocysteine levels checked by your doctor. This is because unsupported MTHFR mutations get in the way of the body’s ability to break down homocysteine, leading to higher levels than normal, and a blood check can tell you if this is the case. Autism is heavily linked to high homocysteine levels.
Folate, B12, and B6 are the front-line vitamins people/doctors often use to support and study this gene.  For some people, those four vitamins, or a combination of, are enough. For me, I required other nutrients, at least short term, so I’m including the link to a Ph.D. nutritionist who believes the research shows that you pee out glycine that needs to be replaced and your creatine pathways have the potential to break down. His solutions worked for me. He advocates that you’ll potentially need to take choline, glycine, creatine, B2, B3, B5 & TMG in addition to the folate, B12 & B6. Because all of the nutrients in our body are there to hand off atoms for various biochemical reactions, choline can be used by your body in place of folate (sort of a way of bypassing the gene’s dysfunction). There are problems with glycine pathways in autism, and from a personal perspective, adding glycine into my diet was one of the major initial game changers, which is why I’m doing more than just briefly mentioning it.  I know this is a long list of vitamins that you might need to support a mutation, and I want to bring up that I’m putting this here more for informational purposes so people can research further. I feel it’s important to show, though, that if you’re really struggling, the support you might need can be pretty immense and that a lot of these vitamins needed are also mitochondrial nutrients, which will improve your body’s ability to make ATP (more spoons!).
If going through his podcast is too overwhelming, here’s a breakdown of what he says:
-<I>5 mg of B2</I> to improve the ability of MTHFR to make methylfolate.
-<I>500 mg TMG 2x a day</I>. This acts as an alternative to methyfolate and helps you get around a poorly-functioning MTHFR.
-<I>5 grams of creatine</I>. This is a pathway that breaks down with MTHFR mutations, and it also helps reduce the need for methylfolate.
-<I>400-600 mcg of methyfolate</I> from food with an option 400 mcg of supplement
-<I>3 grams of glycine per meal</I>. 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. I want to note 9 grams of glycine a day is HIGH. That’s not supported by outside studies, but glycine itself has been studied in lower doses.

The autistic twist: B6 needs B2 as a cofactor to work. A study of 600 ASD kids found all 600 of them functionally deficient in B2. Keeping that in mind, B2 needs selenium, iodine, and molybdenum as a cofactor. Another very small study found a down regulation of molybdenum in 9 out of 11 autistics. That means that you potentially need to take molybdenum AND B2 to be utilizing B6 properly, but most certainly be taking B2. I list more cofactors below. You can use Cronos app to analyze your diet and see what vitamins you may be significantly missing, especially if you have a restricted diet.

Links: Masterjohn –

Dr. Chris Masterjohn: MTHFR Secrets & Testing for Nutritional Deficiencies

https://chrismasterjohnphd.substack.com/p/your-mthfr-is-one-of-26-nutrient

Lack of choline has potentially very large consequences. It is also one of the 21 essential nutrients, and it’s estimated that 90% of Americans are deficient in it. If you’re autistic, you probably have a MTHFR mutation and have higher needs on top of that. RDA for choline averages around 500 mg a day, but there is “vast literature showing that the recommended daily intake amounts are not optimal for brain-related functions.” Lack of choline is linked with “profound changes in the brain” associated with Alzheimer’s, including the development of amyloid plagues and tau tangles. New research has found that mice deprived of choline result in liver damage, enlargement of the heart, and neurologic alterations, significant weight gain, and alterations in glucose metabolism which are tied to diabetes and motor skill deficits. What’s also fascinating in regards to autism is that when mice were fed a high-choline diet, the beneficial effects on the offspring were transgenerational, meaning the subsequent offspring of these mice were protected. Other studies showed that choline fed to female mice throughout life yielded improvements in spatial memory compared with a normal choline regimen. The same study found that a dietary choline deficiency altered important hippocampal networks essential for proper brain function and proteins produced by the liver that a play a role in metabolic function were dysregulated. Another study found choline fed to guinea pigs also improved the diversity of their gut bacteria. No human studies have been done, but it’s very interesting in regards to autism considering we have reduced diversity in our gut, hippocampal changes, and memory issues. Choline has a critical role in neurotransmitter function because of its impact on acetylcholine and dopaminergic function. Studies in animals suggest that CDP-choline supplements increase dopamine receptor densities and can ameliorate memory impairment.

Glycine is an amino acid that the body produces, but we also tend to get about 2 grams a day from the normal diet. Its effect in regards to autism applies to both MTHFR and the gut because it improves gut lining and is needed for MTHFR, according to Chris Masterjohn, Ph.D. It helps with neurotransmitters, helps raise glutathione levels when paired with NAC, and helps the body handle cholesterol. It’s been used to help with addiction, schizophrenia, and bipolar, all conditions that have overlapping pieces with autism. It helps sleep quality. It has a huge role in building connective tissue and managing stress. In pregnancy, it’s used for detox, antioxidation, making collagen, and is one of the main suppliers of methyl groups for making fetal DNA; and with managing preeclampsia, it helps with both oxidative stress and elevated blood pressure.
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.

Note: If you’re autistic, the wrong question to ask is if oxalates impact you. The correct question to ask is how much are they impacting you. The standard diet is often unintentionally a high-oxalate diet, plus your body produces more oxalates internally under stress. Going low oxalate has helped people alleviate ADHD symptoms and various autistic symptoms. You can address oxalates two ways and ideally both: one is to make sure you have enough B2, B6, and potentially biotin to reduce/handle endogenous production; and two is to adjust your diet to remove or limit high-oxalate foods. IMPORTANT NOTE – Going low oxalate quickly can cause major issues and please do not attempt! Learn about oxalates first, find which foods you eat that are major offenders, and reduce slowly.
What it is: Oxalates are an ion used by microbes for communication between fungus and bacteria, and they’re found in foods at varying levels and also produced internally by our own bodies. They present as crystals that form in the body after deriving from oxalic acids. Oxalic acid levels rise in patients on a high oxalate diet (some food has more oxalate than others) or with low B6 levels. Oxalates bind with mainly calcium, (and also other minerals, but less so), which lowers the overall available calcium (look up spinach and oxalate for the most common example of how high oxalates create issues). Our bodies manufacture significantly more oxalates during stress responses. Humans lack an oxalate-degrading gene in our genome so we’re reliant upon our gut bacteria to handle the oxalate. Autism often doesn’t have that necessary bacteria because we have 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.
Treatment: Treatment involves lowering the amount you eat and supporting your body’s stress response. Taking B6 is used to reduce the amount of oxalate your body produces.
Testing: OAT Test – https://mosaicdx.com/test/organic-acids-test
Autistic twists: Vitamin C will be metabolized into oxalate, and it’s recommended to take no more than 250 milligrams of this vitamin. B6 needs B2 as a cofactor to work. A study of 600 ASD kids found all 600 of them functionally deficient in B2. Keeping that in mind, B2 needs selenium, iodine, and molybdenum as a cofactor. Another very small study found a down regulation of molybdenum in nine out of 11 people. That means that you potentially need to take molybdenum AND B2 to be utilizing B6 properly, but most certainly be taking B2. I list more cofactors below. You can use Cronos app to analyze your diet and see what vitamins you may be significantly missing, especially if you have a restricted diet.
Example foods that are high oxalate: Spinach, Swiss chard, almonds and almond flour, all nuts especially almonds, chia seeds, sesame seeds, potatoes, sweet potatoes, chocolate, beets, kiwi and star fruit, soy, celery, black pepper. A day of eating a small amount of chocolate but juicing celery and including a spinach salad with a sweet potato and beets for dinner may sound healthy, but will be causing issues for your ASD. And just because it’s high oxalate doesn’t mean you can’t eat it, but it shouldn’t be limitlessly indulged and not eaten with a lot of other high ox foods.
DO NOT LOWER OXALATE LEVELS QUICKLY! Please review these resources if you want to address this side of our biology.
Links: TLO – Trying Low Oxalates, Facebook group
Wizard of Ox – Youtube videos explaining oxalates – https://www.youtube.com/c/WizardsofOxLowOxalateExperts

What is oxalate and how can it impact your health?

Oxalates – Mosaic Diagnostics

Oxalate Crystals and Pain

What it is – Gut dysbiosis is strongly linked with all of autism, resulting in inflammation of the GI tract and impacts to the nervous system and mental health.
In autism, gut dysbiosis means we have a lower number of good bacteria and too much bad bacteria in our guts, which produce toxins that then burden our bodies, which already struggle with detoxing as it is. I want to highlight lippopolysaccharides in particular as one category of the bad bacteria that is linked with a number of the negative symptoms also found in autism, including hippocampus damage, anxiety, depression, a raised body temperature, etc. Then you’ve also got candida, fungus, yeast, etc., all found in the microbiome and all producing byproducts that impact the body negatively. This imbalance of good and bad bacteria means we have consequences like inflammation, altered metabolism, production of toxic substances, digestive problems, reduced production of beneficial compounds, a weakened immune system, mental health effects, and malabsorption of nutrients. When I say production of toxic substances, harmful toxins like aldehydes, ammonia, and histamine, to name a few, are released, which the body then has to stress itself to handle. Autism is known for not detoxing well and have a reduced ability to handle that burden. Bacteria also like to use our vitamins before we can, like candida, which can impact your B1 status, for example. Heavy metals in the body reduce zinc levels. Lipopolysaccharides, part of the gut dysbiosis, reduce zinc levels. Zinc is used for over 200 processes in the body, including the elusive vitamin D in autism, so we need it. It’s not uncommon for the general population to be mildly or moderately zinc deficient, and autism has factors which deplete it further. Zinc also has a connection to vitamin D and is vital for our melatonin and seratonin production.
I mainly focus on lippopolysaccharides because I feel they’re important to address based on the extent of their impact. They have been strongly linked to the hippocampus damage found in ASD (think hundreds of hits if you search “lippopolysaccharides and hippocampus” in pubmed), anxiety and depression; but to learn more about how they specifically relate to autism, read the website I list below. Lippopolysaccharides are also another place where zinc is being depleted.
Links:

What Are Lipopolysaccharides (LPS)?

14 Factors that May Reduce Lipopolysaccharides (LPS)

more ASD-specific information here –> https://www.microbialinfluence.com/ASD.html
Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide-Mediated Toll-Like Receptor 4–Myeloid Differentiation Factor 88–Nuclear Factor Kappa B Signaling Pathway – https://link.springer.com/article/10.1007/s12264-022-00993-9#:~:text=The%20central%20pathway%20by%20which,and%20cause%20brain%20inflammation%20via
Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal Dopaminergic and mTOR Systems of Offspring – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517817/
Dietary zinc concentration and lipopolysaccharide injection affect circulating trace minerals, acute phase protein response, and behavior as evaluated by an ear-tag–based accelerometer in beef steers https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8525595/

Notes: The general idea that doctors operate off of is that you get enough nutrients in your diet so look elsewhere for the solution.  It’s also very well known that people that are autistic often have a restricted diet, ARFID, and often gastroparesis. In other words, we do not eat your standard varied diet, so those two ideas cannot exist in the same space. Research has shown time and time again that we’re deficient, and there could be a variety of reasons for this, from a limited diet to gut dysbiosis restricting utilization and the body’s ability to absorb nutrients. In the case of gut bacteria, they output toxins that our body then has to deal with that use up more resources. On the flip of that, other beneficial bacteria strains need vitamins to function that we’re often deficient in. Below is a list of examples I’ve started showing how the microbiome interacts with nutrients because I think it’s that important.
Studies:
B vitamin supplementation reduces excretion of urinary dicarboxylic acids in autistic children – https://pubmed.ncbi.nlm.nih.gov/21840465/
-Hydrogen sulfide producing pathogens cause excess vasodilation leading to low blood pressure and poor circulation
-High levels of sulfite producing bacteria (like Bilophila and Candida) deplete thiamine
-Gut microbiota and Autism Spectrum Disorder: From pathogenesis to potential therapeutic perspectives

Notes: Both of these vitamins have studies showing a deficiency in all or almost all of ASD, but I hear very little about them.
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 all 600 had a functional B2 deficiency). Both deficiencies have consequences, but B2 in particular is needed for: promoting butyrate production in the gut (preventing hyperabsorption of oxalate and beneficial for autoimmune), modulating certain gut bacteria (helps gut dysbiosis), helping convert cholesterol to bile (remember we have a cholesterol issue), helping 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, which vitamin D also helps regulate the gut. Molybdenum helps handle sulfur, aldehydes (drinking alcohol creates aldehydes in the body and candida creates excess aldehydes), and mRNA, among other things. Smokers can have higher levels of molybdenum, but otherwise, it’s necessary to get your daily intake from your diet.
You can get molybdenum levels checked by a doctor. Since the study was so small, I had mine checked, and they came back “under detectable levels.” Like the study, I was low.
Studies:
Functional Vitamin B2 Deficiency in Autism: https://www.fortunejournals.com/articles/functional-vitamin-b2-deficiency-in-autism.html
This is a great page that goes very in-depth on B2 with cites – https://b12oils.com/b2.htm
Missing piece surfaces in the puzzle of autism – https://www.sciencedaily.com/releases/2015/08/150804074037.htm
Urinary Essential Elements of Young Children with Autism Spectrum Disorder and their Mothers – https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205186/#:~:text=It%20was%20observed%20in%20one,Warring%20%26%20Klovrza%2C%202000)
https://lpi.oregonstate.edu/mic/minerals/molybdenum

What it is: The idea that inflammation, blood sugar swings, and adrenal stress cause your body to take tryptophan from the brain for other needed purposes. The body cannot create tryptophan on its own, so it takes it where it can, leading to depression, for one thing. In regards to autism, a 2017 study that found the “tryptophan level in ASD subjects is critical and that intake of B vitamins and magnesium with diet might influence its metabolic homeostasis.”
How this applies to autism: Tryptophan is needed for serotonin and melatonin.
Links: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5596045
If you want to read about it in depth, you can here: https://www.beyondmthfr.com/programmed-depression-tryptophan-gut-methylation-connection

What it is: Methylation is the transfer of four atoms – one carbon atom and three hydrogen atoms – so that necessary biological processes can occur. When optimal methylation occurs, it has a significant positive impact on reactions in the body that regulate our cardiovascular, neurological, reproductive, and detoxification systems, including those relating to: DNA production, neurotransmitter production, detoxification, histamine metabolism, estrogen metabolism, eye health, fat metabolism, cellular energy, and liver health.
Part of this process is when your body converts B vitamins into a more usable form using enzymes. The resulting forms are called methylated vitamins. If the conversion doesn’t happen, the original form remains in your blood and doesn’t get used effectively by the body.  If one form of a vitamin doesn’t work for you, it’s very possible others will. I’m including this so people are aware that there are multiple forms of vitamins available that may work with your biochemistry.
Autistic twist: If you want to get your vitamin B6 levels checked and you’re autistic, you need to get the plasma P-5-P levels checked and not the traditional B6 test. Autism will potentially show high B6 in the standard test and low plasma P-5-P because of this methylation issue and potential B2 deficiency not supporting conversion. On the same note, if you test high B12, it could indicate a functional deficiency, which could happen for a variety of reasons. I write this so you know to research abnormal blood work a little deeper than you might otherwise have thought necessary.
“Elevated serum B12 levels may also be associated with a functional deficiency of the vitamin. Functional deficiency has been described despite high B12 concentrations and is due to a failure of cellular uptake or intracellular processing, trafficking or utilization.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7550708/#:~:text=Elevated%20serum%20B12%20levels%20may,intracellular%20processing%2C%20trafficking%20or%20utilization

What it is: This is a gene theory some of us will fall into, my family included. It was organized by a psychologist who noticed a link between certain autoimmune and psychiatric conditions in her patients. She found consistent variations in four genes on a part of the genome dealing with histamine that seemed to account for the connection, especially in autoimmune like lupus and rheumatoid arthritis. ASD is included in the symptoms.
Links: http://www.rccxandillness.com
Genes and Pseudogenes: Complexity of the RCCX Locus and Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362596

What it is: This website talks about monotropism and the spiral it creates that can potentially lead to psychotic phenomena. Monotropism is a theory created by autistic persons describing the autistic experience as “person’s tendency to focus their attention on a small number of interests at any time, tending to miss things outside of this attention tunnel. This cognitive strategy is posited to be the central underlying feature of autism.”

Creating Autistic Suffering: The AuDHD Burnout to Psychosis Cycle- A deeper look

Welcome

What it is: Sometimes you can take a vitamin you need, but it make you feel worse because it tries to start up other reactions in the body that you’re missing the nutrients to support; or it jumpstarts detoxing, and you’re feeling what’s called a Herx reaction . I’m explaining this to show why I’m listing the cofactors of as many vitamins as I can below. Navigating deficiencies isn’t always easy.
Example: This is the simplest example I’ve seen to explain why taking a vitamin you need might initially cause problems. Say you supplement vitamin B2, and so now there’s more B2 to go around for other reactions in the body (alternatively, if you reduced the intake of a vitamin that needed B2, like vitamin A, the same events will happen because vitamin A will not be utilizing B2 so more B2 will be available to go around). So potentially the B2 can now go for other methylation reactions, which includes the production of adrenalin. Producing more adrenaline increased the production of aldosterone, which results in the “turning on” of aldosterone. If you’re also B12 deficient and this happens, aldosterone gets inhibited by the B12 deficiency instead of functioning properly, which causes a potassium dump from the kidneys. It’s also a good example of why the B vitamins are suggested to be taken together. Track what you eat, see where you’re weak, and use cofactors to know what other vitamins you might need for support.

“So far, many studies have reported increased oxidative stress in individuals with ASD, including decreased enzymatic antioxidants, and increased DNA, lipid, and protein oxidation products both in the brain and peripheral circulation. Increased oxidative stress markers have been found in peripheral body fluids and have been linked to ASD severity.” I want to note that many vitamins are antioxidents, and deficiencies in them are only contributing to the problem of oxidative stress.
Links: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921264/

Glutathione is our master antioxident and vital to reducing oxidative stress. Glutathione is one of the biomarkers that is low in autistic populations.

“Glutathione is a sulfur-containing molecule composed of three amino acids, or building blocks of proteins: cysteine, glycine, and glutamic acid. It is a naturally-occurring molecule within cells that participates in the liver’s detoxification of many compounds, such as products from cigarette smoke, alcohol, and overdoses of aspirin and acetaminophen (Tylenol). Glutathione is part of a system of enzymes within all cells that reduce oxidative damage, such as that due to radiation, and it is involved in production of fatty acids1. It also facilitates the development and function of a variety of immune cells. Glutathione was first proposed in autism when signs of oxidative stress in the children’s peripheral blood were documented. Glutathione also “donates” sulfur groups in chemical reactions through its cysteine component and was suggested for use in autism due to inferred deficiency in sulfur availability. Glutathione is not well absorbed when taken by mouth, and oral doses do not raise blood or tissue levels of glutathione. The fragile structure of glutathione cannot survive the gastrointestinal tract. When it is broken down, glutathione releases its component amino acids, two of which are excitatory (glutamate and cysteine) in the nervous system. The body’s cells must generate their own intracellular glutathione for it to be effective over the long term, and glutathione must be in its reduced form to be active within cells. The unreduced form is not metabolically active. Manufacturers do not indicate if their product is reduced. Reduced glutathione is also very expensive compared to the unreduced form.”
Links: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10215789/
https://www.massgeneral.org/children/autism/lurie-center/gluathione

 

Broccoli sprouts – Broccoli sprouts are interesting on two fronts. They contain sulforaphane, which has shown in studies to “significant positive correlation between sulforophane use and ASD behavior and cognitive function.” On a more specific level, sulforaphane activates key genes and enzymes involved in phase I and phase II detoxification, reducing the impact of environmental toxins. Research has shown that sulforaphane activates detoxification genes like GSTM1 and NQO1 in human cells, protecting against environmental damage. It also demonstrates an upper limit for its benefits, as excessive doses can reduce gene expression. Animal studies reveal that broccoli sprout extract induces detoxification enzymes and glutathione synthesis in the liver. Human studies indicate that sulforaphane increases gene expression, with doses over 100g daily showing significant effects on phase II antioxidant enzymes. Clinical trials with broccoli sprout extracts demonstrate a notable increase in detoxification and the excretion of airborne pollutants. For individuals seeking higher doses, broccoli sprout extract supplements can offer support for natural detoxification pathways.”

Links:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527484/
https://www.casi.org/node/1350