My goal is to create a resource that gives more perspective to ways we can help ourselves and significantly improve our quality of life for the long term, all backed by peer-reviewed studies.<\/p>\n
<\/p>\nMolybdenum Cofactor Deficiency - at the heart of the inflammation and, therefore, many symptoms<\/span> I think molybdenum cofactor is the reason that I was able to recoup from burnout so well. \u00a0There 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\u2019t just one nutrient. \u00a0The molybdenum cofactor requires molybdenum, sulfur, and copper together. \u00a0Rosemary 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. \u00a0Combined, we theoretically \u00a0have 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. \u00a0What 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.<\/p>\n <\/p>\n What\u2019s not being recognized is the damage this deficiency can cause and how widespread the effects of a molybdenum cofactor deficiency can reach. \u00a0A environmental, meaning lacking in our diet, molybdenum cofactor deficiency has not been studied. \u00a0The 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. \u00a0Late diagnosis is rare at 2 years old. \u00a0There is one study of a Crohn\u2019s patient who didn\u2019t have any molybdenum in his TPN, and he went into a coma. \u00a0300 mcg corrected it. \u00a0He showed the same diagnostic criteria I\u2019m referencing. What\u2019s 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. \u00a0We\u2019ve also been found to have a downregulation of molybdenum, meaning a little may not be enough.<\/p>\n <\/p>\n I also believe that Navauix\u2019s work shows that the molybdenum cofactor is very much worth addressing in the autistic population. \u00a0Navauix 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. \u00a0Part 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. \u00a0This 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\u2019s no longer in production, to shut down the 19 purine receptors. \u00a0He addresses purine receptors specifically because purinergic signaling releases endogenous ATP and sustains the cell danger response. \u00a0In other words, turning off the purine receptors turns off the \u201cdanger switch\u201d in the body and stops the cell danger response. \u00a0This took some of the ASD kids from nonverbal to verbal in a few hours. \u00a0When the medication wore off, the symptoms returned.<\/p>\n <\/p>\n So here\u2019s the important thing: low molybdenum produces excess purines! \u00a0This is why I say the most important thing I did to address my burnout was actively work to fix my low molybdenum levels. \u00a0What 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. \u00a0I\u2019ll be testing what 3 milligrams of molyb puts me at soon because I\u2019m still having symptom relief as I increase the dose. \u00a0This is the first time in decades I\u2019m at least sometimes dreaming pleasant dreams where I wake up happy. \u00a0Our system is very much based on using the pieces of science that can produce a profit and ignoring the science that isn\u2019t profitable. \u00a0In this scenario, I 100% believe that there\u2019s 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. \u00a0Everyone 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. \u00a0I 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.<\/p>\n <\/p>\n 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. \u00a0There are pharmaceuticals already in existence that could be applied.<\/p>\n <\/p>\n Other important pieces of the cell danger response (CDR):<\/p>\n Evolutionarily conserved metabolic response that protects cells and hosts from harm. \u00a0It\u2019s triggered by encounters with chemical, physical, psychological, or biological threats that exceed the cellular capacity for homeostasis.<\/p>\n 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.<\/p>\n Vitamin D metabolism is altered because D, 24alpha-hydroxalase is increased to support cell inflammation, which actually inactivates vitamin D. \u00a0It 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.<\/p>\n 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).<\/p>\n 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.<\/p>\n Acute activation of the cell danger response stimulated the B6-dependent enzyme histidine decarboxylase to yield histamine because it\u2019s a vasodilator that facilitates the delivery of increased oxyygen to sites of inflammation.<\/p>\n 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.<\/p>\n When the CDR response is active, intracellular conditions favor sequestration of trace and heavy metals, which are not easily mobilized.<\/p>\n Metabolic features of the cell danger response – ScienceDirect<\/u><\/a><\/p>\n Cell-Danger-Response-IHCAN.pdf (aonm.org)<\/u><\/a><\/p>\n <\/p>\n <\/p>\n Function\u00a0of molybdenum –\u00a0Handles four enzyme pathways, but I\u2019m only going to talk about three here: <\/p>\n Urinary Essential Elements of Young Children with Autism Spectrum Disorder and their Mothers – PMC (nih.gov)<\/u><\/a>\u00a0– \u00a0found the participants had a functional deficiency of autism, meaning their body wasn\u2019t using the molybdenum effectively<\/p>\n Olfactory stem cells reveal MOCOS as a new player in autism spectrum disorders – PubMed (nih.gov)<\/u><\/a>\u00a0– – found a down regulation in molybdenum in the majority of partipants<\/p>\n <\/p>\n The Pivotal Role of Aldehyde Toxicity in Autism Spectrum Disorder: The Therapeutic Potential of Micronutrient Supplementation – PMC (nih.gov)<\/u><\/a>\u00a0– This study goes so far as to say the mechanism of autism is aldehyde toxicity. Considering a large portion of us weren\u2019t born from parents that consumed alcohol, it feels very limited. \u00a0But it is worth taking into consideration that candida, which is common in autism, puts off toxic aldehydes, which would require extra molybdenum to handle. \u00a0Basically, the aldehydes could potentially be from other sources other than alcohol.<\/p>\n <\/p>\n B6 study – B6 is a aldehyde B vitamin, meaning it needs molybdenum to be handled by the body. \u00a0Specifically, molybdenum, iodine, and selenium. There are also connections with candida because low B6 sets up an environment for candida to thrive.<\/p>\n Why is vitamin B6 effective in alleviating the symptoms of autism? – ScienceDirect<\/u><\/a><\/p>\n Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements – PubMed (nih.gov)<\/u><\/a><\/p>\n Megavitamin B6 and Magnesium in the Treatment of Autistic Children and Adults | SpringerLink<\/u><\/a><\/p>\n <\/p>\n <\/p>\n Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data (nih.gov)<\/u><\/a>\u00a0– shows purine dysfunction is connected to autism<\/p>\n <\/p>\n High sulfites can inhibit the glutamate to glutamine conversion, leading to glutamate toxicity, which is also a known issue in autism Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders\u00a0– untitled (psu.edu)<\/u><\/a><\/p>\n <\/p>\n Sulfur studies:<\/p>\n Sulfate Deficiency as a Risk Factor for Autism | Journal of Autism and Developmental Disorders (springer.com)<\/u><\/a>\u00a0– concludes that more maternal sulfur intake is connected with milder autistic symptoms Why are we deficient?: Sulfur was historically present in water, now less common due to cleaner\u00a0city water\u00a0removing the sulfur. A restricted diet or ARFID would\u00a0exacerbate a deficiency.\u00a0Potential issues with the sulfur pathway. A high oxalate diet would lower sulfur levels because oxalates and sulfur share the same pathway.<\/p>\n <\/p>\n There is a big connection between candida and autism. \u00a0What\u2019s 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. \u00a0Studies of Suramin, which stops all purine production in the body, show that it is also incredibly effective on candida. \u00a0Low molybdenum interferes with B6 being used in the body because molybdenum is a cofactor of B6.<\/p>\n Anti-Candida albicans IgG Antibodies in Children With Autism Spectrum Disorders – PMC (nih.gov)<\/u><\/a><\/p>\n <\/p>\n Diagnostic criteria I\u2019ve found for the genetic molybdenum cofactor deficiency: accumulation of sulfite, S-sulfocysteine, thiosulfate, taurine. \u00a0There\u2019s\u00a0a reduction in cystine\/cysteine, homocysteine, and PLP\u00a0(what B6 gets converted to in the body). \u00a0Speech delay and dystonia are common in MCD.<\/p>\n Found in autism: \u00a0Speech\u00a0delay is one of the core symptoms of autism, and dystonia has been observed in all levels of autism. \u00a0We have all the other diagnostic criteria except taurine and homocysteine are different because we\u2019re usually high homocysteine and low taurine. In the case I\u2019m presenting here, we don\u2019t have an inability to handle the molybdenum cofactor enzyme. \u00a0Since we have a deficiency, the taurine pathway wouldn\u2019t be blocked; and issues with methylation lead to high homocysteine, whereas in the genetic condition, the body doesn\u2019t have the ability to handle the nutrients needed for homocysteine and present with a complete lack of homocysteine.<\/p>\n Description I\u2019ve found for brain damage for the genetic molybdenum cofactor deficiency: \u00a0“Neuroimaging usually demonstrates severe abnormalities. An early stage of generalized edema is quickly followed by features mimicking severe generalized hypoxic\u2013ischemic 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.\u201d<\/p>\n Damage found in autism: I can\u00a0find studies showing the same brain damage except for hydrocephalus ex vacuo and\u00a0cyst formation.<\/p>\n 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\u2019t really surprising that we have similar diagnostic criteria.<\/p>\n <\/p>\n 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. \u00a0It\u2019s known that we don\u2019t get enough nutrients. \u00a0\u00a0The levels of nutrients I needed for some nutrients in particular was far more than I would get from a multivitamin. \u00a0Molybdenum, zinc, thiamine, magnesium, iodine, tryptophan and glycine all required higher doses initially. \u00a0Glycine in particular. \u00a0I 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. \u00a0In particular, glycine, B6, molybdenum, and iodine all had results that I could really feel were beneficial. \u00a0The others I supplemented off of needs I found after testing. \u00a0With 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. \u00a0It wasn\u2019t 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. \u00a0The best way I have to explain it is it really grounded me and made the world a lot more light.<\/p>\n <\/p>\n Symptoms that resolved with me:<\/p>\n It feels like molyb started taking me out of fight or flight. \u00a0This is the first time I\u2019m having the occasional happy dream in decades. \u00a0My body started moving again comfortably. \u00a0My triggers lessened dramatically. \u00a0I\u2019m more comfortable being in close proximity to people. \u00a0I don\u2019t 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 \u201cstuck\u201d) and my internal resistance to changing activities decreased. \u00a0My body moved – not with frantic energy, but with expression. \u00a0It breathed again. \u00a0My time spent zoning out decreased dramatically. \u00a0\u00a0I went from sleeping 4 hours a night to 7 or 8. \u00a0I was diagnosed with congenital adrenal hyperplasia in 2013, and my hormones have normalized more and more each year since addressing nutrient deficiencies. \u00a0Now they are in the normal range with no steroids. \u00a0My thoughts stopped throwing themselves against my skull. \u00a0I don\u2019t repeat music in my head near as much and my music is varied, although I still stim with some songs. I\u2019m more comfortable taking up space and stating my needs because my nervous system is a lot calmer. \u00a0I still have to \u201cdo the work,\u201dbut the work is easier when I\u2019m not fried.<\/p>\n <\/p>\nMitochondrial Nutrients<\/span>\nWhat it is: Autism is known as a disorder that includes mitochondrial dysfunction and damage.\u00a0 \u00a0Mitochondrial nutrients refer to the nutrients vital for the optimal functioning of mitochondria. Mitochondria are pivotal to generating ATP, which is our energy or \u201cspoons.\u201d. 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.<\/p>\n Here\u2019s the important part and why I bring this up. When I started this research, I assumed that basic B vitamin deficiencies weren\u2019t 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.\u00a0 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.\u00a0 We don’t come even close to having a normal diet or normal ability to take in nutrients properly.<\/p>\n 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.<\/p>\n Links: <\/p>\nMTHFR Gene<\/span> Supporting the MTHFR gene has a lot less to do with folate than we’re led to believe.\u00a0 A riboflavin (B2) deficiency will also interfere with MTHFR enzyme’s ability to function.\u00a0 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.\u00a0 Masterjohn believes the research shows that a folate deficiency depletes glycine.\u00a0 This becomes important when you realize how important glycine is for calming the nervous system and detoxing, along with buffering extra methyl groups. 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\u2019s 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. 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.<\/p>\n Links: Masterjohn –<\/p>\n Dr. Chris Masterjohn: MTHFR Secrets & Testing for Nutritional Deficiencies<\/a><\/p><\/blockquote>\n
\nSulfite to sulfur: without sufficient molybdenum, sulfites accumulate, causing brain damage
\nAldehyde oxidase: Needed to handle aldehydes in the body. Some vitamins, like B6, \u00a0are 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
\nXanthine oxidase: needed to break down purines, which is a known pathway that can cause autistic symptoms.<\/p>\n
\nA Mechanism of Sulfite Neurotoxicity – Journal of Biological Chemistry (jbc.org)<\/u><\/a><\/p>\n
\n(PDF) Sulphur Metabolism in Autism (researchgate.net)<\/u><\/a>\u00a0– one of the early studies
\nSulfur amino acid metabolism and related metabotypes of autism spectrum disorder: A review of biochemical evidence for a hypothesis – PubMed (nih.gov)<\/u><\/a>
\nImpaired Sulfate Metabolism and Epigenetics: Is There a Link in Autism? (mdpi.com)<\/u><\/a><\/p>\n
\nAn energetic view of stress: Focus on mitochondria – https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0091302218300062
\nThe Effect of Mitochondrial Supplements on Mitochondrial Activity in Children with Autism Spectrum Disorder – https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5332922\/
\nThe 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.
\nOxidative Stress in Autism Spectrum Disorder\u2014Current 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.
\nMitochondrial function in the brain links anxiety with social subordination – https:\/\/www.pnas.org\/doi\/10.1073\/pnas.1512653112
\nTreatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study – https:\/\/pubmed.ncbi.nlm.nih.gov\/12195231\/
\nAmino 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\/
\n<\/div>\n
\nWhat\u2019s 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\u2019s 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\u2019s a lot of possible benefit. Folate independently supports mental health so much that there\u2019s a prescription methylfolate called Deplin prescribed for depression.<\/p>\n
\nYour “MTHFR” Is Just a Riboflavin Deficiency<\/a><\/p>\n
\nFolate, B12, and B6 are the front-line vitamins people\/doctors often use to support and study this gene.\u00a0 For some people, those four vitamins, or a combination of, are enough. For me, I required other nutrients, at least short term, so I\u2019m 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\u2019ll 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\u2019s 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\u2019m doing more than just briefly mentioning it.\u00a0 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\u2019s important to show, though, that if you\u2019re 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\u2019s ability to make ATP (more spoons!).
\nIf going through his podcast is too overwhelming, here’s a breakdown of what he says:
\n-<I>5 mg of B2<\/I> to improve the ability of MTHFR to make methylfolate.
\n-<I>500 mg TMG 2x a day<\/I>. This acts as an alternative to methyfolate and helps you get around a poorly-functioning MTHFR.
\n-<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.
\n-<I>400-600 mcg of methyfolate<\/I> from food with an option 400 mcg of supplement
\n-<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.<\/p>\n