What is Methyl-B12 (B12)?
B12 (cobalamin) is a vitamin “family” with five unique family members that each do different things. Out of the B12 family, only methyl-B12 has the ability to activate the methionine/homocysteine biochemical pathway directly which results in more “fuel” to the brain.
B12 works with folic acid to make all the cells in the body. It plays a key role in methylation. Methylation makes ALL of the cells in our body. It is the process of adding genetic material to cells. After conception, the cells in the womb that will later become the fetus are DEMETHYLATED. The process of development depends on methylation.
Increasing evidence is revealing the role of methylation in the interaction of environmental factors with genetic expression in playing a role in developmental issues like autism and ADHD. Differences in maternal care during the first 6 days of life in a mammal can cause different methylation patterns in some genes. Methylation has also been shown to impact inflammation after a child leaves the womb. We know that autism and ADHD are linked to inflammation. Now we are discovering that inflammation, autism and ADHD are linked to impaired methylation.
Methylation is responsible for:
- RNA and DNA (genetic material responsible for every function in the body)
- Immune system regulation
- Detoxification of heavy metals and other harmful substances
- Making GLUTATHIONE (the body’s main detoxification enzyme responsible for removing mercury, lead, cadmium, arsenic, nickel, tin, aluminum and antimony)
- Production and function of proteins
- Regulating inflammation
What connects B12, methylation, glutathione and Autism Spectrum Disorder?
Short answer: Dr. S. Jill James (who has recently received a NIH – National Institute of Health – grant for her research) has shown that children with ASD have impaired methylation and decreased levels of glutathione. Supporting and/or repairing the underlying impairment and deficiency translates into increased social, cognitive and language development.
Long answer: Dr. S. Jill James has also shown that children with ASD have 80% less glutathione in their cells and that 90% of children have defects in their methylation. This means that children with autism cannot effectively fuel the brain and detoxify heavy metals and other harmful substances from their system.
The brain is the only part of the body that has depends entirely on B12 to detoxify. As the the brain is over-burdened with toxic substances, the “wheels” of methylation slow, severely impacting development.
B12 works closely with folic acid. A precursor folic acid molecule must interact with the enzyme MTHFR (methylenetetrahydrofolic acid) to become 5-methyltetrahydrofolic acid (5-MTHF).
5-MTHF gives the methyl group (the “M” part) to B12 so it can become methyl-B12. Unfortunately, many children have a defect in this enzyme. In a recent study by Dr. S. Jill James, 90% of children with ASD were found to have methylation defects.
What connects MB12 and ADHD?
Dr. Richard Deth is a Ph.D and neuropharmacologist at the Northeastern University. His area of research is focused on impaired methylation and oxidative stress in neurological and neuropsychiatric disorders, including autism, ADHD, schizophrenia, and Alzheimer’s disease
Dr. Deth discovered the link between dopamine, methylation and attention which has helped Defeat Autism Now doctors understand why B12 is crucial to treatment of ADHD. Children with ADHD have difficulty bring methyl inside cells to support methylation and therefore development – especially in the areas of attention and focus.
What are the benefits of MB12 treatment?
Enhancement in executive function:
- Eye contact
- Normalized behaviours and interaction
Promotion of speech and language:
- Spontaneous language
- More complex sentences
- Increased vocabulary
Improvements in socialization, understanding and expressing emotion:
- Initiation and interactive play
- Understanding and feeling emotions
- Affection and tolerance to touch
Undesired effects to B12 therapy are a good sign of treatment success. They are not uncommon and include:
- Self Stimulating Behaviour
- Increased mouthing of objects
- Sleep disturbances – which can be managed with other treatments
- Aggression, hitting and biting – caused by frustration due to increased awareness
*Side effects can be mild to severe and are considered transient which means they will pass as treatment progresses*
- MB12 is a treatment, not a cure. However, many children using MB12 combined with other biomedical and non-biomedical therapies make incredible developmental gains and in a small percentage of children, have had their ASD label removed.
- Parents should understand that the maximum results from MB12 therapy occur over years, not months, not weeks. Initial results will be obvious within the first 3-5 week period of time; but MB12’s power is in continued use.
Why is MB12 most effective when injected into the bum?
According to Dr. Neubrander (www.drneubrander.com), “Only the subcutaneous injectable route of administration into the adipose tissue of the buttocks will produce the remarkable results parents want to see!”
All forms of administration work to some degree, and some better than others. Injection has been shown to be, by far, the most effective route of administration. It is through injection that the most dramatic strides in development are seen.
MB12 injection into the buttocks area allows MB12 to surround the cells and stay in the system continually. Oral, transdermal or intranasal forms cause the MB12 levels to fluctuate up and down. All cobalamins are absorbed in the last portion of the small intestine, the terminal ileum. Dr. Wakefield and Dr. Krigsman and Dr. Buie have shown through their research that an extremely high percentage of children on the autistic spectrum have an inflammatory bowel condition that affects this region of the intestinal tract. This makes injection a better choice than depending on the digestive tract for absorption.
Dr. Sonya Doherty, N.D., FMAPS (Cand.)
Dr. Richard Frye is a pediatric neurologist and Chief of The Division of Neurodevelopmental Disorders at Phoenix Children’s Hospital. He’s recognized as an expert on the treatment of autism.
Could you summarize the results of your recent study, “Intravenous Immunoglobulin For The Treatment Of Autoimmune Encephalopathy In Children With Autism”?
Our study recently published in Translational Psychiatry showed that a subset of children with autism spectrum disorder (ASD) who did not respond to standard interventions had autoantibodies in their blood targeting brain tissue which might qualify them for the diagnosis of autoimmune encephalopathy (AIE). The majority of children with ASD had elevated levels of autoantibodies measured by the Cunningham Panel™ (Moleculera Labs, Oklahoma City, OK) along with an elevation in the activation of calcium calmodulin dependent protein kinase II (CaMKII). A few patients had other brain targeted autoantibodies associated with AIE, such as voltage-gated calcium channels autoantibodies.
Some of the patient qualifying for the diagnosis of AIE were treated with intravenous immunoglobulin (IVIG) and their symptoms were monitored with two widely-used validated behavioral questionnaires, the Aberrant Behavior Checklist (ABC) and the Social Responsiveness Scale (SRS). Overall, IVIG was found to improve scores on both the ABC and SRS questionnaires and the great majority of parents reported improvements in additional symptoms related to ASD. The majority of patient experienced side effects from the IVIG treatment but most of the time these were mild and limited to the time around the infusion period. We were also able to divide the patients who received IVIG into those that demonstrate a positive response on the behavioral questionnaires and those that did not. This allowed us to determine if autoantibody titers of the Cunningham Panel™ collected prior to IVIG treatment could predict which individuals would response to IVIG. We found that, overall, the Cunningham Panel™ could predict which individuals would response to IVIG treatment with over an 80% accuracy rate and that the anti-dopamine receptor D2L and anti-tubulin antibodies were particularly sensitive to predicting response to IVIG treatment.
What initially led to your interest in considering immune-mediated factors in autism?
I have built my clinical practice with a vision of discovering new treatments for children with ASD. Some children with ASD do not respond to standard treatments or even new novel treatments and many times a standard medical workup does not reveal any additional obvious treatment targets. Such patients need to be investigated further to determine if there are other factors preventing them from developing skills or causing disruptive behaviors. For me, integrating an investigation of immune factors into my practice was the next step for further determining treatable factors for children with autism.
Do you have a sense for the percentage of children with autism who also have AIE?
The study describes 82 patients that were screened for AIE. This was about 8% of the patients seen in my autism clinic during the study period. 60% of these children were believed to probably have AIE, or about 5% of the children seen in my autism clinic. The percentage of the other 92% of patients seen in my autism clinic that might also have AIE is not known but it is very likely that a significant percentage of these children may have AIE. Many of these children were not investigated further because of various reasons including insurance coverage of testing, parental preference and/or difficultly in drawing blood. Further studies that systematically evaluate the general ASD population for AIE so we have a better understanding of the number of children with ASD that may benefit from treatment for AIE.
While acceptance of post-infectious autoimmune encephalopathy and pediatric acute-onset neuropsychiatric syndrome (PANS) continues to grow, there seems to be a bias within the medical community against considering PANS in children with autism. Would you agree or disagree with this statement and do you have a sense for why this might be?
I believe that the idea that there are physiological abnormalities underling ASD which can be treated is novel concept that is faced by significant skepticism. Also many are skeptical that children with ASD can recover from their disorder at all. This skepticism, I believe, it based on an old concept of children with neurodevelopmental disorders having a “static encephalopathy” in which it is believed the brain is damaged and cannot improve. As new research connects neurodevelopmental and neurobehavioral disorders such as ASD with abnormal physiology and treatments that target these physiological abnormalities, evidence will become more compelling. As treatments are shown to improve function in disorders which previously had few effective treatments, I believe more people in the medical community will embrace treatments that help children with neurodevelopmental disorders.
Some physicians have questioned the validity of the Cunningham Panel due to the fact that many children with autism have positive results. The conclusion by some is that this means the test is producing false positive results. How would you respond to this?
In our study 57% of the children we tested were positive for the Cunningham panel as we defined a positive test. We set a more stringent criteria as compared to others. For our clinical practice, the Cunningham panel is considered positive when one or more autoantibodies are elevated AND CaMKII is elevated. One of the reasons we examined the predictability of the Cunningham panel is too validate and refine the accuracy of the Cunningham panel. Our study points to two particular autoantibodies which appear to predict response. Since the components of the Cunningham panel have been developed based on converging animal and human basic research, it is very clear that these components are very likely to be very meaningful. It is likely that different components (or combination of components) will identify different subgroups of neurobehavioral, neuropsychiatric and/or neurodevelopmental disorders. Further studies are needed to further refine the most accurate use of interpreting the components of the Cunningham panel.
Do you ever treat children who did not have an abrupt or acute onset of neuropsychiatric symptoms, and if so, do they respond similarly to children who did have an abrupt onset?
Abrupt onset of neurological, behavioral or psychiatric systems as well as abrupt loss of previously acquired skills are red flags for an underlying metabolic or immunological disorder. All three cases described in our recent paper had abrupt onset of symptoms and approximately one-third of children with ASD are estimated to have neurodevelopmental regression. However, there are children without a history of an abrupt onset of systems who also respond to immune and metabolic treatments that target medical abnormalities usually associated with an acute onset of disease. Thus, I do not usually use the history of abrupt symptoms onset to guide my workup. Treatments I prescribed are guided by biomarkers.
What is your approach to managing children with autism who develop neuropsychiatric symptoms? How does this differ from your approach to those without autism?
I have found that many children with neuropsychiatric symptoms without ASD have similar metabolic and immune abnormalities as those with ASD. I use the same approach for such children and have had successes in improving their symptoms and ability to function.
Is there any research you’re working on currently that you’d be willing to tell us about?
At this time I am working with several collaborators on the interaction between metabolism and the immune system. Emerging research demonstrates connections between the immune system and metabolism, both mitochondrial disorders and oxidative stress. We have recently published a review article on mitochondrial dysfunction in autism which discussed this (https://www.ncbi.nlm.nih.gov/pubmed/30039193) and previously Dr Rossignol and I published a review article outlining the evidence for connection between these abnormalities in the brain of children with ASD (https://www.ncbi.nlm.nih.gov/pubmed/24795645). I think this is a promising area of research which may pave the way for new treatment targets.
You’ve published “Autism Spectrum Disorder in The Emergency Department: Looking Beyond Behavior.” What should ER physicians, primary care providers, and specialists be considering when a patient with autism presents with acute behavioral or neuropsychiatric symptoms?
It is very important to consider that there may be medical issues that can be driving behavioral decompensation. These medical abnormalities do not have to be complicated immune and/or metabolic abnormalities but may be more basic problems such as sleep disruption, gastrointestinal disorders and/or anxiety which may need to be evaluated and addressed. There may also be other underlying more complicated metabolic and/or immune disorders, so it is important to consider referring the child to a practitioner experienced in looking into these treatable abnormalities. Most importantly, it is important to have a vision of try to treat the underlying biological cause of the symptoms rather than just treating the behavior with medications to suppress it. Indeed, disruptive behavior may be signaling that something that is not obvious needs to be addressed and suppressing this signal may simple make a untreated medical problem worse by allowing it continue and progress without appropriate treatment.
-The Foundation For Children With Neuroimmune Disorders thanks Dr. Richard Frye for taking the time to allow FCND Founder and President Anna Conkey to interview him
This document is intended to provide a simple summary for families and physicians of the major dietary, nutritional, and medical treatments available to help children and adults with autism spectrum disorders. The discussion is limited to those treatments which have scientific research support, with an emphasis on nutritional interventions. This report excludes psychiatric medications for brevity. The dietary, nutritional, and medical treatments discussed here will not help every individual with autism, but they have helped thousands of children and adults improve, usually slowly and steadily over months and years, but sometimes dramatically.
This summary is primarily based on review of the scientific literature, and includes over 150 references to peer-reviewed scientific research studies. It is also based on discussions with many physicians, nutritionists, researchers, and parents. This summary generally follows the philosophy of the Autism Research Institute (ARI), which involves trying to identify and treat the underlying causes of the symptoms of autism, based on medical testing, scientific research, and clinical experience, with an emphasis on nutritional interventions. Many of these treatments have been developed from observations by parents and physicians.
This study involved a randomized, controlled, single-blind 12-month treatment study of a comprehensive nutritional and dietary intervention. Participants were 67 children and adults with autism spectrum disorder (ASD) ages 3–58 years from Arizona and 50 non-sibling neurotypical controls of similar age and gender. Treatment began with a special vitamin/mineral supplement, and additional treatments were added sequentially, including essential fatty acids, Epsom salt baths, carnitine, digestive enzymes, and a healthy gluten-free, casein-free, soy-free (HGCSF) diet. There was a significant improvement in nonverbal intellectual ability in the treatment group compared to the non-treatment group (+6.7 +- 11 IQ points vs. +-0.6 11 IQ points, p = 0.009) based on a blinded clinical assessment. Based on semi-blinded assessment, the treatment group, compared to the non-treatment group, had significantly greater improvement in autism symptoms and developmental age. The treatment group had significantly greater increases in EPA, DHA, carnitine, and vitamins A, B2, B5, B6, B12, folic acid, and Coenzyme Q10. The positive results of this study suggest that a comprehensive nutritional and dietary intervention is effective at improving nutritional status, non-verbal IQ, autism symptoms, and other symptoms in most individuals with ASD. Parents reported that the vitamin/mineral supplements, essential fatty acids, and HGCSF diet were the most beneficial.
Recent evidences highlight that alteration of gut microbiota homeostasis could trigger several human pathologies, among them autism spectrum disorders (ASD). This short hypothesis article summarizes the recent literature and offers a novel, complementary and biomedical drugs/natural agents-combined therapy for treating gastrointestinal issues and microbial biofilms in ASD and chronic illness.