Welcome to the first in our special series sharing insights and recent research from the MEDMAPS 2023 Spring Conference attended by Dr. Potter. MAPS stands for Medical Academy for Pediatric Special Needs and arose from the original Defeat Autism Now organization initially serving parents and providers caring for children with autism spectrum disorder). This Spring Conference focused not only on autism research but on Lyme and other infections, including COVID’s effects on children. Come back in the coming weeks to read more about what I learned at the conference and how Sanctuary is growing in providing cutting edge care to your precious little ones.
The methylation cycle (involving B vitamins such as folate, B12, and B6 among others) and its products, such as S adenosyl methionine (SAMe), choline, and creatine, both play a major role in our health, including our brain development and function. This key role in brain health makes it rather unsurprising that it could be linked to autism. Other studies have linked folate and B12 deficiencies in mom or baby with autism risk. Beyond the simple fact that ones diet may not include enough of these essential nutrients, some people eat plenty, but one part of their body does not get enough folate for proper functioning. When someone has cerebral folate receptor antibodies, they may not get enough folate across their blood brain barrier and leaving the nervous system short of a full tank, In studies this may increase the risk of autism.
Dr. Frye and Dr. Rossingnol at the Rossingol Medical Center care for a large number of autism patients and want to know like the rest of us in the pediatric world, what causes autism. We can all agree that multiple factors contribute to the development of this disabling condition and each child with autism in our clinics have their own unique combination of factors leading to their symptoms. Treating these children and leading them to recovery requires treating all the identified factors once we know them. Dr. Frye and his team may have given us one more target in the fight against autism by looking at these cerebral folate receptor antibodies.
When we eat folate or other nutrients, we are next dependent on our GI tract to pull the nutrients into our blood stream. Once floating in the blood, the nutrients make their way throughout the body. Some simply diffuse into cells easily while others require some type of help by way of energy requiring transport through proteins in cell membranes. This later case is especially true in the nervous system where the blood brain barrier works hard to keep out unwanted chemicals, allowing only desired substances to pass out of the blood and into the brain.
For folate, this process requires a receptor that binds folate floating in the blood, pulls it across the blood brain membrane and passes it along to the nerve cells on the other side of the barrier. Without proper functioning of this receptor mediated transport process, the nerve cells will not get enough folate to run the methylation cycle. Without adequate cycling of methylation, neurotransmitters will not be produced adequately nor metabolized sufficiently. Without this folate, over time less and less choline is made for phosphatidylcholine to provide for nerve cell membranes and the myelin insulation which covers nerve cell axons. The axons from one nerve cell to another convey the electrical signal between cells and the myelin from phosphatidylcholine is necessary for their proper functioning.
In cases where patients develop antibodies to this receptor, the rate of folate entry into the brain slows. The level of folate in the brain’s surrounding fluid lowers. The methylation cycle slows and different symptoms develop. Our clinic as seen such adult patients struggle with anxiety, brain fog, and depression. This study by Dr. Frye first reviewed the medical literature to determine the prevalence of this condition in children with autism. Overall, a significant rate of these antibodies in children with autism was found, but it varied considerably between the studies and case series that Dr. Frye reported. Again, while cerebral folate antibodies may be one factor, it is not the only factor in autism.
Beyond looking at studies which tested for this condition, they also looked at a few studies which used leucovorin, also known as folinic acid in the treatment of these children. While leucovorin is commonly used in chemotherapy to mitigate the effects of certain chemotherapy agents, it is not a chemotherapy itself. It is simply a form of folate like methyl folate which our body can use to keep the methylation cycle going. The studies demonstrated improvements in the autism scores without significant side effects. Dr. Frye concludes that further studies are warranted to determine the extent benefit for this safe and likely effective therapy.
With awareness of this connection between autism and folate receptor antibodies, we will be testing our young patients with autism more frequently than before. We have seen benefits for some of our patients with even low dose folate or folinic (but not folic acid) already. However, if someone has these antibodies, they may need 5 to 10 times higher doses. Knowing this test result will be helpful so that we don’t have to try high dose on every patient. We have found that giving high doses to some patients with methyl folate or methyl B12 can trigger some anxiety and other over-methylation symptoms. Separating out who is most likely to benefit with this test increases chances of success and decreases chances of side effects.
Helping our young patients with autism achieve healthier more abundant present and future health requires staying on the forefront of therapy, applying all the tools we have in our tool box.
Rossignol DA, Frye RE. Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis. Journal of Personalized Medicine. 2021; 11(11):1141. https://doi.org/10.3390/jpm11111141
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.