Episode 595: Can Lyme Affect Folate in the Brain? Dr. Lindsey Wells on Autism, PANS/PANDAS & FRAA
What if some of the depression, anxiety, brain fog, cognitive dysfunction, OCD, speech changes, and other neuropsychiatric symptoms experienced by people with Lyme and other vector-borne diseases involve more than the infection itself?
In this episode of the Tick Boot Camp Podcast, Matt Sabatello sits down with Dr. Lindsey Wells, ND, a Connecticut naturopathic physician whose work focuses heavily on children with Lyme Disease, PANS/PANDAS, autism spectrum disorder, neurodevelopmental conditions, and other vector-borne diseases.
The centerpiece of the conversation is Dr. Wells' newly published research, “Folate Receptor Alpha Autoantibodies in Vector-Borne Disease Populations.”
Her study explored an intriguing question: could some people with Lyme disease, Bartonella, Babesia, or other vector-borne infections also have an immune-mediated problem that prevents enough folate from reaching the brain?
The findings open an important new area of investigation.
What Are Folate Receptor Alpha Autoantibodies?
Folate is essential for neurological function, neurotransmitter production, mitochondrial health, methylation, and numerous other biological processes.
But having adequate folate in the bloodstream does not necessarily mean enough folate is reaching the brain.
Dr. Wells explains how folate receptor alpha autoantibodies, commonly abbreviated FRAAs, can interfere with the folate receptor responsible for helping transport folate across the blood-brain barrier.
These autoantibodies can either block folate from attaching to the receptor or bind to the receptor and interfere with its normal function.
The result may contribute to a condition known as cerebral folate deficiency, where folate availability inside the central nervous system is inadequate despite seemingly normal blood levels.
A Surprising Finding in Vector-Borne Disease Patients
Dr. Wells and her colleagues examined patients with confirmed evidence of vector-borne infections.
Their study found that 61.8% of the vector-borne disease-positive patients tested positive for folate receptor alpha autoantibodies.
That finding immediately raises bigger questions.
Are vector-borne infections contributing to the development or elevation of these autoantibodies?
Can Lyme or another infection be treated while FRAAs remain elevated?
Could persistent FRAAs contribute to symptoms that patients and clinicians continue attributing entirely to infection?
The Borrelia Finding That Caught Dr. Wells' Attention
One of the most intriguing findings involved the soluble folate receptor, an abnormal finding seen much less frequently than standard binding or blocking FRAAs.
Eight patients in the study were positive for soluble folate receptor.
Seven of those eight had confirmed evidence of Borrelia species infection, while the remaining patient had an indeterminate result involving relapsing fever Borrelia.
Dr. Wells discusses why this observation raises questions about whether Borrelia infection, immune activation, inflammation, or another biological mechanism could influence folate receptor function.
Bartonella, PANS/PANDAS and Severe Neuropsychiatric Symptoms
The conversation also goes deep into Bartonella.
In Dr. Wells' clinical experience, Bartonella frequently appears in some of the more complex children she treats with PANS/PANDAS, particularly those experiencing symptoms such as:
- Severe anxiety
- OCD
- Rage and aggression
- Irritability
- Sensory sensitivities
- Cognitive or behavioral regression
- Persistent neuropsychiatric flares
Among FRAA-positive patients in her vector-borne disease study, Bartonella was also the most common individual infection identified.
Dr. Wells explains why she believes clinicians evaluating children with unusually severe or persistent PANS/PANDAS symptoms should consider looking beyond traditional triggers such as strep.
Can Infection Trigger an Autoimmune Process That Continues Afterwards?
One of the most important parts of the interview explores what happens after an infection.
Dr. Wells describes how an infection can activate the immune system, but in susceptible patients the immune response may not simply return to baseline once the original infection improves.
Immune dysregulation and molecular mimicry may potentially allow inflammatory or autoimmune processes to continue.
That creates an important question for Lyme disease:
Could a patient successfully reduce or address an infectious burden but continue experiencing symptoms because another downstream immune or metabolic problem remains?
What Causes FRAAs?
Dr. Wells discusses several factors associated with FRAAs.
One is a non-genetic hereditary pattern in which autoantibodies may be transmitted from a parent.
Another important area is animal dairy consumption.
She discusses research suggesting that proteins associated with animal dairy may share similarities with folate receptor structures. Through a molecular mimicry mechanism, antibodies generated against those proteins could potentially cross-react with folate receptors.
Dr. Wells therefore commonly incorporates dairy removal when addressing FRAA-positive patients.
She also discusses clinical observations suggesting that FRAA levels can fluctuate and may rise during periods of infection or physiological stress.
The FRAT Test
Patients cannot determine FRAA status through a routine folate blood test.
Dr. Wells discusses the FRAT Folate Receptor Autoantibody Test, a specialty blood test designed to detect autoantibodies to folate receptor alpha.
The test evaluates binding and blocking autoantibodies and can also identify the soluble folate receptor finding discussed in Dr. Wells' research.
Folinic Acid and Leucovorin
If FRAAs are interfering with one pathway responsible for transporting folate into the brain, Dr. Wells explains that another approach may be to use an alternative transportation pathway.
That is where folinic acid, including the prescription form leucovorin, enters the discussion.
Rather than eliminating the autoantibodies themselves, folinic acid can utilize another folate transport mechanism to help deliver folate into the central nervous system.
Dr. Wells discusses improvements she has observed clinically in areas such as anxiety, OCD, cognitive function, communication, speech fluency, and other neuropsychiatric symptoms.
Importantly, she emphasizes that dosing needs to be individualized and gradually increased under the guidance of a knowledgeable practitioner.
People interested in the supplemental form discussed during the episode can learn more about Emephysis HI-FOLINIC.
Treating More Than the Infection
One of the themes throughout this conversation is that complex chronic illness rarely comes down to one intervention.
Dr. Wells describes a three-part approach to many of her complex pediatric patients:
Address the microbial burden. Depending upon the individual patient, this may include vector-borne infections and other infectious triggers.
Address immune dysregulation and inflammation. This may involve anti-inflammatory and immunomodulatory strategies.
Support the symptoms affecting daily life. Helping a child function, communicate, sleep, attend school, interact socially, and experience less anxiety or OCD matters while deeper underlying issues are being addressed.
It is an approach that recognizes both the biology of chronic illness and the reality of the person living through it.
Learn More About Dr. Lindsey Wells
Dr. Lindsey Wells practices naturopathic medicine in Trumbull, Connecticut, with a major focus on complex pediatric conditions including PANS/PANDAS, autism, neurodevelopmental disorders, and vector-borne diseases.
Learn more about Dr. Wells and her practice.
Read Dr. Wells' Research
Folate Receptor Alpha Autoantibodies in Vector-Borne Disease Populations