Dr. William Walsh on Autism, OCD, PANDAS

Dr. William Walsh on Autism, OCD, PANDAS,
Depression and Methylation
William Walsh, PhD | August 14, 2014
Sheila Rogers DeMare: Dr. William Walsh, founder and president of the Walsh Research
Institute, is an international expert on nutrient-based psychiatry, including approaches to
methylation. We posed several questions to him that had been received from our readers
and he was kind enough to reply. He is a member of our ACN Latitudes advisory board, and
we greatly appreciate his time and expertise. See WalshInstitute.org
Do you think autism is reversible, and if so, what approach does your research suggest
would be most effective?
Dr. Walsh: Autism is very treatable and complete recovery is
possible in young persons whose brains have not completed the
early development process. I‘ve worked with thousands of patients
with an autism spectrum disorder and seen hundreds who achieved
full recovery after biochemical therapy and a special diet. Early
intervention is essential. We can make more progress in a month
with a two-year-old than in six months with an eight-year old. It’s
becoming increasingly clear that autism is an epigenetic gene-regulation disorder in which
environmental insults alter DNA methylation.
Treatment success requires powerful antioxidant therapy, a toxic-free environment, and
coping with G.I. tract problems. I believe the greatest progress can be made with braindirected therapies that promote development of brain neurons and synapses to enable
improved cognition, speech, and socialization. My personal favorite is metallothioneinpromotion therapy.
Many of our readers deal with obsessive-compulsive disorder (OCD). Would you please
summarize the role of histamine in OCD.
Dr. Walsh: More than 90% of OCD patients are undermethylated with low
neurotransmission at serotonin and dopamine receptors. In addition, many have low activity
at N-methyl-D-aspartate (NMDA) receptors.
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For years we have used whole blood histamine as a laboratory marker for methylation
status. Another good lab test for methylation status is the SAMe/SAH ratio test offered
by Doctors Data, Inc. Neither of these lab tests is perfect, but they are more reliable than
present genetic testing for determining if a patient is undermethylated, overmethylated, or
in the normal range.
If someone seems to have symptoms of low histamine, are there ways to increase
histamine levels? And if histamine is too high, what should be done.
Dr. Walsh: About 30 years ago, the great Carl Pfeiffer, MD, PhD, believed that histamine’s
role as a brain neurotransmitter was a central factor in schizophrenia and other mental
disorders. Since Pfeiffer’s death in 1988, we’ve learned this is not correct and that
methylation imbalances (a) cause abnormal histamine levels and (b) have a major
epigenetic effect on mental health. Methylation is the primary process for metabolizing
(destroying) histamine and there is a convenient inverse relationship between histamine
levels and methylation status. Our treatments are not aimed at normalizing histamine, but
in dealing with the brain disorders associated with overmethylation or undermethylation.
Nutrient therapies for treating undermethylation are well known, but great care must be
used in the case of undermethylated persons with low serotonin activity. Folic acid, folinic
acid, and methylfolate all act as serotonin reuptake promoters by an epigenetic
mechanism,the opposite of what these patients need.
There is increasing evidence that folates act as deacetylase inhibitors that enhance gene
expression of SERT reuptake proteins known as “transporters”. Serotonin reuptake is a far
more dominant factor than the amount of serotonin present. Folate supplements (together
with B-12) are very effective in improving methylation in most undermethylated persons.
However, folate supplements should be avoided for undermethylated patients who suffer
from depression, anxiety, or other mental disorders that involve low activity at serotonin
Recent advances in epigenetic science have provided a roadmap for effective natural
therapies that can regulate activity of serotonin, dopamine and other neurotransmitters
without the side effects associated with antidepressant drugs. I believe that the need for
drug therapies will gradually fade away as brain science advances.
Have you seen any children with a PANDAS/PANS diagnosis, and do you think there is a
nutritional way to avoid or treat such severe behavioral and neurological reactions to
bacterial, viral, or other types of infections?
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Dr. Walsh: PANDAS/PANS has many characteristics of an epigenetic gene-regulation
disorder especially (a) sudden onset, (b) a multitude of serious symptoms, (c) a condition
that is difficult to treat, and (d) a condition that can persist for years after onset. Epigenetic
disorders are caused by environmental insults that alter DNA methylation or other generegulation factors.
I’ve only seen a few dozen children diagnosed with PANDAS and do not consider myself an
expert in this disorder. I have noticed that most of these children exhibit severe
undermethylation and oxidative stress. Also, a high percentage had elevated pyrroles and
zinc deficiency. It’s hard to believe that nutrient therapies to correct these imbalances would
not result in significant improvement. However, I have no outcome data for PANDAS/PANS.
Your research shows there are five types of depression, and you recommend that a
different treatment approach should be taken for each type. How should a parent go
about finding a doctor who can evaluate them to learn which type of depression they may
have, and then offer suitable treatment?
Dr. Walsh: We have identified five chemical biotypes of clinical depression that represent
about 95% of cases. Our classification system is based on studies of 2,800 patients,
including more than 250,000 blood/urine chemistry results and an in-depth medical history.
Until now, most mainstream experts have regarded depression as a single condition with
variations along a central theme – low activity at serotonin receptors.
We have observed low serotonin activity in two of the biotypes, with different brain
disorders dominating the other cases. We reported these findings at the annual American
Psychiatric Association (APA) meeting in New York City this spring.
The undermethylation (38%) and pyrrole disorder (15%) biotypes involve low serotonin
activity with many reports of improvement after SSRI antidepressants. However, these
patients also respond to individualized nutrient therapy. High-copper (17%) depressives
showed little response to antidepressants but reported great improvement after copperlowering nutritional supplements. The low-folate (20%) biotype consisted of patients who
reported severe intolerance to SSRIs, but thrived on supplements of folates and B-12. The
smallest biotype (5%) involved toxic metal overloads such as lead, mercury, cadmium, etc.
At the APA we recommended inexpensive blood/urine tests for all depression patients, and
different treatment approaches for each biotype. This is a medical procedure that requires a
practitioner experienced in these protocols. We are actively engaged in continuing medical
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education (CME) educational programs to enable doctors to incorporate these methods into
their practices.
Our next USA training program will be this October in Illinois. A list of doctors using these
protocols is provided on our website and in the appendix of my book Nutrient Power.
In your opinion, do people fall into either an overmethylated or undermethylated status
or can you be an undermethylator in certain areas of the methylation cycle and an
overmethylator in other areas of the cycle? If someone has some traits of an
undermethylator and some traits of an overmethylator, what would you recommend?
Dr. Walsh: Based on my massive chemistry database, about 22% of the population is
undermethylated and 8% overmethylated. These are inborn tendencies that usually persist
throughout life. Undermethylation usually results from single nucleotide polymorphisms
(SNPs) that weaken MTHFR or other enzymes in the methylation cycle. Overmethylation is
generally caused by enzyme weaknesses (SNPs) in the SAMe utilization pathways.
Nutritional supplements, certain drugs, and special diets can adjust methylation, but the
inborn tendency usually remains. We have evaluated the methylation status of more than
25,000 patients and controls and identified dozens of distinctive symptoms and traits
associated with methylation imbalances. For example most undermethylators report
allergies to ragweed and have a history of strong will, perfectionism, competitiveness, and
OCD tendencies.
Overmethylators are usually characterized by excellence in music and art, empathy,
excellent socialization, high anxiety, and food/chemical sensitivities. All of these traits are
generalities with many exceptions and very few persons exhibit all of the traits associated
with their methylation biotype. However, an experienced practitioner can usually predict the
methylation lab results after a good medical history.
What are your thoughts on using genetic testing, such as “23 and Me” to create an
individual methylation roadmap/treatment plan.
Dr. Walsh: Genetic testing is quite inexpensive, highly accurate, reliable, and will certainly
grow in importance in future years. These tests can already identify predispositions for
many disorders such as breast cancer and Alzheimer’s and may soon obsolete the need for
pap smears. However the reliability of genetic testing for assessing methylation is quite
limited at present. Identifying SNP weaknesses in MTHFR and other methylation-cycle
enzymes does not necessarily mean that individual is undermethylated. There is a “tug-of-
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war” competition between enzyme SNPs that weaken methylation and SNPs in the SAMe
utilization pathway that can produce overmethylation.
Since the genetic information is qualitative and not quantitative, it is often impossible to
determine the net methylation potential from genetic testing. Fortunately there are blood
tests that can test for overall methylation status (the net effect of the competing SNPs), and
I greatly prefer to use them – SAMe/SAH ratio and whole-blood histamine. In addition,
blindly using methylfolate (Deplin) for patients with 677T MTHFR or other weakened
enzymes can produce negative results in patients afflicted by low serotonin activity. Folate
supplements including Deplin tend to drive serotonin activity even lower by an epigenetic
mechanism (see third question, above).
The benefits from improving methylation are overwhelmed by weakened serotonin
neurotransmission for these persons. Methylfolate supplements are a clever approach for
coping with undermethylation in persons with MTHFR enzyme weaknesses. However the
potency of methylfolate has been greatly exaggerated. The methylation cycle spins
constantly with more than a million methylation reactions per second.
The methylation cycle somewhat resembles the Indianapolis Speedway with traffic
constantly spinning around the track. Methylfolate is what I call a “suicidal” nutrient, that is,
a nutrient that acts only once. After a single pass through a portion of the cycle,
methylfolate loses its identity and becomes part of the garden-variety THF pool.
Methylfolate is somewhat more effective that folic acid and folinic acid, but is not as
effective as advertised. The bottom line is that methylfolate and other folate supplements
are very effective in enhancing methylation for autism and other conditions that are not
dominated by low serotonin activity.
In your book Nutrient Power, you frequently use the term “methyl” as in the
methyl/folate balance and in giving methyl to address neurotransmitter imbalances.
What is methyl? Do you mean methylcobalamin.
Dr. Walsh: The occasional use of methyl in my book is shorthand for methyl donors such as
methionine and SAMe. Twenty years ago I presented a paper at the annual APA meeting
describing the opposite effects of folate supplements and methyl donors on
neurotransmitter activity and began using the term methyl/folate ratio. I believe it’s time to
find a better expression for this factor.
Walsh Research Institute website
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Graphic courtesy of Walsh Research Institute
About William Walsh, PhD
Dr. William Walsh is an expert in the field of nutritional medicine. President of Walsh
Research Institute, he conducts physician training in biochemical/nutrient therapies. His
latest book is Nutrient Power. He is an advisory board member for ACN Latitudes.
The nonprofit Association for Comprehensive Therapy (ACN) publishes the website
Latitudes.org. ACN focuses on finding and sharing advanced and natural therapies for
neurological conditions.
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