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How apple cider vinegar may assist overmethylators

This publication suggests that acetate, derived from acetic acid, may assist the brain and other organs in reducing inflammation. That it does so specifically by acetylating DNA histones, explains the effectiveness of products such as organic apple cider vinegar in managing overmethylators.

Overmethylators, who may be identified by a histamine blood test, would benefit because acetyl-CoA competes with methyl compounds at the DNA histone. Whichever molecule binds to the histones determines if the cell turns to the slow mode or fast mode. In other words, histone and methylation control the activation of the cell and the product of their DNA transcription to produce proteins.

In summary, apple cider vinegar’s affect on histones could be very good for overmethylators. And consequently it may not be so good for undermethylators. Inadequately nourished or supplemented overmethylators have a tendency manifest symptoms of verbosity, paranoia, phobias and at the further end of the scale auditory and delusional schizophrenia. Dr William Walsh PhD believes that as many as 46% of persons with schizophrenia are overmethylators.

 

Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression.

Soliman ML1, Rosenberger TA.

Author information

Abstract

Acetate supplementation increases brain, heart, and liver acetyl-CoA levels and reduces lipopolysaccharide-induced neuroinflammation. Because intracellular acetyl-CoA can be used to alter histone acetylation-state, using Western blot analysis, we measured the temporal effect that acetate supplementation had on brain and liver histone acetylation following a single oral dose of glyceryl triacetate (6 g/kg). In parallel experiments, we measured the effect that acetate supplementation had on histone deacetylase (HDAC) and histone acetyltransferase (HAT) enzymic activities and the expression levels of HDAC class I and II enzymes using Western blot analysis. We found that acetate supplementation increased the acetylation-state of brain histone H4 at lysine 8 at 2 and 4 h, histone H4 at lysine 16 at 4 and 24 h, and histone H3 at lysine 9 at 4 h following treatment. No changes in other forms of brain or liver H3 and H4 acetylation-state were found at any post-treatment times measured. Enzymic HAT and HDAC assays on brain extracts showed that acetate supplementation had no effect on HAT activity, but significantly inhibited by 2-fold HDAC activity at 2 and 4 h post-treatment. Western blot analysis demonstrated that HDAC 2 levels were decreased at 4 h following treatment. Based on these results, we conclude that acetyl-CoA derived from acetate supplementation increases brain histone acetylation-state by reducing HDAC activity and expression.

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Methylation and Epigenetics – William Walsh PhD Podcast

Methylation Overview:

New discoveries in the field of epigenetics have led to effective advanced nutrient therapies for children and adults challenged by brain disorders, such as autism, Alzheimer’s, depression, bipolar, schizoaffective disorders, and ADHD/ADD. A Walsh panel can determine a clients’ methylation status, and thus a treatment based on their biochemical individuality. Dr. David Epstein, D.O., offers full assessments and specific recommendations to clients according to the Walsh protocol. Second Opinion Physician is a holistic telemedicine practice, specializing in nutrient therapies developed by Dr William J Walsh and the Walsh Research Institute.

Podcast below provide by:

The CoreBrain Journal Walsh Molecular Series: 

Dr Walsh provides a more detailed description of the significance of methylation and epigenetics and the consequence of undermethylation or overmethylation on mood and mental function. CLICK ARROW BELOW TO BEGIN:

 

About Dr Walsh               

William J. Walsh, PhD, FACN, president of the nonprofit Walsh Research Institute, is an internationally recognized expert in the field of nutritional medicine and a key scientist paving the way for nutrient-based psychiatry and nutritional medicine.  Over the past 30 years, Dr. Walsh has developed biochemical treatments for patients diagnosed with behavioral disorders, attention deficit (hyperactivity) disorder, autism, clinical depression, anxiety, bipolar disorders, schizophrenia, and Alzheimer’s disease that are used by doctors throughout the world.

His book, Nutrient Power: Heal Your Biochemistry and Heal Your Brain [updated May 2014], describes specific findings for his evidence-based nutrient therapy system.

Dr. Walsh’s noted accomplishments include:  (a) groundbreaking studies reporting reduced violent behavior following nutrient therapy, (b) the 1999 discovery of undermethylation and copper/zinc imbalances [Coming: CBJ/034] in autism, (c) the 2000 finding of metallothionein protein depletion in autism, (d) the 2007 published study linking copper overload and post-partum depression, (e) the identification of five biochemical subtypes of clinical depression, (f) the 2011 development of the Walsh Theory of Schizophrenia [Coming: CBJ/042], and (g) the direction of the Beethoven Research Project that revealed that the composer suffered from severe lead poisoning.

His internationally acclaimed presentations, including for the American Psychiatric Association, affirm his important contributions to both functional and traditional medical groups.

Clinical Experience

After earning degrees from Notre Dame and the University of Michigan, Dr. Walsh received a PhD in chemical engineering from Iowa State University.  While working at Argonne National Laboratory in the 1970s, Dr. Walsh organized a prison volunteer program that led to studies of prisoners and ex-offenders researching the causes of their violent behavior.  The collaboration with renowned (late) Carl C. Pfeiffer, MD, PhD, a pioneer in the field of nutritional research therapy, led Dr. Walsh to the development of individualized nutrient protocols to normalize body chemistry and brain chemistry. Dr. Walsh went on to study more than 30,000 patients with mental disorders acquiring an unparalleled database of more than 3 million chemical assays during his clinical and research work.

NB: Dr. Walsh has conducted chemical analysis of more than 25 serial killers and mass murderers, including Charles Manson, Richard Speck, James Oliver Huberty, Patrick Sherrill and Arthur Shawcross.  He has assisted medical examiners, coroners, Scotland Yard, and the FBI in these forensics studies. He has designed nutritional programs for Olympic athletes, NBA players, major league baseball players, a heavyweight boxing champion, PGA and LPGA golfers, and others.

 

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Natural Remedies for Mood Disorders

Pioneers in the field of Nutrient Therapy, such as Carl Pfeiffer, MD, PhD and William J. Walsh, PhD, President of the Walsh Research Institute, have found abnormalities in and elevated or reduced levels of histamines in the body to be central to many different behavioral or mood disorders, such as bipolar disorder, depression, anxiety, panic disorders, and even classical paranoid .  The effects of being over or under methylated or of having abnormalities in histamine levels are vast and often debilitating… but the good news is that there exists completely safe and natural remedies for these imbalances!  And the power, speed, and efficacy of these natural remedies can be a source of great hope and relief for sufferers of mood disorders, including depression, anxiety, and other upsetting conditions that are not uncommon in an increasingly toxic and often stressful modern way-of-life.

BIOTYPE 1 – Undermethylators (38% of depression population):

Some of the common characteristics of this depressive group are: OCD tendencies, calm exterior but high inner tension, competitive, perfectionistic, addictive tendencies, and high libido.  Undermethylators may be benefited by SSRI medications, but often with side-effects.  The Nutrient Therapy approach would most likely include the addition of methionine or SAMe. These amino acids contribute a methyl compound and increase total serotonin production.  Other important supplements include inositol, B6, calcium, magnesium and vitamin C.

Folic acid is absolutely not recommended for these types.

BIOTYPE 2 – Overmethylators (or “Low-Folate Depressives”) (20% of depressed population):

Some of the commonly recurring characteristics within this population are: high anxiety, panic, noncompetitive in sports or games, food/chemical sensitivities, high musical or artistic ability, underachievement, sleep disorders, and low libido.  This subtype tends to do poorly with methylation and in fact do very poorly with SSRI antidepressants. This is because they have plenty of serotonin, but they lack B12 and Folic Acid. Likewise, SAMe and methionine are not recommended.  An effective nutrient therapy would seek to enhance acetylation and suppress methylation for these patients, folate and niacinamide being excellent supplements for this.

Excellent Podcast Below Featuring William Walsh PhD on Bulletproof Radio Discussing Methylation

One-carbon (methyl) groups are integral to the synthesis of neurotransmitters, genetic expression, metabolism, and other crucial biochemical reactions.  Methylation, also referred to as the methyl/folate ratio, turns cells on and off through histone bodies which are connected to the .  DNA is responsible for the production of proteins which can express in the form of enzymes, hormones, inflammatory cells, neurotransmitters, and more.  Methylation affects anything that is produced by the differentiated cells of the body.  As far as brain function is concerned, methylation is a major player in the synthesis of serotonin, dopamine, and norepinephrine, three neurotransmitters whose proper balancing and healthy levels are essential for the maximized functioning of our brains and for the maintenance of a healthy emotional life.

In overmethylated patients there tends to be an abundance of serotonin, dopamine, and norepinephrine whereas undermethylated patients tend to be depleted in these essential neurotransmitters.  Within the realm of behavioral disorders, what is crucial is the enzyme which is responsible for returning serotonin to the originally releasing neurotransmitter (a process referred to as reuptake).

  • When methylation is high (“”), the enzyme levels that return serotonin back to the releasing neuron are low and there is increased serotonin activity.  When methylation is low (“”), the enzyme levels will be in excess and the serotonin activity will be low.
  • Additionally, overmethylation inhibits expression of the genes, of each cell in the body. It does this by causing a folding of the DNA structures. Undermethylation will cause DNA to unfold, making it more expressive.  Folding of the DNA diminishes the activity of that DNA which are responsible for the daily producing of critical hormones, enzymes and other types of proteins etc. All of these factors contribute to conditions ranging from autism to alzheimers, depression and anxiety. Understanding this new science gives us an opportunity to more successfully utilize natural remedies for mood disorders and healthy brain activity in general.

More than two decades ago, Dr. Pfeiffer studied the metabolism of over 20,000 patients suffering from schizophrenia and kept running into the phenomenon of severely deficient levels of histamine in these patients, later referring to this low histamine syndrome as “histapenia”.  Histapenia was found to be common in his classical paranoid schizophrenic patients, as well as those suffering from anxiety and panic disorders.  The histamine deficiency also coincided with nutrient deficiencies, specifically folic and and/or B12, and with an overload of copper.  Based on these findings, Dr. Pfeiffer enacted an aggressive therapy regime using B12, B3, and folic acid for these patients… and had tremendous success!  The patients experienced dramatic improvements, and Dr. Pfeiffer attributed the success to the elevation of histamine levels.  Ensuing studies have pointed to the role of the methyl/folate ratio and its normalization as being critical to these favorable outcomes.

  • Elevated histamine indicates undermethylation, and there are symptoms which may point to this being the case for an individual, for example: seasonal allergies, obsessive-compulsive tendencies, being strong-willed, perfectionism, and high-libido, just to name a few.
  • Some conditions associated with undermethylation are OCD obsessive compulsive disorder, trichotillomania, oppositional-defiant disorder, competitiveness, bulimia, anorexia, impulsivity (gambling/shopping disorders, etc), depression, schizoaffective disorder, and delusions.

On the other hand, overmethylated persons typically suffer from food/chemical sensitivities, dry eyes, and a severe intolerance to SSRI medications (such as Prozac, Celexa, Lexapro, Luvox, Paxil, Zoloft, etc), and have strong association with anxiety and panic disorders, low motivation, paranoid schizophrenia, hyperactivity, anxious depression, learning disabilities, and even hallucinations.

At Second Opinion Physician we request labs to be done for all patients (appropriate to the information gathered at initial consultation) in order to assess nutrient levels, and which includes testing for methylation levels, so that we might then effectively prescribe natural remedies for mood disorders.

  • If a patient is found to be overmethylated we typically treat with folic acid and B12, plus a focus on dietary considerations (for example, perhaps recommending an increase in animal skin, cartilage, and gelatin consumption in order to provide B vitamins and proteins which naturally counter excess methylation).  B12 and folic acid therapies can noticeably slow down methylation symptoms within 2 weeks to 2 months.
  • If methylation is low, we strive to increase serotonin production naturally, with supplements/nutrients such as B6 and Zinc and may recommend adding methionine to the patient’s diet, which comes naturally from muscle meats.  We may also recommend the addition of SAMe, which is a fast-acting and more readily available methylator.  Patients may see major effects with methionine in about 1-3 months, and even more quickly with SAMe treatment.

Methylation and histamine-level balancing is just one example of the nutrient-based approach to health taken by Second Opinion Physician.  By using natural remedies to balance brain chemistry and improve methylation status we can tackle even the most tenacious mood disorders, behavioral disorders, combat anxiety, and treat depression naturally to create more overall health and emotional balance for otherwise suffering individuals.

William Walsh Protocol Practitioners

Listen to William Walsh PhD Podcast with Bulletproof Radio:

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Five Biotypes of Depression

The Five Biotypes of & Advanced Nutrient Therapies with William Walsh, PhD

Second Opinion Physician, David Epstein, D.O., is trained in the Walsh Protocol, developed by Dr. William J. Walsh, PhD, and committed to the natural treatment of depression, as well as other mood and behavioral disorders, thru the use of Nutrient Therapy.  It is estimated that 13.1 to 14.2 million American adults suffer from depression currently and that at least 32 million will similarly face this disease at some point in their lives.  However, the disease can be tricky to tackle for a number of reasons, not least of which are the grave misconceptions regarding depression which are upheld by mainstream psychiatry.  

Mainstream psychiatry typically regards depression as a “single entity with variations along a central theme”, according to Dr. Walsh.  It is also mostly assumed that those suffering from depression have low activity in the receptors in their brains responsible for the handling of serotonin, a monoamine neurotransmitter associated with feelings of “happiness and well-being”.  It is this central belief which informs most decisions as far as the majority of medications being used to treat depressive patients.  Most are prescribed SSRI medications which inhibit the reabsorption of serotonin into its originating receptor, thereby leaving more of the serotonin free to bind to postsynaptic receptors and to have positive effects, allegedly, on the entire organism.  However, after having evaluated 2,800 patients diagnosed with clinical depression, thru the lens of nutrient therapy, Dr. William Walsh is turning both of these centrally held misconceptions about depression and its treatment on their heads.  

By way of his evaluation and ongoing database studies, Dr. Walsh and his colleagues have identified five high-incidence depression biotypes.  These biotypes reference distinct and unique neurotransmitter & nutrient imbalances and symptoms, and therefore, according to Walsh, should be approached as 5 different disorders.  Additionally, he has made links between certain biotypes and the ineffectiveness of SSRI medications, even identifying some subgroups for whom SSRIs are actually dangerous.  

The biotype studies have given us great insight into these different depressive disorders, as well as a more workable look into what causes depression. Using this new revolutionary approach, Second Opinion Physician is able to direct patients towards lab tests which can identify the very nutrient & neurotransmitter imbalances triggering their particular depression, and can then provide recommendations for natural, highly effective, and individualized treatments.  This treatment will most often fall within the spectrum of about 6-8 different natural , along with dosage recommendations specific to the individual’s other biochemical status. 

A brief breakdown of each of the 5 Biotypes of Depression can be found below.

A note from our physician: Any one person will have variable combinations so the treatment must be individualized. I don’t recommend anyone trying to treat themselves based on this information unless a lab test is performed and a trained practitioner is coaching the individual. Follow link to learn more:

BIOTYPE 1 – Undermethylators – 38% of depression population

BIOTYPE 2 – Overmethylators  – or “Low-Folate Depressives” – 20% of depression population

BIOTYPE 3 – Pyrroluria or Pyrrole Depression – 15% of depression population

BIOTYPE 4 – Copper Overload or “High-Copper Depression” – 17% of depression population

95% of the patients in this subgroup are female.  Overly high copper levels can result in elevated norepinephrine and reduced dopamine in patients, high-anxiety and a tendency for panic, a high incidence of postpartum depression, estrogen intolerance, tinnitus, and extremely sensitive skin.  These persons are typically experiencing oxidative stress throughout their body as they have a limited ability to manage free radicals, such as heavy metals. Working to lower copper levels would be the nutrient therapy approach, but caution must be taken to not lower levels too quickly as it will temporarily worsen effects (due to copper leaving tissue and dumping into the blood or digestive tract).  Recommended supplements may include zinc, molybdenum, manganese and chromium (trace elements) and metalothionine producing amino acids. SSRIs are generally reported as ineffective for those suffering from High-Copper Depression.

BIOTYPE 5 – Toxic Metal Depression (5%)

These individuals have an excessive metal burden, such as lead toxicity.  They often exhibit severe oxidative stress, unrelenting depression, abdominal stress, a metallic taste in the mouth and bad breath, high levels of irritability or anger, and food sensitivities.  A gradual detox regimen might include supplements such as ALA, trace elements, metalothionine amino acids and antioxidants.  SSRIs are generally reported as ineffective for the Toxic Metal subgroup of patients struggling with depression.

Thanks to the dedicated work of Dr. William J. Walsh and other pioneers in the fields of nutrient therapy and , we now have more insight into some of the actual causes of depression, and can apply more targeted, individualized, effective, and safe treatments for patients.  Thru the recommendation of lab tests and subsequently the application of the various possibilities for nutrient and supplement based therapy, Second Opinion Physician can help patients finally break free from the painful and often debilitating struggle with depression, and other mood or behavioral disorders, to find relief and reclaim balance and health.d

Watch Video for more details:  Dr. William J. Walsh speaking to the American Nutrition Association about the 5 Biotypes of Depression and Advanced Nutrient Therapies

This is a simple summary followed by video of Dr Walsh explaining this in detail at the American Nutrition Association in 2014.

Any one person will have variable combinations so the treatment must be individualized. I don’t recommend anyone trying to treat themselves based on this information unless a lab test is performed and a trained practitioner is coaching the individual. There is usually about 6-8 different supplements and dosages recommended for the five  biotypes of depression, but it works something like this. 

 

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Bill Walsh Theory of Schizophrenia

This is an excellent summary of the Dr Walsh theory of  from Biobalance Health in Australia:

Thesis 1:  Schizophrenia is in Nature:  A psychotic “breakdown” is usually followed by a lifetime of mental illness and misery. This often permanent change in functioning results from altered chromatin bookmarks that regulate gene expression. Since the deviant marks are maintained during future cell divisions, the condition doesn’t “go away”.

Thesis 2: Weak Antioxidant Protection is a Distinctive Feature of Schizophrenia:  Most schizophrenics exhibit a genetic or acquired weakness in antioxidant protection. Evidence from my extensive chemistry database includes generally low levels of glutathione, cysteine, selenium, zinc, polyunsaturated fats, together with high levels of non-ceruloplasmin copper.

Thesis 3:  Oxidative Overload Produces Deviant Epigenetic Marks in Schizophrenia: Cancer researchers have identified cumulative oxidative stress as a trigger that can transform healthy cells into cancer cells by altering epigenetic marks that permanently change gene expression. Examples include (a) skin cancer developing after years of excessive sun exposure, and (b) lung cancer following years of cigarette smoking. It’s not a coincidence that nearly all schizophrenia patients exhibit excess oxidative stress. The onset of schizophrenia occurs when oxidative stresses exceed the threshold level needed to alter chromatin marks that regulate gene expression.

Thesis 4:   Imbalances Promote Epigenetic Vulnerability to Oxidative Stress:  Abnormal methylation of chromatin is a leading cause of epigenetic errors in gene expression. The combination of oxidative overload and a methyl imbalance can produce gene expression changes that result in a chronic schizophrenia condition. The two most prevalent forms of schizophrenia develop in persons who exhibit either (a) methyl overload or (b) methyl deficiency. The two resulting psychotic disorders exhibit very different brain chemistry and symptoms.

A. – About 46% of persons diagnosed with schizophrenia exhibit excessive methylation of chromatin along with weak antioxidant protection. Mental breakdowns generally occur during severe physical or emotional traumatic events that produce overwhelming oxidative stress and deviant gene marks. This schizophrenia biotype is a sensory disorder that generally involves auditory, tactile, or visual hallucinations. This condition is associated with elevated activity of dopamine and norepinephrine, and reduced glutamate activity at NMDA receptors.  The most common DSM-4 diagnosis is paranoid schizophrenia.

B. Undermethylation – About 28% of persons diagnosed with schizophrenia exhibit low methylation of chromatin together with weak antioxidant protection. Mental breakdowns generally occur during severe physical or emotional traumatic events that produce a separate set of altered gene marks. This schizophrenia biotype essentially is a thought disorder with delusions and catatonic tendencies the primary symptoms. This condition is associated with low activity at serotonin, dopamine, and NMDA receptors. The most common DSM-4 diagnoses are Schizoaffective Disorder or Delusional Disorder.

Thesis 5: Extraordinary Weakness in Antioxidant Protection Can Produce Schizophrenia in the Absence of Methyl Imbalances:  The third major schizophrenia phenotype develops in persons with an inborn severe deficit in antioxidant protection. This condition is arbitrarily termed “Pyrrole Disorder” due to the presence of excessive pyrrole levels in blood and urine. Mental breakdowns occur for these persons during periods of extreme physical or mental stress in which deviant epigenetic marks are established. This condition is characterized by extraordinary anxiety, rapid mood swings, and often involves both auditory hallucinations and delusional beliefs. Brain chemistry abnormalities include (a) depressed glutamate activity at NMDA receptors, and (b) very depressed GABA activity.

Thesis 6:  Failure to Follow Classical Laws of Genetic Inheritance Results From the Epigenetic Nature of Schizophrenia:  Schizophrenia is strongly heritable (runs in families) but fails to obey Mendel’s classic laws of genetic inheritance. There are countless examples of identical twins where one sibling develops the disorder and the other does not. In addition, intensive research efforts to identify the schizophrenia gene (or genes) have met with little success. provides two explanations for the non-Mendelian nature of schizophrenia: (a) Environmental insults are required to produce deviant epigenetic marks and environmental conditions are highly variable for different individuals, and (b) Transgenerational epigenetic inheritance (TEI) contributes to schizophrenia heritability by transmitting deviant epigenetic marks to one’s children and grandchildren.

Purchase Nutrient Power by William J Walsh from The Walsh Research Institute