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.

Listen to William Walsh PhD Podcast with Bulletproof Radio:


Good Foods During Pregnancy

 We are all either undermethylators, overmethylators or normal methylators.

Many persons with depression are under or over methylators. Depressed women during pregnancy are frequently undermethylators. The good news is, there are many foods that provide to reverse the deficiency and lift depression. 

This published study in the Psych Congress Journal suggests that women who have maternal depression and are undermethylated, often give birth to children who experience depression due to their own ensuing condition of .

Whole blood histamine test is a lab that indicates methylation status. An excellent natural therapy may be methionine or SAMe supplements or foods that are high in methionine. If you have high blood histamines you may be undermethylated. Persons with seasonal allergies are frequently undermethylated. I recommend you get your levels tested before indulging in high methionine foods because your depression may in fact be associated with overmethylation, which requires an opposite approach, to lower methionine.

In consideration of the the study below, know your methylation status, particularly if you are depressed, and to combat during pregnancy, eat foods high in methionine and or take supplements. It won’t just make the mother feel better, but improves chance child won’t end up with depression.

Maternal Depression Linked to Methylation Changes in Offspring

by Will Boggs MD, Psych Congress

By Will Boggs MD

Maternal depression is associated with widespread changes in DNA methylation in their offspring that may persist into adulthood, researchers from Canada report.

“These data further demonstrate the potential long-term consequences of maternal depression for the health of future generations and the importance of mental health and social support of mothers and would be mothers for the physical health of newborn and children,” Dr. Moshe Szyf from McGill University in Montreal, Quebec, told Reuters Health by email. “What is remarkable is that the mental state of a mother causes changes in DNA methylation in the newborns in the immune system, not just the brain.”

Maternal mood disorders and stress during pregnancy can result in attention learning deficits during childhood and mood disorders during adulthood for their offspring. Evidence suggests these consequences may be mediated by modifications of DNA methylation levels.

Dr. Szyf’s team investigated possible associations between maternal depression and DNA methylation changes in T lymphocytes from neonatal cord blood and in hippocampal brain tissues from adults with or without histories of maternal depression.

Offspring of depressed mothers, however, showed significant differences in DNA methylation from those of nondepressed mothers in 145 T lymphocyte CG sites. Most (75.5%) were hypomethylated in the maternal depression group compared with the control group.

“One of the main surprises was that we found a larger effect of maternal depression on the babies’ DNA methylation than the maternal DNA methylation,” Dr. Szyf said. “The second surprise was that it seems that the effect is a consequence of lifelong depression rather than depression only around the pregnancy period.”

“For healthy babies to develop into healthy adults it is important to have healthy mothers,” Dr. Szyf said. “And this involves not only physical and metabolic health but also mental and social wellbeing. This hopefully will be an important pillar in prenatal care as well as public policy relating to preconception health.”

“The consequences of maternal depression might suggest using epigenetic interventions for prevention and reversal of the impacts of maternal depression on the offspring,” Dr. Szyf added. “One clinical potential of the data is the possibility of developing biomarkers of maternal depression that might serve as predictors of lifelong health risks and guide early interventions.”

Dr. Joanne Ryan from University of Melbourne’s Murdoch Childrens Research Institute, Australia, who recently reviewed and depressive disorders, told Reuters Health by email, “An important next step in this research is to determine whether these methylation differences and associated with health outcomes in the infants/children. Maternal depression during pregnancy has been associated with long-term negative outcomes in the child — the data from this study should be used to determine whether such effects can be mediated by differential DNA methylation.”

To find out more about good foods during pregnancy to help with low methionine, we checked with our favorite food resource.



Walsh Testing and Targeted Nutrient Protocol for Treating Mood and Behavior Disorders

Second Opinion Physician is an online medical consultant and provider of individualized biochemical testing and analysis. The criteria used, for assessing and supplements protocols utilized, were researched and developed by Dr. William Walsh of the Walsh Research Institute. Dr David Epstein D.O. is a Certified Walsh Protocol Practitioner providing a detailed Assessment and Supplement Plan for each individual based on unique biochemical status.

According to Dr Walsh, as many as 95% of persons with mood imbalance and behavior disorders are experiencing a brain nutrient imbalance that can be easily tested and treated. This is the case with depression, autism, schizophrenia and alcoholism, dementia and anxiety disorders. With imbalanced nutrients, the primary neurotransmitters may be elevated or depressed.

Mood disorders can be debilitating and many folks are treated with medications that cause numerous side effects. Per the Walsh Protocol, treatment is individualized and differs greatly from person to person. For instance, supplements are significantly different for depressives who have low serotonin vs high serotonin depression.

Learn more about your own specific nutrient status and how this might affect mood disorders.

What role do nutrients play in producing neurotransmitters?

Here’s the process to get tested, diagnosed and treated per the Walsh Protocol.

If you’re new to the Walsh protocol or have questions, call or email, to schedule a free appointment with Dr Dave.

Dr David Epstein, D.O. has practiced integrative family medicine and consulting for over 25 years. As a licensed physician he is certified to administer the Walsh Protocol.

“Several years ago I had the good fortune of meeting Dr Walsh at an ACAM (American College for Advancement in Medicine) conference. He was the keynote speaker addressing an audience of integrative medical practitioners, most whom had never heard of his work before. What I learned in 45 minutes completely changed the way I look at conditions of oxidative stress, neurotransmitters and epigenetics that underlie the function of the brain.

His story, the lesson he teaches and his humble service to physicians and patients is a roadmap to treatment of mental disorders. As he continues groundbreaking research and physician training, Dr Walsh has started a movement that will one day revolutionize the practice of psychiatry. In the future, there will be very little need for drug therapies to treat conditions such as depression, schizophrenia, anxiety and dementia.  I am fully convinced that by correcting brain chemistry with nutrient therapy, per the Walsh Protocol, patients will receive the best possible treatment.” 


dr epstein walsh practitioner

Patient Testimonials

“Dear Dr Dave, I’m healthy again–and it’s been a long, difficult haul over the last four years I have been sick both physically and emotionally. Thank you for your great doctoring. Before I contacted you, I suffered thru 4 misdiagnoses, including RA for which I was treated with highly toxic drugs for 2 years! I’m now taking 100mg zinc piccolinate daily, along with 150mg B6. Should I stay at these levels? Or taper down to a maintenance dose? How much would it cost to get updated blood tests? I’m healthy and happy, but basically broke since I haven’t been working for 4 years. But I’ll find the money somehow, if I have to. Again, I deeply appreciate the work you’ve done to help me get better… Warmest regards, David”

David T.Overmethylated

“Dear Dr. Epstein, You might advise other folks to “keep the faith” because, at one point, early on, I didn’t feel any better and I got very discouraged. I’m glad I persevered. Then, about 3 months, it hit me. I felt a distinct reduction in base-line anxiety (a life-long problem from childhood). I waited 4 more days to make sure it stuck, before I told my wife, and we celebrated! The earlier problem of upset stomach and pain from the zinc gradually subsided, but it was touch-and-go for a while. The pain was intense. I reduced the dosage of zinc, and then gradually increased it back to 100mg over a couple of weeks.

PS You may be interested that, over the course of the Zinc/B6 protocol, I was able to reduce my Thyroid Meds (100mcg T4/30mcg T3. extended release) by half!! I expect there may be further reductions. I never had Hashimotos antibodies, although I was tested multiple times, which may indicate the Cu/Zn imbalance was the causative factor. I wonder how many other thousands of people with intractible Hypothyroidism have the same problem.”

Richard DElevated Free Copper

“Hello Dr Epstein, This is me again….but with wonderful news. Just to refresh your memory, Alonzo, my 9 year old son had a terrible day at school 12 days ago which was extremely discouraging for me since at that time he was already in his 7th week of taking the supplements. I thought then that maybe nothing will work. The following week I had a meeting with the principal, and explained the therapy that Alonzo was following as well as all the dietary changes, behavioral therapies already done. I also asked if we can have a partnership helping Alonzo overcome issues. She agreed to explain the teacher and proposed to implement few changes such as allowing Alonzo to sit on a wiggle sit chair cushion (great for fidgeting control:
Thankfully, even before that meeting, Alonzo’s behavior was really improving. It got even better…to the point that the teacher herself wanted to speak to me last Friday, (I should confess I was terrified thinking that more problems had happened). It was completely the opposite. She highly praised him for his participation in class, helpfulness, and attention improvement….I was shocked!!! I never received so many complements for my kid’s behavior!! nor even while on medication!!!! I doubt myself for a moment thinking it might be a dream or my wishful thoughts what I was hearing. I even hesitate to write this email to you thinking it might revert somehow magically the positive effect….But I know is real and I’m so thankful. I understand now that my child will never be a “quiet” kid, but these supplements will help him to be the best version of himself…and, just like anyone, he will have great and bad days. However, now he will have stronger tools to control his behavior and focus better since physiologically, he is getting what he needs.

Dr. David, I know that this improvement is part of a journey, and I don’t know in which state of that journey we are now (I hope for a full recovery). I deeply thank you for your wisdom, knowledge, and availability to help us in this path to restoration. I’ll keep you posted.

God Bless you”

Rosemary LElevated Free Copper

William Walsh PhD Papers and Presentations

5 biotypes of depression walsh

Could brain scans hold the key to diagnosing mental illnesses? Test finds people with schizophrenia and bipolar disorders have biological markers

William Walsh Phd Video

Video of Dr Walsh at ANA Conference : The Five Biotypes of Depression and Advanced Nutrient Therapies with William Walsh, PhD

William Walsh depression treatment

Article Brain World: Will New Brain Biochemistry Findings Clear the Murky Waters of Depression?
Why Nutrient Therapy May Be the Answer to Depression

autism therapy william walsh phd

Autism One Video: Epigenetics and Autism Prevention – William Walsh, PhD

articles william walsh phd depression

Psychology Today: Rethinking mental disease. The future of mental health series.

William Walsh Articles

Publication in the Journal of the Australasian College of Nutritional and Environmental Medicine: The Effectiveness of Targeted Nutrient Therapy in Treatment of Mental Illness

  • Why is elevated copper or free copper a problem?

    Copper is a trace element that behaves like heavy metals when it is inadequately bound to the chelating protein ceruloplasmin. Excessive levels of unbound “free copper” affects neurotransmitters and also indicates that the body is having difficulty with free radicals and other heavy metals. 

  • Pyrrole Disorder; a cause of numerous behavioral disorders.

    Elevation of urinary pyrroles leads to chronic vitamin B6 and zinc deficiency. Zinc is essential for 100’s of processes in the body and is particularly important for healing, immune function, digestion, neurotransmitter activation, physical growth, memory, insulin sensitivity, and control of blood sugars, DNA replication and more.

    Zinc and B6 are essential for production of neurotransmitters such as serotonin (mood elevating), melatonin (sleep hormone), GABA (relaxation hormone), and acetyl choline for memory. They are involved in production of steroid hormones – cortisol and the conversion of oils in the body. The oils EPA/DHA and particularly GLA are low in those with pyrrole disorder and are damaged by oxidative stress/free radicals/toxins created by pyrrole disorder.

  • What is epigenetics?

    “Epigenetics is the natural process of gene regulation that is established in the early days of gestation in the womb. A severe environmental insult later in life can either turn off a necessary gene or turn on a damaging gene, resulting in a disorder that can persist for years.” Click here to read interview with William Walsh PhD describing his “Epigenetic Theory of Autism.”