The Many Consequences of Vitamin D Deficiency

Vitamin D as a Nutri-Epigenetic Factor in Autoimmunity-A Review of Current Research and Reports on Vitamin D Deficiency in Autoimmune Diseases.

Cellular and molecular mechanisms of vitamin D in food allergy.

A Review: Highlighting the Links between Epigenetics, COVID-19 Infection, and Vitamin D. 

Vitamin D: a Review of its Effects on Epigenetics and Gene Regulation. 

Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations. 

Epigenetic regulation of vitamin D deficiency.

 

Is high prevalence of Vitamin D deficiency evidence for autism disorder?: In a highly endogamous population. 

 

 

 

Mast Cells and the Endocrine System

These are my notes from the presentation Endocrinology in Mast Cell Disease
given by Dr. Marla Barkoff for The Mast Cell Disease Society

The 3 areas of endocrinology that Dr Barkoff discusses are thyroid function, bone density, and blood sugar and insulin regulation.  (MCD = Mast Cell Disease)

THYROID HEALTH
The thyroid gland sits at the base of the throat and secrets hormones that are like the “motor” of the body.  When too much hormone is produced the metabolism speeds up, and you will see weight loss, body temp going up (feeling hot and sweaty), bowels speeding up (and possibly diarrhea), anxiety, and tremors.  If not enough thyroid hormone is produced you will see slowing of the metabolism, feeling sluggish, depression, low body temp, heart rate slowing down, bowels slowing down (constipation), and weight gain.  

The first line of treatment is hormone replacement, but this can be problematic for patients with MCD for several reasons.   95% of what the thyroid makes is T4 (meaning it has 4 iodine molecules attached).  T4 is oral and may not be absorbed well in MCD patients because of intestinal inflammation.  Signs of not absorbing T4 are if symptoms don’t improve and lab markers don’t improve.  Trouble-shooting things to try-

-Calcium and iron supplements need to be dosed at least 2 hrs away from T4 to not interfere with absorption. 
-Acid blockers, PPIs, and maybe H2 blockers may block absorption. 
-If still not working calculate full replacement dose (weight in kg multiplied by 1.7 before menopause and 1.6 after). 
-Can switch to a liquid form (tyrosynth) that tends to be much better absorbed.  The solution form has no gelatin which can be better for allergies, halal, kosher, vegan, etc. 
-If still not working, are they having a sensitivity?  Levothyroxine, only the 50mg is white (note- this doesn’t mean no dyes!).  Some brands of T4 are better tolerated including Levoxyl or Euthyrox (all doses are white).  Levothyroxin can be compounded easily.  

T4 is the inactive form of thyroid hormone, an enzyme removes one iodine to make T3 and that is the active form.  Some mast cell mediators released with degranulation can halt or impede the conversion of T4 to T3.  If this is happening it may help to add a low dose of T3 (2.5mcg, rarely need more than 5mcg in AM).  T3 is short lived and fast acting, may need to be dosed again midday.  Dose in ratio of 95%T4 to 5%T3.  Reason not to use “natural” form, which is desiccated from pigs, is that it has a different ratio of T4 to T3.  Never use T3 alone.  

BONE HEALTH
Bone density is the result of two kinds of cells that work together to keep bone healthy and strong.  Osteoblasts build new bone, and osteoclasts break down old bone that is no longer functioning well.  The active process of these two kinds of cells working together is called bone remodeling, and the balance of the actions of these two kinds of cells is essential for bone to be both flexible and strong as it needs to be.  There are many different factors that influence this balance including vitamin D, estrogen, and parathyroid hormone (PTH).  The fact that estrogen is involved is why women lose bone density after menopause. 

If a person is losing bone density, testing for vitamin D and parathyroid hormone (PTH) levels is a good place to start.  Parathyroid glands sit above thyroid gland but are not involved in thyroid function.  If vitamon D levels are inadequate, PTH kicks in.  PTH triggers osteoclasts to degrade bone.  Mast cells release RANK ligand when they degranulate which also stimulates osteoclasts.  Vitamin D levels should be above 30 and PTH level should be less than 45.  PTH can also trigger mast cell degranulation.  The drug Forteo is pharmacological PTH, so might also trigger mast cell degranulation.  What is safer in MCD is the anti-resorbtive including bisphosphonates and Prolea (a monoclonal antibody given in doctor’s office).  

BLOOD SUGAR
Evidence suggests that mast cell degranulation releases pro-inflammatory mediators that can contribute to white fat growth and differentiation and insulin resistance, which causes blood sugar to rise and the body may struggle to produce enough insulin.  Check fasting glucose level, normal is < 100, >126 is diabetes, in between is pre-diabetes.  Also check HbA1c which is average blood sugar over 3 month period, normal <5.7, if >5.7 glucose tolerance test.  Metformin may be good option for MCD patients because it is also anti-inflammatory.   

Stress (Cortisol and Adrenaline)

The inside of the adrenal glands is neurological tissue, which is where adrenaline is made.  The outer part is glandular tissue and is where cortisol is made.  Cortisol is a hormone and adrenaline is a neurotransmitter.  The adrenals release these chemicals in order to help the body to function in situations of short-term stress, but can remain active for a long time.  They are part of the sympathetic nervous system, which is also known as the "fight or flight" system.  The opposing branch of the autonomic nervous system is the parasympathetic response, which is a state of relaxation.  The adrenal glands are not part of the parasympathetic system so that system is unable to "turn them off".  Fear, worry, and anxiety are part of the sympathetic response.  

The Effects of Stress

Stress causes problems with sleeping, often resulting in waking during the night (often around 2 AM) and can mean that a person sleeps best in the morning rather than at night.  Cardiovascular effects include changes in blood pressure and heart rate, and inflammation of the arteries.  Cortisol is an anti-inflammatory hormone. The synthetic version is called prednisone.  Long term cortisol exposure leads to loss of sensitivity by the cortisol receptors on cells, similar to how insulin resistance happens in diabetes.  With cortisol resistance, more cortisol may actually increase inflammatory symptoms in a seemingly paradoxical way.  Diseases that can develop in this situation include arthritis, auto-immune diseases, and joint inflammation.

The Effects of Cortisol on the Immune System

Cortisol affects the white blood cells of the immune system because part of what it does is to "turn off" the immune system.  Cortisol inactivates Natural Killer T-cells, which kills viruses and cancer cells.  It also suppresses the ability of the immune system to fight pathogens in general.  There are even certain bacteria that activate your hypothalamus to activate cortisol so that your body can't defend itself as well.  

Cortisol and Memory

In the short term, cortisol helps in the formation of emotional memories because these memories may help you to survive in the future, but in the long term the hippocampus is damaged, leading to memory loss and brain fog.  This can also result in becoming per-occupied with a few specific problems, which can lead to keeping you awake at night because you can't turn off the worries.  You can get stuck in a problem-solving mindset but it doesn't result in actual helpful solutions.  

Mineral Loss

Long-term exposure to cortisol leads to the loss of potassium, which is a mineral that supports calmness and relaxation.  Loss of potassium leads to more stress and this can create a cycle.  Sugar also depletes potassium.  Thiamine (vitamin B1) is an important anti-stress vitamin that causes relaxation and comfort. Thiamine also increases levels of GABA, which is a neurotransmitter of relaxation and calmness.  It also causes a loss of hydrogen ions, which are acidic, which puts your body into a more alkaline state.  People under a lot of chronic stress become too alkaline, not too acidic.  This leads to tight muscles, twitches, tetany. muscle cramps, can't absorb electrolytes well, and breathing problems can result.  As the acid levels decrease this can cause low levels of stomach acid and poor digestion.  

Catabolic Effect

Catabolism is the process in which muscles are broken down in order to turn the amino acids, the components that muscle proteins are made of, into glucose to fuel the "fight or flight".  Connective tissues including collagen and elastin are also broken down in this process (this is why stress can make a person wrinkly).  Cortisol also demineralizes bone, causing osteopenia and osteoporosis.  

Effect on Kidney Function

Chronically high cortisol levels cause the kidneys to filter less (meaning hold on to less and instead allow more to be lost in the urine), including minerals such as potassium.  Sodium is filtered and saved and this is why kidney problems can lead to water retention.  Addison's Disease is a rare and more serious form of adrenal disease in which potassium is filtered but sodium is lost in the urine.  Cushing Syndrome is related.  

Cortisol and Blood Sugar

Cortisol is also called a "glucocorticoid" because it helps to regulate glucose levels.  It can help make glucose out of non-carbohydrate sources including fats, proteins, and even ketones. It also plays a role in storing and releasing glucose.  Cortisol can activate insulin leading to a "flat tire" around the gut, and this also leads to all the issues associated with high insulin.  

Cortisol and Digestion

The process of digestion is under the control of the parasympathetic system, and becomes compromised when cortisol levels remain elevated.  The digestive system becomes sluggish resulting in bloating, indigestion, poor absorption of nutrients, and even ulcers.  The fact that cortisol also increases insulin levels this can also affect digestion and cause excess belly fat.  

Excess cortisol can lead to low levels of vitamin D which is ironic as vitamin D does many of the same things that cortisol does, but without the negative side effects.  It is an anti-inflammatory and can influence the immune system to lower inflammation rates, in particular it tamps down the cytokine storm.  

How to Lower Stress and Reduce Cortisol

It can lower mental stress to find activities that increase physical stress such as jobs around the house, yard work, etc.  These activities result in a kind of physical tiredness that can improve sleep.  Exercise and other types of physical activity can also be helpful.  Worry and stress are associated with inaction, feeling almost paralyzed, and keeping busy with activities helps keep you moving and keeps your mind from getting stuck on certain topics.  Taking vitamin B1 is very helpful at cutting stress down.  It can have an almost immediate effect if taken when you feel very stressed.  Making sure that you get enough potassium and magnesium is important and both are easily gotten from the diet, especially vegetables.  Reducing carbohydrate intake helps because carbs keep the body stuck in a "fight or flight" response.  Taking vitamin D lowers stress and improves mood.  Implementing a ketogenic diet and intermittent fasting helps to address a lot of the physical symptoms and mood symptoms from high cortisol.  Including adaptogens in your daily routine, as a supplement or tea or other ways, supports healthy adrenal function.  

Learning to breathe so that the inbreath and the outbreath are the same duration helps balance the sympathetic and parasympathetic arms of the autonomic nervous system.  If you practice this when you lay down to go to bed it will help you sleep.  Below is the link to a video made by Dr Berg showing a technique to reduce stress at the end of the day, using a thing that puts pressure on the base of the skull.

Dr.Berg's Webinar On Stress Relieving: Easily Get Rid of Stress & Sleep Like a Baby

This is an adaptogen supplement recommended by Dr Berg

Growth Hormone

Growth hormone is sort-of opposite of cortisol, it protects proteins.  It’s anti-aging whereas cortisol is pro aging.  GH is triggered by sleep,  intense but intermittent exercise, eating enough protein, and intermittent fasting. 

Symptoms and Diseases Caused by Nutrient Deficiencies

For those of us living in industrialized nations, it is assumed that we get a reasonably adequate amount of the nutrients that our bodies need.  This assumption seems based on several things, including the practice of fortification of foods such as adding vitamin D to milk, calcium to orange juice, and B vitamins to wheat flour.  It is also assumed that people living in the first world have access to a range of nutritious foods and can afford to eat a balanced diet.  While there is some truth in these assumptions, and we don't see high levels of many nutrient-deficiency driven diseases in most developed countries, These assumptions can also give a false sense of security.  One of the reasons that some foods are fortified is that much of the nutrition is lost during the processing stage and some of those nutrients are added back in (usually not in the same form that they occurred in in the unprocessed food).  White wheat flour is a good example of this.

There are still a number of reasons why a person living in an industrialized country might still develop one of these diseases, or as is probably much more common, shows some of the signs of deficiency but the deficiency is not severe enough to lead to the full presentation of the disease and is therefore not recognized.  Deficiencies can result from eating primarily processed foods that have the calories we need but very little nutrition, from eating food (even organic food) that was grown in nutrient-depleted soil or given feed that was grown that way, and by eating foods that have been engineered or bred for traits such as shelf-stability and low cost but that contain much less nutrition to begin with. Additionally, people who follow restricted diets, such as people who are vegan or vegetarian, who need to avoid foods due to allergies and sensitivities, who focus on raw and or locally-grown foods, people living in poverty or for other reasons have limited access to healthy food, or for any other reason eat a limited range of foods may need to be particularly aware of their nutrient intake.  Lastly, everyone's body is somewhat different in how it metabolizes various foods and nutrients.  Our bodies use enzymes and various biochemical pathways to transform what we eat into what we need in our bodies and some people have enzymes and pathways that function very differently.

Blindness and Other Vision Problems - including night blindness and other vision problems can result from vitamin A deficiency.  B12 deficiency can cause blurry or disturbed vision (from optic neuropathy caused by damage to the optic nerve). 

Abnormal Bone Growth - when caused by vitamin D deficiency is called Rickets, which causes bones to grow soft or thickened, leading to skeletal deformities such as bowed legs as well as pain.  More on Rickets (from Mayo Clinic)
"Rickets is the softening and weakening of bones in children, usually because of an extreme and prolonged vitamin D deficiency. Vitamin D promotes the absorption of calcium and phosphorus from the gastrointestinal tract. A deficiency of vitamin D makes it difficult to maintain proper calcium and phosphorus levels in bones, which can cause rickets.  Symptoms include delayed growth, pain in the spine, pelvis, and legs; and muscle weakness. In children it can lead to skeletal bone malformations such as bowed legs, thickened wrists and ankles, and breastbone projection."

Neural tube defects - including cleft lip, cleft palate

Poor Immune Function - can be caused by vitamin A deficiency

Diseases Caused by Nutrient Deficiencies

Cerebral Folate Deficiency (CFD)
The basis for folinic acid treatment in neuro-psychiatric disorders. 

Beri Beri

 

Pellagra
"Pellagra is defined by the systemic disease resulting from niacin deficiency, and it is characterized by diarrhea, dermatitis, dementia, and death, which usually appear in this order. GI tract symptoms always precede dermatitis.

 

Pernicious Anemia

 

Chapter 30: historical aspects of the major neurological vitamin deficiency disorders: the water-soluble B vitamins.
Handb Clin Neurol. 2010;95:445-76.
"This historical review addresses major neurological disorders associated with deficiencies of water-soluble B vitamins: beriberi, Wernicke-Korsakoff syndrome, pellagra, neural tube defects, and subacute combined degeneration of the spinal cord.  

Korsakoff described a spectrum of cognitive disorders, including a confabulatory amnestic state following an agitated delirium, occurring in conjunction with peripheral polyneuropathy. Beginning around 1900, investigators recognized the close relationship between Korsakoff's psychosis, delirium tremens, and Wernicke's encephalopathy, but not until several decades later were Wernicke's encephalopathy, Korsakoff's psychosis, and beriberi all linked to the deficiency of a specific dietary factor, i.e. thiamin.

Additional problems caused by vitamin A deficiency include increased susceptibility to infection, and increased childhood mortality.

 
Chapter 29: historical aspects of the major neurological vitamin deficiency disorders: overview and fat-soluble vitamin A.

Subacute combined degeneration and B(12) deficiency: Pernicious anemia was recognized clinically in the mid-19th century by Addison, but the most important neurological manifestation - subacute combined degeneration of the spinal cord - was not recognized clinically and linked with pernicious anemia until the end of the 19th century... In the 1920s, Minot and Murphy showed that large quantities of ingested liver could be used to effectively treat pernicious anemia, and specifically could improve or prevent progression of neurological manifestations, and could extend life expectancy beyond 2 years. Beginning in the late 1920s, Castle demonstrated that a substance elaborated by the gastric mucosa ("intrinsic factor") was essential for the absorption of a dietary factor ("extrinsic factor," later shown to be vitamin B(12)) needed to prevent pernicious anemia. Over two decades, from the late 1920s until the late 1940s, increasingly potent liver extracts were manufactured that could be given either intramuscularly or intravenously. In 1947, vitamin B(12) was isolated by Folkers and colleagues, and nearly simultaneously by Smith. Shortly thereafter the therapeutic efficacy of vitamin B(12) on subacute combined degeneration was demonstrated by West and Reisner and others. By 1955, Hodgkin determined the molecular structure of cyanocobalamin using computer-assisted x-ray crystallography, allowing complete chemical synthesis of vitamin B(12) in 1960 by an international consortium. Beginning in the late 1950s, the absorption and biochemistry of vitamin B(12) were elaborated, and several lines of evidence converged to support an autoimmune basis for pernicious anemia.

More on These Diseases:


Wernicke-Korsakoff Syndrome (from Medscape)

"Thiamine appears to have a role in axonal conduction, particularly in acetylcholinergic and serotoninergic neurons. A reduction in the function of these enzymes leads to diffuse impairment in the metabolism of glucose in key regions of the brain, resulting in impaired cellular energy metabolism.

Acute thiamine deficiency leads to mitochondrial dysfunction and therefore oxidative toxicity in areas of the brain starting with areas with the highest metabolic activity. The exact mechanism of neuronal cell death remains to be elucidated.

Additional findings include increased astrocyte lactate and edema, increased extracellular glutamate concentrations, increased nitric oxide from endothelial cell dysfunction, deoxyribonucleic acid (DNA) fragmentation in neurons, free radical production and increase in cytokines, and breakdown of the blood-brain barrier.

The amnestic component is related to damage in the diencephalon, including the medial thalamus, and connections with the medial temporal lobes and amygdala. The slow and incomplete recovery of memory deficits suggests that amnesia is related to irreversible structural damage.

Mortality may be secondary to infections and hepatic failure, but some deaths are directly attributable to irreversible defects of severe and prolonged thiamine deficiency (eg, coma)."

Keshan Disease

An original discovery: selenium deficiency and Keshan disease (an endemic heart disease).

Keshan disease-an endemic cardiomyopathy in China.

Keshan disease--an endemic mitochondrial cardiomyopathy in China.

New Syndrome of Verbal Apraxia with Dietary Components

The study Syndrome of Allergy, Apraxia, and Malabsorption: Characterization of a Neurodevelopmental Phenotype that Responds to Omega 3 and Vitamin E Supplementation was published in 2009 in which the authors report having found a subgroup of children with Verbal Apraxia who also had food allergy, gluten intolerance, and nutritional deficiencies from malabsorption.  These children had nutrient deficiencies beyond vitamin E, including vitamin D, zinc, carnitine, and zinc.  The low carnitine caught my eye as possibly suggestive of acquired mitochondrial involvement.  An article about this study from Science Daily can be found here.  To summarize in my own words, what the study suggests is that in some children, gut damage linked to gluten intolerance and allergies leads to nutritional deficiencies, which have neurological consequences, including the loss of speech and sensory processing problems.

This is from the press release for the study

"A landmark study conducted by Children's Hospital & Research Center Oakland is the first to reveal a new syndrome in children that presents with a combination of allergy, apraxia and malabsorption. Autism spectrum disorders were variably present. Verbal apraxia has until now been understood to be a neurologically based speech disorder, although hints of other neurological soft signs have been described. The new study, led by Children's Hospital & Research Center Oakland scientist and pediatric emergency medicine physician, Claudia Morris, MD, and Marilyn C. Agin, MD, a neurodevelopmental pediatrician at Saint Vincent Medical Center in New York, however, suggests that the symptoms of verbal apraxia are, at least for a sub-group of children, part of a larger, multifactorial, neurologic syndrome involving food allergies/gluten-sensitivity and nutritional malabsorption."

More on the study "the new study takes a major step toward identifying the potential mechanisms that may contribute to apraxia symptoms. In the study, Dr. Morris collected information from nearly 200 families with children who suffered from verbal apraxia in order to better characterize the symptoms and metabolic anomalies of a subset of children. The data clearly demonstrated a common cluster of allergy, apraxia and malabsorption, along with low muscle tone, poor coordination and sensory integration abnormalities. In addition, Dr. Morris was able to gather laboratory analyses in 26 of the children, which revealed low carnitine levels, abnormal celiac panels, gluten sensitivity, and vitamin D deficiency among others. All children genetically screened carried an HLA gene associated with gluten sensitivity and celiac disease."

And further..."Most significantly, the data indicate that the neurologic dysfunction represented in the syndrome overlaps the symptoms of vitamin E deficiency. While low vitamin E bioavailability may occur due to a variety of different causes, neurological consequences are similar, regardless of the initiating trigger. The study suggests that vitamin E could be used as a safe nutritional intervention that may benefit some children. Growing evidence support the benefits of omega 3 fatty acid supplementation in a number of neurodevelopmental disorders. Anecdotally children with verbal apraxia will often demonstrate leaps in their speech production when taking high-quality fish oil. The addition of vitamin E to omega 3 fatty acid supplementation in this cohort of children induced benefits that exceeded those expected from just speech therapy alone, according to parental report."

"She points out that it is equally important for children given an apraxia diagnosis to receive a more comprehensive metabolic evaluation than what is current practice. Many of the nutritional deficiencies like low carnitine, zinc and vitamin D are easily treated. By not addressing the nutritional deficiencies, the child will continue to suffer from significant medical consequences of those deficiencies. The first step is to identify and treat the deficiencies. The next step is to try to figure out why they have these deficiencies and a fat malabsorption syndrome in the first place."
When I read this I immediately thought of how well Roo did on the supplement called SPEAK, which contains high-dose vitamin E and omega 3.  Zinc and carnitine have also been important for him.  

SNP testing

The term SNP stands for Single Nucleotide Polymorphism, and refers to variation in genes that arise from a single substitution of one nucleotide for another at a specific point along a gene.  Genes are segments of our DNA that are coposed of long sequences of base pairs, which are two of these nucleotides, one from each side of the DNA double helix, that "fit together" like the teeth on a zipper.  A SNP (pronounced "snip") is a variant of a gene that alters the function of the protein that is coded for by the gene.  These proteins can be enzymes, in which case the SNP will alter the rate at which the enzyme works in many cases,  or can be components of cells and tissue, in which case the function of the cell or tissue can be altered.  

Dr Amy Yasko pioneered the use of a person's SNP profile to guide biomedical intervention, which allows dietary, supplement, and other interventions to be more customized and to avoid many potential side effects or poor outcomes.  This testing was very expensive however so not accessible to many.  The company 23andMe has brought the cost way down and provides information on many more SNPs than Yasko testing has.  23andMe has stopped giving out what they call "health info" due to an order from the FDA.  This DOES NOT affect your access to your SNP data which is usually the reason to do the testing.  You can order the test here.  For some basic FAQs about suing 23andMe go here.  Many people feel uncomfortable about having this information about them "out there" so they choose to submit the test kit under a false name.  Forbes has just run an article giving an update about 23andMe's business plan and a possible sale to Genentech, which provides a little more information about what is being done with the data they are collecting.  Once the test is processed, you are sent a link to access your information online.  To find out your SNPs, download your raw data from the 23andMe website, and then run it through one of a number of apps available to generate a SNP report.

Here are some options:

Genetic Genie is free with a suggested donation of $10.  It provides a modest report with some good information about the SNPs found.  You can choose a methylation report or a detox report.

Promethease is another option, it costs $5.  There is a video on the site that gives more information about the service.

I prefer an app called LiveWello, that is more expensive at $19.95 (these costs are all per person, so if you are running 3 people's data from your family you will have to pay for each person).  LiveWello generates a much more comprehensive report, and has a sandbox feature where you can look up your SNPs in any of the raw data by typing in the gene name or rs number (a tutorial for using this feature can be found here).  You also have access to smaller reports made by other users that identify SNPs associated with specific issues, such as Parkinson's, Crohn's Disease, allergies, even production of oxytocin.  If you don't see a template that fits your needs, you can go to google and search for "risk alleles associated with ___" whatever you are interested in.  Then you can copy and paste the rs number into the sandbox feature and find out which SNPs you have for that gene.

BASIC TOOLS TO UNDERSTAND YOUR SNPs

There are a lot of tools available online to help you understand the meaning of your SNPs.  Honestly, I have found Wikipedia to be one of the most helpful resources.  The first step is often to figure out what the gene does, the second step is figure out what affect your variation has on it's function.  In addition to these sources, you can simply google your SNP and look for scientific articles that mention it.

A Catalog of Published Genome-Wide Association Studies

Genetics Home Reference

Tales From The Human Genome is a class presented by Udacity and 23andMe for beginners

SNPedia

Genopedia

dbSNP

OMIM

METHYLATION PATHWAY MAPS AND RESOURCES

Basic map from Heartfixer

Basic map from Dr Yasko

Dr Yasko's methylation maps

Methylation basics from Wikipedia

The Role of Methylation in Gene Expression

RESOURCES FROM DR AMY YASKO

Know Your Genetics will provide a Yasko Methylation Protocol Analysis

This sample MPA (from above) can help you begin to process your SNP information

Amy Yasko's book Autism: Pathways to Recovery

The workbook for Pathways to Recovery

Genetic Bypass by Dr. Amy Yasko

Articles by Dr Yasko

Videos of presentations by Dr Yasko

Slides from Dr Yasko's presentations

Integrative Medicine for Mental Health

The Holistic Psychiatry Podcast by Dr Courtney Snyder, MD

These are my notes for a webinar presented through Great Plains Lab by Dr James Greenblatt MD about integrative medicine for mental health.  You can see his website here, and the site of his practice here.  I really liked this quote from his Comprehensive Resources for Psychiatry site:

"The most significant lesson I relearn with every patient is how complex our uniqueness really is. This individuality defines our core metabolism and biochemistry. Our unique metabolic puzzle supports our ability to pay attention, inhibit unwanted behaviors, and regulate our moods."

The integrative medicine model is one which provides alternatives to the pharma-based approach of conventional psychiatry, in which medications are used to treat symptoms.  It is an Orthomolecular approach, (orthomolecular means "right molecule"), which means that this approach strives to correct imbalances at the molecular level which lead to symptoms.  Each person's symptom picture is unique.  He says the mind is what the brain does, it's the biochemistry.    This is a model not only of treatment, but of prevention.  A model that looks at etiology, which is the "why", and not just the "what".  Conventional psychiatric practice does not look at the "why" at all, only the "what" (the symptoms).

This talk uses depression as the example of what this model and approach look like.  Medications have a place, but this model also identifies underlying cause.  Nearly half of patients treated for depression respond to placebo.  Pharmaceutical companies do less research into new meds for depression because the placebo effect is so strong, that it's hard to come up with meds that perform better than placebo.  Pharma is choosing to put it's research money into other types of meds, which are more likely to generate a profit.  Recently there have been many books that point out the problems with meds, but do not offer an alternative.  Whether or not drugs are the answer, patients need help.  Integrative medicine offers this alternative so that people can be treated and helped.  The DSM is based on symptoms and patterns of symptoms, and medications are developed for symptom complexes with no sense of etiology (the "why") or objective measures, so psychiatry is just monitoring symptoms rather than treating cause.  Integrative medicine looks for biological treatments for causes. 

For example, if 10 patients with the same symptom complex called depression come into a doctor's office, some will have low vitamin D levels, some will have celiac disease, others will have low cholesterol levels (patients often have more than one cause).  Nutritional deficiencies are one of these causes.  Nutrition is not alternative health care.  The name of the disorder is meaningless, what matters for treatment is what needs to be done to heal.  Are there deficiencies?  Is there something the patient needs? Is there something the patient needs to avoid? Are there toxicities?  Bacterial overgrowth?  Heavy metal toxicity?  Food allergies?

Genetics

Genetics and epigenetics are very important, they set the stage.  For all patients with major mental illnesses there are related issues in family members, there is an underlying genetic liability.  Epigentics is not the specific genes that influence us, but the expression of our genes influenced by stress, nutrition, and environmental factors such as toxins and pathogens.  Depression has a strong genetic liability, but the role of environmental factors is even stronger.

 Neurotransmitters

All psychiatric medications influence neurotransmitter levels.  There are hundreds of chemicals that act as neurotransmitters in the brain.  Most are under precursor control, such as by levels of amino acids, which we get from our diet.  Density of serotonin receptors influences risk of depression, so does neurotoxins and diet.  To make neurotransmitters, it takes amino acids such as tryptophan and tyrosine, and many cofactors (B6, vitamin C, etc).  A basic concept of integrative medicine is supping with whatever precursors and/or cofactors are deficient so that the body can produce what it needs on it's own.  Physical exam may not tell us what the cause of the mental illness is, for example both low thyroid and low methylB12 levels can look alike, so testing is often required to identify which precursors are missing.

Nutrition

A perfect diet may not mean correct nutrition.  How can people still have low levels of amino acids,  a big risk factor for depression, even when they feel that they eat a good diet?  Many vegetarians and vegans don't have adequate protein intake, resulting in not enough precursors.  Dr Greenblatt does not suggest vegetarian diets for mental health.  The kind of meat eaten can matter as well, grass fed meat has a much healthier profile of fats than grain-fed meat.  Also, antacid use and other causes of low stomach acid can mean that the nutrients aren't being absorbed from the food eaten.  Amino acid powders can be helpful, and are often customized via testing.  These are not the same as protein powders.  What we eat also influences our gut flora, which in turn can influence our mental health.  Yeast and Clostridia overgrowth in the gut have both been associated with major mental health issues, including OCD and anxiety.  Yeast is not well measured in stool samples, it is more accurate to measure metabolites present in the urine (an Organic Acid Test).  Yeast can also cause problems with regulation of blod sugar levels, which can also contribute to mental health problems. 

Folic acid is a very important nutrient for treating depression.  Folic acid is the synthetic form, folate is the natural form found in food (L-methylfolate is the form the brain uses).  A clear association has been found between low folate and depression, and poor response to anti-depressant medication and a higher relapse rate are also associated with low folate levels.  New beginnings has a quality L-methylfolate supplement.  Folate supplementation in this form, at about 500 mcg per day, has been found to increase the success of anti-depressant medications.  An almost 40% difference in relapse rates for people with low folate levels vs normal levels has been found.  There is evidence of folic acid, the synthetic form,  having toxic effects so it is best to use the l-methylfolate form.

B12 is one of most misunderstood, neglected nutrients.  B12 deficiency can present as hallucinations, dementia, even paranoid schizophrenia.  Also fatigue, panic attacks, OCD, depression, and paranoia.  Many labs set the normal level way to low; the level should be above 500 units not 200.  MMA (methylmalonic Acid) is a very accurate marker for B12 levels, if it's elevated it means that levels of B12 are low (serum B12 levels are often not accurate).  The vitamin cofactors B6 and B12 have been found in research to reduce depression in elderly.  Homocysteine levels can be an indication of methyl-folate problems.  Homocysteine levels increase as B6 , folate, and B12 levels drop.  SAM-e is necessary to make neurotransmitters, and is helpful in treating depression.  When SAM-e is taken (800-1600 mg/day) it improves the response in people who are not responding to meds.  Avoid SAM-e for people with bipolar, as it can cause mania.  

Dietary fat is critical for mental health.  The popularity of  low fat diets has been very bad for mood disorders.  The brain is made mostly of fat.  EFAs are involved at every level of neurotransmission, as is cholesterol.  Fish oil not a quick fix for many people, it can take up to 3 months to see a noticeable change. Skin disorders, dandruff, and keratosis pilaris (chicken skin bumps on the upper arms or legs) can be an indicator of low EFAs.  Patients who avoid fish or fats are at risk for low levels of EFAs.  Lack of bile acid can also mean poor fat absorption.  Research performed in Australia that involved 81 adolescents and adults with sub-clinical psychosis, for those given 1.2 grams of omega3s daily, for 12 weeks, only 5% developed psychosis, as opposed to 28% in the control group. Testing for this is critical.

"Right food may be the wrong food", food allergies and reactions are important to consider.  Celiac is one example, because it can result in patients not absorbing all the nutrients they need from their food.  People with celiac are at least twice as likely to b depressed as those who don't have it.  Also test for allergies and neuropeptides, especially if there is binge eating, autism, OCD, etc.  Casein breaks down into casomorphine, a morphine analog.  Gluten also breaks down into a morphine analog called gliadomorphine.  (when this reaction is present, it indicates both a low level of the enzyme DPP-IV which brekas these peptides down into smaller harmless pieces, as well as leaky gut which allows the morphine-like peptides to cross over out of the gut and into the bloodstream.  This enzyme can be supplemented, but often complete removal of gluten, dairy and soy are necessary to eliminate the symptoms).   

Exercise and the Mind-Body Connection

Exercise is also very effective in treating depression, but is often hard to do for people who are depressed.  Other treatments may be needed first, such as supplements and dietary changes, to give a person the energy to create good exercise habits.  Begin by nourishing the brain, focus on nutrient deficiencies critical for brain function.  Once the foundation is laid, it is important to nurture the mind, and to include mind-body approaches such as mediation and yoga.  It is often necessary to address a person's state of mind to heal.  Spirituality and faith can be protective against mood disorders and depression.

Inflammation

Depression is the result of inflammation, essentially the brain is on fire.  Depression is associated with many chronic illnesses, those that involve a high degree of inflammation.  Depression is "sick behavior", the signs of depression are ways that our bodies react to being sick.  They are the result of having elevated inflammatory cytokines in our systems.  We have all had the flu, and experienced first-hand how being sick can lead to loss of appetite, loss of interest in things we previously found pleasurable, low sex drive, and avoidance of social interaction (in the case of the flu, these symptoms are the result of inflammation caused by a virus).  Another example of the connection between mental illness and inflammation is the fact that many people with schizophrenia have celiac disease. 

The treatments for depression listed above (exercise, proper diet including adequate fats, eliminating allergies) decrease inflammation in the brain.  One of the mechanisms for the connection between inflammation and depression is that inflammatory cytokines produce an enzyme called IDO that breaks down tryptophan and serotonin.  Additionally, lower levels of serotonin means less melatonin is produced, resulting in sleep problems.  Also, quinolinic acid is a toxin that results from inflammation and which destroys neurons in the brain.  Tests can be run for both quinolinic acid and c-reactive protein to give an indication of how much inflammation is present.  The causes of inflammation include the standard American diet (SAD), pathogens such as Lyme and strep, allergies, sleep deprivation, stress, lifestyle, environmental toxins, and chronic dysbiosis in the gut.  Identifying the cause of the inflammation is a major part of understanding and treating a patient's depression.

In Conclusion

Medications for depression have not generally been very effective, how many of those medications work has yet to be identified, and inflammation is a model that can explain the pathology of depression and leads to effective treatments.  This talk has focused on depression, but what has been said applies to mental illness in general.  Integrative medicine also focuses on increasing a person's nutrient reserves for long term health rather than focusing on managing symptoms.  Research has shown that even simple interventions can lead to major changes, for example research in England found that when prisoners were supplemented with EFAs and multivitamins, there was a more than 25% reduction in episodes of violence and serious behavior problems.  Imagine the impact on society as a whole if these changes were implemented on a large scale. 

There are many relevant lessons from history in regards to mental illness.  For example, the disease Pellagra which mimics symptoms of schizophrenia is caused by a deficiency in vitamin B3.  At one point in the early half of the 20th century, nearly half of the people hospitalized with schizophrenia in the southern US actually had Pellagra.  This is a case in which a major illness can have a simple solution.  Abram Hoffer's books are a great source for more information on this topic.  Integrative medicine is preventative, predictive, personalized, and puts the individual patient at the center.  Mental illness is the reflection of multiple errors of physiology; if we can find the cause we can find the cure.  Many patients have both toxic elements and nutritional deficiencies at the root of their illness.  Medications still have a place, but they don't heal people.

There has been an epidemic of diagnosing even very young kids with major mental illness, such as bipolar, and the tragedy is the psychotropic meds that are being given to these children.  Especially for kids under the age of 6 or 7, it is a tragedy to jump to medications first without even considering looking at the child's metabolism.  These young patients can be treated in the integrative medicine model.  As their illness progresses, interventions become more challenging.  Addressing the underlying causes of children's mental health challenges when they are young can prevent mental health problems in the future.   In the case of young children on the autism spectrum, early treatment based on the integrative medicine model can significantly improve their long-term quality of life and even result in recovery. 

The Somali Autism Mystery

People in the autism community have been aware for some time now that the prevalence of autism in the population of Somali immigrants in Minnesota is extremely high.  At first this was purely anecdotal, but as attention has been drawn to this situation and the numbers have been looked at the rate appears to be 1 in 28 children.  This translates to about 360 children per 10,000 which is about 5 times the national average, and at least twice as high as the average rate in Minnesota, a state with an already extremely high rate of autism (about 1 in 56).

In many contexts a discrepancy this large would be considered A CLUE...but in the political world of autism the response by authorities has been to try to dismiss or minimize the importance of this.  Why?   Of course there are many reasons for this- anything indicating that autism has a biological, environmental component is being treated similarly.  The details of this situation indicate that vaccination, vitamin D level, and mitochondrial function may be major factors at play.  This is also not just a single anomaly- similarly high rates have bee found in other East African immigrant communities in northern lands, including Sweden, Montreal, and Ireland.

 Why is is this so interesting and important?  For one thing, these families needs help and support.  This has significance on a larger scale though, as David Kirby put it so well in a piece he wrote on the subject:

 "If it can be demonstrated that US-born children of Somali refugees are more prone to autism than the other kids of Minneapolis - or Somalia - then it shouldn't take too long to discover what it is about them (their genes) that clashed so terribly with the way they were conceived and raised (their environment).
It won't explain every case of autism, of course, but it might open new doors of understanding and knowledge that can be applied to combating autism worldwide."

This is a quote from one of the fathers (from the above article), regarding whether autism exists in Somalia but just "wasn't noticed"-

"And these symptoms? I had never seen anything like it before. We have names for mental retardation or Down syndrome. But the mannerisms, the loss of speech, the tantrums and violence and running out of the house that comes with autism - I think we would have noticed those things. But we've never seen them before in Somalia or Kenya."

Here are several other interesting quotes from the article:

"Some doctors and researchers in Minneapolis that I spoke with were extraordinarily sympathetic toward the Somalis. "Vaccines have to be playing a role," said one very prominent pediatrician and researcher, who is working quietly behind the scenes to change attitudes at the University of Minnesota and elsewhere, and did not want to be named.  "Maybe if we start talking about the individual toxins in vaccines, and not the vaccine program as a whole, others in the medical profession will find it easier to come around," the doctor said."

This is another quote, quite long, which elaborates what is probably another major piece in this puzzle- vitamin D levels:

"Dr. Gregory A. Plotnikoff, medical director for the Institute for Health and Healing at Abbott Northwestern Hospital, said a colleague had noticed an "exceedingly high" rate of morning sickness among pregnant Somali women in Minneapolis, often requiring hospitalizations. 

The doctor began checking Vitamin D levels and found that, on average, they were far below what is considered to be normal and healthy.

Somalis, he said, may start out with naturally low abilities to produce vitamin D from sunlight, (as is the case with many people with Middle Eastern blood in them). That is compounded by the fact that dark-skinned people require far more sunlight to produce vitamin D than light-skinned people and, when Somalis move to areas of higher latitude, with far less sunlight - their vitamin D stores may be virtually depleted, at least for part of the year.

"Vitamin D is crucial for normal brain development, because there are receptors for it throughout the brain," Plotnikoff said. "Vitamin D also plays a role as an anti-inflammatory agent and, besides cutting down on inflammation, it increases concentrations of glutathione, which better supports the brain's capacity to handle heavy metals and oxidative stress."

As an aside, that is very interesting to me as I had severe morning sickness during both my pregnancy with Roo and with his older brother.  My vitamin D levels have been tested several times and are not only very low but are not rising much even with high oral supplementation.  I have also heard that severe morning sickness can be a sign of significant vitamin B6 deficiency, something which both kids and myself are deficient in, and respond well to supplementation of.   Another interesting connection for my family?  We have responded very well to mitochondrial support, and one of the doctors interviewed for the piece by David Kirby had this to say about vitamin D and mitochondrial functioning:

"Finally, vitamin D deficiency in pregnant animals can lead to "dramatic" defects in mitochondrial function in offspring, according to at least one study. The role of mitochondrial dysfunction and autistic regression is only now beginning to be explored. But some researchers believe that poor mitochondrial health (perhaps exacerbated by vitamin D deficiency?) is a precursor to autistic regression in at least one subgroup of children."