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Pyroluria

Pyroluria

What is pyroluria?

Pyroluria is a genetic disorder caused by abnormal hemoglobin synthesis.  Hemoglobin is the protein in red blood cells that contains iron and carries oxygen throughout the body.  During hemoglobin synthesis, by-product compounds called kryptopyrroles are formed.  This is a normal process even though there is no known function of kryptopyrroles in the body.  However, in people with pyroluria, these compounds are produced to excess, especially under stress, and create deficiencies of vitamin B6 (pyridoxine) and zinc.  Because of this, most of the signs and symptoms associated with pyroluria are due to deficiencies of B6 and zinc.

Vitamin B6 and zinc are essential in the body.  Vitamin B6 is required for more than 100 enzyme reactions in the body.  It is specifically required for:

  • Converting food into glucose for energy;
  • Niacin production;
  • lipid metabolism,
  • carnitine synthesis,
  • production of neurotransmitters serotonin, dopamine, norepinephrine, histamine, and GABA;
  • functioning of the immune system;
  • formation of red blood cells;
  • control of homocysteine (along with B12 and folate); and
  • hormone modulation.

 

Zinc is also essential for enzyme function and more than 50 enzymes in the body contain zinc.  Zinc is important for:

  • cell growth and replication;
  • hormone activity and reproduction;
  • vision, especially night vision;
  • immune function;
  • protein metabolism;
  • wound healing and blood clot formation;
  • breakdown of carbohydrates;
  • thyroid function;
  • resistance to stress;
  • maintaining cognitive function, memory, and learning; and
  • normal appetite, taste, and smell.

 

Moderate zinc deficiency is also associated with disorders of the intestine which interfere with food absorption (malabsorption syndromes), which can cause additional symptoms and health conditions.  This may be why tendency to iron deficiency or low iron levels can be seen in patients with pyroluria.

 

Signs and symptoms of pyroluria

This condition is important to know about because a high incidence of pyrrole disorder is found in individuals with many conditions, including:

  • Autism spectrum disorders
  • anxiety
  • depression
  • tics/Tourette’s
  • epilepsy
  • obsessive-compulsive disorder
  • schizophrenia
  • bipolar disorder
  • Asperger’s
  • alcoholism and addictions
  • ADD/ADHD
  • Multiple sclerosis
  • Parkinson’s
  • Lyme disease

 

“As many as 50% of those with autism, 40% of alcoholics, 70% of schizophrenics, 70% of persons with depression and 30% of persons struggling with ADD may have pyroluria underlying these conditions and make them very difficult to reach with traditional and even holistic therapies.  –But pyroluria isn’t limited to these populations.  As much as 10% of the population may have this metabolic condition and not know it…but may have lifelong symptoms associated with it that tend to worsen with age…and stress.” (http://www.primalbody-primalmind.com/do-you-have-pyroluria/)

 

In general, the symptoms of pyroluria can have a mysteriously intractable quality to them, and primarily relate to the B6 and/or zinc deficiencies.  One source also indicated that accumulated pyrroles can also interfere with the conversion of B6 (pyridoxine) to its active form, pyridoxine-5-phosphate (P5P).  The deficiency of P5P can then reduce hemoglobin synthesis, worsening many symptoms.  Lower levels of P5P are also associated with lower glutathione levels, which will further increase oxidative stress and decrease detoxification in the body, causing additional symptoms.

I have listed symptoms gathered from a variety of sources and they may include:

MOOD

  • poor stress tolerance
  • all symptoms worse with stress
  • nervousness
  • anxiety
  • mood swings or instability
  • inner tension
  • irritability or emotional reactivity
  • episodic anger or aggressiveness
  • depression
  • very sensitive to criticism

 

COGNITIVE

  • difficulty concentrating
  • poor short-term memory
  • learning problems, especially with information in written format

 

NEUROLOGIC

  • headaches, especially blinding or cluster type
  • tics
  • poor night vision
  • poor dream recall
  • restless leg syndrome, tingling or tremors
  • motion sickness
  • sensitivity to light, smell, sound, and/or touch

 

IMMUNE

  • frequent or chronic infections
  • slow wound healing
  • tendency to autoimmune disorders

 

MUSCULOSKELETAL

  • muscle weakness
  • joint pain or stiffness, especially knee or leg
  • hypermobile joints, muscle pain
  • gets stitch in the side when running,

especially in children

 

HAIR/SKIN/NAILS

  • hair loss
  • premature graying of hair
  • white spots on nails
  • rough and dry skin
  • tendency to acne, eczema, or psoriasis
  • being pale, having an inability to tan, or sun burning easily

 

DIGESTIVE

  • irritable bowel syndrome
  • allergies
  • gluten intolerance
  • hypoglycemia
  • nausea
  • difficulty digesting protein and fat
  • fat distribution around abdomen
  • diarrhea or constipation
  • abdominal tenderness
  • loss of appetite
  • poor sense of taste or smell

 

BLOOD/CIRCULATION

  • easy bruising/bleeding
  • low blood pressure
  • cold hands and feet, Raynaud’s syndrome
  • spider veins, varicose veins
  • heart disease
  • higher clotting risk
  • tendency to anemia, especially iron deficiency

 

GENERAL

  • fatigue and low energy reserves
  • slow growth
  • sensitivity to medications
  • wide variety of hormonal symptoms or imbalances- thyroid, adrenal, sex hormones

 

 

I have also found two slightly different pyroluria symptom questionnaires that may also be helpful at:

  • https://pyroluriatesting.com/shop/pyroluria-questionare/
  • http://www.antianxietyfoodsolution.com/wp/wp-content/uploads/2014/10/Pyroluria-questionnaire-from-The-Antianxiety-Food-Solution-by-Trudy-Scott.pdf

 

Testing

One important factor in pyroluria is that the doses of zinc and vitamin B6 required for treatment may be toxic for someone with a normal metabolism.  Therefore, testing prior to initiating treatment is important.  False negative results are possible and there is a higher incidence of false negative results in children because they have faster metabolisms than adults.   Children can still be tested; the practitioner just needs to be aware of potential false negatives and a closely monitored trial of B6 and zinc may still be warranted with a negative result but strong clinical indications.  Additionally, because pyroluria is a genetic disorder, other family members should also be tested.

Because pyrroles are excreted in the urine, testing for pyroluria is an easy urine test.  Prior B6 and zinc supplements need to be avoided for 24 to 48 hours prior to testing.  It is important to choose a lab that corrects for the concentration or dilution level of the sample.  Additionally, kryptopyrroles are light sensitive, so the lab should include methods used to prevent the degradation prior to the sample analysis.

Treatment

Fortunately, pyroluria is manageable with the use of regular supplements, typically high doses of zinc and B6, higher than what can be obtained from food.  The type of supplement is important so they can be effectively absorbed; zinc picolinate or gluconate and pyridoxal-5-phsphate (P5P) tend to be the best forms of these nutrients.  However, some patients may do best with a combination of P5P and standard B6.  Supplementation may need to start at low levels and gradually increase.  Supplementation does need to be monitored to avoid toxic levels, as well as ensuring patients are avoiding competing nutrients.  For example, copper-rich foods and copper-containing supplements should be avoided because they are antagonistic to zinc.

People with pyroluria also have a higher than normal need for omega-6 fatty acids, particularly arachidonic acid and gamma linolenic acid (GLA).  Arachidonic acid is found in eggs, butter, red meat and liver, and GLA is found in supplements like black currant seed oil and evening primrose oil.  Other helpful nutrients may include high doses of probiotics; other B vitamins; antioxidants, including glutathione and vitamins A, C, and E; other minerals, including manganese and magnesium; and amino acids, including cysteine, 5-hydroxy tryptophan (5HTP), glutamine, taurine, or glycine.  Proteolytic enzymes may be needed to break up accumulated pyrroles.  Patients will also need digestive, liver, and brain support as well because the effects of zinc and B6 deficiencies can be wide spread through the body.

Ongoing treatment is required and symptom relapses will occur usually within several weeks of stopping supplementation.  Because people with pyroluria have difficulty dealing with the effects of stress, relapses may also occur under different types of mental, emotional, and/or physical stress, including illness, lack of sleep, or injury.  However, with proper, continued supplementation, patients with pyroluria can improve their health.

References

https://umm.edu/health/medical/altmed/supplement/vitamin-b6-pyridoxine

http://www.nutri-facts.org/eng/vitamins/vitamin-b6-pyridoxine/at-a-glance/

https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/

https://www.nlm.nih.gov/medlineplus/ency/article/002416.htm

http://www.webmd.com/vitamins-supplements/ingredientmono-982-zinc.aspx?activeingredientid=982&activeingredientname=zinc

https://ods.od.nih.gov/factsheets/Zinc-HealthProfessional/

https://pyroluriatesting.com

http://www.drkaslow.com/html/pyroluria.html

http://www.health-science-spirit.com/pyroluria.htm (Walter Last)

Dr. Renee Schwartz. Seminar: Nutritional Approaches to Treating Pyroluria and Other Depression Biotypes. November 2014.

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Methylation

Methylation

Methylation is a process where a methyl group (a carbon and three hydrogens) is attached to another substance.   Current research estimates that 30 to 40 percent of the population has abnormalities in one or two of the genes for the enzyme methyltetrahydrofolate reductase (MTHFR).  This enzyme converts folic acid to 5-methylfolate, which is the active form of folate; abnormalities in this enzyme’s activity can lead to decreased methylfolate production, which can have profound biochemical effects in the body.  However, methylation is an extremely complex process involving multiple enzymes and pathways, not just the MTHFR, and abnormalities can occur in other genes/enzymes as well.   Abnormalities anywhere in the methylation cycle can result in overall under- or over-methylation, and as such, just testing for this one gene may not show the entire picture of methylation.

Functions of Methylation: Why Should We Care?

The methylation process can affect every cell and process in the human body.

Gene Regulation

Methylation and acetylation are the two major chemical gene regulators.  Not all genes are active at all times and methylation appears to be one of the major methods by which cells lock genes in the “off” position.  This is particularly important for turning off cancer genes, but all genes need to have a balance of activity; no gene should be active constantly.  Because of this, proper DNA methylation is essential for cell growth and division, and research is indicating links between abnormal methylation with aging, cancer development and progression, and birth defects. Abnormal cell growth can affect any cell that naturally has a rapid turn-over-rate, such as skin, red and white blood cells, and the intestinal lining.

Vitamin Activation

Methylation is required to activate vitamin B12 and folate; without the addition of that methyl group, those vitamins are inactive.  If a person has abnormal methylation, the levels of B12 and folate measured in the blood could be normal, but the body could be functioning at a deficiency because those vitamins aren’t in the active form.   Vitamin B12 and folate are cofactors in many processes and are essential in red blood cell production and therefore, energy metabolism.

Protein Metabolism and Homocysteine

Methylation is also essential for overall protein metabolism and specifically, the conversion of the amino acid homocysteine to methionine or cysteine. Homocysteine is highly inflammatory and a major and independent risk factor for coronary artery disease and heart disease.  Homocysteine levels can be measured in the blood and can be used to evaluate both inflammation levels but also methylation status.  Most labs use a reference range that has a normal level just below a cutoff value (e.g., < 15).  I evaluate a patient’s result using both upper and lower values to provide a balanced range since either too much or too little methylation may be problematic.

 

 

Neurotransmitter Synthesis and BH4 Recycling

Synthesis of neurotransmitters, including serotonin, and dopamine, is dependent on methylfolate, which acts as an enzyme cofactor. If the methylation process is defective, a lower amount of methylfolate may be available, reducing the production of these neurotransmitters.

Methylfolate is also essential for the recycling of tetrahydrobiopterin (BH4), which is an essential cofactor for the production of the neurotransmitters serotonin, melatonin, dopamine, norepinephrine, and epinephrine.  BH4 is also required for the production of nitric oxide, which is a strong vasodilator.   There is some research that indicates a lack of BH4, and therefore, nitric oxide, may be responsible for circulation-related diseases.

Detoxification

One of the other major roles of methylation is detoxification, as it is one of the major Phase 2 detoxification pathways in the liver.  Detoxification occurs in two phases; the first phase occurs by enzymes in the liver cells and it serves to break down a substance so that in Phase 2, another group can be added to it to make it easier for the body to eliminate.  There are a number of different phase 2 pathways, and different substances, including hormones, neurotransmitters, and chemicals, are detoxified through different pathways.  The challenge in this system lies in the fact that often the product of Phase 1 detoxification is more toxic than the original substance and if there are problems with its Phase 2 pathway, that more toxic substance will remain active in the body for a longer time period.

One particular issue with methylation as a detoxification route is that estrogen is one of the main substances that are detoxified by methylation.  Estrogen gets converted to hydroxyl-estrogen via Phase 1, and this form of estrogen is highly toxic, causing DNA damage and contributing to breast cancer risk.  Through Phase 2 methylation, that hydroxyl-estrogen is converted to the much less active and safer methyl-estrogen; this form of estrogen actually appears to have some beneficial cardiovascular effects.  Understanding the role of methylation becomes exceptionally important in looking at a woman’s estrogen exposure and breast cancer risk, separate from her total estrogen level or her breast cancer genetic status.

Impaired methylation can also decrease glutathione production; glutathione is the primary antioxidant in the human body and one of the major detoxification routes, especially for heavy metals.  Methylation is also the breakdown pathway for histamine, and elevated levels of histamine are associated with allergies and brain inflammation.  Blood levels of histamine can be evaluated along with homocysteine to give a window into a person’s actual methylation status.

Cellular energy

Methyl group donation is essential for the synthesis of carnitine and CoQ10.  These two nutrients are required to produce cellular energy in the mitochondria.  Without them, the mitochondria cannot produce energy (ATP), which is the biochemical energy source for every process in the body.

Symptoms of Methylation Abnormality

Many different symptoms can be associated with methylation abnormalities, and patients can be overmethylators or undermethylators.  Not every patient with a methylation abnormality will have all of these symptoms and some of these symptoms can also be associated with other causes besides methylation.  Additionally, there may be overlap between the two patterns.

Symptoms of those two patterns can include:

Overmethylation Undermethylation
Anxiety/ panic attacks Low pain tolerance
ADHD, Hyperactivity, restless legs Frequent headaches
Sleep disorders Perfectionism, rumination about past
Food and chemical sensitivities Fewer food allergies
Lack of respiratory allergies Environmental/respiratory allergies
Dry eyes and mouth Easy tears, saliva
Low libido High libido
Depression but usually  worse on SSRIs Depression better with SSRIs, antihistamines

 

Methylation Support

Normal methylation and methylfolate levels in particular clearly profoundly affect our health.  The question becomes, if a person has one or more of those genetic abnormalities, has evidence of abnormal homocysteine and/or blood histamine levels, and/or has symptoms associated with abnormal methylation, how can we support that process?

There are several supplements we can use to support methylation both directly and indirectly.  These include:

  • 5 MTHF and methylcobalamin (B12): these may act more directly as enzyme cofactors than methyl donors to the entire methylation cycle.
  • Choline, TMG (trimethylglycine or betaine), and DMG (dimethylglycine): Choline is metabolized into TMG, which is involved in SAM(e) synthesis.  DMG is formed when TMG loses one of its methyl groups.  All three provide sources of methyl groups.
  • S-adenosyl methionine [SAM(e)] and methionine: SAM(e) is produced in the liver from the amino acid methionine and is one the best methylating agents available. The challenge is that SAM(e) can be expensive to maintain appropriate dosing levels.  Therefore, supplementing with methionine and supporting liver function may be an alternative solution.

Other nutrients that indirectly support methylation and may be considered include zinc, phosphatidylserine, inositol, calcium, magnesium, B complex, and Vitamins B2, B6, A, C, D and E.  Glutathione or N-acetylcysteine supplementation may be needed because of the effect methylation has on glutathione production.

It is important to note that some patients who undermethylate do not tolerate methylfolate, especially in high doses.  For those patients, other methyl donors may be a better way to support methylation.  Additionally, the dose of methyl supports may need to be titrated up slowly to allow for other enzymes time to upregulate.  For example, the COMT enzyme breaks down the catecholamine neurotransmitters (serotonin, dopamine, and norepinephrine).  If a patient starts a high dose of methyl support and production of those neurotransmitters significantly increases, the COMT enzyme may not be able to keep up with the breakdown, leading to a state of catecholamine excess.  Therefore, methylation support may need to be started slowly to reach a relatively high dose to replete deficiencies, and then decreased down to a maintenance level.

Methylation clearly plays a significant role in human health.  However, this is definitely one situation where one size does not fit all.  Patients need to be evaluated for their methylation status and different methylation supports may need to be used in different doses at different times to support optimal health.

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All you ever wanted to know about thyroid

All You Ever Wanted to Know About Thyroid

 

Thyroid anatomy and physiology

 

Thyroid gland is a butterfly shaped organ located in front of the throat.  The follicular cells of the thyroid gland secrete tetraiodothyronine (T4) and triiodothyronine (T3), which are synthesized by attaching iodine atoms to the amino acid tyrosine.  T3 and T4 combine with tyrosine-binding globulin (TBG), a transport protein in the blood, which carries the hormones throughout the body.  Approximately 75 percent of the thyroid hormone is bound to TBG, and only the free/unbound portion of the hormone can act in the body.

 

More than 90 to 95 percent of the hormone the thyroid secretes directly is the inactive form of T4.  Under normal circumstances, this T4 then gets converted into four different hormones:

 

  • ~60 percent is converted into active T3 by the removal of one iodine atom by the 5’ deiodinase enzyme and 80 percent of this conversion occurs in the liver;
  • ~20 percent is converted into reverse T3 (rT3), which is completely inactive and cannot be reactivated; and
  • ~20 percent is converted into T3 sulfate (T3S) and triiodothroacetic acid (T3AC).  These are inactive until an enzyme in the intestines converts them into active T3.  This process requires healthy intestinal bacteria.

 

T3 is four times as potent as T4, but lasts a much shorter time. Therefore T4 acts as a reserve for thyroid activity because it can be converted to T3 as needed.  There are also specialized cells within the thyroid that secrete calcitonin, which helps regulate calcium levels.

 

Thyroid hormone secretion is controlled by feedback systems with the pituitary and hypothalamus glands as well as the body’s iodine level.  Low levels of T3 and T4 or a lower metabolic rate will trigger the hypothalamus to secrete thyrotropin releasing hormone (TRH).  TRH then stimulates the pituitary to secrete thyroid stimulating hormone (TSH), which stimulates the production and release of T3 and T4 from the thyroid gland.  So as T3/T4 levels begin to decrease in the body, TRH from the hypothalamus and TSH from the pituitary begin to increase, stimulating the thyroid gland to produce more T4.  Production of thyroid hormone will also be stimulated by any situation that increases energy demand, including a cold environment, low blood sugar, pregnancy, and high altitude.

 

Thyroid functions in body

 

Thyroid hormones have a wide variety of functions in the body, including:

 

  • regulating the basal metabolic rate to produce energy and heat;
  • stimulating protein synthesis;
  • enhancing triglyceride breakdown and cholesterol excretion;
  • promoting normal growth and development of bone;
  • affecting production and function of other hormones, including cortisol, testosterone, estrogen, progesterone, insulin, and growth hormone;
  • supporting normal liver and gallbladder function, especially phase 2 detoxification;
  • regulating brain inflammation and brain autoimmunity, especially through effects on microglial cells in the brain;
  • influencing the actions of and receptors for neurotransmitters, including serotonin, dopamine, GABA, acetylcholine, adrenaline and noradrenaline;
  • affecting methylation pathways, and therefore, estrogen metabolism and activity of B12 and folate; and
  • accelerating body growth in children, especially in the nervous system.

 

Symptoms relating to thyroid disorders

 

Thyroid disorders can be generally divided into low (hypo-) or high (hyper-) thyroid, and in general, hypothyroid conditions are more common than hyperthyroid conditions.  Patients with hypothyroid disorders may present with:

 

Metabolic

  • fatigue;
  • weight gain even with reduced calories due to reduced overall metabolic rate;
  • decreased mobilization of free fatty acids from fat tissue;
  • slow degradation of lipids;
  • delayed insulin response to glucose;
  • slow glucose uptake by tissues and decreased glucose absorption in the intestines; and
  • slower degradation of insulin, which may present clinically as hypoglycemia.

 

Musculoskeletal

  • morning headaches that wear off through the day;
  • bone development delay; and
  • muscle cramps and body pain.

 

Neurologic

  • neuropathy;
  • poor brain function;
  • depression, and sometimes anxiety; and
  • high need for sleep.

 

Circulatory/Immune/Dermatologic

  • sensitivity to cold/cold weather and poor circulation in extremities;
  • low body temperature;
  • facial swelling;
  • loss of the outer third of the eyebrows;
  • difficulty recovering from infections/ healing wounds;
  • dry or brittle skin/hair/nails; and
  • hair falling out.

 

Digestive

  • constipation;
  • chronic low stomach acid/poor digestion;
  • decreased intestinal transit time;
  • altered intestinal absorption rates;
  • reduced liver clearance with possible AST/ALT elevations on bloodwork;
  • sluggish gallbladder contraction;
  • abnormal phase II detoxification in the liver;
  • decreased B12, folate, and iron absorption; and
  • increased intestinal permeability to proteins.

 

Endocrine

  • difficult menstrual periods and/or infertility;
  • altered metabolism of androgens and estrogens;
  • altered estrogen metabolism toward forms which increases risk for estrogen-related cell growth;
  • reduced sensitivity at progesterone receptors (progesterone resistance); and
  • increased sex-hormone binding globulin, which affects the free portions of sex hormones.

 

Cardiologic

  • atrial fibrillation

 

There may also be a painless swelling of the thyroid or a sensation of fullness in the throat.  Low levels of thyroid hormone can also affect other hormones, such as estrogen or progesterone, which can then cause their own set of symptoms.

 

Patients with hyperthyroid disorders may present with hypermetabolism, rapid heart rate, and fatigue, weight loss despite normal to increased calories, excess heat, osteoporosis and bone demineralization, nervousness, and tremors.

 

Testing thyroid and what results mean

There are many tests of thyroid function and it is important to know the information that each of these tests does and does not provide.

 

  • TSH is a direct measure of the amount of TSH produced by the pituitary. Many doctors feel this is best means of determining thyroid dysfunction because they feel normal results essentially rule out hyperthyroidism or hypothyroidism.  However, using TSH to evaluate thyroid function doesn’t consider abnormal thyroid-pituitary feedback loops, peripheral thyroid metabolism/conversion issues, or autoimmune thyroid conditions.

 

  • Total T4 (TT4) is a measure of bound and free T4 hormone. Changes in levels of TBG will produce corresponding changes in TT4.

 

  • Free T4 (fT4) is a direct measure of the unbound T4 hormone. This can appear elevated if the TBG levels are decreased.

 

  • Total T3 (TT3) is a measure of bound and free T3 hormone. It tightly bound to TBG (although 10 times less so than T4) and like TT4, TT3 levels are influenced by alterations in serum TBG level and by drugs that affect binding to TBG.

 

  • Free T3 (fT3) is a direct measure of the unbound T3 hormone. This test is usually done to evaluate thyrotoxicosis or when a hyperthyroid patient has normal FT4 levels.

 

  • Reverse T3 (rT3) is a direct measure of the reverse T3 levels. This will be higher primarily under conditions of elevated cortisol and an inability to clear rT3.

 

  • T3 Uptake (T3U) is used to estimate protein binding and measures the number of sites for fT3 to bind with thyroxine binding proteins.

 

  • Free Thyroxine Index (FTI) is a calculated value that corrects TT4 for the effects of varying amounts of thyroid hormone–binding serum proteins and thus gives an estimate of fT4 when TT4 is measured. While it is an older tests, the FTI is readily available and compares well with direct measurement of fT4.

 

  • Thyroid antibodies are measurements of immune activity against different portions of the thyroid. The most common tests are thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies.  These tests are used to identify cases where hypothyroidism (Hashimoto’s thyroiditis) or hyperthyroidism (Grave’s disease) is caused by autoimmune activity, and positive results indicate that treatment must be based on treating autoimmunity in addition to appropriate thyroid support.

 

TPO antibodies target the thyroid peroxidase enzyme, which is important in the synthesis of thyroid hormone inside the thyroid follicular cells. The TPO antibody test is the most sensitive test for detecting any autoimmune thyroid disease and are highest in patients with Hashimoto’s thyroiditis.  Tg antibodies bind thyroglobulin, the major thyroid-specific protein that is crucial to thyroid hormone synthesis, storage, and release; these antibodies can interfere with thyroid hormone production.  Tg is not released into circulation under normal conditions.  However, inflammation, bleeding, or rapid growth of thyroid tumors can cause destruction of the thyroid follicular cells, causing Tg to leak into the blood.  This process can cause the formation of Tg antibodies and the exposure of other thyroid proteins to the immune system, especially TPO.

 

TPO antibodies are positive in 90-100% of cases of Hashimoto’s thyroiditis and 50-80% of cases of Graves’ disease and Tg antibodies are positive in 80-90% of cases of Hashimoto’s thyroiditis and 50-70% of cases of Graves’ disease.  TPO and/or Tg antiobdies may also be present in other autoimmune diseases (40% of cases), pregnancy (14% of cases) and sporadic multinodular goiter, isolated thyroid nodule, and thyroid cancer.  Elevated levels of TPO or Tg antibodies may be present in 40-50% of relatives of patients with an autoimmune thyroid disorder.

 

TPO antibody tests are more sensitive than but equally specific to Tg antibody tests for diagnosing autoimmune thyroid conditions. However, for some patients, only the Tg antibodies are positive and anti-Tg levels should be evaluated if TPO antibodies are negative, but clinical suspicion of autoimmune thyroid disease is high.  According to the Mayo Clinic, “in patients with subclinical hypothyroidism, the presence of TPO antibodies is associated with an increased risk of developing overt hypothyroidism. Many clinical endocrinologists use the TPO antibody test as a diagnostic tool in deciding whether to treat a patient with subclinical hypothyroidism.”

 

  • Radioactive iodine uptake testing is used to help diagnose hyperthyroidism. A trace amount of radioiodine is given orally or IV and a scanner then detects the amount of radioiodine taken up by the thyroid.

 

It is important to know that there are medications that can affect both thyroid functioning as well as thyroid test results.  Medications can:

 

  • decrease TSH secretion;
  • decrease or increase thyroid hormone production;
  • decrease T4 absorption;
  • increase or decrease TBG, thereby increasing or decreasing the free hormone levels;
  • displace T3 and T4 from the transport proteins;
  • increase liver metabolism; and
  • decrease the 5’deiodinase activity.

 

Lab Findings with Thyroid Disorders

Lab test results will vary with different types of thyroid disorders.

 

With hypothyroidism, there will be a high TSH; low-normal TT4, FT4, TT3, FT3, FTI, and T3U; and normal rT3. Antibodies may be negative or positive depending if the cause is autoimmune.  If hypothyroidism is caused by low pituitary functioning, the labs will be the same except that the TSH will be low instead of high.  In that case, the thyroid itself may be able to function normally, but it is not getting the correct stimulation (TSH) from the pituitary.  Other things to consider then include adrenal dysregulation, post-partum, thyroid receptor site resistance, and heavy metal toxicity, all of which will affect pituitary functioning.

 

Subclinical hypothyroidism occurs when the patient has hypothyroid symptoms and the TSH is mildly elevated but FT4 is within lab reference range; over 80% of patients have a TSH of less than 10 mIU/L.  This condition is fairly common and the diagnosis can be supported by positive TPO antibodies.  It may be considered a very early stage of an autoimmune condition because the majority of patients diagnosed do go on to develop full hypothyroidism, especially if those patients have positive TPO antibodies.

 

With hyperthyroidism, there will be a low TSH; high-normal TT4, FT4, TT3, FT3, and FTI; and normal T3U and rT3.  Antibodies are almost always positive for hyperthyroidism because almost all cases are due to autoimmunity (Grave’s disease).

 

Thyroid underconversion is a very common pattern and occurs when the thyroid is producing T4 normally, but the T4 is not being converted to T3 correctly in the body.  In this case, labs will show a normal TSH; high-normal TT4, FT4, and FTI; and low t3U, TT3, FT3, and rT3.  In this case, current or past causes of downregulation of the 5’deiodinase enzyme need be investigated.

 

Thyroid overconversion occurs when too much T4 is converted to T3, and the chronic high T3 can lead to thyroid resistance.  This is typically caused by elevated testosterone and insulin.  In this case, TSH is normal with low-normal TT4, FT4, FTI; high-normal T3U, TT3 and FT3; and normal rT3.

 

Excess estrogen (e.g., oral contraceptives, hormone replacement therapy, pregnancy) can cause elevations of TBG.  In this case, labs will show normal TSH, TT4, TT3, and rT3; low FT4, FT3, and T3U; and low-normal FTI.  In this case, patients often do not respond to nutritional thyroid support or thyroid replacement and eliminating exposure to outside estrogens and balancing estrogen levels needs to be considered.

 

In thyroid resistance, all labs may be within normal ranges or FT4 and FT3 may be elevated.  Patients may have no symptoms, or symptoms of either low or high thyroid function.  This is may be caused by a fairly rare genetic condition or by functional issues, typically high cortisol, which down-regulates some of the thyroid receptor sites, making them unable to respond to thyroid hormone.  For these non-genetic cases, there may also be issues with methylation (high homocysteine), vitamin A deficiency, or insulin resistance.

 

In Wilson’s syndrome, all lab tests are normal except a persistently elevated rT3 and the patient has hypothyroid symptoms.  This is most commonly due to chronically elevated cortisol.

 

Euthyroid Sick Syndrome most commonly occurs when a patient has another chronic illness that begins to affect the thyroid function test results.  The actual results may vary depending on the underlying condition, and for most of these patients, treatment focuses on the underlying illness and thyroid replacement is not recommended.

 

Autoimmune thyroid conditions can be difficult to assess because antibody levels and their resultant impact on thyroid function can fluctuate depending on factors affecting immune activity.  Early cases of Hashimoto’s thyroiditis, patients may present with a high or even normal TSH, hypothyroid and/or hyperthyroid symptoms but no thyroid Abs; in this case there is an autoimmune reaction, but the thyroid tissue has not been attacked enough to cause a change in thyroid test levels.  Without intervention, this patient would very likely continue on to develop Hashimoto’s thyroiditis with hypothyroid lab results.  For a patient with a low TSH, hyperthyroid symptoms and positive antibodies, it could be Grave’s disease or Hashimoto’s thyroiditis in a hyperthyroid state.

 

Treatments for Thyroid Disorders

Treatments for thyroid disorders vary greatly and depend on the specific type of imbalance.  Thyroid hormone replacement can include synthetic T4 (levothyroxine or synthroid), synthetic T3 (cytomel), synthetic combination (thyrolar) and natural thyroid sources, which include both T4 and T3 (e.g., Armour thyroid, Nature-throid, Westhyroid).  Dosing goals should include both achieving optimum lab test results and resolution of patient symptoms.

 

Thyroid supports include nutrients, herbs, and remedies that support normal thyroid function.  These may be helpful in addition to thyroid replacement or in cases where a patient’s lab values are not at optimum, but are still within the laboratory reference ranges.  Supports need to be tailored to each patient, and there are some cautions in using thyroid supports.  For example, while tyrosine and iodine are necessary to produce T3 and T4, excess levels can be suppressive to thyroid function.  If thyroid support is needed, functioning of other hormones should also be addressed.

 

Autoimmune thyroid conditions require broader treatment to include both support for thyroid function as well as addressing the immune dysfunction, the underlying causes for that dysfunction, and other concurrent health issues.  For example, some patients with Hashimoto’s thyroiditis have a defect in the vitamin D receptor which means these patients will require more vitamin D than a “normal” patient.  Additionally, patients with Hashimoto’s thyroiditis may also have other concurrent autoimmune conditions, especially celiac disease, and have a higher risk of developing thyroid cancer or pernicious anemia, type I diabetes, or rheumatoid arthritis.  It is also important to remember that patients with Hashimoto’s thyroiditis can have periods of episodes of hyperthyroidism if there are periods of greater immune activity and thus increased destruction of thyroid tissue and release of stored thyroid hormone.  Autoimmune hyperthyroidism often requires surgical removal or irradiation of the thyroid or pharmaceuticals to significantly suppress thyroid function.

 

There can also be many other influences on thyroid function, and in some cases, abnormal thyroid labs or thyroid-related symptoms are due to a non-thyroid cause.  Thyroid underconversion is most often caused by one or more of the following:

 

  • High cortisol (due to chronic stress, low blood sugar, insulin resistance, anemia, acute or chronic infections, toxicity, surgery, accidents, chronic pain);
  • Estrogen;
  • Hepatic dysfunction;
  • Imbalances in normal intestinal bacteria;
  • Viral infections;
  • Low selenium, zinc, and/or iodine;
  • Heavy metals;
  • Inflammation; and
  • Low glutathione.

 

All of these factors can affect thyroid functioning in general, and any treatment plan needs to investigate these other factors, and provide thyroid support while addressing the underlying cause(s).  This will also be true for the hormone imbalances that lead to thyroid overconversion or elevations of TBG.  Gluten sensitivity, celiac disease, and gut inflammation can also have a negative effect on thyroid function, as can overconsumption of soy, especially the more highly processed forms.  Many of the factors leading to thyroid underconversion may also result in thyroid resistance, and should be investigated when that condition is suspected.

 

 

Sources:

The Merck Manual

Kharrazian, Datis. Functional Blood Chemistry Analysis Seminar.

Thom, Dick. Practical Endocrinology Seminar.

http://www.mayomedicallaboratories.com/

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2664572

 

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Auto-Immune Conditions

Autoimmune conditions occur when the immune system starts attacking the body’s own cells thinking they are abnormal or foreign.  There are two general types of autoimmune diseases: those that affect specific organs, such as the pancreas (Type I diabetes), and those that affect tissues throughout the body, such as joints (rheumatoid arthritis).  There are overlaps between autoimmune diseases and patients may have more than one autoimmune condition at the same time.

The immune system responds differently in the two types of autoimmune diseases.  In organ-specific diseases, two types of antibodies bind to cells that have specific markers on their surfaces.  Once the antibody has attached itself, chemicals and inflammatory proteins are released that bring in other immune cells to destroy the targeted cell.  These cells then also produce chemicals that stimulate the inflammatory response.  In tissue-specific diseases, the immune system produces antibodies that don’t attach to specific cells. Instead, these antibodies are bound up in complexes that travel in the blood. The cells responsible for removing these complexes get overloaded, and the antibody complexes get deposited in different tissues.  These deposits then trigger the release of the chemicals and inflammatory proteins that bring in other immune cells.  As these cells attempt to destroy the complex, the surrounding tissue is also damaged.

The immune system is a complex balance of different cells and signaling chemicals; these cells and chemicals are divided into different groups based on the types of functions they perform. Two of the major groupings of the immune system’s function are Th1 and Th2, named for the two types of T helper cells that are active.  In a Th1 state, killer cells are activated to destroy abnormal (e.g. cancer) cells or cells infected with microorganisms (bacteria, viruses, and fungi).  In a Th2 state, antibody-producing cells are stimulated, and antibodies are used to attack microorganisms still outside the body’s cells.  The Th1 cells also stimulate the Th2 cells when they present proteins from the abnormal cells or microorganisms to the Th2 cells to stimulate antibody production for long-term immunity. In auto-immune conditions, both Th1 and Th2 cells play a role; the Th1 cells present proteins from the body cells to the Th2 cells, which stimulate the production of antibodies.  In general, some conditions tend to be more of a Th1 dominant state (e.g., rheumatoid arthritis, multiple sclerosis, Type 1 diabetes) and some conditions tend to be more of a Th2 dominant state (ulcerative colitis, lupus, scleroderma).  It is important to note however, that these are only general guidelines, the particular balance of Th1 and Th2 can vary greatly from patient to patient, and all immune conditions have some degree of Th1/Th2 imbalance.

I believe treating autoimmune conditions involves three major goals:

  •  Support the functioning of the specific cells/tissues affected;
  • Rebalancing the immune system between the Th1 and Th2 states to reduce antibody production; and
  • Reduce the risks of developing additional autoimmune conditions, cancers, or other complications.

Functional support

Different autoimmune conditions will have different target cells that are affected.  For example, in Hashimoto’s thyroiditis, the cells of the thyroid are destroyed while in Type I diabetes, the insulin-producing cells in the pancreas are destroyed.   Therefore, different functional support would be needed for these two conditions.

Immune System Rebalance

The body produces many different chemicals to signal which type of immunity (Th1 or Th2) should be stimulated, and which chemicals are produced can be influenced by many dietary and lifestyle factors.  The three most common factors that unbalance the immune system are faulty digestion, leading to absorption of partially digested and unusable proteins, which increases the antibody immune response;  white sugar, which directly weakens the functioning of macrophages and natural killer cells, and weakens systemic resistance to all infections; and trans-fatty and omega-6 acids, found in most heated and processed vegetable oils (e.g., soybean, safflower, corn, sunflower, and canola oil) and foods.  The trans-fatty acids weaken killer-T cell activity.  Vegetable oils are acceptable IF they are cold or expeller pressed oils, and stored in the dark.   Other factors to avoid include:

  • chronic infections, Candida (yeast), Streptococcus thermophilus (commonly found in yogurt);
  • asbestos, heavy metals, pesticides;
  • tobacco, alcohol, dehydration;
  • stress, negative emotions, steroids, hormone imbalances, chronic insomnia; and
  • sedentary lifestyle as well as weight lifting or exercising to excess.

Some positive immune factors include:

  • Omega-3 Fatty acids are found in all cold water fish, especially salmon, sardines, mackerel, halibut, and trout, with lesser amounts in dark-green leafy vegetables and sea vegetables and algae.
  • Oleic acids are best found in cold or expeller pressed extra virgin olive oil.  Secondary choices include hazelnut or filbert oil (or the whole nuts), green and ripe olives, and almonds.  Coconut oil can be used alternately with the other beneficial oils, especially for cooking.
  • Glutathione acts as an antioxidant and is essential for balancing the Th1 and Th2 immune states.
  • A healthy balance of intestinal flora change the Th2-Th1 balance of the immune system to re-establish the normal immune tolerance, in other words, the immune system knows what to respond to (i.e., bacterial infection) and what not to respond to (i.e., food).  Continued use of a probiotic is necessary because the entire surface of the upper intestines replaces itself every 72 hours and the colon replaces itself every 12 days.  These new surfaces need to be recolonized because the bacteria are lost with the cell shedding; there will be a loss of colonization over time if there is no replenishing.  There are different forms of probiotics and the most important factors are that the organisms are alive and are in the correct balance and amounts of the Bifidus and Lactobacillus bacteria.  For example, much higher levels are needed after antibiotics because Lactobacillus and Bifidus are highly sensitive to broad-spectrum antibiotics.  Antibiotics can eliminate 90% of these beneficial flora, allowing pathogenic bacteria, parasites, and yeast to increase.  Many probiotics also contain fructo-oligosaccharides (FOS), which is a soluble fiber.  FOS can cause gas for some patients, which is an indicator of a bacterial imbalance in the intestines because pathogenic bacteria produce gas when they encounter FOS.  Gas will decrease as the balance changes back to the beneficial bacterial types because Lactobacillus and Bifidus produce acid in the presence of FOS, not gas.
  • Digestive enzymes break up proteins into usable amino acids.  Apple cider vinegar stimulates hydrochloric acid, which is required to digest protein and activate enzymes. Eating slowly to allow natural salivary enzymes to work and eating only when hungry will also support good digestion. B vitamins are also required to support hydrochloric acid production and magnesium is required by the pancreas to produce enzymes to digest proteins.  Both B vitamins and magnesium are also necessary for proper adrenal functioning.  Chronic infections can also shift immunity toward Th2 and create an additional burden for the immune system, so investigating and treating chronic infections, especially in the digestive tract, is another key step.
  • Sunlight, water, touch, positive attitude, and acupuncture also have a positive effect on immunity.

One dietary change I recommend for all autoimmune conditions is a gluten free diet.  Gluten acts as a causative factor for celiac disease, so people with this diagnosis and/or a known gluten intolerance must avoid it.  However, gluten also seems to increase immune activity for a wide range of other autoimmune conditions, and is best avoided as part of treatment for any autoimmune disease.  Patients with auto-immune conditions should be cautious about adding supplements because many nutrients and herbs have multiple functions in the body.  For example, green tea is considered to be very healthy as an antioxidant source, but it has also been shown to increase Th2 immunity.  This might be a positive factor for a person with a Th1 dominant condition, but could worsen a person who already has a overactive Th2 immunity.  Therefore, I evaluate immune function indicators very carefully and monitor reactions to different supplements closely to try to identify how the immune system is functioning for each patient and helping to rebalance the system accordingly.

Risk Reduction

The diagnosis of an autoimmune condition often carries with it additional risks of developing other immune disorders, primarily cancers of the affected cells or additional autoimmune conditions in other cells.  For example, the risk of developing thyroid cancer or pernicious anemia, type I diabetes, or rheumatoid arthritis is higher for a person who has already been diagnosed with Hashimoto’s thyroiditis.  This is one reason I believe that simply supporting individual organ function or providing symptom relief is not enough for autoimmune conditions.  The immune system as a whole must be treated.  Additionally, supporting a balanced immune state will also allow the body to detect and destroy cancer cells more easily and is therefore, beneficial for cancer prevention.

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Lyme Disease

Lyme disease is a complex array of chronic infection, inflammation, toxicity, and immune dysregulation.  It is the number one vector-borne disease in theUnited Statestoday and is reaching epidemic proportions.  As of 2009, there were approximately 38,000 reported cases of Lyme to the Center for Disease Control (CDC), although estimates may be as high as 500,000 cases in theUnited States.

There is great controversy within the medical community about the prevalence and diagnosis of Lyme.  For example, the CDC provides stringent diagnosis criteria that should be used for research, but are usually used by clinicians to make patient diagnoses.  Additionally, the CDC does not believe there is in fact chronic, ongoing Borrelia infection.  They state that patients who continue to experience symptoms even after antibiotic treatment are suffering from “post-treatment Lyme disease syndrome”, which they feel is only an auto-immune condition.

Cause

Lyme disease is most commonly caused by the spirochete bacteria Borrelia burgdorferi, although there are at least nine other types of Borrelia bacteria, and these other species may also be able to cause Lyme.

Humans are infected when a deer tick (Ixodes species) bites a deer infected with Borrelia and becomes infected itself.  The tick then bites a person and transmits the Borrelia through its saliva.  There are different estimates as to how long a tick needs to be attached to transmit Borrelia, but all sources agree that the longer the time, the greater the chance.

It is also important to know that Borrelia has been found in the 49 contiguous United States and throughout Canada; there are no areas free of Borrelia. Lyme also isn’t spread by deer and deer ticks alone.  Borrelia has been found in gray squirrels, Western fence lizards, Northern Pacific seabirds, robins, and sparrows, as well as mosquitoes and fleas; it can not by transmitted by dog ticks.  There is also evidence that it can be passed via blood transfusion, placental transfer, sexual transmission, and breastfeeding.  However, in these human-to-human cases, it is imperative that a positive test be interpreted in light of a person’s clinical presentation; a positive test may simply indicate a past exposure, rather than a chronic infection.  There are people who can clear the infection without it becoming chronic so not everyone with a positive test needs treatment.

Co-infections and Opportunistic Infections

Other infections, including Babesia, Bartonella, and Ehrlichia, can also be transmitted with Borrelia, and are considered common co-infections.  Babesia is a protozoa that invades red blood cells.  There are more than 100 species and at least four of them have been shown to cause human disease.  Bartonella is a bacteria that also lives within cells and at least six species know to infect humans.  Ehrlichia is a bacteria within the Rickettsiae family (e.g., Rocky Mountain Spotted Fever) and lives within white blood cells and mast cells.

Other infections may not be directly transmitted with Borrelia, but may occur opportunistically due to the immune dysregulation that Borrelia can cause.  These can include bacteria, fungi/yeast, viruses, and parasites.

Because of this, Drs. Daniel Newman and Stacey Rafferty think it might be more appropriate to refer to chronic Lyme Disease as Multiple Chronic Infectious Disease Syndrome (MCIDS).

All of these infections can complicate the diagnosis and symptom picture and may need to be addressed individually as part of the overall treatment plan.  Many of these infections can also trigger auto-immune conditions, which again may create a more complicated clinical picture.

Signs/Symptoms

Signs and symptoms will vary greatly between an acute and chronic infection and may be complicated by other infections, toxicity, and underlying conditions.

Acute

People with an acute infection often manifest with a fever, headache, fatigue, and general flu-like symptoms.  Very few infected people will manifest the classic “bulls-eye” rash; some research indicates only eight to ten percent of people will show this acute manifestation, and often the rash may simply be a solid red area.  Also, very few people remember a tick bite, as the Ixodes ticks are about the size of a poppy seed, and infection can be latent for months to years after the original bite.

Chronic

Main symptoms of a Lyme infection will be neurological symptoms, muscle and/or joint pain weakness that comes and goes and varies in location, fatigue, sleep disturbances, and cognitive dysfunction.  Other symptoms can include:

other rashes                                                  lymphocytoma

fever or low temp                                        chills, sweats

recurring flu-like symptoms                    headache

stiff/cracking neck                                       anxiety

Bell’s palsy                                                       blood pressure instability

getting lost                                                       lightheaded

mood swings                                                  low stamina

sleep disturbances                                       pressure in eyes, blurry vision

heart palpitations                                         shortness of breath

ears ringing                                                     sound sensitivity

poor balance, vertigo                                 stomach upset

digestive irregularities                              menstrual irregularities, lack of menses

irritable bladder                                           abdominal/pelvic pain

electric/numb sensations                         low libido

Many of these symptoms will come on gradually and cycle on usually a four to six week cycle; for menstruating women, symptoms may be notably worse before or during their menses.

On a physical exam, there may be diffuse musculoskeletal pain, clammy hands and feet, vertical ridges in the nails, spasms of the muscles along the spine, hyper-reflexes, extreme cold (oral temperatures of 96-97.9 degrees) and cold extremities, abdominal distention, plantar tenderness in the feet, joint cracking, heart irregularities, mottled or dark spots on skin, psoriasis, yeast, swelling, and browning of teeth.

Additionally, the co-infection organisms can have their own sets of more specific signs and symptoms that may occur with or alternately with those of Borrelia:

  •  Babesia: fever, chills, day/night sweats, anxiety, fear, obsessions/compulsions, pressure headaches, insomnia, joint pain more predominantly in the ankles, wrists, and hands, difficulty taking a full breath(air hunger), easy bruising, red spots on skin (cherry angiomas), dark spots on base of nails, abnormal reflexes, night sweats, joint pain in the knees and ankles, and vertigo
  •  Bartonella: ice pick headache, cognitive difficulties, seizure, painful/burning soles of feet upon rising, photophobia, sensation of pressure behind the eyes, purple stretch marks, browning of the skin, swollen lymph nodes, abdominal tenderness, fever, and very small tremors of the muscles
  •  Ehrlichia: High fevers with sweating, low white blood cell and platelet counts, elevated liver enzymes, extremely tender muscles, and liver enlargement

It is important to know that chronic Borrelia infection can mimic or trigger a huge list of conditions, including:

Multiple sclerosis                                         Amyotrophic lateral sclerosis

Alzheimer’s disease                                     Parkinson’s disease

Rheumatoid arthritis                                  Dementia

Chronic fatigue without pain                  Recurrent acute aseptic meningitis

Charcot Marie-Tooth                                 Guillian Barre

Scleroderma                                                   Lupus

Polymyalgia rheumatica                           Polymyositis/dermatomyositis

Fibromyalgia                                                 Multiple Chemical Sensitivity

Bipolar disorder                                           Schizoaffective disorder

ADHD                                                               Autism

Chronic EBV                                                 Thyroid disease/Hashimoto’s/Grave’s

Hyperparathyroidism                              Addison’s disease/adrenal insufficiency

Reflex sympathetic dystrophy             Fungal hypersensitivity

If a person presents with one of these conditions, Lyme disease should be considered and any testing should be evaluated in light of these diagnoses.

Diagnosis

The CDC recommends two tiers of testing: the Elisa test followed by a Western Blot for confirmation.  The difficulty with this recommendation is that the Elisa is highly unreliable for Lyme- there are some estimates that up to 35-40% of people who have had the Borrelia actually found in their bodies will show a negative Elisa test.  While the Western Blot is more accurate, it is only done to confirm a positive or equivocal Elisa test if one is following the CDC recommendations exactly.

The Western Blot looks for reactivity at different protein weights that creates a banding pattern on the test and different types of spirochetes and/or parasites may give reactivity at these bands.  The IgG bands specific to Borrelia burgdorferi are 18, 21-23, 28, 31, 34, 39, 83, and 93 kD.  Most labs do not include bands 31 and 34 as they were used in the development of a Lyme vaccine (no longer in use).    According to the CDC, a positive test has reactivity at 5 or more of the IgG bands numbers18, 23-25, 28, 30-39, 45, 58, 66, and 93 or 2 or more of the IgM bands numbers 23-25, 39, or 41.  The most important thing to know about the CDC criteria is that they are for use in investigational research, NOT CLINICAL DIAGNOSIS.  IGeneX labs uses a more clinically relevant evaluation system whereby a positive test is indicated by 2 reactive bands of the 23-25, 31, 34, 39, 41, and 93 kD weights.

There are some challenges with the Western Blot test in general.  For example, the test results will be affected by how much of the blood sample was used, how often it was diluted, the types of strips used and how they were stored as well as the skill of the person reading the tests.  Also, there can be cross-reactivity with hepatitis, Epstein-Barr virus, and Herpes simplex virus at bands 31 and 34, and band 41 is specific for some kind of spirochete bacterium, but not necessarily Borrelia.  The current testing is also skewed toward the Borrelia burgdorferi, so testing may be negative if one of the other Borrelia species is the cause.  Also, if the person is highly immunosuppressed, they may show a negative test because their immune systems are unable to make enough antibodies to the Borrelia.  Therefore, results must ALWAYS be interpreted in light of clinical presentation.

Because Borrelia can live in a cyst form, the Western Blot test may also come back as a negative if most of the organism is in this stage.  In cases where there is a negative test but high clinical suspicion, the person may be asked to do a trial of Lyme-specific anti-microbial treatment, especially cyst disruption, and repeat the test.

Currently, the testing for the co-infection organisms can be even more challenging with greater limitations.  Therefore, while a positive result on any of these tests is truly a positive, a negative result does not necessarily rule out the infection.  Again, clinical presentation and possibly response to trial of treatment becomes more important.

Treatment

Treatment for Lyme (and any co or opportunistic infections) must have three main components:

  • Eliminate the infection,
  • Optimize the person’s natural immunity, and
  • Correct imbalances that created the hospitable environment for the infection originally.

Borrelia can live in several different states, including a cyst form, and antimicrobial treatment needs to include therapies that target each of these forms.  Many of the natural anti-microbial treatments can also be effective against other bacteria, viruses, fungi, and protozoa, but there are times when the treatment focus needs to change slightly as one of the other co- or opportunistic infections may become dominant.

It is important to recognize that there is little research on herbal anti-microbials directly with Borrelia and most of the information has come from trials with other spirochete bacteria.  However, many of these formulas have shown clinical success, and that is significant especially with a disease that is so clinically driven.  At times, pharmaceutical antibiotics may be needed, and in those cases, anti-fungal treatments are necessary to prevent worsening fungal imbalances.  In either case, treatment for Lyme, including rebalancing and immune optimization, can take years, especially as the infection will go through its own natural cycle or flaring and dormancy periods.  The good news is that there are many treatment options with emerging clinical success that can be used, and while Borrelia can cause many cognitive and psychological symptoms, I don’t believe Lyme is just “all in your head”.

References:

Center for Disease Control website

Lyme Disease Diagnosis and Integrative Treatment: A Practical Course for Naturopathic Physicians. Dr. Daniel Newman, MD, ND, MSOM and Dr. Stacey Rafferty,BSN,ND, LAc. April 2012.

Rheumatology and Clinical Psychoneuroimmunology and Oriental Medicine. Dr.Satya Ambrose,ND, LAc. February 2010.

Case Management and Treatment for Lyme Disease. Dr.Mikhael Adams,ND. December 2009.

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Tics and Tourette’s Syndrome

 Tics are repetitive, stereotyped, involuntary movements and vocalizations.  They can be classified as transient or simple, chronic, or as part of diagnosing Tourette’s syndrome (TS).  Transient/simple tics are sudden, brief, simple movements.  Common simple motor tics include eye blinking, facial grimacing, head jerking and shoulder shrugging or jerking.  Simple vocal tics can include throat clearing, sniffing, yelping, tongue clicking, or grunting sounds.  Simple tics can also change from one manifestation to another.

 Complex tics involve more muscle groups and are distinct movement patterns.  An example may be a facial expression with a head twist or shoulder jerk.  Some tics may appear voluntary or purposeful, like touching objects, hopping, twisting, or bending, and can include self-harm, such as biting oneself or punching oneself in the head.  Complex vocal tics often include words or phrases, including socially inappropriate words (coprolalia) or repeating others’ words (echolalia); however, coprolalia only occurs in 10 to 15 percent of patients with TS.

TS can only be diagnosed when:

  • “Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently;
  • The tics occur many times a day (usually in bouts) nearly every day or intermittently throughout a period of more than one year.  During this time, there is never a tic-free period of more than three consecutive months;
  • The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning;
  • The onset occurs before 18 years; and
  • The disturbance is not due to the direct physiological effects of a substance (e.g., stimulants) or a general medical condition (e.g., Huntington’s disease or post viral encephalitis).” (Natural Treatments for Tics & Tourette’s, Sheila Rogers)

There are no blood, laboratory, or imaging tests needed for diagnosis of TS.  Imaging or blood tests may be used to rule out other conditions that might be confused with TS when the history or clinical examination is atypical.   Tics related to PANDAs are considered a separate category because they are specifically related to a streptococcal infection.

Tics are often brought on or are worse with excitement, anxiety, stress, or fatigue, and may be better during calm, focused activity.  They are also decreased during sleep but may still occur.  Overall, they can come and go over time, varying in type, frequency, location, and severity.

Environmental triggers or even tics themselves can often cause more tics to occur, and many patients report an urge prior to the tic occurring.  This urge is often only relieved after the tics occur in a certain way or after a certain number of times.  Some people can sometimes suppress or camouflage their tics in certain situations, e.g., work or school.  However, this usually leads to a substantial buildup in tension until the tic must be expressed.  Even though tics can temporarily be suppressed, it should be remembered that tics are not voluntary and the suppression is only temporary and requires a great deal of effort by the patient.

TS is usually first noticed between three and nine years old, but worst symptoms usually occur in early teen years with improvement occurring into adulthood.  It occurs in all ethnic and racial groups, and rates are three to four times higher in males than females.  Current estimates show 200,000 cases in theUSof the most severe form and possibly one in 100 people who show mild or simple tic symptoms.

There are also other neurobehavioral issues that can be associated with TS.  These include inattention, hyperactivity and impulsivity (ADHD); problems with reading, writing, and arithmetic; learning disorders; impulse control problems; sleep disorders; and obsessive-compulsive symptoms such as intrusive thoughts/worries and repetitive behaviors.  Patients may also experience depression or anxiety but it is unclear if these are related to the TS specifically or may be due to the stress that TS can cause.  Patients with TS also experience allergies at higher rates than the general population.  There are also greater numbers of other health issues, including nausea, “sick” feeling in the stomach, general aches and pains, and headaches.

Cause

The cause of TS is currently unknown.  There is evidence that TS is an inherited disorder and that some forms of ADHD and OCD are genetically related to TS.  Current research also indicates that there may be elevated levels of the NT dopamine, which would most likely create abnormal levels of other neurotransmitters (NTs), possibly serotonin and norepinephrine.  There may also be abnormal activity at the dopamine receptors.

Everything You Wanted to Know About Dopamine

Dopamine is synthesized by nerves and the adrenal glands from the amino acid L-tyrosine and is a precursor to norepinephrine (noradrenaline) and then epinephrine (adrenaline).  The production of dopamine from L-Dopa requires vitamin B6, and the conversion from dopamine to norepinephrine requires vitamin C.

Dopamine has many functions in the brain, including important roles in behavior and cognition, voluntary movement, motivation and reward, sleep, mood, attention, and learning, especially with new behaviors.  Dopamine also controls the flow of information from different areas of the brain, and dopamine disorders can cause a decline in cognitive functions, especially memory, attention, and problem-solving.

Dopamine is commonly associated with the pleasure system of the brain, providing feelings of enjoyment and reinforcement to motivate a person to perform certain activities. Dopamine is released by naturally rewarding experiences such as food, sex, drugs, and neutral stimuli that become associated with them. Aggression may also stimulate the release of dopamine in this way.

Sociability is also closely tied to dopamine, and low dopamine receptor-binding is found in people with social anxiety. Traits common to negative schizophrenia, such as social withdrawal and apathy, are thought to be related to a low dopamine level in certain areas of the brain. Manic episodes of bipolar disorder may also be due to an increase in dopamine, because mania can be reduced by dopamine-blocking anti-psychotics.

Dopamine has been demonstrated to play a role in pain processing in multiple levels of the central nervous system. Decreased levels of dopamine have been associated with painful symptoms that frequently occur in Parkinson’s disease. Abnormalities in dopamine neurotransmission have also been demonstrated in painful clinical conditions, including burning mouth syndrome, fibromyalgia, and restless legs syndrome.

Dopamine is eliminated from the body by either conversion to norepinephrine or final detoxification of dopamine itself via the methylation process.  It is broken down by two enzymes: catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO).  COMT transfers a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAMe).  Methylation is a process that occurs as part of our natural detoxification and is the primary method the body uses to clear dopamine, norepinephrine, and epinephrine.  The methylation process requires certain nutrients, including folate, vitamin B12, methionine, choline, and betaine.  In this process, however, folate can only serve if it is in its active form, 5-methyltetrahydrofolate (5-MTHF).  Methylenetetrahydrofolate reductase (MTHFR) is an enzyme that converts folate to 5-MTHF; low levels or genetic variants of this enzyme that decrease its activity could increase levels of dopamine indirectly by reducing its detoxification.

MAO enzymes also breakdown dopamine (as well as melatonin, serotonin, norepinephrine, and epinephrine); a dysfunction in MAO enzymes (too much or too little activity) has been associated with a number of conditions, including ADD, substance abuse, migraines, and schizophrenia. This indicates that these conditions (and possibly others) may relate to increased or decreased levels of these NTs due to changes in the MAO (or other enzyme) activity.  MAOs also contain flavinoids and the bioflavinoids and polyphenols in resveratrol are being investigated in relation to MAO’s link to depression.

Pharmaceutical Treatment

Most people are not disabled by their tics and require no treatment at all.  Currently, allopathic medicine treats TS with neuroleptic medications, including haloperidol (Haldol), clonidine (Catapres), pimozide (Orap), risperidone (Risperdal), fluphenazine (Prolixin, Permitil), and clonazepam (Klonopin). Effective dosages can vary among patients and should be started at low levels and gradually increased under doctor’s supervision.  Some of the undesirable reactions to medications are weight gain, muscular rigidity, fatigue, motor restlessness, cognitive impairment, depression, and social withdrawal, most of which can be reduced with specific medications, dosage reduction, or a change of medication.  Neurological side effects such as tremor, dystonic reactions (twisting movements or postures), parkinsonian-like symptoms, and other dyskinetic (involuntary) movements are less common and are readily managed with dose reduction.  Discontinuing neuroleptics after long-term use must be done slowly to avoid rebound increases in tics and withdrawal dyskinesias. One form of dyskinesia called tardive dyskinesia is a movement disorder distinct from TS that may result from the chronic use of neuroleptics. The risk of this side effect can be reduced by using lower doses of neuroleptics for shorter periods of time. 

Additional medications with demonstrated efficacy include alpha-adrenergic agonists such as clonidine and guanfacine.  These medications are used primarily for hypertension but are also used in the treatment of tics. The most common side effects from these medications are sedation and lowering of blood pressure.  Botox has also been used in recent years in an attempt to freeze the muscles involved with the tic, but results have been mixed.  Nicotine patches may be helpful in reducing the dose of neuroleptic medication, but haven’t been shown to be helpful as single agents.  Drugs for ADHD [methylphenidate (Ritalin) and dextroamphetamine (Dexedrine)] have been described as increasing tics, but this is controversial.  For obsessive compulsive traits that interfere significantly with daily functioning, fluoxetine (Prozac), clomipramine (Anafranil), sertraline (Zoloft) and paroxetine (Paxil) may be prescribed.

Naturopathic Treatment

Like with any condition, we need to understand why a person has the symptoms that are presenting.  In Sheila Roger’s book, Natural Treatments for Tics & Tourette’s, she quotes Dr. Sidney Baker’s basic approach as “Is there something your body needs for which you have some individual, perhaps quirky, requirement that is not being met?  Or, is there something you are getting that you as an individual have some quirky, sometimes unusual, need to avoid?”  This is actually my basic philosophy in working with any patient, although I would add a third question:  “Or, is it both?”

Identifying Tic Triggers

Identifying your particular triggers may be a good start to making changes.  Some of the most common triggers include:

  • Stress, overstimulation, anxiety, worry, fear, self-consciousness
  • Caffeine, sugar, corn syrup, alcohol
  • Noise
  • Video games/TV/movies/flashing, bright, or fluorescent lights
  • Infections
  • Car or bus rides
  • Heat or change of temperature
  • Specific foods, artificial additives
  • Chemical exposures, carpeting, pesticides, paint fumes, gasoline fumes
  • Dust, mold, pollen
  • Scented products (candles, perfume, aftershave, air-fresheners), cigarette smoke

The Association for Comprehensive Neurotherapy (CAN) has a checklist of potential triggers at www.ticsandtourettes.com that you can use as a guide; remember it is not a complete list and you may need to add to it.  You may also need to take detailed notes initially to be able to discern what part of a situation was the trigger: If you got overheated while watching a stressful movie, was it the heat, the stress, the movie, or the combination of all three?  As you are able to record and observe more situations, you may be able to discern more specific trigger patterns.

Diet

I believe diet plays a huge role in health, regardless of the symptom or diagnosis.  Many patients have reported significant changes with dietary changes, both in terms of tics reducing when certain foods were eliminated and observing tics return with the reintroduction of those foods.  Dietary changes may be beneficial because they specifically influence dopamine, reduce systemic inflammation, improve intestinal immunity, and/or provide greater nutrition.

An elimination diet is often a good place to start, although I would also recommend completing a diet diary prior to the elimination so you know which foods may be the worst culprits for you.  The most common foods reported to increase tics are gluten, dairy, egg, sugar, corn, and artificial anything (color, flavors, preservatives).  Salicylates, amines, and MSG can occur naturally in certain foods, and it may be worth investigating those specific foods.  It may also be worth investigating foods that are naturally high in dopamine, including wheat, corn, sugar, apples, bananas, and dairy.  It is interesting that patients report changes in tic behavior associated with four of the six foods on this list.  Because tyrosine is the amino acid used to synthesize dopamine, it may also be helpful to try eliminating foods naturally high in tyrosine (dairy, wild game, pork, chocolate, wheat, egg, duck, and chicken).

As with any condition, one diet does not fit all, and dietary changes may require trial and error before you find the best dietary changes for you.  Food allergy testing may be helpful, but these tests do not always provide perfectly accurate information.  Also remember to read labels carefully because of hidden additives.

Environment

Many patients report environmental triggers for their tics.  Evaluate your exposure to chemicals, cleaners, pesticides, fumes, scented home and personal products, dust, mold, pollen or other environmental allergens, and cigarette smoke at home, work, or other frequented locations.  Also consider how much screen time you have or how much time you are around electrical equipment, including TV, computer, Ipad, wireless networks, and cell phones.    Many patients with TS have sensory sensitivities (overly sensitive, under sensitive, or unusual reactions to stimuli) to heat, touch, smell, sound, light, taste, or movement.  Chapter 9 of Natural Treatments for Tics & Tourette’s has a great discussion of ways to work with different types of sensitivities to reduce their impact.  Occupational therapy may be one option to consider with sensory balancing and integration, especially for multiple sensitivities.

While you are looking at what you might need to remove from your environment, also consider how relaxing your environment is at work, school, and/or home.  While tics and TS are never simply a matter of learning how to relax, many people do report fewer or less severe tics when they are relaxed and in a relaxing environment.

Chronic Infection and Dysbiosis

Many patients with TS are found to an overgrowth of yeast and an imbalance of the beneficial intestinal bacteria (dysbiosis).  I believe yeast overgrowth is an indication of some other immune imbalance, as yeast is a normal part of the intestinal flora in small amounts.  Most commonly, I see yeast overgrowth as an indication of heavy metal toxicity or other chronic infection, especially viral or bacteria.  There is even some evidence that chronic Lyme infection can cause symptoms very similar to TS and could either contribute to TS or be mistaken for it.  So while yeast overgrowth can be treated with natural or pharmaceutical anti-fungals, I believe the reason for the overgrowth must be investigated.  Dysbiosis is best treated with a high quality probiotic appropriate for the particular person both in the type and number of organisms, as well as methods to heal the intestinal lining, decrease toxicity from yeast and pathogenic bacterial toxins, and improve digestion.

Detoxification/ Methylation Support

If tics and TS are due to elevated dopamine, patients may be able to facilitate a change by optimizing detoxification through the methylation pathway.  It is interesting to note that this pathway is also the primary Phase 2 detoxification route for histamine, possibly indicating one way TS and increased allergies could be linked.  Patients do report improvement in tics and allergies with vitamin C, which is known to stabilize the mast cells, preventing histamine release.  Because histamine itself hasn’t been shown to cause tics, I wonder if the decreased load of histamine allows for greater methylation and detoxification of dopamine, thus reducing tics.  It is also interesting that the methylation pathway can be decreased by high estrogen, so balancing hormones may indirectly improve tic symptoms.

Steps to optimizing detoxification for patients with TS would include:

  • identifying past and ongoing sources of toxins, including heavy metals, vaccinations, medications, chemical exposures, dental amalgams, bacterial toxins from dysbiosis, mold, and dietary toxins including gluten and casein;
  • identifying and treating chronic viral, bacterial, fungal, or parasitic infections;
  • identifying and eliminating exposure to allergens to decrease overall inflammation and potential nervous system reactions to allergen exposures and balance neuroimmune connections;
  • identifying and treating hormonal imbalances that may affect liver detoxification, metabolism, and stress management;
  • improve overall liver and kidney function, and all elimination routes; and
  • specifically support the methylation pathway with appropriate doses of active folate, vitamin B12, S-adenosyl Methionine (SAMe), choline, and/or betaine.

Relaxation

Anything a patient can do to relax will be beneficial for TS symptoms and overall health.  People have reported benefit from biofeedback, acupuncture, homeopathy, massage, meditation, deep breathing, and craniosacral therapy.  Chiropractic care may also be beneficial, as structural problems will affect how the nerves function.  Exercise is a great addition, although there could be potential triggers associated with certain activities (e.g., chlorine in a swimming pool or pesticide use on a golf course).

Psychotherapy may also be helpful, especially for children when acceptance by peers is paramount for development.  Many teachers are unaware of TS and other learning tools/environments may be needed to create a supportive classroom.

Nervous System Support

The nervous system is an incredibly complex system with many interactions between NTs and connections with the immune and endocrine systems.  Because of this, I tend to focus on therapies that either provide the nervous system with basic nutrients needed for proper functioning (e.g., omega 3 essential fatty acids and magnesium) or allow the nervous system to rebalance itself (e.g., biotherapeutic drainage remedies and single homeopathics).  I am cautious using individual amino acids and NT precursors because one can easily get out of balance by oversupplementing just one amino acid or NT pathway.  There are tests that can be helpful to evaluate levels of specific NTs to get better information about possible imbalances and nutritional needs.

Individual herbs, such as St. John’sWort to increase serotonin, should also be used cautiously, as not all patients with tic or TS may have low serotonin.  Imbalances in one NT often cause, or are associated with imbalances in other levels, but the exact patterns are not always the same for all patients.  A patient who has normal serotonin may experience no benefit from taking this herb, but in a worse case, could actually creating further imbalance by elevating levels too high.  Herbs can be very powerful and can also have significant interactions with medications, so a patients’ response to herbs and drug-herb interactions should be monitored by a knowledgeable physician.  It is also important to recognize that gluten, heavy metals and other toxic exposures, and chronic infections can all have significant negative impacts on the nervous system.

Prognosis
Currently, there is no cure for TS.  However, many people improve in their late teens and adulthood.  Although TS is considered to be a chronic, life-long condition, up to a third of patients can experience a remission in adulthood.  While many people report a decrease in tics with age, other associated disorders often persist.  However, there are many individual reports of patients who have been able to make significant reductions in tics by identifying and eliminating triggers, changing their diets and environments, and supporting nervous system function.  Patients also report better outcomes when they are supported by family and friends and continue to observe and be creative with the solutions that work for them.  Let’s develop a plan that works for you.

 Resources:

Rogers, Sheila. Natural Treatments for Tics & Tourette’s: A Patient and Family Guide. Association for Comprehensive Neurotherapy:Oklahoma, 2008.

www.latitudes.org

www.ticsandtourettes.com

www.ninds.nih.gov/disorders/tourette/detail_tourette.htm

www.tsa-usa.org (National Tourette Syndrome Association)

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Probiotics

Probiotics are beneficial bacteria that reside in our small and large intestines that support healthy digestive function, regulate our immune systems, produce enzymes that can kill pathogenic bacteria, and provide nutritional support, including production of vitamin K.  Probiotics have been shown to reduce IBS, allergy, and cancer risk.  Levels of these good bacteria can decrease due to many factors, including:

  • Age
  • Antibiotic and other medication use
  • Infection
  • Lifestyle
  • Poor diet, especially low fiber
  • Stress
  • Digestive disorders
  • Travel

 

Probiotics may be found in yogurt and fermented foods, but the highest amounts of beneficial, live cultures are found in high quality supplements.  Sources of probiotic supplements include human, animal, vegetable, and soil.

 

When choosing a probiotic supplement, there are several factors to consider:

  • Are the strains proven to be totally non-pathogenic?
  • Are the strains indigenous and appropriate for humans?
  • Are the strains proven to be capable of colonization?
    • Can the strains resist stomach acid and bile salts, both of which are antimicrobial?
    • Can the strains actually attach to the cells lining the intestine?
    • Have the stains been shown to regulate the immune system in humans?
  • Is there scientific evidence to support their use, i.e., published data from independent, clinical trials in humans?
  • Does the manufacturing company have a quality assurance program that provides its testing information to practitioners?

 

There are also many strains of bacteria that are included in many probiotics.  The biggest question regarding those strains is: do they work?  One well-characterized strain known to work is going to be more effective for a patient than ten strains that don’t work or have no supporting evidence.  For example, if a product contains 100 billion organisms, but none of them adhere to the intestines, then they will all be flushed out and have no or minimal health effects.  Additionally, many enteric coatings don’t dissolve until the end of the small intestine, so the beginning and middle portions of the small intestine (the main areas of colonization) are missed.

 

I use Genestra and Pharmax brands because they meet all these criteria and are the only brands approved by the Medicines and Healthcare Products Regulatory Agency (MHRA) inEuropeto be used in scientific, clinical trials.  These brands also have a 50 percent overage in the number of live organisms at the time of manufacture.  This is done to ensure that the label claim of number of live organisms is still met if the product is kept at room temperature for 24 months.  For example, the label of HMF Forte says there are 10 billion live organisms per capsule.  At the time of manufacture, each capsule has 15 billion and refrigeration will maintain that overage.  Many of their products also contain fructo-oligosaccharides (FOS), which is a form of soluble fiber that serves as food for the probiotics.  Several products also contain glutamine for repairing small intestine permeability and supporting nervous system function.

 

Some guidelines for taking probiotics:

  • Always take probiotic with food to reduce the effects of stomach acid.
  • Maintenance of normal flora levels requires supplementation of 2 to 10 billion organisms/day.
  • Therapeutic effects in the small intestine (e.g., preventing infection, immune system regulation) require doses of ≥25 billion organisms/day.
  • Therapeutic effects in the large intestine (e.g., effects of broad-spectrum antibiotics, inflammatory bowel disease) require doses of ≥ 100 billion organisms/day.
  • Children over 5 years old can receive adult doses.  Children under 5 years old should receive a probiotic specifically designed for young children, as the total amounts and overall balance of organisms will be different than products for adults.
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Gastroenterology seminar

January 21-22 was a great gastroenterology seminar with updated information on celiac and the range of gluten reactions, crohns, leaky gut syndrome, and colon cancer, and new information on small intestine bacterial overgrowth (SIBO).  Gave me lots of ideas!

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Hormones

The Endocrine System in Naturopathic Medicine, The Triple Burner in Chinese Medicine, Chinese Triple Burner Diagnoses

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