Lack of B6 and tics, food allergies, behaviors...

The following addresses TS/OCD/ADD. The diagnosis would lie in the degree of vitamin B6 dependency/deficiency, and how long the person has been in this state. Carl Hansen, Jr. M.D. of Minneapolis describes celiac disease in several of his TS patients. This could be a pathway to vitamin B6 deficiency via malabsorption. Streptococcal infections have also been associated with TS. This could be a combination of the hyaluronidase's (an enzyme produced by the hemolytic strep that depolymerizes the ground substance of tissue) or streptokinase's actions on the blood brain barrier, the drain of vitamin B6 from the bacteria's own useage, the body's requirement of B6 for immunity, and the antibiotic's B6 antagonistic properties. A pre-exising B6 dependency/deficiency could be uncovered. TOURETTE SYNDROME, ALLERGY AND THE B6 DEPENDENCY STATE I have my Bachelor's degree in Biology, specializing in Medical Technology, and in graduate school, I took graduate courses in biochemistry. I work as a medical technologist performing and verifying clinical laboratory tests in Chemistry, Hematology and Blood Bank at Mt.Carmel East Medical Center in Columbus, Ohio. I do not have TS but my son, Jason (13 yrs old) has TS with OCD. ADD has not been formally diagnosed, although he has problems with organization, distractibility, and the ability to switch gears. My son has had allergies since he was a baby. He is sensitive to red dye #40 with tired splitting headaches which make him scream until he is exhausted and sleeps. This, of course, hasn't happened in several years since he has avoided the dye. He also is allergic to sulfa, molds, dust, grass, trees, and most airborn allergens. He has been on the vitamins below for 1.5 months and the teachers have said that he is a different kid. Medications that he had been on made him progressively worse, and so we made a personal decision to discontinue meds altogether. He now is motivated in school, concentrates and finishes his work, and is less disruptive with his tics in class. At home he still has his tics and compulsions, but they are shorter lived and occur less often. He has had a set back this week due to a new semester with a new schedule, plus a very moldy, rainy few days. We gave him a little extra calcium-magnesium and one extra vitamin B3. He said that this gave him relief from his symptoms (he has never said this before with anything else). I solidified my theory on the premise that Jason is probably mildly vitamin B6 dependent. He was either born requiring high amounts of B6, and/or B6 antagonists attacked early in his first year of life. B6 antagonists are hydrazines (plant growth regulators, tartrazine, etc), DOPA found in certain beans, penicillinamine, antioxidants in petroleum, many drugs including penicillin, erythromycin, phenobarbital, tetracycline, corticosteroids, sulfamethoxazole, etc. Amino acids began building up in his system, from decreased transamination, etc. Serotonin became decreased from tryptophan not being able to be utilized. Allergies developed (which is in association with low B6), I believe allergy produces swings in histamine levels which causes a constant fluctuation in neurotransmitters capable of producing mood swings and rages. The conservation of vitamin B6 (when not abundantly available) causes it to be used by the prevailing neurotransmitter system at any given time, leaving other neurotransmitter systems less than optimally functional. Histamine receptors have been found to trigger dopamine receptors directly. Histamine is also a neurotransmitter affected by deficient vitamin B6. Its receptor sites are probably increased to compensate. Kinins released into the body's tissues in response to immune complexes can damage the blood brain barrier, thus altering the sensitivity of brain cells to acetylcholine, serotonin, dopamine, histamine, epineprine and norepineprine. I found that L-dopa doesn't readily form dopamine in B6 deficiency, so probably dopamine is reduced causing an increase in dopamine receptor sites along with an increase the norepinephrine and epinephrine (which are formed from dopamine) receptors sites. These increased receptor sites make the nerves more excitable and false transmitters or true neurotransmitters can set them off with explosive qualities. These false transmitters can be phenolic substances, such as food additives, drugs, etc. The enzyme, phenol sulfotransferase (PST), detoxifies and eliminates phenolics (drugs, food additives, serotonin, dopamine (to name a few). In the brain, sulfation is used while glucuronidation prevails elsewhere. Cysteine requires B6 to enzymatically release sulfur for sulfation of these phenols by PST. Considering this, the neurotransmitters would would be conserved to a certain extent (their sulfation and elimination would be slowed down). ADD may happen when these false transmitters create background "noise", and if there is a real message to get through via other neurons, it is masked. When a true message is fired, it may have too strong of a signal, creating a strong impulsion, which can lead to the development of a tic or compulsion if the impulsion is acted upon and repeated creating a sort of conditioned reflex network of nerves. Mental, motor, and vocal tics can develop this way. According to my_ Biochemistry_ by Lehninger textbook from my graduate student in Biology days, tryptophan is broken down in Vitamin B3 deficiency to make nicotinic acid. Tryptophan is found in meat and is plentiful, if you are a meat eater. Tryptophan is the precursor for serotonin. I also looked up Vitamin B3 and how it could be connected to the issues of allergy and serotonin defiency in the brain. I found that Vitamin B3 is used to make NAD, NADP, which are coenzymes used in making histamine and serotonin (to name a few), and are essential in oxidative-reductive cellular metabolism. The B3 is needed due to tryptophan's inability to be broken down to nicotinic acid without adequate B6. So, if Vitamins B3 and B6 are being used for histamine production, then serotonin production suffers. Tryptophan then must be used in a higher frequency to make nicotinic acid. In Vitamin B6 deficiency, this cannot happen, because the enzyme kynurinase, that catalyzes the cleavage of 3 hydroxykynurine (an intermediate in tryptophan catabolism), contains pyridoxal phosphate (an active coenzyme form of Vitamin B6). In Vitamin B6 deficiency, large amounts of L-kynurenine are excreted in the urine, because of its high plasma levels. This is described in "Elevated plasma kynurenine in Tourette syndrome", _Molecular & Chemical Neuropathology_21(1): 55-60,1994 Jan. Kynurenine itself is metabolised to other substances, several of which are known to have effects on neurones. (per a research study done at University College London Medical School Harlow, England by Sheila L. Handley, BPharm, Ph.D. 1994) Large amounts of tryptophan which is broken down to ineffectively try to produce nicotinic acid reduces the amount of serotonin produced. Ineffective tryptophan utilization also uses alot of oxygen with tryptophan 2,3-dioxygenase. Low serotonin levels could cause obsessive compulsive behaviour, depression, and other mood related disorders. B6 is also required for the decarboxylase step of serotonin, histamine, and catecholamine pathways in the brain. In low B6, conservation takes place, so that B6 is used for fewer enzymes. When allergy strikes, the production of histamine causes a further imbalance of neurotransmitters, causing serotonin and/or catecholamine production to be further depleted. Sherry A Rogers, M.D., a specialist in environmental medicine, reports that all of the TS cases she has seen have a least one nutrient deficiency, and usually several. And she notes that all of these patients have hidden mold, dust, chemical and food sensitivities. ("Tourette Syndrome", _Health Counselor_, Vol.7, No.4) Acetylcholine is produced by acetyl CoA and choline. The choline is supplied through lecithin in Jason's supplements. In vitamin B6 deficiency, acetyl CoA would be made by fatty acid oxidation. So acetycholine could be functional with an adequate supply of fatty acids (evening primrose oil or flax oil might be useful). Acetylcholine could be in shorter supply in the parasympathetic system (relaxation) due to overuse in the sympathetic system where norepinephrine usually rules. The parasympathetic nervous system would need to have more acetylcholine in TS and associated disorders, it seems. Relaxation through the parasympathetic nervous system (which uses acetylcholine), where the heart rate is slowed, the blood pressure is lowered, the food is digested well, etc. is difficult in TS. Acetylcholine is probably overactive in the sympathetic autonomic nervous system, trying to stimulate the low supply of catecholamines, which would be decreased due to B6 deficiency/dependency. The receptors sites for catecholamines would be hyperexcitable and increased in number. The net usage of catecholamines could be normal to decreased due to increased stimulation by acetylcholine, depending on the availability of B6 in the body, and the conservation by low sulfation by PST. Conditions of emotional stress are known to produce more ticcing in TS. In short term stress, norepineprine, dopamine, and epineprine should be able to be produced by the conservation tactics of the body, but in long term stress, these would be exhausted, especially when another B6 dependent system is triggered. Likewise, the same would happen when histamine and serotonin are produced in short term and long term allergy. But as you might expect, the short term conditions would be explosive events with all of those increased receptor sites! Acetylcholine is also involved in the contraction of voluntary muscle cells and many other motor nerves, which are in heavy use in TS. Many people with TS are helped by exercise, where cardiac output and increased body temperature over a period of time inhibit the sympathetic nervous system. It may also help to clear toxic waste, such as kynurenine. Adequate water intake would be required to catabolize acetylcholine by cholinesterase. In my opinion acetylcholine is needed in B6 deficiency/dependency to run the nervous system. Fatty acids are essential to its success in this situation. Fatty acids require NADPH2, and NADH2 for their synthesis, and thus Vitamin B3. Water is also an utmost requirement in keeping acetylcholine from becoming a continuous firecracker. Jason has a water bottle close by most times and drinks tons of water. Water has always calmed him down. It may also dilute the kynurenine, excess amino acids and promote their excretion. If you look at the material written on the Canadian Mennonite families that have been studied with Tourette's disorder, you will see a high frequency of autoimmune and rare conditions. These findings are consistent with what one can expect with other Tourette's patients. For example, there is a high frequency of allergic conditions. My informal survey of TS and allergy results from the online TS support group are: With a total of 25 respondents with TS: 96% have allergies (24 out of 25) 56% have mold allergies 72% have obsessive complulsive traits (18 out of 25) 67% of those with obsessive compulsive traits have mold allergies 3 respondents thought they may have mold allergies, but weren't sure 52% have pollen allergies (ragweed, grass, tree, etc) 56% of those with obsessive compulsive traits have pollen allergy 48 % have animal allergies (cats, dogs, horse) 39% of those with obsessive compulsive traits have animal allergies 40% have dust allergy 39% of those with obsessive compulsive traits have dust allergy 20% have penicillin allergy 28 % of those with obsessive compulsive traits have penicillin allergy 20 % have miscellaneous allergies 11% of those with obsessive compulsive traits have miscellaneous allergies 16 % have food allergies 22 % of those with obsessive complulsive traits have food allergies 8% have sulfa allergy 11% of those with obsessive compulsive traits have sulfa allergy All of our frequent posters responded. The types of allergies are typically respiratory and airborne. Molds and pollens are the top allergens. 79% of the people with mold allergies also had pollen allergies, which are seasonal. Bonnie Grimaldi, BSMT (ASCP) 11283 Meadowcroft St. Pickerington, Ohio 43147 (614) 837-7545

Diamine oxidase breaks down histamine

Enzyme stimulation by S boulardii was associated with significant increases in diamine oxidase activity

Cofactors for neurotransmitters

Tourette Syndrome, B6 dependency, allergy BonnieGr bonniegr at aol.com Thu Feb 8 13:19:55 EST 1996 I have been putting the puzzle pieces together on the subject of Tourette Syndrome, using medline documents, college textbooks, etc. Please read the following long rationale document that I have prepared, and comment by e-mail (BonnieGr at aol.com). It is my hope that more research will be done to validate my theory. Enjoy! The following addresses TS/OCD/ADD. The diagnosis would lie in the degree of vitamin B6 dependency/deficiency, and how long the person has been in this state. Carl Hansen, Jr. M.D. of Minneapolis describes celiac disease in several of his TS patients. This could be a pathway to vitamin B6 deficiency via malabsorption. Streptococcal infections have also been associated with TS. This could be a combination of the hyaluronidase's (an enzyme produced by the hemolytic strep that depolymerizes the ground substance of tissue) or streptokinase's actions on the blood brain barrier, the drain of vitamin B6 from the bacteria's own useage, the body's requirement of B6 for immunity, and the antibiotic's B6 antagonistic properties. A pre-exising B6 dependency/deficiency could be uncovered. TOURETTE SYNDROME, ALLERGY AND THE B6 DEPENDENCY STATE I have my Bachelor's degree in Biology, specializing in Medical Technology, and in graduate school, I took graduate courses in biochemistry. I work as a medical technologist performing and verifying clinical laboratory tests in Chemistry, Hematology and Blood Bank at Mt.Carmel East Medical Center in Columbus, Ohio. I do not have TS but my son, Jason (13 yrs old) has TS with OCD. ADD has not been formally diagnosed, although he has problems with organization, distractibility, and the ability to switch gears. My son has had allergies since he was a baby. He is sensitive to red dye #40 with tired splitting headaches which make him scream until he is exhausted and sleeps. This, of course, hasn't happened in several years since he has avoided the dye. He also is allergic to sulfa, molds, dust, grass, trees, and most airborn allergens. He has been on the vitamins below for 1.5 months and the teachers have said that he is a different kid. Medications that he had been on made him progressively worse, and so we made a personal decision to discontinue meds altogether. He now is motivated in school, concentrates and finishes his work, and is less disruptive with his tics in class. At home he still has his tics and compulsions, but they are shorter lived and occur less often. He has had a set back this week due to a new semester with a new schedule, plus a very moldy, rainy few days. We gave him a little extra calcium-magnesium and one extra vitamin B3. He said that this gave him relief from his symptoms (he has never said this before with anything else). I solidified my theory on the premise that Jason is probably mildly vitamin B6 dependent. He was either born requiring high amounts of B6, and/or B6 antagonists attacked early in his first year of life. B6 antagonists are hydrazines (plant growth regulators, tartrazine, etc), DOPA found in certain beans, penicillinamine, antioxidants in petroleum, many drugs including penicillin, erythromycin, phenobarbital, tetracycline, corticosteroids, sulfamethoxazole, etc. Amino acids began building up in his system, from decreased transamination, etc. Serotonin became decreased from tryptophan not being able to be utilized. Allergies developed (which is in association with low B6), I believe allergy produces swings in histamine levels which causes a constant fluctuation in neurotransmitters capable of producing mood swings and rages. The conservation of vitamin B6 (when not abundantly available) causes it to be used by the prevailing neurotransmitter system at any given time, leaving other neurotransmitter systems less than optimally functional. Histamine receptors have been found to trigger dopamine receptors directly. Histamine is also a neurotransmitter affected by deficient vitamin B6. Its receptor sites are probably increased to compensate. Kinins released into the body's tissues in response to immune complexes can damage the blood brain barrier, thus altering the sensitivity of brain cells to acetylcholine, serotonin, dopamine, histamine, epinephrine and norepinephrine. I found that L-dopa doesn't readily form dopamine in B6 deficiency, so probably dopamine is reduced causing an increase in dopamine receptor sites along with an increase the norepinephrine and epinephrine (which are formed from dopamine) receptors sites. These increased receptor sites make the nerves more excitable and false transmitters or true neurotransmitters can set them off with explosive qualities. These false transmitters can be phenolic substances, such as food additives, drugs, etc. The enzyme, phenol sulfotransferase (PST), detoxifies and eliminates phenolics (drugs, food additives, serotonin, dopamine (to name a few). In the brain, sulfation is used while glucuronidation prevails elsewhere. Cysteine requires B6 to enzymatically release sulfur for sulfation of these phenols by PST. Considering this, the neurotransmitters would would be conserved to a certain extent (their sulfation and elimination would be slowed down). ADD may happen when these false transmitters create background "noise", and if there is a real message to get through via other neurons, it is masked. When a true message is fired, it may have too strong of a signal, creating a strong impulsion, which can lead to the development of a tic or compulsion if the impulsion is acted upon and repeated creating a sort of conditioned reflex network of nerves. Mental, motor, and vocal tics can develop this way. According to my_ Biochemistry_ by Lehninger textbook from my graduate student in Biology days, tryptophan is broken down in Vitamin B3 deficiency to make nicotinic acid. Tryptophan is found in meat and is plentiful, if you are a meat eater. Tryptophan is the precursor for serotonin. I also looked up Vitamin B3 and how it could be connected to the issues of allergy and serotonin defiency in the brain. I found that Vitamin B3 is used to make NAD, NADP, which are coenzymes used in making histamine and serotonin (to name a few), and are essential in oxidative-reductive cellular metabolism. The B3 is needed due to tryptophan's inability to be broken down to nicotinic acid without adequate B6. So, if Vitamins B3 and B6 are being used for histamine production, then serotonin production suffers. Tryptophan then must be used in a higher frequency to make nicotinic acid. In Vitamin B6 deficiency, this cannot happen, because the enzyme kynurinase, that catalyzes the cleavage of 3 hydroxykynurine (an intermediate in tryptophan catabolism), contains pyridoxal phosphate (an active coenzyme form of Vitamin B6). In Vitamin B6 deficiency, large amounts of L-kynurenine are excreted in the urine, because of its high plasma levels. This is described in "Elevated plasma kynurenine in Tourette syndrome", _Molecular & Chemical Neuropathology_21(1): 55-60,1994 Jan. Kynurenine itself is metabolised to other substances, several of which are known to have effects on neurones. (per a research study done at University College London Medical School Harlow, England by Sheila L. Handley, BPharm, Ph.D. 1994) Large amounts of tryptophan which is broken down to ineffectively try to produce nicotinic acid reduces the amount of serotonin produced. Ineffective tryptophan utilization also uses alot of oxygen with tryptophan 2,3-dioxygenase. Low serotonin levels could cause obsessive compulsive behaviour, depression, and other mood related disorders. B6 is also required for the decarboxylase step of serotonin, histamine, and catecholamine pathways in the brain. In low B6, conservation takes place, so that B6 is used for fewer enzymes. When allergy strikes, the production of histamine causes a further imbalance of neurotransmitters, causing serotonin and/or catecholamine production to be further depleted. Sherry A Rogers, M.D., a specialist in environmental medicine, reports that all of the TS cases she has seen have a least one nutrient deficiency, and usually several. And she notes that all of these patients have hidden mold, dust, chemical and food sensitivities. ("Tourette Syndrome", _Health Counselor_, Vol.7, No.4) Acetylcholine is produced by acetyl CoA and choline. The choline is supplied through lecithin in Jason's supplements. In vitamin B6 deficiency, acetyl CoA would be made by fatty acid oxidation. So acetycholine could be functional with an adequate supply of fatty acids (evening primrose oil or flax oil might be useful). Acetylcholine could be in shorter supply in the parasympathetic system (relaxation) due to overuse in the sympathetic system where norepinephrine usually rules. The parasympathetic nervous system would need to have more acetylcholine in TS and associated disorders, it seems. Relaxation through the parasympathetic nervous system (which uses acetylcholine), where the heart rate is slowed, the blood pressure is lowered, the food is digested well, etc. is difficult in TS. Acetylcholine is probably overactive in the sympathetic autonomic nervous system, trying to stimulate the low supply of catecholamines, which would be decreased due to B6 deficiency/dependency. The receptors sites for catecholamines would be hyperexcitable and increased in number. The net usage of catecholamines could be normal to decreased due to increased stimulation by acetylcholine, depending on the availability of B6 in the body, and the conservation by low sulfation by PST. Conditions of emotional stress are known to produce more ticcing in TS. In short term stress, norepineprine, dopamine, and epineprine should be able to be produced by the conservation tactics of the body, but in long term stress, these would be exhausted, especially when another B6 dependent system is triggered. Likewise, the same would happen when histamine and serotonin are produced in short term and long term allergy. But as you might expect, the short term conditions would be explosive events with all of those increased receptor sites! Acetylcholine is also involved in the contraction of voluntary muscle cells and many other motor nerves, which are in heavy use in TS. Many people with TS are helped by exercise, where cardiac output and increased body temperature over a period of time inhibit the sympathetic nervous system. It may also help to clear toxic waste, such as kynurenine. Adequate water intake would be required to catabolize acetylcholine by cholinesterase. In my opinion acetylcholine is needed in B6 deficiency/dependency to run the nervous system. Fatty acids are essential to its success in this situation. Fatty acids require NADPH2, and NADH2 for their synthesis, and thus Vitamin B3. Water is also an utmost requirement in keeping acetylcholine from becoming a continuous firecracker. Jason has a water bottle close by most times and drinks tons of water. Water has always calmed him down. It may also dilute the kynurenine, excess amino acids and promote their excretion. If you look at the material written on the Canadian Mennonite families that have been studied with Tourette's disorder, you will see a high frequency of autoimmune and rare conditions. These findings are consistent with what one can expect with other Tourette's patients. For example, there is a high frequency of allergic conditions. My informal survey of TS and allergy results from the online TS support group are: With a total of 25 respondents with TS: 96% have allergies (24 out of 25) 56% have mold allergies 72% have obsessive complulsive traits (18 out of 25) 67% of those with obsessive compulsive traits have mold allergies 3 respondents thought they may have mold allergies, but weren't sure 52% have pollen allergies (ragweed, grass, tree, etc) 56% of those with obsessive compulsive traits have pollen allergy 48 % have animal allergies (cats, dogs, horse) 39% of those with obsessive compulsive traits have animal allergies 40% have dust allergy 39% of those with obsessive compulsive traits have dust allergy 20% have penicillin allergy 28 % of those with obsessive compulsive traits have penicillin allergy 20 % have miscellaneous allergies 11% of those with obsessive compulsive traits have miscellaneous allergies 16 % have food allergies 22 % of those with obsessive complulsive traits have food allergies 8% have sulfa allergy 11% of those with obsessive compulsive traits have sulfa allergy All of our frequent posters responded. The types of allergies are typically respiratory and airborne. Molds and pollens are the top allergens. 79% of the people with mold allergies also had pollen allergies, which are seasonal. Bonnie Grimaldi, BSMT (ASCP) 11283 Meadowcroft St. Pickerington, Ohio 43147 (614) 837-7545

Histamine's effects

Technical Bulletin - Issue 11 - Histamine July 28, 2004 Issue 11 Editor: Gottfried Kellermann, PhD Contributors for this issue: Mike Bull Joe Ailts Carol Arndt, Bill Wilson, M.D. The Technical Support staff at NeuroScience is proud to bring you another informative newsletter designed to keep you up to date with current developments taking place within our company. Here you will find product reviews, new test parameter announcements, neurotransmitter interpretation suggestions, and anything else relevant to the world of neurotransmitters. The NeuroScience Technical support staff has revised its Technical Guide which reviews of many of the aspects of neurotransmitter testing and amino acid therapy. NeuroScience has a New Website. Please take a moment to visit and review the new information and the new format. Our tenth newsletter reviewed the new biphasic approach to TAAT (Targeted Amino Acid Therapy) that is more effective for patients with fatigue and relevant to this newsletter, increases histamine. Here, in our eleventh issue, we will focus on the neurotransmitter, histamine, a relatively new addition to the NeuroScience testing menu. Feel free to send us your questions and comments to be addressed in this newsletter. Your input is appreciated! Histamine is a recent addition to the NeuroScience testing menu and is now being measured routinely. Research by NeuroScience in the development of assays for neurotransmitters has created this new cost-effective assay and histamine now joins GABA and PEA in our expanding test menu. (A neurotransmitter test for glutamate and a test for the amino acid glutamine have also been developed and are available in the panel listed below. They will be the subject of an upcoming Technical Bulletin.) The actions of histamine are very well-known in the immune system. However, the actions of histamine within the central nervous system (CNS) are less familiar. Immunologically, histamine is released from mast cells or formed via histidine decarboxylase an enzyme that is up regulated in response to inflammatory cytokines. It is the presence of the immune response that triggers the increase in histamine that revs up mucus production to incredible levels and causes runny noses and hacking coughs. Without the immunological assault, e.g. increased cytokines, allergens, or IgE, histamine is a mild-mannered hardworking Clark Kent. Histamine is a neurotransmitter and histamine containing neurons have been found to have a pacemaker function within the brain. The firing rate of these neurons correlate positively with brain activity levels and display distinct day-night rhythms. Within the posterior region of the hypothalamus there are a large number of neurons that synthesize and utilize histamine and these neurons provide the stimulation that maintains or modulates activity in many other regions of the brain. Histamine, like the other biogenic amines (serotonin, dopamine, norepinephrine, epinephrine, and PEA) is stored in presynaptic vesicles and is released into the synapse. Also like other amine neurotransmitters, histamine binds to transmembrane G-protein coupled receptors on the post-synaptic neurons to exert its function. Histamine crosses the blood-brain-barrier very poorly and is synthesized within histamine neurons via the decarboxylation of histidine. Histidine is an essential amino acid and readily crosses the blood-brain-barrier via the LNAAT (large neutral amino acid transporter). The histidine decarboxylase enzyme is not rate-limiting and increasing the availability of histidine will increase the synthesis of histamine. Unlike other monoamines, histamine does not appear to have a specific reuptake mechanism for inactivation. Instead, histamine is inactivated by the ubiquitously present histamine methyltransferase and subsequent deamination by monoamine oxidase B. Some of the effects of histamines are best known because of the effects of antihistamine medications. First generation antihistamines are an excellent example. These medications block (antagonize) the actions of histamine by binding to the histamine receptor and as such prevent histamine from gaining access. First generation antihistamines, by definition, cross the blood-brain-barrier and interact with histamine receptors in the periphery as well as the CNS. Typical examples are: Diphenhydramine (Benadryl), Carbinoxamine (Clistin), Clemastine (Tavist), Chlorpheniramine (Chlor-Trimeton), and Brompheniramine (Dimetane). First generation antihistamines are also associated with significant drowsiness and diphenhydramine is included in OTC sleep aids (Unisom, Sominex, Nytol, etc.), because of this effect. Second generation or the so-called "non-drowsy" antihistamines, in contrast, do not cross the blood-brain barrier. So, while second generation antihistamines block the same receptors, they do not interact with those in the brain and therefore do not block the excitatory activity of histamine. Common examples are: Fexofenadine (Allegra), Loratidine (Claritin), Cetirizine (Zyrtec), and Acrivastine (Semprex). The excitatory action of histamine agrees very well with the observed activity of histamine neurons, which are active during the day, less active at night, and almost completely inactive during REM sleep. There are at least four types of histamine receptors (H1...H4) numbered according to their order of discovery. H1 H1 receptors are located in the periphery in the smooth muscles of intestines, bronchi, and blood vessels, as well as the CNS and are the main target for the antihistamine medications used to address allergies and the immune response. H1 receptors within the central nervous system are also responsible for the stimulatory properties of histamine and the improvement in cognitive function, vigilance, and memory caused by histamine. H2 H2 receptors on neurons are primarily post-synaptically located and receptors are coupled to adenylyl cyclase and increase cAMP for energy production. High densities of H2 receptors are found within the CNS. Activation of these receptors has primarily an excitatory effect on neurotransmission via alterations in ion channel activity that favor neuron depolarization. The H2 receptors are also present in the periphery, including the gastric mucosa, immune cells, and myocytes. Drugs acting on the H2 receptors in the gut prevent histamine from stimulating the secretion of gastric acid and have been widely prescribed for the treatment of gastro-esophageal reflux and peptic ulcer disease. In general, H2 receptor blockers do not cross the blood-brain barrier. Common examples are: Cimetidine (Tagamet), Ranitidine (Zantac), Famotidine (Pepcid), Nizatidine (Axid). In patients with poor digestion increasing gastric acid production by increasing histamine can aid digestion by stimulating acid secretion. H3 H3 are believed to be auto-receptors that act to down-regulate histamine release and synthesis and thereby reduce the effects of H1 and H2 receptors. However the greatest concentration of H3 receptors exist in areas of the brain that have more non-histamine neurons. As such, histamine release, acting via the H3 receptor, can modulate the activity of serotonin and dopamine neurons as well. Behavioral animal studies have shown that enhancing the actions of histamine, through the use of H3 receptor blockers, causes significant improvements in memory and learning. H4 H4 receptors have only recently been discovered and seem in some ways to act like H3 receptors but are located in mast cells as well as in the CNS. They seem to increase calcium mobilization from intracellular calcium stores. Histidine is important in a number of biological functions. The imidazole ring of histidine allows it to act as either an acid or base at physiological pH. Because of this, histidine can catalyze many chemical reactions and is found in the reactive center of many enzymes. Similarly, it is the ability of histidine molecules in hemoglobin to buffer H+ ions in red blood cells that allows for the exchange of O2 and CO2 at the tissues or lungs, respectively. Histidine has also been found to have anticonvulsant properties. Animal models of epilepsy report that histidine will decrease the incidence of seizures. Supporting the importance of histamine are studies which find that histamine blockers can reduce the effectiveness if some antiseizure medication. Many supplements tout histidine supplementation as a way to increase sexual pleasure and orgasm intensity. We are not aware of any research published to support this claim. Permitting a few degrees of separation, histidine, which increases histamine, can increase the release of oxytocin, which is a neuropeptide that is also associated with orgasms. So, a theoretical link is possible. Please send us an email if you have any comments about this. Observations by NeuroScience regarding the use of histidine come from the product ExcitaCor. ExcitaCor and TravaCor have been used in therapy regimens for patients presenting with neurotransmitter deficiencies in epinephrine and dopamine and is chosen over other therapies specifically when these values are accompanied by complaints of fatigue. Details of this protocol were outlined in our tenth Technical Bulletin. We have seen through neurotransmitter testing that ExcitaCor, a histidine containing product will increase histamine levels. Subjects taking histidine containing therapies reported feeling less fatigued and more alert. No allergy symptoms were observed. Neurotransmitter tests in these studies also confirm that the histidine in ExcitaCor will, via the neuromodulatory role of histamine, increase the release of the catecholamines: epinephrine and norepinephrine. We have also seen that young patients with autism or ADHD have higher histamine levels. This could be a contributing factor in the hyperkinetic facet of ADHD as well as an influence in the clinical presentation of the autism patient. We have also observed that high histamine levels are reduced when TAAT products that increase serotonin are used and recommend increasing serotonin when histamine is high. Even if serotonin levels are not low. This is beneficial in two ways. First patients with high histamine levels are more likely to to have an excess of stimulatory neurotransmitter activity and increasing serotonin will minimize that excess. Second, increasing serotonin can reduce allergy symptoms. This has been reported by practitioners using NeuroScience products with their patients as well as in published reports of antidepressants being used in dermatology to eliminate skin rashes. It has been reported that patients with depression have histamine receptors that don't bind histamine as well as the receptors of non-depressed subjects. This reduced function may be overcome by increasing histamine levels. Our observations show that patients suffering from depression have lower histamine levels. * Histamine is an excitatory neurotransmitter * Histamine acts as a pacemaker to increase activity in many regions of the brain * Histamine increases the release of epinephrine and norepinephrine * Supplementation with histidine contributes to the modulation of fatigue and depression. * Neurotransmitter testing data shows that ExcitaCor will increase histamine * High histamine can be reduced by increasing serotonin The mechanism of spontaneous firing in histamine neurons. Stevens DR, Eriksson KS, Brown RE, Haas HL. Behav Brain Res. 2001 Oct 15;124(2):105-12. Review. The physiology of brain histamine. Brown RE, Stevens DR, Haas HL.Prog Neurobiol. 2001 Apr;63(6):637-72. Review. Importance of histamine in modulatory processes, locomotion and memory. Philippu A, Prast H. Behav Brain Res. 2001 Oct 15;124(2):151-9. Review Histidine induces lipolysis through sympathetic nerve in white adipose tissue. Yoshimatsu H, Tsuda K, Niijima A, Tatsukawa M, Chiba S, Sakata T. Eur J Clin Invest. 2002 Apr;32(4):236-41. Central histaminergic system and cognition. Passani MB, Bacciottini L, Mannaioni PF, Blandina P. Neurosci Biobehav Rev. 2000 Jan;24(1):107-13. Review. Anatomical, physiological, and pharmacological characteristics of histidine decarboxylase knock-out mice: evidence for the role of brain histamine in behavioral and sleep-wake control. Parmentier R, Ohtsu H, Djebbara-Hannas Z, Valatx JL, Watanabe T, Lin JS. J Neurosci. 2002 Sep 1;22(17):7695-711. Cataplexy-active neurons in the hypothalamus: implications for the role of histamine in sleep and waking behavior. John J, Wu MF, Boehmer LN, Siegel JM.Neuron. 2004 May 27;42(4):619-34. Histamine activates tyrosine hydroxylase in bovine adrenal chromaffin cells through a pathway that involves ERK1/2 but not p38 or JNK. Cammarota M, Bevilaqua LR, Rostas JA, Dunkley PR. J Neurochem. 2003 Feb;84(3):453-8. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. Hofstra CL, Desai PJ, Thurmond RL, Fung-Leung WP. J Pharmacol Exp Ther. 2003 Jun;305(3):1212-21. Epub 2003 Mar 06. L-histidine is a beneficial adjuvant for antiepileptic drugs against maximal electroshock-induced seizures in mice. Kaminski RM, Zolkowska D, Kozicka M, Kleinrok Z, Czuczwar SJ. Amino Acids. 2004 Feb;26(1):85-9. Epub 2003 May 09. Neuronal histamine regulates food intake, adiposity, and uncoupling protein expression in agouti yellow (A(y)/a) obese mice. Masaki T, Chiba S, Yoshimichi G, Yasuda T, Noguchi H, Kakuma T, Sakata T, Yoshimatsu H. Endocrinology. 2003 Jun;144(6):2741-8. Histamine and prostaglandin interaction in regulation of oxytocin and vasopressin secretion. Knigge U, Kjaer A, Kristoffersen U, Madsen K, Toftegaard C, Jorgensen H, Warberg J.J Neuroendocrinol. 2003 Oct;15(10):940-5. Subcellular distribution of histamine, GABA and galanin in tuberomamillary neurons in vitro. Kukko-Lukjanov TK, Panula P.J Chem Neuroanat. 2003 Jul;25(4):279-92. The role of central histaminergic neuron system as an anticonvulsive mechanism in developing brain. Yokoyama H. Brain Dev. 2001 Nov;23(7):542-7. Review. The use of antidepressant drugs in dermatology. Gupta MA, Guptat AK. J Eur Acad Dermatol Venereol. 2001 Nov;15(6):512-8. Review. We hope you enjoyed this edition of The NeuroScience Technical Bulletin. Copyright 2003, 2004 by NeuroScience, Inc. No part of this newsletter shall be reproduced, stored, or transmitted by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the NeuroScience, Inc. ©NeuroScience,Inc. 2006 Disclaimer The information provided in this newsletter is for informational purposes only and is not intended as a substitute for advice from your physician or other health care professional or any information contained on or in any product label or packaging. You should not use the information in this newsletter for diagnosis or treatment of any health problem or for prescription of any medication or other treatment. You should consult with a healthcare professional before starting any diet, exercise or supplementation program, before taking any medication, or if you have or suspect you might have a health problem. You should not stop taking any medication without first consulting your physician.

Biochemical Individuality and Nutrition

Biochemical Individuality and Nutrition by Bill Walsh, Ph.D. Pfeiffer Treatment Center Introduction Each of us has innate biochemical factors which influence personality, behavior, mental health, immune function, allergic tendencies, etc. Scientists tell us that the number of different genetic combinations possible in a child from the same two parents exceeds 42 million. It’s interesting to note that we do not possess a combination of characteristics from our parents, but instead have a diverse collection of characteristics from many ancestors on both sides of the family. Except for identical twins, each human being has unique biochemistry resulting in quite diverse nutritional needs. Shakespeare was correct when he wrote "One man’s meat is another man’s poison." For example, some of us are genetically suited for a vegetable-based diet and others are not. Some persons can satisfy their nutritional needs by diet alone and others must have nutritional supplements to overcome genetic aberrations. Because of genetic differences in the way our bodies process foods, most of us are quite deficient in certain nutrients and overloaded in others. Even with an ideal diet, most of us have certain nutrients that are at very low levels with many times the RDA required to achieve a healthy balance. The nutrients in overload must be carefully avoided in vitamin supplements or serious health problems can develop. After studying the biochemistry of 10,000 persons, I’ve learned that the greatest mischief is usually caused by nutrients that are stored in excessive amounts, rather than those at depleted levels. The most common nutrients in overload include copper, iron, folic acid, calcium, methionine, manganese, choline, and omega-6 fatty acids. Of course, these same nutrients may be in deficiency in other persons. I am amused by supplement manufacturers who attempt to develop the ideal combination of vitamins, minerals, and amino acids for the general population. This is a bit like trying to determine the ideal shoe size for the population. The truth is that multiple vitamins and minerals are too indiscriminate, and may do as much harm as good. Each of us should ask the question, "Who am I nutritionally?" The answer to this question is important for all, but may be especially critical for persons with mental health problems. Nutrients and Mental Health As we enter the new millennium, the medical and scientific communities agree on the tremendous influence of neurotransmitters on behavior disorders, ADHD, depression, and schizophrenia. Most persons with these disorders were born with a predisposition for these problems due to genetically-aberrant levels of specific neurotransmitters. Our mental health is dependent upon having the proper amounts of these critical brain chemicals. Some psychiatrists express their scorn for nutrient therapies, claiming that they are too puny to have any real clinical potency. They often say, "You really need a drug medication to get the job done for a serious condition like depression." My favorite response begins by asking the question, "Where do our neurotransmitters come from?" The brain is a chemical factory which produces serotonin. dopamine, norepinephrine, and other brain chemicals 24 hours a day. The only raw material for these syntheses are nutrients, namely amino acids, vitamins, minerals, etc. If the brain receives improper amounts of these nutrient building blocks, we can expect serious problems with our neurotransmitters. For example, some depression patients have a genetic pyrrole disorder which renders them grossly depleted in vitamin B-6. These individuals cannot efficiently create serotonin since B-6 is an important co-factor in the last step of its synthesis. Many of these persons report benefits from Prozac, Paxil, Zoloft, or other serotonin-enhancing medications. However, similar benefits may also be achieved by simply giving these patients sufficient amounts of B-6 along with augmenting nutrients. Most neurotransmitter problems appear to be genetic in nature and involve abnormal absorption, metabolism or storage of key nutrients. As neuroscience advances, biochemical treatments to correct brain chemistry become better defined. Nutrient therapy can be very potent and does not involve side effects, since no molecules foreign to the body are needed. This therapeutic approach may eventually eliminate the need for most psychiatric medications. Biochemical Factors In Behavior Disorders, ADHD and Mental Illness The Pfeiffer Treatment Center has amassed a large database of biochemical information from more than 10,000 patients with mental health problems. Examination of this data shows that most of these persons have striking abnormalities in specific nutrients required for neurotransmitter production. The most common chemical imbalances we encounter include the following: Over-Methylation Many persons who suffer from anxiety and depression are over-methylated which results in excessive levels of dopamine, norepinephrine and serotonin. Typical symptoms include chemical and food sensitivities, underachievement, upper body pain, and an adverse reaction to serotonin-enhancing substances such as Prozac, Paxil, Zoloft, St. John’s Wort, and SAMe. They have a genetic tendency to be very depressed in folates, niacin, and Vitamin B-12, and biochemical treatment focuses on supplementation of these nutrients. These persons are also overloaded in copper and methionine and supplements of these nutrients must be strictly avoided. Under-Methylation Many patients with obsessive-compulsive tendencies, oppositional-defiant disorder, or seasonal depression are under-methylated which is associated with low serotonin levels. They generally exhibit seasonal allergies, perfectionism, competitiveness, and other distinctive symptoms and traits. They have a genetic tendency to be very depressed in calcium, magnesium, methionine, and Vitamin B-6 with excessive levels of folic acid. These under-methylated persons may benefit nicely from Paxil, Zoloft, and other serotonin-enhancing medications, although nasty side effects are common. A more natural approach is to directly correct the underlying problem using methionine, calcium, magnesium, and B-6. SAMe, St. John’s Wort, Kava Kava, and inositol are also very useful in treating these individuals. Metal-Metabolism A common problem in ADHD, behavior disorders, and hormonal depression is an genetic inability to control copper, zinc, manganese, and other trace metals in the body due to improper functioning of the metallothionine protein. These patients are often deficient in zinc, manganese, cysteine, serine, and vitamin B-6 and overloaded in copper, lead, and cadmium. They must avoid supplements and "enriched" foods containing copper. In addition we recommend they drink bottled water and limit use of swimming pools and jacuzzis treated with copper sulfate anti-algae agents. Foods to be limited due to high copper content include shellfish, chocolate, and carob. Elevated copper levels are associated with hormonal imbalances and a classic symptom is intolerance to estrogen. Biochemical treatment focuses on stimulation of metallothionein using zinc, manganese, cysteine, serine, and Vitamin B-6. Pyrrole Disorder A common feature of many behavior and emotional disorders is pyroluria, an inborn error of pyrrole chemistry which results in a dramatic deficiency of zinc, Vitamin B-6, and arachidonic acid. Common symptoms include explosive temper, emotional mood swings, poor short-term memory, and frequent infections. These patients are easily identified by their inability to tan, poor dream recall, abnormal fat distribution, and sensitivity to light and sound. The decisive laboratory test is analysis for kryptopyrroles in urine. Treatment centers on zinc and B-6 supplements together with omega-6 essential fatty acids. Glucose Dyscontrol Our database indicates a significant number of our patients have chronic low blood glucose levels. This problem doesn’t appear to be the cause of behavior disorders, depression, etc., but instead is an aggravating factor which can trigger striking symptoms. Typical symptoms include drowsiness after meals, irritability, craving for sweets, trembling, anxiety, and intermittent poor concentration and focus. Treatment includes chromium, manganese, and other glucose-stabilizing nutrients, but the primary focus of treatment is on diet. These patients benefit from six or more small meals daily with emphasis on complex carbohydrates and protein. In essence, they cannot tolerate large meals or quick sugars. Complex carbohydrates provide the necessary glucose in a slow, gradual manner and may be thought of as "time-release" sugar. Toxic Substances Occasionally we encounter a patient whose condition has resulted from a heavy-metal overload (lead, cadmium, mercury, etc.) or toxic levels of pesticides or other organic chemicals. Our database indicates that persons with a metallothionein disorder are especially sensitive to toxic metals, and that over-methylation is associated with severe chemical sensitivities. Effective treatment requires a three-part approach: (1) avoidance of additional exposures, (2) biochemical treatment to hasten the exit of the toxic from the body, and (3) correction of underlying chemical imbalances to minimize future vulnerability to the toxic. Malabsorption Although only 10% of our database case histories involve serious malabsorption, more than 90% of autistics exhibit this problem. There are three primary classes of absorption problems: (1) stomach problems, including excessive or insufficient HCl levels, (2) incomplete digestion in the small intestine, and (3) problems at the brush-border of the intestine where most nutrients are absorbed into the portal blood stream. The consequences can include nutrient deficiencies, irritation of the intestinal tract, candida, and mental health problems. Incomplete breakdown of protein and fats can adversely affect brain neurotransmission, and is associated with impulsivity and academic underachievement. Treatment depends on the type of malabsorption present and may involve adjustment of stomach HCl levels, digestive enzymes which survive stomach acid, nutrients to enhance digestion, and special diets. Essential Fatty Acids The brain is 20% fat (by dry weight) and these fatty substances fulfill very important functions. The myelin sheaths which surround our brain cells contain essential fatty acids which are directly involved in receptor formation and nerve transmission. A 1998 Symposium at the National Institute of Mental Health presented strong evidence of the important roles for omega-3 oils (especially EPA and DHA) and omega-6 oils (especially AA and DGLA) in ADHD, depression, and schizophrenia. A recent Harvard study showed EPA and DHA supplements to be more effective than psychiatric medications in combating bipolar depression. Typical American diets usually result in insufficient omega-3 and excessive omega-6, and some nutritionists routinely recommend supplements of omega-3 oils. However, biochemical individuality also exists with oils and certain persons are innately low in omega-6 oils. A review of symptoms and specialized plasma and red-cell-membrane lab tests can identify individual needs. Health Research Institute Pfeiffer Treatment Center HRI Pharmacy 4575 Weaver Parkway - Warrenville, IL 60555-4039 (630) 505-0300 - (630) 836-0667 fax Questions or Comments:info@HRIPTC.org | Home Page | Services | Pharmacy | Research | Education | Patient Info | Directions | All contents Copyright (c) 2004 Health Research Institute. All rights reserved. HRI is a Not-for-Profit 501c3.

HIstamine Problems

Avoiding High Histamine Foods

Food Sources of Histamine

Histamine occurs in food as a result of microbial enzymes converting the amino acid histidine (present in all proteins) to histamine. All foods subjected to microbial fermentation in the manufacturing process contain histamine. Included in this category are cheeses, fermented soy products, other fermented foods (e.g. sauerkraut), alcoholic beverages, and vinegars.

Foods exposed to microbial contamination also contain histamine in levels determined by the extent and rate of action of the microbes. Histamine levels reach a reactive level long before any signs of spoilage occur in the food. This characteristic has important implications in fin fish, where bacteria in the gut are particularly active in converting histidine to histamine. The longer the fish remains ungutted, the higher the levels of histamine in the flesh.

Some foods such as eggplant and spinach contain high levels of histamine naturally. In addition, a number of food additives such as azo dyes and preservatives mediate the release of histamine.

Some of these chemicals such as benzoates occur naturally in foods, especially fruits, and may have the same effect as the food additive in releasing histamine.

The histamine restricted diet excludes all foods known to contain high levels of histamine or to contain chemicals that can promote the physiological release of histamine.

From the Urticaria Chapter

The foods most commonly reported to induce urticaria are shellfish, fish, egg, nuts, chocolate, berries, tomatoes, cheese, milk, and wheat.

Foods reported to release histamine directly from mast cells are uncooked egg whites, shellfish, strawberries, tomatoes, fish, chocolate, pineapple and alcohol.

Foods containing histamine—Aged protein containing foods and fermented foods commonly have increased histamine levels.

Foods reported to be high in histamine are fermented cheeses (e.g. Camembert, Brie, Gruyere, Cheddar, Roquefort, Parmesan), brewer's yeast, shellfish, many fin fish, canned fish, tomato, spinach, red wine (especially Chianti), beer, unpasteurized milk (e.g., cow, goat or human milk), chicken, dry pork sausage, beef sausage, ham, chocolate, fermented soy products, and all fermented vegetables, such as sauerkraut.

Allowed/Restricted Foods

This diet excludes all:

• foods with naturally high levels of histamine
• fermented food
• artificial food coloring, especially tartrazine
• Benzoates including food sources of benzoates, benzoic acid and sodium benzoate
• Butylated hydroxyanisole (BHA) and butylated hydoxytoluene (BHT)

Blog entry about histamine/PST/supplements for methylation

Found this on a blog by a Pfeiffer patient. Interesting. Sulfation Sulfation is the conjugation of toxins with sulfur-containing compounds. The sulfation system is important for detoxifying several drugs, food additives, and, especially, toxins from intestinal bacteria and the environment. In addition to environmental toxins, sulfation is also used to detoxify some normal body chemicals and is the main pathway for the elimination of steroid and thyroid hormones. Since sulfation is also the primary route for the elimination of neurotransmitters, dysfunction in this system may contribute to the development of some nervous system disorders.

Sulfation was already on my list on "to learn about" since the PTC prescribed phenolic enymes, which break down phenols, which are ordinarly broken down by sulfates. Maybe I was too hasty in the "phase II ok for histapenics" conclusion. Still, methionine is needed for sulfation, and supposedly histapenics have a lot of that. I dont know. Inducers of phase II detoxification enzymes Glutathione conjugation: Brassica family foods (cabbage, broccoli, Brussels sprouts); limonene-containing foods (citrus peel, dill weed oil, caraway oil) Amino acid conjugation: Glycine Methylation: Lipotropic nutrients (choline, methionine, betaine, folic acid, vitamin B12) Sulfation: Cysteine, methionine, taurine Acetylation: None found Glucuronidation: Fish oils, cigarette smoking, birth control pills, Phenobarbital, limonene-containing foods Inhibitors of phase II detoxification enzymes Glutathione conjugation: Selenium deficiency, vitamin B2 deficiency, glutathione deficiency, zinc deficiency Amino acid conjugation: Low protein diet Methylation: Folic acid or vitamin B12 deficiency Sulfation: Non-steroidal anti-inflammatory drugs (e.g. aspirin), tartrazine (yellow food dye), molybdenum deficiency Acetylation: Vitamin B2, B5, or C deficiency Glucuronidation: Aspirin, probenecid reads like a checklist of histapenic supplments, but do not taht ciggarettes, most favored by histadelics, induce phase II detoxification. Pahse III is bile production. Bile. from the liver, stored in the gall bladder. Somehow I recall that Ceruplasmin is involved. I have to check that out.

Impairment of bile flow within the liver can be caused by a variety of agents and conditions. These conditions are often associated with alterations of liver function in laboratory tests (serum bilirubin, alkaline phosphatase, SGOT, LDH, GGTP, etc.) signifying cellular damage. However, relying on these tests alone to evaluate liver function is not adequate, since, in the initial or subclinical stages of many problems with liver function, laboratory values remain normal. Among the symptoms people with enzymatic damage complain of are: Fatigue; general malaise; digestive disturbances; allergies and chemical sensitivities; premenstrual syndrome; constipation.

Hmmmmmmmm. My PMS is fine, but that is interesting. AS noted above, my AST and SGOT are always slightly elevated, and my billirubin is high. If this researches leads to something, I want a refund from all the hospitals who have wasted my time on cr*p I could figure out. I am sick of funding thier student loan payments.

regrettably methionine is listed as the only supplment aiding in bile production, but I have to tell you that I am recently feeling like the methionine and methly cycle is more complex than the PTC is telling me. I dont know on that one.

Bad brain chemistry triggers violence

Behavior - vitamin and nutrient therapy Acts of violence in the workplace or schools often are not as random as they appear to outsiders. Parents of violent children have been telling doctors and educators for years that their kids were born with unique, disruptive, angry, defiant personalities. William J. Walsh, a senior scientist at Health Research Institute and Pfeifer Treatment Center, Naperville, Ill., backs them after 25 years of research. A study of 24 pairs of brothers, one average and one violent, was conducted by Walsh. The results, replicated in three blind, controlled experiments, showed two distinctive patterns in the brain chemistry of violent individuals not found in their siblings. The first included an elevated copper/zinc ratio; depressed sodium, potassium, and manganese; and abnormal calcium, magnesium, and blood histamines. The other revealed very depressed copper; very elevated sodium and potassium; elevated blood histamines, kryptopyrroles, lead cadmium, iron, calcium, and magnesium; and depressed zinc and manganese. How did this translate to behavior? Those having Type 1 levels exhibited Jekyll-Hyde behavior with episodic violence, poor stress control, and genuine remorse, often accompanied by acne, allergies, and academic underachievement. Type 2s were assaultive without remorse; pathological liars who had a fascination with fire; cruel to people and animals; and often had sleep disorders. The researchers later identified two additional distinctive, less-violent behavior types: nonassaultive delinquents who were impulsive, irritable, underweight underachievers in school, and nonassaultive individuals who had sugar craving, drowsiness, and depression. "The brain is a chemical factory that produces neurotransmitters such as serotonin, dopamine, norepinephrine, and other brain chemicals 24 hours a day. The only raw materials for these syntheses are nutrients: amino acids, vitamins, minerals, etc.," Walsh notes. "Most neurotransmitter imbalances appear genetic in nature and involve abnormal metabolism, absorption, and/or storage of food nutrients by the body. However, an individual's biochemistry may change at any time after birth as a result of food allergies, puberty, aging, stress, or trauma. The Pfeiffer Center's treatment consists of nutrient therapy--utilizing vitamins and minerals along with dietary adjustments--to correct brain chemistry imbalances. "Nutrient therapy can be very potent and, unlike most psychiatric medications, does not involve side effects since no molecules foreign to the body are used," he explains. Some violent offenders are psychiatric patients who have stopped taking medications due to the debilitating side effects. Pfeiffer doctors keep patients on prescription medications while balancing brain chemistry. In some cases, they work with the patient's physician in the effort to eliminate or gradually reduce medications and minimize side effects. COPYRIGHT 2002 Society for the Advancement of Education COPYRIGHT 2002 Gale Group

Zinc - the World's Finest Mineral ;-)

http://www.drkaslow.com/html/zinc.html Zinc is a component of more than 80 enzymes. High concentrations have been found in brain hippocampus, and many medical researchers believe that zinc is a neurotransmitter. Low zinc levels at these sites could reduce the inhibition of neuron activity, thus leading to abnormal behavior. Zinc deficiency can result in irritability, anger episodes, impaired immune function, acne, stunting of growth, poor taste and smell sensitivity, and impaired wound healing. There is a high incidence of zinc deficiency in people labeled with ADD, autism, depression, schizophrenia, eating disorders and bipolar disorders. The discovery of zinc "finger proteins" in the past decade has led to a vastly improved understanding of how cells replicate and divide. The role of these proteins in behavior is not yet clarified. Zinc is far more important than often recognized, and low levels of zinc are associated with behavior disorders. Zinc is found in the highest concentration in the middle ear and cochlea, the eye, the brain, and in the prostate and sperm. A large percentage of behavior disordered persons exhibit abnormal levels of copper, zinc, lead, cadmium, calcium, magnesium and manganese in blood, urine, and tissues. This appears to involve a malfunction of the metal-binding protein, metallothionein. Most of these patients have symptoms of zinc deficiency along with depressed levels of zinc in their blood plasma. The high incidence of zinc deficiency in assaultive young males was found in a study by WJ Walsh presented at the Neuroscience Annual Meeting in 1994. He found elevated serum copper and depressed plasma zinc concentration, compared to normal controls. This study confirmed the clinical observations of the Pfeiffer Treatment Center showing zinc depletion in more than 4,000 behavior disordered patients. Clinical observations and research indicate the copper/zinc ratio appears to be more important than either copper or zinc levels alone. Zinc deficiency often results in elevated blood levels of copper, due to the dynamic competition of these metals in the body. Elevated blood copper has been associated with episodic violence, hyperactivity, learning disabilities, and depression. Zinc is antagonistic to cadmium, lead, and mercury. Zinc deficiency is hard to confirm since no single laboratory test is always low. For example, blood levels are sometimes normal in zinc deficient persons due to homeostasis. Urine and hair tissue levels are often elevated in zinc deficiency because of "short circuiting" of zinc through the body and high rates of excretion. The demand for zinc increases under psychological and physiological stress. Four principal factors support a diagnosis of zinc deficiency: 1. Depressed blood level (plasma or red cell) zinc. Since zinc tolerance tests show plasma levels to be affected for six hours following zinc supplementation (Pohit J, "A zinc tolerance test", Clin. Chim. Acta, 1981;114:279 and Pecoud A "Effects of foodstuffs on the absorption of zinc sulfate", Clin. Pharmacol. Ther., 1975:17: 469), zinc supplements are avoided for 24 hours prior to sampling of plasma. The optimal range of plasma zinc is 90-150 mcg/dl. 2. Clinical symptoms compatible with zinc depletion. * Eczema, acne, and/or psoriasis (Molokhia MM, "Zinc and copper in dermatology", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1980), Schmidt K., et.al., "Determination of trace element concentrations in psoriatic and non-psoriatic scales with special attention to zinc", in Trace Element Analytical Chemistry in Medicine and Biology, Vol. 1, Walter de Gruyter, New York (1980), McMillan EM, "Plasma zinc in psoriasis. Relation to surface area involvement", Br. J. Dermatol. 1983;108:301, Ecker RJ, "Acrodermatitis and acquired zinc deficiency", Arch. Dermatol., 1978;114: 937 and Withers AF, "Plasma zinc in psoriasis", Lancet, 1968;ii) * Poor wound healing, including leg ulcers and oral lesions (Van Rij AM., "Zinc supplements in surgery", in Zinc and Copper in Medicine, Charles C. Thomas, Springfield, IL (1982) and Henzel JH, et al., "Zinc concentrations within healing wounds: significance of post-operative zincuria on availability and requirements during tissue repair", Arch. Surg. 1970;349:357) * Lines of Beau on the fingernails (Weismann, K., "Lines of Beau: Possible markers of zinc deficiency", Acta Dermatol. Venereol. 1977;57: 88) * Growth retardation (Collipp PJ., et al., "Zinc deficiency: Improvement in growth and growth hormone levels with oral zinc therapy", Ann. Nutr. Metab. 1982;26:287, Hambridge KM, "Zinc deficiency in infants and preadolescent children", in Trace Elements in Human Health and Disease, Vol. 1, Prasad, A.S. and Oberleas, D., Eds., Academic Press, New York (1976), Golden BE, "Effect of zinc supplementation on the dietary intake, rate of weight gain and energy cost of tissue deposition in children recovering from severe malnutrition", Am. J. Clin. Nutr.1981;34:900 and Laditan AO, "Plasma zinc and copper during the acute phase of protein-energy malnutrition (PEM) and after recovery", Trop. Geogr. Med. 1982;34:77). * Delayed sexual maturation (Sandstead HH, et al., "Human zinc deficiency, endocrine manifestations, and response to treatment", Amer. J. Clin. Nutr., 1967;20:422 ) * Poor taste acuity/ ability (Heinkin, R.I., and Bradley, D.F., "Hypogeusia corrected by nickel and zinc", Life Sci., 1970; 9:701 and Sprenger KBG. et al., "Improvement of uremic neuropathy and hypogeusia by dialysate zinc supplementation: a double-blind study", Kidney Int., 1983;Suppl 16: 5315) * Chronic immunodeficiency and frequent infections (Cunningham-Rundles, C., et al., "Zinc deficiency, depressed thymic hormones and T-lymphocyte dysfunction in patients with hypogammaglobulinemia", Clin. Immunol. Immunopathology, 1981;21:387 and Good RA, et al., "Zinc and immunity", in Clinical, Biochemical, and Nutritional Aspects of Trace Elements, Prasad, A.S. Ed., Alan R. Liss, New York (1982). A "working diagnosis" of zinc deficiency can be made if clinical symptoms of zinc deficiency are clearly evident from the initial physical examination and medical history. Usually more than one or the above symptoms are present in zinc deficiency. Behavioral problems and pyroluria should also raise suspicion of zinc deficiency. 3. Laboratory imbalances that are associated with zinc insufficiency such as elevated carnosine/histidine ratio, phosphoserine, and phosphethanolamine or low levels of leucine, isoleucine, valine, and histidine. 4. Improvement with zinc supplementation. This initial diagnosis is later supported or negated by laboratory analysis for zinc along with observed response (or non-response) to zinc supplementation. Generally a retest for zinc along with clinical evaluation of symptoms is done after 4-6 months of treatment to determine if dosages need adjustment. Zinc depletion is corrected by supplementation with specific forms of zinc along with supporting nutrients. Correction of zinc deficiency is best accomplished under the care of a physician or nutritionist who is experienced in metal metabolism disorders. Zinc toxicity is associated with gastrointestinal irritation, vomiting, changes in HDL and LDL cholesterol ratios, copper deficiency and impaired immunity. Indiscriminant dosages of zinc to persons who do not need it can cause anemia and imbalanced trace metals. Absorption of dietary zinc into the bloodstream is usually about 35-45% efficient, but malabsorption syndromes can reduce zinc uptake to about 10-15%. Once in the bloodstream, zinc concentrations are controlled by the metal-binding protein, metallothionein. Many persons with zinc deficiency appear to have a metallothionein disorder. Patients with an overproduction of pyroles (pyroluria) also develop zinc deficiencies. Treatment of mild or moderate zinc depletion can take months to complete. Some cases of severe zinc depletion require a year or more to resolve. Achievement of a proper zinc balance is slowed by growth spurts, injury, illness, or severe stress. In addition, persons with malabsorption or Type A blood respond to treatment more slowly. The average American typically consumes 10mg of zinc a day which is one third less than the RDA. Zinc deficient individuals usually respond well to supplementation. Many patients who previously experienced years of counseling, psychotherapy, aggressive medication programs, and/or residential treatment become greatly improved and respond to less intensive (and less expensive) therapies. Zinc deficiency can be corrected, but not cured. If treatment is discontinued, zinc deficiency usually will reemerge with all symptoms gradually returning. Zinc deficiency, like diabetes, requires life long treatment. SELECTED REFERENCES 1. Cunnane, S.C., Zinc: Clinical and Biochemical Significance, CRC Press, Inc., Boca Raton, FL (1988). 2. Prasad, A.S., "Deficiency of zinc in man and its toxicity", in Trace Elements in Human Health and Disease, Vol. 1, Academic Press, New York, 1976. 3. Prasad, A.S., "Clinical and biochemical spectrum of zinc deficiency in human subjects", in Current Topics in Nutrition and Disease, Vol 6, New York, 1982. 4. Smith, J.C., Holbrook, J.T., and Danford, D.E., "Analysis and evaluation of zinc and copper in human plasma and serum", J. Amer. College of Nutrition. 1985;4:627-638. 5. Kleimola, V., et al, "The zinc, copper, and iron status in children with chronic diseases", in Trace Element Analytical Chemistry in Medicine and Biology, Walter de Gruyter, New York (1983). 6. Reding, P., DuChateau, J., and Bataille, C., "Oral zinc supplementation improves hepatic encephalopathy", Lancet, 1984; ii: 493.

Methylation Overview

http://www.alternativementalhealth.com/articles/pfeiffer.htm Methylation Effective "markers" for methylation are (1) whole blood histamine (ref. levels 40-70 mcg/dL), available from Quest and LabCorp; (2) Absolute Basophils (ref. levels 30-50), available from Direct Healthcare, Inc in the Chicago area. One-carbon (methyl) groups are involved in numerous important biochemical reactions in the body, including genetic expression, neurotransmitter synthesis and metabolism, etc. Methylation (more properly, the methyl/folate ratio) is a major factor in the rate-limiting step (the tetrahydrobiopterin reaction) in the synthesis of serotonin, dopamine, and norepinephrine in the brain. Undermethylated persons tend to be depleted in these 3 neurotransmitters, and the opposite is true for overmethylation. Inositol is especially helpful for undermethylated persons (for example most persons with OCD), but can cause negative side effects in those who are overmethylated. Since Inositol is one of the primary second messengers in neurotransmission, it's surprising is isn't more commonly used. It's especially useful in reducing anxiety and enhancing sleep. If you can confirm the presence of undermethylation, the patient should benefit from (1) aggressive doses of l-methionine, calcium, magnesium, along with augmenting nutrients zinc, B-6, Inositol, Vitamin A & C and (2) strict avoidance of folic acid, choline, DMAE, and copper supplements. A quick way to test for need for methylation therapy is to carry out a cautious trial of SAMe. Within a week or two you should have your answer. If she clearly is improving on the SAMs (which is frightfully expensive)..... you can get usually the same benefits (albeit more slowly) using methionine plus calcium, magnesium, and B-6. This should be side-effect free unless (a) the methylation is begun too abruptly or (b) the patient has a rare genetic enzyme disorder which disrupts the SAM cycle. We've found that direct methylation is usually more successful than tinkering with the SAM cycle. The primary way humans receive most of their methyl groups is from dietary methionine. It's often hard to improve on Mother Nature. (Jan 20, 2003) Aggressive methylation therapy can be very successful, but usually involves a very slow response. Typically, treatment with methionine, calcium, magnesium, B-6, etc requires about 2 months before the patient before any progress is evident --- and 6-12 months are required for all of the benefits to be attained. Please note that whole blood histamine is a marker for innate methylation tendency, but is not an indicator of wellness or the degree to which undermethylation has been overcome. Undermethylated patients can become quite well without their histamine lab results changing at all. One way to speed up the process of recovery is to use SAMe supplements in the beginning. Undermethylated patients usually report nice progress after the first week or two. SAMe is quite expensive, and can be gradually replaced by methionine after a couple of months. Nearly all severely undermethylated persons have low serotonin levels and present with a history of depression, internal anxiety, and OCD. Many have a history of perfectionism and high accomplishment in the early years. Unfortunately this population also has a tendency for non-compliance with any treatment. The late and great Carl Pfeiffer would occasionally resort to use of the anti-histamines Benedryl or Dilantin in high-histamine persons who were slow to respond. Avoidance of folate supplements is essential for most undermethylated persons, an exception being autism. Some practitioners like to tinker with the SAM cycle to promote conversion of homocysteine to methionine, but this can deplete the cystathione pathway and result in deficiencies of glutathione, cysteine, etc. Some persons have a genetic enzyme weakness which can disrupt the SAM cycle Undermethylated adults typically require 2,000 - 3,000 mg/day of methionine for several months to see good results. Also, augmenting nutrients such as calcium, magnesium, B-6, and zinc are essential. TMG generally provides some benefits to undermethylated persons, but tends to make oxidative stress protections worse by diminishing the amount of homocysteine which converts via the cystathione pathway of the SAM cycle. TMG certainly is a promising nutrient for such persons, and adding some cysteine or glutathione can overcome the cystathione pathway deficit. Personally, I believe the use of SAMe is the quickest way to help an undermethylated, high-histamine person. Most OCD patients (both obsessive thoughts AND compulsive actions) exhibit undermethylation and associated low levels of serotonin, dopamine, and norepinephrine. Choline is anti-dopaminergic and often makes OCD patients worse. Generally OCD patients respond nicely to methionine, SAMe, calcium, magnesium, B-6, inositol, TMG, and zinc. Most OCD patients get worse if given supplements of DMAE, choline, copper, or folic acid. 500 to 1000 mg/day of inositol will probably be needed to provide good response. (9 Jan, 2003) Over-methylation Conditions associated with overmethylation: Anxiety/Panic disorders, anxious depression, hyperactivity, learning disabilities, low motivation, "space cadet" syndrome, paranoid schizophrenia, hallucinations. High in serotonin, dopamine, and norepinephrine. Many persons who suffer from anxiety along with depression are over-methylated. Methyl is an important chemical group consisting of one carbon and three hydrogen atoms (CH3). Over-methylation (too many added methyl groups) results in excessive levels of the neurotransmitters dopamine, norepinephrine, and serotonin. Typical symptoms include chemical and food sensitivities, underachievement, upper body pain, and an adverse reaction to serotonin-enhancing substances such as Prozac, Paxil, Zoloft, St. John’s Wort, and SAMe6. They have a physical tendency to be very depressed in folates (a form of folic acid), niacin and Vitamin B-12, and biochemical treatment focuses on supplementation of these nutrients. These persons are also overloaded in copper and methionine (a sulfur-containing amino acid) and supplements of these nutrients must be strictly avoided. Choline Phosphatidyl choline is also very effective in protecting DHA/EPA from free radical oxidative stress..... another good reason to take it. In my experience DMAE is especially effective for increasing acetylcholine levels in the brain, since it passes the blood/brain barrier & converts to choline. I like to use this for overmethylated persons who have excessive dopamine and norepinephrine levels. However, enhancing acetylcholine activity must be avoided in persons who genetically are overloaded in this NT. Choline, DMAE, and phosphatidyl choline can cause nasty symptoms in these persons (about 10% of the population). Persons with innately high acetylcholine levels tend to be very tense and sometimes nearly catatonic. They have very high anxiety, but usually keep it inside. They also usually have a history of seasonal allergies, perfectionism, and OCD tendencies. Increasing acetylcholine activity can be a disaster for them. Those deficient in acetylcholine usually present with nervous legs, are prone to pacing, and are quite voluble. Their misery is plain to everyone. Therapies to increase acetylcholine activity can be extraordinarily helpful for this population. (March 6, 2003) Inositol can cause negative side effects in those who are overmethylated. Histapenia (Low Histamine - over-methylated) Low-histamine depressives are usually nervous, anxious individuals who are prone to paranoia and despair. No seasonal allergies, but many food allergies and chemical sensitivity. Low libido. Obsessions but not compulsions. Heavy body hair. Nervous legs. Grandiosity. Many have a history of hyperactivity, learning disabilities and underachievement. They are over-methylated which results in elevated dopamine and norepinephrine levels. Treatment focuses on B3, C, B12, with about 2-4 months required for correction of the imbalance. Also DMAE, choline, manganese, zinc, omega-3 essential oils, C and E. They should avoid methionine, SAMe, Inositol, TMG and DMG. One thing that is absolutely certain is that methionine and/or SAMe usually harm low-histamine (overmethylated persons). The generalization that perfume and other chemical sensitivities are associated with overmethylation, low blood histamine, and elevated norepinephaine. is exactly that...a general rule with many exceptions. However, the correlation seems to be above 90 percent in the case of perfume sensitivity. Whenever a patient enters our clinic wearing a mask to filter out inhalant chemicals, we immediately suspect the overmethylation syndrome. The chemical testing usually confirms this diagnosis, but there definitely are a few persons who have severe perfume sensitivity for other reasons. We've evaluated about 19,000 persons, including about 1500 with anxiety disorder or panic disorder. Hundreds of these patients reported sensitivity to perfumes. Nearly 90 percent of the perfume-sensitive group were overmethylated, and reported multiple chemical and food sensitivities. usually in the absence of seasonal inhalant allergies. Perfume sensitivity is a classic symptom of these high nonepinephrine persons, who usually respond beautifully to folate/B-12 therapy [1 Dec -03] SAMe is likely to cause great worsening of symptoms, including mania, if given to an OVER-methylated person. The incidence of overmethylation in our patient database of 1,500 bipolar cases is about 18%. Bipolar disorder is not a single condition, but a collection of very different biochemical disorders under the same umbrella diagnosis. SAMe works great for truly undermethylated patients, but all hell breaks out if given to someone who is overloaded (genetically) with methyl groups. The right way to do this is to (a) first determine the person's innate methylation tendency & then (b) act accordingly. (Jan 31, 2003) Histadenia - (High Histamine - Under-methylation) Elevated histamine and/or elevated basophils indicate undermethylation. Review of symptoms and medical history can bolster the diagnosis. For example, most undermethylated persons exhibit seasonal allergies, perfectionism, strong wills, slenderness, OCD tendencies, high libido, etc. (Overmethylated persons generally exhibit anxiety, absence of seasonal allergies, presence of food/chemical sensitivities, dry eyes, low perspiration, artistic/music interests/abilities, intolerance to Prozac and other SSRI's, etc.) Low in serotonin, dopamine, and norepinephrine. Conditions associated with undermethylation: Anorexia, Bulemia, shopping/gambling disorders, depression, schizo-affective disorder, delusions, oppositional-defiant disorder, OCD. Many patients with obsessive-compulsive tendencies, "oppositional-defiant disorder," or seasonal depression are under-methylated, which is associated with low serotonin levels. They generally exhibit seasonal allergies and other distinctive symptoms and traits. They have a tendency to be very depressed in calcium, magnesium, methionine, and vitamin B-6 with excessive levels of folic acid. These under-methylated persons can have a positive effect from Paxil, Zoloft, and other serotonin-enhancing medications, although nasty side effects are common. A more natural approach is to directly correct the underlying problem using methionine, calcium, magnesium, and B-6. SAMe, St. John’s Wort, Kava Kava, and inositol (a natural sugar alcohol) are also very useful in treating these individuals. 40-70 is optimum histamine range for mental health considerations. Histamine is an important neurotransmitter which affects human behavior. This syndrome often involves seasonal variations in depression, obsessive-compulsive behavior, inhalant allergies, and frequent headaches. In severe cases involving psychosis, the dominant symptom is usually delusional thinking rather than hallucinations. They tend to speak very little and may sit motionless for extended periods. They may appear outwardly calm, but suffer from extreme internal anxiety. Most OCD patients with both obsessive thoughts and compulsive actions are in this category. Associated with under-methylation, which results in low levels of important neurotransmitters such as serotonin, dopamine and norepinephrine. Treatment focuses on the use of antifolates such as calcium, methionine, SAMe, magnesium, zinc, TMG, omega-3 essential oils, B6, inositol, and A, C and E. The dose of inositol is 500 to 1000mg. Choline is anti-dopaminergic and often makes undermethylated patients worse. Also bad are DMAE, copper and folic acid. Three to six months of nutrient therapy are necessary to correct this chemical imbalance. Symptoms will return if treatment is stopped. Two good labs for whole blood histamine are LabCorp and Quest. Also use a special absolute basophil count as a methlyation marker. The count must be direct and not differential. Alcian blue dye is the preferred staining agent. Best lab for this test is Direct Healthcare Access in Glenview IL 847 299 2440 One thing that is absolutely certain is that methionine and/or SAMe are wonderful for high-histamine (undermethylated) persons. Histadelic (undermethylated) persons thrive on methionine, SAMe, Ca and Mg..... but get much worse if they take folates & B-12 which can increase methyl trapping. The bottom line is that undermethylated persons generally exhibit very elevated folate levels.... and these persons get worse if additional folate is given SAMe is very promising for undermethylated persons and a bad idea for those who suffer from a genetic tendency for overmethylation. I don't particularly like the "allopathic" method you referred to which is simply trial & error. SAMe can do great harm if given to the wrong person. I hate going to funerals. (17 Dec, 2002) The mechanisms of action of SAMe and TMG are quite different. Most of our methyl groups come from dietary methionine. The methionine is converted to SAMe in a reaction with magnesium, ATP, methionine-adenosyl-transferase, and water. SAMe is a relatively unstable carrier of methyl groups and is the primary source of methyl for most reactions in the body. Once the methyl group has been donated, the residual molecule is s-adenosyl-homocysteine which converts to homocysteine. TMG (betaine) is a biochemical which can donate a methyl group to homocysteine, thus converting it back to methionine. The TMG route is secondary to the 5-methyl-tetrahydrofolate/B-12 reaction which the primary route for restoring methionine. Methionine and SAMe supplements directly introduce new methyl groups into the body. TMG can provide a methyl group only to the extent that there is insufficient folate/B-12 to do the job. In some persons, the methylation effect of TMG is very minimal. In addition, persons who are undermethylated have a SAM cycle which is "spinning very slowly", much like a superhighway with little traffic. The answer for them is NOT to more efficiently convert the small amount of homocysteine to methionine (using TMG), but rather to directly introduce more methionine or SAMe into the body. A small percentage of persons with sufficient dietary methionine cannot efficiently produce SAMe --- These persons need supplemental SAMe, and not methionine or TMG and are the exception to the rule. In most other cases, methionine supplements alone are sufficient. TMG is a great way to treat individuals with dangerously high homocysteine levels. TMG can be very useful in augmenting methionine therapy along with B-6/P-5-P , serine, etc. The challenge is to supply enough methyl groups to help the patient, without creating dangerously high levels of homocysteine. Use of TMG is an "insurance policy" against this happening. (Jan 22, 2003) OTHER Pyroluria A stress disorder characterized by pronounced mood swings, temper outbursts, anxious depression. Inability to eat breakfast, absence of dream recall and frequent infections. The biochemical signature of this disorder includes elevated urine kryptopyrroles, a double deficiency of zinc and B-6, and low levels of arachidonic acid. Devastated by stresses including physical injury, emotional trauma, illness, sleep deprivation. Sensitivity to light and loud noises, dry skin, abnormal fat distribution, rage episodes, histrionic behavior. They also have low levels of arachidonic acid. Treatment centers on correcting a double deficiency of B-6, zinc essential fatty acids and augmenting nutrients. It is believed to result from abnormal hemoglobin synthesis which depletes the body of these nutrients. A positive response often occurs within the first seven days of treatment, with 1-2 months usually required for correction of the imbalance. Omega 3s can worsen mental symptoms in bipolar or schizophrenic patients.... if they have a pyrrole disorder. This phenotype is dramatically short of arachidonic acid & giving omega 3 oils aggravates the situation since omega 3 and omega 6 EFA's are in competition for delta 5,6 desaturases. We use red blood cell membrane analysis for EFA's if we suspect this problem. Pyroluric mental patients will usually get worse if given fish oils, DHA, EPA, etc. They thrive on Primrose Oil, a good source of AA and other omega 6s. (June 23, 2003) Most persons with pyroluria respond very quickly to the B-6, Zn, C, E therapy..... Major improvements are often seen by the 2nd day, and almost always by the end of the first week. The exceptions are: (1) persons with severe mental illness (schizophrenia or bipolar), (2) persons with other significant chemical imbalances, and (3) patients with a major malabsorptive condition. When pyroluria is diagnosed along with another chemical imbalance, I like to track a patient during the first 6-8 weeks to determine which is the dominant imbalance. If major improvement occurs immediately, it's because pyroluria has been corrected. Some patients report a nice early improvement followed by a plateau, and then another advance. Schizophrenic and bipolar pyrolurics usually report some progress after a few weeks, but it may take 3-6 months to get to steady state. The biggest problem with the Kp analysis is getting a proper sample to the lab. The kryptopyrrole molecule is unstable and will disappear rapidly at room temperature or if exposed to bright light. The urine sample must be placed in a freezer immediately after acquisition. Kp can be lost in the freezer if the temperature isn't well below 32 degrees F. We've also learned that exposure to bright light results in breakdown of the Kp molecule. Finally, the sample must be maintained in a frozen condition during shipment. I would greatly suspect any Kp value below 3.0. Usually this means the sample didn't get to the lab in proper condition. With respect to reference levels: We consider a healthy level to be between 4-8 mcg/dL. We consider persons between 10 and 20 to have mild pyroluria, and a good response to treatment is usually reported. Persons exhibiting 20 to 50 mcg/dL have moderate pyroluria, which can be a devastating condition. Persons above 50 mcg/dL have severe pyroluria.

Mercury and ADD/Autism/Allergies/Immune System

Get your coffee before sitting don to read this one. It's long, but it's full of information! ~L Immune Reactive Conditions: The mercury connection to autism, schizophrenia, ADD, eczema, lupus, asthma, and allergies (snipped from larger study) Bernard Windham- Chemical Engineer The incidence of neurotoxic, allergic, and immune reactive conditions such as autism, scizophrenia, ADD, dyslexia, allergies, asthma, eczema, lupus, psoriasis, childhood diabetes, etc. have been increasing rapidly in recent years(1,2,3,5,23). A recent report by the National Research Council found that 50% of all pregnancies in the U.S. are now resulting in prenatal or postnatal mortality, significant birth defects, or otherwise chronically unhealthy babies(3). Exposure to toxic chemcials or environmental factors appear to be a factor in as much as 28 percent of the 4 million children born each year(3), with 1 in 6 having one of the neurological conditions previously listed.. According to the U.S. FDA, at least 26 million have allergies and at least 17 million have asthma. The largest increase has been in infants (1,2,,5-7,23), with an increase in autism cases to over 500,000 (1,2,23,22), an over 500% increase to a level of almost 1 per 250 infants in the last decade(2), making it the 3rd most common childhood condition, along with similar increases in ADD, and over 10 % of infants- approximately 15 million in the U.S. with such conditions or systemic eczema(1). Studies researching the reason for these rapid increases in infant reactive conditions seem to implicate earlier and higher usage of vaccines containing mercury(thimerosal) as a likely connection(2,2b,23,30,40). A recent study comparing pre- and post-vaccination mercury levels, found a significant increase in both preterm and term infants after vaccination(42), with post-vaccination mercury levels approximately 3 times higher in the preterm infants as compared with term infants. The study found mercury blood levels up to 23.6 ug/L and received an average dose of 16.7 ug/kg. Just this one vaccination gave an exposure to mercury that is many times the U.S. ATSDR adult minimum risk level(MRL) for mercury of .3/ug/kg body weight per day(41). It has been estimated that if all of the vaccines recommended by the American Assoc. of Pediatrics are given and contain thimerosal, then by age 6 months an infant would have received 187 micrograms of ethyl mercury which is more than the EPA/ATSDR health standard for organic mercury(33,41) and by age 3 the typical child has received over 235 micrograms of mercury thimerosal from vaccinations which is considerably more than Federal mercury safety guidelines (41), in addition to significant levels from other sources for many(23). Infants during this period have undeveloped blood brain barriers and much of the mercury goes to the brain, resulting in significant adverse neurological effects in those that are most susceptible(43,3). Because of the evidence the FDA has completed a study and written a letter to vaccine manufacturers asking that mercury be removed from vaccines. The updated letter stated, "The Center for Biologics Evaluation and Research (CBER) has completed its evaluation of the use of thimerosal in vaccines...Our review concluded that reducing or eliminating thimerosal from vaccines is merited(44). The letter pointed to a joint statement by the American Academy of Pediatrics and the United States Public Health Service in 1999, which "called for the removal of thimerosal from vaccines as soon as possible." Many thousands of parents have reported that their child got such conditions after vaccination, and tests have confirmed high levels of mercury in Many of those tested, along with other toxic exposures. An additional source of thimerosal to the fetus of women who are RH negative is the 30 micrograms in the RhoGAM shot they receive. Underweight infants that get the same dose of thimerosal as other infants have also been found to be at special risk. Many of those diagnosed with high mercury levels have also been found to have significant improvement after mercury detoxification(23,30,40,11,35). Thimerosal had been previously removed from similar preservative uses in eye drops and eye medications after evidence of a connection to chronic degenerative eye conditions. After over 15,000 law suits were filed in France over adverse effects of the Hepatitis B vaccine, the French Minister of Health ended the mandatory hepatitis B vaccination program for all school children. Adverse effects included neurological disorders and autoimmune disorders such as multiple sclerosis and lupus. Some hospitals in the U.S. also quit recommending certain vaccinations. Although vaccinations appear to be the largest source of mercury in infants, mercury has been found to be transmitted from the mother to the fetus through the placenta and accumulate in the fetus to higher levels than in the mother’s blood(22). Breast milk of women who have amalgam fillings or eat a lot of fish has also been found to be a significant source of mercury in infants and young children(22,45). A direct mechanism involving mercury’s inhibition of cellular enzymatic processes by binding with the hydroxyl radical(SH) in amino acids appears to be a major part of the connection to these allergic/immune reactive conditions (15-23,36,46). For example mercury has been found to strongly inhibit the activity of xanthine oxidase and dipeptyl peptidase (DPP IV) which are required in the digestion of the milk protein casein(15,16,17,19,20,22), and the same protein that is cluster differentiation antigen 26 (CD26) which helps T lymphocyte activation. CD26 or DPPIV is a cell surfact glycoprotein that is very susceptible to inactivation by mercury binding to its cysteinyl domain. Mercury and other toxic metals also inhibit binding of opioid receptor agonists to opioid receptors, while magnesium stimulates binding to opioid receptors (15). Studies involving a large sample of patients with autism, scizophrenia, or mania found that over 90 % of those tested had high levels of the milk protein beta-casomorphin-7 in their blood and urine and defective enzymatic processes for digesting milk protein(24,25,27), and similarly for the corresponding enzyme needed to digest wheat gluten(24,26).The studies found high levels of Ig A antigen specific antibodies for casein, lactalbumin and beta-lactoglovulin and IgG and IgM for casein. Beta-casomorphine-7 is a morphine like compound that results in neural dysfunction (24,25), as well as being a direct histamine releaser in humans and inducing skin reactions (14,21,25c). Similarly many also had a corresponding form of gluten protein (26). Elimination of milk and wheat products and sulfur foods from the diet has been found to improve the condition. A double blind study using a potent opiate antagonist, naltrexone(NAL), produced significant reduction in autistic symptomology among the 56% most responsive to opioid effects(28). The behavioral improvements was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase in the T-helper- inducers and a significant reduction of the T-cytotoxic-suppressors and a normalization of the CD4/CD8 ratio. Studies have found mercury causes increased levels of the CD8 T-cytotoxic-suppressors(29). As noted previously, such populations of patients have also been found to have high levels of mercury and to recover after mercury detox(23,11,22,30,40). As mercury levels are reduced the protein binding is reduced and improvement in the enzymatic process occurs(22,11). Additional cellular level enzymatic effects of mercury’s binding with proteins include blockage of sulfur oxidation processes and neurotransmitter amino acids which have been found to be significant factors in many autistics(18,36,46,17), plus enzymatic processes involving vitamins B6 and B12, with effects on the cytochrome-C energy processes as well. Epson salts(magnesium sulfate)baths, supplementation with the p5p form of Vit B6 and vit B12 shots are methods of dealing with these enzymatic blockages that have been found effective by those treating such conditions. Mercury has also been found to have adverse effects on cellular mineral levels of calcium, magnesium, zinc, and lithium(39,22,46). Supplementing with these minerals has also been found to be effective in the majority of cases(39) Another of the results of these toxic exposures and enzymatic blockages is the effect on the liver and disfunction of the liver detoxification processes which autistic children have been found to have (30,36,22). All of the autistic cases tested were found to have high toxic exposures/effects and liver detoxification profiles outside of normal(30). Along with these blockages of cellular enzymatic processes, mercury has been found to cause additional neurological and immune system effects in many through immune/autoimmune reactions(11,12,35). Mercury(22) as well as thimerosal (31,32) also have direct neurotoxic effects on brain nucleotid binding proteins through their effect on Ca2+ATPase and Na+/K+ATPase activity. But the effects on the neurological and immune systems of exposure to various toxic substances such as toxic metals and environmental pollutants has also been found to have additive or synergistic effects and to be a factor in increasing eczema, allergies, asthma, delayed food allergies, and sensitivity to other lesser allergens(14-22,35). Most of the children tested for toxic exposures have found high or reactive levels of other toxic metals, and organochlorine compounds (30,40,11,12,35,4). Other than the organochlorines or toxic metals which are discussed later, three common pollutants that have been documented to have effects on such conditions are traffic and industrial pollutants nitrogen oxide, power plant residual oil fly ash, and organochlorine pollutants(4). Another effect of mercury and toxic metals is a reduction in B- lymphocytes (37,38,22). One of these studies(37) dealing with autistic patients and further work with such patients has found this causes a tendency to be more seriously affected by viruses and to develop intestinal disorders including leaky gut, lymphoid modular hyperplasia, and a high incidence of parasites. Allergic contact eczema is the most frequent occupational disease(1,22), and the most common cause of contact eczema is exposure to toxic metals(1, 6- 12,22). The metals most commonly causing allergic immune reactivity are nickel, mercury, chromium, cobalt, and palladium(1,6-14,22). The highest level of sensitization is to Infants, who are most reactive to thimerosal, a form of mercury that has been used as a preservative in vaccines and eye drops(6,7). There is strong suggestive and clinical evidence for a connection between toxic metals and autism(2b,15-40).