Guest guest Posted February 20, 2005 Report Share Posted February 20, 2005 DMSA & Heavy Metal Toxicity Description: Meso-2.3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent for heavy metal poisoning. While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two addition cross-over studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals; in one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hours after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that: 1) A metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) In children, moderate lead exposure impairs renal tubular drug elimination; and 3) A metabolite of DMSA appears to be an active chelator. Availability: Oral capsules in 250 mg and 500 mg. Protocols: There are many protocols for the use of DMSA. We will list all that we have and where the protocol came from. It also depends on whether DMSA is being used for challenge purposes, a treatment program or during amalgam removal. Doctors Data Challenge: 10 mg/kg or maximum of 500 mg t.i.d. for 1 day. Start collecting urine after the first void of the 1st day of dosing DMSA and continue for 24 hours. Treatment-as per Dr. Ted Rozema: 2 week cycle-3 days on DMSA (10 mg/kg, in divided doses (t.i.d.) then 11 days off the drug. 24 hour urine sampling can be done with this therapy. Also, supplement orally/IV essential elements and sulfur containing amino acids can be performed after last dose of DMSA is given. Also, remember not to co-administer any sulfhydryl-containing supplements such as garlic, chlorella, NAC or glutathione and to stop these supplements 24 hours prior to DMSA administration. This cycle is then repeated 5-10 times for the average patients. For the sensitive or ill patient, give DMSA 500 mg daily 3 times a week for 6 weeks, off 2 weeks, and repeat. Perform challenge test every 4th cycle to monitor results. Amalgam Removal Protocol: We suggest DMSA 50 mg (t.i.d.) the day of and the day after amalgam removal. DMSA CHELATION DMSA chelation is sometimes referred to as DMAS chelation. Chelation comes from the Greek word meaning to bond. Simply put, DMSA chelation involves taking capsules that are rich in Sulphur-containing amino acids, which are the building blocks of protein. Sulphur is like a magnet for the metals and flushes them out of the body via the feces and the urine. The day after all the metals have been removed from your mouth, you should see your practitioner for a DMSA or a DMPS provocative. The provocative is a short course of the sulphur-rich amino acids that will give you an idea if your tissue has accumulated toxic levels of metals. I was toxic with 8 metals: aluminum, arsenic, cadmium, copper, lead, mercury, nickel and tin. DMPS is a 7-10 minute IV push that provokes the metals to show themselves. DMPS is very useful for diagnostic purposes but since it should be used, in most cases, for only the initial provocative test. Thereafter, DMSA should be used because it takes the metals out of the lower body and also crosses the blood-brain barrier to pull the metals out of the brain. It is also very cheap and very easy to take in capsule form. In order to discover your metal levels, you must send a urine sample to a reputable lab. For the DMPS, you do a 24-hour urine collection from which a sample is taken and sent to the lab. For the DMSA, you simply collect a urine sample which is sent off to the lab. A few weeks later, the results will come back from the lab and you will then discuss them with your practitioner. Correct interpretation of lab results cannot be overemphasized. Reference values do not necessarily mean, and sometimes absolutely do not mean, normal values. They may define the lower and upper end of values that have been reported to the lab. Lower and upper values may represent extremes, not normal values. It is extremely important to understand this distinction so that you can discuss all this with your practitioner on his or her level as a fully informed participant in the treatment process. Your life may depend on your ability to discuss and understand all this, so be informed. Your test results may not show the whole story, however. This is because the metals are intracellular and different metals bond with the chelating agent at different times. The metals are in the cells in layers, and it takes time for each layer to reveal itself. So it may, for instance, take many months for lead or arsenic to show up in the urine because copper and mercury are being chelated out and eliminated first. One other very interesting and useful aspect to all this is that the urine test results will also show your mineral levels. The chelation process also affects your mineral levels so that as the chelating agent is removing metals from your body, it is also removing minerals as well. If the test results show low levels of some minerals, for example magnesium, calcium, manganese, zinc or selenium, then you would want to remineralize between courses of chelation. If your mineral levels are severely depleted, you would probably be well advised to take one to three months to remineralize before the next course of chelation. Mitochondrial Support Factor plus DMSA Protocol by Apothe' Care Each capsule contains: lipoic Acid ascorbyl palmitate l-glutathione AKG chlorphyllis sodium copper citric acid germanium sesquioxide malic acid calcium EAP succinic acid calcium hydroxyapatite DMSA (12.5mg) magnesium glycinate rubidium CI manganese aspartate cesium CI chromium polynicotinaze horsetail boron citrate molybdenum aspartate The principal is to develop a heavy metal base line from 24-hour urine analysis post DMPS challenge then chelate the heavy metals out with the above formulation. 15 caps per week for 8 weeks (5 capsules daily three times a week). Then, re-test with DMPS and continue using DMPS as a diagnostic only and the DMSA formula as the chelator until heavy metals are at a desired level. Parasites will often flare up during this therapy, as several current practitioners have found, and this is a good time to administer an anti-parasite protocol of which we have several. INFORMATION FROM FACTS AND COMPARISON SUCCIMER Pharmacology: Succimer is an orally active, heavy metal chelating agent; it forms water-soluble chelates and, consequently, increases the urinary excretion of lead. Toxicology: In oral toxicity studies up to 28 days, doses up to 200 mg/kg/day did not produce significant overt toxicity in rats and dogs. However, in 6 and 28 day oral toxicity studies, does >=300 mg/kg/day were toxic and lethal to some dogs. The kidney and GI tract were the major target organs for toxicity. Toxicity was manifested by anorexia; emesis; muccid of bloody diarrhea; increased BUN concentration, AST, ALT, and alkaline phosphatase levels; renal tubular necrosis; purulent nephritis, severe GI bleeding and ulceration. Deaths were due to renal failure. Pharmacokentics: In a study in healthy adult volunteers, after a single dose of 16, 32 or 48 mg/kg, absorption was rapid but variable, with peak blood levels between 1 and 2 hours. Approximately 49% of the dose was excreted; 39% in the feces, 9% in the urine and 1% as carbon dioxide from the lungs. Since fecal excretion probably represented non-absorbed drug, the kidneys excreted most of the absorbed drug. The apparent elimination half-life was about 2 days. In other studies of healthy adult volunteers a single oral dose of 10 mg/kg, succimer was rapidly and extensively metabolized. Approximately 25% of the dose was excreted in the urine with peak blood level and urinary excretion occurring between 2 and 4 hours. Of the total amount of drug eliminated in the urine, approximately 90% was eliminated in an altered form as mixed succimer-cysteine disulfides; the remaining 10% was eliminated unchanged. Clinical Trial: Studies were performed in 18 men with blood lead levels of 44 to 96 mcg/dl. Three groups of 6 patients received either 10, 6.7 or 3.3 mg/kg every 9 hours for 5 days. After 5 days, mean blood levels of the three groups decreased 72.5%, 58.3% and 35.5% respectively. Mean urinary lead excretions in the initial 24 hours were 28.6, 18.6 and 12.3 times the pretreatment 24-hour urinary lead excretion. As the chelatable pool was reduced during therapy, urinary output decreased. A mean of 19 mg lead was excreted during a 5-day course of 30 mg/kg/day. Clinical symptoms, such as headache and colic, and biochemical indices of lead toxicity also improved. Decrease in urinary excretion of d-aminolevulinic acid (ALA) and coproporphyrin paralleled the improvement in erythrocyte ALA dehydratase. Three control patients with lead poisoning of similar severity received edetate calcium disodium (EDTA) IV at a dose of 50 mg/kg/day for 5 days. Mean blood levels decreased 47.4%, and mean urinary lead excretion was 21 mg in controls. Effect on Essential Minerals: In the above studies, succimer had no significant effect on the urinary elimination of iron, calcium or magnesium. Zinc excretion doubled during treatment. The effect of succimer on the excretion of essential minerals was small compared to that of EDTA, which can induce more that a tenfold increase in urinary excretion of zinc and doubling of copper and iron excretion. Succimer vs. EDTA - A study was performed in 15 children ages 2 to 7 years with blood levels of 30 to 49 mcg/dl and positive EDTA lead mobilization tests. Each group of five patients received 350, 233 or 116 mg/m 2 succimer every 8 hours for 5 days. These doses corresponded to 10, 6.7 and 3.3 mg/kg. Six control patients received 1000 mg/m 2/day EDTA IV for 5 days. Following therapy, the mean blood lead levels decreased 78%, 63% and 42 % respectively, in the three groups treated with succimer. The response of the 350 mg/m 2 every 8 hours (10 mg/kg every 8 hours) group was significantly better than that of the other succimer-treated groups as well as that of the control group, whose mean blood level fell 48%. No adverse reactions or changes in essential mineral excretion were reported in the succimer-treated groups. In the EDTA-treated group, the cumulative amount of urinary lead excreted was slightly but significantly greater than in the succimer group. After EDTA, the urinary excretion of copper, zinc, iron and calcium were significantly increased. As with other children, both adults and children experienced a rebound in blood lead levels after discontinuing succimer. In these studies, after treatment with 350 mg/m 2 (10 mg/kg) every 8 hours for 5 days, the mean lead level rebounded and plateaued at 80% to 85% of pretreatment levels 2 weeks after therapy. The rebound plateau was somewhat higher with lower doses of succimer and with IV EDTA. In an attempt to control rebound of blood lead levels, 19 children, ages 1 to 7 years, with blood lead levels of 42 to 67 mcg/dl were treated with 350 mg/m 2 every 8 hours for 5 days and then divided into three groups. One group was followed for 2 weeks with no further therapy; the second group was treated for 2 weeks with 350 mg/m 2 daily, and the third with 350 mg/m 2 every 12 hours. (The remainder of this was not present on the page.) Indications: Treatment of lead poisoning in children with blood lead levels >45 mcg/dl. Not indicated for prophylaxis of lead poisoning in a lead-containing environment; always accompany succimer use with identification and removal of lead exposure. Unlabeled Uses: Succimer may be beneficial in the treatment of other heavy metal poisonings (e.g., mercury, arsenic); further study is needed. Contraindications: History of allergy to the drug. Warnings: Keep out of reach of children. Pregnancy: Category C. Succimer is teratogenic and fetotoxic in pregnant mice when given in a dose range of 410 to 1640 mg/kg/day during the period of organogenosis. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Lactation: It is now known whether this drug is excreted in breast milk. Discourage mothers requiring therapy from nursing their infants. Children: Refer to the Indications and Administration and Dosage sections. There is no therapeutic experience in succimer in children <1 year of age. Precautions: Carefully observe patients during treatment due to limited clinical experience with succimer. Elevated blood lead levels and associated symptoms may return rapidly after discontinuation of succimer because of redistribution of lead from bone stores to soft tissue and blood. After therapy, monitor patients for rebound of blood lead levels by measuring the levels at least once weekly until stable. However, use the severity of lead intoxication (as measured by initial blood level and rate and degree of rebound of blood lead) as a guide for more frequent blood lead monitoring. Renal Function: Adequately hydrate all patients undergoing treatment. Exercise caution in using succimer therapy in patients with compromised renal function. Limited data suggests that succimer is dialyzable, but that the lead chelates are not. Hepatic Function: Transient mild elevations of serum transaminases have been observed in 6% to 10% of patients during the course of therapy. Monitor serum transaminases before the start of therapy and at least weekly during therapy. Closely monitor patients with a history of liver disease. No data are available regarding the metabolism of succimer in patients with liver disease. Repeated Courses: Clinical experience is limited. The safety of uninterrupted dosing > 3 weeks has not been established and is not recommended. Allergic Reactions: The possibility of allergic or other mucocutaneous reactions must be borne in mind on re-administration (and during initial course). Monitor patients requiring repeated courses during each treatment course. One patient experienced recurrent mucocutaneous vesicular eruptions of increasing severity affecting oral mucosa, external urethral areas and perianal areas on third, fourth and fifth courses. The reaction resolved between courses and on discontinuation of therapy. Drug Interactions: Chelation therapy (e.g., EDTA); Co-administration of succimer with other chelation therapy is not recommended. Drug/Lab Test Interactions: Succimer may interfere with serum and urinary laboratory tests. In vitro, succimer caused false-positive results for ketoses in urine using nitroprusside reagents such as Ketostix and falsely decreased measurements of serum uric acid and CPK. Adverse Reactions: The most common events attribute to succimer (i.e., GI symptoms or increases in serum transaminases) have been observed in about 10% of patients (see Precautions). Rashes, some necessitating discontinuation of therapy, have occurred in about 4% of patients. If rash occurs, consider other causes (e.g., measles) before ascribing the reaction to succimer. Rechallenge with succimer may be considered if lead levels are high enough to warrant retreatment. One allergic mucocutaneous reaction has occurred on repeated administration of the drug (see Precautions). The following table presents adverse events reported with the administration of succimer for the treatment of lead and other heavy metal intoxication. Succimer Adverse Reactions (%)I: Body System/Adverse Reaction Children Adults (n=191) (n=134) Digestive: Nausea, vomiting, diarrhea; Appetite loss, hemorrhoidal symptoms: Loose stools, metallic taste in mouth 12 20.9 Body as a Whole: Back, stomach, head, rib, and flank pain; Abdominal cramps, chills, fever; Head cold, headache, moniliasis 5.2 15.7 Metabolic: Elevated AST, ALT; Alkaline phosphatase; Serum cholesterol 4.2 10.4 CNS: Drowsiness, dizziness; Sensorimotor neuropathy, sleepiness; Parasthesia 1.0 12.7 Skin and Appendages: Papular rash, herpetic rash; Mucocutaneous eruptions; pruritus 2.6 11.2 Special Senses: Cloudy film in eye, ears plugged; Otitis media, watery eyes 1.0 3.7 Respiratory: Sore throat, rhinorrhea; Nasal congestion, cough 3.7 0.7 Body System/Adverse Reaction Children Adults (n=191) (n=134) GU: Decreased urination; Voiding difficulty, poteinuria increased 0 3.7 Other: Arrhythmia 0 1.8 Increased platelet count Intermittent cosinophilia 0.5 1.5 Knee cap pain, leg pain 0 3.0 Incidence Regardless of Attribution or Dosage Overdosage: Doses of 2300 to 2400 mg/kg in the rat and mouse produces anorexia, convulsions, labored respiration and frequently death. Induction of vomiting or gastric lavage followed by administration of an activated charcoal slurry and appropriate supportive therapy are recommended. Refer to General Management of Acute Overdosage. (Reference) Limited data indicate that succimer is dialyzable. Patient Information: Instruct patients to maintain adequate fluid intake. If rash occurs, patients should consult their physicians. In young children unable to swallow capsules, the contents of the capsule can be administered in a small amount of food (see Administration and Dosage). Administration and Dosage: The FDA approved Succimer in February, 1991. Start dosage at 10 mg/kg or 350 mg/m 2 every 8 hours for 5 days; initiation of therapy at higher doses is not recommended (see table). Reduce frequency of administration to 10 mg/kg or 350 mg/m 2 every 12 hours (two-thirds of the initial dosage) for an additional 2 weeks of therapy. A course of treatments lasts 19 days. Repeated courses may be necessary if indicated by weekly monitoring of blood lead concentration. A minimum of 2 weeks between courses is recommended unless blood lead levels indicate the need for more prompt treatment. Succimer Pediatric Dosing Chart Weight Dose Number of Lbs. Kg. (mg)1 Capsules 18-35 8-15 100 1 36-55 16-23 200 2 56-75 24-34 300 3 76-100 35-44 400 4 > 100 >45 500 5 To be administered every 8 hours for 5 days followed by dosing every 12 hours for 14 days. In young children who cannot swallow capsules, succimer can be administered by separating the capsule and sprinkling the medicated beads on a small amount of soft food or putting them in a spoon and following with a fruit drink. Identification of the lead source in the child's environment and its abatement are critical to successful therapy. Chelation therapy is not a substitute for preventing further exposure to lead and should not be used to permit continued exposure to lead. Patients who have received EDTA with or without BAL may use succimer for subsequent treatment after an interval of 4 weeks. Data on the concomitant use of succimer with EDTA with or without BAL are not available and such use is not recommended. DMSA Heavy Metal Challenge for 24-Hour Urine Testing Day 1: Give DMSA capsules 500 mg (2 x 250 mg) TID Day 2: Give DMSA capsules 500 mg (2 x 250 mg) TID and start collecting urine AFTER the first urination of the day. Day 3: Continue collecting urine but just the first void in the AM. Number of DMSA 250 mg to order per test is 12. Apothe' Cure, Inc. 1-800-969-6601 or 972-960-6601. - " " < <traditional_Chinese_Medicine >; Cc: <gearoidr; <likemlist >; <pA-L >; <pVA-L >; <swynndvm Sunday, February 20, 2005 9:37 AM CORRECTION: DMSA therapy and Doses Hi Alon, Chris & All, Susan, please post to VBMA if you judge chelation therapy a suitable topic. I wrote: > I have not used DMSA, but a Google suggests circa 10mg/kg > bodyweight/d. See: http://tinyurl.com/555tn NOTE: My bald statement, " circa 10mg/kg bodyweight/d " , was not accurate. Apologies: I should not have made a simplistic statement like that. I based it on a brief Google search, without spending sufficient time reading the small print. See more accurate [but non-expert and incomplete] comments below. Chris replied: > I guess ... if we want to use the reference ranges of the lab that does > the sample, we get to follow the dosage set by the lab. Otherwise, the > results will be less meaningful. Chris, IMO, the LAB role is to TEST samples and report results, including the normal reference ranges. Clinicians should ensure that the lab holds a current International Standard ISO Certificate for EACH TEST of interest. Few labs hold such certificates. One should avoid using labs that do NOT hold the relevant Certificates. IMO the role of the LAB does NOT extend to recommending therpeutic dosages. IMO, that role should rest with clinicians (physicians, or other qualified therapists) and clinical researchers who have published the data to support the recommended doses. DMAS dose varies depending on the PURPOSE (diagnosis or therapy) for which it is used, the ROUTE of administration (oral, rectal or parenteral), and on the AUTHORITY (reference sources) that one follows. For example, the most important and most recent Consensus Position Paper by the AUTISM RESEARCH INSTITUTE http://autismwebsite.com/ari/dan/treatmentoptionsmercurymetal.pdf " Treatment Options for Mercury/Metal Toxicity in Autism and Related Developmental Disabilities: Consensus Position Paper (February 2005) AUTISM RESEARCH INSTITUTE, 4182 Adams Avenue, San Diego, CA 92116 www.AutismResearchInstitute.com says [re TESTING whether or not there is an undesirable mercury load to be stripped]: Oral DMSA (9-dose): Dosage of 10 mg/kg-dose, 3x/day, for 3 days. Just before administering the last dose, void the bladder, and then collect all urine for the next 8-10 hours. This test has the advantage that Bradstreet et al.1 have established a reference range for typical children, based on a study of 18 typical children vs. 221 children with autism. Using Doctor's Data Laboratory, they reported levels of 1.29 +/- 1.54 mcg Hg/g-creatinine, 15.0 +/- 9 mcg Pb/g-creatinine, and 0.46 mcg Cd/g-creatinine in typical children given DMSA. Children with autism had, on average, 3x higher levels of Hg excretion. 6 Oral DMSA (single dose): Dosage of 20-25 mg/kg-dose, 1x. Void bladder and then administer DMSA, and collect all urine for 6-10 hours. (Do not use only 10 mg/kg, as a study by Adams et al. found no major difference between 15 children with autism vs. 15 controls). Some physicians do not recommend this higher single dose due to concerns about adverse reactions, and prefer the series of lower doses mentioned previously. Rectal DMSA (single dose): 25mg/kg of body weight as a single bolus dose with urine collection beginning the next morning in potty trained children and through the night with pediatric urine collection bags in those children who aren't. Collection time varies between 12-24 hours depending on the physician's preference and family logistics As regards DMSA THERAPY to strip mercury away after adequate testing that this is desirable, reference 52 at http://www.nationalautismassociation.org/pdf/tbinstockcitations.pdf says that the therapeutic dose was 10mg/kg bodyweight, 3 times/day for 3 days (for one course), with 11 days off before the next course: Ref 52: " A. Holmes, S. Cave, and J.M. El-Dahr. OPEN TRIAL OF CHELATION WITH MES0-2,3- DIMERCAPTO SUCCINIC ACID (DMSA) AND LIPOIC ACID (LA) IN CHILDREN WITH AUTISM. As submitted to IMFAR, June 2, 2001. " Over 400 patients with autism are currently undergoing treatment for removal of heavy metals. Patients are treated with DMSA alone at doses of 10 mg/kg/dose 3 times a day for 3 days in a row (shorter duration than lead protocol to decrease side effects) with 11 days " off " to allow metals to re-equilibrate. After at least 2 rounds of DMSA alone, the thiol antioxidant lipoic acid (hypothesized to aide in removal of heavy metals across the BBB) is added to each dose of DMSA at 2-3mg/kg/dose. In general, noticeable improvements in language, self-help skills, interaction, and core autistic features are not seen until the patient has been on DMSA with LA for 2-3 months. " In summary, chelation therapy using DMSA is a most valuable way to strip undesired or toxic trace-metals from the body BUT it carries some risks. Therefore, DMSA therapy should be monitored carefully and communication between patient, guardians, DMSA therapist and the family physician should be open and total. Best regards, Tel: (H): +353- or (M): +353- WWW: " Man who says it can't be done should not interrupt man doing it " - Chinese Proverb Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 20, 2005 Report Share Posted February 20, 2005 For the DMPS, you do a 24-hour urine collection from which a sample is taken and sent to the lab. >>>We do 6 hours for DMPS Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 20, 2005 Report Share Posted February 20, 2005 I seem to get better results with 24 ...great smokies HMT - " " <alonmarcus <Chinese Medicine > Sunday, February 20, 2005 10:20 AM Re: DMSA-FYI > > For the DMPS, you do a 24-hour urine collection from which a > sample is taken and sent to the lab. >>>>We do 6 hours for DMPS > > > > Quote Link to comment Share on other sites More sharing options...
Guest guest Posted February 20, 2005 Report Share Posted February 20, 2005 great smokies >>>Great smokies is one of the labs we are testing Quote Link to comment Share on other sites More sharing options...
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