Acute toxicity

• Environmental, industrial accidents, or terrorist acts (9/11)
• Accidents – broken Hg thermometers or Hg lamps
• Iatrogenic (caused by medical treatment itself): vaccinations with ethyl mercury (controversial) and other medications

Chronic toxicity

• Amalgam fillings
• Professional hazards — work in dental office
• Passing from mother — through placenta and through breast feeding
• Consuming contaminated food (large predatory fish)
• Polluted environment
• Multiple vaccinations (controversial)

Gross

Ataxia, intention tremors, uncoordinated, dysarrthria (inarticulate speech), psychomotor retardation

Subtle

• Motor affects: progressing incoordination, imbalance and fine motor tremors in muscles that perform fine motor control like fine tremors of the tongue, lips or outstretched fingers.
• Hypersalivation (excessive saliva) with pooling of saliva
• Cold but erythematosus (reddish) hands and feet
• Unstable, changeable mood (emotional lability)
• Insidious loss of mental capacity (progressively affecting memory and logical reasoning)

A personality characterized by irritability, anxiety, depression, and restlessness, with lapses in concentration, memory and cognitive function

• Clinical picture which is characterized by: neurological, psychiatric symptoms or unexplained symptoms, like fibromyalgia, chronic fatigue, treatment resistant depression, anxiety or Obsessive Compulsive Disorder
• Mercury fillings in childhood and adolescence, or more than 3 fillings in adulthood
• Metal taste
• Tremor
• Erethism

We all are different. There are several factors involved that can affect how and if we manifest symptoms of toxicity:

1. How exposed we are to toxic metals:
   1. how many fillings we have in our mouth;
   2. how big they are, or how early in life they were put in;
   3. how much large predatory fish we are consuming;
   4. are there other metals in our mouth, such as gold or metal crowns;
   5. are we consuming any other heavy metals in foods or from our surrounding environment?
2. Is our body overloaded with different toxins that prevent us from being able to excrete them appropriately?
3. Does our diet support healthy defenses and elimination?
4. Are we under excessive stress psychologically, spiritually and/or physically?
5. Was our health affected by excessive vaccinations negatively affecting our immune system?
6. Were we physically or sexually abused in our childhood?

All of the above factors can have a tremendous effect. The last factor would be our genes.

Apoliprotein E significance

Apoliprotein E (APO E) has been strongly implicated as a risk for developing Alzheimer’s disease. There is also a connection to heavy metal toxicity.

Apoliprotein E (APO E) has 299 amino acids with different ratios of cysteine and arginine at positions 112 and 158.

APO-E2 has 2 cysteins, APO-E3 has one cysteine and one arginine and APO E4 has two arginines. Arginine, unlike cysteine looks at the sulphydryl (SH) groups to potentially bind bivalent metals such as mercury, lead, copper or zinc. It becomes a logical possibility that metal accumulation increases in those chronically exposed individuals who had not inherited APO- E 2.

Lack of sulphydryl (SH) groups to bind bivalent metals such as mercury, lead, copper or zinc increases the accumulation of heavy metals. (Roses, AD, et “Apolipoprotein E genotyping as a diagnostic adjunct for Alzheimer’s disease”. Int Psychogeriatrics. 119; 9 (suppl 1)277-288 and 317-321)

Distribution of Apoliprotein genotype in the population was examined in New Zealand by M. Godfrey:

1-2% of the population has homozygous APO-E4/4. 20% has heterozygous APO—E3/4, 50-60% has APO-E3/4; Reminder: E-2/2, E- 2/4, E-2/3. Chronic mercury toxicity is more common among people with APO-E 4/4 and APO- 3/ 4. (M. Godfrey, et. “Apolipoprotin E genotyping as a potential biomarker for mercury neurotoxicity”. J. of Alzheimer’s Diseases 5 (2003)189-195)

• Acute toxicity (poisoning) by blood, urine and stool testing – only valid for 30 to 60 days following acute toxicity. This form of toxicity is very rare in everyday life. If we test routine blood, stool or urine from the patient, there will be no elevation in the mercury level; therefore, doctors may assume that there is no mercury toxicity. This test will be negative in cases of chronic toxicity. However, this is the test most frequently used by conventional MD’s. This may explain why most cases of chronic toxicity are missed.
• To diagnose chronic toxicity we should use:
  • Urine random / provocation testing
  • Hair testing (controversial and most of the time negative; it is illegal in NY)
  • Stool random / provocation (difficult to collect)
  • Urine porphirin testing — not well established
  • Kinesiological testing — it is the least proven test; its accuracy depends on the tester. (It is my favorite test to see if toxicity is present and is later used to track the progress of chelation.)

Why do we need provocation testing?

Without testing we cannot be sure that toxicity is actually present even though a lot of medicine is practiced without ever looking at what is causing the particular problem (for example, treatments for depression, anxiety, hypertension and other conditions). Patients can be exploited when they are told to buy dubious supplements that have never been proven effective for chelation; furthermore, without proper testing we cannot assume that toxicity is present. Patients can be tricked into using supplements that they do not need.

In the body, mercury is bound to a tissue, primarily the nervous cells, thus causing damage. A Provocation test can reveal the total burden to the body, i.e. how much mercury is in the whole body. It does not, however, specify which organ is affected. The test just gives an idea how severely the patient is affected by heavy metal toxicity. One of the best laboratories to do this testing is Doctor’s Data (http://doctorsdata.com/home.asp).

A Provocation test should always be preceded by a Random Test. The test will show how much the body is able to excrete (get rid of) mercury through urine. Random and provocation tests are compared. If there is little difference between them it can be because:

• Patient does not have an issue with heavy metal toxicity.
• There was an error in collecting, processing the test, or the provocation agent was defective.
• Patient has difficulty excreting heavy metals, even though he/she has toxicity suspected by the clinical picture (false negative results).

Kinesiological testing may be one of the most reliable indicators of toxicity. It can also point to organs where mercury is still present. The only drawback is that it is not formally tested in medical studies and is not accepted by the medical establishment.

Is the provocation test dangerous?

For testing, we are using medications that can potentially cause side effects. Most of the side effects, however, are caused by using DMPS intravenously for provocation; we are using DMPS orally, not intravenously. The potential benefits and side effects should be considered in the process of deciding whether or not to do the test. I require patients to sign a consent form before the procedure. In my personal experience, and in the experience of sever al other experienced practitioners such as Drs. Klinghardt and Wojcik, serious side effects are extremely rare when DMPS is used orally and not intravenously, as it had been in the past. Patients should have a complete blood work prior to testing to be sure that he/she has adequate kidney and liver function.

Agents used for provocation testing

• DMPS in doses of 500 mg or less, according to body weight or physical status, with urine collection for 6 or 24 hours. (Instructions for DMPS provocation test) Side effects are infrequent when DMPS is given as an oral agent. This test has become a gold standard in the industry. Intravenous DMPS is used very rarely for provocation testing because it can cause undesirable side effects for patients with reduced kidney function.
• DMSA in doses of 500 mg orally, with subsequent urine collection for 6 or 24 hours. DMSA has less affinity for mercury, so it is not as revealing.
• EDTA is not an effective oral agent, but sometimes it is used intravenously as a provocation agent. I do not use it at all.

Acute toxicity can be determined by a blood mercury level, but under regular circumstances it is almost never needed.

Chronic toxicity is determined if there is a 10 fold increase between the pre- and post- challenge urinary mercury levels; or the post-challenge test is >5 mcg/g Creatine. Other norms exist and depend on the laboratory testing involved. (M. Dauderer “Mobilization test for environmental metal poisoning” Forum des practische und Algenende Artes 28 (1989), 88-90(transl))

Specific Urinary Porphyrin Profile- assesses chronic exposure to Mercury. Hg changes activity of uroporphynogen decarboxylaze (UROD) and coproporphynogen oxidase (CPOX). This test is available in some US laboratories, but it is not approved for use in NY.

There has been very little interest in financing and doing outcome studies on chronic heavy metal toxicity. I will review some that are primarily applicable to psychiatry, roughly divided into four categories:

• Studies in which amalgam fillings were replaced and patients were evaluated before and after;
• Studies where amalgam fillings were replaced and antioxidant therapy was provided;
• Studies were amalgam fillings were replaced and chelation or homeopathic treatment was provided;
• Studies of autistic children.

R. Siblerud, Ph.D. conducted several small studies using psychological measurements evaluating patients with psychiatric conditions. In one study, before and after treatment scores on the Minnesota Multiphase Personality Inventory-II (MMPI- II) were compared. 20 people were recruited through newspaper advertisement. They were given a choice to replace their amalgam fillings, or put sealant to prevent mercury from escaping. 11 manic depressive subjects who had their amalgams removed and 9 subjects with amalgams who were told they were being given a placebo or sealant were compared. The amalgam removal group improved significantly on 87 scales, as did their anxiety, anger, schizophrenia, paranoia and other behaviors. All scores of the nine dimensions in the symptom Check List 90 improved significantly in the group with amalgam removed. The amalgam removal group reported a 42% decrease in the number of somatic health problems after amalgam removal, compared to 8% increase in somatic symptoms in the placebo/sealant group. R. Siblerud, et: “Psychometric Evidence that Dental Amalgam Mercury may be an Etiological Factor in Manic Depression” J. of Orthomolecular Medicine; Vol. 13, No.1, 1998

In another study, scores of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), the Milton Clinical Multiracial Inventory II (MCM-II) and Symptom Checklist-90 (SCL-90) were compared before and after dental amalgam removal of eight schizophrenic patients to scores six months after amalgam removal. Significant improvement was found in forty-one of the sixty-one component scales of MMPI-2 and 12 of 20 subscales including schizophrenia, hysteria, paranoia and anger. Four of nine dimensions improved significantly on the SCL-90 including depression, and psychotic and obsessive-compulsive behaviors. R. Siblerud, et al: “Psychometric Evidence that Dental Amalgam Mercury May be an Etiological Factor in Schizophrenia” J. of orthomolecular Medicine; Vol. 14. No 4, 1999

These studies show that by replacing amalgam fillings even patients with serious psychiatric conditions have chances to significantly improve their symptom.s

In a study done in Sweden by Ulf Lindh, 463 consecutively enrolled patients were referred by medical practitioners and dentists to the Center for Metal Biology, Uppsala, Sweden from 1991 to 1996. All of the patients experienced chronic, long-lasting, severe disease not explained by thorough examinations and laboratory tests. Out of 30 symptoms, the median number of symptoms was 19; 7% of patients experienced all 30 symptoms. Patients were found to have hypersensitivity or allergy to metals comprising dental alloys as diagnosed by MELISA (Memory Lymphocyte Immuno Stimulation Assay). They underwent removal of incompatible dental materials, such as dental amalgam (mercury compounds), gold alloys or non precious metal alloys and they completed a 30 question medical questionnaire before, during and after amalgam removal. In addition, patients underwent a very simple oral anti-oxidant treatment:

• Vit. C 1900 mg/day
• Vitamin B complex : B 1- 30 mg/day, B2- 30 mg/day, B3-150 mg/day B6-6 mg/day; Vit. E- 400-600 Units/day; Selenium- 400 mcg/day
• Methylcobolamine-10 mg/Sq/week; and Folic Acid-10 mg /day for patients with positive markers for vitamin deficiency 72 % (334) of the patients had positive changes; 13.6 % (63) patients showed no difference in life quality and 12.9% (60) patients had negative consequences. (Ulf Lindh, “Removal of dental amalgam and other meal alloys supported by antioxidant therapy alleviates symptoms and improves quality of life in patients with amalgam-associated ill health” Neuroendocrinology letters, Nos. 5/6 Oct-Dec, Vol. 23, 2002)

There was again a significant improvement in the quality of life for 72 % of patients. The reason could be hypersensitivity or allergy to metals comprising dental alloys. It is a remarkable percentage considering that patients had not responded to any conventional treatment modality.

The most interesting study was done by Damian P. Wojcik, MD from New Zealand. (Damian P. Wojcik, et “Mercury toxicity presenting as a chronic fatigue, memory impairment and depression: Diagnosis, treatment, susceptibility, and outcomes in New Zealand general practice setting (1994-2006) Neuroendocrinology Letters, Vol. 27, no 4 2006 415-423). This was a retrospective study in which he examined and analyzed diagnostic and treatment results of over 1000 patients in a general New Zealand community practice over a ten year period. Patients who were clinically suspected of having Chronic Mercury Toxicity (CMT) were compared using a 124 symptoms questionnaire based on International Academy of Oral Medicine and Toxicology (www.IOMT.org). Intravenous DMPS provocation testing was done wherever possible. (He did not report any significant negative reaction to intravenous use of DMPS- MG., private communication.) Most of these patients had symptoms not responding to any contemporary medical approach, including patients with chronic fatigue and fibromyalgia, depression, manic-depressive illness and Alzheimer’s. Those patients who had identifiable signs of mercury toxicity and whose provocation test results were significantly above what would be normally expected, were treated for mercury toxicity. Patients with Chronic Mercury Toxicity (CMT) were advised to abstain from mercury contaminated fish, replace their amalgams with non-mercury composite restorations, and then complete a 3 month course of oral mercury chelation with DMSA (Di-mercapto-succinic acid) at a dose of 500 mg nightly thrice weekly (Mon, Wed, Fri) on alternative weeks for a total of 9 grams. Chlorella 3 grams per day was given for the DMSA weeks, as well as nutrient and anti-oxidant support. Only 33 patients completed follow-up DMPS provocation testing. Patients served as their own control.

Below are tables illustrating the results of the study:

Figure 1. MEAN SYMPTOM SCORE POST TREATMENT

As we can see the best results were achieved when amalgam replacement was combined with DMSA chelation.

Figure 2a. FATIGUE SCORE

Significant improvement was obtained when dental work was done in conjunction with DMSA chelation. Homeopathy appears to be an acceptable alternative for those who are reluctant to use DMSA.

Figure 2b. LOSS OF MEMORY SCORE

Figure 2c. DEPRESSION SCORE

Remarkable that treatment resistant depression can be treated using DMSA chelation.

Figure 3
SIMULTANEOUS DMPS URINE Hg TEST WITH SYMPTOM SCORES PRE AND POST TREATMENT

This study can provide an inspiration in approaching difficult to treat patients with complicated medical/psychiatric issues. What is remarkable is that not only did patients’ symptoms improve and in many cases get completely resolved, but most patients were followed for over eight years and the level of improvement was maintained. There is no other medical treatment that is available in psychiatry for the treatment of depression that will maintain a depression-free status after only three months of treatment.

However this study did have a number of issues. The main one being that design and testing changed several times and groups were put together artificially. A big obstacle was that the patients had to pay out of their pockets for many things, including heavy metal testing, dental work and some other treatments, so there was no consistency in treatment.

It is, however, the only study that compared those who removed amalgam fillings with those who did not; those who had DMSA chelation, or homeopathic treatment with those who did not. The study gives us practical unbiased direction in treatment alternatives!

The last set of studies deal with autism. Several studies, many practitioners and many parents have emphasized the possible connection between the autism epidemic and mercury toxicity. One of the hypotheses is that since 1984 the number of vaccinations given to children has dramatically increased and even though it may appear that the amounts of mercury that infants and toddlers were receiving were relatively small, injecting vaccines into the muscles and under the skin bypasses the usual defenses of the gastrointestinal tract and directly affects the central nervous system. In addition, the vaccines themselves have severe impact on the underdeveloped immune system. The autism epidemic onset coincides with the increased number of vaccinations given. The only groups of children free of autism are Pennsylvania Amish and 35,000 + children from a Chicago area of Christian believers receiving home schooling. Both groups have refused vaccinations. The incidences of asthma, allergies and ADHD in these groups are also extremely small. (Kenneth Bock, M.D. “Healing the new childhood epidemics: Autism, ADHD, Asthma and Allergies” Ballantine books, 2007).

The Autism Research Institute has been conducting an ongoing study of the parents of autistic children, collecting information on what intervention works and what does not. The most effective intervention has been chelation. Out of 627, 3% of the children got worse, 24 % did not improve and 73% had improvement! See “Parent Ratings of Behavioral Effects on Biomedical Interventions” for more information.

This is a list of pharmaceutical agents used for chelation.

Abbreviations:
IV — intravenously
BBB — blood brain barrier

EDTA is primarily used intravenously for the treatment of heart conditions. Currently there is a large double blind control study underway funded by NIH to assess the effectiveness of this treatment. If results are positive, it may change the way heart patients are treated. However, only 5 % of EDTA is absorbed from the gastrointestinal tract, so it is a poor oral agent. It also has low affinity for mercury; therefore those who have undergone treatment with EDTA may still have plenty of mercury in their organs, particularly in the brain.

DMPS is not available as a prescription medication in the US, but is available through compounding pharmacies. It is one of the most effective medications to remove mercury, particularly from the kidneys, but it is quite expensive. It is an agent used for provocation testing to assess the total body burden of heavy metals. It does not cross the blood brain barrier so it may not be an effective agent for people with emotional issues.

DMSA is an agent used in the Wojcik study and in many autistic children. It is my drug of choice for most of the patients.

Cupramine has not gained popularity and is rarely used, possibly due to some of its side effects.

In addition to the medications, there are several supplements being promoted for chelation. Unfortunately, there is no credible information confirming their effectiveness. Their use may be based on hype and promotional tactics without much evidence that they are effective. One of the most widely promoted agents is Metal Free, but it is quite expensive and has not been proven to be effective.

Protocol for Chelation

Find a .pdf version of the Protocol for chelating / removing toxic metals from the body

Additional notes on how to do chelation protocol:

Chelation is an important process of eliminating toxic metals from the body. The process may take from two to twelve months. We will be going through the steps of oral chelation. There are, however, some important tenets to follow:

1. A high fiber diet is required (see additional notes on diet). In order to eliminate toxins from your system, your body must be maintained in an alkaline state. This may be accomplished by eliminating junk food (sugar, processed food, and refined carbohydrates), red meat, alcohol, etc.
2. You should have at least 1-3 bowel movements daily. If a problem exists, use stool softeners such as sugar-free Metamucil and One Beyond Fiber.
3. Drink 3 quarts of water daily to hydrate the system and wash out the toxins.
4. On the days that you take Chemet (DMSA), finish taking any minerals by 3PM.
5. Repeat blood work and provocation test every two months.

Steps of oral chelation

1. DMSA (Chemet) is the main chelating agent that you will use. Take it 3x/week at least 2 hours after dinner (Monday, Wednesday and Friday nights before bedtime). The usual dose is 10mg/kg/dose or 30mg/kg/day (1lb=0.45kg; 1kg=2.2lbs). To minimize side effects, start with 100mg at night and gradually increase to a full dose over a 2-3 week time frame. The most common side effects are gastrointestinal: nausea, diarrhea, loss of appetite, loose stools and/or metallic taste in mouth. There can also be transient liver enzyme elevation. If gastrointestinal symptoms bother you, use Peppermint tea or tablets, or activated charcoal (2-3caps at night). If a rash occurs notify a physician.
2. L-Glycine is a non-essential amino acid abundantly present in food. Consume 2 hours prior to DMSA. Its role is to transport metals from inside the cells to the outside of the cells where it can be bound by DMSA and removed from the body. The dose is 45mg/kg. Possible contraindications include psychosis, high ammonia levels and/or kidney stones (oxalic acid).
3. Multivitamins with minerals are essential. We are using a comprehensive mineral/vitamin/amino acid complex called “Doc‘s Best”.
4. Vitamin C (Ascorbic Acid) reduces toxicity by eliminating multiple toxins, including heavy metals. Vitamin C dosage is calculated by using the Vitamin C flush test (see below).
5. NAC (N-acetyl-cysteine) increases glutathione body levels. This is the main amino acid helping in detoxification.
6. Alpha-lipoid acid is a powerful antioxidant that mobilizes heavy metals to enhance the chelation process. It has a protective effect on the nervous system.
7. Zinc Picolinate increases the body’s production of metallotionen. It protects the kidneys by blocking the absorption of arsenic, cadmium, and mercury. It improves the glutathione level as well.
8. Magnesium is one of the most deficient nutrients in toxic patients. They tend to excrete high amounts of magnesium. Magnesium is an essential element in over 400 enzymatic body reactions. It is essential for proper liver function activity. We use Magnesium Taurate 125mg capsules (2-3caps, 2x/day). If the dose is too high, the only side effect would be loose bowel movements.
9. Selenium Picolinate is an essential mineral that increases the glutathione level and reduces toxicity. A deficiency results in chelation side effects.
10. Liver function and Psyllium are needed to bind toxins in the bowel thus preventing their re-absorption. They also increase hepatic enzyme activity, increase daily fecal bile concentration and excretion, lower cholesterol and lower elevated blood sugar.
11. Vitamin E 400 IU as mixed tocopherols is an important antioxidant for membrane stabilization. It reduces the body mercury level.
12. MSM (Methylsulfonylmethane) enhances the liver detoxification process.
13. Probiotic therapy is important for restoring normal levels of good bacteria in the intestines.
14. Cilantro is an herb that assists in the mobilization of mercury from the brain.
15. Garlic is an important herb that restores normal levels of intestinal bacteria and improves chelation. Consume fresh or freeze-dried garlic. Chew parsley to decrease odor.
16. Uva Ursi 75mg and Marshmallow 75mgs are herbs that protect the kidneys from the heavy metals that are being eliminated.
17. Copper 1-4mg/day replenishes levels that were chelated and excreted.
18. Potassium 3000mg (Potassium Citrate aids in mercury removal from the body) has enhancing effects with DMSA and alkalinizes the urine.

Notes: 1×2= 1 cap twice daily; 2×2 = two caps twice daily; 3×2 = 3caps twice daily.

Vitamin C Flush test

We differ in how much Vitamin C (Vit C) or ascorbic acid we need at any given time of our lives. Vit C needs change and vary depending upon our health and nutritional state. If we have a cold, or body toxicity, our Vit C needs are greater than usual. The body has several ways to regulate Vit C levels. The first is the intestinal transport mechanism which limits the amount of Vit C tolerated. The rationale of this mechanism is being used in the Vit C flush test.

It is important to know which type of Vit C is being consumed. Different forms of Vit C are commercially available. Most forms are usually synthetic ascorbic acid. Ascorbic acid comes in 2 forms or polymers: left (L) or right ®. They are look-alike mirror images but only the L polymer is biologically active, i.e. has value for our body functions. The human body can only utilize the L form of ascorbic acid. Unfortunately, most of the commercially sold ascorbic acid does not make a distinction between forms L and R. One company I recommend is Perque Potent C Guard, buffered ascorbate, which uses 100% L-ascorbate. It comes in 2 forms, pill or powder. Powder is easier to absorb, but pills are easier to handle. Vit C is an essential component in the chelation protocol. It is a known free-radical scavenger and has its own chelating properties.

How to do the Vitamin C flush test

Several hours are required for test completion. Plan to have close access to the bathroom throughout testing. It is easier to do the test with the powdered form of buffered Vit C. You will need to keep notes each time you take Vit C. Start the dose on an empty stomach.

Start taking 1/2tsp of Vit C powder diluted in water or juice, every 15 minutes and record the time of each dose. If after 4-5 doses there is no diarrhea, start taking 1 tsp of Vit C powder. When you have repetitive loose bowel movements, your intestines are signaling that they have reached a critical tolerance level of Vit C absorption. Give your body a rest for a few days.

Each tsp contains 3000 mg (3 gms) of Vit C. If you are taking pills, it is easier to dose but takes much longer for absorption and for your body to respond. Your Vit C body requirements can vary between 5ooo mg and 40000 mg.

For the next week or so you will need to take 75% of the achieved dose per day, in divided doses. For example, if you began running to the bathroom after taking 10,000mg Vit C, then your daily dose for the next week should be 7500mg/day divided into 3 doses making it 2500mg/dose. You can ingest the Vit C as pills or dissolved powder. Keep the dissolved powder with water in a dark bottle. Keep refrigerated and sip it all day long.

You may need to repeat the Vit C flush test weekly or every other week. In due time your tolerance will decrease and you will require less dosage.