Saturday, January 13, 2007

A Comprehensive Review of Heavy Metal Detoxification and Clinical Pearls from 30 years of Medical Practice by Dietrich Klinghardt, MD.,Ph.D

A. Introduction:
Heavy Metals appear in the mammalian system because they have become part of our environment.

We are in a constant exchange with our environment which is goverened by the laws of osmosis.

If mercury is in the fish we eat, over time we have mercury in our system. We cannot keep our system pristine and clean, because we are seperated from our toxic environment only by semi-permeable membranes: skin and mucosal surfaces.

Maintaining relative cleanliness requires a number of inherentdetox systems to work overtime against the osmotic pressure of the incoming toxins. As the toxixity of our environment increases so does the osmotic pressure, pushing the often man- made poisons into our body.

Toxins almost never come alone. They come in synergistically acting package-deals. Mercury alone is toxic. Together with zinc it is many times more toxic, add in a little copper and silver, as in dental amalgam fillings and the detrimental effect to the body increases manyfold.

Together with mercaptan and thioether (dental toxins) the toxic amalgam effects grow exponentially.

Add in a little PCB and dioxin, as in fish, and the illness causing effect of the methyl mercury in fish increases manyfold. Toxicology is to a large degree the study of synergistic effects.

In synergy 1 plus 1 = 100. Heavy metals are primarily neurotoxins. There is a synergistic effect between all neurotoxins which is responsible for the illness producing effect.

Making the neurotoxin elimination a major part of my practice has been an amazing experience.

Many illnesses considered intractable respond when the related issues are successfully resolved.

What are Neurotoxins?

Neurotoxins are substances attracted to the mammalian nervous system. They are absorbed by nerve endings and travel inside the neuron to the cell body. On their way they distrupt vital functions of the nerve cell, such as axonal transport of nutrients, mitochondrial respiration and proper DNA transcription. The body is constantly trying to eliminate neurotoxins via the available exit routes: the liver, kidney, skin and exhaled air.

Detox mechanisms include acetylation, sulfation, glucuronidation, oxidation and others. The liver is most important in these processes. Here most elimination products are expelled with the bile into the small intestine and should leave the body via the digestive tract. However, because of the lipophilic/neurotropic nature of the neurotoxins, most are reabsorbed by the abundant nerve endings of the enteric nervous system (ENS) in the intestinal wall. The ENS has more neurons than the spinal chord. From the moment of mucosal uptake the toxins can potentially take 4 different paths:

1. Neuronal uptake and via axonal transport to the spinal chord (sympathetic neurons) or brainstem (parasympathetics) – from here back to the brain.
2. Venous uptake and via the portal vein back to the liver
3. Lymphatic uptake and via the thoracic duct to the subclavian vein
4. Uptake by bowel bacteria and tissues of the intestinal tract

i) Heavy metals:
mercury, lead, cadmium, iron, manganese and aluminum (are the most common).Common Sources: metallic mercury vapor escapes from dental amalgam fillings (they contain about 50% mercury, the rest is zinc, silver copper, tin and trace metals). Cadmium: car fumes, cigarette smoke , pigment in oil paint Lead: outasing from-paint, residues in earth and food chain from time when lead was used in gasoline, contaminated drinking water Aluminum: cookware, drinking water

ii) Biotoxins:
such as tetanus toxin, botulinum toxin (botox), ascaridin (from intestinal parasites), unspecified toxins from streptococci, staphylococci, lyme disease, clamydia, tuberculosis, fungal toxins and toxins produced by viruses. Biotoxins are minute molecules (200-1000 kilodaltons) containing nitrogen and sulfur. They belong to a group of chemical messengers which microorganisms use to control the host´s immune system, host behaviour and the host´s eating habits.

iii) Xenobiotics (man-made environmental toxins):
such as dioxin, formaldehyde, insecticides, wood preservatives, PCBs etc.
iv) Food Preservatives, excitotoxins and cosmetics:
aspartame (diet sweeteners), MSG, many spices, food colourings, fluoride, methyl-andpropyl -paraben, etc.

Heavy Metal Toxicity
Metals can exist in the body with different kinds of chemical bonds and as different molecules. Mercury appears to be the king-pin in the cascade of events in which metals become pathogenic. Mercury can be present as metallic mercury (HgO), as mercury salt (e.g. mercury chloride – HG+), or as methyl mercury (HG++). Methyl mercury is 50 times more toxic than metallic mercury. Methyl-Hg is so firmly bound to the body that it has to be first reduced to HG+ before it can be removed from the cell. This is achieved with reducing agents (“antioxidants”) e.g. intravenous vitamin C and reduced glutathione.

To remove Hg-Salts or metallic Hg from the outside of the cell, other agents are useful Mercury belongs to a group of metals that oxidize in the presence of sulfur and form compounds with sulfur (sulfhydryl affinitive metals). Methyl mercury is already oxidized to its maximum and bound firmly to sulfur in the different proteins of the body. The following metals belong to the sulfhydryl affinitive group and respond to similar detoxification methods: Copper, arsenic, cadmium, lead, mercury. Aluminum and iron for example would not respond a sulfur compound. Some detox agents have multiple mechanisms by which they bind to metals. The algal organism chlorella has over 20 known such mechanisms.

Other metals oxidize with oxygen. Iron turns to rust when oxidized. Rust is nontoxic to the body, whereas iron is. Iron overdose responds to a chemical called desferoximin (desferal). Aluminum responds to the same detoxification agent. A recent Japanese study showed that Chinese parsley, cilantro, is a powerful elimination agent for aluminum stored in bone and the brain.

Other facts:
· Some metals are extremely toxic, even in the most minute dose, whereas others have very low toxicity, even in high doses. However, dependent on the dose, all metals can become toxic to the body. Iron can cause severe oxidative damage, copper may compromise liver function and visual acuity, selenium and arsenic have been known to be used to murder people and so on.
· Most metals serve a functional role in the body. For example, selenium is needed in the enzyme that restores oxidized glutathione back to its functional form as reduced glutathione. Another important function of selenium is its role as a powerful antioxidant in preventing cancer.
· Some metals have a narrow physiological range. That means the difference between a therapeutic dose and toxic overdose is very small. Selenium is an example of this. Magnesium on the other hand has a wide physiological range and thus is more difficult to overdose.
· Some metals have no physiological function. Mercury, lead, aluminum are in this group. Even the smallest amounts have negative physiological-effects.
· biochemical individuality: some people may react more or less than others to the presence of heavy metals in the tissues. Some people may develop a severe chronic illness after exposure of a few molecules of mercury, whereas others may be more resistant to it. Genetic deficiencies in the enzymes responsible for the formation of the metallothioneins and glutathione production and reduction are examples.

Possible side-effects during heavy metal detox:
Every patient can be affected by metals in two ways:
1. Through their non-specific toxic effects
2. Through the system´s allergic reactions to the neurotoxins
Often these two distinctive types of symptoms cannot be easily distinguished. During a detox program, the patient may also temporarily become allergic to the various substances that help to carry out the toxins. This is based on a physiological mechanism called ‘operant conditioning’.

Every time the detoxifying substance is given, mercury emerges from its hiding places into the more superficial tissues of the body, where mercury can now be detected by the immune system. The immune system however is fooled into thinking that the detoxifying substance itself is the enemy. The immune system now starts to react to the detoxifying substance as if it was the mercury itself. This reaction typically resolves spontaneously after six weeks of not using the detox agent in question. This type of conditioned reflex can also be easily treated with simple techniques e.g. NAET, PK (APN), or by giving the detox substance in a homeopathic dilution for a few days. Often the basal membranes in the kidney will swell as a sign of the allergic reaction, causing low back pain, anuria or inability to concentrate urine.

Neuraltherapy or microcurrent stimulation of the kidneys quickly resolves the issue. Muscle aches indicate the redistribution of toxins into the connective tissue and an insufficient program. Depression, headaches, trigeminal neuralgia, seizures, increased pain levels indicate redistribution of metals into the CNS and an inappropriate detox program. Eye problems and tinnitus that occurs during detox indicates redistribution of metals into these organs and requires selective mobilization from these locations before the program is continued. I use a specific type of microcurrent for this purpose

Some recently published findings related to the metal issue:
Iron/mangnese: A recent paper on Parkinsons disease (Neurology June 10, 2003;60:1761-1766)revealedthat just by eating iron and manganese containing foods such as spinach or taking supplements containing Mn or Fe - the risk of developing PD increased almost 2 fold. This demonstrates that even dietary supplements or organically grown foods are amongst the possilbe culprits in metal toxixity.

Methylmercury:
There are two major sources:
1. mercury escaped from dental amalgam fillings is converted by oral and intestinal bacteria to methylmercury, which then is bound firmly to proteins and other molecules. Methyl mercury crosses the blodd brain barrier and the placental barrier leading to massive prenatal exposure. Earlier studies determined that over 90% of the common body burdon of Hg is from dental fillings. Recent studies show that eating fish is starting to compete with amalgam fillings for the leading position as a risk factor.
2.Seafood
A recent study (JAMA, April 2, 2003;289(13):1667-1674) revealed the following It is estimated that nearly 60,000 children each year are born at risk for neurological problems due to methylmercury exposure in the womb. One in 12 U.S. women of childbearing age have potentially hazardous levels of mercury in their blood as a result of consuming fish, according to government scientists. The U.S.FDA recommends that pregnant women and those who may become pregnant avoid eating shark, swordfish, king mackerel, and tile fish known to contain elevated levels of methylmercury, an organic form of mercury. Nearly all fish contain some amount of methylmercury. Mercury accumulates in the system, so larger, longer-lived fish like shark or swordfish contain the highest amounts of mercury and pose the largest threat if eaten regularly.
The National Center for Policy Research for Women & Families published in May 2003, that the following fish are lowest in methyl mercury:
· Catfish (farmed)
· Blue Crab (mid-Atlantic)
· Croaker
· Fish Sticks
· Flounder (summer)
· Haddock
· Trout (farmed)
· Shrimp
The FDA also recommends these fish as safe to eat:
haddock, tilapia, wild alaskan salmon,and sole

Ethylmercury:
A recent quote from Boyd Haley, PhD: “our latest research clearly points to the ethylmercury exposureas being causal in autism. The tremendous enhancement of thimerosal toxicity by testosterone and the reduction of toxicity by estrogen explains the fact that 4 boys to 1 girl getting the disease and the fact thatthe bulk of severe autistics are boys. Most importantly, this autistic situation clearly shows that exposureto levels of mercury that many "experts" considered safe was capable of causing an epidemic of a neurological disease”.

B. Symptoms
Other authors have tried to specify typical symptoms for each metal. Because of the synergistic effects and simultaneous occurence of several toxins at the same time. The best source of literature on the effects of specific metals on the system are the old homeopathic textbooks ‘materia medica’ (Kent, Boericke).

I prefer to look at a client in a systemic way, not focussing on single issues . A manganese typical symptom (ie violent behaviour) may be a lot more worrysome in a given patient then their particular mercury related symptom (ie insomnia). However, the practical focus of detox should be almost always on the mercury first. If mercury is adressed appropriately, the manganese often leaves the body as a side effect of mercury detox. The opposite is not true.
Any illness can be caused by, or contributed to, or exagerated by neurotoxins. Here is a short list:
· Neurological problems: Fatigue, depression, insomnia, memory loss, blunting of the senses, chronic intractable pain (migraine, sciatica, CTS etc.), burning pain, paresthesia, strange intracranial sensations and sounds, numbness. Autism. Seizure disorder. Hyperactivity syndromes. Premature ejaculation and inorgasmia
· Emotional problems: inappropriate fits of anger and rage, timidness, passivity, bipolar disorder, frequent infatuation, addictions, depression, dark mood, obsession, psychotic behaviour, deviant behaviour, psychic attacks, inability to connect with god, etc.
· Mental problems: memory loss, thinking disorder, messy syndrome (cluttering), loss of intelligence, AD, premature aging
· GI problems: candida, food allergy, leaky gut syndrome, parasites, inflammatory bowel disease
· Orthopedic problems: joint arthritis, persisiting musculo-skeletal pain, fibromyalgia, TMD,recurrent osteopathic lesions
· Immunological disorders (autoimmune diseases, hypothyroid disorders, MS, ALS, Sjogen´s Syndrome, CFIDS, MCS etc.)
· Cardiovascular disorders ( vascular disease, arrythmias, angina, increased heartbeat)
· Cancer –mercury, arsenic, copper etc. can be a trigger
· ENT disorders: chronic sinusitis, tinnitus, glandular swelling,
· Eye problems: macular degeneration (dry and wet), optic neuritis, iritis, deteriorating eye sight, etc.)
· Internal medicine problems: kidney disease, hypertension, hypercholesterinemia, syndrome X
· OB/gyn: difficulties of pregnancy, impotence, uterine fibroids, infertility, etc.
C. Diagnosis:
· History of Exposure: (Did you ever have any amalgam fillings? How much fish do you eat and what kind? A tick bite? etc)
· Symptoms: (How is your short term memory? Do you have areas of numbness, strange sensations,etc)- A complete neurotoxin questionaire is available from AANT@425 462 1777
· Laboratory Testing: direct tests for metals: hair, stool, serum, whole blood, urine analysis,breath analysis
· Xenobiotics: fatty tissue biopsy, urine, breath analysis
· Indirect tests: cholesterol (increased while body is dealing with Hg), increased insulin sensitivity, creatinine clearance, serum mineral levels (distorted, while Hg is an unresolved issue), Apolipoprotein E 2/4, urine dip stick test: low specific gravity (reflects inability of kidneys to concentrate urine), persistently low urine ph (metals only go into solution in acidic environments - which supports detoxing), urine porphyrins
· Autonomic Response Testing: (Dr. Dietrich Klinghardt M.D., Ph.D.)
· BioEnergetic Testing (EAV, kinesiology etc.)
· Response to Therapeutic Trial
· Functional Acuity Contrast Test (measure of Retinal Blood Flow)
· Non-specific neurological tests: upper motor neuron signs (clonus, Babinski, hyperreflexia), abnormal nerve conduction studies, EMG etc . non-specific MRI/CT findings: brain atrophy as in AD, demyelination
· Several ‘challenge tests’ are used today. They generally involve measuring the urine metal content,then administering an oral or iv. mobilizing agent and re-mesuring the metal content in the urine after a few hours. Most well known is the DMPS challenge test: However, there is agreement amongst most researchers, that the urine Hg content does not reflect total body burdon – only the currently mobilizable portion of Hg in the endothelium and kidneys. If nothing comes out, there can still be detrimental but non-responsive amounts of Hg in the CNS, connective tissue and elsewhere.
· I have developed a simple approach that works well. I use autonomic response testing (muscle biofeedback) to determine what metal is stored where and what detox agents would be most suitable for this individual. I obtain a hair sample and have it analyzed. It may or may not show any toxic metals. Metals reach the root of the hair via the blood stream. Hair only can show those metals, that have been in the blood in the last 6 weeks. That means, hair only reflects acute toxicity or recently mobilized metals but not the true body burdon. Then we embark on the detox and mobilizing program. In 6 weeks another hair samle is send to the lab and analyzed. If for example manganese is now high, mercury starting to rise (mostly it is methyl Hg, that is reflected in hair), aluminum is at the same value as before, it means, that this program is starting to mobilize Mn ad Hg, but not Al.

Through minor adjustments and following the client closely, we observe as the levels in the hair may rise for months or years before returning to low or absent levels. That is the end point. At that time biochemical challenges with Ca EDTA, DMPS or DMSA can be valuabe to see if there are still hidden pockets of metals somewhere in the system that have been ovrlooked with the other methods. In general, the hair-mineral analysis is often overinterpreted. Hair minerals are a reflection of the toxic-metal induced distortion in mineral metabolism.

D. Treatment:
Why would we want to treat anyone at all? Is it really needed? Can the body not eliminate these toxins naturally on its own?

First we need to consider a multitude of risk factors, which influence later decisions:
Here is a short list of independent risk factors which can either cause accumulation of metals in an otherwise healthy body - or slow down, or inhibit the bodys own elimination processes.
· Genetics – Several genes are involved in coding for the production of inherent detox mechanisms. Example: ApoE being the major repair protein in neuronal damage and responsible for removing mercury from the intracellular environment.

There are 4 different subtypes, one of them making the individual prone to accumulating Hg: (Danik, M. and Poirier, J. Apolipoprotein E and lipid mobilizatin in neuronal membrane remodeling and its relevance to Alzheimer's disease. In: Brain Lipidsand Disorders in Biological Psychiatry, edited by Skinner, E.R.

Amsterdam:
Elsevier Science, 2002,p.53-66). Also well known and studied are the individual genetic differences in glutathione availability. Several companies in the Integrative Medicine Field are offering genetic testing today. So far my clinical results were not impressive when I based my detox program on genetic testing only.

· prior illnesses (i.e. kidney infections, hepatitis, tonsillitis etc.)
· surgical operations (scars often restrict the detoxifying abilities of whole body sections, such as the tonsillectomy scar with it´s effect on the superior cervical ganglion - restricting lymph drainage and blood flow from the entire cranium)
· medication or ´recreational´ drug use (overwhelming the innate detox mechanisms)
· emotional trauma, especially in early childhood. This issue is huge and almost never appropriately adressed
· social status (poor people may still drink contaminated water)
· high carbohydrate intake combined with protein malnutrition (especially in vegetarians)
· use of homeopathic mercury (may redistribute Hg into deeper tissues)
· food allergies (may block the kidneys, colon etc.)
· the patients electromagnetic environment (mobile phone use, home close to power lines etc.Omura showed that heavy metals in the brain act as micro antennae concentrating damaging electro smog in the brain)
· constipation
· compromise of head/neck lymphatic drainage (sinusitis, tonsil ectomy scars, poor dental occusion)
· number of dental amalgam fillings over the patients life-time, number of the patients mothers amalgam fillings

Detox Methods
There are many considerations in choosing detox agents. After choosing the appropriate agent for the individual client and particular metal and exact chemical form of it, we have to consider the body compartment where the metal is stored.

For example, the algae chlorella is ideal for removing virtually all toxic metals from the gut but has too little effect on mercury stored in the brain. Intravenous glutathione may reach the intracellular environment, even in the brain, but is fairly ineffective in removing mercury from the gut.

Each agent has a primary place of action, which determines when, how much and for how long it is used. Agents that have multiple effects on compounds of different metals in the various body compartments are the basis for our detox program. Most specific agents are used for special situations only.

High protein, mineral, fatty acid and fluid intake
Rationale:
· proteins provide the important precursors to the endogenous metal detox and shuttle agents, such as coeruloplasmin, metallothioneine, glutathione and others. The branched-chain amino acids in cow and goat whey have valuable independent detox effects. Amino acid supplements, especially with a concentrate of brached chain amino acids are valuable.

· Metals attach themselves only in places that are programmed for attachment of metal ions.

Mineral deficiency provides the opportunity for toxic metals to attach themselves to vacant binding sites.

A healthy mineral base is a prerequisite for all metal detox attempts (selenium, zinc, manganese, germanium, molybdenum etc.). Substituting minerals can detoxify the body by itself. Just as important are electrolytes (sodium, potassium, calcium, magnesium), which help to transport toxic waste across the extracellular space towards the lymphatic and venous vessels.

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