Heavy Metal Toxicity

Majid Ali, M.D.

At the energetic-molecular level, the boundary between health and the state of absence of health is marked by oxidosis, acidosis, and dysoxygenosis (dysox).1-4 Microbial toxins and mercury are the most potent and common inciters of those three furies in the oral cavity. Regrettably, there is little, if any, appreciation of those crucial important causes of systemic disease among physicians. I have yet to meet a neurologist who seriously considers the role of mercury in the causation of multiple sclerosis, or a rheumatologist who searches for etiologic factors in oral microabscess of a patient presenting with lupus erythematosus. Nor have I met a cardiologist who suspects oral mycotoxicosis as the cause of cardiac arrhythmia. Later, I present data about one such case to underscore the importance of this relationship.

The general community of dentists has not fared much better in the past. Except for some enlightened biologic dentists, the crucial importance of oral toxicity in triggering, amplifying, and perpetuating systemic inflammatory and infectious disorders has largely been ignored by dentists. That is not so because the relationship between oral pathologies and systemic disease has not been recognized. Indeed, it has been described since antiquity, including some texts devoted to this subject written by an Arab physician.5 Fortunately, that is changing. An ever-enlarging community of dentists is becoming increasingly aware of issues of oral dysoxygenosis and how to effectively address it.

Oxygen and Biofilms

Below is reproduced some text from Heavy Metal Load and Toxicity, the seventh volume of The Principles and Practice of Integrative Medicine,6 to provide a framework of reference for presenting ozone therapeutics.

Biofilms are microbial tribes abiding by Darwinian imperatives—adapting to dynamic changes in the oxygen order and availability of their growth requirements in their microecologic conditions. Oral dysoxygenosis is the state in which oxygen homeostasis is regionally disrupted by local conditions in the mouth. Mercury from dental amalgams appears to be one of the most, if not the most, potent disrupters of oxygen metabolism in the oral cavity. Other such disrupters are thioethers and other microbial toxins. Those factors also alter the local conditions that either inhibit or foster microbial growth, so facilitating biofilm formation. Such dynamics seem to play crucial roles in the pathogenesis of systemic disorders rooted in the oral cavity.

In the classical sense, Costerton described biofilms as complex, heterogeneous bacterial colonies embedded in a protective slimy, polymeric polysaccharide matrix that they themselves produce.7-9 Such microbial communities are well known for their resistance to various antibiotics and are increasingly recognized as the roots of many chronic and indolent infections.10,11 Disruptions of local tissue architecture — fibroproliferative or occlusive lesions, for instance — facilitate biofilm formations and so impede healing with resolution. Antibiotic resistance of biofilms has been attributed to differentiated, structured groups of cells with communal characteristics that are distinct from those of the parent cells. Some Candida albicans biofilms examined were composed primarily of yeast and hyphal forms, with some pseudohyphae. Upper regions of such biofilms were made up of tangled masses of hyphae with openings between germ tubes about 10 to 50 mM across. Such biofilm architecture markedly alters effective diffusion coefficients of various substances, such as chlorhexidine digluconate. Such changes in diffusion rates are of considerable consequence in terms of diminished fungicidal activities of various agents employed to eradicate infections caused by Candida and other mycotic species.

Biofilms also appear to play central roles in initiating, amplifying, and perpetuating anomalous and unremitting inflammatory responses — locally in the oral cavity and other locations as well as systemically in tissues far removed from the sites of biofilm formation. Such phenomena also set the stage for chronic and indolent lesions—infectious as well as noninfectious — again, not only locally in the dental, periodontal, and sinusoidal tissues, but also systemically in tissues distant from the oral and sinusoidal cavities.

The biofilm studies of direct relevance to the subject of oral dysoxygenosis, of course, are those that directly examine the oxygen dynamics and effects of reactive oxygen species on the biofilm formation and how the characteristics of biofilms, in turn, affect oxygen metabolism. In essence, we are interested in how dysfunctional oxygen metabolism may lead to biofilm formation and how biofilms increase the degree of local dysoxygenosis. In the context of dental amalgams, such considerations lead to the larger question of the impact of the “mercury-dysoxygenosis -biofilm dynamics” on the health/dis-ease/disease continuum in the oral cavity as well as in systemic tissues.

Oxygen mediates several of the bioelectric phenomena involving biofilms. It seems safe to predict that it will eventually be proven to influence all types of bioelectric effects in biofilms. In view of the enormous functional diversity of oxygen, I expect that oxygen among the products of electrolysis—protons, hydrogen, reactive oxygen species, hydroxyl ions and heat—would exert important effects on the system, though some might think reactive oxygen species might be more important. In the case of some species of Pseudomonas aeruginosa, in the biofilms at least, the role of oxygen in moderating the biofilm dynamics has been documented with experimental work. Electrolytically generated oxygen accounts for a major part of the electrical enhancement of efficacy of tobramycin against P. aeruginosa biofilm. The addition of sodium thiosulfate—an agent that rapidly neutralizes reactive oxygen intermediates—does not abolish electrical enhancement of microbial killing by the antibiotic. Interestingly, the increase in microbial killing with bubbling of gaseous oxygen through the chamber alone—without electric current—was far less than that with electrolysis.

Complex multispecies biofilms develop in the oral cavity under diverse conditions. In certain cases, pathogens in such films exist largely when supported by other nonpathogenic species in the biofilm, and vice versa. For example, Porphyromonas gingivalis and Streptococcus gordonii exist in oral biofilms only in the presence of each other. In this relationship, P. gingivalis adheres to S. gordonii by interacting with a specific region of the streptococcal SspB polypeptide, designated BAR.12 P. gingivalis in oral biofilm is of interest since it appears to play some role in the pathogenesis of atherosclerosis.

Of direct relevance to the mercury-related oxygenative dysfunction (MROD) model presented here are the altered redox dynamics in biofilms. The protective role of catalase and biofilm resistance to hydrogen peroxide has been investigated in Pseudomonas aeruginosa by comparing the susceptibility to hydrogen peroxide of wild-type strain PAO1 and the katA and katB catalase mutants.13-15 One-hour wild-type cell viability decreased steadily in planktonic cells exposed to a single dose of 50 mM H2O2, whereas biofilm cell viability remained at approximately 90% when cells in that film were exposed to a flowing stream of 50 mM H2O2. The katB mutant, lacking H2O2-inducible catalase katB, exhibited a pattern of H2O2 resistance similar to that of wild-type strain, whereas plankton katA mutant cultures, possessing no detectable catalase activity, were hypersensitive to a single dose of 50 mM H2O2. Biofilms were capable of a rapid response to oxidant stress, as revealed by significant katB catalase induction detected by increased catalase activity bands in nondenaturing polyacrylamide gels.

Mercury, Biofilms, and Oxidative Coagulopathy

In the oral cavity, mercury-induced molecular and cellular injury, biofilm formation, osteonecrosis, and regional oxidative coagulopathy form a spectrum, the various aspects of which can be separated only in a theoretical sense. From the clinical standpoint, it is essential that that spectrum be seen as a continuum and that all involved factors be addressed integratively.

Biofilms pose special hazards to the structural and functional integrity of tissues in their vicinity. A very common histopathologic feature of all infectious lesions, as well as non-infectious inflammatory processes, is a prominent endothelial response designated as endothelial hyperplasia. Such endothelial responses are more pronounced in the vicinity of biofilms. Endothelial lining of arteries and capillaries is very responsive to changes in the concentration and partial pressure of oxygen circulating within those vessels. A host of genes and proteins—most notably belonging to the hypoxia-inducible factor (HIF) cascades—are involved in endothelial responses.16,17 This subject is presented at length in the chapter entitled “Dysoxygenosis.” Alterations in the pathophysiology of nitric oxide are equally important in endothelial dynamics. That subject is discussed in Nature’s Preoccupation With Complementarity and Contrariety, the first volume of this textbook.18

Biofilm-triggered and/or enhanced endothelial responses directly induce oxidative coagulopathy, since such responses are oxidative in nature.19 Microbial populations of biofilms also exaggerate the degree of oxidative coagulopathy initiated and perpetuated by other etiologic factors. Beyond inflicting endothelial injury, biofilms also facilitate invasion of the subendothelial stroma by their microbial residents. Collagen in the stroma is thought to provide a favorable microenvironment to microbial species spreading from biofilms, including the availability of receptors for some bacterial metabolites which serve as anchors for microbes. Not unexpectedly, those changes also put in jeopardy the structural and functional integrity of the bone in proximity to biofilms. The osseous tissue devitalized or rendered ischemic by periodontal infections and root canal procedures is especially vulnerable to necrosis. Those observations led some investigators to propose that a large number of cases of myocardial infarction and cerebrovascular accidents are related to a hypercoagulable state produced by oral biofilms.

Oxytherapeutics in Dentistry

The clinical presentation of osteonecrotic lesions located in the craniofacial area is routinely diagnosed as another type of pathology. Patients routinely present in the dental office with diffuse symptoms that are episodic in nature. If the symptoms are attributable to a tooth or an area of a previously extracted tooth, then standard dental diagnostic procedures are initiated. These procedures consist of:

Clinical examination

Diagnostic Imaging

Percussion testing

Electrical pulp testing

Thermal testing

Local anesthetic block

Other testing as indicated

If more than one of the diagnostic procedures are positive for potential pathology, then the tooth and/or area in question is evaluated and treated with:

Occlusal (bite) adjustment

Oral appliances to reduce pressure on the teeth and temporomandibular joint

Sedative fillings in sensitive teeth

Root canal treatment for sensitive/painful/abscessed teeth

Re-treatment of teeth with previous root canal therapy

Surgery to remove the apex of the root of the tooth (apicoectomy) and debridement of the area

Surgery to remove infected tissues from “jaw bone cavitations

Extraction of the tooth/teeth in question

Application of oxygen/ozone gas in the affected area

There has been controversy in the dental community with regard to the specific cause of many pathologic conditions of the craniofacial area. As more information is accumulated it is apparent that these areas (bone cavitations) of chronic infection in the craniofacial area are very real and the probable cause of multiple painful conditions in the head, neck and tooth area. This is due in part to the progressive loss of vascularity in the jaw bones and associated structures. This allows the pathogenic anaerobic microbial population to exist and create a chronic infected, inflamed area. This area is effectively isolated from the circulatory system which is responsible for delivering any anti-microbial medications to the infected area. However, if the medications could penetrate these areas of the infected bone cavity, the chance that all the pathogens present would be sensitive to the medications is very small.

These types of bone cavities have also been shown to have accumulations of toxic heavy metals, as well as the pathogenic microbes. Two of the authors, ( PM, RH) are practicing Dentists who were introduced to ozone therapy for managing those lesions while studying Integrative Medicine at Capital University of Integrative Medicine in Washington, D.C. There were Naturopathic and Medical protocols in place for treating various pathologic conditions, but very was little was written about oral/dental/facial protocols. Reviews of the literature produced no significant oxygen/ozone protocols for dental procedures. The literature was consistent in the area of the oxidant effect of mixtures of oxygen and ozone. In vitro the oxidant effect of ozone produces a bactericidal, fungicidal and virucidal action. In vivo it provides a “therapeutic oxidative burst” and immune activating effect.

The collaborated on possible dental uses and began to develop protocols for Integrative Medical and Dental applications. Some stand alone dental applications were developed and initially were investigated for their efficacy by trials utilizing the authors and other interested physicians and dentists as the first recipients of treatment. After an overwhelming success in the initial clinical trial, the authors, (P.M. & R.H.) applied for an Institutional Review Board (IRB) approved research study. The IRB of Capital University of Integrative Medicine granted approval for the study of oxygen/ozone therapy for osteonecrosis for the head, neck, face, teeth, and associated structures. This is research project is ongoing and is currently training and certifying dentists in the use of oxygen/ozone therapy. If the practitioner receives certification, he/she is invited to join the research project as a remote facility for the research project.

The following areas of research and study are currently under evaluation:

Endodontic Treatment (Root Canal Treatment) The infected/abscessed tooth is opened for drainage and the root canal system has a mixture of oxygen/ozone gas injected into the root canal system. The periapical and periodontal areas also receive treatment.

Endodontic Re-treatment of failing root canal treated teeth. The periapical and periodontal areas are treated with a precise mcg/ml ratio of oxygen/ozone

Periodontal Treatment (Treatment of the soft tissues surrounding the teeth) These areas can be treated with ozonated water, direct injections, direct infusions or custom silicone trays that cover the teeth and gum tissues.

Bone infection following extraction or root canal treatment (Neurlagia Inducing Cavitational Osteitis – (NICO lesions) These areas require injection of oxygen/ozone gas into or adjacent to the NICO lesion.

Oral soft tissue infections ( apthous ulcers, herpetic lesions, coxsackie viral ulcerations, etc.)

Case Studies

The following case studies are of patients with dental problems who did not resolve with standard dental care procedure but responded well to integrative oxystatic therapies:

Case # 1: A 42 year old male presented with a draining fistula in the periapical of tooth #3. He had endodontic treatment performed on the tooth with no resolution of the symptoms. He then had an apicoectomy and retrofill of the apices with amalgam performed. The infection and drainage from the fistula persisted even though he had several courses of antibiotic therapy and repeated incision and drainage of the lesion. He presented for oxygen/ozone treatment of the tooth on 10-9-04. The area was anesthesized and oxygen/ozone gas was injected into the fistula, the periapical area and the periodontal ligament. This procedure was performed four times at seven to ten day intervals. The infection and inflammation of the tissues resolved over the one month period. His primary care dentist has noted no further symptoms and improved bone density on follow-up radiographs.

Case #2: A five year old female presented with a diagnosis of Hand, Foot and Mouth Disease from her Pediatrician. She was advised to rinse and swallow a solution of ozonated water six to eight times a day. The ulcerations resolved in three days. The pediatrician had prescribed a solution of kaopectate and benadryl for palliative relief and told the parent that the virus would “run it’s course” in fourteen to twenty-one days.

Case # 3: A 51 year old male who presented with stage four squamous cell carcinoma located in the right pharyngeal-tonsil space. EG underwent conventional therapy with little to no success. Clinical exam revealed cavitational osteonecrotic lesion in the area of the lower right third molar. Soft tissue exam revealed swollen and inflamed pharyngeal arches, bilateral tonsilar inflammation and enlargement. Extraoral palpation revealed minor swelling of lymphatic nodes on the right side. Treatment goal was not to treat the cancer but to eradicate the infective state in the head and neck. EG was placed on a 3 month head and neck oxygen/ozone protocol developed by Dr. Mollica. This protocol was inclusive of direct and indirect infusion of 21 micograms/cc of oxygen/ozone into the afflicted areas. The afflicted areas being the osteonecrotic lesions, soft tissues, and lymphatic tissue. In addition to the oxygen/ozone therapy nutritional and drainage support was provided. Within a month after the completion of the protocol EG was given an exam which included a PET scan. No trace of the cancer or any activity associated with the lesion was found. Attributed to spontaneous remission.

Case # 4: A 53 year old male who presented with pain from a lower left first molar. Clinical exam revealed a crowned tooth with a draining fistula adjacent to the buccal roots. Radiographic evidence revealed a large peri-apical lesion surrounding the two roots of the previous treated root canal tooth. The diagnosis was failing root canal. The tooth under standard treatment would be extracted. TS was put on a 8 week root canal protocol. This protocol included direct infusion of oxygen/ozone into the afflicted area via the fistula tract and canulation. The range of concentration of oxygen /ozone was 16-21 micorgrams/cc. In addition an indirect route included infusion of 1cc of oxygen/ozone into the inferior alveolar neurovascular bundle area. Lymphatic drainage support was given. Within 4 weeks the fistula resolved. By eight weeks radiographic evidence revealed completed resolution of the lesion and clear re-ossification of the area.

Table 1. Frequency of Body Burden of Toxic Metals Considered Outside the “Laboratory Range” for the General Public in 100 Randomly Selected Persons with Chronic Diseases






Both Sexes



















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3. Ali M: Fibromyalgia: an oxidative-dysoxygenative disorder (ODD). J Integrative Medicine 1999; 3:17- 37.

3. Ali M. Oxygen and Aging. (Ist ed.) New York, Canary 21 Press. Aging Healthfully Book 2000. .

4. Ali M. September Eleven, 2005. New York, Aging Healthfully Book 2003.

5. Ali M. The Principles and Practice of Integrative Medicine Volume II: The History and Philosphy of Integrative Medicine. 2001. Washington, D.C. Capital University Press (in collaboration with Canary 21 Press, New York).www.cuim.edu. http://www.Canary21press. com)

6. Ali M. The Principles and Practice of Integrative Medicine Volume VII: Heavy Metal Load and Toxicity. 2003. Washington, D.C. Capital University Press (in collaboration with Canary 21 Press, New York). http://www.cuim.edu. http://www.Canary21press.com)

7. Costerton JW, Stewart PS, Greenberg, EP. Bacterial Biofilms: A Common Cause of Persistent Infections,” Science, 284(5418):1318- 1322 (1999).

8. Costerton JW, Camper AK, Stewart PS, et al. The Problem: Not Just Bacteria – Bacterial Biofilms,” The Analyst, 6(3):18-25 (1999). Abstract 99-015

9. Costerton JW, Cook G, Lamont R. The Community Architecture of Biofilms: Dynamic Structure and Mechanisms,” H.N. Newman, and M. Wilson, et al. (eds) Dental Plaque Revisited: Oral Biofilms in Health and Disease, BioLine, Cardiff, UK Antony Rowe Ltd. 1999, pp. 1-13. Abstract 99-007.

10. Cook GS, Costerton JW, Lamont, RJ. Biofilm Formation by Porphyromonas gingivalis and Streptococcus gordonii,” J. Periodontal Research, 33:323-327 (1998). Abstract 98-024.

11. Suci PA, Vrany JD, Mittelman MW. Investigation of Interactions Between Antimicrobial Agents and Bacterial biofilms Using Attenuated Total Reflection Fourier Transform Infrared Spectroscopy,” Biomaterials, 19:327-339 (1998). Abstract 98-012.

12. Elkins, J.G., D.J. Hassett, P.S. Stewart, H.P. Schweizer, and T.R. MCDermott. Protective Role of Catalase in Pseudomonas aeruginosa Biofilm Resistance to Hydrogen Peroxide,” Appl. Environ. Microbiol., 65(10):4594-4600 (1999). Abstract 99-020

13. Gerlach, R., A.B. Cunningham, and F. Caccavo, Jr. Chromium Elimination with Microbially Reduced Iron: Redox-reactive Biobarriers,” In: Leeson, A.L. & Alleman, B.C., Eds.: Bioremediation of metals and inorganic compounds, Proceedings from the Fifth In Situ and On-Site Bioremediation Symposium, April 19-22, 1999 in San Diego, CA; Battelle Press: Columbus, Richland, pp 13-18. Abstract 99- 042

14. Glueck CJ, McMahan RE, Bouquet JE, Tnplett D, Gruppo R, Wang P. Heterozygosity for the Leiden mutation of the factor V gene, a common pathoetiol- ogy for osteonecrosis of the jaw, with thrombophilia augmented by exogenous estrogens. Lab Clin Med 1997; 130: 540-543. 17.

15. Liu X, Roe F, Jesaitis A, et al. Resistance of Biofilms to the Catalase Inhibitor 3-amino-1,2,4-triazole,” Biotechnol. Bioengrg., 59(2):156-162 (1998). Abstract 98-013

16. Krieg M, Haas R, Brauch H, et al. Up-regulation of hypoxia-inducible factors HIF-1 and HIF-2 under normoxic conditions in renal carcinoma cells by von Hippel-Lindau tumor suppressor gene loss of function. Oncogene. 2000;19:5435-5443.

17. Ramirez-Bergeron DL, Simon MC. Hypoxia-inducible factor and the development of stem cells of the cardiovascular system. Stem Cells. 2001;19:279-86.

18. Ali M. The Principles and Practice of Integrative Medicine Volume I: Nature’s Preoccupation With Complementarity and Contrariety. 2000. Washington, D.C. Capital University Press (in collaboration with Canary 21 Press, New York). http://www.cuim.edu & http://www.Canary21press.com)

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