- Email: [email protected]
Personalization of Multiple Sclerosis Treatments: Using the Chelation Therapy Approach
CASE REPORT
PERSONALIZATION
MULTIPLE SCLEROSIS TREATMENTS: USING CHELATION THERAPY APPROACH OF
THE
Sante Guido Zanella, MD1# and Paolo Roberti di Sarsina, MD1,2,3
Though Multiple Sclerosis (MS) sufferers are probably genetically predisposed, toxic metal poisoning (TMP) does seem an increasingly likely environmental trigger. The technique for measuring and clearing TMP was chelation therapy using ethylene-diamine-tetracetic acid (EDTA), which revealed aluminum accumulation in both cases. The first patient, initially benefiting from removing dental fillings that had leaked mercury, also showed gadolinium accumulation from scan contrast medium, and a genomic deficiency of glutathione transferase M1. Glutathione production was impaired and hence also liver detoxification functions. The personal protocol involved glutathione administration and deutrosulfazyme to enhance oxygenation and alleviate oxidative stress. As aluminum began to clear with EDTA infusion, the extracellular/ intracellular water ratio was carefully monitored, and carbohydrates limited. In the second case, aluminum poisoning
responded to EDTA chelation therapy with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), multivitamins, and glutathione administration, again followed by deutrosulfazyme, water ratio control, and dietary correction. The two personalized protocols presented here tend to confirm the hypothesis of TMP as an environmental or iatrogenic trigger for MS, especially when inadequate detoxification lies at the root. Cleansing by chelation therapy, properly understood, can be efficacious, especially bearing in mind the altered cellular water ratio.
INTRODUCTION Multiple Sclerosis (MS) is a neurodegenerative, de-myelinating autoimmune disease occurring in the context of central nervous system (CNS) inflammation. It typically affects young adults (20–50 years) with a slight female bias (2:1). At present some 2,000,000 people suffer from MS worldwide,1 and the incidence is steadily increasing. To date the etiology of MS is unknown. The best credited theories point more and more towards a genetic predisposition triggered by environmental factors.2 The importance of environmental factors seems borne out by the increased incidence of the disease when people change abode from where incidence is rare to where it is more common. One such environmental cause, toxic metal poisoning (TMP), has begun to gain more attention in the medical and scientific community. MS is characterized by degeneration of the axons and chronic inflammation with loss of myelin, which is then replaced by fibrotic tissue. There is also damage to the blood–
brain barrier which leaks fibrinogen and other inflammatory proteins into the brain, triggering onset and progression of the disease. T-lymphocytes, macrophages, and other immunological cells attack the brain and generate large amounts of reactive oxygen species (ROS) as oxidative stress sets in. In 85% of cases the disease initially manifests as relapsing– remitting MS, followed within 10 years by secondary onset in 50% of cases: secondary progressive is marked by progression of impairment between one relapse and the next. Ten percent of cases present as primary progressive without any remission stages. Diagnosis is based on neurological examination, magnetic resonance imaging (MRI) scan, visual evoked potentials, and examination of cerebrospinal fluid. Conventional therapies include steroids, immunomodulants (acetate glatiramer and interferon), immunosuppressant (mitoxandrone, azathioprine, methotrexate, and cyclophosphamide), and monoclonal antibodies (natalizumab and tysabri); these are rarely effective, so that over 70% of MS patients resort to alternative treatment to reduce pain, fatigue, and stress.3
1 Charity “Association for Person-Centered Medicine”, Bologna, Italy 2 High Council of Health, Ministry of Health, Italy 3 Observatory and Methods for Health, University of Milan, Bicocca, Italy
Toxic Metals and Other Triggers Toxic metals (aluminum, mercury, and lead) are pollutant substances that work their way into our organisms via foodstuffs, contaminated air and water, common hygiene products, drugs, dental amalgam, and vaccines.4 Chronic low-dose exposure is insidious since such metals often exert their toxic
# Correspondence address: Via Solferino, 45, 40124 Bologna, Italy e-mail: [email protected]
244
& 2013 Elsevier Inc. All rights reserved. ISSN 1550-8307/$36.00
Key words: MS, aluminum poisoning, personalized EDTA chelation (Explore 2013; 9:244-248 & 2013 Elsevier Inc. All rights reserved.)
EXPLORE July/August 2013, Vol. 9, No. 4 http://dx.doi.org/10.1016/j.explore.2013.04.003
effect at concentrations only marginally higher than physiological. Toxic metal poisoning may have a major role in the onset and development of MS, especially in subjects with reduced liver capacity for detoxification due to a glutathione deficit. Glutathione is the main antioxidant produced by our body and the main substrate for phases I and II of liver detoxification. It is a molecule formed of three aminoacids—glutamate, cysteine, and glycine. Production begins to fall off after 40 years, while some patients with genomic fragility5 produce inadequate quantities of it and are prone to intoxication earlier in life once the toxin load exceeds the clearance capacity. The toxic metals involved in neurodegenerative pathologies are principally aluminum and mercury, both universally recognized as neurotoxic substances that can trigger an autoimmune reaction against myelin.6 Aluminum easily crosses the blood–brain barrier by bonding to specific carriers; as it accumulates in the brain it causes neurodegenerative symptoms.7 In nature aluminum is normally found in bauxite rock and extracted by a long and complicated process. It intoxicates man through various sources: contaminated food and water, drugs containing aluminum salts (antacids, aspirin, vaccines, and anti-diarrheal), commonly used hygiene products (deodorants, talcum powder, and shaving foam), and cigarette smoke. Aluminum exposure has been correlated with many neurological diseases, including Alzheimer's, dementia, Parkinson's, and amyotrophic lateral sclerosis (ALS).8–10 Mercury is a potentially fatal poison for all living creatures. Contamination usually occurs by vapor released from dental amalgams, eating large-sized fish, and vaccines containing the preservative Thimerosal. The symptoms of mercury poisoning are varied and complex, often including trembling, irritability, depression, memory loss and impaired attention, delirium, psychosis, language and behavioral disorders, and immunosuppressant effects.11–16 Accumulation of iron in some parts of the brain may also be involved in the genesis and onset of MS symptoms.17,18 Iron is essential for neuron metabolism, including production of mitochondrial energy and myelination; however an excess of iron causes oxidative stress and neuro-degeneration. Undue iron accumulation has been detected in various chronic neurological diseases, including MS. Many MS sufferers also have high levels of gadolinium, the contrast medium used in MRI scans and meant to be expelled swiftly from the body after testing. In patients with renal impairment or candidates for liver transplantation, gadolinium may cause a serious adverse reaction known as Nephrogenic Systemic Fibrosis.19 Vitamin D deficiency has also been implicated in the development of MS and may increase the frequency of episodes in those predisposed. Chelation Therapy Evaluating the whole-body burden of toxic metals can be difficult. Currently the most widely utilized method is the chelation test that uses ethylene-diamine-tetracetic acid (EDTA) injected intravenously; the EDTA attracts toxic metals into its structure, inactivates them, and eliminates them in the urine.20 After drip administration a urine sample is taken to assess the
Personalization of Multiple Sclerosis Treatments
quantity of metals expelled. From the urinary levels one can diagnose if toxic metal poisoning is present. EDTA is also used therapeutically to reduce the body burden of toxic metals. We now report on the outcomes in two patients with MS who were found to have elevated levels of toxic metals and were treated with chelation as well as nutritional supplementation21 with a substantial improvement in their condition. Two Cases The first patient presented in 2006 with a diagnosis of Multiple Sclerosis. The disease had first appeared in 1997 when diplopia suddenly set in, followed by other symptoms including reduced skin sensitivity, upper limb motor impairment, loss of balance, and difficulty in walking. In 1998, a cerebral MRI scan and cerebrospinal fluid examination led to the diagnosis of Multiple Sclerosis. The patient was put on cortisone (Solumedrol 1 g per day for 8 days) and the symptoms temporarily regressed. November 1998 brought another cycle of steroids to correct instability and loss of coordination in lower limb movement. From April 1999 to 2001 the patient was treated with Azathioprine 100 mg at increasing doses. In 2003, the patient had four dental fillings containing mercury removed and his symptoms greatly improved. In 2005, following home renovation work entailing use of paints, the patient had a relapse of symptoms characterized by vertigo, impaired motor coordination of lower limbs, and loss of strength in the left arm. The symptoms worsened and walking was impaired (max. 10 m) with constant need for support. Micturition became disturbed and there was urinary incontinence. He returned to hospital and underwent another steroid cycle. A further MRI brain scan showed a marked increase in CNS lesions and many focal hyperintensity zones; when gadolinium was used as the contrast medium, two lesions were recorded in the right temporal periventricular zone and the left semioval center. At this time his MS developed into secondary progressive. Laboratory tests all proved normal except for a slight increase in bilirubin and thyroidstimulating hormone (TSH), as well as a dearth of vitamin D. The patient was also found to have genetic deficiency of the GSH transferase M1. This leads to an impairment in detoxification capacity since glutathione production is reduced. This may have been one explanation of why large quantities of toxic metals had accumulated in the tissues in this particular patient. In 2006 the patient was put on a therapy cycle of mitoxandrone; the symptoms got steadily worse. At this point the patient spontaneously opted to discontinue conventional treatment and begin chelation therapy. In September 2006 he had his first infusion of EDTA; the metals measured in the urine pre- and post-challenge test showed aluminum poisoning: 79 mcg/l (normal o 20) whereas mercury, cadmium, and lead were normal. After the third infusion the patient had a significant regression of symptoms and regained nearly all the use of his left hand. To reduce inflammation he received eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), as well as multivitamins/trace elements, to integrate the loss of electrolytes through the chelating agent. At the same time the patient began receiving glutathione stabilized with vitamin C (Ultrathione 500) in order to restore
EXPLORE July/August 2013, Vol. 9, No. 4 245
detoxification functions, and deutrosulfazyme (Cellfood drops) to enhance tissue oxygenation and reduce oxidative stress. Cellfood is a nutritional supplement containing trace elements and minerals combined with 34 enzymes and 18 aminoacids all suspended in a solution of deuterium sulfate, which may help protect glutathione and DNA from oxidation.22 After every five infusions, his urine was checked for toxic metals and the state of elimination thereof. By the fifth infusion the aluminum value had apparently normalized (15 mcg/l); however in our experience is frequent at this stage (aluminum normalization) but elimination of metal deposits in the CNS respond later in the process of chelation. This is thought to occur by diffusion after the peripheral tissues are cleansed, since EDTA cannot directly cross the blood–brain barrier. As we have seen in other cases, on the next testing (after the 10th treatment), the urinary aluminum value rose again (43). We feel that a critical component of this stage of the process involves administering buffer systems to correct the extracellular/intracellular water ratio, which in turn supports the diffusion of toxic metals out of the CNS. These parameters were measured by the BioTekna BIA ACC apparatus, a noninvasive device that measures the intracellular and extracellular bioimpedance.23 This combination of removing metals actively via chelation and supporting the body's ability to remove these naturally by correcting the function of the natural buffering system is what we believe underlies this patient's recovery.
By the 40th infusion, the aluminum value was again extremely high (177 mcg/l), which we believe reflected the process of removal of toxic metals from the CNS. At this point, and then subsequently after undergoing another MRI scan with gadolinium the patient experienced a worsening of his MS symptoms. The next post-EDTA infusion evaluation showed extremely high gadolinium levels at 61 mcg/g creat. (normal o 0.019 mcg/g creat.) (Figure 1). Later infusions brought the gadolinium value down to almost the normal range (Figure 2) and the patient's symptoms improved again (Tables 1 and 2). The second patient had her first onset of MS in 1996 in the form of left-hand paresthesia after being vaccinated against hepatitis B. In our experience, MS often manifests after vaccination or booster shots since vaccines may contain metals as emulsifiers or adjuvants that depress the immune system. In the past many vaccines contained Thimerosal, a potential neurotoxin. Our patient was immediately put on a cycle of cortisone and the symptoms temporarily receded. Three years on from this first episode she had a relapse, the symptoms now involving the right leg with pronounced motor impairment. She was put on interferon-β (Rebif) therapy administered subcutaneously three times weekly; this
Figure 1. Urine toxic metals after MRI. MRI, magnetic resonance imaging. (Color version of figure is available online.)
Figure 2. Urine toxic metals. (Color version of figure is available online.)
246 EXPLORE July/August 2013, Vol. 9, No. 4
Personalization of Multiple Sclerosis Treatments
Toxic Metal
Result
Reference
Aluminum (first sample), mcg/l Aluminum (second sample), mcg/l Cadmium (first sample), mcg/g creat. Cadmium (second sample), mcg/g creat. Mercury (first sample), mcg/g creat. Mercury (second sample), mcg/g creat. Lead (first sample), mcg/g creat. Lead (second sample), mcg/g creat.
1 79 0.24 0.98 4 12 2.4 20.4
o20 o20 o5 o5 o35 o35 o150 o150
EDTA, ethylene-diamine-tetracetic acid.
treatment was suspended when debilitating side effects set in. Through physiotherapy this patient managed to improve slightly but was still significantly disabled. The laboratory tests were broadly within range except for an inverse zinc/ copper ratio and vitamin B12 at the low end of the range. The chelation test (Table 3) revealed aluminum poisoning at 117 mcg/l (normal value: o20 mcg/l). The patient began taking EPA/DHA to reduce production of inflammatory cytokines, multivitamins to compensate the loss of electrolytes, and glutathione stabilized with vitamin C to restore proper liver detoxification. By the fifth infusion check, she still had an extremely high aluminum level of 123.2 mcg/l. After each treatment from this point she began to progressively regain her balance and her general state improved to the point of resuming activities she had had to abandon. By the tenth infusion the aluminum level had soared to the value of 157.6 mcg/l while symptoms continued slowly but steadily to improve. We then added deutrosulfazyme (Cellfood drops) to improve tissue oxygenation and reduce excess free radicals, and a buffer system (Melcalin Base) was added to correct the extracellular/intracellular water ratio. At the 15th infusion the aluminum count dropped but then it peaked again by the 20th (162 mcg/l), we believe here again indicating that aluminum was leaving the CNS by diffusion. By drip 25 the aluminum was down to 50.6 mcg/l and it then normalized after 40 infusions. BIA ACC (BioTekna) analysis revealed the total body water to be 45%, below the normal range and evidence of tissue dehydration, while the extracellular water Table 2. Aluminum Dosage During Chelation Therapy Aluminium
jan-09
jul-08
oct-08
june-08
june- 08
may-08
may-08
jan-08
mar-08
jul-07
normal value < 20
nov-07
feb-07
Toxic Metal
Result
Reference
Aluminum (first sample), mcg/l Mercury (first sample), mcg/g creat. Lead (first sample), mcg/g creat.
117 9,8 0
o20 o35 o150
Table 4. Aluminum Dosage During Chelation Therapy Aluminium
180 [mcg/l] 160 140 120 100 80 60 40 20 0
normal value < 20
was high (53%) denoting inflammation. Correction of dietary habits and administration of an acid–alkali buffer system brought these values back to normal and slightly reduced the extracellular water (42%) suggesting a reduced state of inflammation (Tables 3 and 4). CONCLUSIONS The two case histories presented here demonstrate the potential benefit in MS of a treatment approach that combines the removal of toxic heavy metals with a balancing of the body's natural buffering and anti-inflammatory systems. They also demonstrate the dangers of iatrogenic factors that can compound the disease—gadolinium, for example, used as a contrast medium in scans, and certain mercury-containing vaccines—which can be particularly dangerous when inadequate detoxification systems co-exist with Multiple Sclerosis. It is important for clinicians to note that removing the toxic substances by EDTA chelation therapy may initially bring some alarming results until one understands the various phases of the cleansing process (first the periphery, later the CNS). A personalized approach to the detoxification process, incorporating an awareness of buffering systems as well as physiological contributors to systemic inflammation is critical in the successful management of MS. REFERENCES
200 [mcg/l] 180 160 140 120 100 80 60 40 20 0 sep 2006
Table 3. Toxic Metals After First Chelation
jul 2009 nov09 jan 10 apr10 set10 nov10 feb11 dec11
Table 1. Urinary Dosage of Toxic Metals After First Infusion of EDTA Chelation Therapy
Personalization of Multiple Sclerosis Treatments
1. Risco J, Maldonado H, Luna L, et al. Latitudinal prevalence gradient of Multiple Sclerosis in Latin America. Mult Scler. 2011;17(9):1055–1059. 2. Exley C, Mamutse G, Korchazhkina O, et al. Elevated urine excretion of aluminium and iron in Multiple Sclerosis. Mult Scler. 2006;12:533–540. 3. Horowitz S. CAM interventions for Multiple Sclerosis. Alternative and complementary therapies. Mary Ann Liebert, Inc. 2011;17:156–161. 4. Marrie RA. Environmental risk factors in Multiple Sclerosis etiology. Lancet Neurol. 2004;3(12):709–718.
EXPLORE July/August 2013, Vol. 9, No. 4 247
5. Bolt HM, Their R. Relevance of the deletion polymorphisms of the glutathione S transferases GSTT1 and GSTM1 in pharmacology and toxicology. Curr Drug Metab. 2006;7:613–628. 6. Clarkson TW. Metal toxicity in the central nervous system. Environ Health Perspect. 1987;75:59–64. 7. Kawahara M, Negishi MK. Aluminium and human health: its intake, bioavailability and neurotoxicity. Biomed Res Trace Elem. 2007;18:111–120. 8. Exley C, Begum A, Woolley MB, Bloor RN. Aluminium in Tobacco and Cannabis and Smoking Related Disease. Am J Med. 2006;119(3):276.e9–e11. 9. Flaten TP. Aluminium as a risk factor in Alzheimer's diseases with emphasis on drinking water. Brain Res Bulletin. 2001;55 (2):187–196. 10. Johnson FO, Atchison WD. The role of environmental mercury, lead and pesticide exposure in development of amyotrophic lateral sclerosis. Neurotoxicology. 2009;30:761–765. 11. American Academy of Pediatrics. Thimerosal in vaccines. An interim report to clinicians, American Academy of Pediatric Policy Statement 1999;104(3):570–574. 12. Blaxill MF, Redwood L, Bernard S. Thimerosal and autism? A plausible hypothesis that should not be dismissed Med Hypoth. 2004;62:788–794. 13. Ozuah PO. Mercury poisoning. Curr Probl Pediatr. 2000;30: 91–99. 14. Corsello S, Fulgenzi A, Vietti D, Ferrero ME. The usefulness of chelation therapy for the remission of symptoms caused by
248 EXPLORE July/August 2013, Vol. 9, No. 4
15.
16.
17.
18.
19. 20. 21. 22.
23.
previous treatment with mercury containing pharmaceuticals: a case report. Case J. 2009;2:199. Patrick L. Mercury toxicity and antioxidants. Role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002;7:456–471. Siblerud R, Kienholz E. Evidence that mercury from silver dental fillings may be an etiological factor in Multiple Sclerosis. Sci Total Environ. 1994;142:191–205. Sfagos C, Markis CA, Chaidos A, et al. Serum ferritin, transferrin and soluble transferrin receptor levels in Multiple Sclerosis patients. Mult Scler. 2005;11:272–275. Sing AV, Zamboni P. Anomalous venous blood flow and iron deposition in multiple sclerosis. J Cereb Blood Flow Metab. 2009;29:1867–1878. Tomsen HS. Nephrogenic systemic fibrosis: a serious late adverse reaction to gadodiamide. Eur Radiol. 2006;16(12):2619–2621. Chappel T. Application of EDTA chelation therapy. Altern Med Rev. 1997;2(6):426–432. De Caterina R. n-3 Fatty acids in cardiovascular disease. N Engl J Med. 2011;364:2439–2450. Benedetti S, Palma F, Canestrari F. The antioxidant protection of Cellfood against oxidative damage in vitro. Food Chem Toxicol. 2011;49(9):2292–2298. Baumgartner RN, Chumlea WC, Roche AF. Estimation of body composition from bioelectric impedance of body segments. Am J Clinic Nutr. 1989;50:221–226.
Personalization of Multiple Sclerosis Treatments
PERSONALIZATION
MULTIPLE SCLEROSIS TREATMENTS: USING CHELATION THERAPY APPROACH OF
THE
Sante Guido Zanella, MD1# and Paolo Roberti di Sarsina, MD1,2,3
Though Multiple Sclerosis (MS) sufferers are probably genetically predisposed, toxic metal poisoning (TMP) does seem an increasingly likely environmental trigger. The technique for measuring and clearing TMP was chelation therapy using ethylene-diamine-tetracetic acid (EDTA), which revealed aluminum accumulation in both cases. The first patient, initially benefiting from removing dental fillings that had leaked mercury, also showed gadolinium accumulation from scan contrast medium, and a genomic deficiency of glutathione transferase M1. Glutathione production was impaired and hence also liver detoxification functions. The personal protocol involved glutathione administration and deutrosulfazyme to enhance oxygenation and alleviate oxidative stress. As aluminum began to clear with EDTA infusion, the extracellular/ intracellular water ratio was carefully monitored, and carbohydrates limited. In the second case, aluminum poisoning
responded to EDTA chelation therapy with eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), multivitamins, and glutathione administration, again followed by deutrosulfazyme, water ratio control, and dietary correction. The two personalized protocols presented here tend to confirm the hypothesis of TMP as an environmental or iatrogenic trigger for MS, especially when inadequate detoxification lies at the root. Cleansing by chelation therapy, properly understood, can be efficacious, especially bearing in mind the altered cellular water ratio.
INTRODUCTION Multiple Sclerosis (MS) is a neurodegenerative, de-myelinating autoimmune disease occurring in the context of central nervous system (CNS) inflammation. It typically affects young adults (20–50 years) with a slight female bias (2:1). At present some 2,000,000 people suffer from MS worldwide,1 and the incidence is steadily increasing. To date the etiology of MS is unknown. The best credited theories point more and more towards a genetic predisposition triggered by environmental factors.2 The importance of environmental factors seems borne out by the increased incidence of the disease when people change abode from where incidence is rare to where it is more common. One such environmental cause, toxic metal poisoning (TMP), has begun to gain more attention in the medical and scientific community. MS is characterized by degeneration of the axons and chronic inflammation with loss of myelin, which is then replaced by fibrotic tissue. There is also damage to the blood–
brain barrier which leaks fibrinogen and other inflammatory proteins into the brain, triggering onset and progression of the disease. T-lymphocytes, macrophages, and other immunological cells attack the brain and generate large amounts of reactive oxygen species (ROS) as oxidative stress sets in. In 85% of cases the disease initially manifests as relapsing– remitting MS, followed within 10 years by secondary onset in 50% of cases: secondary progressive is marked by progression of impairment between one relapse and the next. Ten percent of cases present as primary progressive without any remission stages. Diagnosis is based on neurological examination, magnetic resonance imaging (MRI) scan, visual evoked potentials, and examination of cerebrospinal fluid. Conventional therapies include steroids, immunomodulants (acetate glatiramer and interferon), immunosuppressant (mitoxandrone, azathioprine, methotrexate, and cyclophosphamide), and monoclonal antibodies (natalizumab and tysabri); these are rarely effective, so that over 70% of MS patients resort to alternative treatment to reduce pain, fatigue, and stress.3
1 Charity “Association for Person-Centered Medicine”, Bologna, Italy 2 High Council of Health, Ministry of Health, Italy 3 Observatory and Methods for Health, University of Milan, Bicocca, Italy
Toxic Metals and Other Triggers Toxic metals (aluminum, mercury, and lead) are pollutant substances that work their way into our organisms via foodstuffs, contaminated air and water, common hygiene products, drugs, dental amalgam, and vaccines.4 Chronic low-dose exposure is insidious since such metals often exert their toxic
# Correspondence address: Via Solferino, 45, 40124 Bologna, Italy e-mail: [email protected]
244
& 2013 Elsevier Inc. All rights reserved. ISSN 1550-8307/$36.00
Key words: MS, aluminum poisoning, personalized EDTA chelation (Explore 2013; 9:244-248 & 2013 Elsevier Inc. All rights reserved.)
EXPLORE July/August 2013, Vol. 9, No. 4 http://dx.doi.org/10.1016/j.explore.2013.04.003
effect at concentrations only marginally higher than physiological. Toxic metal poisoning may have a major role in the onset and development of MS, especially in subjects with reduced liver capacity for detoxification due to a glutathione deficit. Glutathione is the main antioxidant produced by our body and the main substrate for phases I and II of liver detoxification. It is a molecule formed of three aminoacids—glutamate, cysteine, and glycine. Production begins to fall off after 40 years, while some patients with genomic fragility5 produce inadequate quantities of it and are prone to intoxication earlier in life once the toxin load exceeds the clearance capacity. The toxic metals involved in neurodegenerative pathologies are principally aluminum and mercury, both universally recognized as neurotoxic substances that can trigger an autoimmune reaction against myelin.6 Aluminum easily crosses the blood–brain barrier by bonding to specific carriers; as it accumulates in the brain it causes neurodegenerative symptoms.7 In nature aluminum is normally found in bauxite rock and extracted by a long and complicated process. It intoxicates man through various sources: contaminated food and water, drugs containing aluminum salts (antacids, aspirin, vaccines, and anti-diarrheal), commonly used hygiene products (deodorants, talcum powder, and shaving foam), and cigarette smoke. Aluminum exposure has been correlated with many neurological diseases, including Alzheimer's, dementia, Parkinson's, and amyotrophic lateral sclerosis (ALS).8–10 Mercury is a potentially fatal poison for all living creatures. Contamination usually occurs by vapor released from dental amalgams, eating large-sized fish, and vaccines containing the preservative Thimerosal. The symptoms of mercury poisoning are varied and complex, often including trembling, irritability, depression, memory loss and impaired attention, delirium, psychosis, language and behavioral disorders, and immunosuppressant effects.11–16 Accumulation of iron in some parts of the brain may also be involved in the genesis and onset of MS symptoms.17,18 Iron is essential for neuron metabolism, including production of mitochondrial energy and myelination; however an excess of iron causes oxidative stress and neuro-degeneration. Undue iron accumulation has been detected in various chronic neurological diseases, including MS. Many MS sufferers also have high levels of gadolinium, the contrast medium used in MRI scans and meant to be expelled swiftly from the body after testing. In patients with renal impairment or candidates for liver transplantation, gadolinium may cause a serious adverse reaction known as Nephrogenic Systemic Fibrosis.19 Vitamin D deficiency has also been implicated in the development of MS and may increase the frequency of episodes in those predisposed. Chelation Therapy Evaluating the whole-body burden of toxic metals can be difficult. Currently the most widely utilized method is the chelation test that uses ethylene-diamine-tetracetic acid (EDTA) injected intravenously; the EDTA attracts toxic metals into its structure, inactivates them, and eliminates them in the urine.20 After drip administration a urine sample is taken to assess the
Personalization of Multiple Sclerosis Treatments
quantity of metals expelled. From the urinary levels one can diagnose if toxic metal poisoning is present. EDTA is also used therapeutically to reduce the body burden of toxic metals. We now report on the outcomes in two patients with MS who were found to have elevated levels of toxic metals and were treated with chelation as well as nutritional supplementation21 with a substantial improvement in their condition. Two Cases The first patient presented in 2006 with a diagnosis of Multiple Sclerosis. The disease had first appeared in 1997 when diplopia suddenly set in, followed by other symptoms including reduced skin sensitivity, upper limb motor impairment, loss of balance, and difficulty in walking. In 1998, a cerebral MRI scan and cerebrospinal fluid examination led to the diagnosis of Multiple Sclerosis. The patient was put on cortisone (Solumedrol 1 g per day for 8 days) and the symptoms temporarily regressed. November 1998 brought another cycle of steroids to correct instability and loss of coordination in lower limb movement. From April 1999 to 2001 the patient was treated with Azathioprine 100 mg at increasing doses. In 2003, the patient had four dental fillings containing mercury removed and his symptoms greatly improved. In 2005, following home renovation work entailing use of paints, the patient had a relapse of symptoms characterized by vertigo, impaired motor coordination of lower limbs, and loss of strength in the left arm. The symptoms worsened and walking was impaired (max. 10 m) with constant need for support. Micturition became disturbed and there was urinary incontinence. He returned to hospital and underwent another steroid cycle. A further MRI brain scan showed a marked increase in CNS lesions and many focal hyperintensity zones; when gadolinium was used as the contrast medium, two lesions were recorded in the right temporal periventricular zone and the left semioval center. At this time his MS developed into secondary progressive. Laboratory tests all proved normal except for a slight increase in bilirubin and thyroidstimulating hormone (TSH), as well as a dearth of vitamin D. The patient was also found to have genetic deficiency of the GSH transferase M1. This leads to an impairment in detoxification capacity since glutathione production is reduced. This may have been one explanation of why large quantities of toxic metals had accumulated in the tissues in this particular patient. In 2006 the patient was put on a therapy cycle of mitoxandrone; the symptoms got steadily worse. At this point the patient spontaneously opted to discontinue conventional treatment and begin chelation therapy. In September 2006 he had his first infusion of EDTA; the metals measured in the urine pre- and post-challenge test showed aluminum poisoning: 79 mcg/l (normal o 20) whereas mercury, cadmium, and lead were normal. After the third infusion the patient had a significant regression of symptoms and regained nearly all the use of his left hand. To reduce inflammation he received eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA), as well as multivitamins/trace elements, to integrate the loss of electrolytes through the chelating agent. At the same time the patient began receiving glutathione stabilized with vitamin C (Ultrathione 500) in order to restore
EXPLORE July/August 2013, Vol. 9, No. 4 245
detoxification functions, and deutrosulfazyme (Cellfood drops) to enhance tissue oxygenation and reduce oxidative stress. Cellfood is a nutritional supplement containing trace elements and minerals combined with 34 enzymes and 18 aminoacids all suspended in a solution of deuterium sulfate, which may help protect glutathione and DNA from oxidation.22 After every five infusions, his urine was checked for toxic metals and the state of elimination thereof. By the fifth infusion the aluminum value had apparently normalized (15 mcg/l); however in our experience is frequent at this stage (aluminum normalization) but elimination of metal deposits in the CNS respond later in the process of chelation. This is thought to occur by diffusion after the peripheral tissues are cleansed, since EDTA cannot directly cross the blood–brain barrier. As we have seen in other cases, on the next testing (after the 10th treatment), the urinary aluminum value rose again (43). We feel that a critical component of this stage of the process involves administering buffer systems to correct the extracellular/intracellular water ratio, which in turn supports the diffusion of toxic metals out of the CNS. These parameters were measured by the BioTekna BIA ACC apparatus, a noninvasive device that measures the intracellular and extracellular bioimpedance.23 This combination of removing metals actively via chelation and supporting the body's ability to remove these naturally by correcting the function of the natural buffering system is what we believe underlies this patient's recovery.
By the 40th infusion, the aluminum value was again extremely high (177 mcg/l), which we believe reflected the process of removal of toxic metals from the CNS. At this point, and then subsequently after undergoing another MRI scan with gadolinium the patient experienced a worsening of his MS symptoms. The next post-EDTA infusion evaluation showed extremely high gadolinium levels at 61 mcg/g creat. (normal o 0.019 mcg/g creat.) (Figure 1). Later infusions brought the gadolinium value down to almost the normal range (Figure 2) and the patient's symptoms improved again (Tables 1 and 2). The second patient had her first onset of MS in 1996 in the form of left-hand paresthesia after being vaccinated against hepatitis B. In our experience, MS often manifests after vaccination or booster shots since vaccines may contain metals as emulsifiers or adjuvants that depress the immune system. In the past many vaccines contained Thimerosal, a potential neurotoxin. Our patient was immediately put on a cycle of cortisone and the symptoms temporarily receded. Three years on from this first episode she had a relapse, the symptoms now involving the right leg with pronounced motor impairment. She was put on interferon-β (Rebif) therapy administered subcutaneously three times weekly; this
Figure 1. Urine toxic metals after MRI. MRI, magnetic resonance imaging. (Color version of figure is available online.)
Figure 2. Urine toxic metals. (Color version of figure is available online.)
246 EXPLORE July/August 2013, Vol. 9, No. 4
Personalization of Multiple Sclerosis Treatments
Toxic Metal
Result
Reference
Aluminum (first sample), mcg/l Aluminum (second sample), mcg/l Cadmium (first sample), mcg/g creat. Cadmium (second sample), mcg/g creat. Mercury (first sample), mcg/g creat. Mercury (second sample), mcg/g creat. Lead (first sample), mcg/g creat. Lead (second sample), mcg/g creat.
1 79 0.24 0.98 4 12 2.4 20.4
o20 o20 o5 o5 o35 o35 o150 o150
EDTA, ethylene-diamine-tetracetic acid.
treatment was suspended when debilitating side effects set in. Through physiotherapy this patient managed to improve slightly but was still significantly disabled. The laboratory tests were broadly within range except for an inverse zinc/ copper ratio and vitamin B12 at the low end of the range. The chelation test (Table 3) revealed aluminum poisoning at 117 mcg/l (normal value: o20 mcg/l). The patient began taking EPA/DHA to reduce production of inflammatory cytokines, multivitamins to compensate the loss of electrolytes, and glutathione stabilized with vitamin C to restore proper liver detoxification. By the fifth infusion check, she still had an extremely high aluminum level of 123.2 mcg/l. After each treatment from this point she began to progressively regain her balance and her general state improved to the point of resuming activities she had had to abandon. By the tenth infusion the aluminum level had soared to the value of 157.6 mcg/l while symptoms continued slowly but steadily to improve. We then added deutrosulfazyme (Cellfood drops) to improve tissue oxygenation and reduce excess free radicals, and a buffer system (Melcalin Base) was added to correct the extracellular/intracellular water ratio. At the 15th infusion the aluminum count dropped but then it peaked again by the 20th (162 mcg/l), we believe here again indicating that aluminum was leaving the CNS by diffusion. By drip 25 the aluminum was down to 50.6 mcg/l and it then normalized after 40 infusions. BIA ACC (BioTekna) analysis revealed the total body water to be 45%, below the normal range and evidence of tissue dehydration, while the extracellular water Table 2. Aluminum Dosage During Chelation Therapy Aluminium
jan-09
jul-08
oct-08
june-08
june- 08
may-08
may-08
jan-08
mar-08
jul-07
normal value < 20
nov-07
feb-07
Toxic Metal
Result
Reference
Aluminum (first sample), mcg/l Mercury (first sample), mcg/g creat. Lead (first sample), mcg/g creat.
117 9,8 0
o20 o35 o150
Table 4. Aluminum Dosage During Chelation Therapy Aluminium
180 [mcg/l] 160 140 120 100 80 60 40 20 0
normal value < 20
was high (53%) denoting inflammation. Correction of dietary habits and administration of an acid–alkali buffer system brought these values back to normal and slightly reduced the extracellular water (42%) suggesting a reduced state of inflammation (Tables 3 and 4). CONCLUSIONS The two case histories presented here demonstrate the potential benefit in MS of a treatment approach that combines the removal of toxic heavy metals with a balancing of the body's natural buffering and anti-inflammatory systems. They also demonstrate the dangers of iatrogenic factors that can compound the disease—gadolinium, for example, used as a contrast medium in scans, and certain mercury-containing vaccines—which can be particularly dangerous when inadequate detoxification systems co-exist with Multiple Sclerosis. It is important for clinicians to note that removing the toxic substances by EDTA chelation therapy may initially bring some alarming results until one understands the various phases of the cleansing process (first the periphery, later the CNS). A personalized approach to the detoxification process, incorporating an awareness of buffering systems as well as physiological contributors to systemic inflammation is critical in the successful management of MS. REFERENCES
200 [mcg/l] 180 160 140 120 100 80 60 40 20 0 sep 2006
Table 3. Toxic Metals After First Chelation
jul 2009 nov09 jan 10 apr10 set10 nov10 feb11 dec11
Table 1. Urinary Dosage of Toxic Metals After First Infusion of EDTA Chelation Therapy
Personalization of Multiple Sclerosis Treatments
1. Risco J, Maldonado H, Luna L, et al. Latitudinal prevalence gradient of Multiple Sclerosis in Latin America. Mult Scler. 2011;17(9):1055–1059. 2. Exley C, Mamutse G, Korchazhkina O, et al. Elevated urine excretion of aluminium and iron in Multiple Sclerosis. Mult Scler. 2006;12:533–540. 3. Horowitz S. CAM interventions for Multiple Sclerosis. Alternative and complementary therapies. Mary Ann Liebert, Inc. 2011;17:156–161. 4. Marrie RA. Environmental risk factors in Multiple Sclerosis etiology. Lancet Neurol. 2004;3(12):709–718.
EXPLORE July/August 2013, Vol. 9, No. 4 247
5. Bolt HM, Their R. Relevance of the deletion polymorphisms of the glutathione S transferases GSTT1 and GSTM1 in pharmacology and toxicology. Curr Drug Metab. 2006;7:613–628. 6. Clarkson TW. Metal toxicity in the central nervous system. Environ Health Perspect. 1987;75:59–64. 7. Kawahara M, Negishi MK. Aluminium and human health: its intake, bioavailability and neurotoxicity. Biomed Res Trace Elem. 2007;18:111–120. 8. Exley C, Begum A, Woolley MB, Bloor RN. Aluminium in Tobacco and Cannabis and Smoking Related Disease. Am J Med. 2006;119(3):276.e9–e11. 9. Flaten TP. Aluminium as a risk factor in Alzheimer's diseases with emphasis on drinking water. Brain Res Bulletin. 2001;55 (2):187–196. 10. Johnson FO, Atchison WD. The role of environmental mercury, lead and pesticide exposure in development of amyotrophic lateral sclerosis. Neurotoxicology. 2009;30:761–765. 11. American Academy of Pediatrics. Thimerosal in vaccines. An interim report to clinicians, American Academy of Pediatric Policy Statement 1999;104(3):570–574. 12. Blaxill MF, Redwood L, Bernard S. Thimerosal and autism? A plausible hypothesis that should not be dismissed Med Hypoth. 2004;62:788–794. 13. Ozuah PO. Mercury poisoning. Curr Probl Pediatr. 2000;30: 91–99. 14. Corsello S, Fulgenzi A, Vietti D, Ferrero ME. The usefulness of chelation therapy for the remission of symptoms caused by
248 EXPLORE July/August 2013, Vol. 9, No. 4
15.
16.
17.
18.
19. 20. 21. 22.
23.
previous treatment with mercury containing pharmaceuticals: a case report. Case J. 2009;2:199. Patrick L. Mercury toxicity and antioxidants. Role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002;7:456–471. Siblerud R, Kienholz E. Evidence that mercury from silver dental fillings may be an etiological factor in Multiple Sclerosis. Sci Total Environ. 1994;142:191–205. Sfagos C, Markis CA, Chaidos A, et al. Serum ferritin, transferrin and soluble transferrin receptor levels in Multiple Sclerosis patients. Mult Scler. 2005;11:272–275. Sing AV, Zamboni P. Anomalous venous blood flow and iron deposition in multiple sclerosis. J Cereb Blood Flow Metab. 2009;29:1867–1878. Tomsen HS. Nephrogenic systemic fibrosis: a serious late adverse reaction to gadodiamide. Eur Radiol. 2006;16(12):2619–2621. Chappel T. Application of EDTA chelation therapy. Altern Med Rev. 1997;2(6):426–432. De Caterina R. n-3 Fatty acids in cardiovascular disease. N Engl J Med. 2011;364:2439–2450. Benedetti S, Palma F, Canestrari F. The antioxidant protection of Cellfood against oxidative damage in vitro. Food Chem Toxicol. 2011;49(9):2292–2298. Baumgartner RN, Chumlea WC, Roche AF. Estimation of body composition from bioelectric impedance of body segments. Am J Clinic Nutr. 1989;50:221–226.
Personalization of Multiple Sclerosis Treatments