Biomonitoring of Metal Intoxication. Basis for successful Detoxification and Nutritional Replacement Therapy. Trace Minerals Intern.

Transcription

1 Biomonitoring of Metal Intoxication Basis for successful Detoxification and Nutritional Replacement Therapy 1

2 What we need to know about metal testing Each test reflects a specific biochemical pathway No test tells all No test is the best 2

3 I. Blood Mineral Analysis Blood is transport medium for nutrient and toxic metals to and from cells Blood values reflect mineral concentration in circulating blood stream Note - use metal-free vacutainers 3

4 1. Intake and Circulation Every element has its own unique distribution in body fluids, tissues and organs Concentrations fluctuate throughout the day in body fluids, and over longer periods in solid body tissues Acute exposures have different effects than exposures over longer periods 4

5 Specifics of Blood Minerals Analysis Allows detection of immediate and acute Toxic Metal exposure within maximal 72hrs after exposure. Thereafter, metals have been deposited in target storage tissue or have been elimated 5

6 What type of blood for mineral analysis? Whole blood reflects extraand intracellular levels 95% of cadmium is bound to erythrocytes- thus whole blood analysis recommended For heavy metal evaluation use special, metal-free tubes 6

7 Sikorski R, Paszkowski T, Slawinski P, Szkoda J, Zmudzki J, Skawinski S. The intrapartum content of toxic metals in maternal blood and umbilical cord blood.pmid: [PubMed - indexed for MEDLINE] Cadmium and mercury levels measured on both sides of placenta did not differ significantly while lead levels in maternal blood were significantly higher than its cord blood values. In all three metals studied, the concentrations in maternal blood strongly correlated with the corresponding cord blood values. A significant, positive correlation was established between the parity of the examined women and the umbilical cord blood contents of lead and mercury. The obtained results support the opinion that human placenta does not form an effective barrier to toxic metal intake by the fetus. 7

8 Cd und Hg in Blut und Urin deutscher Kinder Quelle: Schulz,Becker. Bundesumweltamt Parameter Deutschland West Ost N GM N GM N GM Cadmium in blood (µg/l) *** Cadmium in urine (µg/l) *** Mercury in blood (µg/l) *** Mercury in urine (µg/l) *** Mercury in urine (µg/g Crea) *** N= Testpersonen GM = Geometric mean *** statistisch signifikanter Unterschied (P 0.001) 8

9 Blood evaluation Rumanian school children 95percentile 3µg/l CDC Ref.Range <1µg/l 9

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11 II: Urine Metal Analysis (UMA) Assessment of renal clearance of essential and toxic elements Monitors chelation efficacy (not all chelated patients are able (genetically or otherwise) to detoxify Allows physician to individualize chelation therapy Provides proof of treatment progress 11

12 TMI Logic for Reference Ranges TMI Baseline urine evaluation of 120healthy people plus <300 patients with no signs of metal toxicity Present evaluation in progreess at TMI: typical mean value for each chelating agent 12

13 Sampling before Provocation Collect 10ml of first morning urine. Best to urinate directly in cup or tube to prevent contamination 13

14 Post Urine collection Patient must empty bladder before start of treatment After treatment has started, collect for 2 to 6 hr depending on chelating agent used Fluid intake (2-3 cups) should be constant Food intake: best to stay fasting Do not take supplements or algae during chelation 14

15 Lead and Arsenic in Algae products 15

16 Evaluation of mean Urine creatinine (g/l) in pre and post urines of children and adults children <12 adults # of tested persons: Baseline urines: N = 977 adults N = 355 children pre post Post urines: N = 4018 adults N = 101 children 16

17 Limitations of 24-hr urine collection Main problem: Patient compliance Factors influencing urine excretion results Food and drink (coffee, tea) Smoking or smoke exposure Medication Cosmetics 17

18 III. Hair Mineral Analysis Internationally researched at recognized universities and institutions Largely Misunderstood Often Misrepresented Instruments do not know how to differentiate between specimen. 18

19 Hair sample preparation Key to reliable results 19

20 Hair is Body Tissue Hair follicle receives nutrients and toxins from circulating blood What has been stored will remain locked in this inert tissue and thus hair can be stored indefinitely. In fact, hair has been used as an ideal forensic tissue for decades 20

21 Hair mineral analysis provides a record of past exposure or nutritional inadequacies reflecting the specific growth period (i.e. Hair growth is 1mm/day or 3cm/months. If taken close to scalp now, we evaluate the mineral exposure of last month) 21

22 % of patients showing high values Al -Aluminum MTM Study N=10000 random collection 80.0% 70.0% 60.0% Germany United States Brazil 50.0% 40.0% 30.0% 20.0% 10.0% Brazil 0.0% United States and up Germany 22

23 mcg/kg Mercury Distribution in Body Tissues 4,5 4 3,5 3 2,5 2 1,5 1 0,5 0 Mercury Bone Brain Skin Hair Muscle Heart Colon Liver Kidneys Source: Thomas L. Labor & Diagnose, Med.Verlag pg

24 mcg/kg Physiological Distribution of Lead in Human Tissue Lead Bone Brain Skin Hair Muscle Heart Colon Liver Kidneys Source: Thomas L., Labor & Diagnose, Med.Verlag Marburg 24

25 Average Level (ppm) Pb - Lead - Chumbo - Blei Germany United States Brazil Brazil United States Germany and up 25

26 Case of Oliver Sch. 26

27 What about problem patients? Consideration: Reduce toxic exposure (lifestyle changes etc) Evaluate nutritional status (and supplement accordingly) Evaluate toxic status (hair analysis) Change chelating agent or combine chelating agents 27

28 Enzyme systems needed for detoxification Glutathione S-TransferaseM1 (GSTM1) Glutathione S-Transferase T1 (GSTT1) Glutathione S-Transferase P1 (GSTP1) Superoxide dismutase 2 (SODs) Manganese and/or Copper-dependant for functioning 28

29 GSTM1 deletion genotype- common in Asians Groups such as Pacific Islanders and Malaysians have a reported frequency of no enzyme activity of 62%-100%. Other Asian populations have high-reported frequencies of the deletion genotype ranging from 48%-50% for Japanese and 35%-63% for Chinese. A population-based study conducted among Chinese reported a frequency of 51% for the GSTM1 deletion genotype. Two Korean case-control studies found frequencies of 53% and 56% for the GSTM1 deletion genotype 29

30 Genetic testing once in a lifetime 30

31 Why testing? Individuals with homozygous deletions of either the GSTM1 or the GSTT1 locus have no enzymatic functional activity of the respective enzyme. This population has to be made aware of lifestyle risks Chelation treatment is more often needed then by those who do have proper enzyme function Greater nutritional support is needed 31

32 Presence of GSTM1 0/0 Polymorphisms at certain diseases 32

33 Summary: Diagnostic Screening for difficult cases 1. Metal screening -hair and/or blood 2. Detoxification treatment with chelator of choice, depending on metal exposure including pre and post urine 3. If insignificant metal excretion, resume treatment using different chelating agent and/or use combination of chelating agents. Record doses used. and repeat post urine (pre not necessary) 4. Consider genetic test panel GSTM1, GSTT1, GSTP1 and SODs 33

34 Thank you! 34