I include this section solely because of the difficulty I have had in getting anyone to pay attention to my low NO hypothesis sufficiently to understand it, while paying great attention to ideas which are obviously and demonstrably wrong. I am particularly annoyed with the “mercury causes autism” idea, which is completely wrong, and for which there is no physiological explanation, or any actual data supporting it and which contradicts much of which is well known about ASDs and mercury physiology. I call it an “idea”, because it does not meet minimal standards for “hypothesis”. It is not consistent with much that is well known. A “hypothesis” that is inconsistent with much that is well known is rejected (by scientists) as a failed hypothesis (as the “mercury causes autism” idea should be). People with ASDs do not have the most important and diagnostic symptom of mercury poisoning, an elevated level of mercury. We are now some 6 years beyond the suggestion that autism is caused by exposure to mercury[i], and there has not been a single publication demonstrating any association between elevated mercury exposure, or elevated mercury levels and autism or severity of ASD symptoms. Mercury is easy to measure, cheaply and with high precision in minimally invasive specimens, blood, urine, hair. There have been multiple industrial human exposures to mercury, which have been accurately measured and toxicity symptoms correlated with accurately measured levels in hundreds or thousands of individuals. There have been publications showing no association between mercury and autism.[ii] The proponents of the “mercury causes autism” idea have continued to press their case in the popular press, and in the courts, and at least one child has been killed by chelation treatments[iii]. The complete absence of data in the scientific literature is telling.
There has been no offered explanation as to how a toxin (mercury), could cause the most characteristic symptom of ASDs, larger brains, with a larger number of neurons. There is little similarity between symptoms of mercury toxicity diagnosed by measurement of elevated mercury levels and the symptoms of ASDs.[iv]
The paper that completely disproves the “mercury causes autism” idea is actually one by proponents of the idea[v]. This paper shows a very strong inverse association of mercury with ASD symptomology. That is, people with the most severe ASD symptoms had significantly (p < .0000004) lower mercury levels in their first haircut baby hair. The highest Hg level measured was in one of the normal controls, which was ~100 times higher than the average of the most severely affected individuals (19 ppm (n=1) vs. 0.21 ppm (n=24)). There were >10 most severely affected individuals with Hg levels less than 1/100th that of the highest control (by eye from their fig. 2.). The ad hoc “explanation” that is given, that people with ASDs are “non-excreters” of mercury is completely non-physiologic, and is unsupported by data in that paper, or published before or since. If true, it would contradict much that is well known about mercury physiology.
In the body, Hg and CH3Hg are mostly transported as conjugated thiol and disulfide complexes. That includes complexes with cysteine, homocysteine and glutathione[vi]. These Hg complexes are then ported into cells either with the large neutral amino acid transporter (LAT), or the organic anion transporter (OAT)[vii]. One reason the kidney is a target organ is that much of homocysteine metabolism occurs there and Hg is transported as a homocysteine disulfide.[viii],[ix]
Once the Hg is in the kidney, it causes the expression of metallothionein which sequesters Hg. Typically, Hg is taken up rapidly by the liver, but over the course of several days, after the kidney expresses metallothionein, the liver loses Hg and the kidney takes it up.[x] , [xi] CH3Hg in vivo is slowly oxidized to Hg(0).[xii] The major excretion pathway is via the stool. Bile salt anions and thiols (glutathione GSH) are co-excreted in the bile.[xiii] I suspect that thiol mercury complexes are excreted in the bile via the OAT1, which excretes bile anions and also mercapturic acids[xiv], and then enteric bacteria break the complex, then demethylate it with the Hg(0) being bound to something (porphyrin?, sulfides?) or not reabsorbed. In any case, bile excretion is coupled to GSH excretion. Conjugation of GSH to xenobiotic (and normal metabolites) is an important pathway for detoxification and excretion. If this pathway were disrupted by several orders of magnitude (necessary for the “non-excreter” idea), no doubt there would be effects (jaundice, fat malabsorption, liver failure, gall stones?).
In utero (guinea pig), Hg is primarily located in the fetal liver bound to metallothionein. This Hg then redistributes in neonates.[xv] Metallothionein is normally used to store Zn, with Zn being the most abundant transition metal in proteins (~300 Zn containing proteins plus 900 Zn finger transcription factors) after Fe. Interestingly, NO is involved in the mobilization of Zn from metallothionein and its association with the right protein.[xvi] Selenium is important in coupling the redox states of metallothionein and GSH with Zn release and thiol oxidation state[xvii].[xviii] Hg level of hair grown in utero may have a different relationship of Hg(hair) to Hg(total) to Hg(serum) than in the neonate or adult due to the different levels of metallothionein in the fetal liver and different fetal redox state. Metallothionein holds Hg much more strongly than it does anything else. It is likely that metallothionein is the most stable Hg species in the body. Metal ions in MT are coordinated to multiple cysteine residues (4 for Hg, Cd, Zn and 3 for Cu). The stability of metallothionein metal complexes is Hg> Cu > Cd > Zn > Ni.[xix] The absolute binding constants for these metals are: l019 to 1017 for copper, 1017 to 1015 for cadmium, and 1014 to 1011 for zinc.[xx] The binding constant for mercury is likely >1020, but how much greater is uncertain.
Metallothionein expression is increased under conditions of low folate,[xxi] under conditions of oxidative stress,[xxii] and under conditions of heavy metal exposure.[xxiii] Different organs require different levels of different metals to induce metallothionein. Basal expression of MT RNA is higher in the brain, but in the brain isn’t much changed by exposure to metal (Cd). In contrast that in the kidney is somewhat lower initially, but can be 10x higher than brain post Cd exposure.
Hair is primarily crystalline keratin fibers dispersed in an amorphous matrix.[xxiv] The keratin is cross linked by ionic and disulfide bonds. Keratin has a high cysteine content. Hg is trapped both as CH3Hg and as Hg2+. There has been significant work on the speciation of Hg in hair that has reliable demonstrated this. Interestingly, there is a significant correlation with hair color, with dark hair tending to have a significantly higher Hg content than light hair. I haven’t seen a good explanation for this, but there is also a tendency for hair Hg levels to be higher at higher latitudes. This may be due to photochemical reduction of Hg in the hair, followed by its release after deposition.
Hair can pick up Hg from the environment, but once there it is likely pretty stable, so long as the hair is not treated too “harshly”. Treating hair with commercial artificial waving agent (probably derivatives of thioglycolic or thiolactic acid) removed significant (~30%) Hg with each treatment (total of 3 treatments tested).[xxv] Artificial waving agents break the RS-SR double bonds, either via raising the pH, or by using thioacids. A high pH shampoo with EDTA will likely extract some Hg from hair once the R-S-Hg-S-R bonds have been broken. It is doubtful that much Hg would be extracted from crystalline keratin, but it might be from the amorphous matrix. The two different pools likely have the same Hg content when formed (derived from the R-S-Hg-S-R ported in via amino acid transporters as substrate to make keratin. The stability constant for Hg-EDTA (3x1021) is greater than for Hg-cysteine (2.5x1014). It is unlikely that first haircut baby hair was subjected to thiol waving agents or harsh shampoos with high EDTA, so low Hg content reflects low blood Hg while the hair grew. There have been many studies showing moderate to high levels of Hg in hair, 5, 10, 20 PPM among people who eat lots of fish. There is excellent correlation between Hg levels in cerebellum vs. hair (R=0.853) and cerebellum vs. liver (R=0.873), n=39.[xxvi]
Much of the “evidence” supporting a “mercury causes autism” idea is the anecdotal observation by some parents, that their child’s autism was promptly “triggered” by a vaccination, and presumably the vaccine contained thimerosal. However mercury poisoning is almost never acute, unless there is a very large dose (the dose of thimerosal from a single vaccination is not large, and is expected to have essentially non measurable physiological effects). In most of the industrial mercury poisoning episodes, there is significant exposure to mercury (as measured retrospectively in hair) long before there are any symptoms.[xxvii] In the exposure of Iraqis to CH3Hg in grain made into bread, latencies of weeks to months were observed. In the case of a heavy metal researcher exposed to a lethal dose of dimethyl mercury, she exhibited no symptoms for 5 months, however hair growing during those 5 months had extreme levels of mercury, at times exceeding 1000 ppm[xxviii] (over 5,000 times greater than what was observed in the “most affected” ASD group in the first hair cut baby hair study), yet she exhibited no symptoms. It was estimated that she was exposed to about 1344 mg Hg as 0.44 mL dimethyl mercury. The quantity of Hg in vaccines due to thimerosal is variable, about 12.5 to 25 μg per dose. The woman who experienced no symptoms for 5 months was exposed to about 100,000 times more. The promptness of any purported symptoms is strong evidence that those symptoms are not due to mercury. A more plausible “cause”, is immune system activation, the eliciting of which is the reason that vaccines are administered, and which is very prompt. Immune system stimulation alone can have prompt fatal consequences through anaphylaxis, which was an early complication of vaccine usage before modern Good Manufacturing Practices (GMP) and antibacterial preservatives such as thimerosal.[xxix]
I suspect that the lower Hg levels in baby hair of those with most severe ASD symptoms reflect greater fetal and neonatal liver metallothionein due to increased oxidative stress in utero. This might even be reflected in a reduced cord blood Hg concentration. In sheep, in utero, the Hg concentration of liver and kidney due to elemental exposure (amalgam) is ~10x that of brain.[xxx] It looks like a “steady state” Hg uptake was reached. I consider it very unlikely that there is some unknown protein in the brain that is sequestering Hg better than metallothionein (no such protein has ever been shown to exist), and that the sequestering of Hg adversely affects the function of that hypothetical protein such that it causes autism. Metallothionein binds Hg via coordination to 4 sulfur atoms. What type of coordination would a hypothetical protein require to achieve greater stability? Mercury doesn’t usually coordinate to more than 4 atoms. A protein where mercury coordinates to selenium? To multiple selenium atoms? Proteins are only synthesized under the direction of RNA. Presumably children inherit DNA to make such a protein from their parents. If there was maternal expression of such a protein, the Hg would never make it to the placenta. Presumably such a hypothetical protein couldn’t be on the Y chromosome because females get ASDs. If such a hypothetical protein were important in ASDs, it would have been identified in the many genetic studies that have been done.
For ASD individuals to be “non-excreters” of mercury there would need to be a disruption in cysteine and GSH metabolism sufficient to allow 3 or 4 orders of magnitude difference in the blood/brain/hair partitioning for ASD individuals vs. non-ASD individuals. No individual with a correlation several orders of magnitude necessary for the “non-excreter” idea has ever been reported in humans, or animals. Such an extreme disruption in essential amino acid physiology with no other apparent effects seems extremely unlikely. Amino acid transport is extremely well conserved. There are multiple and redundant pathways for amino acids to be transported in and out of cells. Hair is a minor Hg excretion pathway. If hair cells lacked amino acid transporters for cysteine, hair could not grow. If the ASD individual lacked such transporters, such a defect would either be fatal in utero, or would preclude the placenta (which is 100% fetal derived), from absorbing Hg from the mother.
In any case, if mercury were confined to the brain such that it is non-measurable in other tissue compartments such as blood, it could not cause ASD symptoms in other organs.
There is a significant correlation in the baby hair study between maternal anti-D prophylaxis and autism. Anti-D prophylaxis is used to reduce hemolysis of fetal blood cells due to rho D antibodies which pass the placenta. Despite use of anti-D prophylaxis, there is still increased hemolysis as indicated by hyperbilirubinemia[xxxi]. Hemolysis causes release of hemoglobin into the plasma, where it is ~650 times more effective at destroying NO[xxxii] than the equivalent Hb level in RBCs. Hemolysis during the first trimester during neurulation and other early neurodevelopment events could perturb NO physiology without hyperbilirubinemia being present at birth. The correlation may relate to the correlation between Rh incompatibility and oxidative stress (low NO), rather than to the minimal amount of mercury present in the anti-D prophylaxis vaccine.
Jaundice at birth is significantly more common among autistic children than controls, as is RH incompatibility[xxxiii]. I suspect that “subclinical” hyperbilirubinemia may be important too. The relevant development time may be the first trimester. Hemolysis then might reduce NO levels at critical development times, and then be unapparent at term. The low NO causes oxidative stress, which increases expression of metallothionein and greater sequestering of Hg in the liver and kidney. This might be the cause of the decreases in levels of Fe, Zn, and Cu which have been anecdotally reported. However, the level that is important is the level in the target organs, not necessarily the blood. For Fe, blood is a significant “target organ” where hemoglobin contains most of the Fe. But mitochondria also contain lots of Fe. NO has been shown to be important in Fe, Zn and Cu metabolism.[xxxiv],[xxxv] This may be the mechanism for anemia in autism[xxxvi], a consequence of oxidative stress induced metallothionein upregulation. Correcting the low Fe, Cu, and Zn levels therapeutically should be considered carefully. If the underlying oxidative stress is not corrected (by raising the NO level), then increased transition metals may make it worse.
The one study that purports to show elevated mercury levels in ASDIs, actually does not.[xxxvii] This “study”, was a report of children some with ASDs, some without, whose parents presented them to the International Child Development Resource Center for chelation. The “cases” were children diagnosed with ASDs, the “controls” were children with no known ASDs, and no known exposure to mercury who were presented for chelation by their parents (who presumably were willing to pay out of pocket). Testing of blood levels of mercury was not done, the only “testing”, was on urine after the 9th dose of meso-2,3-dimercaptosuccinic acid. The only “data” that is presented, is from a statistical analysis of the results. For the cases (221), the low, mean, high and standard deviation were 0, 4.06, 58.65 and 8.59 μg/g creatinine. The standard deviation is considerably higher than the mean, showing a highly skewed distribution. For the 18 “controls”, the levels were 0, 1.29, 6.2 and 1.54. Still a highly skewed distribution.
I requested the raw mercury levels from the corresponding author so I could do my own statistical analysis and my request was never acknowledged or complied with.
For the mean Hg level to be 4.06 μg/g, and with a high of 58.65 there had to be many (actually most) with levels below 4.06. What change to a body burden does that actually represent? If we assume the average child is 20 kg, normal creatinine excretion is 15 to 25 mg/kg/day.[xxxviii] That would make about 400 mg creatinine/day for a 20 kg child. The two levels of mercury excretion per day are then 1.62 and 0.52 micrograms/day. The difference is 1.1 microgram. Over 3 days, that is 3.3 micrograms. Remember, the average excretion was less than that, and some had no measurable excretion, that is 0.
It is interesting that the mercury excretions discussed in this publication were considered important enough by the authors to publish, yet there was no mention of the resolution or improvement of any ASD symptoms in this, or in any other publication before or since. Demonstrating resolution of ASD symptoms would of course be much more important than demonstration of (a clinically unimportant) increased excretion of a single microgram of mercury, the average amount of mercury in 10 grams of canned light tuna (n=347)[xxxix] (or 1 ounce of tuna over 3 days). Their use of the term “significant”, may accurately denote statistical significance is misleading in that it can easily be misinterpreted to mean clinically significant which it is not.
In short there has been no data in the literature to support the idea that “mercury causes autism”, and abundant data to show it has no merit. It is time the proponents of it stopped subjecting children to chelation, to “remove” mercury which isn’t present, before another child is uselessly killed.
[i] Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism: a novel
form of mercury poisoning. Med Hypotheses. 2001;56:462–471.
[ii] Ip P, Wong V, Ho M, Lee J, Wong W. Mercury exposure in children with autistic spectrum disorder: case-control study. J Child Neurol. 2004 Jun;19(6):431-4.
[iii] Sinha Y, Silove N, Williams K. Chelation therapy and autism.
BMJ. 2006 Oct 7;333(7571):756.
[iv] Nelson KB, Bauman ML. Thimerosal and autism? Pediatrics. 2003 Mar;111(3):674-9.
[v] Amy S. Holmes, Mark F. Blaxill, and Boyd E. Haley. Reduced Levels of Mercury in First Baby Haircuts of Autistic Children. International Journal of Toxicology, 22:277–285, 2003.
[vi] Tracey A. SIMMONS-WILLIS, Albert S. KOH, Thomas W. CLARKSON and Nazzareno BALLATORI. Transport of a neurotoxicant by molecular mimicry: the methylmercury–L-cysteine complex is a substrate for human L-type large neutral amino acid transporter (LAT) 1 and LAT2. Biochem. J. (2002) 367, 239-246.
[vii] Rudolfs K. Zalups, Amy G. Aslamkhan, and Sarfaraz Ahmad. Human organic anion transporter 1 mediates cellular uptake of cysteine-S conjugates of inorganic mercury. Kidney International, vol. 66 (2004), pp 251-261.
[viii] Christy C. Bridges and Rudolfs K. Zalups. Homocysteine, System b0,+ and the Renal Epithelial Transport and Toxicity of Inorganic Mercury. (Am J Pathol 2004, 165:1385–1394.
[ix] VERNON T. CANNON, RUDOLFS K. ZALUPS, and DELON W. BARFUSS. Amino Acid Transporters Involved in Luminal Transport of Mercuric Conjugates of Cysteine in Rabbit Proximal Tubule. JPET 298:780–789, 2001.
[x] RUDOLFS K. ZALUPS and JAMES KOROPATNICK. Temporal Changes in Metallothionein Gene Transcription in Rat Kidney and Liver: Relationship to Content of Mercury and Metallothionein Protein. JPET 295:74–82, 2000.
[xi] RUDOLFS K. ZALUPS. Molecular Interactions with Mercury in the Kidney. PHARMACOLOGICAL REVIEWS Vol. 52, No. 1. p.114.
[xii] JOHN C. SMITH AND FRED F. FARRIS. Methyl Mercury Pharmacokinetics in Man: A Reevaluation. TOXICOLOGY AND APPLIED PHARMACOLOGY 137, 245–252 (1996).
[xiii] Bouchard G, Tuchweber B, Yousef IM. Bile salt independent flow during bile salt-induced choleresis and cholestasis in the rat: role of biliary thiol secretion. Liver. 2000 Feb;20(1):27-37.
[xiv] Pombrio JM, Giangreco A, Li L, Wempe MF, Anders MW, Sweet DH, Pritchard JB, Ballatori N. Mercapturic acids (N-acetylcysteine S-conjugates) as endogenous substrates for the renal organic anion transporter-1. Mol Pharmacol. 2001 Nov;60(5):1091-9.
[xv] Minoru Yoshida. Placental to fetal transfer of mercury and fetotoxicity. Tohoku J. Exp. Med., 2002, 196, 79-88.
[xvi] Linda L. Pearce, Karla Wasserloos, Claudette M. St. Croix, Robin Gandley, Edwin S. Levitan and Bruce R. Pitt. Metallothionein, Nitric Oxide and Zinc Homeostasis in Vascular Endothelial Cells. J. Nutr. 130: 1467S—1470S, 2000.
[xvii] Yu Chen and Wolfgang Maret. Catalytic selenols couple the redox cycles of metallothionein and
glutathione. Eur. J. Biochem. 268, 3346±3353 (2001).
[xviii] WOLFGANG MARET AND BERT L. VALLEE. Thiolate ligands in metallothionein confer redox activity on zinc clusters. Proc. Natl. Acad. Sci. USA Vol. 95, pp. 3478–3482, March 1998.
[xix] Kirk B. Nielson and Dennis R. WingeS. Order of Metal Binding in Metallothionein. THE JOURNAL OF BLOLOGICAL CHEMISTRY Vol. 258, No. 21, Issue of November 10, pp. 13063-13069, 1983.
[xx] Dean H. Hamer. METALLOTHIONEIN. Ann, Rev, Biochem. 1986. 55:913-51
[xxi] Wei-Yong Zhu and Peter W. Melera. Metallothionein Is Overexpressed by Hamster Fibroblasts Selected for Growth in 15 pM Folinic Acid and Provides a Growth Advantage in Low Folate1. CANCER RESEARCH 59, 4194–4199, September 1, 1999.
[xxii] Masao Sato and Masuo Kondoh. Recent studies on metallothionein: protection against toxicity of heavy metals and oxygen free radicals. Tohoku J. Exp. Med., 2002, 196, 9-22.
[xxiii] Diane M. Durnam and Richard D. Palmiter. Transcriptional regulation of the mouse metallothionein-I gene by heavy metals. J Bio Chem, 256 (11) 5712-5716, 1981.
[xxiv] LESLIE N. JONES, Hair Structure Anatomy and Comparative Anatomy. Clinics in Dermatology Y 2001;19:95–103.
[xxv] Akira Yasutake, Miyuki Matsumoto, Masako Yamaguchi and Noriyuki Hachiya. Current hair mercury levels in Japanese: Survey in five districts. Tohoku J. Exp. Med., 2003, 199, 161-169.
[xxvi] E. Haca, M. Krzyzanowskib, J. Krechniaka. Total mercury in human renal cortex, liver, cerebellum and hair. The Science of the Total Environment 248 2000 37-43.
[xxvii] Weiss B, Clarkson TW, Simon W. Silent latency periods in methylmercury poisoning and in neurodegenerative disease. Environ Health Perspect. 2002 Oct;110 Suppl 5:851-4. Review.
[xxviii] Nierenberg DW, Nordgren RE, Chang MB, Siegler RW, Blayney MB, Hochberg F, Toribara TY, Cernichiari E, Clarkson T. Delayed cerebellar disease and death after accidental exposure to dimethylmercury. N Engl J Med. 1998 Jun 4;338(23):1672-6.
[xxix] Wilson GS. The Hazards of Immunization. New York, NY: The Athlone Press; 1967:75-84. (cited in Thimerosal in Vaccines, http://www.fda.gov/cber/vaccine/thimerosal.htm)
[xxx] M. J. VIMY, Y. TAKAHASHI, AND F. L. LORSCHEIDER. Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings. Am. J. Physiol. 258 (Regulatory Integrative Comp. Physiol. 27): R939-R945,1990.
[xxxi] A Maayan-Metzger, T Schwartz, J Sulkes, P Merlob. Maternal anti-D prophylaxis during pregnancy
does not cause neonatal haemolysis. Arch Dis Child Fetal Neonatal Ed 2001;84:F60–F62.
[xxxii] Xiaoping Liu, Mark J. S. Miller, Mahesh S. Joshi, Halina Sadowska-Krowicka, David A. Clark, and Jack R. Lancaster, Jr. Diffusion-limited Reaction of Free Nitric Oxide with Erythrocytes. THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 273, No. 30, Issue of July 24, pp. 18709–18713, 1998.
[xxxiii] Naya Juul-Dam, Jeanne Townsend and Eric Courchesne. Prenatal, Perinatal, and Neonatal Factors in Autism, Pervasive Developmental Disorder-Not Otherwise Specified, and the General Population. Pediatrics, 2001;107;63.
[xxxiv] Ralph N. Watts and Des R. Richardson. The mechanism of nitrogen monoxide (NO)-mediated iron mobilization from cells. Eur.J.Biochem. 269, 3383–3392 (2002), FEBS 2002.
[xxxv] Masaru Shinyashiki, Kenneth T. Chiang, Christopher H. Switzer, Edith B. Gralla, Joan S. Valentine, Dennis J. Thiele, and Jon M. Fukuto. The interaction of nitric oxide (NO) with the yeast transcription factor Ace1: A model system for NO-protein thiol interactions with implications to metal metabolism. PNAS, March 14, 2000, vol. 97, no. 6, 2491–2496.
[xxxvi] Latif, A. Heinz, P. Cook, R. Iron deficiency in autism and Asperger syndrome. Autism 2002, Mar, 6(1):103-14. (abstract)
[xxxvii] Jeff Bradstreet, David A. Geier, Jerold J. Kartzinel, James B. Adams, Mark R. Geier. A Case-Control Study of Mercury Burden in Children with Autistic Spectrum Disorders. Journal of American Physicians and Surgeons Volume 8 Number 3 Summer 2003 76-79.
[xxxviii] Normal Reference Laboratory Values. N Engl J Med, 1998; 339: 1063-1072.
[xxxix] US FDA Mercury Levels in Commercial Fish and Shellfish (http://www.cfsan.fda.gov/~frf/sea-mehg.html) (accessed 03/26/07)
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15 comments:
Mercury is sequestered into tissues. This is a physiologic phenomenon that presumably takes place to help make the toxin less toxic.
A "Provocation Test" is required first to adequately measure HG levels. A small amount of a chelating agent is administered and after three days the blood is tested. Only then can levels be measured.
This is a scientifically verifiable finding. Medical Doctors have been testing for Mercury incorrectly. Legally they have reason to do so.
Have a nice day.
No, that is nonsense. You are correct that real MDs don't use that method for legal reasons. To do so would be malpractice and most real MDs are actually trying to practice good medicine according to what is the "standard of care". Only fraudulent chelation quacks use that method. They use it for marketing purposes to trick their unsuspecting and gullible marks into thinking chelation has removed "toxic" levels of mercury. That notion is complete nonsense. The levels actually measured are very small and of no medical relevance.
The amount of mercury released during "provocation" is tiny. In the Bradstreet et al paper I cite, they measure the average release of a few micrograms of mercury. How is the amount of mercury in a single bite of a tuna sandwich "significant"? It is "significant" in a statistical sense in that it can be measured. It is of no significance medically. It is "significant" as a marketing tool for the fraudulent chelation quacks. They can point to the "number", fraudulently claim it is "significant", and delude the unsuspecting marks into paying for another round, and another, and another. When does chelation remove enough mercury to "cure" this "mercury poisoning"? It never does. People stop chelating when they run out of money. Or when the child being chelated has been so injured he/she can't take it any more and the parents stop subjecting them to these harmful faith based treatments/experiments.
There is a conspiracy; it is among the fraudulent chelation quacks. A conspiracy to make money by subjecting children to what ever chelation treatments their parents will pay for. Preying on the parents fears and hopes, making them poorer while injuring their children.
I continue to have an open mind about it. Cite something with evidence and I will read and consider it. I have already read just about everything that the chelation quacks have produced and none of it supports the fraudulent claims they make. I know you can't cite something other than something fraudulent because there is no reality in the "mercury causes autism" idea, only smoke, mirrors and lies.
Thanks for the info. Just out of curiousity, are you familiar with the work of Dr. William Walsh and Dr. Anjum Usman, relating to the defective functioning of metallothionein protein (MT) as a distinctive feature of autism? It's interestign stuff, and Usman goes into the oxidative stress angle.
I am somewhat familiar with metallothionein physiology. I looked up Walsh and Usman and couldn’t find anything either of them had written on it. I consider dysfunction of MT physiology in autism to be very unlikely and in a brief look found nothing to suggest that MT physiology is abnormal in autism. If you have a link I will look at it.
I agree that autism is a state of oxidative stress, but it isn’t the oxidative stress that is the problem, it is the low NO that necessarily accompanies every state of oxidative stress that is the problem. That problem can only be fixed by increasing NO levels. Antioxidants do absolutely nothing to reduce a state of oxidative stress.
Here's a link to a presentation Dr. Anjum Usman gave. It has the most details of the study he and Dr. Walsh conducted. It starts at slide 20.
file:///C:/Documents%20and%20Settings/carlsona/Local%20Settings/Temporary%20Internet%20Files/Content.IE5/F1MCMK12/586,13,Jill James, PhD. : Findings of Cysteine and Methionine Transulfuration Abnormalities Presentation DAN Conference Oct. 2003
I looked at this link
http://www.bhare.org/usman.ppt
From what I see in the presentation, it is completely clear that Anjum Usman is a quack. He advocates using homeopathy. That makes him a complete quack. If his medical judgment is such that he thinks homeopathy is a useful treatment, then his judgment is so flawed that what ever else he says is completely unreliable and useless.
A number of the studies shown in the presentation I discuss in my blog. They are complete crap. I specifically discuss the Bradstreet study. They found a difference of 7 micrograms of mercury? That is the amount of mercury in less than an ounce of canned albacore tuna. How can that be important?
http://www.cfsan.fda.gov/~frf/sea-mehg.html
The James paper on glutathione was done in plasma. Plasma is a completely unimportant tissue compartment for glutathione. Where it is important is inside cells where the level is 3 orders of magnitude higher than in plasma. That is 1000 times higher. If there were a change in cellular levels of glutathione, that might mean something. Plasma levels likely mean nothing.
If you are looking for useful treatments, understanding or therapies from Anjum Usman, you are wasting your time and money. I see nothing in this presentation other than he is a quack and is unable to differentiate reliable information from bogus crap.
Sorry to be so harsh, but he is a quack.
Continuation of comment in http://daedalus2u.blogspot.com/2008/10/theory-of-mind-vs-theory-of-reality.html
The reason I am very leery of mercury is that I've been mercury intoxicated. The probable cause was removal of an old amalgam finding, but no definitive evidence could be found. (Symptoms were erethism-like and visual disturbance.)
So while I agree with you and the evidence that thimerosal in vaccines is not a likely cause of neurological damage I prefer to reserve judgment until further studies of thimerosal farmacokinetics etc have been done.
On the other hand there is a certain degree of confusion in definitions. Discussions often don't distinguish between autism and non-autism like neurological damage. Part of which is likely caused by the hopes of taking legal action against vaccine producers.
The major problem with mercury is that no clear evidence has been presented of at what minimum level toxic effects occur for various Hg-compounds and if time of length of (chronic) exposure at low level is relevant.
Nevertheless ample research show that clear damage to various brain structures is caused by methyl-Hg and Hg0 and divalent Hg. And we do obviously agree on this.
But since (a) recent murine research suggest possible large differences in sensitivity between females and males. 100% of the males died, zero of the females at the same level. (Branch DR, Gender-selective toxicity of thimerosal. Exp Toxicol Pathol. 2008 Sep 2.)
And (b) that developmental methylmercury exposure causes severe learning impairement and induction of epigenetic changes in gene expression.
(Developmental mercury exposure elicits acute hippocampal cell death, reductions in neurogenesis, and severe learning deficits during puberty. J Neurochem. 2007 Dec;103(5):1968-81 and Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury.J Neurochem. 2008 106(3):1378-87).
And (c) especially that "exposure to MeHg at concentrations comparable to the current developmental exposure (via cord blood) of the general population in many countries inhibited spontaneous neuronal differentiation of neuronal stem cells"
(High susceptibility of neural stem cells to methylmercury toxicity: effects on cell survival and neuronal differentiation. J Neurochem. 2006 97(1):69-78. and
Neurobehavioural and molecular changes induced by methylmercury exposure during development. Neurotox Res. 2007 11(3-4):241-60)
I prefer to take a "better safe than sorry" stance. (Quite probably CFLs will be more problematical because of Hg0 release at breakage. Levels up to 50000 ng/cubic meter were recorded in the Compact Fluorescent Lamp Study by the Maine Department of
Environmental Protection.)
In addition to that there is also the question of health effects by the alteration of DNA binding sites by Hg in zinc finger proteins. Which are not well studied.
BTW. As yuo mention porphyrins it may also be interesting that a study found a correlation between symptoms of mercury exposure and a genetic polymorphism of coproporphyrinogen oxidase.
(The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans. Neurotoxicol Teratol. 2006 28(1):39-48)
In summ ou are of course correct in noting that, if Mg levels in vaccines are discussed, exposure from fish, dental amalgams and certain idustrial sources are notably higher, even if adding a safety margin. But as I said I prefer to be very cautious.
/S
As I mentioned, all in vitro studies of mercury exposure using mercury concentration in the culture media as a dosage point are highly flawed. Cell membranes are permeable to all mercury compounds, even inorganic mercury (less so to elemental mercury). Once inside the cell the mercury gets irreversibly tied up by thiols. The cell then takes in more mercury from the culture media. Cells concentrate mercury ~1000 fold or more over the media they are in. This can only happen when a few cells are grown in abundant mercury containing media. It is not the case in vivo where many cells are in contact with the fluid. In vivo, mercury is present as thiol conjugates both inside and outside of cells or as elemental mercury.
I completely agree with “better safe than sorry” and that mercury is bad. Treatments should only be used when there is potential for therapeutic benefit that is greater than the potential for harm. Chelation for treatment of autism has never been shown to have any benefit, and it does have side effects.
In many cases of autism there is no evidence of any neurological damage. It is completely wrong to characterize autism as a type of neurological damage. Neurological damage can cause autism-like symptoms, but damage is not necessary or sufficient for autism.
NO regulates metallization of Zn finger proteins. BDNF is involved in pathways that involve NO. Porphyrin physiology is very involved with NO. The cytochrome P450 enzymes are regulated by NO.
I strongly suspect that the target in chronic mercury poisoning is mitochondria biogenesis. I presume you are familiar with the case of the woman exposed to dimethyl mercury who had no symptoms for 5 months even though she had a lethal body burden? I cite it above xxviii. I discuss that a little more in my blog on mitochondria shutdown following immune system stimulation.
http://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failure.html
That does explain the visual symptoms, I think they somewhat mimic Leber’s hereditary optic neuropathy which I see as an energy crisis in the optic nerve due to not enough mitochondria. In Leber’s that is due to a mitochondrial defect, in chronic mercury poisoning I think it is an inhibition of mitochondrial biogenesis (which is regulated by NO). Mitochondrial shut down following immune system stimulation has nothing to do with any “toxins” in vaccines, not mercury, not aluminum, not “anti-freeze”. Immune system stimulation from actually getting the disease is a lot worse than from a vaccine that prevents the disease. Low NO prior to an immune system stimulation will make that stimulation worse due to what I call the “low NO ratchet”. The basal NO level can “ratchet” lower with each immune system stimulation until the system “saturates”. In adults you then end up with chronic fatigue, in children I think you get regression. I think that CFS or regression can be reversed at any time by increasing NO levels. I think if you do it quickly enough, then normal neurodevelopment can resume with no long term adverse effects.
I only saw the abstract of the Branch paper. Females do have higher levels of NO due to the effect of estrogen on the estrogen receptor which activates nitric oxide synthase. Women do have higher NO levels, men have lower NO levels. Females should be less susceptible to injuries that are mediated through reductions in NO levels.
http://jap.physiology.org/cgi/content/full/101/4/1252
So then if Mercury is not the cause of this "autism outbreak" then what is?? The statistics have gone from 1 in every 150,000 to 1 in every 150 (with the highest 'outbreaks' between 1997 & 2001). That's pretty scary. What is causing this?? Surely this cannot be some kind of "genetic" epidemic. SOMETHING is causing this and it needs to be found out because it is debilitating our youth which in turn is our future. Possibly all the hormones injected into our food supply? The antibodies? There is NO WAY I am going to believe there is no viable explanation. There are just too many cases for our medical fields to not have some inclination. Why is it that in this day and age nothing can be found? Autism is a neurological disorder with a spectrum that just continues to grow and expand. There MUST be some kind of logical explanation. I also find it funny how since the uproar of possible vaccination causes, there seems to be a reduction of new cases. Hmmm...something is not right. Sounds to me like some kind of cover up. Maybe during those crucial years there was a 'bad batch' of the MMR vaccine being distributed, unbeknownst to our doctors, until the uproar started then the batch disappeared and was sent out of the country where all of a sudden..boom! An autism outbreak in that country (I have heard of China having a large outbreak..isn't that where these vaccines were sent?). I have also heard that the thimersol in the MMR vaccine can be seen wrapped around certain neurotransmitters in an autistic brain. What is going on here?? As for homeopathic doctors, don't knock them. Natural sources are where ALL of our medications are derived from. They just do not include all the synthetic garbage. Parents of autistic children are desperate to help their children and are willing to try anything possible so their children can live normal productive lives. Of course if something is going to harm these children then it should not be done. It seems as if it is a "trial and error" experiment. I know, my son is on the spectrum and it is a very hard and draining life to live - for the entire family. I am desperatley doing anything and everything possible to help my son live a normal life and I certainly would never do anything to cause more harm. But when no one has an answer and you know it is not genetically caused (genetic testing) then there HAS to be an alternative treatment to help. We just want answers and I think we are entitled to them.
Anonymous 7:16, The only way we are going to get answers that I find satisfactory is by starting with facts and using rigorous logic. That is the only way to get to a scientific answer. My opinion is that those in the "mercury causes autism" camp are not interested in a scientific answer. They are not interested in facts, they are not interested in trying to connect those facts together with logic. The "mercury causes autism" idea is dead. It was dead two years ago when I wrote this blog, it is even deader now. There is not a shred of evidence in favor of it, and a great deal of evidence that contradicts it.
Sixty years ago, mercury exposure in children was much higher than it is now. Mercury was used in teething powder. 65,000 micrograms of HgCl per dose was used in many teething powders, which were sold by the tens of millions of doses. Many millions of children received many thousands of times more mercury from teething powders than any child ever received from vaccines. Over a thousand children died from mercury poisoning due to that exposure.
I believe there is a viable explanation too. If you read the rest of my blog, you will find that I subscribe to the low NO hypothesis of autism, that autism spectrum disorders consist of two components both of which are produced by low NO. The low NO hypothesis of autism is consistent with all that has been published about autism and with all that has been published about NO physiology. One of the reasons I am having trouble getting anyone to pay attention to it is because of the noise being generated by the anti-vaccine zealots. They are forcing money to be wasted chasing the dead end that is vaccines. They are driving researchers out of the field through threats of violence.
First, low NO in utero causes the characteristic neuroanatomy of autism, neuronal hyperplasia, larger brains, disrupted mirror neurons, increased minicolumns, increased asymmetries, increased neuron number. None of these symptoms are caused by or have ever been found to be associated with mercury poisoning.
Second, low NO reduces functional connectivity and so modifies the function of the brain, particularly in social areas where NO is an important neurotransmitter.
The idea that mercury or vaccines cause autism is nonsense. It is wrong. It is being pushed by quacks who sell their quack products to gullible parents. It is being pushed by lawyers trying to win the legal lottery by tricking the court into ruling (falsely) that vaccines or thimerosal cause autism. Those quacks are the ones you should be angry with, not the scientists who are trying to figure out what is going on. Homeopathy is pure quackery. It is a placebo, nothing more.
There was never thimerosal in MMR. There can't be because MMR is a live-virus vaccine. Thimerosal would kill the virus. Anyone who tells you different is lying. Why don't you go and ask the person who told you that there was thimerosal in MMR why they lied to you?
You say " I certainly would never do anything to cause more harm." But you are doing things that cause more harm. By following the anti-vaccine zealots you are causing harm. A child died from a measles infection because not enough people were vaccinated to prevent the spread of measles. That is the harm that the anti-vax zealots are causing.
I am not a medical type; so much of the medical discussion gets by me. There are aspects of this problem that are not addressed in the article. On the Internet are sites that presumably show that the number of cases of autism have increased as much as 10 fold from 1992-1993 to 2003-2004. One site claims the numbers come from the Department of Education. These numbers would need to be disputed. If not, one conclusion that can be made is that mercury could be the cause of the increase but the mechanism is unknown. A main reason for the controversy is that many parents have noticed an onset of autism within a few weeks of their child getting a vaccination. This cannot be dismissed.
I have read that infants are vaccinated within the first few weeks of birth and by the age of a few years have a staggering number of vaccinations. If there has been a large increase in cases and many parents have noticed onset soon after a vaccinated, vaccines are a logical suspect. Mercury is only one aspect to consider, but has taken front seat. Are there side effects from all these vaccines? What else is in the vaccine? Or better said, what are in the vaccines and where do they come from? Mercury may be a ruse to shift attention from other areas. People likely have a lower opinion of the pharmaceutical-medical complex than used car dealers and lawyers. The public will see medical jargon as a smoke screen.
Isaac Asimov said that if a someone knows there subject well they can explain it to the average lay person. Like global warming, we all know the conclusion, but where are the data presented in a way we can understand to support it. The increase in the number of cases is the claim and is what the public can understand. Dispense with that and no medical argument is needed.
There is essentially zero likelihood that mercury is the cause. Real mercury poisoning looks nothing like autism, the levels of mercury that have been measured in autistic children are small and normal.
Then there is the experience with pink disease from teething powder. In the first half of the 20th century, mercury was put into teething powders, a grain per dose. That is 65,000 micrograms of mercurous chloride per dose. That is about 4,000 times the dose of mercury in a thimerosal containing vaccine. Children got multiple doses. Over a thousand children died from mercury poisoning from mercury containing teething powders. Tens of millions of doses were sold by multiple companies per year.
Many millions of children received many thousands of times more mercury from teething powders than ever received in total from vaccines. Why was there no epidemic of autism when many tens of millions of children were receiving many thousands of times more mercury? For the simple reason that mercury doesn't cause autism.
One of the most characteristic feature of autism is a larger brain with more neurons comprised of more minicolums with smaller neurons. The number of minicolumns is fixed at 8 weeks gestation in utero. A vaccine years later can't increase the number of minicolums, nothing can.
The only people pushing anti-vaccine stuff are people trying to scam either the vaccine court or parents of children with autism. The only people pushing mercury are those scamming parents by selling chelation.
There is no reasonable data to support vaccine causation, no reasonable idea as to how vaccines could cause autism (how do toxins produce a brain that is larger and with more neurons?).
I was interested in reading your Blog as a dear friend of mine emailed me a case against Usman.
And so i googled his name and found your blog which I find interesting if flawed. Doctors 'practice' medicine. Patients seek answers from wherever they are drawn. A couple of weeks ago I was diagnosed with MND even though there is no known cause and no known cure. How can a Dr. say with any degree of certainty that a disease is a disease. I am exploring and taking homeopathic supplements, have been since April and the difference has been quite amazing. My muscle strength and density has improved. My energy levels is up. Sure my right leg and arm are weak, that has been ongoing since january. I trust my Naturopath who also happens to be a fully registered MD. I look to others with this 'condition' and see what they say. I detox with a daily sauna, I exercise to keep my lungs working at a capacity I am comfortable with. I have been measured with high levels of lead, mercury and arsenic. So, for you to something Crap and someone a Quack makes me laugh. Have you walked in the shoes of an Autistic child? Or in the shoes of anyone who you are trying to 'fix'? It seems, reading your Blog, that you have not. Feel free to read of my real life experiences at www.kiwicafe.com. These are simply my thoughts and experiences.
I offer you a name you may wish to search . . . http://www.stuff.co.nz/dominion-post/news/5664162/Sir-Paul-uses-intravenous-vitamin-C-treatment
enjoy your life, Richard.
"looked at this link
http://www.bhare.org/usman.ppt
From what I see in the presentation, it is completely clear that Anjum Usman is a quack. He advocates using homeopathy. That makes him a complete quack. If his medical judgment is such that he thinks homeopathy is a useful treatment, then his judgment is so flawed that what ever else he says is completely unreliable and useless.
A number of the studies shown in the presentation I discuss in my blog. They are complete crap. I specifically discuss the Bradstreet study. They found a difference of 7 micrograms of mercury? That is the amount of mercury in less than an ounce of canned albacore tuna. How can that be important?
http://www.cfsan.fda.gov/~frf/sea-mehg.html
The James paper on glutathione was done in plasma. Plasma is a completely unimportant tissue compartment for glutathione. Where it is important is inside cells where the level is 3 orders of magnitude higher than in plasma. That is 1000 times higher. If there were a change in cellular levels of glutathione, that might mean something. Plasma levels likely mean nothing.
If you are looking for useful treatments, understanding or therapies from Anjum Usman, you are wasting your time and money. I see nothing in this presentation other than he is a quack and is unable to differentiate reliable information from bogus crap.
Sorry to be so harsh, but he is a quack."
If you feel that magic placebos like homeopathy make you feel better, then good for you. My blog is for people who want to be members of the reality based community. If you can't handle reality, then you should not read it.
I see over at LB/RB why Anju Usman is in the news.
http://leftbrainrightbrain.co.uk/2011/10/defending-alternative-medicine-and-autism-the-charges-against-anju-usman/
http://leftbrainrightbrain.co.uk/2011/10/illinois-charges-dan-doctor-with-unethical-behavior/
with a very nice article in the Chicago Tribune.
http://www.chicagotribune.com/news/local/breaking/chi-illinois-regulators-seek-to-discipline-autism-doctor--20111013,0,3736752.story
It is good to see that mainstream media is going after these quacks and that medical boards are too. Exploiting vulnerable patients is unconscionable, even if they want to be exploited.
This won't really have success, I consider like this.
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