Metals and trace elements in the diet
and by injection
|
|
Metals and trace
elements
Thimerosal |
Certain essential metals and metal ions are required for the action of the human body, generally by their action on permitting the activity of enzymes and allowing specific carrier molecules to work adequately (e.g. haemoglobin). However, some are toxic. There have been specific worries in ASD concerning mercury in that it is not essential and is noted to be associated with mental illness when present in the body in excess. The inoculation of thimerosal (also known as thiomersal, and mercurothiolate) as a disinfectant in vaccines has been pointed at as a cause of excess mercury. However it has been difficult in actually demonstrating reliably this excess, and the levels shown are below that found as causing mental illness in adults. Attempts to remove it using standard medical procedures have been claimed as producing an improved mental condition in ASD. Thimerosal breaks down to ethylmercury and the 25micrograms per vaccine dose (largely in the past as most is not now used), is excreted faster than the methyl mercury daily dose of 0.47micrograms/kg/day as being safe. Hence a 5kg child would have expected to be safe in less than 10 days per vaccine. Much of the data is published not in scientific journals but as part of WHO, CDC, UK (NHS) and Australian official databases, which should be viewed to get a background to mercury toxicity effects. However, these documents do not explain the apparent advantages shown by some cases when mercury is removed from the body or the lack of high levels of mercury appearing in the urine when the drugs are used that cause their the mercury excretion. Other metals have been considered as being in excess or in depletion for reasons that may be associated with pica (very young children eating dirt), or as a result of other biochemical effects that might decrease their ability to be absorbed or retained in the body. One problem with this is that for side effects to be found in experimental animals, experiments often have to have none of these metals at all, and extremely low levels to be present in the body, whereas in the autistic children the levels found, although lower than the normal range found in children of the same age, may not be expected to show signs of inadequacy. At the moment much of this is under argument and many alternative results have been found as to metal levels in hair and skin despite good control studies e.g. Wecker. It is all quite complicated to report in that various researchers have tested for different levels of metal groups in the tissues of autistics compared to controls. |
Are toxic biometals destroying your children's future? Drum
DA. Biometals.
2009 Feb 11 Cadmium, arsenic, lead, and
mercury have been linked to autism, attention deficit disorder, mental
retardation and death of children. Mercury in thimerosal found in many vaccines
and flu shots contributes significantly to these problems. Decomposition of the
thimerosal can produce more toxic compounds, either methylethylmercury or
diethylmercury, in the body. These compounds have a toxicity level similar to
dimethylmercury. Within the human body, a mitochondrial disorder may release
the more toxic form of mercury internally. Young children and pregnant women
must minimize internal exposure to the vaccines and flu shots containing
mercury.
Mercury
There has been a disagreement as to whether there is an
excess in the body at all. Tests done
on the teeth and hair of children with autism vs controls seemed to disagree on
whether the levels were high or not.
Certainly
A comprehensive review of mercury provoked autism. Geier DA, King PG, Sykes LK, Geier MR. Indian J Med Res. 2008 Oct;128(4):383-411. Review.
But…..
The rise in autism and the mercury myth.
Scahill L, Bearss K. J Child Adolesc Psychiatr Nurs.
2009 Feb;22(1):51-3. Review. No abstract available.
Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Autism:
a novel form of mercury poisoning. Med Hypotheses. 2001 Apr;56(4):462-71.
Review. Bernard et al showing that the symptoms of autism were very similar to
those of people suffering from infantile exposure to mercury poisoning.
James et al,. Am J Med Genet B Neuropsychiatr Genet. 2006
Dec 5;141(8):947-56. found that children with autism had low levels of
glutathione, which is the body’s primary defence against mercury. Metabolic endophenotype and related genotypes
are associated with oxidative stress in children with autism (probably more
associated with the paper below…)
James SJ, Slikker W 3rd, Melnyk S, New E, Pogribna M, Jernigan S. Thimerosal neurotoxicity is associated with glutathione depletion: protection with glutathione precursors. Neurotoxicology. 2005 Jan;26(1):1-8. (Environmental methyl mercury has been shown to be highly neurotoxic, especially to the developing brain. Because mercury has a high affinity for thiol (sulfhydryl (-SH)) groups, the thiol-containing antioxidant, glutathione (GSH), provides the major intracellular defense against mercury-induced neurotoxicity. Cultured neuroblastoma cells were found to have lower levels of GSH and increased sensitivity to thimerosol toxicity compared to glioblastoma cells that have higher basal levels of intracellular GSH. Thimerosal-induced cytotoxicity was associated with depletion of intracellular GSH in both cell lines. They also found a protective effect of N-acetyl cysteine)
Nataf R, Skorupka C, Amet L, Lam A, Springbett A, Lathe R. Porphyrinuria
in childhood autistic disorder: implications for environmental toxicity.
Toxicol Appl Pharmacol. 2006 Jul 15;214(2):99-108 A large study by Nataf et al.
found that over half of children with autism had abnormal levels of a porphyrin
in their urine that highly correlates with a high body burden of mercury.
Bradstreet J., Geier DA, Kartzinel JJ, Adams JB, Geier MR, A Case-Control Study of Mercury Burden in Children with Autistic Spectrum Disorders, J. Am. Phys. Surg 8(3) 2003 76-79. The study found that children with autism excreted 3-6x as much mercury as did typical children when both were given DMSA.
Holmes AS, Blaxill MF, Haley BE. Reduced levels of mercury in
first baby haircuts of autistic children. Int J Toxicol. 2003
Jul-Aug;22(4):277-85. Found that children with autism had unusually low levels
of mercury in their baby hair (1/8 normal), suggesting a decreased ability to
excrete mercury or to put it into hair?)
Adams JB, Romdalvik J, Ramanujam VM, Legator MS. Mercury, lead, and zinc in baby teeth of children with autism versus controls. J Toxicol Environ Health A. 2007 Jun;70(12):1046-51. A small pilot study found that children with autism had 2x more mercury in their baby teeth than did typical children, suggesting that they had a higher body burden of mercury during their infancy when the teeth formed. That study also found that children with autism had a much higher usage of oral antibiotics during their infancy, similar to their baby hair study.
Windham
GC, Zhang
L, Gunier
R, Croen
LA, Grether
JK. Autism spectrum disorders in relation to distribution of
hazardous air pollutants in the
Palmer RF, Blanchard S, Stein Z, Mandell D, Miller C Environmental
mercury release, special education rates, and autism disorder: an ecological
study of
Palmer RF, Blanchard S, Wood R. Proximity to point sources of environmental mercury release as a predictor of autism prevalence. Health Place. 2008 Feb 12.
Soden SE, Lowry J,
Garrison CB, Wasserman G. 24-hr provoked
urine excretion test for heavy metals in children with autism and typically
developing controls, a pilot study.
Clinical Toxicology 2007;45;476-81.
15 autistics were treated for heavy metal toxicity using DMSA and none
was found (As, Cd, Pb, Hg). It should be noted that when the urine of the
children that were being detoxified was tested for mercury, it was simply not
found to any great degree in a way different from controls.
Singh VK, Rivas WH. Detection of antinuclear and antilaminin antibodies in autistic children who received thimerosal-containing vaccines. J Biomed Sci. 2004 Sep-Oct;11(5):607-10. In fact his decision was that the finding in autistic and non-autistic children (both of whom had been vaccinated) of the antibodies was identical. He could find no association with the thimerosal and says it again in another paper:
Singh VK, Hanson J. Assessment of metallothionein and antibodies to metallothionein in normal and autistic children having exposure to vaccine-derived thimerosal. Pediatr Allergy Immunol. 2006 Jun;17(4):291-6. (the idea is that as metallothionein interacts with mercury, then antibodies to it may be found. None were found) Singh VK. Thimerosal is unrelated to autoimmune autism. Pediatr Allergy Immunol. 2007 Feb;18(1):89. (Singh is determined)…however another group found that there was an increase in anti-metallothionein in the family. See Russo AF. Anti-metallothionein IgG and levels of metallothionein in autistic families. Swiss Med Wkly. 2008 Feb 9;138(5-6):70-7. (they showed that there was a large excess compared with controls of antibodies to metallothioneins in blood…but this did not seem to correalate with the type of autism or other factors. They take this as indicating that it was not the cause itself but may actually be secondary in some way)
Walker SJ, Segal J, Aschner M. Cultured lymphocytes from autistic children and non-autistic siblings up-regulate heat shock protein RNA in response to thimerosal challenge. Neurotoxicology. 2006 Sep;27(5):685-92. (no difference with siblings i.e. normal levels. I.e. they produced more metallotheionine just as well as they should do in order to get rid of the ethyl mercury from the thimerosal, so if there was a problem with the children’s biochemistry then it was not something that appeared in vitro to a single cell group)
Cohly HH, Panja A. Immunological findings in autism. Int Rev Neurobiol. 2005;71:317-41. Review. Discusses the effect of mercury on astrocytes. This may not be significant.
Geier DA, Geier MR. A case series of children with apparent mercury toxic encephalopathies manifesting with clinical symptoms of regressive autistic disorders. J Toxicol Environ Health A. 2007 May 15;70(10):837-51.
Geier DA, Geier MR. A two-phased population epidemiological study of the safety of thimerosal-containing vaccines: a follow-up analysis. Med Sci Monit. 2005 Apr;11(4):CR160-70. Epub 2005 Mar 24. (basically showing that the authors found an association between the vaccines and the autism and it is this publication that the claimants of lack of toxicity will have to explain).
Geier
DA, Geier MR. A comparative evaluation of the effects of MMR immunization
and mercury doses from thimerosal-containing childhood vaccines on the
population prevalence of autism. Med Sci Monit. 2004 Mar;10(3):PI33-9. (showing that the vaccine seemed to be
associated with autism but could not be shown to be the cause) There have been nine epidemiological studies
of the link between thimerosal in vaccines and autism. Four published studies
by the Geiers have consistently found that children who received thimerosal in
their vaccines had a 2-6x higher chance of developing autism than those who
received thimerosal-free vaccines. Four published studies by groups affiliated
with vaccine manufacturers have failed to find a link, and one was inconclusive.
Three of the studies were conducted in other countries where the usage of
thimerosal is much less and the incidence of autism is much lower, so those
results have limited relevance to the
Geier
DA, Mumper E, Gladfelter B, Coleman L, Geier MR. Neurodevelopmental disorders, maternal
Rh-negativity, and Rho(D) immune globulins: a multi-center assessment. Neuro Endocrinol Lett. 2008 Apr;29(2):272-80.
(They looked to see if the Rh-negative mothers, that would therefore receive
anti-D that was preserved with thimerosal, had an excess of autistic
children. They claim that immunoglobulin
did appear to be associated with this).
Kern JK, Grannemann BD, Trivedi MH, Adams JB. Sulfhydryl-reactive metals in autism. J Toxicol Environ Health A. 2007 Apr 15;70(8):715-21. difference between sulfhydryl-reactive metals (mercury, lead, arsenic, and cadmium) in the hair of 45 children with autism (1-6 yr of age) as compared to 45 gender-, age-, and race-matched typical children. Hair samples were measured with inductively coupled mass spectrometry. Some studies, such as Holmes et al. (2003), suggested that children with autism may be poor detoxifiers relative to normally developing children. Metals that are not eliminated sequester in the brain. Their study found that arsenic, cadmium, and lead were significantly lower in the hair of children with autism than in matched controls. Mercury was in the same direction (lower in autism) following the same pattern, but did not achieve statistical significance.
Geier DA, Sykes LK, Geier MR. A review of Thimerosal (Merthiolate) and its ethylmercury breakdown product: specific historical considerations regarding safety and effectiveness. J Toxicol Environ Health B Crit Rev. 2007 Dec;10(8):575-96. Review (Thimerosal (Merthiolate) is an ethylmercury-containing pharmaceutical compound that is 49.55% mercury and that was developed in 1927. He simply explains the history of its use and how it grew in usage in vaccines over a very long period)
Young HA, Geier DA, Geier MR. Thimerosal exposure in infants and neurodevelopmental disorders: An assessment of computerized medical records in the Vaccine Safety Datalink. J Neurol Sci. 2008 May 14. (they try to calculate the ongoing chance of autism in specific groups of thimerosal-exposed children and claim that compared to controls, the risk was higher). This is the sort of research that is needed, and to be repeated in an ongoing manner with specific groups during a period in which thimerosal is removed from vaccines.
Early thimerosal exposure and neuropsychological outcomes
at 7 to 10 years. Thompson
WW, Price C, Goodson B, Shay DK, Benson P, Hinrichsen VL, Lewis E, Eriksen E,
Ray P, Marcy SM, Dunn J, Jackson LA, Lieu TA, Black S, Stewart G, Weintraub ES,
Davis RL, DeStefano F; Vaccine Safety Datalink Team. N
Engl J Med. 2007 Sep 27;357(13):1281-92. (including autistic-type behaviour)
Hviid A, Stellfeld M, Wohlfahrt J, Melbye M. Association between thimerosal-containing vaccine and autism. JAMA. 2003 Oct 1;290(13):1763-6. (They found no association between the vaccinations – this included all the ones involved – and autism. However there was argument in the journal after this)
Havarinasab S, Hultman P. Organic mercury compounds and autoimmunity. Autoimmun Rev. 2005 Jun;4(5):270-5. Epub 2005 Jan 5 Recent studies have confirmed that organic mercurials such as methyl mercury (MeHg) and ethyl mercury (EtHg) are much more potent immunosuppressors than inorganic mercury (Hg). They tried to demonstrate this with further compounds. Havarinasab has done further work on immunosuppression and organic mercury. His work should be looked up on PubMed.
Clarkson TW, Magos L. The toxicology of mercury and its chemical compounds. Crit Rev Toxicol. 2006 Sep;36(8):609-62. (a major review article)
Desoto MC, Hitlan RT. Blood levels of mercury are related to diagnosis of autism: a reanalysis of an important data set. Child Neurol. 2007 Nov;22(11):1308-11. They disagree with the findings of Aschner M. Re: Blood levels of mercury are related to diagnosis of autism: a reanalysis of an important data set. J Child Neurol. 2008 Apr;23(4):463; author reply 463-5. (Desoto claims that the data show that the autistic children have an excess of mercury in the blood whereas Ashner disagrees).
Mercury, vaccines, and autism, revisited. Silbergeld EK. Am J Public Health. 2008 Aug;98(8):1350; author reply 1350-1.
Association with Amalgam used
in dental fillings: All very
difficult in that it would need to be done as research not just as calculations
or measurements but also with prevalence and distribution of disease. For instance the increase in autism has been
has been associated with a decrease in fillings in the
Mutter J, Naumann J, Guethlin C. Comments on the article "the toxicology of mercury and its chemical compounds" by Clarkson and Magos (2006). Crit Rev Toxicol. 2007;37(6):537-49; discussion 551-2. (quite a determined article indicating the large amount of data that we have concerning mercury amalgam and potential toxicity overall. He also show that: Dental amalgam is the main source of human total mercury body burden, because individuals with amalgam have 2-12 times more mercury in their body tissues compared to individuals without amalgam; there is not necessarily a correlation between mercury levels in blood, urine, or hair and in body tissues, and none of the parameters correlate with severity of symptoms.)
Magos
L, Clarkson
TW. Overview of the clinical
toxicity of mercury. Ann Clin Biochem. 2006 Jul;43(Pt
4):257-68 This goes into the problems
very clearly and the references concerning amalgam up to 2005.
Mutter J, Naumann
J, Walach
H, Daschner
F. Amalgam risk assessment with coverage of references up to 2005] Gesundheitswesen. 2005 Mar;67(3):204-16. (Mutter makes it quite clear that in his
opinion. Mercury accumulates in
some organs, particularly in the brain, where it can bind to protein more
tightly than other heavy metals (e. g. lead, cadmium). Therefore, the
elimination half time is assumed to be up to 1 - 18 years in the brain and
bones. Mercury is assumed to be one of the most toxic non-radioactive elements.
No message concerning autism)
Clifton JC 2nd. Mercury exposure and public health. Pediatr Clin North Am. 2007 Apr;54(2):237-69, viii. (takes the association between vaccination and autism as being disproved)
Martin
MD, Woods
JS.The safety of dental amalgam in children. Expert Opin
Drug Saf. 2006 Nov;5(6):773-81
(admits that there is worry concerning amalgam and its usage in being
associated with autism. He states that
there has only been 2 controlled trials to show whether amalgam is safer or
more dangerous than other methods and goes into the possibility of autistic
factors being involved. No autistic
involvement could be demonstrated adequately using these methods).
DeRouen TA, Martin MD, Leroux BG, Townes BD, Woods JS, Leitão J, Castro-Caldas A,
Luis H, Bernardo M, Rosenbaum G, Martins IP.
Neurobehavioral effects of dental amalgam in children: a randomized clinical
trial. JAMA. 2006 Apr
19;295(15):1784-92. (this was an 8 year
period in which children with neurological problems of various kinds were either
treated with dental restorative amalgam or not.
During this period the amount of mercury excreted in urine was measured
(it was the same), and neurological
effects were attempted to compare the groups. In this
study, children who received dental restorative treatment with amalgam did not,
on average, have statistically significant differences in neurobehavioral
assessments or in nerve conduction velocity when compared with children who
received resin composite materials without amalgam. These findings, combined
with the trend of higher treatment need later among those receiving composite,
suggest that amalgam should remain a viable dental restorative option for
children. There was large amounts of
discussion about the study from other authors afterwards
A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity. Geier DA, Kern JK, Geier MR. Acta Neurobiol Exp (Wars). 2009;69(2):189-97. This study examined increased Hg exposure from maternal dental amalgams during pregnancy among 100 qualifying participants born between 1990-1999 and diagnosed with DSM-IV autism (severe) or ASD (mild). Logistic regression analysis (age, gender, race, and region of residency adjusted) by quintile of maternal dental amalgams during pregnancy revealed the ratio of autism:ASD (severe:mild) were about 1 (no effect) for </=5 amalgams and increased for>=6 amalgams. Subjects with>=6 amalgams were 3.2-fold significantly more likely to be diagnosed with autism (severe) in comparison to ASD (mild) than subjects with </=5 amalgams. Dental amalgam policies should consider Hg exposure in women before and during the child-bearing age and the possibility of subsequent fetal exposure and adverse outcomes.
Treatment: Mercury. Unfortunately much of this has been carried
out by individuals and poorly studied using psychological techniques.
Aremu DA, Madejczyk MS Ballatori N. N-acetyl cysteine as a potential antidote and biomonitoring agent of methylmercury exposure. Environmental Health Perspectives 2008;116:26-31
Miller AL. Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998 Jun;3(3):199-207. (Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound’s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.)
Adams et al. found that DMSA (chelation) resulted in a great improvement or normalization of RBC (red blood cell) levels of glutathione after just 1 round (3 days) of DMSA treatment, with benefits lasting at least 1-2 months.
Adams et al, Preliminary
results of DMSA treatment study, presentation at Fall DAN! Conference
2006. Also: higher usage of oral
antibiotics than did typical children, which is important because usage of oral
antibiotics almost completely stops the body’s ability to excrete mercury.
Gregus Z, Stein AF, Varga F, Klaassen CD. Effect of lipoic acid on biliary excretion of glutathione and metals .Toxicol Appl Pharmacol. 1992 May;114(1):88-96. Administration of lipoic acid enhanced the biliary excretion of reduced glutathione in a dose-dependent fashion. Despite increasing glutathione output, Lipoic acid (150 mumol/kg, iv) did not increase, but rather decreased, the biliary excretion of methylmercury, cadmium, zinc, and copper. In contrast, biliary excretion of inorganic mercury, which is minimally affected by glutathione depletion, was dramatically enhanced (12- to 37-fold) by LA administration).
Patrick L. Mercury toxicity and antioxidants: Part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev. 2002 Dec;7(6):456-71. (an excellent article going through the different ways in which a person may be exposed to mercury, and how the drugs would be expected to mobilise the mercury from inside cells and cause it to be excreted from the body in bile. A well written article but says little about DMSA except using in vitro models)
Aposhian HV, Morgan DL, Queen HL, Maiorino RM, Aposhian MM. Vitamin C, glutathione, or lipoic acid did not decrease brain or kidney mercury in rats exposed to mercury vapor. J Toxicol Clin Toxicol. 2003;41(4):339-47. (this would argue with the arguments of Cutler, see above)
Gonzalez-Ramirez
D, Zuniga-Charles M, Narro-Juarez A, Molina-Recio Y, Hurlbut KM, Dart RC,
Aposhian HV. DMPS
(2,3-dimercaptopropane-1-sulfonate, dimaval) decreases the body burden of
mercury in humans exposed to mercurous chloride.
J Pharmacol Exp Ther
. 1998 Oct;287(1):8-12. (i.e. calomine lotion produced inAposhian
HV. Mobilization of
mercury and arsenic in humans by sodium 2,3-dimercapto-1-propane sulfonate
(DMPS).
Environ Health Perspect
. 1998 Aug;106 Suppl 4:1017-25. (this is a major article that DMPS is excellent stuff for use for testing the patient to see if they have an excess of mercury in their body. It explains large amounts concerning the mechanism and doses for the treatment of mercury toxicity but does not mention autism. It is easy to read for many people)Frumkin H, Manning CC, Williams PL, Sanders A, Taylor BB, Pierce M, Elon L, Hertzberg VS. Diagnostic chelation challenge with DMSA: a biomarker of long-term mercury exposure? Environ Health Perspect. 2001 Feb;109(2):167-71. (it didn’t seem to work but they felt it was probably because of the long period between the mercury exposure and test, which was years)
Soden SE, Lowry JA, Garrison CB, Wasserman GS. 24-hour provoked urine excretion test for heavy metals in children with autism and typically developing controls, a pilot study. Clin Toxicol (Phila). 2007 Jun-Aug;45(5):476-81. (see above. The authors are quite certain that mercury toxicity can be demonstrated using oral DMSA)
Return
to home page.
Return to top of page
Not significant
Apparent temporal association autism onset and lead exposure (Clinical Pediatrics 27: 1; 41-44 1988)
Cohen DJ, Johnson WT, Caparulo BK. Pica and elevated blood lead level in autistic and atypical children. Am J Dis Child. 1976 Jan;130(1):47-8. (it was the pica that made the increase and not just being autistic)
Shearer TR, Larson K, Neuschwander J, Gedney B. Minerals in the hair and nutrient intake of autistic children. J Autism Dev Disord. 1982 Mar;12(1):25-34. (no lead change found, 62% decrease compared to controls in cadmium)
Chisolm JJ Jr. Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with elevated blood lead concentrations. J Toxicol Clin Toxicol. 2000;38(4):365-75. (this makes it clear that oral DMSA did cause lead excretion in the urine, and was associated with the metal being removed from the body. There was not much data about the period over which this was needed)
Return
to home page.
Return to top of page
little data suggesting association
Mahanand et al. Serum
copper and zinc in autistic patients and controls. In Coleman M. Ed.
Jackson MJ, Garrod PJ. Plasma zinc, copper, and amino acid levels in the blood of autistic children. J Autism Child Schizophr. 1978 Jun;8(2):203-8. (no abnormal levels were found)
Adams JB, Romdalvik J, Ramanujam VM, Legator MS. Mercury, lead, and zinc in baby teeth of children with autism versus controls. J Toxicol Environ Health A. 2007 Jun;70(12):1046-51. Higher mercury but normal lead and zinc
Özgür Yorbik ,
Cemal Akay , Ahmet Sayal , Adnan Cansever ,
Teoman Söhmen , Ayhan O. Çavdar. Zinc status in autistic children. The Journal of
Trace Elements in Experimental Medicine
2004;17:101 – 107. Plasma and erythrocyte zinc levels in the autistic
children were found to be significantly lower than normal (P < 0.05). The
mean hair zinc level of the patients was also low when compared with that
obtained from normal Turkish children.
Sullivan et al., “Metallothionein Expression Is Increased in Monocytes and Erythrocytes of Young Men during Zinc Supplementation”, J. Nutr. 128:7077-713 (1998). (probably of no significance unless tested in autistics)
Higher Copper/Zinc ratios in autistic children. (J.
Applied Nutrition 48: 110-118, 1997) (I could not find this article)
Return
to home page.
Return to top of page
Lithium.
Claims of low levels of lithium in the child and mothers’ hair has not been agreed and the variations seen in lithium levels in people with other mental conditions suggested that treatment using lithium may be of value. However this has not been shown to be successful currently.
Wecker L, Miller SB, Cochran SR, Dugger DL, Johnson WD. Trace element concentrations in hair from autistic children. J Ment Defic Res. (1985 Mar;29 ( Pt 1):15-22 (The concentrations of 14 elements were determined in scalp hair samples from control, autistic and autistic-like children. Significant differences were noted between normal males and females for calcium, magnesium and mercury. The autistic population had significantly lower levels of calcium, magnesium, copper, manganese and chromium and higher levels of lithium as compared to sex- and age-matched controls. Children with autistic features (autistic-like), classified as having childhood-onset pervasive disorder, had lower levels of magnesium, cadmium, cobalt and manganese as compared to controls. Discriminant function analysis using the 14 trace elements correctly classified 90.5% of the normal and 100% of the autistic population.)
Adams
JB, Holloway CE, George F, Quig D.
Analyses of toxic metals and essential minerals in the hair of
Return
to home page. Return
to top of page
Cadmium:
no specific involvement currently considered.
Shearer TR, Larson K, Neuschwander J, Gedney B. Minerals in the hair and nutrient intake of autistic children. J Autism Dev Disord. 1982 Mar;12(1):25-34. (calcium, magnesium, zinc, copper, lead, as in controls but and cadmium 62% lower) But this was not agreed with by:
Wecker L, Miller SB, Cochran SR, Dugger DL, Johnson WD. Trace element concentrations in hair from autistic children. J Ment Defic Res. 1985 Mar;29 ( Pt 1):15-22. (this found no difference in cadmium but lower levels of calcium, magnesium, copper, manganese and chromium, but higher ones of lithium)
Toxic trace elements in the hair of children with autism.
Fido A, Al-Saad S. Autism. 2005 Jul;9(3):290-8. In-hair concentration levels of antimony, uranium,
arsenic, beryllium, mercury, cadmium, lead and aluminum from 40 boys with
autism and 40 healthy boys were determined by Perkin-Elmer mass spectrometry.
The children with autism had significantly (p<0.001) higher in-hair
concentration levels of lead, mercury and uranium. There was no significant
difference between the two groups in the other five toxic elements.
Soden SE, Lowry JA, Garrison CB, Wasserman GS. 24-hour provoked urine excretion test for heavy metals in children with autism and typically developing controls, a pilot study. Clin Toxicol (Phila). 2007 Jun-Aug;45(5):476-81. (see above. The authors are quite certain that mercury toxicity can be demonstrated using oral DMSA). Always a problem with finding excess cadmium or arsenic (or mercury in this case) is that there are simply not enough cases being tested and not enough data for the controls. Here the mercury data may be of value but for cadmium it is not clear.
Sulfhydryl-reactive metals in autism. Kern JK, Grannemann BD, Trivedi MH, Adams JB. J Toxicol Environ Health A. 2007 Apr 15;70(8):715-21. Sulfhydryl-reactive metals (mercury, lead, arsenic, and cadmium) in the hair of 45 children with autism compared to controls. They found that the levels in the hair was actually lower in the autistics but this was not significant.
Return
to home page.
Return to top of page
Magnesium
(low levels found in the blood etc) and trials with B6 (with
and without magnesium).
The worry being that B6 may require magnesium in adequate amounts to be effective. As a result treatments with high levels of B6 (or its phosphate called P5P) in the diet and modified methods of magnesium treatment. Claims for advantage should be repeated and Martineau’s data are statistically significant and open to repeat in ASD cases where B6, B6P and Mg might be involved.
Saladino CF Jr, Sankar DV. Studies on erythrocyte magnesium and potassium levels in childhood schizophrenia and growth. PDM. 1973 Jan-Dec;4-5(9-12;1-8):107-10.
Gentile
PS, Trentalange
MJ, Zamichek
W, Coleman
M. Brief report: trace elements in the hair of autistic and control
children. J
Autism Dev Disord. 1983 Jun;13(2):205-6.
Hayek J. Intracellular magnesium in autistic
subjects. Brain Dysfunction 1991. (book)
Strambi M, Longini M, Hayek J, Berni S, Macucci F, Scalacci E, Vezzosi P. Magnesium profile in autism. Biol Trace Elem Res. 2006 Feb;109(2):97-104. (cellular Mg was equal in control and autism but extracellular Mg was much lower in autism). This article was well carried out and should be repeated by another team. As such it may again show a biochemical factor that must be explained in autism.
Lelord G, Callaway E, Muh JP. Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children. Acta Vitaminol Enzymol. 1982;4(1-2):27-44. (In 1973 Rimland reported that some autistic children responded favorably to high doses of vitamin B6. Since this finding, different studies were performed to identify apparently B6 responsive subjects and to critically evaluate clinical and biological B6 responsiveness. In a first open trial 15 out of 44 children exhibited moderate clinical improvement with worsening on termination of the trial. Thirteen responders and 8 non responders were re-tested in a 2-week crossover, double-blind trial and the responses to the open trial were confirmed.
Mousain-Bosc
M, Roche
M, Polge
A, Pradal-Prat
D, Rapin
J, Bali
JP. Improvement
of neurobehavioral disorders in children supplemented with magnesium-vitamin
B6. II. Pervasive developmental disorder-autism. Magnes Res.
2006 Mar;19(1):53-62 (15/33 children
were improved in the first three groups of symptoms. When the Mg-B6 treatment
was stopped, PDD symtoms reappeared in few weeks. A statistically significant
relationship was found in intraerythrocyte (Erc)-Mg values from children before
treatment and their mothers. In conclusion, this study suggests that the
behavioral improvement observed with the combination vitamin B6-magnesium in
PDD/autism is associated with concomitant modifications of Erc-Mg values. They discuss multiple studies also)
Martineau J, Garreau B, Barthelemy C, Callaway E, Lelord G. Effects of vitamin B6 on averaged evoked potentials in infantile autism.Biol Psychiatry. 1981 Jul;16(7):627-41. (During treatment of the autistic children with B6, an increase of amplitude of middle-latency evoked potentials and a decrease of urinary homovanillic acid were found.)
Martineau J, Barthelemy C, Garreau B, Lelord G. Vitamin B6, magnesium, and combined B6-Mg: therapeutic effects in childhood autism. Biol Psychiatry. 1985 May;20(5):467-78. (Goes through the findings to show the changes seen with the treatment. A review)
Nye C, Brice A. Combined vitamin B6-magnesium treatment in autism spectrum disorder. Cochrane Database Syst Rev. 2002;(4):CD003497. Review of various clinical studies. Indicates that Mg-B6 treatment cannot be recommended currently with the data available. Particularly following Fielding’s results:
Findling RL, Maxwell K, Scotese-Wojtila L, Huang J, Yamashita T, Wiznitzer M. High-dose pyridoxine and magnesium administration in children with autistic disorder: an absence of salutary effects in a double-blind, placebo-controlled study. J Autism Dev Disord. 1997 Aug;27(4):467-78. (found no advantage)
Adams JB, George F, Audhya T. Abnormally high plasma levels of vitamin B6 in children with autism not taking supplements compared to controls not taking supplements. J Altern Complement Med. 2006 Jan-Feb;12(1):59-63. (Children with autism had a 75% higher level of total vitamin B6 than the controls (medians of 56 versus 32 ng/mL, respectively, p = 0.00002). Most of the autistic children (77%) had levels that were more than 2 standard deviations above the median value of the controls. Beware: this does depend on the method used to measure B6 as its activity requires activation and these forms were not measured independently.
Kozielec T, Starobrat-Hermelin B. Assessment of magnesium levels in children with attention deficit hyperactivity disorder (ADHD).
Magnes Res. 1997 Jun;10(2):143-8. (Magnesium deficiency was found in 95 per cent of those examined, most frequently in hair (77.6 per cent), in red blood cells (58.6 per cent) and in blood serum (33.6 per cent) of children with ADHD. The conclusion from the investigations is that magnesium deficiency in children with ADHD occurs more frequently than in healthy children. Analysis of the material indicated the correlation between levels of magnesium and the quotient of development to freedom from distractibility.)
Bernstein AL. Vitamin B6 in clinical neurology. Ann N Y Acad Sci. 1990;585:250-60. Review Lower serum Magnesium than controls (Mary Coleman, The Autistic Syndromes 197-205, 1976)
Barthélémy C, Garreau B, Leddet I, Sauvage D, Muh JP, Lelord G, Callaway E. [Value of behavior scales and urinary homovanillic acid determinations in monitoring the combined treatment with vitamin B6 and magnesium of children displaying autistic behavior] Neuropsychiatr Enfance Adolesc. 1983 May-Jun;31(5-6):289-301. (one of the important factors to this is that they had tried to look at other biochemical responses and not just psychological effects)
Martineau J, Barthelemy C, Lelord G. Long-term effects of combined vitamin B6-magnesium administration in an autistic child.
Biol Psychiatry. 1986 May;21(5-6):511-8. (I could not get a copy)
Martineau
J, Barthelemy C, Cheliakine C, Lelord G.
Brief report: an open middle-term study of combined vitamin B6-magnesium
in a subgroup of autistic children selected on their sensitivity to this
treatment. J Autism Dev Disord. 1988 Sep;18(3):435-47
Jonas
C, Etienne
T, Barthélemy
C, Jouve
J, Mariotte
N. [Clinical and biochemical value of Magnesium + vitamin B6 combination in
the treatment of residual autism in adults]
Therapie. 1984 Nov-Dec;39(6):661-9.[Article in French]
Martineau
J, Barthelemy C, Roux S, Garreau B, Lelord G. Electrophysiological effects of fenfluramine or combined vitamin B6 and
magnesium on children with autistic behaviour.
Dev Med Child Neurol. 1989 Dec;31(6):721-7. (they admit that not all the
cases responded to the Mg plus B6 and not all were helped with
fenfluramine. They try to discuss which
aspects made the effects predictable in some way and review the findings from
earlier periods. )
Combined vitamin B6-magnesium treatment in autism spectrum disorder. Nye C, Brice A. Cochrane Database Syst Rev. 2005 Oct 19;(4):CD003497. They looked at numerous studies with oral B6 and Mg supplements to see if there was any advantage. Some of the studies they ruled out as being poorly organised, and some being not cross over design. One study, which used a cross-over design (Tolbert 1993) provided insufficient data to conduct an analysis. Another crossover study (Findling 1997) yielded no significant differences between treatment and placebo group performances following the B6 intervention on measures of social interaction, communication, compulsivity, impulsivity, or hyperactivity. The latest study (Kuriyama 2002) was motivated by evidence from epilepsy research and was focussed on a subgroup of children with pervasive developmental disorders (PDDs) who exhibited clinical features similar to those with pyroxidine-dependent epilepsy. This small study (n=8) only measured IQ and 'Social Quotient' and found a statistically significant benefit for IQ (5.2, 95% CI = [0.2 to 10.3]) when in the treated group, by using change scores. It is exceptionally difficult to carry out this type of study that is required by Cochrane but with the few studies that they accepted, they could not show there to be any advantage to the treatment.
Low activated B6 (P5P) in 42%. Autistic group also higher in serum copper. (Nutr. And Beh 2:9-17, 1984) (I could not find this article)
Rimland
B, Calloway E, Dreyfus P. The effect of high doses vitamin B6 on autistic
children: a double-blind crossover study. Am J Psychiatry 1978;135:472-475. (an
advantage: for further study)
Calcium
The
data on this is complex and difficult to follow. The idea is that increased intracellular
calcium levels give rise to changes in many other factors in brain cells, which
would allow a complicated change in the neurological action of the brain. Have a look at web site http://autismcalciumchannelopathy.com/ and you will see the various ways in which
calcium may be involved. It must always
be remembered that in many human illnesses, when calcium channels are involved
with disease, they are almost always secondary factors and it is some other
aspect that has given rise to the calcium changes.
Altered calcium homeostasis in autism-spectrum disorders:
evidence from biochemical and genetic studies of the mitochondrial
aspartate/glutamate carrier AGC1. Palmieri L, Papaleo V, Porcelli V,
Scarcia P, Gaita L, Sacco R, Hager J, Rousseau F, Curatolo P, Manzi B,
Militerni R, Bravaccio C, Trillo S, Schneider C, Melmed R, Elia M, Lenti C,
Saccani M, Pascucci T, Puglisi-Allegra S, Reichelt KL, Persico AM. Mol Psychiatry. 2008 Jul 8 Temporocortical gray matter from six matched
patient-control pairs was used to perform post-mortem biochemical and genetic
studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates
in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and
is physiologically activated by calcium (Ca(2+)). AGC transport rates were
significantly higher in tissue homogenates from all six patients, including
those with no history of seizures and with normal electroencephalograms prior
to death. Expression of AGC1, the
predominant AGC isoform in brain, and cytochrome c oxidase activity were both
increased in autistic patients, indicating an activation of mitochondrial
metabolism. Furthermore, oxidized mitochondrial proteins were markedly
increased in four of the six patients.
They could find no genetic changes in the gene involved. Excessive Ca(2+) levels are responsible for
boosting AGC activity, mitochondrial metabolism and, to a more variable degree,
oxidative stress in autistic brains.
Return
to home page.
Return to top of page