this study is really fascinating for several reasons. first thing i noticed is that DMSA does not leach out significant amounts of essential minerals. secondly, ONE ROUND of DMSA normalizes body glutathione levels! and thirdly, its quite clear that chelating with DMSA has many positive effects on the children with autism.
on thing i noticed is that the children all seemed to have high lead levels. once chelation therapy started they excreted much more lead than mercury. i am now wondering if autism isn't primarily about lead poisoning, and secondarily about mercury poisoning.
it also very clearly shows that DMSA is safe, its effective, and it does not deplete necessary nutrients from the body.
and it would seem they actually followed something very close to the cutler protocol!
* Started with 82 participants
* 1 did not qualify due to elevated liver enzymes
* 4 stopped after physical exam
* 11 stopped after initial blood draw (2 could not collect baseline urine)
* 1 collected urine after DMSA but did not send to lab (busy family)
* 65 collected urine after DMSA and sent to lab for testing
Toxic Metal Excretion after DMSA – 1st & 9th dose
% changes in median values (N=63)
Loss of essential minerals
1st dose – lost 27% of RDA;
9th dose: lost 12% of RDA;
So 1st day probably lost about 75% of RDA, 2nd day about 55% of RDA, and 3rd day about 40% of RDA; p<.0000000001
Equivalent to loss of about 7 bananas worth of potassium over 3 days
However, blood levels normal when tested 3-4 weeks later, so no long-term effect
Chromium: 1st dose – lose 45% of RDA; 9th dose – lose 15% of RDA; p=0.0005; so, several days of DMSA results in several days loss of chromium
Loss of essential minerals (cont.)
Molybdenum – decreased excretion by 6% on 1st day, 30% on 9th dose. Probably not a concern.
Sodium: 1st dose – increased excretion of 30%, normal by 9th dose; not a concern
Copper and Zinc: Increased excretion, but less than 1% of RDA
Vanadium – small loss (about 1/3 of daily intake)
Little change: calcium, phosphorus, magnesium, sulfur, selenium
Conclusion: DMSA causes some loss of potassium and chromium, small loss of vanadium; excretion of other minerals is unimportant
Recommendation: when using DMSA, eat extra fruits/vegetables for potassium (cannot supplement it), and supplement chromium and possibly vanadium.
Initial Glut: 31-1033 - many lower/higher than adult RR of 427-714
Final Glutathione: 355-695 - almost all within reference range
For low RBC glutathione, DMSA greatly increased values to normal
For high RBC glutathione, DMSA reduced values towards normal
Why are some RBC Glutathione unusually low and high?
Initial glutathione correlates with Pb-9 (.25), Sb-b (0.26), Cd-9 (0.30), Al-9 (0.29), and inversely correlates with Hg-9 (-.27).
Hypothesis: body responds to Pb, Sb, Cd, Al by making more glutathione. But, mercury blocks production of glutathione, and decreases it.
Why does 1 round of DMSA normalize glutathione?
* Change in glutathione correlates with Hg-9 (0.31), and inversely correlates with W-9 (-0.45) and Cd-9 (-0.47).
* So, removing some mercury increases low glutathione, and removing tungsten and cadmium reduces high glutathione.
Changes in Blood Chemistry after 1 round of DMSA (measured 3-6 weeks later, n=41)
Major Tests – no major problems, possible improvement of kidney function
Other changes (none were statistically significant)
Bilirubin -15%, n.s.
Suggests no major safety concerns for 1 round;
Platelet levels improve (less inflammation);
BUN/creatinine often high, since creatinine low, BUN high
Transition to Phase 2
* 8 children not allowed to continue due to low excretion of toxic metals
* 1 child not allowed to continue due to extremely high lead
* 1 family left on extended travel
* 1 family wanted to try other treatments
* 1 child discontinued due to extended use of Antibiotics due to urinary tract infections
* 1 family too busy/overwhelmed
* 1 child had extreme anxiety over blood draws
* 1 wanted to start private treatment (avoid risk of placebo)
* 1 had mild adverse reactions (lethargy, increased appetite)
* 2 dropped due to family reasons (parents busy, parent died)
* 2 dropped due to lack of improvement
* 4 dropped due to behavior problems
o Mild – slept very little, but not tired (on DMSA)
o Moderate – behavior worsened, more stimming – (on placebo)
o Moderate – behavior worsening, regressing – (on placebo)
o ???? – parents reported gain and lose skills, similar pattern for 2 years prior to study, but ADOS scores improved (on DMSA)
* 41 finished full study, including 4 in treatment group who finished early due to low excretion after 3rd round
Long-term Effect of DMSA on Urinary Excretion of
Toxic Metals – Changes in Median Values
Treatment Group Only (n=26)
Summary of long-term metal excretion
* For 5 children, DMSA treatment resulted in substantial decrease in excretion of lead, so they were only treated for 3-4 rounds
* For most of the children receiving DMSA (19), lead excretion continued at a high level.
* Moderate excretion of mercury, tin, thallium.
* Al excretion initially decreased, then increased.
Changes in Blood Chemistry after 7 rounds of DMSA n=21
No major problems; platelets improved; kidney function remains abnormal
Triglycerides: +47%, p=0.06 (trend) - initially zero high, then 2 high
Other changes (not significant):
Eosinophils: -19%, p=0.08 3 high, then 2 high
Basophils +50%, n.s. - all normal
Alkaline Phosphatase + 12%, n.s. all normal, then 5 high (growth spurt?)
Changes in blood chemistry after 1 round DMSA, 7 rounds placebo
Platelets: -13%, p=0.01 initially 1 high, then all normal; measured 3-4 months after treatment, so effects are long-lasting
Similar to 7 dose case (-18%)
Nothing else significant (no long-term effects; safe)
Regression analysis of Platelets
Change in platelet level could be partially explained (adjusted R2=0.41, p=0.02) with major factors being excretion of Thallium (p=0.002), Arsenic (p=0.01), Cadmium (p=0.03), and change in glutathione (p=0.04)
Evaluations of Autism Symptoms
* Severity of Autism Scale
* ATEC – parents
* Global Impressions
Changes in all four scales can be partially explained (28-75%) in terms of urinary excretion of metals
Arsenic, thallium, lead, and change in glutathione are most important
When glutathione increases, symptoms generally decrease.
When metal excretion increases, symptoms generally decrease
Effect of Age on Improvement
Slight negative correlation suggests that older children possibly tended to improve slightly more than younger children (not significant)
Test Correlation with age
Conclusions - benefits
* DMSA greatly increases excretion of lead, and some increase in excretion of tin, mercury, thallium.
* 1 round of DMSA dramatically normalized glutathione levels for at least 1-2 months, and helped normalize platelet levels (marker of inflammation) for at least 4 months
Conclusions - safety
* DMSA increases excretion of potassium and chromium; suggests need for more vegetables/fruit and modest chromium supplementation during chelation
* DMSA had little effect on other essential minerals
* DMSA had no adverse effect on liver enzymes, kidney function, or complete blood count (CBC)
* DMSA possibly raised triglycerides – concern to watch for
* Check cysteine levels, since 90% of DMSA is excreted bound to 1-2 cysteine.
Conclusions – Effect on Symptoms
* Both groups had significant improvements on autism scores
* 7-round group had slightly more improvements on ATEC and ADOS, but not significant
* More improvement in those with low glutathione and high initial metal excretion – strong correlations and regression analysis strongly suggest that improvement is real (not just placebo effect)
Toxic metals (especially lead, antimony, and mercury) account for 22-49% of autism severity.
DMSA is a safe way to remove toxic metals, normalize glutathione, normalize platelets/inflammation
Correlation of improvement in autistic symptoms with glutathione and metal excretion suggests DMSA did result in reduction of some symptoms of autism.
Longer treatment needed by most children to decrease lead levels – unknown if longer treatment might provide additional behavior benefit.
Double-blind, placebo-controlled study of DMSA needed
Other chelators may be needed for mercury and other metals (arsenic, antimony).
More research should be done!
* Will longer treatment with DMSA result in more benefit?
o Probably, but need to study
* How to test for and remove antimony?
o DMPS, somewhat Ca-EDTA
* How to test for and remove mercury?
o DMPS challenge, urinary porphyrins, other
* Many children and parents who participated in the study
* ARI and Wallace Foundation for funding
* Doctor’s Data for urine testing
* Immunosciences for RBC glutathione and immune testing