Proximity to freeways increases autism risk, study finds

[alp227]

Children born to mothers who live close to freeways have twice the risk of autism, researchers reported Thursday. The study, its authors say, adds to evidence suggesting that certain environmental exposures could play a role in causing the disorder in some children.

"This study isn't saying exposure to air pollution or exposure to traffic causes autism," said Heather Volk, lead author of the paper and a researcher at the Saban Research Institute of Children's Hospital Los Angeles. "But it could be one of the factors that are contributing to its increase."

Reported cases of autism cases increased by 57% between 2002 and 2006, according to the Centers for Disease Control and Prevention, although professionals still debate whether rates have actually risen or a greater proportion of autistic children is being diagnosed. An estimated 1 in 110 children is diagnosed with autism today. There is no cure, although research has shown that various therapies can mitigate some symptoms, especially if begun early in life.

In the current study, published online in the journal Environmental Health Perspectives, researchers looked at 304 children with autism and, for comparison, 259 children who were developing normally. The children, between the ages of 24 months and 60 months at the start of the study, lived in communities around Los Angeles, San Francisco and Sacramento.

Each family was evaluated in person, and all of the children received developmental assessments. Researchers collected data on where each child's mother lived during pregnancy and at the time of birth, and the proximity of the homes to a major road or freeway.

Children living about 1,000 feet from a freeway at birth — about 10% of the sample — had a two-fold increase in autism risk. The link held up even after researchers controlled for other factors that may influence development, such as ethnicity, parental education, maternal age and exposure to tobacco smoke.

Full story: http://www.latimes.com/health/la-he-autism-20101217,0,2040535.story

[RandomThoughts]

1. If that is correct, then the correlation should be true in higher density cities.

If living by a 'freeway' creates that situation, and you assume it is byproducts in smog, then there should be a higher level of that ailment in many cities.


Unless it is some metaphor, or they say it is about something other then smog.

[On the Road]

2. That's Right,

and relatively speaking it shouldn't be too hard to get some confirmation.

This study was just in LA. But I would think most other studies would have maintained address as well as some of the other factors that need to be controlled. All that would be necessary is to classify home according to some measure that would correlate with pollution or whatever they think is causing this.

[mhatrw]

3. Well, you are also closer to malls & fast food places.

Just saying.

[alp227]

4. Response by Science Based Medicine

http://www.sciencebasedmedicine.org/?p=9103

[HysteryDiagnosis]

5. Response to science based medicine

http://www.google.com/url?sa=t&source=web&cd=1&ved=0CBgQFjAA&url=http%3A%2F%2Fautism.asu.edu%2FAdditional%2FSummaryofDefeatAutismNow.doc&ei=-RYdTezPNMP38Aah0JWwDg&usg=AFQjCNHxr6Z-NZek1QUyqznWwRRAY_aHIQ

Opioid Peptides: Karl Reichelt, Ph.D., presented a summary of many years of work by himself and others on the role of opioid peptides in autism. Protein is made of peptides, which are made of amino acids. Basically, his lab and several others have published many articles in the scientific literature on their findings of unusual proteins and peptides in the urine of people with autism. Those proteins and peptides come from casein (dairy) and gluten (wheat and related grains), and they have an opioid-like effect on the brain, with a potency several times that of morphine. The peptides enter the blood due to 2 major biological flaws: 1) a failure of the digestive track to fully digest/break-down the casein and gluten molecules into amino acids, and 2) a “leaky gut” which allows the undigested proteins/peptides to pass into the blood stream. The failure of the gut to properly digest the proteins is apparently due to a lack of peptidases (digestive enzymes), which he hypothesizes could be due to genetic defects (other speakers also discussed environmental and nutritional causes). Recent work by Dr. Cade (1999) found antibodies (IgA) to gluten and casein in the mucous membranes of 12 of 44 people with autism. These opioid peptides can have many behavioral and physical effects, and could cause many of the symptoms of autism.



A single-blind, 2-year study found that children with autism improved on a gluten-free, casein-free (GFCF) diet, but regressed if the diet was stopped. A recent 2001 study by Cade found that digestive enzymes helped, but were only half as effective as a GFCF diet. Currently, the best labs have about a 5-10% false negatives and positives, so he recommends everyone with autism try a GFCF diet.



Summary: Gluten and casein, from dairy and wheat, appear to have an opioid-effect in autism, so a trial of total avoidance is strongly recommended.



Immunology – Dr. Gupta gave a very detailed talk on immunological abnormalities in autism. Basically, the immune system is composed of T cells (to fight viruses and fungi), B cells (to fight bacteria), Natural Killer cells. T cells consist of TH1 and TH2 cells. In autism, there is a major shift from TH1 to TH2. The decrease in TH1 may explain the increased susceptibility to viral and fungal infections in autism. The increase in TH2 may explain the increased autoimmunity, such as his findings of antibodies to myelin basic protein (MBP) and neuronal axonal filaments in the brain. Also, there is an increase in tumor necrosis factor (TNF) in autism, which could lead to decreased blood flow into the brain, a loss of Purkinje cells (often found on autopsy), alterations in neurotransmitters and neuropeptides, and possibly demyelination, as found in multiple sclerosis (MS). The decrease in TH1 could explain the “leaky gut” in autism, due to more viruses causing the lymphoid cells to multiply rapidly (as found by Dr. Wakefield in many cases), and causing more peptide absorption (as found by Dr. Reichelt and others). Mercury could also play an important role, as it can poison mitochondria (the part of every cell that produces energy), and it can denature DNA, alter membrane permeability, induce autoimmunity, and cause apoptosis (cell death). In a test-tube, very low (micromolar) concentrations of thimerosoal were found to cause cell death, and the addition of glutathione was found to block thimerosal and reduce cell death. One possible therapy for autism is intravenous Immunoglobulin, which can neutralize bacteria and viruses and promote phagocytes to attack bacteria and fungi.



Summary: In autism, there is a major change in the immunological system, making people with autism vulnerable to bacteria, fungi, and viruses, and causes the immune system to attack the body (autoimmunity). Mercury is a possible cause of this.



Sulfation: Susan Owens substituted for Rosemarie Waring, and presented Dr. Waring's data on sulfate in autism. Basically, people with autism were found to excrete roughly twice as much sulfate in their urine, so that they had only 1/5 the normal level of sulfate in their bodies. Sulfur is an essential mineral, and is needed for many functions in the body. AIDS patients have also been found to exhibit a loss of sulfur in their urine, leading to a loss of extracellular sulfated structures in the brain. This has not yet been investigated in autism, but may be the same. In AIDS patients, treatment with N-acetyl cysteine was found to be beneficial.



In autism, TNF (tumor necrosis factor) is elevated, which can inhibit the conversion of cysteine to sulfate.



Low sulfur levels could cause many problems.

· Sulfur is needed to sulfate the hormone CCK, which stimulates oxytocinergic neurons to release oxytocin. So, a lack of sulfur could explain the low oxytocin levels found in autism, which is important for socialization.

· Sulphate is important for detoxification of metals and other toxins.

· Sulphation requires activated sulfate, which requires magnesium.

· Boys excrete more sulfur than girls, so they may be more susceptible to sulfation problems.

· Wakefield's group found that the ileum of the intestine lacks sulfur, which would lead to a leaky gut.

· Sulphate is needed to release pancreatic digestive enzymes.

· Many enzymes would be impaired if sulfur levels were low.

· The perineuronal nets around neurons, which modulate their function, are primarily composed of chondroitin sulfur. Low sulfur would thus yield less modulation of neurons

· The hepatitis B vaccine was found to inhibit sulphation chemistry for one week in typical people.



Summary: Almost all people with autism have very low levels of sulfur in their blood, which could cause many of the problems associated with autism. Sulfur could be replaced by Epsom salt baths, sulfate creams (now available from Kirkman labs), or possibly with cysteine or n-acetyl cysteine (but Pangborn has concerns about the use of cysteine or n-acetyl cysteine). Since sulfate leaves the blood in 4-8 hours, it should be used at least 1x/day, and possibly more often.



Mercury: Jim Laidler discussed the latest statistics from the US Dept of Education on the number of people with autism, which show a 10-fold increase in the number of people with autism over the last 7 years. Also, they show that, unlike other disabilities, the number of people with autism is heavily skewed towards the younger ages (twice as many in the 6-11 as the 12-17 group).



Some similarities between autism and mercury toxicity include restriction of visual field (tunnel vision), autoimmune abnormalities, and many other symptoms.



Mercury detoxification is best done with DMSA. Chlorella and cilantro should be avoided because, although they gather mercury from the environment, they do not bind mercury as strongly as human tissue, so they will tent to release mercury into humans. DMSA can best be used on a 3 day on, 11 day off cycle, with dosing every 8 hours (4 hours vs. 8 does not seem to make much difference). DMSA may cause some fatigue or irritability, since it seems to cause GI dysbiosis temporarily. DMSA does not transport mercury into the brain. Once DMSA has lowered the level of heavy metals, alpha lipoic acid can be added on the days of DMSA, and will increase excretion of mercury. Doses for alpha lipoic acid can start at 1-3 mg/kg-day, and increase up to 10 mg/kg-day. Chelation should be stopped either when metal excretion is not detectable, or when no further improvements are observed. Since some people with autism improve on DMSA even when little metal is being excreted, DMSA may be having other effects, such as acting as a powerful antioxidant, removing cysteine, or binding to gliotoxin (a toxin from yeast that affects neurons).



He also discussed the possible connection between the NMDA (n-methyl d aspartate) receptor and autism. Blockage of that receptor could cause reduced pain, tunnel vision, inability to shift attention, auditory problems, repetitive behaviors, dilated pupils, and language problems. The reason is that it controls pruning of brain cells during development, modulates pain, and modulates dopamine and serotonin.



Summary: The increase in the number of people with autism could be explained by mercury in vaccines. Many symptoms of autism could be explained by mercury toxicity. DMSA, followed by DMSA and alpha lipoic acid, are effective in decreasing mercury levels, and can improve the symptoms of autism in some cases.





Lab Tests: Jon Pangborn discussed biochemical types of autism. These include:

· PKU variants: may involve dihydrobipterin-to-tetrahydrobiopterin (DPR or DHR reductase)

i. Phenylalanine -> Tyrosine

ii. Tryptophan -> 5-HTP -> Serotonin

· Fragile X: may involve deficiency of deoxyuridine to deoxythymidine transformation due to 5,10 methylene THF dysfunction

· Histidinemia: Histidine -> 5-Formimino THF

· Adenylosuccsinate Lyase Deficiency

i. Adenylosuccate -> AMP + Fumarate

ii. Purine synthesis decreased before formation of inosine

· 5-PRPP Synthesis Deficient: - initial and rate limiting step for purine synthesis; 5-PRPP also needed for pyrimidine synthesis

· Inosine Phosphate Dehydrogenase Weakness

i. Inosine phoshate -> guanine phosphate, which makes biopterin

· Lesch-Nyhan Disease

i. Hypoxanthine -> Inosine Phosphate

ii. Increase in uric acid and oxidants

· Purine autism – adenosine deaminase deficiency

· DPPIV weakness – adenosine deaminase binding protein (CD 26) – inability to digest casein and gluten



For each of the disorders listed above, he provided a flow chart of how each of them can affect metabolism. He also listed specific lab tests for Hyperphenlyalaninemia / uria, Histidineemia, Fragile X, Rett, Lesch-Nyhan Syndrome, and Purine Autism.



He briefly discussed the many factors that could weaken DPPIV, the enzyme need to digest gluten and casein, and he mentioned an open (non-blinded) study of EnZymAid and how it helped improve several symptoms of autism.



Finally, he gave examples of typical findings in elemental analyses of packed red blood cells and hair, amino acid testing, detox profiles, comprehensive digestive stool analyses, yeast sensitivity, bacterial sensitivity, and fatty acid analysis. This is all discussed in more detail in the new DAN! Protocol, which he co-authored.



Treatments: Woody McGinnis (from Practitioner Training session 1):

Autism and ADHD are similar, with multiple underlying problems, and the gut and nutrition are of paramount importance. There has been extensive reports in the literature of GI problems. In particular, 85% of children suffering from night awakening were found to have reflux esophagitis – stomach acid rose into their esophagus when they lay down, burning it.



GI problems lead to poor nutrient digestion and absorption, a leaky gut, microbial overgrowth, and possibly altered signaling to the brain (80% of vagus nerves go from gut to head).



Low zinc can lead to low stomach acid, which is critical for digestion. 45% of people with ADHD have low stomach acid, and probably similar for autism.



Greater oxidative stress is common. Hence, give vitamins C, E, A, zinc, selenium, and taurine. Both the gut and brain are very sensitive to oxidative stress.



To help with detoxification, give B6, B12, folate, Mg, zinc, selenium, lipoic acid, and methionine.



Possible treatments include: diets (GFCF, low sugar, organic (esp. meat), purified water, no Nutrasweet), digestive enzymes, probiotics, vitamin/mineral supplements (esp. zinc and C), cod liver oil (for vitamin A and D), fish oil and evening primrose oil (for omega 3 and omega 6 fatty acids), anti-viral medications, secretin, DMSA/alpha lipoic acid (to remove heavy metals), and bethanecol (helps intestinal mucosa, stimulates digestive enzymes).



Recommends full nutritional assay. This includes checking stool pH (easy at home), IgE or IgG food testing, and urinary pyroles (25% of autistics have bad toxin; Vitamin Diagnostics is one possible lab).



For constipation problems, recommends magnesium citrate, fiber, vitamin C, and bethanecol.



Glutamine can be great to feed intestine, but avoid if blood ammonia high.


Extra: Jeff Bradstreet

First, Jeff unveiled his plans to create an integrated campus facility to treat the biological, behavioral, and nutritional needs of people with autism. He hopes to raise $20-$30 million in private funds to create it.



Then he began discussing the biological problems in autism and how to treat them. First, he explained that vaccines and vaccine additives can shift the immune system from TH1 to TH2. In some cases these additives are added specifically to stimulate antibody production, but in the case of autism it may overstimulate it, causing autoimmunity problems.



Next, he discussed the etiology of autism in the following series:

1) autistic enterocolitis creates an abnormal environment for bad bacteria, yeast, and parasites

2) Mercury exposure alters the type of microorganisms in the gut (also occurs when DMSA is used to excrete mercury)

3) In his small study, he found that on a DMSA challenge test, autistic children excrete 5x as much mercury as normal children (8.63 mcg per 24 hr, vs. 1.48 mcg per 24 hr). Thus, either they were exposed to high amounts and/or they have a limited ability to excrete it. The mercury can have many effects, including completely inhibiting the DPPIV, needed to digest gluten and casein.

4) In terms of nutritional abnormalities:

a. Zn deficiency exists in 90% of autistic children

b. Cu excess exists in 90%

c. Calcium and magnesium deficiencies are common

d. Omega 3 deficiency exists in nearly 100%

e. Fiber deficiency exists in nearly 100%

f. Antioxidant deficiency exists in nearly 100%

5) The damaged GI tract causes poor protein digestion. This results in:

a. Deficiency of essential amino acids

b. Extra food for bad bacteria, causing high levels of ammonia (a toxin) – substances that reduce ammonia may reduce brain fog (alpha keto glutaric acid is one option)

c. Gluten and casein peptides, which act as opioids

d. Undigested proteins causing allergic reactions in gut and blood



He also listed treatment options for various disorders. These include:

Treatment for Viral Infections:



Monolaurin: ¼ tsp., 3x/day: active vs. measles, HHV-6, pathogenic bacteria; seemed to have helped 2 kids



Treatment for Weakened Immune System

· Zinc: 20-200 mg
· Selenium: 100-200 mcg

· Beta-glucan (activates macrophages, the part of the blood that eats foreign matter)

· Caution: easily becomes rancid, so make sure you get a good brand

· IP-6 (from Enzymatic Therapy): activates Natural Killer cells; 1-2/day on empty stomach

· Transfer Factor: from Chisolm

· Oral immune globulin – prescription only



Treatment for Mercury and other Heavy Metals

(See Consensus Treatment for Metal Detoxification for Children with Autism)

· DMSA: but it can cause temporary regression, possibly by the undigested amount feeding gut bacteria

· Alpha Lipoic Acid: but caution, it can make some children worse

· Glutathione: oral, transdermal, or intravenous

· Colostrums (Kirkman's Super Colostrum Gold)

· Monolaurin

· Vancomycin or flagyl – to fight bad bacteria

· Fiber (Miralax is one option)

· Reduce sugars

· Eat vegetables

· Essential fatty acids



Treatment for Protein Maldigestion:

· morselation: chew food into smaller pieces, so more surface area for digestion

· Digestive Enzymes: options include EnzymAid, Creon, others for all meals/snacks



Treatment for Ammonia Excess

· It is a neurotoxin. To test for it, ship blood only on dry ice.

· To treat it, follow treatment for protein maldigestion. Also, reduce/eliminate glutamine. Finally, use alpha keto glutaric acid, 100-300 mg, 2x/day



Treatment for Nutritional Deficiencies
· Multivitamin/mineral supplement

· Essential fatty acids

· High-quality food (no junk food, soda, etc)

· Eat smaller portions, more frequently



Treatment for Food Allergies
· Test for food allergies at a lab like Immunolabs – remove allergic foods

· Rotation diet (don’t eat the same thing)

· Digestive enzymes

· IV Immunoglobulin and mercury detoxification may help



Treatment for Detoxification:
· Oral sulfur: taurine, glucosamine sulfate, MSM, n-acetyl cysteine

· Transdermal magnesium sulfate (Kirkman), Epsom salt baths

· Glutathione – transdermal or IV

· Milk Thistle – to support liver



Summary:

1) gut damage creates breeding ground for bad bacteria and fungi

2) mercury causes GI problems

3) many nutritional deficiencies exist

4) poor protein digestion causes nutritional deficiencies and food for bad bacteria



Effective treatments for the above conditions exist and can help.



Also, at the meeting Kirkman Laboratories distributed a free 176 page Guide to Intestinal Health in Autism Spectrum Disorder. You can request a copy from Kirkman Labs, 1-888-KIRKMAN.





Day 2:



Yeast Treatments: Sidney Baker:

Dr. Baker discussed the importance of first evaluating the severity of each symptom on a simple scale (3=mild, 6=moderate, 9=severe, 12=incapacitating), and then trying different treatments and evaluating their effect. Ie, treat the child, not the tests.

He mentioned GFCF diets, anti-fungal treatments, vitamin/mineral supplements, and essential fatty acid supplements.



He especially discussed an unusual anti-fungal treatment, saccharomyces boulardi (available from 1-800-426-2831), which is a yeast that attacks other yeast. It produces lactic acid that promotes good flora. As with any effective anti-fungal, it can cause a die-off reaction (when the yeast die all their toxins are released at once), and activated charcoal (from a pharmacy, 4x/day) can help absorb those toxins. He also listed several nonprescription anti-fungal treatments, including capryllic acid, undecelynic acid, citrus seed extract, oil of oregano, and garlic. Both organic acid tests and stool tests can sometimes be contradictory and misleading.



He mentioned that high methylmalonic acid is an indicator of vitamin B12 deficiency, and recommends B12 injections in those cases (absorption of B12 is very low in the digestive tract). Only Vitamin Diagnostics has a good direct test for B12 test. B12 injections can help within hours to days.



Secretin – Walter Herlihy (RepliGen)

Initial collection of parental reports by the Autism Research Institute (Bernie Rimland) helped them determine that a single infusion of secretin seemed to help for 3-5 weeks.



In order to win FDA approval for secretin, there are three phases of testing. For secretin, Phase 1 (safety) and Phase 2 (establish dosing) have been completed. They are now hoping to start Phase 3 (statistical proof of efficacy).



In reviewing the Phase 1 trials, most of them were small, so that although they showed some improvement the results were not statistically significant. However, pooling all of the results into a meta-analysis did show a positive benefit of secretin.



In the phase 2 trials, 126 patients at 5 labs were involved in a double-blind, placebo-controlled study including 3 infusions. The results of the two standardized tests (GARS and CARS) showed only minor improvement, and were not statistically significant. Clinical Global Impressions (CGI, a very simple 1-7 scale rating whether they became better or worse) was rated by parents and by professionals. The parents results showed a 0.43 improvement on the scale compared to controls, which was statistically significant, but the professionals found only a 0.22 improvement, which was not statistically significant. The ADOS test, which has become the gold standard for assessing severity of autism, found some improvement, but again not statistically significant. The MacArthur Language Inventory found a small effect of secretin, but it was not statistically significant. Finally, there was an evaluation of GI function, but there was no difference between the children who received the placebo vs. the secretin.



However, analysis of stool samples found that many of the children had abnormal levels of chymotrypsin (29% had low levels) or calprotectin (26% had elevated levels). These abnormalities seemed to result in more day-to-day variation in behavior, and made it harder to evaluate. So, the data was re-analyzed without those children, leaving 64 children to be analyzed. Those results were more positive, and statistically significant results were found in the data was then re-analyzed to only count children who did not have chymotrypsin or calprotectin abnormalities in the stool, as those seemed to cause a lot of day-to-day variation in behavior. In this case, the CGI-parent and CGI-professional scores, the ADOS, and the MacArthur Language Inventory all showed statistically significant results.



In addition, his lab searched for opioid peptides, but did not find any in the 120 patients that they investigated, which is a curious contradiction with work by Reichelt, Cade, Shattock, and several other researchers who have found them.



Conclusion: The phase II study showed some statistically significant benefit for secretin, especially when considering only the subset of children who did not have chymotrypsin or calprotectin abnormalities. The benefits included language, but did not include GI function.



Disordered Metal Metabolism: William Walsh first discussed his data on 503 children with autism, which found an elevated Cu: Zinc ratio in nearly all the children. Specifically, 85% had very high Cu: Zinc ratios, 8% were receiving zinc supplements and had only moderate imbalances, 6% has a severe pyrole disorder (indicating severe zinc depletion), and only 4 of the 503 children did not have a serious Cu: Zinc imbalance. The average Cu: Zinc ration was 1.63 in autism, vs. 1.15 in the controls, and was highly statistically significant (p<0.0001). This is a very important finding from a very large study.



Walsh hypothesizes that the Cu: Zinc imbalance could be due to a defect in metallothionein function, since metallothionein proteins regulate Cu and Zinc levels. The primary functions of metallothionein include: development of brain neurons; cell transcription; regulation of Cu and Zinc; detoxification of heavy metals; maturation of GI tract; powerful antioxidant; immune function; deliver of zinc to cells. It is the primary defense of the body against heavy metals. If a defect in metallothionein exists, it could be due to a genetic impairment or due to environmental damage.



There are four metallothionein proteins:

MT-I and MT-2 are present in all cells throughout the brain and periphery

MT-III is a neuronal growth inhibitor found primarily in brain

MT-IV is found primarily in skin and GI tract.



A defective metallothionein could explain many of the symptoms of autism, including sensitivity to heavy metals, zinc depletion and copper overload, reduced stomach acid, incomplete breakdown of proteins. Since metallothionein production is enhanced by estrogen and progesterone during early development, females will be better protected than males against heavy metals.



Researchers studied a MT-knockout mouse (a mouse without any metallothionein) and found that it had a very weakened immune system and had a high incidence of seizures.



The activity of metallothionein is primarily enhanced by zinc, glutathione, selenium, and n-acetyl cysteine. Of secondary benefit are vitamins B6, A, C, D, E, genistein, biochanin A, and glucorticoids.



In Wilson's disease, copper overload can be treated by removing excess copper and long-term zinc therapy. This may also help in autism, and may lead to reduced GI problems, improved behavior and cognition, and reduced vulnerability to heavy metals. His lab (Pfeiffer Labs) is investigating nutritional interventions to promote metallothionein and thereby reduce symptoms of autism.



However, there are no commercial lab tests for metallothionein, and the children with autism did not have their metallothionein levels tested.



Also, their lab found that 45% of children with autism were undermethylated (needed folate and DMAE), whereas 15% were overmethylated.



Conclusion: In a very large and important study of 503 children with autism, a very high Cu: Zinc ratio was found. This could have a wide-reaching effect since copper and zinc play many roles in the body. It is hypothesized that the Cu: Zn imbalance is due to a defect in metallothionein, and such a defect could explain many of the biochemical abnormalities in autism. Nutritional interventions with zinc and other supplements are recommended for treating this imbalance.



Paul Shattock (AKA Robert Redbird):

Paul humorously discussed the great increase in the incidence of autism, which now affects 1 in 150 children. He thinks it is due to a combination of a genetic susceptibility and an increase in an environmental toxin(s). These could include vaccines, pesticides, dietary changes, gut dysbioses, heavy metals, plasticizers, toxic fumes, food additives, and drug residues in food and water.



In his studies of the urine of people with autism, they often find peptides that are similar to opioids, several times as potent as morphine. Opioids are known to decrease sociability, decrease memory and learning ability, increase stereotopy and hyperactivity, cause constipation and lower body temperature. These peptides could interfere with the central nervous system, and affect many functions, including perception, cognition, behaviors, mood, emotions, CNS development, immune system, and gut function.



Based on the levels of one type of peptide (IAG), there seem to be two types of autism:



Type 1: elevation in many peptides, including IAG

Type 2: elevation in many peptides, but normal IAG

Type 2 is the more recent type, and occurs about 10% of the time in the UK and 50% in the US, suggesting it is due to vaccine exposure which is more recent and higher in the US. Type 2 children tend to be more social, have unusual thirst, have an abnormal gait, and have bowel problems.



Elevated IAG levels are also found in Gulf War veterans.



Freeman had found dermorphin, a peptide 2000x more potent than morphine, in some children with autism.



Waring had found that people with autism had only 1/5 as much sulfur in their blood as normal, which could cause several problems, including:

1) neurotransmitters not being processed after use

2) reduced ability to eliminate metals

3) leaky gut

4) proliferation of yeast in gut



Organophosphate pesticides act by blocking enzymes in insects, and may also affect enzymes in humans and IAG levels.



Sunderland treatment protocol (available at www.osiris.sunderland.ac.uk/autism)

1) test for celiac disease and amino acids

2) vitamin/mineral supplements

3) GFCF diet, and keep a food diary to determine if other foods should be avoided

4) Test vitamin/mineral levels, and test for allergies

5) Comprehensive digestive stool analysis

6) Increase sulfation with Epsom salts

7) Try betaine HCl to increase stomach acid

8) Fatty acid supplements

9) L-glutamine to feed intestinal mucosa

10) 5-HTP

11) possibly try chelation



Summary: There are elevated peptides in the urine of people with autism that have an opioid effect, and could cause many of the symptoms of autism.


Vaccines: Jeff Bradstreet

The US Dept of Education now estimates that 1 in 150 children in the US have autism. This increase could be due to the increased use of vaccinations. Vaccines contain mercury (a preservative), aluminum (to increase antibody production), crude toxoids, and live viruses. Prof. Singh has found antibodies to myelin basic protein in many autistic children, and this is likely related to an atypical measles infection.



He has tested the mercury excretion of 200 children with autism using DMSA, and found that it varies greatly with age, peaking around age 5 and again around age 10.



In collaboration with researchers in Indonesia, a study of 27 children with autism found that 23/27 had autoimmunity, 6 of 27 had elevated mercury, and 25 of 27 had elevated mercury in their hair.



Elevated ammonia is common in autism, and a study of 65 children with autism found that 70% had levels above the reference range of the lab.



Thrombophilia, a coagulation disorder, was found in 70% of the children with autism, and in many of the parents (he advised all parents to have it tested)



Day 1 Summary: Ken Bock provided a summary of what was covered on Day 1.



Day 2: Bernard Rimland gave an overview of the history of the fight against autism. He provided several articles on the importance of B6 and magnesium, and discussed the effectiveness of DMG in enhancing the immune system. He discussed his survey results of thousands of parents on treatment efficacy (see www.ari.org for full report).
Intervention: % benefited % worse

Nutritional supplements 40-67% 0-7%

Special diets 41-52% 1-2%
Antifungal medications 47-66% 5-6%

Psychiatric medications 16-46% 15-47%



Supplements included calcium, DMG, folic acid, melatonin, vitamin B3, vitamin B6 with magnesium, vitamin C, and zinc.



Diets included candida, Feingold, rotation, no chocolate, no dairy, no eggs, no sugar, no wheat.



Antifungal medications included nystatin and diflucan.



Summary: Nutritional supplements, special diets, and antifungal medications have been reported by parents to be beneficial in roughly half the cases, with minimal risk of becoming worse.





Omega 3 Fatty Acids: Andrew Stolle:

Omega 3 fatty acids have been evaluated for the treatment of a wide range of psychiatric disorders, including schizophrenia, depression, postpartum depression, and bipolar disorder. DHA (found in flaxseed) does not help those conditions, but EPA (found in fish oil) does help. In fact, EPA was often more beneficial than conventional medications.



In his previous study of bipolar disorder, he found that 10 g/day of fish oil helped.



Eskimos consume 15-19 g/day of omega 3 fatty acids (EPA and DHA), but in the US we consume less than 1 g/day, probably far less than is needed. Omega 3 oils are created only by phytoplankton (algae), and are then consumed by fish. Animals cannot make omega 3 oils. The primary sources of omega 3 oils are flaxseed (which has some drawbacks), seaweed (which may be contaminated), fish oil, and Country Hen eggs (chickens fed flaxseed and fish, so the eggs are high in omega 3).



In Japan, although they consume a large amount of fish, they do not seem to be affected by the high level of mercury in their diet.



Most commercial fish oils are low quality. Need one that does not have a rancid flavor. One option is Omega Brite, which is highly concentrated.



There has been a theoretical concern that too much omega 3 could cause bleeding, but studies of over 15,000 patients taking omega 3 found that there was no evidence of increased bleeding.



Dose: He recommends 2-5 g of omega 3, 1-2x/day, with the EPA level much higher than the DHA level (except possibly for young children, who need some DHA for their brain development, since the brain in 60% DHA.



For more information, read his book, The Omega 3 Connection.



Summary: EPA has recently proven to be beneficial in a number of psychiatric disorders, whereas DHA has not. There has not been any formal research on its use in autism, but it may be beneficial. High-quality fish oil is a good source of omega 3 fatty acids.





Omega 3 Fatty Acids: Paul Hardy

Dr. Hardy discussed his experience with treating many people with autism with omega 3 fatty acids and other nutritional supplements. He hypothesizes that some people diagnosed with ASD may actually have bipolar disorder.



During the last 100 years, brain size has decreased 10%, and this could be due to a lack of omega 3 fatty acids since they make up over 60% of the brain. Dietary intake of omega 3 fatty acids has greatly decreased in the US. Farm-raised fish are usually raised on corn, so they have little or no omega 3 fatty acids (which are made by algae). Also, the use of cod liver oil as a medication was largely stopped in the 1960s for no apparent reason. Finally, baby formulas do not contain any essential fatty acids.



In his clinical experience, he finds that many people with autism have an omega 3 deficiency, and often have elevated arachidonic acid (a bad fatty acid). Also, since omega 3 levels are very low in the US, the reference ranges of the testing labs may be too low. He estimates that 90% of people with ASD need omega 3 fatty acids.



He recommends 2-5 g/day of combined EPA and DHA, starting at a lower level and increasing.


Mercury: Jane El-Dahr

(All her viewgraphs are on the www.ari.org website; she also recommends going to www.safeminds.org)



She recommends a new book, What Your Doctor May Not Tell You About Children's Vaccinations, by Stephanie Cave (just released).



Hypothesis: In genetically susceptible individuals, prenatal and early childhood exposure to mercury may cause neurological damage leading to autism. This hypothesis is supported by symptom comparisons, toxicity studies, case studies, and epidemiology. The most likely sources of the mercury are maternal dental fillings, maternal fish consumption, consumer products (eye drops, nasal sprays, others), Rho-gam shot, Influenza vaccine during pregnancy, and childhood vaccines. The increase in autism appears to correlate with the increased use of vaccinations. In children who are fully vaccinated, by the sixth month of life they have received more mercury from vaccines than recommended by the EPA.



There are many similarities in symptoms between mercury toxicity and autism, including social deficits, language deficits, repetitive behaviors, sensory abnormalities, cognition deficits, movement disorders, and behavioral problems. There are also similarities in physical symptoms, including biochemical, gastrointestinal, muscle tone, neurochemistry, neurophysiology, EEG measurements, and immune system/autoimmunity.



In an analysis of the Vaccine Safety Database (two HMOs, covering 110,000 children born from 1992 to 1997), found that there were statistically significant associations between cumulative exposure to thimerosal-containing vaccines and risk for developmental delays, tics, ADD, language/speech delay and neurodevelopmental delay. However, there were too few children to determine if there was a risk for autism.



Conclusion: Mercury may be the cause of some of the cases of autism. Children were exposed to high amounts of mercury through childhood vaccinations, and there is a strong similarity in symptoms between mercury toxicity and autism.


Treatment of Mercury Toxicity: Amy Holmes

Dr. Holmes discussed the treatment of mercury toxicity with DMSA, followed by DMSA plus alpha lipoic acid. It is very difficult to test for mercury toxicity, because it clears quickly from blood, urine and hair (within months or less) and resides in tissue. Instead, she recommends testing for the effects of mercury, including urine organic acid, fractionated urine porphyrins, immune system test, and other blood tests. She especially favors looking for sulfate wasting in urine, as that indicates kidney dysfunction, and mercury binds strongly to kidneys. (Note that Waring has found sulfate wasting in most children with autism).



Before beginning mercury detoxification, first clear up the gut of bacteria and yeast, and keep it clean. Also, remove all sources of mercury, including removing dental mercury-silver fillings, stop seafood consumption, and avoid thimerosal exposure from vaccines or other sources. Also, nutritional supplements are important.



Then, in step 1, use DMSA alone to remove mercury from the body. Take a maximum dose of 10 mg/kg, 3x/day, for 3 days, then 11 days off. Repeat several times. Glycine can be added, but has only a very small effect on mercury excretion (5%). Test urine after 2-5 rounds, since the metals are mostly excreted in the urine. Continue until little mercury/heavy metals are being eliminated.



Then, in step 2, take the DMSA with alpha lipoic acid, at a ratio of DMSA: LA from 2:1 to 6:1. Whereas DMSA cannot cross the blood-brain barrier, LA can, and causes the mercury to mostly be excreted in the stool. Thus, the addition of LA will result in much more mercury being excreted, possibly from the brain. Test the stool every 4-6 months, to determine how much is eliminated, and continue until it is in the normal range. If stool is difficult to obtain, hair can be used instead.



Step 2 was greatly slowed if lead or tin were still present, so it is important to remove those before adding the LA to the DMSA.



During step 2, common side effects are: worse behavior initially, diarrhea, headache, fatigue, overgrowth of intestinal yeast and bad bacteria. Also, must monitor complete blood counts, liver enzymes, and mineral problems. These are uncommon effects, affecting only 0.5%



She summarized their preliminary results for treating 152 children with DMSA + LA after 6 months. Note that some children, probably the older ones, might need longer treatment times.



Child’s age Level of Improvement

Marked Moderate Slight None

1-5 yr. 36% 39% 15% 9%

6-12 15% 35% 36% 15%

13-17 0% 17% 54% 29%

18+ 0% 14% 14% 71%



Marked improvement means little/no autistic symptoms. The degree of improvement correlated with the amount of metals being excreted on DMSA + LA. The children who responded most quickly were the ones who had developed normally and then regressed. The other children may take longer. Much more research is needed.



Conclusion: DMSA followed by DMSA + alpha lipoic acid is effective in removing mercury and other heavy metals, and results in significant improvements, especially in younger children and in those who had developed normally and then regressed.




Bug in the Gut: Andrew Wakefield

Dr. Wakefield first summarized his research on autistic enterocolitis. First, there is evidence of a persistent viral infection in the blood of many children with autism, based on decreased CD3 lymphocytes, raised IgG1, and low IgG4 and IgG2. Also, biopsies of children with autism reveals inflammation of the gut, including the epithelium (lining), usually throughout the entire small intestine, large intestine, and colon. Live measles virus was found in 76 of 83 children with autism, vs. 1 of 35 controls. Genetic testing revealed that it was from the vaccine strain, not the wild strain. Dr. Singh tested autistic children and found that they tended to have elevated levels of antibodies to measles, but not to other viruses. Altogether, this data suggests that MMR could be causally related to autism.

To test that hypothesis, he considered a challenge/re-challenge study. Basically, he looked at children with autism who seemed to have regressed after their first MMR. He then followed the children to see what happened if they had a second MMR, and compared them against children who did not have a second MMR. He looked at a wide range of types of data, including behavior, physical symptoms, macroscopic and microscopic pathology, and growth charts. In those children who had a second MMR, over half of them had a second regression shortly after that MMR, whereas few/none of the children without a second MMR had additional regression. This appears to be strong evidence that the MMR can cause autism.



At the end of the conference, there was a Q&A period for the mercury panel, and then Sidney Baker summarized what we had learned. Overall, it was clear that many of the physicians and researchers agreed on many points, although sometimes with different emphases.

[semillama]

6. Response to cut and paste from DAN! enthusiast:

Karl Reichelt - not supported by subsequent testing.
Cass H, Gringras P, March J, McKendrick I, O’Hare AE, Owen L, Pollin C., Absence of urinary opioid peptides in children with Autism. Arch Dis Child. 2008 Mar 12 - “There were no significant differences between the HPLC urinary profiles of the children affected by autism and the typically developing controls. In those cases where HPLC showed peaks in the locations at which opioid peptides might be expected to be found, MALDI-TOF established that these peaks did not, in fact, represent opioid peptides at all.”
and Hunter et al (Opioid peptides and dipeptidyl peptidase in autism. Dev Med Child Neurol. 2003 Feb;45(2):121-8.)-

“Opioid peptides were not detected in either the urine of children with autism (10 children; nine males, one female; age range 2 years 6 months to 10 years 1 month) or their siblings (10 children; seven males, three females; age range 2 years 3 months to 12 years 7 months) using liquid chromatography-ultraviolet-mass spectrometric analysis (LC-UV-MS).”

Various tired flogging of mercury/vaccines manufactureversy:
http://www.sciencebasedmedicine.org/?p=14


finally, citing Andrew Wakefield? really?

[HysteryDiagnosis]

7. Let me see if you can read this first sentence:

From the fourth paper below:

>>The significant elevation in the concentration of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity.
PMID: 20625937 <<


Acta Neurobiol Exp (Wars). 2010;70(2):177-86.
Blood mercury levels in autism spectrum disorder: Is there a threshold level?
Geier DA, Audhya T, Kern JK, Geier MR.
Institute of Chronic Illnesses, Inc., Silver Spring, MD, USA.
Abstract
Mercury (Hg) may significantly impact the pathogenesis of autism spectrum disorders (ASDs). Lab results generated by Vitamin Diagnostics (CLIA-approved) from 2003-2007, were examined among subjects diagnosed with an ASD (n=83) in comparison to neurotypical controls (n=89). Blood Hg levels were determined by analyzing Hg content in red blood cells (RBC) using cold vapor analysis, and consistent Hg measurements were observed between Vitamin Diagnostics and the University of Rochester. Adjusted (age, gender, and date of collection) mean Hg levels were 1.9-fold significantly (P<.0001) increased among subjects diagnosed with an ASD (21.4 microg/L) in comparison to controls (11.4 microg/L). Further, an adjusted significant (P<.0005) threshold effect >15 microg/L) was observed for Hg levels on the risk of a subject being diagnosed with an ASD in comparison to controls (odds ratio=6.4). The weight of scientific evidence supports Hg as a causal factor in subjects diagnosed with an ASD.
PMID: 20628441 Free Article

Pediatr Int. 2010 Jul 4.
Toxicity Biomarkers in Autism Spectrum Disorder: A Blinded Study of Urinary Porphyrins.
Kern JK, Geier DA, Adams JB, Mehta JA, Grannemann BD, Geier MR.
Genetic Consultants of Dallas/ASD Centers, LLC., Allen, Texas.
Abstract
Abstract Background: Recent studies suggest children diagnosed with an autism spectrum disorder (ASD) have significantly increased levels of urinary porphyrins associated with mercury (Hg) toxicity, including pentacarboxyporphyrin (5cxP), precoproporphyrin (prcP), and coproporphyrin (cP), compared to typically developing controls. However, these initial studies were criticized because the controls were not age- and gender-matched to the children diagnosed with an ASD. Methods: Urinary porphyrin biomarkers in a group of children (2-13 years of age) diagnosed with an ASD (n=20) were compared to matched (age, gender, race, location, and year tested) group of typically developing controls (n = 20). Results: Participants diagnosed with an ASD had significantly increased levels of 5cxP, prcP, and cP in comparison to controls. No significant differences were found in non-Hg associated urinary porphyrins (uroporphyrins, hexacarboxyporphyrin, and heptacarboxyporphyrin). There was a significantly increased odds ratio for an ASD diagnosis relative to controls among study participants with precoproporphyrin (odds ratio = 15.5, p < 0.01) and coproporphyrin (odds ratio = 15.5, p < 0.01) levels in the second through fourth quartiles in comparison to the first quartile. Conclusion: These results suggest that the levels of Hg-toxicity-associated porphyrins are higher in children with an ASD diagnosis than controls. Although the pattern seen (increased 5cxP, prcP, and cP) is characteristic of Hg toxicity, the influence of other factors, such as genetics and other metals cannot be completely ruled-out.
PMID: 20626635

Acta Neurobiol Exp (Wars). 2010;70(2):209-26.
The biological basis of autism spectrum disorders: Understanding causation and treatment by clinical geneticists.
Geier DA, Kern JK, Geier MR.
The Institute of Chronic Illnesses, Inc., Silver Spring, Maryland, USA.
Abstract
Autism spectrum disorders (ASDs) also known as pervasive developmental disorders (PDD) are a behaviorally defined group of neurodevelopmental disorders that are usually diagnosed in early childhood. ASDs disproportionately affect male children. Mercury (Hg) a heavy metal, is widespread and persistent in the environment. Mercury is a ubiquitous source of danger in fish, drugs, fungicides/herbicides, dental fillings, thermometers, and many other products. Elevated Hg concentrations may remain in the brain from several years to decades following exposure. This is important because investigators have long recognized that Hg is a neurodevelopmental poison; it can cause problems in neuronal cell migration and division, and can ultimately cause cell degeneration and death. Case-reports of patients have described developmental regressions with ASD symptoms following fetal and/or early childhood Hg exposure, and epidemiological studies have linked exposure to Hg with an elevated risk of a patient being diagnosed with an ASD. Immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with ASDs were reported following Hg intoxication with similarities extending to neuroanatomy, neurotransmitters, and biochemistry. The sexual dimorphism of ASDs may result from synergistic neurotoxicity caused by the interaction of testosterone and Hg; in contrast, estrogen is protective, mitigating the toxicity of Hg. Mercury exposure may significantly increase androgen levels, and as a result, patients diagnosed with an ASD may significantly benefit from anti-androgen therapy. Finally, the clinical geneticist has a wealth of biomarkers to evaluate and treat patients diagnosed with an ASD.
PMID: 20628444 Free Article

Biol Trace Elem Res. 2010 Jul 13.
Level of Trace Elements (Copper, Zinc, Magnesium and Selenium) and Toxic Elements (Lead and Mercury) in the Hair and Nail of Children with Autism.
Lakshmi Priya MD, Geetha A.
Department of Biochemistry, Bharathi Women's College, Chennai, 600 108, Tamil Nadu, India.
Abstract
Autism is a multi-factorial pathology observed in children with altered levels of essential and elevated levels of toxic elements. There are also studies reporting a decrease in nutritional trace elements in the hair and nail of autistic children with healthy controls; moreover, bioelements have been shown to play an important role in the central nervous system. Therefore, the purpose of the present study was to assess the levels of trace elements like copper (Cu), zinc (Zn), magnesium (Mg), and selenium (Se) and toxic elements like mercury (Hg), and lead (Pb) in the hair and nail samples of autistic children and to evaluate whether the level of these elements could be correlated with the severity of autism. The subjects of the study were 45 autistic children with different grades of severity (low (LFA), medium (MFA), and high (HFA) functioning autism) according to Childhood Autism Rating Scale, n = 15 children in each group and 50 healthy children (age and sex matched). The boys and girls ratio involved in this study was 4:1, and they were 4-12 years of age. The study observed a valid indication of Cu body burden in the autistic children. The children with different grades of autism showed high significance (p < 0.001) in the level of copper in their hair and nail samples when compared to healthy controls. The level of Cu in the autistic children could be correlated with their degree of severity (more the Cu burden severe is autism). The study showed a significant elevation (p < 0.001) in the levels of toxic metals Pb and Hg in both hair and nail samples of autistic children when compared to healthy control group. The elevation was much pronounced in LFA group subjects when compared among autistic groups MFA and HFA. The levels of trace elements Mg and Se were significantly decreased (p < 0.001) in autistic children when compared to control. The trace element Zn showed significant variation in both hair and nails of LFA group children when compared to control group and other study groups. The significant elevation in the concentration of Cu, Pb, and Hg and significant decrease in the concentration of Mg and Se observed in the hair and nail samples of autistic subjects could be well correlated with their degrees of severity.
PMID: 20625937