Throwing children into oncoming traffic: The truth about Autism

[CrackSmokeRepublican]

 Throwing children into oncoming traffic: The truth about Autism

By: Kenneth Stoller, MD, FAAP with Anne McElroy Dachel

Tuesday, April 24th, 2007

I have been a practicing pediatrician for over 20 years. I saw my first child with autism in the early 90's – before that I had never seen an autistic child, and I never saw an autistic child in all my years at school. The boy was 4 years old and you could see the frustration in his face as he wanted to speak but nothing intelligible would come from his mouth except shrieks of anguish.  

As I studied his tortured face, it was as if there was an old time telephone switchboard operator inside his head trying to plug in the correct phone cables but not being able to complete the call. This family had known me from an old practice I worked at in another city, but they had traveled to see me because they trusted me and were looking for answers that no one seemed to have for them, but I too had no answers and I could see the mom was greatly disappointed. After the family left my office I poured over a few dusty textbooks and wondered if I had just seen a very rare disorder, a disorder that affected one child in 10,000 children...autism.  

I had been involved in pediatrics for a decade by the time I saw this boy and it wasn't as if I had no experience working with rare disorders. I had been able to identify a boy with Fragile-X syndrome and his mom ending up starting the Fragile-X support group at Children's Hospital in Los Angeles.  

I had noticed there was a strange upswing in children with attention disorders and impulsivity problems. I wasn't a neurologist, but had studied with one of the finest at UCLA. While I was still a pediatric resident I spent time in his office where he helped me study the parade of unusual maladies that was starting to afflict children. I considered myself a closet neurologist, because that was what I had really wanted to specialize in – not pediatrics, but during my neurology rotation in medical school I learned some discouraging news. The attending neurologist, whom I greatly admired, had taken me on rounds for the first time and I watched him brilliantly explain to the family of a stroke patient how he had figured out where in the brain the blood clot had lodged. Then he stood up and walked out of the room and I asked him what therapy he was going to prescribe for the patient so he could recover from his stroke, "therapy?" he said, "there is no therapy."  

Well, I scratched neurology off my list...diagnosis was only meaningful if you could offer a treatment and it seemed neurology had few treatments to offer.  

My second patient with autism came to me in the mid 1990's, but to my relief the purpose of the visit was only to treat worms. I dutifully prescribed the medicine for pinworms and went on to my next patient. Later that afternoon I received a call from the autistic boy's mom who wanted to know what was that medicine I had given her son for pinworms....her boy was starting to make eye contact, show affection and communicate with his family. She said it was amazing! I told her I didn't really didn't know what was in the pinworm pill but immediately prescribed enough pills for her son to take everyday for a month (normally you only take one or two pills to treat pinworms).  

I called up the pharmaceutical company that manufactured the pinworm pill and spoke to one of their technical staff. They told me the pill worked by blocking the transport of molecules of a certain size from crossing cell membranes, so in the case of the hapless pinworms they were unable to absorb the sugars they feed upon in the lower intestines of their victims.  

What did that have to do with this boy's newly found improved behavior? Either one of two things were going on: 1) the drug was either blocking a molecule that shouldn't be passing across the gut to the blood and then the brain and that molecule was having a drug-like affect on the brain, or; 2) the drug was blocking a molecule that normally crossed from the gut into the blood but in certain children these molecules had a strange drug-like affect.  

I made several calls across the country to find a researcher who might be interested in this serendipitous finding which could be an important clue into this disease, because no where had I found anything saying that the guts of these children were involved in their disease. Unfortunately, no one I talked to was interested.  

Testifying to Congress...

In May 2004, I had been invited to testify in front of the Government Reform Committee to discuss new developments in treating children with Autism Spectrum Disorders. I had been invited because of the work I was doing with hyperbaric oxygen in treating brain injured children, including fetal alcohol syndrome. Hyperbaric oxygen is where oxygen is given under pressure in chambers that are used to treat scuba divers who get the bends. I and several other physicians had found that hyperbaric oxygen was returning functionality to the brains of affected children.  

Sitting next to me was a physician who told the story of his son who had become autistic after receiving vaccine and how he discovered his son was retaining toxic heavy metals, specifically mercury. Over the course of a year this physician had given his son a chemical to pull out the mercury and his son began speaking again and in fact jumped on his dad's lap and addressed the Committee members having been restored to be a healthy boy without any signs of his autism.  

In the 1990's I had known there was a problem with many of the vaccines because they contained the preservative Thimerosal (50% mercury) and I had discouraged many parents from getting vaccine containing Thimerosal – there is no safe level of mercury, and it didn't make sense to inject the most toxic non-radioactive element on the planet into children, but I never made the connection between autism and mercury. I knew what Thimerosal was because while I was in college my brother had a very bad reaction to the Thimerosal that used to be used in contact lens solution.  

I was taken aback that something so obvious had not registered with me, but I didn't realize that I and my physician colleagues had been subjected to a disinformation campaign to make us think there was no connection between mercury and autism. It has been known for sometime that mercury was causing autism, but someone was running interference. The question was who was running interference?  

In February 2007, the watchdog agency on America's health, the Centers for Disease Control and Prevention (CDC), made the official announcement that a breath-taking one in 150 kids is autistic in the U.S. If you go to the CDC website on autism (http://www.cdc.gov/ncbddd/autism) you'd see lots of pictures of smiling happy children with autism and we'd be told that autism spectrum disorders are "a group of developmental disabilities defined by significant impairments in social interaction and communication and the presence of unusual behaviors and interests."  

You won't be told that for many parents autism is a nightmare from which they never wake up.  "Significant impairments" can mean that a child is violent and self-abusive, non-verbal, and physically sick. You won't be told that this is a medical disease where most autistic children have significant inflammation in both gut and brain including colitis, super-infections and severe food allergies.  

Even though autism affects one in 90 boys (four boys affected for every girl) in the U.S., the CDC can't seem to tell us exactly why.  The CDC states, "We still don't know a lot about the causes of Autism Spectrum Disorders (ASDs). Scientists think that both genes and the environment play a role, and there might be many causes that lead to ASDs."  

The site also doesn't mention that only one in 10,000 children in the 1970s, and one in 2,500 in the 1980s were autistic.

The CDC site also doesn't tell us about a secret meeting that was held in June of 2000 where over 50 individuals from the CDC, WHO, NIH, American Academy of Pediatrics, and many representatives from pharmaceutical interests discussed data from the CDC Vaccine Data Sets showing that the increase in mercury exposure from the stepped-up vaccine schedule in the 1990's caused an 11 fold increase in neurobehavioral disorders (http://www.autismhelpforyou.com/Simpson ... 20Rico.htm). What you will see on the CDC website is "Several studies have looked at whether there is a relationship between vaccines and autism. The weight of the evidence indicates that vaccines are not associated with autism."  

Evidence? Someone at the CDC was 'cooking the books' and what they told the public was not what they knew to be the case. You see, the CDC was put in the untenable position of helping to develop vaccines, mandate the vaccines, promote the vaccines, pay for their administration and be responsible for their safety – Ye olde fox watching the hen house scenario with the inevitable untoward result. There will always be a problem with vaccine safety until this responsibility is moved out of the CDC. Today, the CDC and its vaccine public-relation front group's answer to any criticism is that the motivations of those that are critical of any part of the vaccine program are because they really want to destroy the vaccine program.  

The truth is that the CDC has been very effective in laying the foundation to destroy the vaccine program all by themselves and their double speak is analogous to someone saying you can't be against war and support the troops at the same time, you're either for us or against us, etc. It is actually illegal for a federal agency to propagandize the American public, but that is exactly what the vaccine division of the CDC does. It has used the tactic of generating fear and it has earned billions of dollars for this agency.

Once the public loses trust in public health programs it can take many years to regain that trust. I am reminded of the Tuskegee syphilis experiments that are still a cause of distrust of public health programs amongst Black Americans.

Losing the Public Trust...

The cover-up at the CDC surrounding the mercury preservative found in so many vaccines (up until about 2003) has had very serious far-reaching implications. The children whose lives were forever changed by being injected with Thimerosal preservative were giving us a global 'heads-up.' They were showing us that the background level of mercury pollution has increased to the point that it is beginning to take its toll on the human species, but the CDC turned its head away from this crisis because it conflicted with what they were promoting in the vaccine program.

As I said before, mercury is the deadliest non-radioactive element on Earth, and 1000s of tons are spewed into the environment every year. With each coal-fire power plant that comes on line we are one step closer to exterminating human life on this planet. However, mercury is politically protected because of its connection with the fossil-fuel industry, dentistry (amalgam dental filings), and vaccine.

Thimerosal is still in the flu vaccine for children above the age of 3 and they are receiving as much as half of the dose of mercury that the child in the '90's received. Thimerosal was not removed from vaccine in 1999. That was when the promise was made, but promises weren't kept. Thimerosal is also in the meningitis vaccine.

Lower IQ levels linked to mercury exposure in the womb cost the USA $8.7 billion a year in lost-earnings potential according to a study done by the Mount Sinai Center for Children's Health and the Environment (http://fusion.mssm.edu/media/content.cfm?storynum=252). If it were publicly acknowledged that mercury pollution was the trigger for the autism epidemic this number would be in the trillions of dollars. One in six children is born to mothers with dangerous levels of mercury in their blood – perhaps the same one in six that the CDC admits have a neurobehavioral disorder.

Our regulatory agencies, such as the FDA and the EPA, have been taken over by the very industries they were mandated to regulate and the revolving door between industry and top-level appointees at these regulatory agencies has eliminated many of the normal safeguards we have relied on for our protection.

There is no disputing the numbers.  Last month the Tonawanda News in New York reported "cases of autism in the state jumped from fewer than 2,000 in 1992 to 9,500 in 2003."  Even worse was the number of affected children in New York schools in 2005-2006 according to the Dept. of Education.  New York's autism total had increased to 12,257.  

Maybe what we really need to be made aware of is what the eventual cost of autism will be to the U.S.  The Autism Society of America tells us that autism is growing by 10-17% a year.  They also say that it currently costs $90 billion a year and it's projected to increase to $200-400 billion annually in ten more years.  A Harvard study out last year put the cost of lifetime support conservatively at $3.2 million per individual.  

April was Autism Awareness month, but why are we only asking for awareness and not for answers?   This is a glaring omission when we're talking about so many affected children.  Awareness, treatment, and identification are critical but so is preventing autism.

If we were talking about children going blind read how obscene this would sound:

"The number of children diagnosed with blindness is rapidly increasing. According to a study from the Centers for Disease Control and Prevention, nearly one in every 150 U.S. children is blind. These numbers are startling and this disability is affecting more and more families. Twenty years ago blindness was a very rare case. Today blindness is becoming a frightening statistic in every community.  April is Blindness Awareness Month and I encourage everyone to take this opportunity to learn more about this disability..."

It would be absurd to relate this information about blindness without giving any explanation about what was causing it.  Everyone would be demanding answers, and I dare say there would be protests in the streets to say the least.

The CDC and Autism...

CDC director Julie Gerberding announced the new autism rate of one in every 150 children with a flourish. She said that while there were more kids being diagnosed with autism, it doesn't mean the autism was necessarily on the rise. No one in the press seemed concerned that the CDC has been counting kids with autism for years and still can't tell us if there are actually more of them. After all, it's just "better diagnosing by doctors" and "better statistics by the Centers for Disease Control." And now we learn that the Autism Genome Project (AGP) recently uncovered evidence shows that autism is caused by "genetic flaws."  

Common sense would tell us that pushing children onto a busy street, observing that some of them were injured, and then looking for a genetic reason why some of them were hit defies credulity.

No other disease in history has been subjected to the spin that has been put on autism.

Dr. Ezra Susser, chairman of epidemiology at Columbia University's Mailman School of Public Health in New York indicated that he believed the new genetic findings would help scientists to understand how "the environment might lead to autism by causing genetic changes."

Susser said, "It shows us that we need to think about many environmental factors that might influence autism."

The new genetic findings on autism got a lot of coverage from major news outlets and reports made it look like we're on the cutting edge of a major autism breakthrough. But let's do a reality check here, genes don't just spontaneously and randomly mutate all by themselves. There has to be an environmental agent affecting these genes.

Some will have you believe that autism is some medical mystery that's always been around but we just haven't been able to get a handle on. So, show me the 30 year olds with autism, the 40 year olds with autism, and the 50 year olds with autism. Guess what? They aren't there for the most part. The explosion in the number of children with autism is real but most of the scientific community has ignored this. Let's face it they have been encouraged to ignore it, and anyone getting close to the truth finds that they get their NIH research grants pulled.

That's right...science is being manipulated so that a big lie can stay alive and those culpable can remain unaccountable.

It seems the scientific world isn't concerned that more children will be diagnosed with autism this year than with AIDS, diabetes and pediatric cancer combined. News stories about autistic kids are now beginning to reveal the duplicity of CDC officials. These reports clearly show that this isn't something we have all the time in the world to theorize and ponder about.

All the experts searching diligently for those elusive genetic mutations seem blissfully unaware of the impact of autism on our schools and the impending disaster, as these autistic children become autistic adults. Anyone looking at the graphs and charts based on Department of Education statistics showing the soaring autism numbers has got to be worried. The dramatic increase in children in our schools disabled with autism is a scary preview of the impact they will have on the Social Security System in the next five to ten years.

Michael Ganz's Harvard study last year conservatively put the lifetime care cost for one autistic individual at $3.2 million dollars.

Robert Krakow from Lifespire gives us estimates that put the lifespan cost at $10.125 million per autistic individual. This figure is based on an annual rate for each person of $225,000 with a life expectancy of 66 years. It doesn't include the cost for the period up to age 21.

One of the many questions we need to ask ourselves is if the very integrity of the biosphere on this planet is in jeopardy unless there is an immediate curtailment of manmade mercury pollution. Coal miners don't look at a dead canary and blow it off or say they have just "gotten better at diagnosing dead canaries," or "that dead canary just had a genetic defect so pay no heed." Yet that is exactly analogous to the situation we find ourselves. We continue to pollute the planet and ourselves (there is no separation), yet the very governmental agency that would normally be taking the lead in sounding this 5 alarm alert has been compromised and remains less than silent. Mercury pollution should be considered a global crime against humanity, against mammalian life on this planet and there should be zero tolerance.

If you want to know why more isn't being done for autistic children, why there has been a strange cover-up of the facts, then simply follow the mercury and those that benefit from its use.

Kenneth Stoller, MD, FAAP is medical director of the Hyperbaric Medical Center of New Mexico (http://www.hbotnm.com) and the Hyperbaric Oxygen Clinic of Sacramento (http://www.hbot.info). He is President of the International Hyperbaric Medical Association. He can be reached at: amdachel@msn.com.

 http://www.bolenreport.net/feature_arti ... cle058.htm

[CrackSmokeRepublican]

http://www.latimes.com/features/health/ ... 1598.story


Researchers find common genetic variations in autistic people
Findings show that many autistic people have a deviation in a portion of their DNA that affects the way brain cells connect with one another. The discovery may lead to treatments.

By Trine Tsouderos
April 29, 2009
Reporting from Chicago -- Researchers have found that many people with autism share common genetic variations, a discovery that may improve diagnosis and offers the promise of developing treatments for the frustratingly mysterious disorder.

Their findings, published in the journal Nature, compared the genomes of thousands of autistic people with those of thousands of people without the disorder -- a massive task that new technology has only recently made possible. The genome is the complex system of DNA coding that builds and runs the human body.

[CrackSmokeRepublican]

Autism and the Human Gut Flora       Print        E-mail
Articles - Autism Articles

by Dr. Max Bingham
Food Microbial Sciences Unit, Science and Technology Centre, Earley Gate, University of Reading, Whiteknights Road, Reading, Berkshire, UK. RG6 6BZ

Abstract

Previous research into autism has raised the possibility that a link exists between the disorder and the human gut microflora. Research has remained limited due to the unwillingness of the orthodox medical establishment to adopt treatments suggested by this research. This short review aims to summarise the research completed to date and evaluate the relevance of a link between autism and a possible imbalance in the human gut microflora. It appears that yeasts (Candida species in particular) and clostridia may play an important role in the development of autistic symptoms. It is suggested that the control of the growth of these species may reduce the severity of autistic symptoms but is unlikely to offer a cure.

Introduction

Previous research into autism has raised the possibility that a link exists between the disorder and the human gut microflora. However the relevance of this to sufferers of Autism has remained somewhat un-researched. As a consequence, it appears that the treatments suggested previously have remained unused and regarded by the orthodox medical establishment as irrelevant. This short review will consider the limited research completed to date.

Autism

The term autism is usually associated with the syndrome first described by Kanner (1943). In more recent years specific criteria have been set out to aid in the diagnosis of the disorder (Shaw et al, 1999). Autism typically develops early in childhood, however causality, explanation and treatment are often hotly debated. Symptoms can include (but not necessarily), hyperactivity, loss of eye contact, decreased vocalisation (i.e. loss of language), stereotypical behaviours, poor academic performance and other similar social deficits. Other similar disorders exist. These include Asperger Syndrome, Attention Deficit Hyperactivity Disorder (ADHD), Pervasive developmental disorder (PDD) and many others, where symptoms are similar to Autism but specific differences are demonstrated.

Yeast metabolites in the Urine of Autistic Children

Yeasts constitute only a very small proportion of the population of the gut (Holzapfel et al, 1998) under normal conditions – possibly kept from growing via competition from bacterial species and certain immune functions. However, Shaw et al (1999) has proposed that Autism (or at least many of the symptoms) may be a consequence of an overgrowth of candida species and a selective IgA deficiency. Following treatment with antifungal drugs and a gluten and casein free diet, a child rated as having severe autism improved such an amount as to be classed as a higher functioning individual with autism.*

It has been shown previously that children exhibiting autistic features have increased excretion of arabinose and the analogs of Krebs Cycle metabolites (including tartaric acid) (Shaw, Kassen & Chaves, 1995). Using Gas Chromatography/Mass Spectrometry (GC/MS) to test for urinary metabolites, it was found that the children had extremely high values of tartaric acid. The only source of tartaric acid is yeast (Shaw, 1999). Many reports have suggested that the onset of autism may be related to the occurrence in children of otitis media (Kontstantareas & Homatidis, 1987). It is common to treat otitis media with some sort of broad-spectrum antibiotic. Intestinal overgrowth of yeast and certain anaerobic bacteria are a well documented outcome of the administration of broad spectrum antibiotics (Kennedy & Volz, 1983; Danna et al, 1991; Ostfield et al, 1977; Kinsman et al, 1989; Van der Waaij, 1987; Samsonis et al, 1993, 1994a,b).

To evaluate this, it is known that Shaw (1999, 1996) has used GC/MS to test the urinary content of metabolites following the administration of Nystatin, an antifungal drug. Accordingly it was found that urinary tartaric acid declined to zero after about 60 days. When the Nystatin dose was cut to half, levels appeared to rise. Associated with this was seen an improvement in eye contact, a reduction in hyperactivity and an improvement in sleep patterns. It is unclear as to the method used, however these are interesting results. In other work, Shaw (1999) has evaluated the progress of the Herxheimer reaction of yeast die off. Values for the microbial metabolites described above increased dramatically during the first three days and began to normalise near day four. It is unclear as to the relevance of the point that many children take antibiotics for a whole series of illnesses, but do not develop autism.

Gupta et al (1996) have studied some possible modulating factors in Autism. These include immunodeficiencies and probable differences in biochemical detoxication factors which appear to be very common in autism,. It has been estimated that a high percentage of autisitic children have a significant immune dysfunction that may include myeloperoxidase deficiency, a genetic deficiency that impairs the action of white blood cells on yeast cells, IgA deficiency, complement C4b deficiency, IgG deficiency or IgG subclass deficiency (Gupta et al, 1996). In the above study, a complete remission of autisitic symptoms was achieved by infusions of gamma globulin in one case. Shaw (1999) has suggested that it seems increasingly likely that the immune system takes an inventory of bacteria and yeast cells present in the gut soon after birth. This inventory is performed by CD5+ B-cells. These cells may play a role in regulating the secretion of IgA, the antibody class that is secreted into the intestinal tract and which may select which microorganisms are tolerated in the gut. Continuing, it is suggested that the eradication of the normal gut flora when antibiotics are administered repeatedly during infancy may cause the CD5+ cells to reject normal cells and award immune tolerance to species that potentially could cause harm. Either antibiotic use in infancy or yeast infection of the mother during pregnancy may result in later tolerance to yeast. This would possibly extend any remission from symptoms induced by methods of treatment suggested for autism.

Yeast and Tartaric Acid Toxicity

Shaw, Kassen & Chaves (1995) noted in their initial study of the two brothers with autism, that in addition to their autistic characteristics, they exhibited severe muscle weakness. Both of these brothers excreted large amounts of tartaric acid in their urine. It is known that tartaric acid is an analog of malic acid. Malic acid is a key intermediate in the Krebs cycle which is responsible for the extraction of most of the energy from food substrates. Tartaric acid is presumably seen as toxic since it would inhibit this pathway and limit energy production. This may be the reason for the muscle weakness seen in the two autistic brothers. It has also been shown that Candida albicans produce gliotoxins (Shah and Larsen, 1991 and 1992) and immunotoxins (Podzorski et al, 1989; Witken, 1985), which may further impair the immune system. This would have relevance in terms of promoting yeast growth and increasing the chances of additional infections from bacteria leading to antibiotic usage again.

Arabinose, Yeast and Autism

Shaw, Kassen & Chaves (1995), also identified high levels of arabinose in the urine of the autistic children. The exact biochemical role of arabinose is unknown, but a closely related yeast alcohol, arabitol has been used as a biochemical indicator of invasive candidiasis (Kiehn et al, 1979; Wong et al, 1990, Roboz & Katz, 1992). It is thought that arabitol produced by the yeast in the gut is absorbed into the portal circulation and then converted to arabinose by the liver. Elevated protein-bound arabinose has been found in the serum glycoproteins of schizophrenics (Varma & Hoshino, 1980) and in children with conduct disorders (Varma et al, 1983).

Arabinose reacts with the epsilon amino group of lysine in a wide variety of proteins and may then form cross-links with arginine residues in an adjoining protein (Sell & Monnier, 1989). Arabinose has therefore been implicated in protein modification via cross-linking the proteins and altering both biological structures and functions of a wide variety of proteins. Shaw et al (1999) has proposed that this may include proteins involved in the interconnection of neurons. Decreased clinical symptoms of autism after antifungal treatment might be due to decreased arabinose and pentosidine formation (cross-linked proteins described above). This would result in fewer random neural connections and increased numbers of neural connections that are oriented to the child's environment. The influence of a number of vitamins on candida activity and the operation of many metabolites of candida has been discussed (Mahler & Cordes, 1966). It is commonly found that children with autism experience improved symptoms following removal of gluten and casein from the diet (Shattock et al 1990, 1991, 1996, 1997; Reichelt et al, 1981, 1986; Knivsberg et al, 1990). It is unclear whether there is a link with arabinose and pentosidine formation, however given the wide distribution of these proteins in foods, there may be a relevant process involved with respect to autistic symptoms. Research into this may be useful.

Clostridia and Autism

Bolte (1998) outlined the possibility of a subacute, chronic tetanus infection of the gut as the underlying cause for symptoms of autism observed in some individuals. Here it is postulated that a percentage of individuals with autism have a history of extensive antibiotic use. As above it is known that oral antibiotics significantly disrupt protective gut microflora, creating a favourable environment for colonisation by opportunistic pathogens. Clostridium tetani is a ubiquitous anaerobic bacillus that is known to produce a potent neurotoxin. The normal site of binding for tetanus neurotoxin is the spinal cord, yet the vagus nerve is capable of transporting tetanus neurotoxin, providing a route of ascent from the intestinal tract to the central nervous system and bypassing the spinal cord. The result would be the typical symptoms of a tetanus infection would not be evident. Once in the brain the tetanus neurotoxin disrupts the release of neurotransmitters. This may explain the wide variety of behavioural deficits apparent in autism. Bolte (1998) presents evidence of lab animals exhibiting many of these behaviours after being injected in the brain with tetanus neurotoxin, and also of children with autism showing a significant reduction in sterotyped behaviour following treatment with antimicrobials effective against intestinal clostridia.

Shaw (1999) has developed a similar technique to yeast metabolite analysis by GC/MS for clostridia metabolites. While it has not been fully identified it has been shown that tyrosine derivative, a compound very similar but not identical to 3,4-dihydroyphenylpropionic acid is raised in the urine of children with various conduct disorders. It has also been pointed out that tyrosine, a substrate used by the body for the production of neurotransmitters, might imply that this unidentified product is important in altering key biochemical pathways for neurotransmitters in the brain. The relevance to autism remains unclear. Clearly a treatment to reduce the numbers of clostridia in the gut might help to reduce the effects of this inhabitation. However, clostridia are spore forming meaning recolonisation is possible even after treatment. The relevance of probiotic and prebiotic treatments has not been researched, yet this appears a reasonable approach to aid suppression of the clostridia species.

Human Gut Flora and Gluten and Casein Intolerance in Autistic Children

Yeasts, including Candida albicans are known to secrete a number of enzymes. These may include phospholipase, which will break down phopholipids and proteases such as secretory aspartate protease which break down proteins. These enzymes may partially digest the gut membranes and lining itself. Furthermore, it is known that the mycelium and chlamydospore are capable of tissue invasion (Nolting et al, 1994). It is likely that such factors could increase the permeability of the gut. This has important consequences in terms of food absorption and digestion. In terms of autism symptoms this may be highly relevant. It has been shown that incompletely broken down portions of gluten and casein may be crossing the gut into the blood and having an opioid effect in autistic children. Their symptoms being a consequence of this opioid action (Reichelt, 1981; Shattock et al, 1990). While many mechanisms have been suggested for this incomplete breakdown, it seems key that a yeast and/or clostridia overgrowth would affect this in some way.

Conclusions

Products of the human gut microflora in relation to autism and its symptoms appear to have been largely ignored in the past. However they appear to be relevant certainly in terms of yeast and clostridia species. Abnormal bacterial metabolites of tyrosine appear to be elevated in autism and this seems related largely to an overgrowth in clostridia species. Treatments to control this have resulted in significant clinical improvement or complete remission of symptoms in some cases. The issue of whether probiotic and prebiotic treatments are relevant, needs to be researched. Elevation of yeast metabolites such as tartaric acid and arabinose appears to be even more common in autism. The arabinose appears to be involved in abnormal protein binding which may adversely affect neuron connection and this may have relevance to the appearance of autistic symptoms. Given the intolerance autistic children appear to have to gluten and casein, an involvement of arabinose may be important. However, the exact biochemical role of arabinose remains unclear. Tartaric acid from the yeast overgrowth may have a direct toxic effect on the muscles and is a key inhibitor of the Krebs Cycle that supplies raw materials for gluconeogenesis. The implications of this appear to be detrimental to autistic function.

While it is clear that abnormal metabolites from the human gut flora may contribute to autistic symptoms, it is certain that many other systems and pathways are involved. It is possible that many are functioning simultaneously but at varying levels between individuals. This may give rise to the differences in symptoms exhibited by sufferers. This may also explain the similarity of autism and other chronic behavioural disorders such as Asperger Syndrome, PDD, ADHD, ADD and Rett syndrome. While other pathways may exist, research into the role of human gut flora and the full identification of species involved may allow for more directed treatments. While it will not cure the disorder, modifications of gut flora function might improve symptoms significantly.

* The Childhood Autism Rating Scale, an observational measure of various aspects of autism, for the child in question decreased from 43 (severely autistic) prior to introduction of these therapies to a value of 29 (non-autistic) after therapy.

http://www.ei-resource.org/articles/aut ... gut-flora/

[CrackSmokeRepublican]

Autism and GI Problems
By Jody Goddard

Recent research shows that more than 50% of children with autism have GI symptoms, food allergies, and maldigestion or malabsorption issues (Horvath). It's obvious from talking to parents that GI problems are a major concern in children with autism. Listservs dealing with autism have discussions on GI issues all the time. Antifungal use, both prescription and alternative remedies, is a common topic. Parents have tried "anti-yeast" diets, prescription drugs and natural remedies, but nothing seems to be "the answer" to the chronic microbial problems these kids face. Many parents wish to pursue chelation for their children, but are unable to do so because of their inability to get their children's gut pathogens under control.

Altered intestinal permeability was found in 43% of autistic patients, but not found in any of the controls (Harvard University). Intestinal permeability, commonly called "leaky gut", means that there are larger than normal spaces present between the cells of the gut wall. When these large spaces exist in the small intestine, it allows undigested food and other toxins to enter the blood stream. When incompletely broken down foods enter the body, the immune system mounts an attack against the "foreigner" resulting in food allergies and sensitivities. The release of antibodies triggers inflammatory reactions when the foods are eaten again. The chronic inflammation lowers IgA levels. Sufficient levels of IgA are needed to protect the intestinal tract from clostridia and yeast. The decreasing IgA levels allow for even further microbe proliferation in the intestinal tract. Vitamin and mineral deficiencies are also found due to the leaky gut problem.

http://www.breakingtheviciouscycle.info ... oblems.htm

[nik]

I'm deeply interested in this. Many thanks for this thread.

[CrackSmokeRepublican]

Good Show on the origination of Autism and Vaccinations:

http://www.wellsphere.com/healthy-eatin ... gut/749712


Mannose likely plays a factor as well:

http://www.bio.davidson.edu/courses/imm ... r/MBL.html

[CrackSmokeRepublican]

Before going this far, I'd first:

1.  Clear out the gut with a heavy programme of the old style Pinworm medicines
http://www.bolenreport.net/feature_arti ... cle058.htm

2.  Rebuild the flora with Fermented Foods
3.  Keep up the Pinworm Medicine while eliminating Celiac, Wheat and refined sugars from the diet
4. If this fails, start the Helminth treatment
5. These kids are likely "Tripping"



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Evidence for Immunotherapy in the form of Helminthic Therapy for the treatment of Autism

It is well documented that there is an association between autism and immune dysfunction (DelGuidice, 2003). Post-mortem brain tissues from 11 autistic patients have demonstrated the presence of an active and ongoing neuroinflammatory process in the cerebral cortex and white matter, and notably in the cerebellum. Cerebral Spinal Fluid (CSF) assays from patients with autism following developmental regression were found to have a proinflammatory profile of cytokines compared to a control group (Pardo et al., 2005; Zimmerman, 2006).

The details of what is going on are very complex, may vary amongst autistics, and are incompletely understood. So the use of helminths based on their anti-inflammatory effects is speculative and arose largely because of the observations and experiences of a father of an autistic boy, Stewart Johnson. After reading widely on the subject and trying various therapies, he settled upon using Trichuris suis ova (TSO) from Ovamed. TSO was the first commercially available helminthic therapy and can be obtained directly from this web site.

Johnson observed remarkably positive changes in his son, you can read about them here.

As a result of other parents' experiences using TSO to treat their autistic children we were approached in the spring of 2007 by Judy Chinitz, whose account of her experiences appears below.

Hookworm was an attractive alternative to TSO to many parents because of the expense. Over the long term hookworm are potentially a great deal less expensive than TSO. We all believed it would provide similar or better results because with hookworm as opposed to TSO the organism is meant to live in humans and is therefore better adapted to reducing inflammation in humans. And as opposed to TSO there is not a cycle of dosing, response, die off, decline in the level of benefit from TSO. Instead the response was very different.

Hookworm infection appears to result in an improvement in cognitive function in those we have provided it to (see Judy's account below). But it does not produce the kinds of benefits that TSO does, as described by Stewart Johnson. Hookworm do not result in an improvement in social function.

We have currently treated eight juvenile autistics, with varying severity of autism. All those far enough along with what has been a slow approach to infection with hookworm have shown some degree of increase in cognitive function, and we have learned a great deal about how to treat autistic children using hookworm safely. We have since changed the treatment protocol to accelerate treatment, having learned how to do so safely.

But we now believe, based on a recent research paper suggesting this, that a combination of helminths will produce better results, as is apparent in those using TSO and hookworm together. We have obtained a second helminth, Trichuris trichiura (the human equivalent of Trichuris suis marketed by Ovamed), to add to the treatment for autistic children.

We have not yet treated any of our current autistic population of clients with Trichuris trichiura, although we expect to start in May of 2009. We do not yet know what the results will be and expect that it will be early 2010 before we have a clear idea how effective this approach will be.

It is important to understand that while results with TSO and Hookworm, and potentially with Trichuris trichiura ova (TTO) are promising, they are not a magic bullet that is likely to restore any autistic child. Furthermore the experience of both hookworm and TSO is variable and cyclical, and is not straightforward. For instance use of IvIg therapy concurrent with hookworm is not recommended.

Please contact us to discuss the complex issues surrounding Autism and helminthic therapy. For autistic patients, and only for autistic patients, we offer both organisms for the price of hookworm alone, although this offer will be available only until we have learned what the benefits of combined therapy are.

Because Judy wrote such a well-referenced account we do not provide a separate section for science on this page.

Please note: if you are interested in exploring treatment options for autism we require that you complete a one hour consultation with Judy Chinitz at New Star Nutrition before approaching us. We have seen the financial impact of autism on too many families and are not as well equipped to counsel parents of autistic children as Judy is. Judy is person you can trust, she receives no financial compensation for referrals to AIT, and Judy is a published author on autism, mother of an autistic child, and is very experienced with all of the available treatments for autism. She has expertise with the Specific Carbohydrate Diet (SCD) and helminthic therapy in particular. Her fee is $175.00 for the consultation and her advice alone will probably save you 100 times her fee over the next ten years as you battle this terrible disease.

Autism and the immune system: a brief overview
- by Judy Chinitz, MS, MS

In 1964, Dr. Bernard Rimland published his book , Infantile Autism: The Syndrome and Its Implication for a Neural Theory of Behavior, proving that autism was a physiological – as opposed to a psychological – condition. By the 1970s, researchers noted immune system abnormalities in these children. In the 1980s, researchers like Dr. Reed Warren clearly demonstrated that those with autism had abnormal lymphocyte responsiveness (that is, their white blood cells don't respond normally to germs) and abnormal levels of various types of immune cells, including low levels of natural killer cells. (This means that children on the spectrum have a hard time fighting pathogens like yeast, viruses and bacteria.)

In 1998, Dr. Sudhir Gupta, of the University of California at Irvine, published a paper in the Journal of Neuroimmunolgy entitled, "Th1- and Th2-like cytokines in CD4+ and CD8+ cells in autism." This paper states that the "...data suggest that an imbalance of Th1- and Th2-like cytokines in autism may play a role in the pathogenesis of autism." His work has been replicated many times since.

What does this mean? Simply put, there are different parts of our immune system. The innate immune system causes an initial inflammatory response when a pathogen is introduced into our bodies. The adaptive immune system forms antibodies over the course of a few days – which, in turn, provides us ongoing immunity if those same pathogens make their way into our bodies at a later time. In autism, there are abnormalities in both these parts of the immune system. Some major immunological insult, sometime very early in life, has seriously disrupted the normal immune balance in children with ASD (autistic spectrum disorders).

A few of the specific abnormalities found in autism include:

   1. In an unstimulated state, individuals with autism have higher levels of proinflammtory cytokines (chemical messengers of the immune system) than controls.
   2. With stimulation of the immune system (i.e. with the introduction of pathogens), individuals with ASD have markedly higher levels of proinflammatory cytokines than controls.
   3. Specific proinflammatory cytokines that have been found to be high in people on the spectrum include Tumor Necrosis Factor alpha (TNF-alpha) in both the blood and the gut; interferon gamma (IFN-gamma) in both blood and the gut; levels of IL-12 are higher in the blood.
   4. Individuals with ASD have lower levels than controls of regulatory cytokines (those chemicals that turn off inflammation) like interleukin-10 (IL-10).

About 60% of our immune system is in the mucus lining of our digestive (and nasal) passages. Many, if not most, children with autistic spectrum disorders have digestive symptoms if not outright gut pathology. One of the greatest bits of wisdom ever shared with me came from Dr. Sidney Baker, co-founder of the Defeat Autism Now! Team of clinicians and researchers. "Inflammation is inflammation." It may sound so simple but the implications are vast. These chemicals of inflammation are not just affecting how these individuals respond (or don't respond) to disease-causing microbes; they also affect the health of the digestive system and the function of the brain itself.

Dr. Martha Herbert, an Assistant Professor of Neurology at Harvard Medical School, a Pediatric Neurologist at the Massachusetts General Hospital in Boston, who is a foremost authority on autism, has stated over and over that the brain is downstream from the digestive system, meaning that if the latter is compromised, the former suffers. It's also a fact that if the digestive system is compromised, the entire immune system is as well – and vice versa. The brain, the digestive system, the immune system are all one – and inflammation is inflammation.

Another well-established fact is that individuals with ASD have abnormal gut microbiota. What does this mean? The human body contains about 90 trillion microbes, a number that is nearly 10 times more than the cells in our body. No one really knows what we are meant to have and in what proportions. Certainly, this will have wide variance too, depending on what microbial populations are native to our environment. We do know though that there should be something like 500 different species of bacteria living in our intestines and amongst these should be species like acidophilus. Multiple researchers have now established that individuals with ASDs have not only abnormal amounts of bacteria living in their digestive systems, but also seemingly abnormal kinds as well. It's a chicken and egg scenario: abnormal gut microbiota leads to abnormal gut conditions compromising the immune system, but the reverse is also true. Abnormal immune functioning will lead to abnormal microbiota.

There is a movement running through the medical community that believes that we have become "too sterile." Better put, with the advent of germ theory 100 years ago (the recognition that many diseases arise from specific germs), we have concentrated our efforts on eradicating bacteria and the like before we really know what they do in the human body. H. pylori is a prime example of this. In 1984 it was identified as a cause of stomach ulcers and has also now been linked to cancer. The current treatment for stomach ulcers in which H. pylori has been implicated is a course of antibiotics. However...

Over 50 percent of people in the western world have H. pylori in their stomachs and only a tiny percentage develop ulcers. More than that, bacteria in our digestive systems are a vital part of our immunological defenses. In 1999, H. pylori was shown to secrete antimicrobial substances that kill potentially pathogenic bacteria.

So, where does this leave us? Yes, individuals with autism generally have very abnormal gut microbiotia and very abnormal immune functioning. How best to handle this is not yet known. Many doctors focus on killing off the bad stuff – antibiotics for bad bacteria, antifungals for Candida, etc. And this helps...sometimes. Another line of thought though is to shift the immune system and gut back into normalcy by ADDING good flora and fauna, rather than, or as well as, subtracting bad...especially when the lines between good and bad may be more blurred than originally thought.

Enter parasites.

As you will read elsewhere on this site, parasites were a normal part of the evolving humanoid species up until 75 or so years ago. We lived on and with the soil and thus, our intestines were filled with not only bacteria and yeasts, but protozoa and other parasites too – including helminths. Human hookworm, Necator Americanus, was a NORMAL part of our gut ecology.

With our current anti-germ way of thinking, many are immediately horrified when they first think about "infecting" themselves with parasites. "Aren't parasites bad?" is the typical first question from those first learning about this form of therapy. Well, sure. Some parasites are bad. A 30 foot tape worm living in your intestines might be considered nasty (hookworm are one centimeter long fully grown and invisible to the naked eye at the time of treatment). Then again, we are all very well aware of the health benefits of yogurt – with its live, active cultures. That is, your yogurt is swarming with bacteria. Do you equate this with eating salmonella on purpose? Like bacteria, some parasites are good and some are bad. And like bacteria, some are meant to be in us. An absence of good bacteria in the gut will seriously compromise the health of the individual. More and more research suggests that an absence of good parasites does the same.

In 2007, Dr. Kevin Becker of the National Institute of Health, published an article in Medical Hypothesis entitled, "Autism, asthma, inflammation, and the hygiene hypothesis." Dr. Becker concludes, "Altered patterns of infant immune stimulation may hypersensitize the early immune system not toward allergic sensitivity and bronchial hypersensitivity but to inflammatory or cytokine responses affecting brain structure and function leading to autism. It is well documented that immune cytokines play an important role in normal brain development as well as pathological injury in early brain development. It is hypothesized that immune pathways altered by hygiene practices in western society may effect brain structure or function contributing to the development of autism."

Elsewhere on this site, there is more information on exactly what is currently known about the immunological effects of hookworm. So just briefly: they raise levels of regulatory cytokines (those chemicals that turn off inflammation) and they lower levels of inflammatory cytokines, including TNF-alpha and INF-gamma. That is, they do exactly what is needed to improve the immunological functioning of individuals on the spectrum.

Will they work though? It is too soon to say. There are so few children with autism currently inoculated with hookworm that there is very little by way of anecdotal reports, let alone any data from large-scale clinical trials.

However, over the last year, more and more parents have put their children on courses of TSO (trichuris suis) – porcine (from pigs) whip worms. As these are not native to humans, they live for only 2 to 3 weeks in the human gut. Anecdotal reports have been astounding, to say the least. The children are showing global improvements which are sometimes dramatic. The incidence of negative side effects is almost zero.

My son, Alex, is 14 years old and profoundly autistic. In 2002, an endoscopy/colonoscopy showed that he had horrific bowel disease and his immune system was so compromised that to live he required gamma globulin (human antibodies) IVs for 7 years. I first read of parasite therapy and the "hygiene hypothesis" (the idea that we are too sterile, too devoid of normal microbiota) in 1999, in an article in the New York Times, which described the work being done with TSO by Dr. Joel Weinstock, who was then at the University of Iowa. Dr. Weinstock had tested these worms in 7 individuals with inflammatory bowel disease, and had 6 of them entered remission. The 7th also dramatically improved. I tried to get the University of Iowa to treat Alex, but as he fit none of their criteria, they would not. It took me 8 years of waiting to be able to get TSO but when I finally did (in October, 2007) Alex's response was as dramatic as I always knew it would be.

Within 10 weeks his perpetual stomach bloating began to disappear. His evening screaming attacks stopped as the pain from the gas subsided. His mood become more and more stable – he was happy almost all the time. The changes were remarkable, and this in a child who has rarely responded to any treatment.

At the time of writing this, many children with autism have responded extraordinarily well to TSO. However, TSO is so expensive at the moment that it is beyond the reach of many families, especially considering that it must be done continuously. I myself could not continue with it indefinitely so I needed to find an alternative – a reasonably priced substitute. This is how I came upon Autoimmune Therapies.

To anyone's knowledge Alex is the first child with autism to have been (purposely) inoculated with hookworm. On April 21st, 2008, he received his first dose of 3 worms. At this time, Alex has 16 mature worms and has now been off TSO for 5 weeks. We have lost none of the behavioral and physical improvements he gained on TSO and in fact, since the introduction of hookworm Alex has shown distinct cognitive improvements, including academic gains (which he has never made in his life).

As of now, there is far more we don't know than we do about the immunological causes of autism, the events that have triggered the abnormalities, and mostly the way to remediate the situation. Parasite therapy may seem radical to many, but after 12 ½ years of battling my son's tremendous immune and digestive disorders, and after many months of research on the topic, I made the decision (the right one, as it turns out) to proceed. My philosophy was beautifully expressed by Dr. Herbert at the Autism One conference in Chicago, in May, 2008. I don't remember the exact words, but what she said was, when faced with prolonged scientific uncertainty, use your best judgment.

Additional information regarding therapies for autism

You can read more by Judy Chinitz about her experiences with autism, TSO, and hookworm, and with the Specific Carbohydrate Diet (SCD) here.

Bibliography

Ashwood, P., Anthony, A., Torrente, F., Wakefield, A.J. (2004). Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. Journal of Clinical Immunology 24(6):664-73.

Ashwood, P., Wakefield, A.J. (2006). Immune activation of peripheral blood and mucosal CD3+ lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms. Journal of Neuroimmunology173(1-2):126-34.

Bashir, M.E.H., Andersen, P., Fuss, I., Shi, H.N, Nagler-Anderson, C. (2002). An enteric helminth infection protects against an allergic response to dietary antigen. The Journal of Immunlogy 169:3284-3292.

Becker, K. (2007). Autism, asthma, inflammation, and the hygiene hypothesis. Medical Hypothesis, doi:10.1016/j.mehy.2007.02.019.

Croonenberghs, J., Bosmans,E., Deboutte, D., Kenis, G., Maes, M. (2002). Activation of the inflammatory response system in autism. Neuropsychobiology 45(1):1-6.

Elliott, D.E., Summers, R.W., Weinstock, J.V. (2007). Helminths as governors of immune-mediated inflammation. International Journal of Parasitology: 37(5):457-64.

Feillet, H., Bach, J.F. (2004). Increased incidence of inflammatory bowel disease: the price of the decline of infectious burden? Current Opinion in Gastroenterology:20(6):560-4.

Gupta, S., Aggarwal, S., Rashanravan, B., Lee, T. (1998). Th1- and Th2-like cytokines in CD4+ and CD8+ cells in autism. Journal of Neuroimmunlogy 85(1):106-9.

Hamilton, G. (2008). Why we need germs. The Ecologist Report. Retrieved August 4, 2008 from http://www.mindfullly.org/Health/We-Need-Germs.htm.

Jyonouchi, H., Sun, S., Le H. (2001). Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. Journal of Neuroimmunology 120(1-2):170-9.

Maizels, R.M., Yazdanbakhsh, M. (2003). Immune regulation by helminth parasites: cellular and molecular mechanisms. Nature Reviews/Immunlogy, volume 3.

Molloy, C.A., Morrow, A.L., Meinzen-Derr, J., Schleifer, K., Dienger, K., Manning-Courtney, P., Altaye, M., Wills-Karp, M. (2006). Elevated cytokine levels in ch ildren with autism spectrum disorders. Journal of Neuroimmunlogy 172(1-2):198-205.

Newman, A.(1999). In pursuit of autoimmune worm cure. The New York Times on the Web. Retrieved March, 25, 2008 from the New York Times.

Schnoeller, C., Rausch, S., Pillai, S., Avagyan, A., Wittig, B.M., Loddenkemper, C., Hamann, A., Hamelmann, E., Lucius, R., Hartmann, S. (2008). A helminth immunomodulator reduces allergic and inflammatory responses by induction of IL-10-producing macrophages. The Journal of Immunology 180:4265-4272.

Summers, R.W., Elliott, D.E., Qadir, K., Urban, J.F. Jr, Thompson, R., Weinstock, J.V. (2003). Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. American Journal of Gastroenterology Sep;98(9):2034-41.

Summers, R.W., Elliott, D.E., Urban, J.F. Jr, Thompson, R., Weinstock, J.V. (2005) Trichuris suis therapy in Crohn's disease. Gut:54:87-90.

Warren, R.P., Margaretten, N.C., Pace, N.C., Foster, A. (1986). Immune abnormalities in patients with autism. Journal of Autism and Developmental Disorders 16(2):189-97.

http://autoimmunetherapies.com/helminth ... erapy.html

[veritasvincit]

excellent research on this topic

[CrackSmokeRepublican]

Found this one as well. Interesting facts about Mannose and Mycobacteria.

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Scientists at the University of Liverpool have found how a bacterium, known to cause illness in cattle, may cause Crohn's disease in humans.

Crohn's is a condition that affects one in 800 people in the UK and causes chronic intestinal inflammation, leading to pain, bleeding and diarrhoea.

The team found that a bacterium called Mycobacterium paratuberculosis releases a molecule that prevents a type of white blood cell from killing E.coli bacteria found in the body. E.coli is known to be present within Crohn's disease tissue in increased numbers.

It is thought that the Mycobacteria make their way into the body's system via cows' milk and other dairy products. In cattle it can cause an illness called Johne's disease - a wasting, diarrhoeal condition. Until now, however, it has been unclear how this bacterium could trigger intestinal inflammation in humans.

Professor Jon Rhodes, from the University's School of Clinical Sciences, explains: "Mycobacterium paratuberculosis has been found within Crohn's disease tissue but there has been much controversy concerning its role in the disease. We have now shown that these Mycobacteria release a complex molecule containing a sugar, called mannose. This molecule prevents a type of white blood cells, called macrophages, from killing internalised E.Coli."

Scientists have previously shown that people with Crohn's disease have increased numbers of a 'sticky' type of E.coli and weakened ability to fight off intestinal bacteria. The suppressive effect of the Mycobacterial molecule on this type of white blood cell suggests it is a likely mechanism for weakening the body's defence against the bacteria.

Professor Rhodes added: "We also found that this bacterium is a likely trigger for a circulating antibody protein (ASCA) that is found in about two thirds of patients with Crohn's disease, suggesting that these people may have been infected by the Mycobacterium."

The team is beginning clinical trials to assess whether an antibiotic combination can be used to target the bacteria contained in white blood cells as a possible treatment for Crohn's disease.

The research was funded by Core and the Medical Research Council and is published in Gastroenterology.

LIVERPOOL UNIVERSITY
Liverpool
L69 3BX
http://www.liv.ac.uk

http://www.medicalnewstoday.com/articles/91955.php

[CrackSmokeRepublican]

Autism and the Human Gut Microflora

Max Bingham

Food Microbial Sciences Unit

Science and Technology Centre, Earley Gate, University of Reading, Whiteknights Road, Reading, Berkshire, UK. RG6 6BZ

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Contents

Introduction
Gut Microbiology
Factors affecting the Human Gut Microflora
Antibacterial Drugs
Age as a factor affecting the Gut Microflora
The Autistic Human Gut Microflora
Candida spp
The Herxheimer Reaction
Considerations of Gluten and Casein Removal
Clostridia and Autism
Sulphate Reducing Bacteria
Dermorphin and Deltorphin
Treatments
Probiotics, Prebiotics and Synbiotics
Probiotics
The alternative approach - prebiotics
Synbiotics
Relevance to Autistic Symptoms
On going research at Reading
Summary
References
Introduction

Research to date has suggested that there may be a link between the development of autistic symptoms and an abnormal human gut microflora. It has been shown previously, that autistic subjects tend to exhibit an elevated level of yeasts (particularly Candida spp) (Shaw, Kassen & Chaves, 1995) and/or certain gut anaerobes in their lower intestines. Other reports have suggested that the onset of certain Autistic Spectrum Disorders may be related to the occurrence of otitis media (ear infections) (Kontstantareas & Homatidis, 1987) or maybe other typical childhood illnesses. It is common to treat this sort of infection with some sort of broad-spectrum antibiotic. Intestinal overgrowth of yeast and certain anaerobic bacteria are a well documented outcome of administration of broad spectrum antibiotics (Kennedy & Volz, 1983; Danna et al, 1991; Ostfield et al, 1977; Kinsman et al, 1989; Van der Waaij, 1987; Samsonis et al, 1993, 1994a,b).

While the onset of otitis media/ other childhood illnesses and the occurrence of a yeast/ selected gut anaerobe overgrowth may not be the cause of autistic symptoms, it appears there may be a link. Products of the human gut microflora in relation to autism and its symptoms appear to have been largely ignored in the past. However they appear to be relevant certainly in terms of yeast species and certain gut anaerobes.

This report will outline the currently available evidence for a possible link between the development of autistic symptoms and abnormal human gut microflora. It will consider the roles species may take in this development and consider methods currently available that may help treat these abnormalities and as a result help alleviate the severity of some symptoms seen in autism.

Gut Microbiology at Reading

Research at the Food Microbial Sciences Unit utilises expertise in gut microbiology, anaerobic bacteriology and molecular biology to reliably identify species and systems involved in a wide variety of applications. The Human Gut Microflora is an extremely complex mixed culture comprising mainly of bacteria living in a state of dynamic equilibrium. It is estimated that as many as 500 different species reside in the colon at any one time. In the small intestine and stomach much lower numbers can be found (Figure 1).


Figure 1: Location of the Human Gut Microflora

The colon is regarded as one of the most metabolically active sites in the human body and this is due to the human gut microflora. Until recently, research on the human gut microflora has been limited by the fact that only about 88% of cells observed under the microscope are cultureable. A much smaller number are easily cultureable. More recently, the use of molecular based techniques such as DNA extraction and sequencing has meant research can be extended into areas that were previously not possible.



Figure 2: A micrograph of human faeces showing various bacteria and food particles

Figure 3: The major groups of bacterial species found in the human gut with some functions described

Figure 4: The alternative view of the human gut microflora

Factors affecting the Human Gut Microflora

The population of bacteria in the gastro-intestinal tract is determined by a great variety of factors. The most important of these factors are drugs, disease, age and diet. The consequences of these factors may be wide and varied. Figure 5 shows many of the factors.


Figure 5: Factors affecting the Human Gut Microflora (Adapted from Mallet and Rowland, 1988)

Antibacterial Drugs

The use of antibiotics, particularly via the oral route, often results in the suppression of some, though not all, components of the human gut microflora. This suppression will depend upon the antibiotic used and partly on the resistance of the bacteria in the gut. Once established, the gut microflora exhibits a remarkable stability in terms of a dynamic equilibrium. It is a major factor in preventing the establishment of potentially pathogenic or exogenous organisms. This is colonisation resistance. This factor can be significantly disrupted through the use of antibiotics. The strictly anaerobic components of the microflora appear to be the most crucial to the maintenance of colonisation resistance (Van der Waaij, 1979)

Age as a factor affecting the Gut Microflora

At birth the gut exhibits sterility but becomes rapidly colonised by microorganisms passed from the mother and from the environment. Lactobacillus spp and Bifidobacterium spp reach high numbers initially. Shortly after birth, facultative anaerobes such as Streptococcus spp and E.coli can be detected. This population remains fairly stable during suckling. With the introduction of solid food, major changes occur as strict anaerobes such as Bacteroides spp gain supremacy. These changes may significantly affect the susceptibility of the infant to foreign substances. Any disruption to the gut microflora might therefore affect the development of the child. The use of antibiotics could affect this balance of gut microflora.

The Autistic Human Gut Microflora

Many autistic subjects exhibit a range of gut disorders. These can include diarrhoea, constipation, gas retention and abnormal faeces. Imbalances in the gut microflora may be responsible for these problems. Research into the characteristics of the autistic human gut microflora has been extremely limited. It now seems increasingly likely that imbalances in the gut microflora and the development of autistic symptoms may be linked. Certain unusual species of microorganisms may be implicated. These include certain yeasts (Candida spp), certain clostridia may be important and most recently it is thought that sulphate reducing bacteria could be included in this list. Controlling the growth of these organisms may help to alleviate some symptoms of autism.

Candida spp

Candida normally constitutes only a very small proportion of the human gut microflora. Competitive inhibition and certain immune functions keep growth under control. Previous research has led some groups to suggest that certain autistic characteristics may partially be a consequence of an overgrowth of Candida spp. Elevated yeast metabolites such as tartaric acid and arabinose appear to be relatively common in autism. The arabinose appears to be involved in abnormal protein binding which may adversely affect neuron connection and this may have relevance to the appearance of autistic symptoms (Sell & Monnier, 1989; Shaw et al, 1999). Given the intolerance that autistic subjects appear to have to gluten and casein, an involvement of arabinose and pentosidine formation may be important. However the exact biochemical role of arabinose remains unclear.

Tartaric acid from a yeast overgrowth may have a direct toxic effect on muscles and is a key inhibitor of the Krebs cycle that supplies raw materials for gluconeogenesis (Shaw, Cassen & Chaves, 1995). The implications of this appear to be detrimental to autistic function. Furthermore, it has been shown that Candida albicans can produce gliotoxins (Shah & Larsen, 1991, 1992) and immunotoxins (Podorski et al, 1989; Witken, 1985), which may have further relevance to the development of autisitic symptoms.

Over 160 species of Candida have been identified (Barnett et al, 1990). They are described as ovoid budding yeasts that typically reproduce vegetatively and may exhibit hyphae. Figures 6 and 6a are micrographs demonstrating certain characteristics of Candida.

Figure 6: An ovoid budding Candida cell. Micrograph from http://research.amnh.org/exhibitions/ep ... robes.html

Figure 6a: Candia exhibiting hyphae and reproducing vegetatively
http://www.medsch.wisc.edu/medmicro/myc ... icans.html

Six Candida species have been implicated as human pathogens. Candida albicans and Candida tropicalis are thought to cause the majority of Candida infections. Clinical manifestations of a Candida overgrowth vary widely but can include fatigue, mood lability, depression, inability to concentrate, headaches, loss of energy, food cravings, mould sensitivity and multiple food and chemical intolerances. In children, chronic recurrent infections are common and these often require antibiotics. Carbohydrate cravings and central nervous system dysfunction are also seen (Kroker, 1987).

Candida albicans may interfere with immune function at a number of levels. This can include interfence with correct Candida antigen presentation by macrophages; secretion of hyphal substances; subsequent release of by-products and toxins into circulation and this generalised impairment in cellular immunity may encourage further development of Candida colonisation.

The metabolic and toxic potential of Candida albicans includes the capacity to produce multiple toxins. Many yeast organisms can metabolise sugars to pyruvate and this in turn is anaerobically converted to acetaldehyde and carbon dioxide. Chronic CO2 production may account for the persistent bloating and gas noted clinically by many patients with chronic candidiasis. Some strains of Candida can reduce acetaldehyde to ethanol. This would be rapidly absorbed and contribute to a raised blood alcohol level and state of chronic alcohol intoxication can ensue. It may be that chronic acetaldehyde production is important. Truss (1984) proposes that this may be responsible for multiple central nervous system dysfunctions through:

Acetaldehyde induced loss of red blood cell flexibility with resultant diminished oxygen tissue delivery.
Acetaldehyde binding to amine groups of neurotransmitters.
Acetaldehyde oxidation leading to a chronically elevated NADH/NAD ratio with multiple potential neuronal metabolic problems.
Vitamin deficiencies are commonly seen with a Candida overgrowth. Lowered vitamin B6 and B2 are most often seen. This could conceivably contribute to multiple symptoms including fatigue, depression, neuropathic problems, heightened oedema formation and additional metabolic dysfunction.

Clinical expression of fatty acid deficiency is often seen in-patients with candidiasis. Galland (1985) reported nearly 66% of candidiasis patients he studied had two or more clinical signs of fatty acid deficiency. Non-specific signs such as dry stiff hair, dry scaly skin, brittle nails and follicular dermatitis where noted in many of these patients.

Figure 7: A model of Candidiasis (adapted from Kroker, 1987)

Shaw et al (1999) speculated that many of the symptoms of autism might be related to an overgrowth of Candida and a selective IgA deficiency. Treatment with anti-fungal drugs and a gluten and casein free diet led to the improvement in symptoms seen in a severely autistic child. In further work Shaw (1999) was able to show that children exhibiting autistic features have increased excretion of abnormal metabolites (citramalic, tartaric and 3-oxoglutaric acids). It was speculated the source of these might be yeasts. Gas Chromatograpy/ Mass Spectrometry was used to evaluate the urinary content of metabolites on autistic subjects following the administration of Nystatin. Urinary tartaric acid declined to zero after 60 days. Associated changes included improvement in eye contact, a reduction in hyperactivity and an improvement in sleep patterns. When Nystatin dose was cut to half, levels rose and the improvement regressed.

The Herxheimer Reaction

Following the start of anti-fungal treatment, patients often exhibit a transient worsening of symptoms. Values for microbial metabolites often increase dramatically during the immediate period. However levels then fall after 4 days to two weeks. This is a systemic reaction due to the rapid killing of yeast and the consequent absorption of large quantities of fragmented yeast products.

Considerations of gluten and casein removal

It is commonly found that children with autism experience an improvement in symptoms following the removal of these proteins. Many systems have been proposed for the success of this intervention. Certain Candida spp are known to secrete enzymes including phospholipase and proteases. This might have consequences for gut permeability. It is also known that the mycelium and chlamydospore of certain strains are capable of tissue invasion. This would have significant and important consequences for food absorption and digestion. This may be important for autistic symptoms.

Clostridia and Autism

Bolte (1998) outlined the possibilty of a subacute, chronic tetanus infection of the gut as an underlying cause of autism in some individuals. Extensive antibiotic use creates a favourable environment for colonisation by opportunistic pathogens. Clostridium tetani is a ubiquitous anaerobic bacillus known to produce a potent neurotoxin. The normal site of binding for the toxin is the spinal cord. However, the vagus nerve is capable of transporting tetanus neurotoxin, thus providing a route of ascent from the intestinal tract to the central nervous system and thus bypassing the spinal cord. Once in the brain this may disrupt the release of neurotransmitters. This may explain the characteristics of some autistic symptoms

Sulphate Reducing Bacteria

These strictly anaerobic bacteria are spherical, ovoid, rod-shaped, spiral, or vibrioid shaped. They are 0.4 to 3.0 m m in length and occur singly, in pairs or sometimes as aggregates. This group of bacteria has the capacity to reduce sulphate to H2S. These bacteria can metabolise both hydrogen (from the fermentation of other bacteria) and sulphate (from dietary sources). The products are sulphite and/or hydrogen sulphide (H2S). Hydrogen sulphide is a toxic gas with a characteristic smell of rotten eggs.

Sulphation problems in autism have been proposed for many years now. Waring (2001) has shown that around 95% of autistic children have low serum sulphate, about 15% of that found in control children. This is seen as significant since sulphation is required in the inactivation of certain neurotransmitters in the brain involved in the modulation of mood and behaviour. Reduced sulphation also affects the mucin proteins that line the gastrointestinal tract and this finding is linked with increased gut permeability and inflammatory bowel disease.

The important question remains of why autistic children tend to exhibit such low levels of serum sulphate. Waring (2001) outlined the possibility the cytokines, which are peptides produced in inflammatory processes, may be responsible. It was found that autistic children often have high cytokine levels, and this would have the indirect effect of greatly reducing the production of sulphate. Continuing Waring (2001) describes other studies that shown many autistic children excrete high levels of sulphite in the urine.

This raises the possibility that sulphate-reducing bacteria in the gut have a role in this process. These strains of bacteria would have the capacity to reduce levels of sulphate in the gut by metabolising it to H2S and/or sulphite particularly if the population levels are abnormally high. No research has been completed to date and this remains pure speculation. However, it seems inevitable that these bacteria would have some role to play in this process and may therefore be of importance in the development of the symptoms of autism.

Dermorphin and Deltorphin

The concept of a gluten and casein free diet for alleviating the symptoms of autism is accepted now as relevant intervention. However more recent research into this has raised the possibility of a role for dermorphin and deltorphin in autistic symptomology.

In unpublished work, Friedman (2000) has found dermorphin and deltorphin in the urine of autistic children. Dermorphin and deltorphin are compounds which until now had only been found in the skin secretions of certain frogs belonging to the genus Phyllomedusinae. These include poison dart frogs which have been used for their hallucinogenic properties and also for tipping darts to stun targets. These compounds have been estimated to be many times more potent than morphine on a molar basis. Of great interest is the fact that these compounds are only generated on the skin of these frogs when they are in the wild, but not when raised in captivity outside their natural environment. It is possible that these products might be the consequence of a bacteria or fungal organism on the skin. Since dermorphin and deltorphin have been found in urine from autistic children, it is possible that a bacterial species or fungal organisms are responsible for generating such substances. In support of this, the amino acid form is the D enantiomer and therefore of non-human origin.

It has been suggested by Friedman (2000) that autistic children are deficient in dipeptydyl peptidase IV which appears to be responsible for breaking down morphine related peptides in the gut. The absence of this enzyme might be responsible for the failure to break down these opiate peptides. There are two possibilites for this dysfunction - the enzyme is missing or the enzyme is being inhibited. The bacteria responsible for producing these opiates may be present ubiquitously. However, since autistic children are known to have significant gastro-intestinal problems, it might be that dermorphin and deltorphin are absorbed abnormally and affect the central nervous system. We will have to wait for data to be published before this hypothesis can be reviewed and verified. No research has been completed thus far and so this remains somewhat speculative.

Treatments

Many interventions and treatments have been suggested previously. These include pharmacological treatment, dietary interventions, nutritional supports and phytochemical preparations. Many remain unresearched and questionable in terms of their effectiveness.

Approaches towards Candida Infection

Antifungal therapy is an exceedingly important part of treatment. Nystatin or Diflucan are examples of anti-fungal treatment. This will remove the Candida infection but does not affect bacteria in the gut. Nutritional management is required such that food substrates known to stimulate Candida spp are limited in the diet. Since a Candida infection can induce certain nutritional deficiencies, supplementation is often useful.

Approaches towards an overgrowth of gut bacteria outlined above

There are limited possibilities. Antibiotics are about the only option. However, these may not work since some are now resistant to antibiotics. Also, since antibiotics are thought to have been a root cause of many problems, a reoccurrence of infection may be an outcome.

Probiotics, Prebiotics and Synbiotics

It has been speculated that autistic symptoms and imbalances in the human gut microflora may be linked. This raises the possibility that some autistic symptoms may be managed effectively through dietary procedures that target the gut microflora. Reports suggest that these products have been used as part of interventions aimed at alleviating symptoms of autism.

Probiotics

These are a live microbial feed supplement which beneficially affects the host (Fuller, 1989). Examples include lactobacilli and bifidobacteria. Many strains are used including Lactobacillus acidophillus, Lactobacillus caesi Shirota and Bifidobacterium bifidum. The choice of strain and the number of strains used varies considerably between products. Various mechanisms have been proposed for their success including the production of short-chained fatty acids, lowering of gut pH, competition for nutrients, competition for mucosal adhesion sites, production of antimicrobials (bacteriocins), modulation of the immune system, modulation of the human gut microflora and modification of microbial enzyme activities.

However the success of probiotics is seen as limited for a number of reasons. Initially there is a question of survivability in the product. Often the nutritional environment and transportation conditions mean that many cells are non-vialble by the time the product is consumed. Often the products are not aesthetically pleasing i.e. taste, smell and mouth feel are not pleasent. This also raises a question over their use in infants. A major barrier to success is that the bacteria must survive the extreme conditions of the stomach (i.e gastric acid gives a stomach pH of about 2) and the small intestines (where bile and pancreatic secretions mean survival is questionable. The residual population of ingested bacteria then have to compete with the resident bacteria of the large intestine where it is questionable whether such a limited population would survive.

The alternative approach - prebiotics

These are non-digestible food ingredients that selectively stimulate a limited number of bacteria in the colon, to improve host health (Gibson and Roberfroid, 1995)

Figure 8: Characteristics of prebiotic ingredients

Figure 9: The Bifidobacterium Barrier. Activities resulting from promotion of bifidobacteria

Recognised prebiotics in Europe include:

Fructo-oligosaccharides
Lactulose
Trans-oligosaccharides
Prebiotics under evaluation

Soybean oligosaccharides
Lactosucrose
Xylo-oligosaccharides
Isomalto-oligosaccharides
Gluco-oligosaccharides
Second generation prebiotics
Multifunctional prebiotics
Prebiotics are thought to selectively stimulate the beneficial bacteria (e.g. lactobacilli and bifidobacteria) and selectively inhibit non-beneficial organisms that may cause intestinal upset or other gut problems. Importantly, prebiotics can inhibit pathogen colonisation in the gut by competitive inhibition. Some reported health benefits of prebiotics include prevention of gut infections, reduced risk of colon cancer, reduction in cholesterol and blood lipids and increased bioavailability of minerals. Applications for prebiotics include (currently) beverages and fermented milks, health drinks and spreads, infant formulae and weaning foods, cereals, biscuits and food supplements. Table sugar, candy, frozen yoghurt, ready to eat puddings, drinks, vinegar, biscuits, sausages, powdered drinks and chocolate are all typical vehicles for prebiotics in Japan.

Synbiotics

Synbiotics are a combination of probiotics and prebiotics. They may allow for the dual benefits of both applications to be promoted while reducing the limitations. Appropriate prebiotic use should enhance probiotic survival. Much research is currently ongoing and certain products are now available in Europe. Symbalance, enriched yoghurt from the Swiss dairy company Tonilait, was one of the first synbiotics. It contains three probiotic strains and the branded prebiotic Raftiline from Orafti. More recent launches include Jour apres Jour, a UHT skimmed milk enriched with vitamins, trace elements of micronutrients and the branded soluble fiber Actilight from Beghin Meiji Industries. The European Commission's Scientific Committee on Food (SCF) has approved Actilight, made up of fructo-oligosaccharides obtained from beets. It is said to have technical functions similar to sugar, such as water retention; high viscosity; stability at different temperatures; and a stable pH level.

German companies have also been active in developing these synbiotic products. Bauer launched Probiotic Plus Oligofructose, which contains two probiotic strains and the prebiotic, Raftilose. In addition, prebiotics are suitable for a wider application range than probiotics, such as the recently launched Ligne Bifide range from Vivis in France, which includes biscuits, soups and ready meals that contain Actilight.

Relevance to Autistic Symptoms

Recolonisation of the gut with beneficial bacteria is the aim following the removal of pathogenic bacteria (outlined above). Prevention of colonisation by non-beneficial bacteria is necessary. Probiotics may not survive or re-colonise the gut on their own. Prebiotics may help boost their ability to recolonise in the autistic gut. Both (synbiotics) may provide the host with adequate protection from recolonisation by pathogenic microorganisms (such as candida or certain gut anaerobes. A transient improvement in the gut environment may be seen. A transient improvement in autistic symptoms may be seen. The chances of recolonisation by pathogenic bacteria and subsequent relapse of symptoms is reduced.

On going research at Reading

Major themes include, molecular tracking of the human gut microflora, the fermentation process, gastrointestinal health and disease, in-vitro human gut modelling and isolation and development of specific probiotics, prebiotics and synbiotics. Research into autism, until recently, was not an area that the Food Microbial Sciences Unit has been involved with. However, over the past year we have been reviewing on-going research in the area. We now view this as an important area of gut microbiology. We are currently involved with a collaberative research project aimed at characterising about 140 faecal bacterial isolates from autistic children. We have also been investigating the proliferation of Candida species in in vitro human gut models and have been able to isolate and characterise a bacterial species with possible anti-candidal properties. It is hoped that by the end of 2001, the Food Microbial Sciences Unit will be in a position to launch a full research programme looking at the human gut microflora and autism.

Summary

Some autistic symptoms may be the result of unusual gut flora activity. Certain yeast and gut anaerobe species may be responsible. The release of toxins and other unusual metabolites may result in the development of some autistic characteristics. This raises the possibility of managing some symptoms through dietary techniques aimed at the gut microflora. Probiotics, prebiotics and synbiotics may help alleviate the severity of some autistic symptoms.

References

Barnett JA, Payne RW and Yarrow D, (1990). Yeasts: Characterisation and identification (Second edition). Cambridge: Cambridge University Press.

Bolte ER, (1998). Autism and Clostridium tetani. Medical Hypotheses 51(2): 133-144.

Danna P, Urban C, Bellin E and Rahal J, (1991). Role of Candida in pathogenesis of antibiotic associated diarrhoea in elderly patients. Lancet 337: 511-14.

Friedman (2001). Explaination of Diet. At: http://www.gfcfdiet.com/Explanationofdiet.htm

Fuller R, (1989). Probiotics in man and animals. Journal of Applied Bacteriology 66: 365 - 378.

Gibson GR and Roberfroid MB (1995). Dietary Modulation of the human colonic microbiota: Introducing the concept of prebiotics. Journal of Nutrition 125: 1401-1412.

Galland L, (1985). Nutrition and Candidiasis. Journal of Orthomolecular Psychiartry 15: 50 - 60.

Kennedy M and Volz P (1983). Dissemination of yeasts after gastrointestinal inoculation in antibiotic-treated mice. Sabouradia21: 27-33.

Kinsman OS and Pitblado K, (1989). Candida albicans gastrointestinal colonization and invasion in the mouse: effect of antibacterial dosing, antifungal therapy, and immunosuppression. Mycoses 32: 664-74.

Kontstanareas M and Homatidis S, (1987). Ear infections in autistic and normal children. Journal of Autism and Developmental Disorders 17: 585

Kroker GF, (1987). Chronic Candidiasis and Allergy In: Brostoff J and Challacombe SJ (eds). Food Allergy and Intolerance. pp 850 – 872. London: Bailliere-Tindall.

Mallet AK and Rowland IR, (1988). Factors affecting the Gut Microflora. In: Rowland IR (ed) Role of the Gut Flora in Toxicity and Cancer. London: Academic Press.

Ostfeld E, Rubinstein E, Gazit E and Smetana Z, (1977). Effect of systemic antibiotics on the microbial flora of the external ear canal in hospitalized children. Pediatrics 60: 364-66.

Podzorski R, Herron M, Fast D & Nelson R (1989). Pathogenesis of candidiasis. Immunosuppression by cell wall mannan catabolites. Archives of Surgery 124: 1290-1294.

Samonis G and Dassiou M, (1994a). Antibiotics affecting gastrointestinal colonization of mice by yeasts. Chemotherapy 6: 50-2.

Samonis G, Gikas A and Toloudis P, (1994b). Prospective evaluation of the impact of broad-spectrun antibiotics on the yeast flora of the human gut.
European Journal of Clinical Microbiology & Infectious Diseases 13: 665-7.

Samonis G, Gikas A and Anaissie E, (1993). Prospective evaluation of the impact of broad-spectrun antibiotics on gastrointestinal yeast colonization of humans. Antimicrobial Agents and Chemotherapy 37: 51-53.

Sell D & Monnier V, (1989). Structure elucidation of a senescence cross-link from human extracellular matrix. Implications of pentoses in the aging process. Journal of Biological Chemistry 264: 21597-21602.

Shah D & Larsen B, (1992). Identity of a Candida albicans toxin and its production in vaginal secretions. Medical Science Research 20: 353-355.

Shah D & Larsen B, (1991). Clinical isolates of a yeast produce a gliotoxin-like substance. Mycopathologica 116: 203-208.

Shaw W, Baptist J, Geenens D, (1999). Immunodeficiency, gastrointestinal Candidiasis, wheat and dairy sensitivity, abnormal urinary arabinose and autism: a case study. Unpublished: Great Plains Laboratory, Overland Park, Kansas 66204.

Shaw W, (1999) Role for certain yeast and bacteria byproducts discovered by organic acid testing in the etiology of a wide variety of human diseases. Bulletin of The Great Plains Laboratory. Overland park, KS 66204 (913) 341-8949.

Shaw W, Kassen E and Chaves E, (1995). Increased excretion of analogs of Krebs cycle metabolites and arabinose in two brothers with autistic features. Clinicla Chemistry 41: 1094-1104.

Truss CO (1984). Metabolic abnormalities in patients with chronic candidiasis: the acetaldehyde hypothesis. Journal of Orthomolecular Psychiartry 13: 66-93.

Van der Waaij D, (1979). Colonisation resistance of the digestive tract as a major lead in the selection of antibiotics for therapy. In: New Criteria for antimicrobial therapy - maintenance of digestive tract colonisation resistance (eds D van der Waaij and J Verhoef), pp 271-280. Amsterdam: Excerpta Medica.

Van der Waaij D, (1987). Colonization resistance of the digestive tract--mechanism and clinical consequences. Nahrung31: 507-17.

Waring (2001). Sulphate, sulphation and gut permeability: are cytokines involved? In: The Biology of Autism - Unravelled. Conference proceedings 11th May 2001, Institute of Electrical Engineers, Savoy Place, London.

Witken S (1985). Defective immune responses in patients with recurrent candidiasis. Infections in Medicine May/ June pp 129-132.

http://askwaltstollmd.com/archives/lgs/100742.html

[CrackSmokeRepublican]

Caltech Researchers Discover That Gut Bacteria Affect Multiple Sclerosis
Main Category: Multiple Sclerosis
Also Included In: GastroIntestinal / Gastroenterology;  Infectious Diseases / Bacteria / Viruses;  Neurology / Neuroscience
Article Date: 20 Jul 2010 - 5:00 PDT


Biologists at the California Institute of Technology (Caltech) have demonstrated a connection between multiple sclerosis (MS) - an autoimmune disorder that affects the brain and spinal cord - and gut bacteria.

The work - led by Sarkis K. Mazmanian, an assistant professor of biology at Caltech, and postdoctoral scholar Yun Kyung Lee - appears online the week of July 19 in the Proceedings of the National Academy of Sciences.

Multiple sclerosis results from the progressive deterioration of the protective fatty myelin sheath surrounding nerve cells. The loss of myelin hinders nerve cells from communicating with one another, leading to a host of neurological symptoms including loss of sensation, muscle spasms and weakness, fatigue, and pain. Multiple sclerosis is estimated to affect about half a million people in the United States alone, with rates of diagnosis rapidly increasing. There is currently no cure for MS.

Although the cause of MS is unknown, microorganisms seem to play some sort of role. "In the literature from clinical studies, there are papers showing that microbes affect MS," Mazmanian says. "For example, the disease gets worse after viral infections, and bacterial infections cause an increase in MS symptoms."

On the other hand, he concedes, "it seems counterintuitive that a microbe would be involved in a disease of the central nervous system, because these are sterile tissues."

And yet, as Mazmanian found when he began examining the multiple sclerosis literature, the suggestion of a link between bacteria and the disease is more than anecdotal. Notably, back in 1993, Caltech biochemist Leroy Hood - who was then at the University of Washington - published a paper describing a genetically engineered strain of mouse that developed a lab-induced form of multiple sclerosis known as experimental autoimmune encephalomyelitis, or EAE.

When Hood's animals were housed at Caltech, they developed the disease. But, oddly, when the mice were shipped to a cleaner biotech facility - where their resident gut bacterial populations were reduced - they didn't get sick. The question was, why? At the time, Mazmanian says, "the authors speculated that some environmental component was modulating MS in these animals." Just what that environmental component was, however, remained a mystery for almost two decades.

But Mazmanian - whose laboratory examines the relationships between gut microbes, both harmful and helpful, and the immune systems of their mammalian hosts - had a hunch that intestinal bacteria were the key. "As we gained an appreciation for how profoundly the gut microbiota can affect the immune system, we decided to ask if symbiotic bacteria are the missing variable in these mice with MS," he says.

To find out, Mazmanian and his colleagues tried to induce MS in animals that were completely devoid of the microbes that normally inhabit the digestive system. "Lo and behold, these sterile animals did not get sick," he says.

Then the researchers decided to see what would happen if bacteria were reintroduced to the germ-free mice. But not just any bacteria. They inoculated mice with one specific organism, an unculturable bug from a group known as segmented filamentous bacteria. In prior studies, these bacteria had been shown to lead to intestinal inflammation and, more intriguingly, to induce in the gut the appearance of a particular immune-system cell known as Th17. Th17 cells are a type of T helper cell - cells that help activate and direct other immune system cells. Furthermore, Th17 cells induce the inflammatory cascade that leads to multiple sclerosis in animals.

"The question was, if this organism is inducing Th17 cells in the gut, will it be able to do so in the brain and central nervous system?" Mazmanian says. "Furthermore, with that one organism, can we restore to sterile animals the entire inflammatory response normally seen in animals with hundreds of species of gut bacteria?"

The answer? Yes on all counts. Giving the formerly germ-free mice a dose of one species of segmented filamentous bacteria induced Th17 not only in the gut but in the central nervous system and brain - and caused the formerly healthy mice to become ill with MS-like symptoms.

"It definitely shows that gut microbes have a strong role in MS, because the genetics of the animals were the same. In fact, everything was the same except for the presence of those otherwise benign bacteria, which are clearly playing a role in shaping the immune system," Mazmanian says. "This study shows for the first time that specific intestinal bacteria have a significant role in affecting the nervous system during MS - and they do so from the gut, an anatomical location very, very far from the brain."

Mazmanian and his colleagues don't, however, suggest that gut bacteria are the direct cause of multiple sclerosis, which is known to be genetically linked. Rather, the bacteria may be helping to shape the immune system's inflammatory response, thus creating conditions that could allow the disease to develop. Indeed, multiple sclerosis also has a strong environmental component; identical twins, who possess the same genome and share all of their genes, only have a 25 percent chance of sharing the disease. "We would like to suggest that gut bacteria may be the missing environmental component," he says.

For their part, Th17 cells are needed for the immune system to properly combat infection. Problems only arise when the cells are activated in the absence of infection - just as disease can arise, Mazmanian and others suspect, when the species composition of gut bacteria become imbalanced, say, by changes in diet, because of improved hygiene (which kills off the beneficial bacteria as well as the dangerous ones), or because of stress or antibiotic use. One impact of the dysregulation of normal gut bacterial populations - a phenomenon dubbed "dysbiosis" - may be the rising rate of multiple sclerosis seen in recent years in more hygienic societies.

"As we live cleaner, we're not just changing our exposure to infectious agents, but we're changing our relationship with the entire microbial world, both around and inside us, and we may be altering the balance between pro- and anti-inflammatory bacteria," leading to diseases like MS, Mazmanian says. "Perhaps treatments for diseases such as multiple sclerosis may someday include probiotic bacteria that can restore normal immune function in the gut... and the brain."

The paper, "Pro-inflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis," was also coauthored by former Caltech postdoctoral scholar Juscilene Menezes and Yoshinori Umesaki of the Yakult Central Institute for Microbiological Research in Japan. The work was supported by funding from the California Institute of Technology, the Weston Havens Foundation, and the Edward Mallinckrodt, Jr. Foundation.

Source:
Kathy Svitil
California Institute of Technology

http://www.medicalnewstoday.com/articles/195274.php

[CrackSmokeRepublican]

Last Updated: Monday, 8 September, 2003, 11:31 GMT 12:31 UK

Belly bug could treat diabetes

By Jonathan Amos
BBC News Online science staff, in Salford

Bugs that cause stomach upsets in travellers are leading scientists to a vaccine for diabetes and arthritis.

Could bacteria make insulin injections redundant?

UK researchers will soon start human trials of a drug derived from the toxin of a bacterium that causes diarrhoea in globe trotters.

It has already been tested in mice successfully, reducing the incidence of illness in model rodents from 80% to about 15%.

"And in arthritis, we saw two things," said Dr Neil Williams, of the University of Bristol. "We saw not only a reduction in the incidence but also in the mice where disease did occur, we saw a decrease in severity.

Dr Williams has been presenting details of his work at the British Association's annual science festival, which this year is in Salford, Greater Manchester.

Immune setting

The researchers are targeting so called auto-immune diseases - diseases which arise when the immune system goes wrong and starts to attack the body's own components.

The Bristol team's work focuses on a group of proteins which have the effect of resetting control mechanisms, preventing the body's own tissues from being damaged.

"We've discovered a molecule from an E. coli bacterium that seems to be able to change the way the immune system works - in a sense re-educating it.

"This provides an example of where vaccines may be used to turn off rather to turn on the immune system."

The team is using just a transport component of the bacterium's toxin molecule. Called ETxB, the component is separated off from the rest of the protein so there is no chance of a vaccine causing stomach upsets in patients.

MS possibilities

Scientists have discovered that ETxB on its own is sufficient to stimulate so-called T regulatory cells, which in healthy patients act to suppress auto-immune diseases.

The Bristol group hope that by giving an ETxB vaccine to patients recently diagnosed with rheumatoid arthritis and type 1 diabetes they can significantly slow the progression of the diseases.

"We hope to be in healthy volunteer trials in the early part of next year and then if that goes well, we hope to be in patient groups towards the end of the year.

"Diabetes and arthritis are where we have focussed but in the longer term we would hope that a similar approach would work in other autoimmune disease, such as multiple sclerosis and Crohn's disease."

http://newsvote.bbc.co.uk/mpapps/pageto ... 089974.stm

[CrackSmokeRepublican]

'Traveller's tummy' may be cured by E. Coli patch

By Jeremy Laurance

Thursday, 12 June 2008

For sufferers of holiday tummy, relief may be at hand. Scientists have developed a vaccine patch that can cut the incidence of traveller's diarrhoea by 75 per cent.

Traveller's diarrhoea lasts on average between four and five days, involves 18 trips to the loo and leaves sufferers dehydrated and debilitated.

The patch, worn on the upper arm, delivers a tiny dose of toxin produced by E. Coli bacteria, the most common cause of diarrhoea, which stimulates the body's immune response. It is applied for a six-hour period three weeks before travel. A "booster" dose is delivered through a second patch applied one week before travel.

A trial using 170 volunteers in America found it significantly reduced the incidence and severity of diarrhoea. Researchers from the IOMAI Corporation in Gaithersburg, Maryland, found 21 per cent of those given a placebo had a moderate to severe attack of diarrhoea, compared with 5 per cent of those who received the vaccine. The results are published in the journal The Lancet.

http://www.independent.co.uk/life-style ... 45134.html

[CrackSmokeRepublican]

http://en.wikipedia.org/wiki/Albendazole

Albendazole

Mode of action

As a vermicidal, albendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Due to diminished energy production, the parasite is immobilized and eventually dies.

Albendazole also has been shown to inhibit the enzyme fumarate reductase, which is helminth-specific. This action may be considered secondary to the effect on the microtubules due to the decreased absorption of glucose. This action occurs in the presence of reduced amounts of nicotinamide-adenine dinucleotide in reduced form (NADH), which is a coenzyme involved in many cellular oxidation-reduction reactions.

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http://mic.sgmjournals.org/cgi/content/full/152/8/2443

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Gut Microorganisms and Autism: the Latest Research

LPS and Autism
   
We have collected many research articles to show that the toxins found in microorganisms play an important role in the suspected causes of ASD, in particular, lipopolysaccharide ( LPS) the bacterial toxins from gram negative bacteria that inhabit the guts of autistic children. LPS toxicity works synergistically with mercury and other heavy metal poisonings to expand damage. These heavy metals increase harm from LPS.[1] In addition, LPS decreases glutathione levels making it even more difficult for the body to detoxify heavy metals.[2]

One explanation for why symptoms of mercury are so similar to the symptoms of LPS could be the fact that mercury inhibits carbohydrate absorption in the gut. Unabsorbed food does not get into the blood stream quickly; when it remains in the gut, it becomes available as a food supply for bacteria. Consequently, gram negative bacteria multiply and produce LPS. [3] This raises a strong suspicion that some of the symptoms commonly attributed to mercury could be directly caused by LPS and only indirectly by mercury.

LPS also renders toxins from Candida Albicans more damaging.[4] The poisonous effects of LPS are so potent that they produce symptoms of autism even without the help of Candida Albicans and heavy metals. All collected experiments on the following website involve laboratory mice injected with only LPS and exhibiting the same symptoms as those in ASD.

LPS induces a depressive syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. This result has been replicated so many times by different research studies that the names, "Sickness Behavior" and "Endotoxemia" are now applied to this condition. [5][6][7]

The mission of this website is to collect and display links to some of the available research articles from PubMed, a service from the National Library of Medicine and the National Institute of Health, that link LPS to the varied and diverse symptoms of ASD. We were able to find and collect experiments for almost every possible neurological and biological symptom of ASD in order to prove that most symptoms of ASD, have a corresponding experiment on Medline that proves each is a symptom of LPS toxicity.

The articles on this website are just a tiny fraction of the available research The amount of evidence is overwhelmoing, for example, performing a search for "hippocampus lps", in PubMed will retrieve 222 citations.

The number of similarities between ASD and LPS toxicity is sufficiently impressive to demand attention and cannot be ignored. The following are symptoms of LPS poisoning; these symptoms are also found in children with autism:

BRAIN

Reductions in oligodendrocyte or myelin markers
A marked cerebral cytokine response
White matter injury
Changes in amygdala
Change in dopamine and serotonin levels
Reduction of blood flow to the brain
Changes in blood-brain barrier permeability for large (protein) molecules
Increased the number of pyramidal and granular cells in the hippo-campus

EMOTIONS AND BEHAVIOR

Anxiety
Depression
Reduction in social behavior
Lack of social interaction
Increase in addiction
Lack of exploratory behavior

DIGESTIVE

Weight loss
Breakage and depletion of microvilli
The tight junctions widen and become disrupted.
IBS and IBD
Gut inflamation
Leaky Gut
Digestive symptoms
Disrupted Intestinal Transit
LPS is linked to the problems of gluten,soy and dairy in ASD children

IMMUNE FUNCTION

Increase in TNF alpha.
Increases in certain NK cells and monocytes
Increases in lymphocytes

OTHER

Low Levels of Thyroid
Low Levels of Glutathione
Low Levels of Amino Acids
Impairment of Bile Flow
Increasing the Number of Viable Candida Albicans
An increase in pain sensitivity

Researchers at the UC Davis M.I.N.D. Institute found clear differences in cellular responses between autistic children and neurotypical children following exposure to LPS, bean lectin and bacterial agents. At the Institute this was discovered to be a major and important difference between children with ASD and typical children.[8]

"Lipopolysaccharide (LPS) is localized at the exterior leaflet of the outer membrane and serves as the major surface component of the bacterial cell envelope. This remarkable glycolipid is essential to virtually all Gram-negative organisms and represents one of the conserved microbial structures responsible for activation of the innate immune system. For these reasons, the structure, function, and biosynthesis of LPS has been an area of intense research."[9]

The majority of the research articles involve mice or humans displaying symptoms of toxemia after being given an injection of LPS. Another method to assess the important influence of bacterial toxins is to observe the changes in ASD children after removal of the neurotoxin-producing bacteria. Both Vancomycin and the Specific Carbohydrate Diet (SCD) are treatments for removal of bacteria. Both treatments produce a decrease in the symptoms of ASD. However, the changes from vancomycin were only short term because the bacteria develop a resistance to the medication. Changes from SCD diet are more powerful because they are long lasting. Even adults with ASD who live in group homes have been shown to lose many of their symptoms after being on the diet. SCD now also eliminates beans during the early months of the diet and encourages parents to only use beans later provided there are no adverse reactions.

UC Davis M.I.N.D. Institute reports in its findings concerning the reaction of autistic children to LPS, bacterial agents and lectin from beans "may lead to significant advances in the early detection, prevention and treatment of this complex neurological disorder."[8]

We are in total agreement, and offer as our own evidence, scientific articles and many positive results from using a diet that eliminates neurotoxin-producing bacteria and fosters intestinal healing.

In view of the research, we have to consider Lipopolysaccharide (LPS) a poison, as toxic as mercury and other heavy metals, LPS has drastic consequences for those in the ASD Community. Fortunately, dramatic improvements may result after its removal.

Increasing awareness of LPS to doctors, researchers and parents, will hopefully result in an increase in recovery rates for autism.

The links on the upper side of this website provide comprehensive research about LPS from around the world.

References

[1] Rumbeiha WK, Fitzgerald SD, Braselton WE, Roth RA, Kaneene JB: Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-Dawley rat. Toxicology. 2000 Aug 21;149(2-3):75-87.
[2] Zhu Y, Carvey PM, Ling Z : Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide. Neurochem Int. 2007 Mar;50(4):671-80. Epub 2007 Jan 13.
[3] Read the articles in the "Treatments for LPS" section of this website
[4] Akagawa G, Abe S, Yamaguchi H. Mortality of Candida albicans-infected mice is facilitated by superinfection of Escherichia coli or administration of its lipopolysaccharide. J Infect Dis. 1995 Jun;171(6):1539-44.
[5] Singal A, Tirkey N, Pilkhwal S, Chopra K. Green tea (Camellia sinensis) extract ameliorates endotoxin induced sickness behavior and liver damage in rats. Phytother Res. 2006 Feb;20(2):125-9.
[6]R. YIRMIYA, Y. POLLAK, M. MORAG, A. REICHENBERG, O. BARAK, R. AVITSUR, Y. SHAVIT, H. OVADIA, J. WEIDENFELD, A. MORAG, M. E. NEWMAN, T. POLLM�CHER (2000) Illness, Cytokines, and Depression Annals of the New York Academy of Sciences 917 (1), 478�487.
[7]Marvel FA, Chen CC, Badr N, Gaykema RP, Goehler LE: Reversible inactivation of the dorsal vagal complex blocks lipopolysaccharide-induced social withdrawal and c-Fos expression in central autonomic nuclei. Brain Behav Immun. 2004 Mar;18(2):123-34.
[8] Link to the anouncement from the M.I.N.D. Institute.
[9] Trent, M. Stephen1; Stead, Christopher M.1; Tran, An X.1; Hankins, Jessica V.(2006). Diversity of endotoxin and its impact on pathogenesis. Journal of Endotoxin Research, Volume 12, Number 4, August 2006, pp. 205-223(19)
[10]Autism: Effective Biomedical Treatments (Have We Done Everything We Can For This Child? Individuality In An Epidemic) by Rimland, Ph.D. Bernard (Introduction), M.D. Sidney Baker (Author), Ph.D. Jon Pangborn (Author) Boston DAN! April 2005 edition. Page 24

http://www.microbialinfluence.com/

[CrackSmokeRepublican]

Structure of L-arabinose-binding protein from Escherichia coli at 5 A resolution and preliminary results at 3.5 A.
G N Phillips, Jr, V K Mahajan, A K Siu, and F A Quiocho
Small right arrow pointing to: This article has been cited by other articles in PMC.

Abstract

The three-dimensional crystal structure of the L-arabinose-binding protein from E. coli, an essential component in the active transport of L-arabinose, has been solved at 5 A resolution using the method of multiple isomorphous replacement. Five heavy atom derivatives were used. A preliminary 3.5 A electron density map has also been calculated. The results indicate that the molecule is ellipsoidal with approximate dimensions 68 A X 38 A X 30 A. Two similar domains within the molecule (which is a single polypeptide chain) are related by an approximate noncrystallographic rotation-translation axis. This relationship involves approximately 20% of the structure.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC430489/


==========


J Proteome Res. 2010 Jun 4;9(6):2996-3004.
Urinary metabolic phenotyping differentiates children with autism from their unaffected siblings and age-matched controls.

Yap IK, Angley M, Veselkov KA, Holmes E, Lindon JC, Nicholson JK.

Biomolecular Medicine, Division of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington Campus, London, United Kingdom.
Abstract

Autism is an early onset developmental disorder with a severe life-long impact on behavior and social functioning that has associated metabolic abnormalities. The urinary metabolic phenotypes of individuals (age range=3-9 years old) diagnosed with autism using the DSM-IV-TR criteria (n = 39; male = 35; female = 4), together with their nonautistic siblings (n = 28; male = 14; female = 14) and age-matched healthy volunteers (n = 34, male = 17; female = 17) have been characterized for the first time using (1)H NMR spectroscopy and pattern recognition methods. Novel findings associated with alterations in nicotinic acid metabolism within autistic individuals showing increased urinary excretion of N-methyl-2-pyridone-5-carboxamide, N-methyl nicotinic acid, and N-methyl nicotinamide indicate a perturbation in the tryptophan-nicotinic acid metabolic pathway. Multivariate statistical analysis indicated urinary patterns of the free amino acids, glutamate and taurine were significantly different between groups with the autistic children showing higher levels of urinary taurine and a lower level of urinary glutamate, indicating perturbation in sulfur and amino acid metabolism in these children. Additionally, metabolic phenotype (metabotype) differences were observed between autistic and control children, which were associated with perturbations in the relative patterns of urinary mammalian-microbial cometabolites including dimethylamine, hippurate, and phenyacetylglutamine. These biochemical changes are consistent with some of the known abnormalities of gut microbiota found in autistic individuals and the associated gastrointestinal dysfunction and may be of value in monitoring the success of therapeutic interventions.

PMID: 20337404 [PubMed - in process]

http://www.ncbi.nlm.nih.gov/pubmed/20337404

[CrackSmokeRepublican]

Glutamine

Also known as: Gln

Description
Glutamine is an Amino Acid that is an Amide of Glutamic Acid.

Health Benefits of Glutamine

Cardiovascular System
   Glutamine helps to prevent Anemia.

Digestive System
   Glutamine (18 grams (18,000 mg) per day for three days prior to the commencement of Chemotherapy) reduces the incidence of Gastrointestinal discomfort and Diarrhea in people undergoing Chemotherapy. research
   Glutamine strongly enhances the health of the Digestive System.
   Glutamine can significantly improve survival times for a deadly form of Colitis: research
    
-   Glutamine improves the condition of Crohn's Disease patients (primarily by supporting the health/function of the Intestinal Mucosa).
   Glutamine is a major source of energy for the Intestines and helps to prevent fluid loss from the Intestines.
   Glutamine enhances the growth of the Pancreas.
   Glutamine accelerates the healing of Peptic Ulcers (including Gastric Ulcers).
   Glutamine alleviates the Diarrhea, Ulcers, abdominal Pain, weight loss and food Allergies associated with Ulcerative Colitis: research
    
-   Glutamine lowers Lipopolysaccharides levels in Ulcerative Colitis patients. research
   Glutamine is an essential "fuel" for the Villi cells of the Intestinal Wall. research

Immune System
   Glutamine improves the function of the Immune System. research
   Glutamine (5 - 10 grams per day) helps to prevent Bacterial & Viral Diseases (especially in persons who experience Glutamine depletion as a result of excessive Exercise or Endurance Exercise): research
    
-   Glutamine enhances the ability of Neutrophils (cells of the Immune System) to destroy Detrimental Bacteria. research
   Glutamine supplementation can minimize the loss of Immune System function that occurs as a side-effect from Burns.
   Glutamine helps to minimize the damage caused by Chemotherapy in Cancer patients: research
    
-   Glutamine enhances the repair of Intestines damaged by Chemotherapy.
-   Glutamine (18 grams (18,000 mg) per day for three days prior to the commencement of Chemotherapy) reduces the incidence of Gastrointestinal discomfort and Diarrhea in people undergoing Chemotherapy.
-   Glutamine helps to repair the damage that Chemotherapy causes to the Immune System (when Glutamine is supplemented in chemotherapy subjects the infection rate drops to 3%, compared to 100% without Glutamine).
-   When Glutamine is supplemented as an adjunct to Chemotherapy in the treatment of Cancer, tumors decrease in size by 45% - compared to 25% when Glutamine is not supplemented.
-   Glutamine increases the survival rate of Chemotherapy patients.
-   Glutamine (up to 30 grams per day) alleviates the Pain of and quickly heals open sores in the Mouth (oral mucositis) caused by Chemotherapy.
   Glutamine (5 - 10 grams per day) counteracts the suppression of the Immune System that occurs in people who engage in Endurance Exercise. research
   Animals that are totally devoid of Glutamine quickly contract Immunosuppressive Diseases and die.
   Glutamine stimulates the growth of and serves as a fuel source for Lymphocytes. research
   Glutamine serves as a fuel source for Macrophages. research
   Glutamine enhances the ability of Monocytes to function as Phagocytes. research
   Glutamine enhances the ability of Neutrophils to destroy Antigens and to destroy Detrimental Bacteria. research
   Glutamine stimulates the growth of Phagocytes. research

Metabolism
   Glutamine reduces the craving (Appetite) for Carbohydrates.
   Glutamine reduces elevated Blood Sugar (by up to 50%).
   Glutamine improves the health of people who regularly engage in strenuous Exercise: research
    
-   Glutamine counteracts the Acidosis (Lactic Acidosis resulting from Lactic Acid production) that often occurs as a result of strenuous Exercise.
-   Glutamine can prevent the breakdown of Proteins within the Muscles (i.e. it can prevent catabolism and Muscle loss) during and after intensive Exercise.
-   When excessive quantities of Lactic Acid are produced as a result of strenuous Exercise (resulting in Lactic Acidosis), Glutamine is catabolized from the Muscles and transferred to the bloodstream where it is utilized in the detoxification of Lactic Acid - supplemental Glutamine therefore "spares" the body's existing Glutamine reserves in the Muscles.
-   Intensive Exercise causes the depletion of Glutamine from the Muscles, Liver and Blood Plasma.
-   Glutamine counteracts the suppression of the Immune System that occurs in people who undertake Endurance Exercise. research
   Glutamine alleviates Fatigue.
   Glutamine alleviates Hypoglycemia.
   Glutamine protects the Liver from Alcohol-induced toxicity.
   Glutamine functions as a Nitrogen shuttle - it "picks up and drops off" Nitrogen around the body. research
   Glutamine reduces body weight in persons afflicted with Obesity (by approximately 10%). research
   Glutamine reduces cravings for Simple Sugars.

Musculoskeletal System
   Glutamine stimulates the synthesis of endogenous Proteins within the Muscles, thereby facilitating Muscle Growth (i.e. it is anabolic). research
   Glutamine concentrates in the Muscles (it comprises 10.4 mg per 100 grams of total Muscle weight and comprises 50% of the total free Amino Acid content of Muscles). research
   Glutamine prevents Muscular Atrophy (wasting of the tissues of the Muscles).

Nervous System
   Glutamine alleviates Aggressiveness.
   Glutamine improves Alertness.
   Glutamine is helpful in the treatment of Alzheimer's Disease.
   Glutamine is a valuable adjunct to the treatment of Autism.
   Glutamine converts to Glutamic Acid within the Brain in order to provide Energy to the Brain.
   Glutamine is the most abundant Amino Acid present in the Cerebrospinal Fluid. research
   Glutamine improves Concentration.
   Glutamine (250 - 1,000 mg per day) improves Mood in Depression patients. research
   Glutamine increases Intelligence. research
   Glutamine increases Learning ability.
   Glutamine improves Memory.
   Glutamine alleviates Mental Retardation - supplemental Glutamine has increased the IQ of intellectually impaired children. research
   Glutamine improves Mood. research
   Glutamine reduces the sensation of Pain. research
   Supplemental Glutamine improves the recovery from Stroke. research

Respiratory System
   Glutamine indirectly accelerates the recovery from severe Pneumonia. research

Sexual System - Male
   Glutamine alleviates Male Impotence.

Skin
   The concentration of Glutamine is 58% lower in Burns patients than in non-burned humans.
   Glutamine facilitates the excretion of waste products from the Skin.
   Glutamine accelerates the healing of Wounds.

Surgery
   Glutamine is one of the most important nutrients of all to supply to people before and after they have undergone Surgery.

Glutamine Enhances the Function of these Substances
Amino Acids
   Glutamine supplementation increases the production of Arginine (in the Kidneys). research
   Glutamine (which can pass through the Blood-Brain Barrier) converts within the Brain to Glutamic Acid (which cannot pass through the Blood-Brain Barrier) which then combines with Ammonia to reform back into Glutamine.
   Glutamine is integral to the production of Glutathione within the body (Glutamic Acid is extracted from Glutamine's chemical structure within the Liver for incorporation into the Glutathione molecule). research
   Proline can be manufactured within the body from Glutamine.
   Glutamine enhances the function of Tryptophan.

Carbohydrates
   Glutamine is a precursor for the endogenous production of Glucosamine.
   Glutamine is required for the formation of Glycogen. research

Hormones
   Glutamine supplementation (of at least 2,000 mg per day) increases plasma Human Growth Hormone (hGH) levels by up to 400%. research
   Glutamine stimulates the production of Insulin.

Minerals
   Glutamine is one of the preferred Amino Acids for chelation with Copper.

Neurotransmitters
   Glutamine is a precursor for the formation of Gamma Aminobutyric Acid (GABA).

Nucleic Acids
   Glutamine supplies the required Nitrogen atom for the manufacture of Deoxyribonucleic Acid (DNA).

Pharmaceutical Drugs
   Glutamine improves the ability of Methotrexate to inhibit the growth of Cancer Cells and reduces its toxicity (thereby allowing larger dosages of Methotrexate to be utilized in the treatment of Cancer. research

Proteins
   Glutamine is a component of Gliadin (a Prolamine) which in turn is a component of Gluten.
   Glutamine is an essential component of all Prolamines.

Glutamine Counteracts the Toxic Effects of these Substances
Amino Acid By-products
   Glutamine facilitates the elimination of Ammonia from the body:
    
-   Glutamine converts within the Brain to Glutamic Acid which then combines with Ammonia to reform back into Glutamine.

Pharmaceutical Drugs
   Glutamine counteracts Paracetamol poisoning (by preserving Glutathione levels in the Liver of persons affected by Paracetamol poisoning). research
   Glutamine counteracts the ability of Prednisone to suppress the Immune System and reduces the likelihood of Prednisone-induced increases in susceptibility to Bacterial and Viral Diseases. research

Recreational Drugs
   Glutamine counteracts some of the toxic effects of excessive consumption of Alcohol (ethanol): research
    
-   Glutamine protects the Liver from Alcohol-induced damage.
-   Glutamine reduces the craving for Alcohol in persons afflicted with Alcoholism when used in conjunction with Vitamin B3 (Nicotinic Acid form) - the main drawback to this approach is that the equivalent human dose of Glutamine to that used in animals would be a massive 35,000 mg (35 grams) per day. research

These Substances Enhance the Function of Glutamine
Amino Acids
   Alpha-Ketoglutarate (AKG) facilitates the endogenous production of Glutamine (it provides the Carbon skeleton for a portion of Glutamine synthesis).
   Glutamine is converted to Glutamic Acid - which otherwise cannot pass through the Blood-Brain Barrier - within the Brain (Glutamic Acid is converted to Glutamine when an additional Nitrogen atom is added to Glutamic Acid and Glutamine is converted to Glutamic Acid when the additional Nitrogen atom is removed from Glutamine).
   Glutamine can be manufactured endogenously (within the body) from Isoleucine.
   Endogenous Enzymes in Skeletal Muscles and the Liver convert supplemental Ornithine Alpha-Ketoglutarate (OKG) to Glutamine. research
   Glutamine can be manufactured endogenously (within the body) from Valine.

Enzymes
   Glutaminase catalyses the breakdown of Glutamine into Ammonia and Glutamic Acid.

Hormones
   Melatonin (10 mg per day) enhances the ability of Glutamine to stimulate the release of Human Growth Hormone (hGH) from the Pituitary Gland. research

Minerals
   Manganese is required for the synthesis of Glutamine.

Dietary Sources of Glutamine
Fruits:       Papaya           
Vegetables:       Celery       Parsley   
        Spinach       Cabbage   
        Dandelion Greens       Brussels Sprouts   
        Lettuce       Carrots   

These Substances Interfere with Glutamine
Amino Acids
   Aspartic Acid inhibits the absorption of Glutamine.

Hormones
   Cortisol decreases the body's Glutamine levels.

Microorganisms
   Candida albicans yeast destroys Glutamine.

These Ailments Interfere with Glutamine
Nervous System
   Stress increases the body's requirement for Glutamine as excessive Stress causes severe depletion of Glutamine. research

Other Factors that Interfere with Glutamine
Exercise
   Exercise causes depletion of the body's Glutamine reserves (a single bout of non-intensive Exercise can cause a 45% reduction in plasma Glutamine compared to pre-Exercise plasma Glutamine levels): research
    
-   Endurance Exercise causes severe depletion of the body's Glutamine reserves (a single bout of Endurance Exercise can cause a 50% reduction in plasma Glutamine for up to six days compared to pre-Exercise plasma Glutamine levels). research

Dosage Recommendations
Therapeutic Dosages
   The usual therapeutic dosage of Glutamine for the treatment of Alcoholism varies from 2,000 to 35,000 mg per day. This dosage may decrease the craving for Alcohol in Alcoholics. The wide range of dosages is due to some clinical studies showing effects with as little as 2,000 mg of Glutamine, while others have shown no effect until at least 35,000 mg (35 grams) of Glutamine is used per day.
   The usual therapeutic dosage of Glutamine for persons undergoing Chemotherapy is 18,000 mg per day. Clinical trials involving the use of Glutamine in people underoing Chemotherapy have involved the use of 3 x 6,000 mg doses (= 18,000 mg per day) for at least three days prior to the commencement of Chemotherapy.
   The usual therapeutic dosage of Glutamine for the treatment of Depression is 2,000 mg per day.
   The usual therapeutic dosage of Glutamine persons who Exercise is 2,000 mg per day. This dosage increases plasma Glutamine levels by 19% in people who undertake intensive Exercise, thereby restoring Glutamine levels to normal ranges.
   The usual therapeutic dosage of Glutamine for persons who undertake Endurance Exercise is 5,000 - 10,000 mg per day. This is the dosage required to prevent suppression of the Immune System in people who participate in Endurance Exercise.
   The usual therapeutic dosage of Glutamine for increasing Human Growth Hormone (hGH) levels is 2,000 mg per day. Some studies have shown that this dosage increases hGH levels by up to 400%.

Safe Dosage
   Supplemental Glutamine has been certified to be safe at daily supplementation of up to 70,000 mg per day (70 grams per day).

Bioavailability
   Orally-administered Glutamine supplements effectively increase serum Glutamine levels (when a dose of 5 grams of Glutamine is ingested, serum Glutamine levels increase by approximately 50% within 30 minutes).

Commercial Availability of Glutamine Supplements
"Singular" Oral Glutamine Products
   Glutamine supplements are available from health food stores and mail order supplement companies (worldwide) in the form of:
    
-   loose Glutamine powder
-   500 - 750 mg capsules
-   400 - 1,000 mg tablets

Chemical Data
   Glutamine is a unique Amino Acid in that it contains 2 Nitrogen molecules - this feature gives Glutamine all of its unique health benefits.

Chemical Names
   L(+)-Glutamic acid-5-amide
   2-aminoglutaramic acid

Molecular Formula
   C5H10N2O3

Return Catabolism
Catabolism is the process of reusing or excreting substances within cells that are worn out or are no longer required by the body. It involves them being broken down (decomposed) into smaller molecules. Catabolism involves the release of Energy from those decomposed substances and (like all of the processes involved in Metabolism) is catalyzed by Enzymes.

Return Anabolism
Anabolism is the process of building new molecules to replace the structures within cells that must periodically be replaced. It involves the utilization of Energy to achieve Growth and repair.