Autism, Enzymes and the Brimstone Demons

If you are sensitive to sulfites, you may be quite surprised at the connection to autism. I know I was. Although I am not outwardly autistic, I seem to share many of the chemical markers common in autism. These include problems with sulfur chemistry, dysfunctional vitamin B6 metabolism and mutations to genes in the molybdenum cofactor pathway. The comparisons are so strong, I decided to write a book, "Autism, Enzymes and the Brimstone Demons." It is available on Amazon as an eBook or a Paperback. The introduction and an executive summary are included below.

Introduction: Hello, my name is Rick Williams. I grew up in Southern California just after the end of the Second World War. Had I grown up in America today, half a century later, I believe I would be autistic.

Brimstone DemonAll things considered, I'm a healthy adult. My major complaint is a sensitivity to sulfites and sulfur dioxide, chemicals which I like to call Brimstone Demons. They are oxides of sulfur and brimstone is the ancient name of sulfur.

I must carefully watch what I eat or I'm cursed with headaches that can last for 24 hours. Why am I at risk for autism? I have disturbed sulfur and vitamin metabolism which are helped by supplementing with molybdenum, vitamin B6 and mineral water. This leads me to believe I have genetic mutations that depress a chemical called the molybdenum cofactor. In turn, this damages several enzymes, including sulfite oxidase which is responsible for clearing sulfite preservatives.

In my body, the Brimstone Demons hang around much too long, causing mischief all the while. In the process, sulfate metabolism suffers which blocks toxin removal. Many children with autism share similar mutations which have the potential to interfere with brain development in addition to causing symptoms like my headaches. In 1950, when I was young, sulfite and sulfur dioxide preservatives were quite rare. Today, they are very common. In 1950, autism was virtually unknown. Today, this is sadly not the case.

Autism is a brain disorder affecting social interaction, communication and behavior. Parents usually notice signs in the first two years of life. Symptoms may progress gradually or they may appear suddenly followed by swift regression. Due to many varied symptoms, it is often labeled as Autism Spectrum Disorder. This includes classic autism (with repetitive behavior) along with Asperger Syndrome (high functioning autism). Many adults with Asperger's learn to cope with their unique mix of strengths and weaknesses, yet are ever aware they are apart from the crowd.

Autism is widely believed to be caused by a combination of genetic and environmental factors. Currently, it affects 1 out of every 68 American children and the statistics are similar worldwide. Boys are 4 to 5 times more likely to be afflicted than girls, with a male ratio of 1 in 46. According to American estimates, the lifelong cost of treating and caring for autistic individuals may approach four million dollars each. Outside of the USA, health care is usually more cost effective and the price may be closer to one million dollars. Applying such numbers to the world population, this disorder would stabilize at 110 million autistic humans over our lifetime. And the cost could be estimated at 110 trillion dollars. For sheer numbers, this epidemic rivals the Bubonic Plague and the Spanish Flu.

Why should you read this book? It won't be an easy read. It's not the latest adventure of Indiana Jones. It is chock full of data and scientific terms. But that's what makes it valuable. This book is a serious attempt to unravel the mystery of autism. I believe the Brimstone Demons coupled with genetic mutations within the molybdenum cofactor pathway are the major causes of autism. The chapter titled “Sulfate Statistics” presents evidence that supports these conclusions. And the chapter titled "Horse Sense" discusses why boys are more strongly affected.

Who am I and what are my credentials? Although I have degrees from the California Institute of Technology, they relate to engineering, not medicine. My expertise comes from a lifetime of fighting the Brimstone Demons and 20 years of experiments and research. I am not funded by any government or corporation, except my own small electronic business, Rybett Controls. So, I am free to critique the work of the medical establishment when warranted. This establishment generally believes that sulfite issues were solved by legislation in the 1980's. That sulfa antibiotics are wonder drugs. And sulfates are a mild threat with no significant benefit. They are wrong. I back this opinion with scientific data and a thousand headaches. I hope this book is a major step on the march to understand autism. And I hope you enjoy the journey with me.

Executive Summary: This book attempts to unravel the mystery of autism, identify the root cause and suggest the means of prevention. The focus is sulfur chemistry, more specifically, the three oxides of sulfur: sulfite, sulfur dioxide and sulfate. I am personally affected and the oxides of sulfur cause me so much trouble, I call them the Brimstone Demons. Sulfites and sulfur dioxide are bad demons, causing difficulties for people with autism. They are found in food/drugs and have been on the rise for the last 70 years. Sulfate is a good demon, acting as a shield against many aspects of autism. Sulfates in our water supply have been falling for 70 years. When coupled with genetic mutations to the Moco Pathway, the Brimstone Demons cause autism. The Moco Pathway creates a chemical called the molybdenum cofactor which is crucial for several important enzymes, including sulfite oxidase and aldehyde oxidase. When dysfunctional, these enzymes unbalance sulfite, sulfate and vitamin B6 metabolism.

Clues to the Mystery: Following World War II, autism was virtually unknown with a prevalence of just 1 out of 10,000. Today, the rate is 1 in 68 and even worse for boys at 1 in 46. That's two percent for heaven's sake. The human genome has not changed, so a powerful environmental trigger must be at play. That trigger must have been rising for 70 years and it must still be potent the world over. The Brimstone Demons satisfy this condition.

ChemistMedical literature reveals the following clues. Vitamin B6 levels in autistic children are elevated but spread wide by a standard deviation 3 times normal. This places one third of the autistic population at low levels of  the bioactive form of B6, known as PLP (or P5P). Bioactive B6 is a necessary cofactor for 140 different chemical pathways in the human body. Therefore, low PLP has wide ranging detrimental effects, including a condition called PLP Deficient Epilepsy. Many with autism also suffer from epilepsy at about the same rate as those with low PLP.

Autistic children have elevated levels of sulfite in their urine. Elevated may be too weak a description as sulfite is 51 times normal. A high level of sulfite has many negative consequences. An interesting one is depression of an enzyme called AASA dehydrogenase which clears a chemical that traps and inactivates bioactive B6. Sulfite interferes with this enzyme and low PLP results. In addition to causing epilepsy, this also affects the Moco Pathway as PLP is a necessary cofactor. In turn, sulfite oxidase is impacted and a bad feedback loop established, increasing sulfite even further.

Sulfite oxidase clears sulfite by converting it to sulfate. So, high sulfite and low sulfate are two sides of the same problem. In many respects, sulfate functions as a nutrient, deeply connected to tissue growth including that required by brain development. It is also a key player within the Sulfation Pathway which removes toxins and waste from the body. Sulfate ions are attached to biological trash for identification and removal. This includes environmental toxins which stubbornly afflict all modern humans.

Recent research in France has identified genetic mutations within the Moco Pathway, detected in the olfactory stem cells of 91% of a small sample of 11 autistic children compared to 11 controls. These mutations to the MOCOS and AOX genes directly affect aldehyde oxidase, the enzyme responsible for the removal of excess vitamin B6. Since overall B6 is elevated in autism, this tracks nicely with depressed aldehyde oxidase. The mutations indirectly affect levels of sulfite and sulfate, probably by causing defective aldehyde oxidase to over express, thereby reducing the available stores of the molybdenum cofactor and starving sulfite oxidase enzyme.

French FriesThe Brimstone Theory: The Moco Pathway mutations have been around for hundreds, if not thousands of years. They upset body chemistry by increasing sulfite, decreasing sulfate and interfering with vitamin B6 chemistry. But not so much as to cause outright disease or developmental issues. Along comes sulfite in food and sulfur dioxide in prescription drugs. They push susceptible children over the edge. Many fastfood outlets serve french fries and instant potato flakes, adding 2,600 ug to our sulfite load. Sulfa drugs like Cotrim are prescribed to children and pregnant mothers. They release a whopping 30,000 ug in a typical dose. This bumps sulfite levels in autistic bodies to dangerous levels, as high as 95 uM over baseline. Body chemistry is affected including the temporary depression of bioactive B6. In turn, this impacts 140 pathways and initiates epileptic episodes.

Blood plasma levels of sulfate are depressed, as low as 11% of normal. So, the protective benefits of sulfate largely disappear for those with autism. The sulfate deficit may be estimated at 510 mg per day, looking at losses in urine. This can be corrected by drinking water with a high sulfate content, mineral water for instance. Pellegrino naturally provides 459 mg of sulfate in each liter bottle. Unfortunately, most tap water is not as sulfate rich. The EPA estimates that the median public water system provides only 24 mg/l. And this has been falling as autism has risen. Two trends are responsible. One is a shift from rural to urban water as people migrate to cities. Rural water is typically from mineral rich wells. Urban water is usually obtained from more prolific surface sources which contain less sulfate.

The second trend is a real eye opener. The Clean Water Act has empowered the EPA to force urban water systems to clean up dangerous toxins, certainly a noble goal. Of course, when you remove the bad stuff, sulfate gets reduced, too. I guess the baby got thrown out with the bath water. The medical community is not concerned about sulfate, considering it a mild nuisance. It is recommended to stay below 250 mg/l for flavor and below 500 mg/l to avoid diarrhea. For most people, sulfated water has no obvious benefit. But for those with autistic chemistry, sulfated water can make up for sulfate lost in the toilet. These are bold assertions. Can they be backed up with evidence?

IDEA legislation (Individuals with Disabilities Education Act) requires tracking of autism in our public schools. If you extract data for 6 through 11 year olds with autism, you can calculate prevalence numbers for each of the 50 states. This shows large differences between states. The worst states are Minnesota, Maine, Oregon and Connecticut with rates as poor as 1 in 62. The best states are Iowa, Louisiana, Colorado and Oklahoma with rates above 1 in 200. What about sulfate in the water? For each of the best and worst states, I created a list of the most populous cities. I searched the internet for water quality reports and weighted sulfate levels against population to get an idea of the mean level of sulfate in each state. I compared sulfate to autism and the correlation was striking. The worst states had an averaged sulfate level of only 13 mg/l. The best states averaged 113 mg/l.

Most people drink about 2 liters of water per day. This means citizens in the best states were getting an additional 200 mg of sulfate compared to the worst. This extra sulfate reduced the rate of autism by a factor of 4. What would happen if you increased the sulfate even more, say double?  A conservative guess might be a reduction in autism by a factor of 8. What would autistic birth numbers look like in the United States under these improved conditions if the Brimstone Theory is true:

Current rate: 1/68 causing 58,000 autistic births/year.
125 mg/l sulfate: 1/272 with 14,500 autistic births/year.
250 mg/l sulfate: 1/544 and only 7,250 autistic births/year.

Bottled water is a player, too. The typical American buys 160 liters of bottled water every year. And the numbers are similar world wide. That replaces a lot of tap water. What about sulfate? Oh, the Brimstone Demons are a clever crew. Most bottled water is distilled tap water with the sulfate removed. This is true for Desani, Aquafina and Pure Life. Spring waters like Poland Spring are not much better. Bottled water is a multi billion dollar growth industry, probably outpacing autism over the years.

Is there more proof? Autism is a strongly male condition with 4 to 5 times as many boys. A good argument can be made connecting sulfate to estrogen, the dominant female hormone. There are four chemicals that we loosely call estrogen. Estradiol is the most potent type while estrone is the form regulated by the enzyme estrone sulfotransferase, which requires sulfate. Low sulfate halts regulation, resulting in excess estrone. Competitive inhibition, in turn, interferes with estradiol creation. This shifts estrogen activity away from estradiol and toward estrone, lowering the overall potency. For girls, this is no big deal since they start off with lots of estrogen. For boys, it's more problematic since estrogen levels are naturally low. When estrogen drops through a threshold, problems arise and autism is one bad result.

Conclusion: It may be possible to reduce the incidence of autism by controlling the Brimstone Demons, avoiding the bad and supplementing the good. For instance, by minimizing sulfite in food, avoiding sulfur dioxide in sulfa drugs and supplementing drinking water with sulfate. A cure will be more difficult, since the brain may have been permanently altered. However, symptom relief should be practical by the same methods used for prevention. These ideas are explained in detail within the book. The appendix contains tables of sulfited ingredients, troublesome foods and problematic drugs. A recipe for creating home brew mineral water is also included. Is the Brimstone Theory true? That is the 100 trillion dollar question. The next page describes our Mothers Project which will examine the sulfate content of water actually drank by mothers of children with autism. If you wish to participate in our project, your help will be greatly appreciated.

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