History of the Autism Oxalate Project

Many months ago, a lady spoke to me who was familiar with autism, and she had a chronic pain condition which had been researched by a scientist named Clive Solomons. She told me how Dr. Solomons' research had found that tissue pain may be associated with having high urinary oxalates (called hyperoxaluria), and she told me that he had also discovered that this pain might diminish on a diet restricted to include only low oxalate foods. Other scientists had studied how oxalates find their way to tissues that are damaged and why they stop in those tissues and form crystals and cause oxidative damage that may cause additional pain. She wanted to know: Could a mechanism involving oxalates be prolonging gut issues and pain in children with autism?

I began examining the literature on oxalates and found that scientists have described a condition called enteric hyperoxaluria that develops when the bowel is inflamed, such as in the conditions ulcerative colitis and Crohns disease, and these are very similar to autistic enterocolitis. Hyperoxaluria may also develop whenever there is poor digestion of fats (steatorrhea) such as happens in celiac sprue, or it may also develop when excess oxalates are easily absorbed through a "leaky gut". Could the gut issues in autism be associated with hyperoxaluria as well?

There are many links between oxalates and known biochemical problems in autism, and oxalate problems are improved by many already successful autism therapies. You may remember that many years ago Dr. Bernard Rimland was involved in many studies that showed B6 was a very effective therapy in autism. We have known B6 was important in the conversions along the sulfur pathway, yielding cysteine, glutathione, taurine and sulfate. All of these molecules may be at abnormal levels in autism but they also have specific roles in the oxalate chemistry. An enzyme called AGT directs the precursor of oxalate into less harmful directions, but this enzyme will fail when pyridoxine (Vitamin B6) is deficient. The result is that other enzymes take over and they produce excess oxalates. One of those enzymes, glycolate oxidase, is inhibited effectively from making oxalate by alpha lipoic acid, which many with autism have used as a chelating agent. Oxalate production is ordinarily restricted by other sulfur molecules like cysteine and glutathione when they bind to oxalate's precursors, but these "thiols" cannot protect us from oxalate production when they themselves are deficient.

Oxalates cause oxidative stress and lower glutathione levels, and lead to a high GSSG:GSH ratio. These problems are exactly what Jill James found when she examined the sulfur chemistry in autism. A related molecule called an oxalyl ester will complex with thiols in a way that regulates some hormones and also influences a major enzyme that recycles glutathione in the kidney. All of these common threads with the sulfur metabolism leave us with the haunting question: To what degree are the sulfur compounds in children with autism tied up with high oxalate or its precursors, removing sulfur compounds from the ability to do their other jobs?

Oxalates form crystals with certain amino acids, such as beta-alanine. They also crystallize with calcium, removing that calcium from other uses. This is why hyperoxaluria might lead to osteoporosis or delays in bone or tooth maturity. Citrate, zinc, magnesium and Vitamin A protect us from forming oxalate crystals, but oxalates make us waste zinc but not copper into the urine, and that may cause copper/zinc imbalances. Some bacteria use oxalates for fuel, but other fungi and bacteria may themselves generate more oxalates as a response to metals like zinc, copper, and cadmium. In fact, oxalates are recognized chelating agents. How do they fit in with heavy metal issues in autism?

Since there is so much evidence of potential associations, we had to consider that oxalates could be a major issue in autism. We decided to test seven children with autism for high oxalates, selecting our candidates from children who seemed to have pain or behavior problems with sudden onset or they had urinary problems like the ones associated with hyperoxaluria in other conditions.

The testing we used on the seven children worked this way: we collected a new sample every time the child urinated for 24 hours, and Dr. Solomons’ lab tested for bound and free oxalates. When we got the results back, it was easy to see that there were big swings in the oxalate levels which you would expect to find with enteric hyperoxaluria. Only one child had levels that were steadily very high. For most of the children, their oxalate level doubled at certain times of day. These high levels seemed to occur in the urine collection that followed the time of day when the children were having pain or behavior issues. Because of these variations, we concluded that the standard 24 hour oxalate tests that are used to identify stone-related kidney disease may not always catch the children whose oxalates are coming from the diet because their levels may be normal at times of day that are not influenced by meals. We also concluded that children with varying levels would be the children most likely to benefit from the low oxalate diet. At this point, we asked the parents if kidney stones ran in the families of our test subjects. The answer was yes in most of them, but not all.

The mothers in our pilot group agreed to do a trial of a low oxalate diet, and soon things were changing in their children. One child who had urinary issues had been craving and eating citrus rind, which is a very high oxalate food. He also characteristically used a huge amount of salt on his food. After beginning a lower oxalate diet (but not yet a low oxalate diet) his urinary issues improved considerably and he stopped wanting to use the salt shaker, and this astonished his mother. Another child with a mother who has been particularly careful to exclude oxalates, found that her son rapidly lost the chronic diarrhea he had experienced his entire life. This improvement went far beyond what had changed on the early SCD diet or by medical treatment. To our great surprise, though, over the next weeks on the diet, this child also made impressive gains in speech, motor skills, and cognition, as recognized by his therapists and teachers. He also lost some lingering autistic behaviors, and grew two inches in two months. That left us with a challenge: Could oxalates be harming gut function and be creating neurological problems in autism that are not seen in genetic hyperoxalurias?

In order to find out if any such ideas were being entertained by oxalate scientists, I attended the FASEB oxalate conference, a conference which only occurs once every three years, but provides a meeting place for the top scientists in the oxalate field. There I was privileged to meet personally about sixty oxalate scientists and was able to brainstorm with many of them who will help us on this project.

There are many other organizations for diseases associated with oxalates. They have done the preliminary work on how to implement a low oxalate diet, but our autism population presents some special challenges, because children on the spectrum tend to be already on a very restricted diet. That is why I set up a yahoogroup where people can learn from each other how to manage this diet and can learn which foods have high oxalates. With this knowledge, a parent can determine if his child is eating a high oxalate diet and can watch to see if exposures to those foods seem to influence behavior, cognition, or urinary and bowel issues.

We hope that this diet will heal the gut enough that the children may be able to eat foods that needed restriction previously. A few families are finding they can expand the diet a little from where it was before the diet. New foods are being introduced that are succeeding in putting smiles on faces, for the list has some wonderfully creative cooks. We will also be discussing which supplements reduce the absorption, toxicity, or endogenous production of oxalates and will be borrowing, as much as seems appropriate, from work on other conditions where people have developed successful methods of repairing tissues that were injured by oxalates.

Unfortunately, Dr. Solomons retirement at the end of June meant he permanently closed the lab that did the testing for us. We are negotiating right now with a lab which will hopefully begin to offer the same sort of testing (with improvements) that will allow us to properly distinguish the oxalate issues in autism. As that testing comes on board, we will get better at identifying the best candidates for this diet in ways that are objective. Working with the DAN! doctors, parents will also be able to determine ways that may reduce excess oxalates the children are making themselves.

Please feel free to join those who are exploring this diet at the new yahoogroup called Trying_Low_Oxalates@yahoogroups.com. The website includes links to other organizations with experience with this diet and food lists. The members are compiling lists which will enable the reader to determine if a particular food meets qualifications for this diet or for many other diets used in the autism community. The list is also monitored by a nutritionist named Carol Simontacchi who also attended the FASEB conference with me.

We look forward to working with parents, doctors, and other researchers and organizations to see if this new area offers a promise for an even greater recovery in those with autism who are improving with biomedical treatment.

Susan Owens

Member of the DAN! Thinktank of the Autism Research Institute
Listowner of sulfurstories@yahoogroups.com
Lecturer on the sulfur system and its role in autism