Healing autism - No finer a cause on the planet
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A Comment from the Autism Oxalate Project
By Susan Owens
As head of the Autism Oxalate Project, I am glad to see Dr. Shaw's enthusiasm about the role of oxalates in autism, "Great Plains Laboratory Says 'Oxalates Control Is A Major New Factor In Autism Therapy.'" but I feel compelled to give a little history of this project before I comment on some matters in the announcement that was published in the Schafer Report yesterday.
The Autism Oxalate Project began in early 2005 under the inspiration of the Pain Project run by the Vulvar Pain Foundation and their researcher, Dr. Clive Solomons. His project had discovered that oxalates were inflicting further tissue destruction in damaged vulvar tissue. The protocols they developed to reduce oxalate and heal tissues were found to greatly help their members with other issues like bowel disorders, fibromyalgia, and interstitial cystitus. Dr. Solomons began this research in the 1980's, and the VP Foundation had thousands of members who had successfully treated their pain disorders. We felt reducing oxalates in a similar way might help to heal some problem areas in autistic children.
The first goal of our project was to do a thorough review of the oxalate literature which took about three months of fulltime work. The literature on enteric hyperoxaluria confirmed that it was probable that oxalates from food might be another substance besides opioid peptides that was being absorbed through a leaky and inflamed gut. We wanted to find out if oxalate in autism might be contributing and prolonging the pain, inflammation, and functional problems in the gut. We also hoped this diet might alleviate urinary issues in those with autism: something that had generally been out of the focus of autism research.
We conducted a pilot study of six children using testing that was then available through the Solomons lab, but which was unfortunately discontinued when he rapidly closed his lab in a move towards retirement.
These samples were collected each time the child voided for an entire day.
All of the children in this group showed some degree of periodic hyperoxaluria, meaning their oxalate level in urine was intermittently quite high during the day, but not necessarily high all the time. Periods of bad behavior or pain were recorded and the time noted by parents on the day of the test. After we got the results back, we saw that some behaviors seemed to occur an hour or two before oxalates became elevated in the urine which may have been from intestinal pain, and others with urinary issues seemed to have pain and behaviors at the same time as the oxalates were high. The pattern and extent of oxalate excretion and its association to pain and behavior were compelling enough that we suggested to the parents that a low oxalate diet might provide a benefit. Once on the diet, the results were rapid and astonishing, and included behavioral improvements, growth, urinary improvements and the resolution of bowel issues in some of our participants. We then began the expansion of this project to include setting up an internet list called Trying_Low_Oxalates@yahoogroups.com for helping others with the diet, and we began gleaning research help from the international oxalate community.
When I recently attended the International Urolithiasis Conference held in Indianapolis, I showed Bill Shaw's data on autism from his advertising brochure to the director of oxalate research at Mayo Clinic who has been helpful since the early months of the Autism Oxalate Project. This doctor/researcher quickly made many comments about the chart that reported oxalate in the urine in those with autism. She was concerned that the chart lumped urinary data of children of different ages because the urinary data was expressed in ratio to creatinine. She said this is a problem because differences in creatinine production at different ages shifts significantly the results of such testing, so children of different ages shouldn't be reported together in the same chart. To study this properly, the lab should have looked at what influences creatinine, so they should have furnished the height of each child, the age of each child, the creatinine level in each sample, and the weight or muscularity of each child in both the study group and in the control group. If they didn't do this, she knew the younger children would skew the results to be high. The reader couldn't tell from the chart the proportion of younger children that were in the autism group vs. controls. The report also, to be scientifically valid, needed to tell us how they determined the child's diagnosis and how they selected the children for the control group. The researcher at Mayo also said there were not enough children in the control group, The children in the two groups should have been age and sex matched, and also, the samples should have been sent to the lab blinded as to the diagnostic status of the child.
While the Great Plains pilot study didn't meet the standards of scientific studies in the oxalate community, this type of informal data from them was still a nice first move past the lab data in our very small pilot study.
I'm happy that this laboratory has an interest in this area, and even happier that they have some sort of oxalate test to offer the public, as well as a way to correlate that data to a report that is familiar to many doctors. Even so, readers should be aware that there are just a few other minor issues in the brochure that I have pointed out to Dr. Shaw as being a concern to me, but I won't go over them here. Overall, it is a very colorful and interesting presentation of this new area of research that the Autism Oxalate Project began exploring almost two years ago followed several months later by our pleas for the development of appropriate lab support.
Concerns about yeast issues
I am concerned that yesterday's announcement and the brochure say that increased oxalates are mostly coming from production of the intestinal yeast, candida. Although I am aware that yeast overgrowth is suspected in some cases of autism, normal rates of colonization of candida in autism were reported years ago by Sophie Rosseneu of the Royal Free Hospital who spoke at several DAN! Conferences. No other gastroenterologist that I am aware of has reported anything different from what she said. Has anyone proven the overgrowth of candida in the gut in autism using tests other than those measuring organic acids? Have those data ever been correlated to oxalate levels by anyone using conventional means of diagnosing and quantifying yeast overgrowth in the intestine while measuring changes in oxalate levels in stool and urine and blood? The scientific standards for such testing should come from microbiologists and gastroenterologists.
Only certain substrates like arabinose can be used as a food for candida or other microbes to make a precurser to oxalate (d-erythroascorbic acid). (PMID: 8841374,7612007) We do not know the source of the arabinose, but it might be the hyaluronic acid that is produced under the direction of gamma delta T cells in an inflamed gut. We also don't know if there are conditions outside of the elevation of arabinose that would provide an environment in the gut that was suited for a particular quantity of yeast or other microbe to succeed in making an amount of oxalate that would be greater than oxalate coming from other sources. If Dr. Shaw has references to quantitative data about the production of oxalate by yeast in the human intestine, with controls in place that would exclude other sources of oxalate, I would be very interested in seeing this work, especially if this has been done in children with autism. The data that I found available on fungal production of oxalate was very limited (mainly about aspergillus) but this pathway in yeast was discussed in my powerpoint at the USAAA conference last spring.
Potential sources of oxalate
There are many possible sources of oxalate in autism. Everyone makes some oxalate daily in their own cells. Extra oxalate production may derive from problems in the sulfur chemistry because of places in the pathway where thiols are important inhibitors of oxalate production, or where sulfur compounds change oxalate trafficking. Sulfur issues in autism were described a decade ago by Rosemary Waring and have been followed by more work by Jill James. Many readers may remember the numerous studies that Dr. Bernard Rimland described showing the efficacy of pyridoxine therapy in autism. Pyridoxine deficiency is a cause of problems in the sulfur chemistry but it is also one of the major reasons for abnormal production of oxalate in human cells that are not genetically defective. This was emphasized in a presentation I heard at the FASEB oxalate conference in the summer of 2005. Also, excesses of glycine, and deficiencies of vitamins like thiamine and minerals like magnesium can lead to excess production of oxalate. Some amount of ascorbic acid is converted into oxalate in the body, with some studies reporting a conversion rate as great as 60% under some circumstances, although this conversion is very slow.
Considering all of these other possible sources, still, the most probable source of excess oxalate in autism may come from a condition called enteric hyperoxaluria. This condition, well-studied and described in the medical literature as a risk for developing kidney stones, is related to a hyperabsorption of oxalate mainly from the colon, but the source is soluble oxalate that comes from food. Usually most of the oxalate from food stays in the stool bound to calcium or is degraded by microbes. Scientists have found, though, that these protections won't work, and there will be excess absorption of dietary oxalate into the blood whenever there is intestinal inflammation, diarrhea, constipation, steatorrhea or leaky gut. This same set of intestinal issues have individually been documented in people with autism by many investigators. It is difficult to find a child with autism who has none of these intestinal issues.
To say WE KNOW anything for certain at this point about WHICH of these sources of oxalate is most important in one child or in the whole autism population is speaking way beyond the current data, in my opinion.
In my presentation at the DAN! conference this past fall, I emphasized that this project, though it has made great progress, is still at the very beginning of the scientific process. With the help of more than a thousand parents now, we are making observations of the changes of many children who have been on the low oxalate diet for many months to longer than a year. By recognizing changes in these children (and in some adults with autism), we have been able to compare what they are experiencing to what is described in the medical literature as related to oxalates. There have been many surprises as we have found astonishing improvements in behavioral areas and in growth, speech, and motor skills and overall cognitive development we did not anticipate. We are actively working on determining what the appropriate behavioral and biochemical tests will be to capture and study this change. We must determine which chemistry in which compartments of the body will need to be measured in order to form an hypothesis that can be appropriately investigated with scientific rigor.
The oxalate literature makes it clear that we still do not have in place all of the appropriate lab tests to measure important parts of this disease process. I'm glad we have the oxalic acid test in the organic acid test at Great Plains, but it is important to know that people with autism differ from those with kidney disease because the oxalate in their diets seems to produce problems in the GI system more often than it produces problems in urinary areas. The oxalate may be trafficked differently. According to responses to a survey done earlier this year, five times as many improvements are occurring in gastrointestinal areas for people with autism on the diet compared to improvements in urinary areas. These improvements include for some a resolution of dysbiosis and "yeast" issues that have plagued them for years. After months on the diet many have reported that they no longer require antifungal or antibacterial treatment when those treatments were absolutely necessary before.
Urinary tests of oxalate were developed for diseases of the kidney, but the excellent work of Robert Freel and Marguerite Hatch in studying the regulation of the enteric secretion of oxalate into the stool tells us where autism research in this area needs to focus: the gastrointestinal regulation and handling of oxalate. This means the appropriate study of oxalate issues in autism will require fecal testing as well as urinary and blood testing.
For more information
More information about the scientific issues can be found in discussions on the Trying_Low_Oxalates yahoogroup which was started in July of 2005. On this list parents of children with autism and a much smaller number of patients with other conditions have been exploring the use of a low oxalate diet. This support group has almost 1300 members and there are about 13,000 messages in the archives and an extensive files section with references to the literature. Information on the scientific reasons that we began this project is also on the site and has been presented at the USAAA conference and the AutismOne Conference and in Madrid, Spain, where Dr. Shaw first heard the presentation. The low oxalate diet was discussed at the main session of the DAN! Conference this October, and in a presentation that I did jointly with Dr. Shaw as a breakout session at the last DAN! conference. This diet has also been discussed thoroughly several times in the last year on programs on AutismOne radio and has been presented with hundreds of references within more than two hundred emails in public correspondence with DAN! physicians and researchers.
The powerpoint slides on this topic and the paper "Mechanisms Behind the Leaky Gut" have been available on the AutismOne.org site since last spring: http://autismone.org/uploads/Owens%20Susan%20Powerpoint%20USE.ppt http://autismone.org/uploads/Owens%20Susan.doc
I was a bit unfamiliar with the Schafer Report being used for advertising new projects. It didn't occur to me to seek publication from the report at the beginning of our project when we announced its beginning to the autism community a year and a half ago.
Since that time (and since before that time) our project has been securing the help of key scientists to explore the necessary basic science that is needed to do the clinical studies in the right way. Two scientists are already actively doing some of the required basic science research and their results should be published fairly soon. Clinical work is being held up right now by the lack of availability of fecal, sputum and RBC oxalate testing and a proper test for periodic hyperoxaluria. We are also in development of a test of the oxalate-degrading capacity of the stool, which should help us identify children whose oxalate problems may stem from antibiotics that killled their oxalate-degrading flora.
The sulfation problems already described in autism mean that the trafficking of oxalate to the urine should not be expected to be normal because of issues of sulfate/oxalate exchange in the proximal tubule. For that reason, urinary tests alone cannot be assumed to adequately reflect the body burden of oxalate or the trafficking of oxalate in autism until proven so.
- Susan Owens Head of the Autism Oxalate Project at ARI Member of the DAN! Thinktank,
A project of the Autism Research Institute RA, Husson Science Research Instititute Listowner, Trying_Low_Oxalates@yahoogroups.com and Sulfurstories@yahoogroups.com
We welcome collaborations with other researchers in this project. Contact .Susan Owens at LWO@iadfw.net
Donations for this project can be given to the Autism Oxalate Project at the Autism Research Institute, a 501(c)3.
Be sure and designate this project for your donation if that is where you want it to go.
Lenny Schafer, email@example.com
The Schafer Autism Report is a non-profit corporation.