Owens on LOD with permission

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Something new for autism Soon some collaborators will be putting together a study to examine therelevance of oxalates to autism. Already a small pilot study has shownthat oxalates may be high among those with autism with certainsymptomatology. This would not have surprised us if we had already knownmuch about oxalates because for years scientists have described anelevation of oxalates that occurs in inflammatory bowel conditions likeCrohn's or ulcerative colitis, called enteric hyperoxaluria. Sinceautistic enterocolitis has so many similarities to those bowel conditions,and because of the well-characterized "leaky gut", and for other reasonsthat will be discussed below, it would have been surprising NOT to findproblems with oxalates in autism. Oxalates are a very simple sort of molecule that links up with calcium andthen crystalizes under some conditions, including when they encounterdamaged tissues. The crystals formed this way can be quite irritating andpainful to tissues where they form, causing or increasinginflammation. These crystals can be especially painful if they lodgethemselves in places where they get in the way of the movement of otherthings through tight places. These physical issues are easy to understand,but there are still many secrets nature has about how oxalates interactwith other parts of the metabolism. Where do oxalates come from? Oxalates are present in a lot of plants and fruit that we eat and invirtually all seeds and nuts. Ordinarily, the gut won't absorb much of theoxalate from the diet, and the oxalate will be metabolized by the flora orjust leave the body with the stool. Under other conditions, a lot of thedietary oxalate is absorbed. Overabsorption is far more likely to occurwhen the tight junctions between the cells which line the gut open up andlet molecules pass through between the cells in a condition called the"leaky gut" which is similar to a condition in the bladder with openjunctions called the "leaky bladder". How does this happen and why is it a problem? When substances move to the blood by going around intestinal cells, theybypass the regulation that is present when these same substances moveinstead through the cells. When the transport occurs through cells, thecells themselves control the quantity that crosses by regulating the numberof transporters that allow that substance into the cell. After thesubstance crosses the cell, it can leave the cell to join the blood bymeans of a different set of transporters that are on the blood or "exit"side. With this kind of regulation coming from both sides of the cell, whenthe body recognizes that you don't need more of a substance from food, thecell won't let more of that substance cross through. The body obviouslyloses that regulation when substances are absorbed through the "leaky"junctions between cells. Oxalates are just one of the substances wherethis is a problem, but whenever more oxalates are absorbed like this, theresult may be high levels of oxalates in blood and urine and intissues. Scientists call the high levels in urine hyperoxaluria. Eating food high in oxalates is not the only way to get high oxalatessystemically. Our bodies make oxalates on their own, especially whencertain enzymes aren't balanced in their activity. Normally, onceoxalates are in the gut, they may encounter particular species of bacteriawhich will digest them and turn them into something else that isn't soirritating. This system of microbial digestion may be why the body seemsto purposefully route excess oxalate from the rest of the body to thegut. Unfortunately, the very microbes we need to do this digesting ofoxalates for us are subject to being killed by antibiotics in commonuse. Even if there was no exposure to antibiotics, these microbes mightnot have colonized yet in very young children, for it does not tend to bein breastmilk, but must be picked up from the environment. Lactobacillus acidophilus is an oxalate-eating species, but when oxalatesare in excess, lactobacillus can be killed off. It will be interesting tolearn whether this may explain why certain children on the spectrum have agreat difficulty colonizing lactobacillus acidophilus. Fortunately, aprobiotic formulation of a bacteria called oxalobacter formigenes thathelps digest oxalates even better than lactobacillus is under developmentfor patients with hyperoxaluria and related conditions. How do oxalates function in the body? There is a positive side to oxalates because they help us manage calcium,but the management of oxalates themselves will fall down when cells are lowin glutathione and also in oxidative stress. Oxalates add to thatoxidative stress. Plants use oxalates to protect themselves from infection or from beingeaten, as these crystals can tear up the mouths of the bugs that eat them,but we haven't learned nearly enough about the positive side of oxalates inhumans. We know a lot of negatives about oxalates, but we are juststarting to learn what chemistry will change when both the sulfur andoxalate chemistry are disrupted at the same time. We certainly have toconsider that problems in the sulfur chemistry may be why oxalates producesymtpoms in autism that are not seen in the genetic hyperoxalurias. We have learned recently that there is common regulation between the sulfurchemistry and oxalates. You may have heard that years ago Dr. Rimland wasinvolved with inspiring or conducting many studies that found that vitaminB6 was very effective in decreasing autistic symptoms. We now know thatVitamin B6 (pyridoxine) is a necessary cofactor for enzymes that helpprevent the formation of oxalates, but this vitamin, when deficient, willalso wreak havock with the sulfur chemistry in many places along the sulfurpathway. We have also learned that when sulfur is deficient, it becomesextremely difficult to keep the body from making excess oxalates. Pain, Urinary and Fungal Issues The association of hyperoxaluria with pain in tissues all over the body hasbeen explored in research by Dr. Clive s, a connective tissueresearcher working together with the Vulvar Pain Foundation (VPFoundation). That collaboration over many years learned that any tissuewhich has been injured may be a site where oxalate may cause additionaldamage and pain and destruction of tissues. Those observations make sensein light of scientific studies that find oxalates add much additionaloxidative stress to tissues and that their presence may further activateinflammatory cascades. An injury to a tissue is an invitation tocrystallization because this sort of crystal begins by calcium binding andthen oxalate binding to a type of phospholipid (phosphatidyl serine) thatis ordinarily on the inside of membranes and not accessible. That type ofphospholipid may be exposed on the outside of membranes when there has beentissue injury, and that begins the process of adding more and more calciumoxalate to that crystal. Dr. s and the foundation working with him found that high oxalateswere associating with conditions like vulvodynia, prostatitis, irritablebowel syndrome, fibromyalgia, interstitial cystitis, and skinsensitivity. These conditions improved on the low oxalate diet and withother natural treatments they developed that were found to reduce oxalates.This collaboration also found that high oxalates seemed to be giving somepeople a sense of urinary urgency and frequent urination, and sometimes thepatient would have trouble urinating. As people with these conditions shared their stories with each other, theyalso learned that many of them had spent years being treated for bladder orfungal infections, only to have their conditions worsen. The same patientsfound relief after years of pain and treatment by addressing the oxalateissue. Their improvements after lowering oxalates should not be surprisingsince it is known that oxalates tie up calcium, and calcium is critical tothe effectiveness of many antifungal and antibacterial strategies,including that of the immune system. The usual context of hyperoxaluria You will find that most doctors know about calcium oxalates because ofkidney stones, but the levels of oxalate in the urine or diet do notperfectly predict the risks for such stones. Curiously, men are abouttwice as likely as women to form stones and there are also racialdifferences and only some people with higher oxalates form these stones.There are two very serious genetic conditions where an enzyme defect meansthe body will generate extremely high levels of oxalates and the stones mayeventually induce organ failure. We have not yet heard of any family witha child with autism where either of those genetic defects has been in thefamily history. Nevertheless, in our initial pilot study group, after ourlab reports came in showing high oxalates, we asked the parents, and foundthere was a high incidence of kidney stones in the families in thisgroup. A familial association with kidney stones has been described ininterstitial cystitis, another condition that improves by restrictingoxalates in some sufferers. That and other research in the oxalate fieldsuggest there could be predispositions to high oxalates that are lessserious than the primary hyperoxularias. The condition of making kidneystones is not very rare (about 10% in the general population), so it willbe interesting to find out if a family history of kidney stones ends upbeing an important predictor of which children with autism will either havehigh oxalates in urine or will react behaviorally to oxalates. As mentioned earlier, the literature has long recognized an associationbetween inflammatory bowel conditions and having excess oxalates in theurine. We don't know whether oxalates in the GI tract are what isirritating the gut and perhaps leading to problems with either constipationor diarrhea or pain. Just as likely, the inflammation and the oxalates mayhave developed as consequences of something else or their coexistence maybe an unfortunate convergeance of unrelated things. Regardless of what will eventually end up being the explanation, oxalatesfrom the diet may further injure an already inflamed gut. That is why itmay make sense for someone with high oxalates or chronic bowel problems orproblems with urinary urgency or inflammation to do a trial of a lowoxalate diet just to see if this will help heal the gut and restore urinarycontrol. The handful of children on the spectrum who were tested and found to haveelevated oxalates were chosen for testing because they were experiencingproblems with diarrhea or constipation or urinary issues. That means, atthis point, we don't know if children with autism without these issuesmight also be high in oxalates. We had another intriguing surprise. Onechild in our study group craved and ate a lot of one high oxalate foodbefore the diet, but he was also one who typically loaded down his foodwith salt. When his dietary oxalates were lowered, he completely stoppedthat salting habit, and began ignoring the salt shaker. This actuallymakes sense because of how sodium is related to oxalate regulation. Getting the research done You can see why it is important that we are forming a research team thatwill look at the levels of oxalates in urine while correlating those levelswith other information. The s lab, which pioneered the researchcorrelating oxalate levels to tissue pain, has recently closed due to Dr.s' retirement. Since he won't be able to help us, I knew that theautism community would need to work with other scientists experienced inoxalates in order to design studies properly. For that reason, I have justgotten back from the FASEB international scientific meeting on oxalates,where I got to feel the pulse in this field, and meet the people who willbe able to help us address the scientific issues. While it becomes clear which one of those scientists will be able to helpus conduct the formal studies, there will be plenty of other work to do inthe meantime to insure that we know as much as possible before beginning todesign the study. For several months, I have been reading the literatureon oxalates in order to learn what is known about oxalates, such as theirpurpose, their regulation, and what they might be changing that mightcorrelate to known biochemical features of autism. I've been doing thiswork while remembering another time when the autism community learned thehard way that studies performed on a clinical level before anyoneunderstands the biological mechanisms can lead to the premature dismissalof a therapy that may have significantly improved the lives of a selectedpopulation. We need to have some inkling about who will benefit fromreducing oxalates, so that is why we're trying to do our homework now. Trying the low oxalate diet Some people, hearing of successes in our study group, have alreadyexpressed an interest in trying this diet. Even though it will take sometime before we can begin the formal study, that doesn't mean that peoplecannot be learning about oxalates in the mean time. To make this learningeasier, and to make it easier for people to share experiences with thisdiet, I've started a new group calledTrying_low_oxalates . This list will be a place wherepeople exploring the use of this diet can compare their results and helpeach other out with the details and support. I am not going to restrictthis list to people involved with autism only, because there is a need fora forum also for people trying the diet for other conditions, includingthose mentioned earlier. This cross-pollination should be helpful. Thissite will have links to information about which foods have high oxalates orwhich foods will generate high oxalates when other chemicals in food aremetabolized. The food charts referenced on the site were developed forpatients with hyperoxaluria, and they are useful to read to evaluate theoxalate content of what is now the normal diet for any potential candidatesfor this change. If you would like to have someone tested before trying the low oxalatediet, you can have your doctor order a 24 hour urine oxalate test which isthe screening tool for hyperoxaluria. Sometimes oxalates are measured onorganic acid profiles, so some people who have used that test may alreadyknow that their child has high oxalates. The standard 24 hourhyperoxaluria test, which is more specific, can be ordered from standardlabs that work with your insurance company. Unfortunately, this test,because it pools all the urine from the whole day, will not tell youanything about changes in oxalate levels during the day. Why is that a problem? Dr. s found that there is a diurnal rhythmto the oxalate levels which is not the same from person to person and thelevels increase in response to the activity of different enzymes processingother food chemicals into oxalates. For some people, the issue may not be as much the level of the oxalates inthe system as much as it is previous injuries to tissues that will makeexposure to oxalates feel a bit like someone is pouring alcohol or acid onan open wound. I'm just saying that to alert us that the 24 hourcollection may not always identify people whose sudden onset of pain or badbehavior is caused by an equally sudden increased level of oxalate. Internet and other resources In autism circles, we are all "newbies" to this diet, but we are veryfortunate that the VP Foundation and the Oxalosis and HyperoxaluriaFoundation both have resources that they have developed for theirmembers. For that reason, please feel free to visit the followingwebsites. http://www.vulvarpainfoundation.org/vpfoxalate.htmhttp://www.ohf.org Athttp://www.vulvarpainfoundation.org/vpfcookbook.htm, you will find anadvertisement for a cookbook whose next edition (available in fall of 2005)will include a new and more comprehensive list of the oxalate content of foods. Since lowering oxalates represents a new strategy for autism, if you decideto try the low oxalate diet, right now there is no one who can predict howthis diet might be different for a child on the spectrum compared to thewomen in the foundation who have used this diet in the past, or frompatients with primary and secondary hyperoxuluria who have used thediet. For that reason, and for general reasons of safety, please be sureto seek the help and oversight of your child's doctor because he or she mayhave staff that can help you be sure that your child is getting adequatenutrition. Ordinarily, this wouldn't be too much of a worry, because thehigh oxalate list is not as restrictive as a lot of diets, but somechildren may already be on diets that are very restricted, and we will wantto be sure that after adding in these additional changes that they willstill be getting enough food and the right things to eat! The two following sites offers the best "quick list" to help you categorizefoods as high, medium or lowoxalate. http://www.branwen.com/rowan/oxalate.htmhttp://www.ohf.org/docs/Oxalate2004.pdf Members of our earlier pilot studyare working at consolidating the lists that are available, which will makeimplementing this diet easier for everybody. Will a low oxalate diet solve the problem of high oxalates in every patient? Probably not. The body itself makes way too much oxalate when someone isdeficient in vitamin B6, or is under oxidative stress, or is eating moremeat than his body's enzymes can break down properly. Even gluten can be asource of oxalates, as it contains a chemical that is converted intooxalate. When the body is too alkaline, the body may turn vitamin C intooxalates. Also remember that oxalates may not be the only thing that mightbe a problem for a child with some of these foods. For that reason, wewill probably find out that some children react to medium or low oxalatefoods as seriously as the high oxalate foods, but it may be for a differentreason. It might be helpful to start with a time of eating only the low oxalatefoods, then if improvements occur, after a few weeks, you can slowly see ifany medium oxalate foods are tolerated without losing progress. We havealready learned from one family that you need to be very careful and slowto increase the oxalates, and it will help to be familiar with some oxalatelowering nutrients which will be mentioned on the website. The whole ideais for you to be able to learn what makes your child do better. To do thatmore effectively, it would be helpful to keep a journal that records bothfoods and behaviors as you try varying the oxalate content of the diet. We are very early in the process of learning what may change on a lowoxalate diet, but our pilot group has already experienced surprisingchanges on this diet, especially in areas we did not anticipate. Thatmakes us hopeful that removing the high oxalate foods in the propercandidates may improve bowel function and pain, may relieve bladderurgency, frequent urination or inflammation, and may reduce some types ofautistic behavior while improving development. We look forward to seeingif these changes will be seen in a wider group. I hope this document answers most questions about this diet, but for moreinformation, please see the website, especially as we gradually addresources there. This letter may be copied to individuals inquiring aboutthe low-oxalate diet without additional permission from me, butdistribution to groups should be done only after contacting me for permission. Best wishes, OwensA member of the DAN! thinktank, a project of the Autism Research InstituteListowner of sulfurstories Lecturer on the sulfur system and its role in autism Afterword: How this project happened: The oxalate issue and its relationship to pain came up in someconversations I had with a woman who was familiar with autism, but who hasirritable bowel syndrome and also has one of the pain syndromes that Dr.s studied. For ten years, she had used the protocols developed byDr. s and the VP Foundation, and found them to be effective. As shethought about autism, she wondered if the protocols they used to help thebody process oxalates and heal the damaged tissues could be of benefit toautistic children with bowel and urinary issues. As she discussed thisidea with me, and as I began studying the literature about oxalates, itbecame clear to me that oxalates might have been an area we missed thatcould be important. The s test for oxalates involved collecting ten separate urinesamples over a 24-hour period to determine both bound, and free-formoxalate production at different times of the day. Dr. s would makerecommendations for use of certain protocols based on the time of day thebody was excreting high oxalates. These, "timed tests" are currentlyunavailable, but hopefully will be available soon through another lab. About two months ago, before the s lab closed, we put together astudy group to see if oxalates might be high in children with autismcorrelating with certain sets of symptoms. Our initial particpants usedthese timed tests, and we did find high oxalates according to Dr. s'established ranges. We also found that there seemed to be an associationbetween the times of day when the oxalates were high and the time ofmeltdowns in behavior. We are currently working with these same motherswith the diet and other protocols, and learning of other methods to reduceoxalates. The initial results of this small group were very encouraging,especially in demonstrating improvements we did not expect, such asimprovements in speech and cognitive function, improvements in sleeppatterns and mood, reductions in hyperactivity, reduced urinary urgency,and improved urinary and bowel control. We look forward to seeing if otherchildren will respond similarly.