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Oxalates In Autism

Soon some collaborators will be putting together a study to examine the relevance of oxalates to autism. Already a small pilot study has shown that oxalates may be high among those with autism with certain symptomatology. This would not have surprised us if we had already known much about oxalates because for years scientists have described an elevation of oxalates that occurs in inflammatory bowel conditions like Crohn's or ulcerative colitis, called enteric hyperoxaluria. Since autistic enterocolitis has so many similarities to those bowel conditions, and because of the well-characterized "leaky gut", and for other reasons that will be discussed below, it would have been surprising NOT to find problems with oxalates in autism.

Oxalates are a very simple sort of molecule that links up with calcium and then crystalizes under some conditions, including when they encounter damaged tissues. The crystals formed this way can be quite irritating and painful to tissues where they form, causing or increasing inflammation. These crystals can be especially painful if they lodge themselves in places where they get in the way of the movement of other things through tight places. These physical issues are easy to understand, but there are still many secrets nature has about how oxalates interact with other parts of the metabolism.

Where do oxalates come from?

Oxalates are present in a lot of plants and fruit that we eat and in virtually all seeds and nuts. Ordinarily, the gut won't absorb much of the oxalate from the diet, and the oxalate will be metabolized by the flora or just leave the body with the stool. Under other conditions, a lot of the dietary oxalate is absorbed. Over absorption is far more likely to occur when the tight junctions between the cells which line the gut open up and let molecules pass through between the cells in a condition called the "leaky gut" which is similar to a condition in the bladder with open junctions 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, they bypass the regulation that is present when these same substances move instead through the cells. When the transport occurs through cells, the cells themselves control the quantity that crosses by regulating the number of transporters that allow that substance into the cell. After the substance crosses the cell, it can leave the cell to join the blood by means 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, when the body recognizes that you don't need more of a substance from food, the cell won't let more of that substance cross through. The body obviously loses that regulation when substances are absorbed through the "leaky" junctions between cells. Oxalates are just one of the substances where this is a problem, but whenever more oxalates are absorbed like this, the result may be high levels of oxalates in blood and urine and in tissues. Scientists call the high levels in urine hyperoxaluria.

Eating food high in oxalates is not the only way to get high oxalates systemically. Our bodies make oxalates on their own, especially when certain enzymes aren't balanced in their activity. Normally, once oxalates are in the gut, they may encounter particular species of bacteria, which will digest them and turn them into something else, that isn't so irritating. This system of microbial digestion may be why the body seems to purposefully route excess oxalate from the rest of the body to the gut. Unfortunately, the very microbes we need to do this digesting of oxalates for us are subject to being killed by antibiotics in common use. Even if there was no exposure to antibiotics, these microbes might not have colonized yet in very young children, for it does not tend to be in breast milk, but must be picked up from the environment.

Lactobacillus acidophilus is an oxalate-eating species, but when oxalates are in excess, lactobacillus can be killed off. It will be interesting to learn whether this may explain why certain children on the spectrum have a great difficulty colonizing lactobacillus acidophilus. Fortunately, a probiotic formulation of a bacteria called Oxalobacter formigenes that helps digest oxalates even better than lactobacillus is under development for 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 low in glutathione and also in oxidative stress. Oxalates add to that oxidative stress.

Plants use oxalates to protect themselves from infection or from being eaten, 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 in humans. We know a lot of negatives about oxalates, but we are just starting to learn what chemistry will change when both the sulfur and oxalate chemistry are disrupted at the same time. We certainly have to consider that problems in the sulfur chemistry may be why oxalates produce symptoms in autism that are not seen in the genetic hyperoxalurias.

We have learned recently that there is common regulation between the sulfur chemistry and oxalates. You may have heard that years ago Dr. Rimland was involved with inspiring or conducting many studies that found that vitamin B6 was very effective in decreasing autistic symptoms. We now know that Vitamin B6 (pyridoxine) is a necessary cofactor for enzymes that help prevent the formation of oxalates, but this vitamin, when deficient, will also wreak havoc with the sulfur chemistry in many places along the sulfur pathway. We have also learned that when sulfur is deficient, it becomes extremely 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 has been explored in research by Dr. Clive Solomons, a connective tissue researcher working together with the Vulvar Pain Foundation (VP Foundation). That collaboration over many years learned that any tissue, which has been injured, might be a site where oxalate may cause additional damage and pain and destruction of tissues. Those observations make sense in light of scientific studies that find oxalates add much additional oxidative stress to tissues and that their presence may further activate inflammatory cascades. An injury to a tissue is an invitation to crystallization because this sort of crystal begins by calcium binding and then oxalate binding to a type of phospholipid (phosphatidyl serine) that is ordinarily on the inside of membranes and not accessible. That type of phospholipid may be exposed on the outside of membranes when there has been tissue injury, and that begins the process of adding more and more calcium oxalate to that crystal.

Dr. Solomons and the foundation working with him found that high oxalates were associating with conditions likevulvodynia, prostatitis, irritable bowel syndrome, fibromyalgia, interstitial cystitis, and skin sensitivity. These conditions improved on the low oxalate diet and with other natural treatments they developed that were found to reduce oxalates. This collaboration also found that high oxalates seemed to be giving some people a sense of urinary urgency and frequent urination, and sometimes the patient would have trouble urinating.  

As people with these conditions shared their stories with each other, they also learned that many of them had spent years being treated for bladder or fungal infections, only to have their conditions worsen. The same patients found relief after years of pain and treatment by addressing the oxalate issue. Their improvements after lowering oxalates should not be surprising since it is known that oxalates tie up calcium, and calcium is critical to the 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 of kidney stones, but the levels of oxalate in the urine or diet do not perfectly predict the risks for such stones. Curiously, men are about twice as likely as women to form stones and there are also racial differences and only some people with higher oxalates form these stones. There are two very serious genetic conditions where an enzyme defect means the body will generate extremely high levels of oxalates and the stones may eventually induce organ failure. We have not yet heard of any family with a child with autism where either of those genetic defects has been in the family history. Nevertheless, in our initial pilot study group, after our lab reports came in showing high oxalates, we asked the parents, and found there was a high incidence of kidney stones in the families in this group. A familial association with kidney stones has been described in interstitial cystitis, another condition that improves by restricting oxalates in some sufferers. That and other research in the oxalate field suggest there could be predispositions to high oxalates that are less serious than the primary hyperoxularias. The condition of making kidney stones is not very rare (about 10% in the general population), so it will be interesting to find out if a family history of kidney stones ends up being an important predictor of which children with autism will either have high oxalates in urine or will react behaviorally to oxalates.

As mentioned earlier, the literature has long recognized an association between inflammatory bowel conditions and having excess oxalates in the urine.We don't know whether oxalates in the GI tract are what is irritating the gut and perhaps leading to problems with either constipation or diarrhea or pain. Just as likely, the inflammation and the oxalates may have developed as consequences of something else or their coexistence may be an unfortunate convergeance of unrelated things.

Regardless of what will eventually end up being the explanation, oxalates from the diet may further injure an already inflamed gut. That is why it may make sense for someone with high oxalates or chronic bowel problems or problems with urinary urgency or inflammation to do a trial of a low oxalate diet just to see if this will help heal the gut and restore urinary control.

The handful of children on the spectrum who were tested and found to have elevated oxalates were chosen for testing because they were experiencing problems with diarrhea or constipation or urinary issues. That means, at this point, we don't know if children with autism without these issues might also be high in oxalates. We had another intriguing surprise. One child in our study group craved and ate a lot of one high oxalate food before the diet, but he was also one who typically loaded down his food with salt. When his dietary oxalates were lowered, he completely stopped that salting habit, and began ignoring the salt shaker. This actually makes 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 that will look at the levels of oxalates in urine while correlating those levels with other information. The Solomons lab, which pioneered the research correlating oxalate levels to tissue pain, has recently closed due to Dr. Solomons' retirement. Since he won't be able to help us, I knew that the autism community would need to work with other scientists experienced in oxalates in order to design studies properly. For that reason, I have just gotten back from the FASEB international scientific meeting on oxalates, where I got to feel the pulse in this field, and meet the people who will be able to help us address the scientific issues.

While it becomes clear which one of those scientists will be able to help us conduct the formal studies, there will be plenty of other work to do in the meantime to insure that we know as much as possible before beginning to design the study. For several months, I have been reading the literature on oxalates in order to learn what is known about oxalates, such as their purpose, their regulation, and what they might be changing that might correlate to known biochemical features of autism. I've been doing this work while remembering another time when the autism community learned the hard way that studies performed on a clinical level before anyone understands the biological mechanisms can lead to the premature dismissal of a therapy that may have significantly improved the lives of a selected population. We need to have some inkling about who will benefit from reducing 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 already expressed an interest in trying this diet. Even though it will take some time before we can begin the formal study, that doesn't mean that people cannot be learning about oxalates in the mean time. To make this learning easier, and to make it easier for people to share experiences with this diet, I've started a yahoogroup called This email address is being protected from spambots. You need JavaScript enabled to view it. . This list (with over 1500 members in 2007) is a a place where people exploring the use of this diet can compare their results and help each other out with the details and support. I am not going to restrict this list to people involved with autism only, because there is a need for a forum also for people trying the diet for other conditions, including those mentioned earlier. This cross-pollination should be helpful. This site will have links to information about which foods have high oxalates or which foods will generate high oxalates when other chemicals in food are metabolized. The food charts referenced on the site were developed for patients with hyperoxaluria, and they are useful to read to evaluate the oxalate content of what is now the normal diet for any potential candidates for this change.

If you would like to have someone tested before trying the low oxalate diet, you can have your doctor order a 24-hour urine oxalate test that is the screening tool for hyperoxaluria. Sometimes oxalates are measured on organic acid profiles, so some people who have used that test may already know that their child has high oxalates. The standard 24 hour hyperoxaluria test, which is more specific, can be ordered from standard labs that work with your insurance company. Unfortunately, this test, because it pools all the urine from the whole day, will not tell you anything about changes in oxalate levels during the day.

Why is that a problem? Dr. Solomons found that there is a diurnal rhythm to the oxalate levels which is not the same from person to person and the levels increase in response to the activity of different enzymes processing other food chemicals into oxalates.

For some people, the issue may not be as much the level of the oxalates in the system as much as it is previous injuries to tissues that will make exposure to oxalates feel a bit like someone is pouring alcohol or acid on an open wound. I'm just saying that to alert us that the 24 hour collection may not always identify people whose sudden onset of pain or bad behavior is caused by an equally sudden increased level of oxalate.

Last modified on Thursday, 27 September 2012 18:01

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