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ALL NATURAL ADVANTAGE Natural Healthcare And Education |
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Oxalates In Autism Susan
Owens A
member of the DAN! thinktank, a project of the Autism Research Institute Listowner
of sulfurstories@yahoogroups.com Lecturer
on the sulfur system and its role 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 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 like
vulvodynia,
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 Trying_low_oxalates@yahoogroups.com.
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. Internet
and other resources In
autism circles, we are all "newbies" to this diet, but we are very
fortunate that the VP Foundation and the Oxalosis
and Hyperoxaluria Foundation both
have resources that they have developed for their members. For that reason,
please feel free to visit the following websites.
www.vulvarpainfoundation.org/vpfoxalate.htm At
www.vulvarpainfoundation.org/vpfcookbook.htm
, you will find an advertisement 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 decide to try the
low oxalate diet, right now there is no one who can predict how this diet might
be different for a child on the spectrum compared to the women in the foundation
who have used this diet in the past, or from patients with primary
and secondary hyperoxuluria who have used the diet.
For that
reason, and for general reasons of safety, please be sure to seek the help and
oversight of your child's doctor because he or she may have staff that can help
you be sure that your child is getting adequate nutrition. Ordinarily, this
wouldn't be too much of a worry, because the high oxalate list is not as
restrictive as a lot of diets, but some children may already be on diets that
are very restricted, and we will want to be sure that after adding in these
additional changes that they will still be getting enough food and the right
things to eat! The
two following sites offers the best "quick list" to help you
categorize foods as high, medium or low oxalate. www.branwen.com/rowan/oxalate.htm www.ohf.org/docs/Oxalate2004.pdf Members
of our earlier pilot study are working at consolidating the lists that are
available, which will make implementing 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 is deficient in vitamin B6, or is under oxidative stress, or is
eating more meat than his body's enzymes can break down properly. Even gluten
can be a source of oxalates, as it contains a chemical that is converted into
oxalate. When the body is too alkaline, the body may turn vitamin C into
oxalates. Also remember that oxalates may not be the only thing
that might be a problem for a child with some of these foods. For that reason,
we will probably find out that some children react to medium or low oxalate
foods as seriously as the high oxalate foods, but it may be for a different
reason. It might be helpful to start with a time
of eating only the low oxalate foods, and then if improvements occur, after a
few weeks, you can slowly see if any medium oxalate foods are tolerated without
losing progress. We have already learned from one family that you need to be very
careful and slow to increase the oxalates, and it will help to be familiar with
some oxalate lowering nutrients which will be mentioned on the website. The
whole idea is for you to be able to learn what makes your child do better. To
do that more effectively, it would be helpful to keep a journal that records
both foods and behaviours as you try varying the oxalate content of the diet. We
are very early in the process of learning what may change on a low oxalate diet,
but our pilot group has already experienced surprising changes on this diet,
especially in areas we did not anticipate. That makes us hopeful that removing the high oxalate foods
in the proper candidates may improve bowel function and pain, may relieve
bladder urgency, frequent urination or inflammation, and may reduce some types
of autistic behavior while improving development. We look forward to
seeing if these changes will be seen in a wider group. I
hope this document answers most questions about this diet, but for more
information, please see the website, especially as we gradually add resources
there. This letter may be copied to individuals inquiring about the low-oxalate
diet without additional permission from me, but distribution to groups should be
done only after contacting me for permission. Afterword: How this project happened: The
oxalate issue and its relationship to pain came up in some conversations I had
with a woman who was familiar with autism, but who has irritable bowel syndrome
and also has one of the pain syndromes that Dr. Solomons studied. For ten years,
she had used the protocols developed by Dr. Solomons and the VP Foundation, and
found them to be effective. As she thought about autism, she wondered if the
protocols they used to help the body process oxalates and heal the damaged
tissues could be of benefit to autistic children with bowel and urinary issues.
As she discussed this idea with me, and as I began studying the literature about
oxalates, it became clear to me that oxalates might have been an area we missed
that could be important. The
Solomons test for oxalates involved collecting ten separate urine samples over a
24-hour period to determine both bound, and free-form oxalate production at
different times of the day. Dr. Solomons would make recommendations for use of
certain protocols based on the time of day the body was excreting high oxalates.
These, "timed tests" are currently unavailable, but hopefully will be
available soon through another lab. About
two months ago, before the Solomons lab closed, we put together a study group to
see if oxalates might be high in children with autism correlating with certain
sets of symptoms. Our initial particpants used these timed tests, and we did
find high oxalates according to Dr. Solomons' established ranges.
We
also found that there seemed to be an association between the times of day when
the oxalates were high and the time of meltdowns in behaviour.
We
are currently working with these same mothers with the diet and other protocols,
and learning of other methods to reduce oxalates. The
initial results of this small group were very encouraging, especially in
demonstrating improvements we did not expect, such as improvements in speech and
cognitive function, improvements in sleep patterns and mood, reductions in
hyperactivity, reduced urinary urgency, and improved urinary and bowel control.
We look forward to seeing if other children will respond similarly.
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