Page Title

September 16, 2006
VITAMIN K DEFICIENCY AS A CAUSE OF AUTISTIC SYMPTOMS

Catherine Tamaro, B.S.M.E.
Mercer Island, Washington

Vitamin K overview

Vitamin K is a fat-soluble vitamin important in blood coagulation and bone metabolism. One of its
functions is to keep calcium in the bones and out of soft tissues, blood vessels, and the nervous
system. Vitamin K1, the predominant circulating form, is found in green leafy vegetables, some
dietary oils including olive, hemp, canola, soybean & cottonseed oils, liver, and fish meal. Vitamin
K2 can be found in chicken egg yolk, butter, cow liver, certain cheeses, and fermented soybean
products such as natto, and it is also produced by intestinal bacteria. Vitamin K3 is a synthetic form.
1 Many of the recent studies on Vitamin K have found that the K2 form is the most effective in
calcium and bone health.2

Vitamin K has a number of interesting functions, many of which relate specifically to autism:

• Vitamin K regulates calcium in the body through osteocalcin and the matrix G1A protein.3 Both
bone proteins are active only after undergoing carboxylation, a process in which Vitamin K is a
required cofactor. Carboxylated bone proteins have a strong affinity for calcium and control its
movement, directing it to the bones and teeth and preventing its deposition in soft tissues.

Calcium management appears to be dysregulated in people with the E4 form of Apolipoprotein.
4,5,6 Osteocalcin is found in the brain; in its absence, it appears that brain cells become more
vulnerable to the effects of calcium.

Vitamin K deficiency appears to play a role in the development of osteoporosis and in the
deposition of calcium into blood vessels.7,8 Calcification of the arteries, known as
“arteriosclerosis,” contributes to heart attacks and strokes.

• Vitamin K, an anti-oxidant that is more powerful than Vitamin E or CoQ10, is able to potently inhibit
glutathione depletion-mediated oxidative cell death.9,10

• Vitamin K inhibits production of Interleukin-6, an inflammatory cytokine.11

• Vitamin K is found in high concentration in the pancreas and appears to be involved in controlling
blood sugar.12

• Vitamin K is involved in the development of the nervous system.13

• Vitamin K has a role in glutamate conversion14 and its absence affects the rate of activity of the
enzyme glutamate dehydrogenase15.

In this paper I am proposing that a deficiency in Vitamin K causes unregulated calcium movement
and deposition in the body of the autistic child, and that unregulated calcium is a cause of many of
the symptoms associated with autism. I am also proposing that a Vitamin K deficiency is the cause
of the calcium oxalate crystals found in many autistic children.

Calcium, in tandem with the neurotransmitter glutamate, is essential to the functioning of the
excitatory cells of the nervous system: once glutamate opens the neuronal cell’s calcium channel,
calcium pours into the channel and triggers the neuron to fire. The concentration of glutamate
within the nervous system is therefore carefully regulated by the nervous system (specifically the
astrocytes, which can be negatively affected by mercury and by neurotoxins produced by Lyme
spirochetes) because excess glutamate will keep the calcium channels open, allowing calcium to
continue to enter, and excite, the neurons. Dr. Russell Blaylock, among others, has written
extensively about the neurotoxicity associated with an excess of glutamate.16 However, I believe
that unregulated calcium may play an unappreciated role in triggering the incessant neuronal firing
and resultant cell death that are a hallmark of excess glutamate in the nervous system. If a child is
unable to regulate calcium due to a Vitamin K deficiency, that child may display signs of glutamate
toxicity and uncontrolled neuronal firing that manifest as the cluster of behavioral disorders called
autism.

Russell Blaylock, M.D., characterizes glutamate as

“one of the most common neurotransmitters in the brain. Its role is primarily that of
an excitatory substance, that is it causes the brain to be stimulated, much the way cocaine does.
Using biochemical mapping techniques, we now know that many areas of the brain (such as the
cortex, striatum, hippocampus, hypothalamus, thalamus, cerebellum, and the visual and auditory
system) all contain an extensive network of glutamate type neurons. This means that glutamate is
involved in a wide variety of brain functions. It has also been demonstrated that activation of cortical
glutamate neurons can in turn activate other neurons within the nuclei located deep within the
brain, even those not using glutamate as a neurotransmitter…

“After studying a number of brains specifically stained for these special receptors, scientists
determined that the glutamate receptor is located on the cell body of the neuron and its dendrite –
on the fibers emanating from the neuron cell body like the branches of a tree. Being excitatory
transmitters, glutamate and aspartate both are involved in activating a number of brain systems
concerned with sensory perception, memory, orientation in time and space, cognition, and motor
skills.”a

a Russell L. Blaylock, M.D., Excitotoxins: The Taste That Kills, (Santa Fe, NM), 1997, pp. 31-32

Dr. Blaylock explains that glutamate causes neurons to fire by opening their calcium channels. He
explains the process this way:

“It has been known for some time that many cells, especially neurons, contain special pores or
channels that regulate the entry of calcium into the cell. These special pores are named calcium
channels. These channels plan an important role in the normal functioning of the neurons. In fact, it
is thought that the calcium channels play a vital role in activation of neurons and transmission of
their impulses. When a neurotransmitter (the chemical messenger or key) comes into contact with
the receptor (the lock) on the neuron fiber’s membrane, the calcium channel opens and the in-
flowing calcium triggers the neuron to fire or be activated.

“Normally this opening and closing of the calcium channel is carefully regulated. When stimulated
this channel opens for only a fraction of a second, allowing minute amounts of calcium to enter the
neuron. Like glutamate concentrations outside the cell, calcium concentrations inside the cell are
carefully controlled by special protective mechanisms. Should too much calcium enter the cell,
special calcium pumps drive the excess back out of the neuron. Some of the calcium is also
captured and stored within the endoplasmic reticulum of the cell, a long wavy structure within the
cytoplasm.

“It appears that several of the excitotoxins, including glutamate and aspartate, work by opening the
calcium channels, at least on certain subtypes of receptors. When these neurotransmitters are
allowed to come into contact with the receptor in too high a concentration or for too long a period of
time, the calcium channel gets stuck in the open position, allowing calcium to pour into the cell in
large amounts.

“When this happens the protective mechanisms are triggered. But, as with the glutamate pumps,
the calcium pumps also require large amounts of energy as ATP. This energy must be supplied
continuously, especially if the calcium continues to enter in large amounts and for a prolonged
period of time.”b

Dr. Blaylock’s book concerns the toxicity of glutamate, and he warns readers of the hazards of
ingesting dietary glutamate. He describes the role of the calcium channels but does not address
the questions of how much calcium is or should be present in the extracellular fluid, how it got
there, how it is removed, or whether its presence is or should be controlled. He does, however,
implicate calcium deposits in the brain in the etiology of age-related neurodegenerative diseases.

Given its potential toxicity to the nervous system if uncontrolled, it appears that one of the important
functions of Vitamin K is to regulate the availability and concentration of calcium throughout the
nervous system. Calcium that is regulated is essential to life. Calcium that is unregulated is
hazardous to neuronal and organ functioning. If

b Ibid, pp. 42-43

uncontrolled it will leave its proper storage places, which are the bones and teeth, because it has
not been firmly cemented into place, and instead it will be deposited in the soft tissues and blood
vessels of the body. If it enters the nervous system unaccompanied by its carboxylated “escort”
proteins, it seems possible that it could enter the calcium channels in excessive amounts and
trigger uncontrolled neuronal firing. I believe that once the autistic child’s body has an adequate
intake of Vitamin K it will be able to carboxylate the bone proteins, which will then be able to control
calcium and keep excess amounts out of the nervous system. This should lead to an amelioration
of the child’s neurological symptoms.

Recent research into the etiology of autism has targeted mutations or polymorphisms of the genes
controlling the glutamate receptors and the calcium channels as areas of interest. Studies looking
at mutations of the glutamate receptor genes have produced mixed results.17,18,19 However, a
paper published in September 2006 examined 116 autistic subjects and found a problem in a
gene regulating the calcium channels.20 It seems possible that a mutation in a calcium channel-
controlling gene, coupled with a Vitamin K deficiency and resultant lack of carboxylated proteins,
could lead to uncontrolled neuronal firing that presents as neurological or “psychiatric” symptoms.c
It is also possible that mutations, deletions or substitutions exist in the gene(s) encoding the
enzymes that require Vitamin K as a cofactor, making those enzymes less efficient and thereby
increasing the need for Vitamin K.

Vitamin K and Oxalic Acid Production

Calcium dysregulation appears to play an important role in the development of calcium oxalate
deposits in humans, a topic whose relationship to autism is currently being explored by autism
researchers. Oxalic acid is an organic dicarboxylic acid produced by plants, sometimes in
abundance, in order to manage and store calcium. Oxalic acid can be produced endogenously by
humans in situations of deficiency of certain vitamins and it can be produced by various species of
fungi including Aspergillus niger. Oxalic acid is highly corrosive, with a pH of approximately 1.4-1.6.
Much but not all of the oxalic acid in plants is bound to calcium, thereby making it insoluble. When
oxalate-containing plants are eaten by humans, the soluble and insoluble oxalates are normally
degraded in the GI tract by the anaerobic bacterium Oxalobactor formigenes, which is easily
destroyed by antibioticsd. Insoluble oxalates that are not degraded in the GI tract tend to pass out in
the stool. The soluble oxalate can also bind to calcium consumed in food, thereby becoming
insoluble. However, if the soluble oxalate is not either degraded by bacteria or bound to calcium
consumed in food, then it can be absorbed through the intestinal membrane. Soluble oxalate,
whether absorbed by the digestive tract, produced by the human liver, or produced by infectious
fungi, will either bind to calcium and other

c It is worth remembering that most vaccines contain glutamate in various forms. Infants have not developed the
enzyme system necessary to handle exogenous loads of glutamate, so the regular injection of glutamate from the
many infant vaccines could either initiate or accelerate the process of neuronal hyperexcitation.
d The vaccine preservative thimerosal, if excreted through the baby’s biliary system into the stool, would also have
acted as an antibiotic on gastrointestinal flora.

minerals and become insoluble or will be carried into cells on the same transporters that carry
sulfate, bicarbonate, and chloride. (Oxalic acid binds to cations, including calcium, zinc, sodium,
potassium, and magnesium.)

Calcium oxalate (CaOx) salts are insoluble and are found in many different locations in the body,
including areas that have already sustained injury, causing or increasing inflammation. CaOx salts
can be found in organs, soft tissues, blood vessels, and joints. They will upregulate inflammation,
they will cause mechanical damage, and they will interfere with the electrical signaling that is the
means by which the nervous system communicates with the body.

Kidney stones, for example, are often composed of CaOx, and they cause both inflammatory and
mechanical damage to the kidney tubules. Vitamin K deficiency appears to be a factor in the
formation of kidney stones,21 and Vitamin K-dependent carboxylase enzymes are found in the
kidney tubules.22

The Low Oxalate Diet (LOD) was developed by the Vulvar Pain Foundation (VPF) to ameliorate the
vulvar pain that was found by Dr. Clive Solomons to be linked to the presence of oxalates. Dr.
Solomons discovered the role of oxalates in triggering pain, and the assumption was made that the
major source of oxalates was dietary. Over time the VPF developed a diet low in oxalates that was
designed to lower dietary oxalate intake, with the goal of reducing body stores of oxalates and
therefore reducing pain. The VPF’s diet has recently been presented as a solution to some of the
behavioral and health problems plaguing children with autism.

The LOD as presented by the VPF and the listserve Trying_Low_Oxalates (TLO) does not
contemplate or advise the use of Vitamin K. Since the purpose of LOD is to lower dietary oxalates, it
discourages the consumption of leafy greens which are high in oxalates but which are a main food
source of Vitamin K1. LOD does encourage the use of citrate minerals, namely calcium citrate and
magnesium citrate, because citrate seems to be able to chelate calcium from the CaOx salts in the
body.

The Low Oxalate Diet developers do not appear to have examined the question of what happens to
the calcium freed from the calcium oxalate salts. However, at least in the case of autistic children, it
is probable that they have low levels of Vitamin K and therefore low levels of carboxylated bone
proteins. Thus the children presumably have little ability to manage this freed calcium, which will
circulate unimpeded into the nervous system and other organs and tissues. This influx of
unmanaged calcium into circulation and then into the nervous system is, I believe, the reason that
so many autistic children are exhibiting adverse responses to the LOD, including seizures,
behavioral regression, hyperactivity, and depression. These symptoms do not indicate that oxalates
have moved from storage into circulation for transport to the disposal sites (termed “oxalate
dumping” on the TLO listserve), but rather reflect the deleterious effects of an influx of unmanaged
calcium into the nervous system. Some of the autistic children on the LOD begin to experience
heavy nosebleeds, which could reflect an exacerbation of an existing Vitamin K deficiency since on
the LOD, Vitamin K-containing vegetables have been removed from the diet. The body’s first priority
use of Vitamin K is manufacture, in the liver, coagulation factors that prevent bleeding and clotting
disorders. If Vitamin K is withheld from the diet to the point where nosebleeds develop, then other,
less apparent problems with clotting may be present also.

I believe that most if not all children with autism are producing oxalic acid endogenously and that
they have large body stores of insoluble oxalates, primarily in the form of calcium oxalate crystals.
Humans produce oxalic acid in the liver, which is the only organ in the human body that stores
Vitamin K.23 Humans are known to produce oxalic acid in response to certain vitamin deficiencies;
at this time it is known that a deficiency of Vitamin B6 will cause the human liver to manufacture
oxalic acid. I believe it is probable that the liver is also producing oxalic acid in response to a
Vitamin K deficiency.e If this is true, then reducing dietary intake of oxalates will not solve the
problem of endogenous production but could in fact increase oxalate production since a low-
oxalate diet excludes dietary sources of Vitamin K1 such as leafy greens.

Vitamin K-dependent enzymes are found in the kidney tubules, a fact which seems to indicate that
the kidneys have a mechanism for disposing of oxalic acid while preventing it from crystallizing with
calcium. However, without Vitamin K these enzymes cannot work, which may lead to the formation
of numerous CaOx crystals in the kidney tubules. Once the kidney tubules become “clogged” they
will have difficulty in excreting many substances, including oxalic acid, metabolic waste products,
toxins, and heavy metals.

Another means of disposal of oxalic acid is across the intestinal lumen into the GI tract, where
intestinal bacterial degrade the acid into harmless substances. However, oxalate-degrading
bacteria, which includes Oxalobactor formigines and various form of lactic acid bacteria (and
Vitamin K-producing bacteria too) are easily destroyed by antibiotics so the intestinal flora of most
autistic children probably does not include these types of “good” bacteria. Therefore if kidney tubule
efficiency is reduced due to the presence of CaOx crystals, and the intestines don’t contain the
types of bacteria that can degrade oxalates, the autistic child will have difficulty disposing of the
oxalic acid via either urine or stool, so it will remain in the body to form mineral crystals.

However, once the Vitamin K deficiency is rectified, I believe that the child’s body will slow or cease
its endogenous production of oxalic acid. Consumption of lactic acid bacteria, especially those
found in the commercial preparation VSL#3, will introduce bacterial species into the intestines that
are capable of degrading oxalates.24 Soluble oxalate secretion across the intestinal membranes
will then increase, and once the soluble oxalate reaches the intestinal contents, the probiotics will
degrade it. The probiotics should able to degrade dietary oxalates (soluble and insoluble), allowing
the child to consume the healthy vegetables containing both oxalates and Vitamin K. The probiotics

e Dr. Clive Solomons found that, if the diet is very low in oxalates, the dieter would begin to produce oxalates
endogenously. The very-low-oxalate dieter is by definition eating few or no leafy greens, the main dietary source of
Vitamin K1, lending some credence to the hypothesis that a Vitamin K deficiency is one reason the liver would
manufacture soluble oxalates.

should also begin to degrade any insoluble oxalate crystals attached to the intestinal lumen.

Vitamin K appears to be capable of chelating the calcium from calcium oxalate crystals, thus
dissolving them and opening up the kidney tubules as another avenue for disposal of soluble
oxalate. As CaOx crystals deposited around the body begin to dissolve, the autistic child’s behavior
should improve. Therefore' once Vitamin K supplementation and VSL#3 consumption have been
established the Low Oxalate Diet is probably unnecessary.

Baths or footbaths of Epsom salts, baking soda, and sea salt may accelerate the process of
draining oxalic acid from the body. Oxalic acid shares the same cellular transporters as sulfur,
bicarbonate, and chloride; when the circulatory levels of these three latter substances are
increased, they are more available for transportation into cells to replace the oxalic acid. This will
bring more oxalic acid into circulation. As the kidneys absorb the sulfate, bicarbonate, and chloride,
they should be able to increase their rate of oxalic acid secretion into the urine.

Vitamin K, Calcium, and the Intestinal Membrane

A recent paper by Susan Owens, MAIS entitled “Mechanisms Behind The Leaky Gut”25 points out
the importance of calcium in regulating the opening and closing of the “tight junctions” of the
intestinal membrane:

“I've put a study at the end of this article whose authors discovered that some of this process of
opening and closing the tight junctions appeared to be mediated through an interaction with
calcium. This did not involve the concentration of calcium that was inside the intestinal cells, but it
only involved the calcium that was outside the cell. Removing the calcium from either side of that
tight junction could really change things, but changing the level of calcium inside the rectangle
(representing the inside of the cell) made no difference at all."

“Right next to where that gate is located on the basolateral (or blood side) are some molecules and
a "sensor" that picks up calcium that is travelling in the fluid on this basolateral or blood side. I've
represented that sensor as an asterisk. If there is adequate calcium at that sensor, then the leaky
gut closes, just as if it had been zipped up. In fact, calcium is actually a key ingredient used to close
the zipper. When there is not enough calcium present to close the gate, the gate stays open so that
calcium from the food side can come in through the gap until there is enough calcium to close the
gate again. In fact, at times, there are oscillations that occur as this gate opens and closes in
response to calcium.” f

Owens’ paper does not address the role of Vitamin K in regulating the extracellular calcium, but
several interesting question present themselves: Is the calcium needed to regulate the tight
junctions either not present or not usable, due to lack of carboxylated

f Susan Owens, MAIS, ‘Mechanisms Behind The Leaky Gut’, 2006, page 3

“escort” proteins? Would the addition of Vitamin K as a dietary supplement provide usable calcium
to improve the GI tract’s functionality?

Vitamin K, Calcium, and the Specific Carbohydrate Diet

Some parents have noted that their children experience problems with the Specific Carbohydrate
Diet (SCD), a diet designed to bring order and balance to the intestinal flora. It is quite possible that
the regressions the parents are witnessing are actually due to the movement of uncontrolled
calcium into circulation, regressions that would be more pronounced if the regressing children
were consuming the yogurt recommended by the SCD designers. Yogurt made according to SCD
directions would contain large amounts of both Lactobacillus acidophilus and Streptococcus
thermophilus, both of which are known to degrade oxalates. If these two bacterial species begin
degrading insoluble oxalates in the autistic child’s intestinal tract, thereby liberating calcium, the
child will experience neurological problems if he/she is deficient in Vitamin K, which is probably the
case. Therefore it seems that once the Specific Carbohydrate Diet incorporates Vitamin K, more
children will be able to tolerate and benefit from it.

Recommended Dose of Vitamin K

There is considerable uncertainty about what constitutes an adequate intake of Vitamin K. The RDA
is essentially the amount the liver needs for its clotting functions; the amount the bone proteins
need is unknown.

The Japanese studies on osteoporosis in adults used 15 mg of Vitamin K2, three times daily. This
dose was well-tolerated and without toxic effects. To adjust this dose for a child, divide the child’s
weight by 150 and apply that fraction to the adult dose. Vitamin K2 is available in liquid, gelcap or
capsule form. Because it is a fat-soluble vitamin it must be consumed with dietary fat.

Conclusions

It is possible that the unregulated movement of calcium in the autistic child is responsible for some
of the neurological symptoms of the disease: calcium triggers the neurons to fire; excess calcium,
or uncontrolled calcium, may cause the neurons to fire until they die. Vitamin K is an essential
cofactor in the development of bone proteins that can control calcium and most if not all autistic
children are probably severely deficient. The dietary addition of Vitamin K would activate the bone
proteins that manage calcium, thereby controlling that calcium and bringing some order to the
metabolic chaos that is autism. It is possible that children with autism have problems with the gene
(s) controlling glutamate management, calcium channel function, and/or Vitamin K-dependent
enzyme production.

A Vitamin K deficiency may be a contributing factor in the autistic child’s endogenous production of
oxalic acid, which can bind to and immobilize calcium. If the renegade calcium is bound to oxalates
it cannot make its way into the nervous system and cause damage. The human body seems to
have a reason for producing oxalic acid: to control and manage calcium. It also has the means to
dispose of it once the diet contains adequate Vitamin K again: the Vitamin K triggers carboxylation
of bone proteins, which can then chelate the calcium from the crystals and put the calcium where it
belongs. Meanwhile the oxalic acid will be disposed of, via secretion either through the kidney
tubules or across the intestinal membrane. However, if the kidney tubules are not filtering well due
to the presence of CaOx crystals, or if the intestines do not contain oxalate-degrading bacteria, then
the oxalic acid will remain in the body and re-crystallize. Disposal of any other waste product or toxin
will be compromised also.

The Low Oxalate Diet is a poor method of addressing the problem of CaOx crystals. LOD uses
dietary manipulation and citrate minerals to dissolve CaOx stones, but as the child has low Vitamin
K the calcium influx is unmanaged and causes additional damage to the nervous system. The
avoidance of Vitamin K1-containing vegetables means that the child’s stores of Vitamin K will be
depleted and yet the liver will continue to produce oxalates.

There exists the distinct possibility that the heavy metal chelators (e.g. DMPS, DMSA, EDTA) cause
dissolution of CaOx stones. The regressions and problems that children experience when
undergoing heavy metal chelation are consistent with the effects from the release of uncontrolled
calcium into circulation. Therefore perhaps heavy metal chelation should be halted while Vitamin K
deficiencies are addressed and calcium, including the calcium bound to oxalates, is brought under
control.

It is possible that the leaky gut cannot be closed until controlled calcium is brought to the tight
junctions.

In conclusion, Vitamin K has a number of essential roles in the human body and it would appear its
importance has been overlooked thus far. Vitamin K deficiency may be a cause of chronic neuronal
hyperexcitement, which could manifest as autistic symptoms; it may also be a cause of the
development of calcium oxalate crystals and stones, which may well be found in abundance in all
autistic children. The administration of pharmacological doses of Vitamin K to children with autism
disorders would appear to hold great promise in turning around some of the symptoms of the
disease.

APPENDIX A
SOURCES
1. www.pdrhealth.com/drug_ingo/nmdrugprofiles/nutsupdrugs/vit_0267.shtml accessed
09/01/2006.

2. Zitterman A, Effects of Vitamin K on calcium and bone metabolism, Curr Opin Clin Nutr Metab
Care, 2001 Nov;4(6):483-7.

3. www.pdrhealth.com/drug_ingo/nmdrugprofiles/nutsupdrugs/vit_0267.shtml accessed
09/01/2006.

4. Veinbergs I, et al, Neurotoxic effects of apolipoprotein E4 are mediated via dysregulation of
calcium homeostasis, J Neurosci Res., 2002 Feb 1;67(3)379-87.

5. Wang XS, et al, Rapid elevation of neuronal cytoplasmic calcium by apolipoprotein E peptide, J
Cell Physiol, (1997) 173:73-83.

6. Tolar M, et al, Truncated Apolipoprotein E (ApoE) Causes Increased Intracellular Calcium and
May Mediate Apo Neurotoxicity, The Journal of Neuroscience, August 15, 1999, 19(16):7100-7110.

7. www.pdrhealth.com/drug_ingo/nmdrugprofiles/nutsupdrugs/vit_0267.shtml accessed
09/01/2006.

8. Seyama Y, et al, Comparative effects of vitamin K2 and vitamin E on experimental
arteriosclerosis, Int J Vitamin Nutr Res., 1999 Jan;69(1):23-6.

9. Vervoort LM, et al, The potent antioxidant activity of the vitamin K cycle in microsomal lipid
peroxidation, Biochem Pharmacol, 1997 Oct 15;54(8):871-6.

10. Jianrong L, et al, Novel Role of Vitamin K in Preventing Oxidative Injury to Developing
Oligodendrocytes and Neurons, The Journal of Neuroscience, July 2, 003, 23(13):5816-5826.

11. Reddi K, et al, Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is
potently inhibited by naphthoquinone (vitamin K) compounds, Cytokine, 1995 Apr;7(3):287-90.

12. Sakamoto N, et al, Low vitamin K intake effects on glucose tolerance in rats, Int J Vitam Nutr
Res, 1999 Jan;69(1):27-31.

13. Tsaioun KI, Vitamin K-dependent proteins in the developing and aging nervous system, Nutr
Rev., 1999 Aug;57(8)231-40.

14. Sugiura I, et al, Propeptide and glutamate-containing substrates bound to the vitamin K-
dependent carboxylase convert its vitamin K epoxidase function from an inactive to an active site,
Proc. Natl, Acad Sci. USA, Vol. 94, pp. 9069-9074, August 1997.

15. Lider VA, The effect of vitamin K on the activity of glycolysis and pentose phosphate cycle
enzymes, Vopr Med Khim., 1988 May-June;34(3):64-7 [Article in Russian].

16. Russell L. Blaylock, M.D., Excitotoxins: The Taste That Kills (Santa Fe, NM), 1997

17. Ramoz N, et al, Linkage and association of the mitochondrial aspartate/glutamate carrier
SLC25A12 gene with autism, Am J Psychiatry, 2004 Apr;161(4):662-9.

18. Segurado R, et al, Confirmation of association between autism and the mitochondrial
aspartate/glutamate carrier SLC25A12 gene on chromosome 2Q31, Am J Psychiatry, 2005 Nov;162
(11):2182-4.

19. Rabionet R, et al, Lack of association between autism and SLC25A12, Am J Psychiatry, 2006
May;163(5):929-31.

20. Laumonnier F, et al, Association of a Functional Deficit of the BKCa Channel, a Synaptic
Regulator of Neuronal Excitability, With Autism and Mental Retardation, Am J Psychiatry, 2006 Sep;
163(9):1622-1629.

21. Chen J, et al, Decreased renal vitamin K-dependent gamma-glutamyl carboxylase activity in
calcium oxalate calculi patients, Chin Med J (Engl), 2003 Apr, 116(4):569-72.

22. Friedman PA, et al, Localization of renal vitamin-K dependent gamma-glutamyl carboxylase to
tubule cells, J Biol Chem., 1982 Sep 25;257(18):11037-40.

23. Guyton & Hall, Textbook of Medical Physiology, Tenth Edition, 2000

24. Campieri C, et al, Reduction of oxaluria after an oral course of lactic acid bacteria at high
concentration, Kidney Int., 2001 Sep;60(3):1097-105.

25. Susan Owens, MAIS, ‘Mechanisms Behind The Leaky Gut,’ 2006

APPENDIX B
CALCIUM OXALATES
In the urinary sediment, one can find two forms of calcium oxalate crystals. The most frequent form
is the di-hydrated calcium oxalate. The mineralogical name of the calcium oxalate 2(H2O) is
Weddellite. The second form is the mono-hydrated calcium oxalate whose mineralogical name is
Whewellite. The two forms have different crystallographic characteristics. It seems that the
calcium/magnesium ratio plays an important role in the formation of the calcium oxalate crystals.
Crystals of calcium oxalate are found mainly in an acidic urine, but these can also be seen in
slightly alkaline specimens.

Weddelites: Calcium oxalates 2(H2O)

The weddelite or calcium oxalate di-hydrate crystallizes in the tetragonal system. The classic crystal
shape is the eight-face bi-pyramid. In bright field microscopy, the weddelite crystals are recognized
easily by their shape that reminds a mail envelope. More complex shapes of weddelite are
possible. The dumbbell shape is not rare. The former has no precise angles or sides. This form is,
in reality, an microcrystalline agglomerate that takes the shape of a biconcave disc.
Weddelite crystals are poorly birefringent and do not show any interference pattern under polarized
light.

Weddelite crystals are usually of little clinical value. Many specimens develop weddelite crystals on
standing.

Whewellites: calcium oxalates (H2O)

The whewellite crystal is a rare form of crystallization of calcium oxalate. In theory, the whewellite, or
calcium oxalate mono-hydrate crystallizes in a monoclinic leave shape, but in the majority of cases,
the former precipitates as an oval egg shape. The dumbbell structure is often erroneously
associated to this form of oxalate. X-ray analysis have shown that the dumbbell structure can also
represent weddelite crystals. Contrarily to the weddelite, the whewellite is found in situations of
massive calcium oxalate precipitation. According to Berg, the abundance of oxalates formed of
ovoid structures strongly agglutinated, twin structures, and microliths, is an indication of a
pathological massive precipitation. Urines of patients with a calcium oxalate urolithiase have a
tendency to have a sediment with some of the preceding characteristics.

Source: http://www.agora.crosemont.qc.ca/urinesediments/doceng/doc_025.htm, accessed
09/01/2006

Note: My 9-year-old son, diagnosed with Autism Spectrum Disorder, is urinating large amounts of
crystals that appear to be whewellite CaOx crystals.

APPENDIX C

Suggested Approach to Oxalate Degradation and Disposal

1. Vitamin K2, adjusted for the child’s body weight by dividing the child’s weight by 150 and applying
that fraction to the adult dose of 15 mg TID. (I am using the liquid from Thorne Research.)

2. Magnesium, which closes the calcium channel.

3. The commercial probiotic preparation VSL#3 (www.vsl3.com), which contains strains of lactic
acid shown to be able to degrade oxalates in the GI tract. I have found that consuming yogurt
cultured with VSL#3 is more effective in controlling the diarrhea induced by oxalates leaving the
body than the probiotic alone. I use two envelopes of VSL#3 and two quarts of goat milk and culture
it for 24 hours. I believe that, once established on Vitamin K, children who were previously dairy-
intolerant may be able to tolerate dairy products, because their bodies can now control the
absorbed calcium.

4. Baths or footbaths of Epsom salts, baking soda, and sea salt to exchange with soluble oxalates
and encourage their release from cells.

5. Other supplements as required by the individual child.

6. The Specific Carbohydrate Diet. This diet is absolutely essential to re-establishing healthy GI
flora.

7. When Oxalobactor formigenes becomes available as a prescription product it will be a useful
addition to the child’s arsenal of “good” GI bacteria. But its presence is not essential to the removal
of oxalates from the body.

Vitamin K appears to be able to chelate the calcium from the CaOx salts, leaving behind oxalic acid
that can be either filtered through the kidneys or secreted across the intestinal membrane for
disposal. If the child’s GI tract contains oxalate-degrading bacteria, the concentration of oxalates
inside the GI tract will remain less than the concentration in the body, signaling the body to continue
secreting oxalates across the intestinal membrane. Magnesium closes the calcium channels and
will assist in controlling neuronal firing. The sulfate, bicarbonate, and chloride can all exchange
with the oxalic acid inside cells, allowing the oxalic acid to leave the cell and be disposed of. The
Specific Carbohydrate Diet (SCD) will address the obvious imbalances in GI flora that have led to
this situation, which include the absences of both O. formigenes and Vitamin K-producing bacteria.
Children experiencing setbacks on the Specific Carbohydrate Diet, especially those consuming
yogurt, may actually be manifesting the effects of a release of uncontrolled calcium from calcium
oxalate crystals. The lactic acid bacteria L. acidophilus and S.thermophilus, the classic yogurt-
making bacteria used in the SCD, have been found to degrade oxalates effectively. Again, as I have
stated elsewhere in this paper, degradation of calcium oxalate crystals results in the release of
calcium, and if the child is Vitamin K-deficient, the released calcium will be uncontrollable and
therefore potentially harmful to the nervous system.