http://www.newtreatments.org/fromweb/sulfur.html



Part 1:

This is a LONG discussion on the phenol-sulphotransferase issue, but
it is very informative and I recommend you print it out and study it
if you think your child might have this problem.

This is a condition that affects 80% to 90% of the children with
autism. It is vital that you understand the symptoms, and if they
affect your child, you must "unload the donkey". PST (phenol-
sulfotransferase) is a Phase II enzyme that detoxifies leftover
hormones and a wide variety of toxic molecules, such as phenols and
amines that are produced in the body (and even in the gut by
bacteria, yeast, and other fungi) as well as food dyes and chemicals.
These reactions include the breakdown of bilirubin and biliverdin,
which are the breakdown products of hemoglobin. There are many
varieties of phenols. This may indicate why children's intolerances
vary. Remember, Bolte notes that tetanus infection of the intestines
leads to the formation of toxic phenols, and states that these are
particularly formed by overgrowth of the Clostridium family of
bacteria. The toxins formed can peel the lining of the colon right
off the organ, and lead to an explosive, debilitating form of
diarrhea. She notes that tetanus also attacks the Purkinje cells of
the brain potentially reducing the production of the amino acid GABA,
a calming neurotransmitter known to affect speech.

"The PST enzyme is only one of many sulfotransferases, and various
other body chemicals can increase the quantity of some
sulfotransferases, and that would increase their activity....Sulfate
must be grabbed by any sulfotransferase before the enzyme can attach
it to something else, like phenols or MHPG (3 methoxy-4-
hydroxyphenylglycol, a natural breakdown product of a class of
neurotransmitters called catecholamines). If the PST enzyme activity
towards something is low, you can boost it by two approaches. The
first is to increase the amount of sulfate available to it. The
second is to increase the amount of the enzyme so it has an easier
job finding the available sulfate."-Susan Owens.

The PST enzyme links an oxidized sulfur molecule (a sulfate) to these
various toxic substances to solubilize them so the kidneys can
dispose of them. Obviously, if sulfate is low or missing, this can't
happen effectively. Hence, the problem can be twofold: there may be a
lack of phenol-sulfotransferase enzymes, or of the sulfates (due to
the absence of protein and of sulfur carrying raw vegetables in the
diet, the poor absorption of sulfur from the diet, a failure to
metabolize sulfur into sulfate form, or increased urinary excretion
of sulfite and sulfate).

Dr. Rosemary Waring's research shows that the lack of sulfate is the
primary problem in 73% of these children (another study found low
levels in 92%), but all of those Waring checked had a low PST level
too. Similar sulfate deficiencies have been reported in people with
migraine, Rheumatoid Arthritis , jaundice, and other allergic
conditions all of which are anecdotally reported as common in the
families of people with autism. Adequate sulfoxidation requires
adequate supplies of B-vitamins, especially vitamin B6. The PST
enzymes are inhibited or overloaded by chocolate, bananas, orange
juice, vanillin, and food colorants such as tartrazine. Removal of
these from the diet and supplementation of sulfates may well relieve
all these symptoms. The lack of sulfation could well be due to the
largely carbohydrate diet of most of these children. It is likely a
combination of all these things. In any case, toxic compounds of
these aforementioned chemicals can build to dangerous levels. A high
value for the tIAG (?) as well as a high reading for DHPPA (rather
HPHPA-a phenolic metabolite of tyrosine) both indicate a PST problem.

There are two pathways by which the Phase II enzymes process these
toxins. One attaches the sulfates as mentioned, and the other
attaches glucuronide. Dr. Waring has found that in autistic patients
there is not nearly enough sulfate to glucuronate ratio. She and her
associates feel that the "leaky gut", that causes a need for a Gf/Cf
diet, is caused by this lack of adequate sulfate to provide sulfation
of the glucosaminoglycans (sulfated sugars). They found that the
glucosaminoglycans (gags) in the gut were very under sulfated, and
that this causes a thickening of the basement membrane of the gut.
IGF (insulin-like growth factor) is important for cell growth. IGF-1
(which is reduced in zinc deficiency) increases the incorporation of
sulfate in glucosaminoglycans.

Unfortunately, a lack of sulfated gags in the kidneys will allow loss
of these sulfates. There is often found low plasma sulfate and high
urine sulfate and high urinary thiosulfate as if the kidneys are not
able to retain (recycle) sulfate. This needed retention requires the
work of a transporter that has been found in "in vitro" studies to be
blocked almost completely by mercury and by excess chromium (but not
as thoroughly). One study found urinary sulfite to be elevated due to
a lack of molybdenum in 36%. Supplementing moly showed improvements
in clinical symptoms. Sugar increases the amounts of calcium,
oxalate, uric acid, and glucosaminoglycans being wasted in the urine.

Sulfates have a negative charge and repel each other, so that charge
forms a barrier on the outside of the cell called the matrix, or the
glycocalyx. Sulfate is often found in the glycoprotein film also.
Glycoprotein is a sugar/protein film that enables cell-cell
communication. This film is on all cells of the body, so if systemic
sulfate is low, you most likely have a big problem that is quite
general to the whole body. Specifically, the more densely sulfated
the GAGs, the more they can resist all kinds of infection. These
sulfate molecules govern or influence the ability of the cell to
produce its unique set of specialized proteins. It is not something
you want to be operating from a deficit, yet that is the condition of
most autistic children.

Dr. Waring found that 92% of autistic children seem to be wasting
sulfate in the urine; for blood plasma levels are typically low and
urinary levels are high. There is also an abnormal cysteine to
sulfate ratio. Cysteine is the amino acid that should be used to make
sulfate, so it appears that the sulfate is probably being utilized
far faster than the cysteine can be converted, leaving a deficit of
sulfate (sugar wastes it), or the cysteine is not being metabolized
to sulfate. That may cause the cysteine to build up to toxic levels.
Cysteine is formed from the essential amino acid methionine.
Homocysteine, an intermediate between methionine and cysteine, and
cysteine are powerful excitotoxins. In the aged, and in chronic
disease, methionine is not efficiently converted to cysteine, but
builds homocysteine. This can create a deficiency of this vital amino
acid, cysteine, and a lack of sulfate. A deficiency of cysteine, or a
failure to metabolized it to sulfate, will produce multiple chemical
sensitivities and food allergies . Being a major part of the powerful
antioxidants alpha lipoic acid and glutathione, a deficiency of
cysteine, or a failure to metabolize it into these antioxidants,
would greatly affect the liver's ability to detoxify, and would lead
to destruction throughout the body by free radicals This would also
allow buildup of the heavy metals lead, cadmium, mercury, and
aluminum. Supplementation of vitamin B2, B6, B12, folic acid,
magnesium, and TMG may normalize metabolism of methionine into
cysteine, but vitamin C is needed to prevent cysteine (which
contributes its sulfur more readily) from converting to cystine, its
oxidized form.

What could be one source of interference with sulfation? Swimming!
High concentrations of chlorate were detected in samples from a
number of pools; in one case as high as 40 mg/l. Higher chlorate
concentrations were associated with those pools using hypochlorite
solution as a disinfecting agent, while relatively low chlorate
concentrations were found in pools treated with gaseous chlorine.
Chlorate IS the biological substance of choice to block sulfation.
Additionally, chlorate is known to inhibit hematopoiesis [the making
of new blood cells], a problem with many of our kids. Additionally,
hypochlorite reportedly combines with any phenolic compound, even in
very dilute solutions, to form an aromatic compound that can react in
the body. This combining of chemicals can be very toxic to
susceptible individuals. One Mom found that an Epsom Salts bath
immediately following eliminated after swimming problems in behavior.
So, if you must swim, do the bath immediately after coming from the
pool. For home pools, one Mother reports, "An ionizer cuts down
chlorine use by 70-80%. Since installing this, we don't see the
reactions anymore."

The excess-cysteine/low-sulfate condition that Waring observed may be
because of a deficiency of the amino acid histidine that can be run
low by seasonal allergies and the medications taken to treat them.
Metal toxicities, common in these kids, can run it low. Experimental
deficiency of histidine causes an excess of free iron in the blood.
This can adversely affect the enzyme cysteine dioxygenase (CDO), the
essential nutritional components of the enzyme being histidine and
iron. A deficiency of this amino acid, possibly caused by allergies,
heavy metals poisoning, and medications, not only affects HCl
production (histidine delivers zinc to the cells, and together they
produce HCl), but it will likely cause a toxic build up of the amino
acid cysteine, and a lack of sufficient taurine and sulfate
contributing to the PST problem. High histidine lowers zinc and
copper by chelating them from the body. Supplementing taurine, the
sulfur containing amino-acid that is at the end of the metabolic
chain, has been helpful in meeting this need for taurine; and, being
the immediate precursor, may supply needed sulfates. Taurine is
reported to have an anti-opioid effect (Braverman 1987).

Those with inadequate protein in the diet, or with poor assimilation,
resulting in a deficiency of histidine and other nutrients, form
poorly sulfated GAGS robbing the cells of ability to resist infection
(that describes 100% of these children). Additionally, it produces
dysbiosis (flora imbalance) in the gut. Those with chronic infection
shed and replace GAGs so quickly that inadequate sulfate is available
even with adequate protein intake. Vitamin A deficiency has been
shown to produce an accelerated turnover of GAGs as well as their
undersulfation. When the live viral, measles vaccine is given, it
depletes the children of their existing supply of Vitamin A. The
measles virus hidden in the gut is able to create a chronic vitamin A
deficiency. Natural Vitamin A (cis form) is important for activation
of T and B cells for long-term immune memory to develop, and it is
necessary for optimal Natural Killer Cell function, Cis Vitamin A can
bypass blocked G-protein pathways and turn on central retinoid
receptors. Available zinc controls the amount of vitamin A the liver
will release.

In one study, the urinary GAGs changed to normal when the vitamin A
deficiency was corrected, but if protein starvation caused the
undersulfation of GAGs, the urinary GAGs did not return to normal
with adequate protein intake, but did improve quite a bit. Most
autistic children are vitamin A deficient. Do you or your child have
bumps on shoulders, thighs, elbows, and calves? Supplement with pure
amino acids, Seacure™, Brewer's yeast, or desiccated liver for their
protein, and with Evening Primrose oil (for its GLA), and cod-liver
oil for its EPA, DHA, and vitamins A and D. Seacure™ may help.

It was Dr. Andrew Wakefield's work that showed that at the core of
the problem might be an inflammation of the gut caused by a chronic
measles infection. Dr. Wakefield's work is being vindicated by other
researchers. Under oath before Congress on April 6, 2000, Professor
John O'Leary told how his state-of-the-art laboratory had identified
the measles virus, something that certainly should not have been
there, in samples taken from the intestines of 24 of the 25 patients.
From Japan: "The sequences obtained from the patients with Crohn's
disease shared the characteristics with wild-strain virus. The
sequences obtained from the patients with ulcerative colitis and
children with autism were consistent with being vaccine strains. The
results were concordant with the exposure history of the patients.
Persistence of measles virus was confirmed in PBMC (blood cells) in
some patients with chronic intestinal inflammation"-Kawashima H, Mori
T, Kashiwagi Y, Takekuma K, Hoshika A, Wakefield A, Department of
Paediatrics, Tokyo Medical University, Japan. From Canada: "The
presence of measles virus in the brain tissue was confirmed by
reverse transcription polymerase chain reaction. The nucleotide
sequence in the nucleoprotein and fusion gene regions was identical
to that of the Moraten and Schwarz vaccine strains; the fusion gene
differed from known genotype A wild-type viruses"-Bitnun A, Shannon
P, Durward A, Rota PA, Bellini WJ, Graham C, Wang E, Ford-Jones EL,
Cox P, Becker L, Fearon M, Petric M, Tellier R; Department of
Critical Care Medicine, The Hospital for Sick Children, Toronto,
Ontario, Canada. Clin Infect Dis 1999 Oct;29(4):855-61. From
Sweden: "This study provides evidence that measles virus can spread
through axonal pathways in the brain. The findings obtained in the
gene-manipulated mice point out that a compromised immune state of
the host may potentiate targeting of virus to the limbic system
through olfactory projections"-Urbanska EM; Chambers BJ; Ljunggren
HG; Norrby E; Kristensson K, Department of Neuroscience, Karolinska
Institute, Stockholm, Sweden.

The gut sheds sulfated glucosaminoglycans during inflammation which
could account for the low levels there and the high levels in urine.
This leads to a "Leaky Gut" condition, and to the excess opioid
problem. Not only do macrophages (scavenging white blood cells) eat
GAGs and release inorganic sulfate, there is a transporter the
intestines use to absorb sulfate from the diet, called the DRA
transporter. Its levels will decrease five-to-seven fold when the gut
is inflamed. That would make it extremely difficult to absorb
adequate sulfate from food or from oral supplements. The problem is a
nutritional one, but it is not one easily solved by oral
supplementation of a missing substance. The gut must be healed.

Since sulfur intake is low, and its oxidation is slow in many
autistic children, sulfate is low, and PST activity is slower than it
would be otherwise. It would seem that this sub optimality of
sulphotransferase activity is a function of low plasma sulfate levels
rather than of deficits in the actual enzyme. Cellular level
enzymatic effects of mercury's binding with proteins include blockage
of sulfur oxidation processes and of the neurotransmitter amino
acids. These have been found to be significant factors in many
autistics. Thus, mercury, and any foodstuff that requires or uses up
sulfate ions during its metabolism, will make the situation worse.
These foodstuffs include foods that supply neurotransmitters, like
bananas (serotonin), chocolate (phenylethylamine), and cheese
(tyramine), apple juice (and one mother reports her child drank a
quart a day!), citrus fruit juices, and paracetamol (Tylenol™). For
instance, one or two minutes after a dose of Tylenol™, the entire
supply of sulfate in the liver is gone!

In fact, any chemicals with a high proportion of phenolic groupings
will have this effect, and will enhance the problems referred to
above. Many coloring materials, whether of natural or synthetic
origin, possess phenolic groupings. Phenol, an organic compound, has
other names such as hydroxybenzene. If the PST enzyme is deficient or
sulfoxidation is lacking in some 70% to 80% of autistic kids as some
say, it behooves mothers to seriously heed the information in this
section, and to carefully guard their children from certain obvious
sources of trouble.

It is interesting to note Dr. Waring's statement that those with the
PST/low sulfation problem have central nervous system problems from
the toxic amines. For example migraine sufferers usually have low PST
activity, and are readily affected by dietary "triggers", especially
those with amines. Compounds such as flavonoids (red wine and citrus
fruits), aged cheese, beers, chocolate, and strong odors inhibit PST
leading to headache in the less resistant. Apple juice, citrus
fruits, chocolate, and paracetamol (Tylenol™) were precisely those
that were known to precipitate migraine attacks in susceptible
individuals. It should be noted that many multivitamin supplements,
grapeseed extract, Pycnogenol™, Quercetin, and other antioxidants
contain high amounts of flavonoids. Quercetin is found in 78% of the
foods. It is useful in hay fever (suppress the histamine release),
some forms of cardiovascular disease, and it chelates metals to
prevent oxidation. It decreases vascular fragility, but stimulates
adrenaline release (decreasing thymus weight), reduces general
metabolism (reduces temperature and oxygen consumption), suppresses
thyroid activity, inhibits p450 (Phase I) liver enzyme activity, and
it is linked with male impotence. From this list of negatives, one
can see it should not be used in quantity for long term.

Modifications of serotonin (5-HT), dopamine (DA), and DA metabolites
[homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC)] were
assessed at urinary levels. Responders and nonresponders showed a
significant decrease of urinary 5-HT levels on fenfluramine (appetite
suppressant related to amphetamine). The main differences between the
two groups of subjects were found with HVA, the major metabolite of
dopamine. Fenfluramine (an amphetamine) significantly increased HVA
levels in responders whereas no significant modification was found in
nonresponders. Moreover, the initial level of HVA (lower in
responders) significantly differentiated the two groups. These
results suggest that the clinical response to fenfluramine could be
related to the dopaminergic action of this drug and that urinary DA
metabolite levels could be considered as indicators of the
responsiveness to fenfluramine treatment in children with autistic
behavior-Barthelemy C; Bruneau N; Jouve J; Martineau J; Muh JP;
Lelord G Source: J Autism Dev Disord, 1989 Jun, 19:2, 241-54. Drugs
such as Ritalin™ and ADDerol™ affect dopamine activity, and thus
stimulate the part of the brain that monitors the arousal system,
resulting in better regulation. There are safer ways to build
dopamine than psychostimulants, amphetamines and alcohol. In France,
scientists found administration of NADH (ENADA™) caused more than a
40% increase in production of dopamine and norepinephrine, which are
vital for strength, coordination, movement, cognitive function, mood,
and sex drive (Birkmayer 1996). The amino acid tyrosine builds
dopamine and norepinephrine also.

"... dopamine sulphotransferase (ST) activity was inhibited strongly
by (+/-)-catechin, (+)-catechin, octyl gallate, tartrazine (yellow
#5), and vanillin (synthetic vanilla). Sulphation of the xenobiotic
steroid (foreign to the body) 17 alpha-ethinyloestradiol (EE2) was
inhibited by vanillin, erythrosin B, and octyl gallate [antioxidant
used in margarine]....Vanillin was found to inhibit 50% of liver EE2
ST activity ..."-Common Food additives are Potent Inhibitors of Human
liver 17 Alpha-ethinyloestradiol and Dopamine Sulphotransferases.-
Bamforth KJ, Jones AL, Roberts RC, Coughtrie MW, Biochem Pharmacol
1993 Nov 17;46(10):1713-20.