Phenols , PST and Sulphur Metabolism

This is an amalgamation of two links on phenols, PST and sulphur metabolism.  The two links to the original docs are:

http://www.newtreatments.org/ga.php?linkid=252
http://www.allnaturaladvantage.com.au/Sulphation_diagram.htm

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.

There are a number of consequences attributable to PST/sulfate
deficiency including effects upon the impaired breakdown and
metabolism of classical neurotransmitters such as serotonin and
dopamine; impaired breakdown and metabolism of the bile pigments
bilirubin and biliverdin; impaired action of the hormone CCK on CCKA
receptors which would result in decreased secretion of pancreatic
enzymes and of bile from the gall bladder and biliary tract into the
intestines. This would result in low uptake of certain vitamins and
other nutrients from the intestines; reduced activity of gastrin (and
subsequent reduced secretion of stomach acid, mucus, and pepsin in
the stomach), and, probably, reduced production of secretin farther
downstream. Secretin (esp. at high concentrations) inhibits the
histamine releasing action of gastrin and pentagastrin reducing HCl
as the stomach empties.

Because there is a lack of serotonin available to the brain, which
causes many of the most distressing symptoms of autism, it seems
reasonable to build the available serotonin by providing its
precursor 5-HTP. The use of 25-50 mg three or four times a day
(unless it causes a drowsiness that interferes with school) should be
most beneficial. If drowsiness interferes with school, reduce the
amount and/or give it later in the day. Giving 100 mg one to four
hours before bedtime has safely improved the sleep of many.
Nevertheless, a PST child may not tolerate it. If hyperactivity or
sleeplessness is observed, please discontinue.

Those with these PST deficits cannot readily excrete the phenols,
amines, and other listed toxic substances. These substances are
strongly acidic, and they exert toxic effects in the brain, where
normally certain enzymes prevent their accumulation. They build up to
abnormal levels and interfere with the neurotransmitters serotonin,
dopamine, and noradrenaline among other things. Symptoms of
PST/sulfate deficiency are excessive thirst, normal urination, night
sweats, odorous bed clothes, black eye shadows, facial flushing, and
red ears. These vary with the degree or level of toxic buildup.
Certain foods may cause fevers, and some, especially those taking
Paracetamol™ (Tylenol™), may go up to 24 hours without urination.

A phenolic compound may cause a variety of different symptoms in
various individuals. There is evidence of immune suppression on
exposure to testing doses of phenolics. There may be a drop in T-
suppressor cells or total T-cell numbers. An overabundance of B-cells
was interpreted as a reflection of toxic image to the immune system.
An increase in helper cells, antibody formation, and elevation of
some immunoglobulins was also noted. Other findings on phenolic
exposure have been depressed serotonin, elevated histamine and
prostaglandins, abnormal complement and immune complex formation.
These compounds can contribute to the toxic overload in PST, or they
can precipitate an allergic reaction.

Neurologic symptoms: In severe phenol poisoning, initial signs and
symptoms may include nausea, diaphoresis (heavy perspiration),
headache, dizziness, and tinnitus (ringing ears). Seizures, coma,
respiratory depression, and death may ensue quickly. Coma and
seizures usually occur within minutes to a few hours after exposure
or after a delay of up to 18 hours. Phenol also may cause
demyelination and axonal damage of peripheral nerves. Typically,
transitory central nervous system (CNS) excitation occurs, then
profound CNS depression ensues rapidly. Metabolic acidosis and acute
renal failure may complicate the condition. Vomiting and diarrhea are
common effects of phenol toxicity by any route. Peristalsis is
increased in the intestine and distribution of blood is altered by
these phenolics because of sensitizing smooth muscles to epinephrine,
norepinephrine, and other physiological stimulants.

Nutritional deficiencies will affect the body’s ability to detoxify
foreign chemicals. For example, magnesium is important in over 300
enzyme systems that relate to Phase and Phase II detoxification;
however, the average American diet is low in magnesium. The Phase I
enzymes alcohol dehydrogenase and aldehyde dehydrogenase are zinc
dependent, and NAD, the coenzyme form of niacin, activates these two
enzymes that break down alcohol and acetylaldehyde (AH). Magnesium
and NAD are both dependent on adequate supplies of vitamin B6, in the
form P5P. Aldehyde oxidase requires molybdenum. A deficiency of P5P,
NAD, zinc, magnesium, molybdenum, or the amino acid histidine could
significantly impair the ability to detoxify those chemicals,
especially the toxins of candida (acetylaldehyde).

By supplementing molybdenum and histidine (needed in the molybdenum-
histidine containing enzymes, sulfite oxidase and cysteine
dioxygenase, that oxidize sulfur), along with iron, and the B-complex
(preferably in coenzyme form), glucosamine/chondroitin sulfate
(stimulates synthesis of the GAGs we studied about above, and is
mildly anti-inflammatory without inhibiting the synthesis of
Prostaglandins, and more effective when taken together), minerals in
sulfate form, such as iron sulfate, and Epsom salts (magnesium
sulfate-taken orally it is a good laxative for those that need it),
one may supply both the minerals and the sulfate needed to detoxify
phenols and other metabolites. When glucosamine gives up its sulfate,
it supplies glutamine. Chondroitin is comprised of N-acetyl-D-
galactosamine and D-glucuronate. Collagen Type II™ may be even better
for it supplies at least 50 other types of sulfate such as heparan,
keratan, and dermatan sulfate. Curiously, bread is sulfate rich. This
program will increase the number and enhance the efficiency of the
available PST enzymes in doing their job.

Buy a quality brand (one using Good Manufacturing Practices) of
glucosamine/chondroitin sulfate that uses low molecular weight
ingredients the use of which will supply adequate GAGs to enable the
cells to resist infection. There are 4 different methods of
manufacturing glucosamine capsules. According to sources at Jarrow
Formulas, both glucosamine hydrochloride and N-Acetyl-glucosamine
have been stripped of the “sulfate” component in the manufacturing
process. Neither of these forms are expected to have any anti-viral
effect against lipid envelope viruses like HIV, EBV, CMV and HHV-6,
and of course, they would not supply needed sulfate for PST.
Published scientific research indicates that only the sulfated
polysaccharides and one sulfated monosaccharide (glucosamine sulfate)
have a powerful effect against lipid envelope viruses. If the
word “hydrochloride” or “N-Acetyl” appears anywhere on the label, do
not buy it unless you are planning to use it exclusively for
arthritis or rheumatism. Remember to choose capsules instead of
tablets.

In addition, take an Epsom salts bath (two cups or more in a tub of
hot water). It may be best not to use soap as there may be chemical
reactions that could be adverse. Soak it up through the skin for 20
minutes, and don’t rinse off-and don’t worry if the child drinks some
of the water. This bath has been shown to increase sulfur content of
the blood up to four times. Sleep is improved immediately, as the
child is relieved of pain and calmed.

I should mention that there is a small chance of magnesium toxicity.
Decreasing kidney function, common in the elderly, may prevent
magnesium from being excreted normally leading to a toxic condition.
Initially, symptoms include: drowsiness, lethargy and weakness. At
higher levels, nausea, vomiting, and serious arrhythmia (irregular
heart beat) may occur. If this be the cause of these symptoms, they
will disappear quickly once the use of magnesium bearing products is
discontinued. -Dr. Richard M. Ratzan, University of Connecticut
Health Center. This could only occur with very poor kidney function
for the toxic level is approximately 6000 mg daily. If there has been
any indication that the child’s kidneys are not functioning fully
(possibly high creatinine levels), check with your doctor before
using magnesium (or potassium), and have him monitor
magnesium/potassium levels. Strive for high normal levels. Adequate
potassium stimulates the kidneys to excrete poisonous body wastes
(usually toxic protein acids from inadequate protein digestion).

Be sure to filter chlorine, fluoride, and other poisons from the
water you drink and bath in. Chlorine in bath water is breathed and
absorbed, especially from hot water. This is important as chlorine is
a deadly poison. It can produce fatigue and tiredness after the bath.
Industrial chemist, J.P. Bercz, Ph.D., showed in 1992 that
chlorinated water alters and destroys unsaturated essential fatty
acids (EFAs), the building blocks of people’s brains and central
nervous systems. The compound hypochlorite, created when chlorine
mixes with water, generates excess free radicals; these oxidize EFAs,
turning them rancid. Both chlorine and fluoride inhibit the stomach’s
ability to produce HCl, and impair the ability of beneficial flora to
grow in the gut. Do not buy a filter that uses silver as a
bactericide. It is known to leak into the water and elevate levels in
the blood dangerously.

While taking a warm shower or lounging in a hot tub filled with
chlorinated water one inhales chloroform. Even worse, warm water
opens the pores, causing the skin to act like a sponge. One will
absorb and inhale more chlorine in a 10-minute shower than by
drinking eight glasses of the same water. This irritates the eyes,
the sinuses, throat, skin and lungs, makes the hair and scalp dry,
worsening dandruff. It can weaken immunity. A window from the shower
room open to the outdoors removes chloroform from the shower room
air, but to prevent absorption of chlorine through the skin, a shower-
head that removes chlorine from shower water is a must. The
ShowerWise™ filter and shower head can be ordered for $69, plus two
filters $129. They last about one year. An extension hose can be used
to fill the tub with filtered water.

For those times when the bath is not convenient (camping), or when
one wants to increase the amount of magnesium, but bowels are
sensitive to it, one can have the benefits of the bath with a cream.
Kyle, for whom it was developed, prefers the cream. Rub 1/2 teaspoon
of the cream on the tender parts to obtain 250 mg magnesium. The
cream is especially formulated by Key Pharmacy, 1-800-878-1322 or 1-
416-633-2244, FAX: 1-416-633-3400. Ask for the Epsom Salts Cream. A 4
oz. jar for $29.89, plus shipping, has approximately 48 servings. All
ingredients seem safe for our children, for it contains fatty acids,
a form of lecithin, and magnesium sulfate. The use of the cream
should avoid the following possibility.

One researcher makes this observation, “I have no doubt that sulfate
is a substrate to feed (some strains of) candida. It probably takes
some energy from the SO4 form and excretes it as H2S, and robs the
energy it may be able to get from reducing the sulfur, excreting
toxic H2S.” H2S is very foul smelling, so if an increased foul-
smelling gas is created in following these recommendations, you will
need to deal with the yeast overgrowth.

Sulfate is the most oxidized form of sulfur. It doesn’t need to be
oxidized any more, so supplementing or bathing in sulfate supplies
what is lacking because of the body’s inability to oxidize the sulfur
in foods. Oral sulfate will be poorly absorbed; so, supplement a gram
or more of sulfate each day. Some will get through. Supplementing
papain enhances absorption of sulfates. SAMe (SAM) is said to improve
sulfoxidation, in fact, it is necessary to the manufacture of all
sulfur-containing compounds in the body. Dr. Jeff Bradstreet, MD,
father of an autistic child, has this to offer: “If the child has an
unusual odor at night or their bedclothes do, or if they sweat while
asleep (PST defect), use methylsulfanylmethane (MSM), 1500 to 3000
mgs per day. In the study, 83% of autistic children were PST
abnormal, and MSM should help this. It did in our son’s situation.”

MSM works with copper in many functions, and may get depleted with
copper supplementation or when high copper levels are present.
Additionally, our soils are depleted of sulfur, and such sulfonyl as
there is in foods is lost in cooking. MSM is a white, crystalline
powder that is odorless and somewhat bitter tasting. It mixes in
water more easily than sugar, and just barely affects the taste. In
juice or other beverages, it is undetectable. MSM is effective in
ameliorating gastrointestinal upsets such as that produced by the
ingestion of aspirin and other pharmaceuticals, or that from
parasitic infections. Individuals with gastrointestinal symptoms such
as diarrhea, chronic constipation, nausea, hyperacidity and/or
epigastric pain (having been reported more effective than Tagamet™),
or inflammation of mucous membranes also will experience dramatic
relief. Individuals presenting symptoms of pain and inflammation
associated with various musculoskeletal system disorders, including
arthritis, report substantial and long-lasting relief. Those lacking
in sulfite oxidase cannot metabolize MSM, or the sulfite used in
Chinese foods or on some green salads, to sulfate, and may get
headache, dizziness, fatigue, wheezing, leg pain, and other symptoms.
MSM also seems to cause hair loss when there is heavy metals
poisoning, particularly mercury. This may be overcome by
supplementing molybdenum and vitamin B6, and this will enable more
efficient metabolism in this pathway relieving the sensitivity to
sulfur-bearing foods, and producing needed sulfates. Many cannot
tolerate more than 500 mg MSM, yet show very positive benefits from
even this amount. So, start low and increase dosage as you can
tolerate it. Always supplement molybdenum when taking MSM. Two
hundred to 300 mcg a day may be enough, but moly absorbs poorly, and
adults may require 1000 mcg twice daily for three or four months or
longer to overcome this aversion to sulfur-bearing foods.

One should note that mercury binds to the -SH (sulphydryl) groups,
resulting in inactivation of sulfur and blocking of enzyme function,
producing toxicity. Sulfur is essential in enzymes, hormones, nerve
tissue, and red blood cells. Mercury also blocks the metabolic action
of manganese and the entry of calcium ions into cytoplasm. Mercury
thus has the potential to disturb all metabolic processes. Under
these conditions MSM should be most helpful.

DMSO is being used as the solvent in transdermal secretin. This is
essentially the same as MSM. At least one Mom is reported to have
found good results with DMSO alone. When she added secretin further
gains were noted, but when she ran out of secretin, the gains
continued with DMSO alone! DMSO has long had a reputation as a
panacea for about everything that ails you. A case in point, applying
it to the abdomen has alleviated all symptoms of colitis and
Irritable Bowel Syndrome. Both it and MSM work wonders for arthritis.
To avoid skin dryness, dilute it 15% with distilled water.

If the child can metabolize organic sulfur (like MSM/DMSO) all the
way to sulfate, then MSM is a good way of increasing sulfate.
However, if the enzyme sulfite oxidase is not working well, then MSM
is a bad idea. Sulfite oxidase requires molybdenum as a cofactor, and
since mercury depletes selenium; and mercury, MSM, oral sulfate, and
copper tends to deplete molybdenum, selenium and molybdenum must be
supplemented. Conversely, tungsten inhibits the action of molybdenum
and thus of the molybdenum-based enzymes sulfite oxidase, xanthine
oxidase, and aldehyde oxidase. This would likely cause an excess of
molybdenum to accumulate. Thus, both excess mercury and excess
tungsten would create a shortage of the listed enzymes.

A coenzyme, vitamin B-complex supplement of moderate potency should
be supplemented. One mother in supplementing molybdenum reports that
her daughter, who was doing quite well, regressed into severe,
autistic symptoms for three days, including 18 hours of screaming-
possibly due to detoxifying. Her doctor urged her to cease, but she
stayed the course, and today her daughter is far and away better!
This is serious stuff.

Incidentally, a gross deficiency of molybdenum manifests as
tachycardia, headache, mental disturbances, and coma. An excess
intake of 10-15 mg daily (for adults) can cause a gout like syndrome
because of an elevated production of uric acid. Dosage range should
not exceed 1 mg per day (adult), bearing in mind that more than 0.5
mg causes a loss of copper. Very little molybdenum is needed, but it
is an important element in several important metalloenzymes (xanthine
oxidase, aldehyde oxidase, and sulfite oxidase) that participate in
crucial liver detoxification pathways.

Until the body regains its ability to oxidize sulfur, it may be
desirable to limit high sulfur containing foods (cruciferous
vegetables, broccoli, onions, garlic, turnips, eggs, red meat,
turkey, dairy products); and supplements like alpha lipoic acid,
glutathione, L-cysteine, and N-acetylcysteine (NAC can be better
tolerated when used with its team mates, the amino acids glycine and
glutamine in ratio 2:1:1, and the B-complex vitamins. It should be
tried for the glutathione it produces is so vital). Those who have a
problem with these foods likely have an impaired sulfur oxidation (a
cysteine oxidation) problem, and should be alert to cysteine
toxicity. Even those who do not oxidize cysteine well can usually
tolerate NAC at 500 mg daily (adult dose) without contributing to
cysteine toxicity. Supplying any of these sulfur foods may be a
problem to some of these kids who do not oxidize sulfur well. One
indicator may be fatigue after eating these. Unless a problem is
observed, however, these foods should not be restricted unnecessarily
for that will cause a reduction of the vital antioxidant glutathione,
and interfere with the conversion of T4 thyroid hormone into T3.

Blueberry extract, grape seed extract, pine tree bark, Resveratrol,
green tea, and other things have phenols, salicylates, and other
stuff that are normally detoxified by PST.

Some recent studies indicate that salicylate has an effect on PST, an
enzyme needed by the brain and the gut to metabolize high-phenolic
compounds like the artificial colors and flavors. Salicylate
suppresses PST enzymes up to 50%. Phase II has been shown to be low
for people with ADHD or autism. Excess boron interferes with the
metabolism (breakdown and excretion) of phenols. Ritalin, used in the
treatment of ADHD, inhibits the metabolism of coumarins (phenols).
Supplementing boron reduces calcium losses by 30%, but excess boron
increases copper in the body. High copper levels reduce the vitamin
B1, and this reduces oxygen supply to the brain. Excess boron reduces
the vitamin B6 levels in the body also. Boron is found in apples,
pears, grapes, nuts, leafy green vegetables, and legumes. Supplying
these substances, especially apples, pears, and grapes, or their
juices in large amounts to PST deficient children, will cause a build
up of phenols, amines, salicylates, and other toxic substances
normally cleared by PST.

In fact, any chemicals with a high proportion of phenolic groupings
will have this effect, and will enhance the problems referred to
above. Methyl Salicylate: (Salicylic Acid, Wintergreen Oil) is one
such. This phenolic is toxic in moderate concentrations. It is used
in birch beer, chewing gum (in high concentrations), grape, mint,
root beer, sarsaparilla, spice, walnut and wintergreen flavor in
baked goods, beverages, candy, ice cream, ices, syrups, mint-scented
cleaning products, and in perfumery. Symptoms of methyl salicylate
poisoning are acidosis, pulmonary edema and vomiting. This compound
has lethal drug interactions with many substances including
anticoagulants, tricyclic antidepressants, indocin, and methotrexate.
Gallic Acid is another. Gallic Acid is found in food coloring agents
and is, unquestionably, the most important of all phenolics.
Neutralization of gallic acid is the basis of the Feingold Diet,
which eliminates salicylates.

Beef patties containing 30% fat and grilled over mesquite wood had 24
aromatics at a total concentration of 549 g/kg of meat while the same
beef cooked over hardwood (hickory) charcoal had 16 aromatics
representing 68 g/kg. A heavy smoke flavor would produce a higher
concentration of phenols than light smoke. Hamburgers barbecued with
lots of smoke (especially in a covered grill) may be a potential
phenol problem as well as smoked bacon. Smoked bacon cured with
nitrates is even more toxic than phenols by themselves.

Additionally, fruit sugars will feed the candida causing an explosive
overgrowth with increased acetylaldehyde toxins. Candida also
produces arabinose and tartaric acid. Dr. Wm. Shaw of The Great
Plains Laboratory, Inc. thinks that high concentrations of arabinose
may inhibit the liver’s production of glucose, causing hypoglycemia
and impairing neurological function. Cheney described two boys
diagnosed as autistic. Their urine test showed high levels of
arabinose and tartaric acid. Tartaric acid looks like malic acid, and
poisons cells by interfering with the Krebs Cycle. Both boys had been
on repeated antibiotics for recurring ear infections, and had not
been autistic until recently. They were about six years old. In these
unusual cases, when the boys were treated with Nystatin™, they both
recovered, and were no longer autistic!

Many coloring materials (porphyrin), whether of natural or synthetic
origin, possess phenolic groupings. For this reason, some
practitioners recommend the removal of all pigmented foods from the
diet (Sara’s Diet). This may not be necessary due to the nature of
enzyme activity (the greater the need, the faster it works), but you
must at least eliminate juices (or limit to a little pear juice), and
eliminate all artificial colors and flavors. Avoid “deodorant” soaps
and deodorants containing “triclosan,” a chlorophenol. It should be
noted that problems relating to inhibition of cytochrome p450 liver
enzymes (Phase I liver detoxing) are involved with porphyrin in the
foods and supplements named in the above paragraphs. Additionally,
potatoes, tomatoes, and egg plant contain glycoalkaloids, that, even
in small amounts, can greatly slow the metabolism of anesthetic
agents and muscle relaxants, requiring up to 10 times longer to
recover from an anesthetic.

DPT immunization in inbred mice has been shown to result in decreased
synthesis of cytochrome p450, and of phosphosulfotransferase, and of
the messenger RNA necessary for their production. A decrease in
production of the liver enzymes phosphosulfotransferase and the
cytochrome p450 family of enzymes causes failure to break down food
proteins (including gluten and casein) into amino acids. The
resulting intermediates, called peptides, can cross into the blood.
Anything that further inhibits these cytochrome p450 liver enzymes
would compound the problem of toxicity, and further contribute to the
opioid problem. “Treatment of the latter (candida) with conventional
synthetic antifungal agents often causes impairment of liver
detoxification functions, and a decrease in the synthesis of
phosphosulfotransferase, an enzyme necessary to cleave food proteins,
e.g. casein, into smaller easily absorbable peptides.”-Dr. Hugh
Fudenberg, MD. Many drugs and opiates interfere with the immune
system. Opiates increase apoptosis (cell suicide) of T-lymphocytes
from the norm of 5% to 30%. Additionally, multiple chemical
sensitivities and liver pain would likely result.

Metallothioneins (MT) are small (short) cysteine-rich proteins that
do more than just help cells detoxify, scavenge free radicals, and
regulate metals. They are involved in cell growth and cell
specialization (differentiation) and homeostasis. Growth factors such
as epidermal growth factor (EGF) cause rat liver cells to grow and
secrete MT. Zinc also stimulated MT and EGF+ zinc made the effect
additive (the EGF effect plus the zinc effect). It is believed that
lots of growth factors that influence liver regeneration play a major
role in regulating MT synthesis and secretion.

William Walsh, senior scientist, Health Research Institute and
Pfeiffer Treatment Center of Naperville, Ill., in his study of 503
children with PDD, Asperger’s, and autism, found all but four were
missing MT, which the body needs to bind with toxic metals-like
mercury-so it can be excreted before it damages the brain and gut.
Walsh believes a child who lacks MT may develop any of these
developmental conditions if he gets mercury in his system. This may
explain why some children become autistic after receiving a mercury-
enhanced vaccine. It also explains why autism hits before the age of
3. After that, the brain and the gut have matured enough to withstand
further doses of mercury, although the child may develop ADD and
lesser developmental problems.

Glutathione (along with L-histidine and zinc) is a key resource for
the formation of metallothionein (MT). This molecule prevents
cellular toxicity by creating a stable storage molecule for excesses
of both essential minerals such as copper and zinc, and toxic metals
such as mercury and cadmium. In 1995, Sato et al. reported that
inhibition of glutathione-S-transferase induces decreased expression
of MT. Walsh recently reported that 91% of autistic patients had a
deficiency of metallothionein, and suggested this deficiency is
likely to be genetic, and may be a primary susceptibility factor for
neurotoxicity from heavy metals including vaccinal thimerosal. The
cumulative effects of ingesting mercury can cause brain damage.
Thimerosal, a mercury compound, is used as a preservative in
hepatitis B, diphtheria, pertussis and acellular pertussis, tetanus
and HIB vaccines. Most infants have received a total of 15 doses of
these mercury-containing vaccines by age six months! Studies document
thimerosal as both an allergen and a toxin to sodium channels.

Another interesting connection: Some cysteine is broken down into
taurine and sulfates unless the essential enzyme cysteine dioxygenase
is lacking. In some cases, the sulfur-oxidation of cysteine is
defective. About 30% of the population are slow sulfur-oxidizers and
2% are “nul” S-oxidizers, but in a small study of autistics, 45.8%
were “null” oxidizers! It appears that, in a high percentage of
autistics, oxidation of cysteine is impaired. Slow S-oxidation
appears to be inherited, and has been associated with a number of
disease states, especially rheumatoid arthritis and allergy that are
five times more common in the families of autistic children. One
study of severe food and chemical allergies found 94% had low S-
oxidation capacity and reduced plasma sulfate. It appears, then, that
the PST-troubled kid has numerous allergies, a light-colored stool, a
failure to digest fat from a lack of taurine-formed bile, and is
phenol toxic for want of sulfates. This condition might be indicated
by an elevated copper and mercury reading indicating not enough bile
is being made by the liver. This can sometimes be improved by taking
taurine, and glycine, and the overall condition can be improved by
supplementing sulfates. This seems to be added reason to supplement L-
histidine and molybdenum. The liver should be supported as indicated
elsewhere in this paper. Clinical studies showing that autistic
children with significant allergy problems have elevated
cysteine/sulfate ratios in their blood, and there are other
indications of disordered sulfur amino-acid chemistry.

High plasma cysteine/sulfate ratio indicates a problem of the body
either consuming or wasting sulfate too fast, or not properly forming
sulfate in the enzyme cascade. Cysteine itself is usually in normal
or elevated range, and the problems are concerning the sulfate.
Sulfite oxidase is the enzyme at the end of the metabolic chain from
methionine > cysteine > taurine > sulfate, and is a histidine-
molybdenum enzyme. Supplementing sulfate would surely be a benefit
for the problems directly related to not having enough sulfate for
completing detox and sulfating GAGs. However, some health problems
may be caused by the intermediate products of the impaired sulfur-
oxidation, and not just the lack of sulfate. High plasma or tissue
cysteine, that is, cysteine that is above the normal range,
irrespective of the sulfate levels, is actually quite a different
problem, indicating a failure of the first enzyme step in
metabolizing cysteine. This enzyme, cysteine dioxygenase (CDO), is an
iron-histidine enzyme.

People with high cysteine levels will report discomfort and illness
as a direct result of eating methionine/cysteine rich meats and
plants such as garlic and broccoli. Don’t take the glutathione
precursors that contribute directly to the cysteine pool. Both L-
cysteine and whole glutathione do this. It’s of interest to note that
cysteine is commonly incorporated into pharmacological preparations
as a stabilizer for peptides such as secretin. Standard chemical
calculations show that a rapid infusion of 1.0 mg cysteine HCl, as
contained in a vial of porcine secretin, will produce a significant
increase in the plasma concentration of cysteine. Since secretin is
not currently given in a weight dependent manner, the lower the
weight of an individual, the greater the increase in cysteine’s
plasma concentration. The increase in the cysteine level from one
vial of secretin is negligible in adults, but almost doubles the
plasma concentration in a 30 pound child. This could have very
definite toxic effects for some with a sulfoxidation problem (PST
kids).

Cysteine possesses excitatory neurotransmitter properties, acting
centrally and peripherally at NMDA (N-methyl-D-aspartate) type
glutamate receptors (Parsons et al., 1997). This effect in the CNS
may be responsible for hyperactivity reported by some parents soon
after a child receives secretin. In the presence of bicarbonate ions
in the GI tract (such as the bicarbonate-rich pancreatic fluid
induced by secretin), cysteine becomes a potent excitotoxin (Williams
et al., 1991) which could account for anecdotal reports of loose
stools or diarrhea a few days after a secretin infusion. NAC does not
contribute directly to cysteine toxicity unless you take massive
amounts of it. Around 500 mg/day (adult) you stand to benefit without
significantly increasing risk of cysteine toxicity. The common thread
in all of these failing enzymes is the need for adequate L-histidine.
L-histidine is used by the body in many metal/mineral bearing
enzymes, storage molecules, transport and excretion molecules. People
having metal/mineral enzyme problems, or metal/mineral disregulations
should be looking at supplementing this amino acid in addition to
adjusting their source of minerals such as molybdenum, copper, iron,
zinc, and manganese. In fact, histidine is such a powerful chelator
of heavy metals and minerals that it should probably be used only
under medical supervision lest a deficiency of necessary minerals be
created.

Following the Feingold diet plan will benefit these kids by exclusion
of foods known to include phenols. Salicylates, dyes, sodium
benzoate, BHA, BHT, FD&C yellow dye #5 (tartrazine), vanillin,
eugenol are all phenolic compounds. For a small membership fee, The
Feingold Association will provide a listing of foods to avoid, as
well as a continually updated list of safe foods. Their address is:
Feingold Association of the United States, PO Box 6550, Alexandria,
VA 22306, 1-800-321-3287.

Short of avoiding all these otherwise good foods containing phenols
and malonic acid, what can a PST child do to counter these
undesirable happenings? Take a teaspoon of apple cider vinegar
several times a day as recommended elsewhere in this paper. Two
mothers report that Cranberry juice has reduced or eliminated these
effects, probably by reducing the yeast overgrowth. One should use
Schizandra Chinensis, a very important liver herb. It protects the
liver function and tissue from toxic damage, and has demonstrated a
clinically significant influence on the detoxification process.
Schizandra extract enhances liver glutathione status, and increases
Phase I and Phase II liver enzyme activity. It has no toxic activity.
Glutathione is a substrate for Phase II activity, and particularly
for glutathione-S-transferase (GST), a Phase II enzyme that adds a
glutathione group to Phase I products.

Ambrotose®, Phyt•Aloe®, Dandelion, Ligustrum lucidum, Bovine
colostrum, Shark liver oil, excipients of powdered rice bran,
Schizandra, Green Tea, vitamins A, C, E, undenatured whey, and wheat
grass all produce glutathione effectively without any adverse
toxicity or without messing with the Phase I or Phase II enzyme
activity. A number of foods stimulate the body to produce more of the
Phase II enzymes. These foods have been shown to improve liver
detoxification, and to decrease the risk of developing cancer. They
include members of the cabbage family (crucifers), which includes not
only cabbage but broccoli, cauliflower, bok choy, Brussels sprouts,
green onions, garlic, and kale (all but one are in Phyt•Aloe®). These
vegetables contain compounds called aryl isothiocyanates which
directly stimulate the activity of an enzyme, glutathione S-
transferase, an important component of the Phase II system.
Unfortunately, these same vegetables contain high levels of phenols
which is the toxin not being excreted adequately in PST kids. They
also supply high sulfur that some cannot tolerate, and of course,
some are allergic to them.

Some have found Essaic™ tea helpful in this condition. Dr. Hugh
Fudenberg uses it with his immune-compromised patients, and states
that it heals the endothelial cells of the GI tract and the liver. It
is a proprietary formula of Burdock Root (arctium lappa), Slippery
Elm (ulmas vulva), Sheep Sorrel (rumex acetosella), and Indian
Rhubarb (rheuma palmatum). It probably should be used intermittently
for Burdock is toxic to the liver and peripheral blood mononuclear
cells (PBMC). Sheep Sorrel enhances cytochrome p450 (Phase I) liver
enzymes which will deplete fatty acids, steroids, estrogen,
Prostaglandins, retinoic acid (vitamin A), glycine, and body alcohols
faster, and make many drugs less effective. At least be aware, and if
you use it, supplement fatty acids (Evening Primrose and cod-liver
oil if your child can tolerate them) and glycine, and have the doctor
watch the liver and PBMC functions carefully. For limited periods,
use of herbs that enhance Phase I liver enzyme action would seem
beneficial to those without the PST/sulfoxidation problem. It can be
dangerous for PST kids because the more toxic metabolites of Phase I
action cannot be cleared effectively by PST (Phase II deficient)
types.

Nevertheless, enhancement of Phase I could enhance breakdown of
protein to amino acids, and limit the peptides that upon entering the
blood stream produce opioids. Some nontoxic herbs that do that are
Milk Thistle, Bistort, Ginger, Royal Jelly, and the aforementioned
sheep sorrel. Dandelion is nontoxic, a good chelator and detoxifier,
and has no effect on the Phase I function, thus it may be the best
choice for strengthening the liver function. I strongly advise that
you get the small book “The Liver Cleansing Diet, Love Your Liver and
Live Longer” by Sandra Cabot, MD, and follow this liver friendly
guide to eating. Half the small book consists of recipes. It can make
a world of difference when the liver functions as it should-otherwise
nothing else really works.

Three things that build the liver, even reversing hepatitis, are
Alpha Lipoic acid, Milk Thistle (for short time use), and selenium.

———————————
Still on the topic of PST kids, if you are looking for a phase I AND
II liver support here is a product:

Pls see original link for this diagram:  http://www.allnaturaladvantage.com.au/Sulphation_diagram.htm

Foods that inhibit PST (Phenyl sulphur transferase)

                                    (Oranges, spinach, radish,

                                    grapefruit, beetroot, pumpkin, tomatoes)

Diet                             Supplements            

Protein                         Vitamin B6 (> 100mg/d), molybdenum (excess)

(cysteine, taurine)                                Up regulators of PST                                                           Inhibitors

                                                                        Magnesium                                                                  Salicylates (food dyes)

Cysteine oxidase                                                                                                                                  Phenolic compounds

Molybdenum                                                                                                                                Products of Hb

                                                                                                                                                            (bilirubin, biliverdin)

                                                                                    Grains, dried fruit, nuts                                 

                        Sulphur transferase / Sulphite oxidase                             Sulphate transport protein (Nas1)            Liver Detoxification

Sulphur                                X                                   Sulphate                                                                      (Sulphation)

(Intolerance to)           (Phenyl-sulphur-transferase-PST)

                                    B6 / Mg                                                                                                                       X                         Overload

                                                                                                                                                                                                Phenolic Symptoms

                                                Symptoms                                                                                           Removal from body    Night waking

Supplements                                                             Also Required For                                                                            Night sweating

Epsom salts (MgSO₄)                                                  Nerve growth                                                                                                Irritability

                                                                                    Bone, cartilage growth                                                                                Eczema & other skin

                                                                                    Neurotransmitter inactivation                                                                    conditions

                                                                                    Mucus production in gut               

            Loss through

Family History (of kids with a PST def)                 Steroids, bile acids                               kidneys and gut                                    Phenol intolerance or

Migraine                    Parkinson’s diseases                                                                                  (Sulphate transport and Yeast?

RA                              Schizophrenia                                                                                              Nas1 gene abnormality)

Allergic conditions   Motor Neurone disease                  Low Sulphur Metabolism à excess sulphur formation                                    Immune Deficiencies

Alzheimer’s               Cirrhosis                                                                                                                                            ¯ cell mediated immunity

Chemical Sensitivities                                                                                                                                                                    ¯ NK cell function

 

 

                                  Intolerance to Sulphur

Some people appear to be intolerant to many foods and supplements containing sulphur, including some B vitamins.  This also includes glutathione shots and oral Lipoceutical Glutathione. 

There are bacteria in the small and large intestine that convert (reduce) sulphate compounds from sulphur-containing foods and supplements to hydrogen sulphide gas (H₂S). Excess hydrogen sulphide is a potent neurotoxin  – affecting both the brain and nervous tissue. Candida yeast also produces some hydrogen sulphide gas when it ferments carbohydrates.

 

If someone is having difficulty with all sulphur-containing substances except taurine and sulfate, the problem may be at the sulphite oxidase step in the metabolism of sulphur.  All the chemically reduced forms of sulphur except taurine must eventually pass through this step to get to sulphate, the most oxidized form of sulphur.  Excess sulphate is excreted in the urine, as is excess taurine.

In some rare cases, the problem at the sulphite oxidase step is genetic, involving the formation of the active form of molybdenum (molybdopterin).  People with this problem have severe disease.  However, in many cases, just taking more molybdenum will help.  Molybdenum is the cofactor for the enzyme sulphite oxidase.  Molybdenum is also a cofactor for two other enzymes in the body, xanthine dehydrogenase and aldehyde oxidase.  People with molybdenum deficiency therefore can have low urate (uric acid) levels as well as intolerance of alcohol.

Sulphate is required for:

• ·          mucin proteins: Mucin protein production is very important. If there is a deficiency in sulphation there are known links with gut dysfunction and irritable bowel. There must be enough sulphur attached to these proteins otherwise the gut wall will allow peptides through.
• ·          steroids
• ·          bile acids
• ·          phenols
• ·          cholecystokinin: Cholecystokinin (cck-8) protein allows the gut to be linked with the brain structure. This stimulates the secretion of enzymes, gastric acid and gall bladder contraction. It also controls food intake.
• ·          Gastrin must be sulphated to release active pepsin. Pepsin activates secretin release and cholecystokinin, which when sulphated, stimulates the pancreas to release pancreatic enzymes.
• ·          catecholamines
• ·          formation of connective tissue.

 

The average plasma sulphate level is 4.9 in normal children but 0.49 in autistic children.

Sulphation

Sulphation inactivates some neurotransmitters in the brain. Low sulphation à ­ residual neurotransmitters

Mucins that make up the mucus within the intestines are sulphated, ¯ sulphate à ¯ mucin à poor gut integrity à gut dysfunction and irritable bowel.

Cholecystokinin (cck-8) stimulates the secretion of enzymes, gastric acid and gall bladder contraction. It also controls food intake.

Sulphation must also be present for digestive hormones to function properly.

Gastrin must be sulphated to release active pepsin. Pepsin activates secretin release and cholecystokinin, which when sulphated, stimulates the pancreas to release pancreatic enzymes.

Foods that inhibit these sulphation enzymes are: oranges, spinach, radishes, grapefruit, beetroot, peppers, pumpkins and tomatoes. Other foods that inhibit sulphation are bananas, cheese and chocolate.

Sulphation is also reduced by excessive levels of molybdenum or vitamin B6 (> 100mg/ day).

PST Deficiency Symptoms

 

Some typical symptoms indicating your child may have a phenol problem are [not all of these need be present]:

• o         Dark circles under the eyes,
• o         Red face/ears,
• o         Diarrhoea,
• o         Hyperactivity,
• o         Aggression,
• o         Headache,
• o         Head banging or other self-injury,
• o         Inappropriate laughter,
• o         Difficulty falling asleep at night
• o         Night waking for several hours
• o         Night sweats

 

Testing: A subjective test for PST efficiency is to observe a reaction to Tylenol or acetaminophen – either hyperactivity or lethargy. Therefore Panadol should be avoided for kids with a PST problem (One source suggested that one or two minutes after a dose of Tylenol™, the entire supply of sulphate in the liver is gone!)

Sulphate Transport and NaSi-1 Gene Mutation

 

Sulphate is ingested as a mineral in food such as grains, dried fruit and nuts, is absorbed in the small intestine and circulates in blood plasma where it is used by almost every cell in the body. For example it is required for nerve growth in the brain, detoxification processes in the liver and bone and cartilage growth. As sulphate is hydrophilic, it requires a transporter system to pass across plasma cell membranes. The kidney transporter proteins reabsorb sulphate to saturation point, and then sulphate is excreted in the urine. Autistic individuals have lower serum sulphate levels compared to normal controls. As sulphate transporter proteins control plasma sulphate levels, research is being undertaken to see if the transporter proteins are defective in autistic individuals. Autistic individuals excrete large amounts of sulphate compared to non-autistic individuals.

Sulphate transporter genes, such as the NaSi-1 gene, encode a sulphate transporter protein that is expressed in the proximal tubule of the kidney. When 20 autistic individuals were compared to controls, two mutations were found in the gene that changes the function of the NaSi-1 protein. One mutation caused complete loss of function of the protein, the other caused a partial loss of function.

In a mouse model where the NaSi-1 gene has been knocked out, the mice excrete large amounts of sulphate in their urine and exhibit some behavioral abnormalities and gastrointestinal disturbances, such as soft stools, which parallel symptoms of autistic individuals. Autistic individuals have ‘leaky gut’. Sulphate loss also occurs through the intestine and it is believed that autistic individuals are losing sulphate through both the kidneys and the intestine, as the NaSi-1 gene is expressed in both organs. Autistic individuals usually have a five-fold lower level of serum sulphate compared to control individuals.

Some neurotransmitters in the brain are inactivated by sulphation, so sulphate plays a major role in maintaining the balance required for proper NS function. It is also suggested that glutamate and serotonin levels are altered in the brains of autistic individuals. If there is insufficient sulphate present to remove neurotransmitters this leads to residual neurotransmitters that cause problems. As sulphate is lower in autistics the brain may not be getting enough sulphate to get rid of those neurotransmitters that are no longer required. Mucins, a group of glycoproteins that make up mucus in the small intestine, are lower in NaSi-1 knockout mice. Mucins are sulphated, a process that helps them in their function of forming a protective layer against infection in the gut. The under sulphation of mucins may also be present in autistic individuals, which would make them more prone to infection.

Ion transport may hold autism clues. Susan Williamson. Australian Life Scientist; Aug/ Sept, 2004.

Loss Through Kidneys And Gut

Large amounts of sulphate are excreted via kidneys (defective sulphate transporter genes; NaSi-1) and intestines (leaky gut).

 

 

Foods & Supplements That Inhibit PST

 

Vitamin B6

B6 in the form of P5P (pyridoxal-5-phosphate) inhibits PST (phenol sulphur-transferase) activity. (This could be why some children show adverse effects when supplements high in P5P are started) However the same study showed that increasing magnesium supplementation reverses this inhibition.

ARI got Rosemary Waring to do the research that showed that B6 can inhibit human sulfotransferases, but they are activated by magnesium so that if you have at least a 1:1 mix of B6:Mg there is no problem.  This is why, if you have a problem with B6, try to see if taking magnesium will help.

 

Foods that inhibit these sulphation enzymes are: oranges, spinach, radishes, grapefruit, beetroot, peppers, pumpkins and tomatoes. Other foods that inhibit sulphation are bananas, cheese and chocolate.

Sulphation is also reduced by excessive levels of molybdenum or vitamin B6 (> 100mg/ day).