Download Sulfur Part II: Sulfur and Sulfur Compounds in the Human Body

Sulfur Part II:
Sulfur and Sulfur Compounds in the Human Body
by
Mark J. Donohue
Introduction
Sulfur is an element of the earth and is vital to the human body, without it we would not survive. Sulfur is the sixth most
abundant macro-mineral in human breast milk and the eight most abundant mineral in the body. Sulfur is an essential
nutrient and therefore cannot be synthesize by the human body and instead must be obtained from the diet.
Sulfur is not present as an isolated element in the body, but in combination with other elements and complex molecules
(compounds). The primary placement of sulfur in the human body is in the sulfur-containing amino acids (SAA):
methionine, cysteine and taurine. The human body is composed of 0.2 – 0.3% sulfur:
Liver - 7000 to 12000 p.p.m.
Muscle - 5000 to 11000 p.p.m.
Bone - 500 to 2400 p.p.m.
Blood – 1800 mg/dm-3
Sulfur is found in every cell in the human body and is
involved in a wide range of biochemical functions.
Sulfur’s involvement in the human body ranges from:
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Cellular energy production / metabolism.
Maintaining blood glucose levels.
Protects nerve tissue – synthesizes neurotransmitters, improves memory and dampens excessive firing.
Antioxidant protection - scavenges or neutralizes free radicals and recycles oxidized antioxidants.
Blood flow – produces both blood clotting factors as well as anticoagulants.
Joint Health – production of glycosaminoglycans (GAGS), chondroitin sulfate and hyaluronic acid.
Detoxification – by means of conjugation and chelation.
Regulation of DNA replication and transcription.
Digestion – production of hydrochloric acid.
Supports healthy lipoprotein balance – cholesterol, LDL, and HDL.
Adrenal gland support and hormone production – cortisol, aldosterone, testosterone, etc.
Proper immune response – enhancing proliferation of lymphocytes, cytotoxic T cells and NK cells.
Lungs – protects against mucous formation in lungs.
Eyes - decreases cataract development.
Formation of skin, hair and nails.
Luckily, sulfur and sulfur compounds are ubiquitous. They are found naturally occurring in the soil, plants, animals and
atmosphere and easily gain entry to the human body. Unfortunately, as mentioned in the previous report many toxic
sulfur compounds exist in our environment as man-made by-products (pollutants) which also gain easy access to the
human body.
“Natural” Sources of Sulfur and Sulfur Compounds in the Human Body
The human body is a carbon based (organic) organism. Therefore, compounds in humans that contain sulfur are referred
to as organic sulfur compounds or commonly known as – organosulfur compounds. More specifically, it is the sulfur
containing functional group within a compound that defines it as an organosulfur compound. A functional group is a
group of atoms that reacts as a single unit and determines the properties and structure of a class of compounds.
There are several dozen organosulfur compounds, all classified according to their sulfur-containing functional group.
Listing and describing all of them is beyond the scope of this report. Rather, we will focus on a select few, their sulfur
content and their function in the body as well as their sources. A list of the organosulfur functional groups which pertain
to this report are (* R- usually denotes carbon side chain):
Thiol or Sulfhydryl or Mercaptan (R-SH) is a compound that contains the functional group
composed of a sulfur-hydrogen bond. Many, but not all, thiols have strong odors resembling that
of garlic. Examples of thiols are the amino acids cysteine and glutathione, as well as coenzyme A.
Sulfide or Thioether (R-S-R) form when two organic groups are bonded to a sulfur atom. Many
fungicides and herbicides incorporate organically bound sulfide sulfur.
Disulfide and Polysulfide (R-S-S-R) – a unique property of sulfur is the ability to form chains of
sulfur atoms (from 2 – 20) with organic groups at either end. Cystine is an example of a disulfide.
Sulfoxide or Sulfinyl (R2-S=O) – is an organic compound containing sulfur and oxygen. The best
known sulfoxide is dimethyl sulfoxide (DMSO).
Sulfones or Sulfonyl (R2-SO2) – is an organic sulfur compound attached to two oxygen atoms and
two carbon atoms. Several drugs are manufactured with this functional group.
Sulfonic Acid or Sulfo (R-SO3H) – is an organic acid where R is usually attached to a hydrocarbon
(hydrogen-carbon compound) side chain. Sulfonic acids and their salts – sulfonates (R-SO2O-),
and their amides – sulfonamide (R-SO2NH2) are used extensively in a diverse list of products such
as detergents, dyes, antibacterial drugs and sulfa drugs.
Isothiocyanate (R-N=C=S) - cruciferous vegetables are rich sources of sulfur-containing
compounds called glucosinolates. Isothiocyanates are biologically active hydrolysis
(breakdown) products of glucosinolates. Cruciferous vegetables contain a variety of
glucosinolates, each of which forms a different isothiocyanate when hydrolyzed.
Food
The main source of organosulfur compounds in humans comes from food. Organosulfur compounds occur in the bodies
of all living creatures in the form of certain essential amino acids, enzymes, coenzymes, vitamins, and hormones. Foods
containing high amounts of organosulfur compounds are:
Protein:
Meat
Cheese-all (T)
Fish
Whey (T)
Eggs (T)
Dairy-all (T)
Milk (T)
Soy-all (T)
Vegetables:
Arugula
Bean Sprouts (T)
Cauliflower (T, I)
Garlic (T)
Kale (T, I)
Mushrooms
Rutabaga (T)
Spinach (T)
Turnips (T, I)
Asparagus (T)
Brussels Sprouts (T, I)
Cabbage (T, I)
Green Beans (T)
Leek (T)
Onion (T)
Red Peppers (T)
Split Peas (T)
Truffle
Artichokes (T)
Bok Choy (T, I)
Collard Greens (T)
Greens (T)
Mustard Green (I)
Peas (T)
Shallots (T)
Swiss Chard
Watercress (I)
Broccoli (T, I)
Chive (T)
Daikon (T)
Horseradish (T, I)
Mustard (I)
Radish (T, I)
Sauerkraut (T)
Turmeric (raises T)
Beans:
Beans-all (T)
Lentils-all (T)
Grains:
Oats (T)
Wheat Germ (T)
Fruit:
Pineapple (T)
Papaya (T)
Nuts:
Peanuts (T)
Misc.:
Coffee (T)
Carob (T)
Chocolate (T)
** T – indicates high level of Thiol content, I – indicates high level of Isothiocyanate content.
From the list above the most important source of organosulfur compounds in the human diet is from proteins. The
organosulfur compounds found in protein come from the sulfur containing amino acids methionine and cysteine. Sulfuramino acids (SAAs) are the primary source of sulfur in the human diet. The average person takes in (dietary intake)
around 850 – 930 mg. of sulfur per day, mainly in the form of protein.
Nutritional supplements are commonly taken today and therefore can also be considered as a source of organosulfur
compounds. One intention for taking nutritional supplements is to provide nutrients (vitamins, minerals, amino acids,
etc.) that are missing or are not consumed in sufficient quantity in a person’s diet. Another intention is to reinforce or
increase the effectiveness of certain body compounds, by consuming “like” compounds.
The remainder of this report lists and details some of the more common organosulfur compounds that are either:
a) Naturally synthesized by the body.
b) Found in food
c) Taken as a nutritional supplement
Biotin, Thiamine (B1), Pantethine
 Biotin (C10H16N2O3S) – also known as vitamin B7, is a water-soluble Bcomplex vitamin. A vitamin is an organic compound required as a
nutrient in tiny amounts with the B-complex vitamins (8 of them) playing
important roles in cell metabolism.
Functions
Biotin is attached, as a cofactor/ coenzyme (enzyme helper) at the
active site of several enzymes known as carboxylases. Each carboxylase
catalyzes an essential metabolic reaction, for example:
Acetyl-CoA carboxylase I and II are required for the synthesis of
fatty acids.
Pyruvate carboxylase is a critical enzyme in gluconeogenesis
(glucose from amino acids)
Methylcrotonyl-CoA carboxylase is involved in the breakdown of leucine (amino acid)
Propionyl-CoA carboxylase is involved in the metabolism of certain amino acids, cholesterol and fatty
acids.
Sources
Biotin is synthesized by bacteria that normally colonize the small and large intestine. However, whether biotin is
released and absorbed in meaningful amounts remains unknown.
Biotin is found in many foods, but generally in lower amounts than other water-soluble vitamins. Found in
microgram (mcg) dosages, the richest sources of biotin are from liver, egg, yeast, salmon and pork.
Biotin is also manufactured as a nutritional supplement.
 Thiamine (B1) (C12H17N4OS) – is a water soluble B-complex vitamin. Thiamine is synthesized in bacteria, fungi and
plants but not in animals or humans. Therefore, thiamine must be obtained from foods.
Functions
a) Thiamine is essential for energy-yielding metabolism, especially
carbohydrate metabolism via the coenzyme thiamine pyrophosphate
(TPP).
b) Thiamine is important to the health of nerves and the nervous
system, possibly because of its role in the synthesis of acetylcholine (neurotransmitter). With a lack of
thiamine, the nerves are more sensitive to inflammation.
c) Thiamine is involved in the production of hydrochloric acid in the stomach.
Sources
All plant and animal foods have thiamine though at low concentrations. Higher levels of thiamine are found in
many nuts, seeds, brown rice, seafood, and whole-grain products. Sunflower seeds are a particularly good
source. Thiamine is destroyed by prolonged high temperatures and ultraviolet light, but not by freezing. Because
there is very little thiamine stored in the body, depletion can occur as quickly as within 14 days.
Thiamine is also manufactured as a nutritional supplement.
 Pantethine (C22H42N4O8S2) – is the biologically active form of pantothenic acid (B5), another water-soluble Bcomplex vitamin. Though pantethine is not to be confused with pantothenic acid (B5). Rather, the making of
pantethine is the very reason the body needs pantothenic acid (B5) in the first place. That is, pantothenic acid’s (B5)
whole purpose in the body is to serve as a raw material for the synthesis of pantethine.
While pantothenic acid is a single molecule, pantethine is composed of two molecules of pantothenic acid (B5)
linked by cysteamine (sulfur) bridge group.
Functions
a) Cysteamine is theorized to bind to and thus inactivate sulfur-containing amino acids in liver enzymes
involved in the production of cholesterol and triglycerides. Therefore, as a supplement, pantethine is used
to support healthy levels of blood lipids and lipoproteins – such as cholesterol, triglycerides, low density
lipoprotein (LDL – the “bad” cholesterol), and high-density lipoprotein (HDL – the “good” cholesterol). It is
important to note - pantothenic acid (B5) does not have these cholesterol-balancing effects.
b) Pantethine serves as the precursor for synthesis of coenzyme A (CoA), a critical factor in cellular energy
production.
c) The adrenal glands require CoA for the synthesis of the powerful hormones through which the body adapts
to stress. Stress can therefore seriously deplete the body of pantothenic acid (B5) and supplemental
pantothenic acid (B5) can help correct for this stress-induced deficiency. However, pantethine provides
much more powerful support for adrenal function than does pantothenic acid (B5).
d) One important subfamily of the detoxification phase II enzyme family is the group that conjugates toxins
using acetyl groups (C2H3O+) – a process which requires CoA. It is therefore not surprising that pantethine
supplements, by boosting CoA levels, support the detoxification of a variety of toxic molecules and protect
the liver from many damaging chemicals. For instance, pantethine supplementation reduces the formation
of the toxic alcohol byproduct acetaldehyde.
Sources
Pantethine is naturally synthesized by the body from pantothenic acid (B5). Pantothenic acid (B5) is found in
most foods, while pantethine is not found in any foods.
Both pantothenic acid (B5) and pantethine are manufactured as nutritional supplements. Though pantethine is
the more biologically active form it is less stable and decomposes over time if not kept refrigerated.
Coenzyme A, Acetyl-CoA
 Coenzyme A (C21H36N7O16P3S) (THIOL) – also referred to as CoA, is a coenzyme / cofactor found in every cell in the
body and is one of the most important substances involved in cellular metabolism.
Functions
a) CoA is required to metabolize the three major forms of energy (fat, carbohydrates, and protein). As the
initiator of the body's energy cycle (known variously as the TCA, Kreb or citric acid cycle), it produces more
than 90% of the energy the body requires to sustain life. It is specifically involved in the conversion of
pyruvate into acetyl-coA via the enzyme pyruvate dehydrogenase.
b) CoA is also required to initiate the chemical reactions required by the human body to utilize Coenzyme Q10,
Coenzyme 1 (NADH) and many of the other nutrients the body needs to stay healthy.
c) CoA is also involved in a variety of other functions in the body such as: – the synthesis of the acetylcholine,
the steroid hormones and the sex hormones. It supports immune function, including the repair of DNA and
RNA, plus healing from physical injury. It facilitates the manufacture of important components of connective
tissue necessary to joint health, particularly chondroitin sulfate and hyaluronic acid. Coenzyme-A also
enhances physical performance and prevents sore, stiff muscles by reducing the buildup of lactic acid during
physical activity.
Sources
Coenzyme A is constantly expended by the metabolic processes in the body and constantly needs replenishing.
CoA is synthesized in the body from pantethine, cysteine and adenosine triphosphate (ATP). CoA is not found in
foods, but it is manufactured as a nutritional supplement.
 Acetyl-CoA (C23H38N7O17P3S) – is formed as a result of an acetyl
group (C2H3O) attaching to coenzyme A’s sulfur molecule. This takes
place during the first step of the Kreb / citric acid cycle which occurs
in the matrix of the mitochondria (cell’s power plant). It is here
where pyruvate, the end product of glycolysis (glucose to
pyruvate), is acted upon by pyruvate dehydrogenase and coenzyme
A to form acetyl-coA.
Functions
a) Acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions.
b) Acetyl -CoA forms the basis from which steroids are synthesized.
c) Acetyl-CoA is also an important component
in the synthesis of the neurotransmitter
acetylcholine. Choline, in combination with
Acetyl-CoA, is catalyzed by the choline
acetyltransferase to produce acetylcholine.
Sources
Acetyl-CoA is not found in foods nor is it
manufactured as a nutritional supplement.
Acetyl-CoA can only be found as a naturally
synthesized compound in the body.
Methionine, S-Adenosylmethionine (SAM-e), Homocysteine
 Methionine (C5H11NO2S) – is an essential amino acid and is the body’s primary
source of sulfur.
Functions
a) Methionine is necessary for the synthesis of proteins and is an important methyl
group donor (-CH3).
b) Methionine helps prevent fatty liver through its ability to form choline. Methionine can also lower
acetaldehyde levels after alcohol ingestion.
c) Methionine is converted into S-adenosyl methinonne (SAMe), by the enzyme methionine
adenosyltransferase. SAMe also serves as a methyl group donor.
Sources
Because methionine is an essential amino acid, this means the body does not synthesize it and therefore
methionine must come from the intake of foods. High levels of methionine can be found in sesame seeds, brazil
nuts, fish, meats, and dairy products. Most legumes, fruits and vegetables contain very little methionine.
Methionine is also manufactured as a nutritional supplement.
 S-Adenosyl methionine (SAM-e) (C15H22N6O5S+) – is a naturally occurring compound that is found in almost every
tissue and fluid in the body, though most SAM-e is produced and consumed in the liver.
Functions
a) SAMe has a fundamental role in transmethylation (the transfer of a methyl group from one compound to
another). This process is mandatory for the synthesis of phospholipids and the maintenance of membrane
fluidity.
b) SAMe is involved in producing neurotransmitters such as serotonin, melatonin and dopamine. Indicating
possible value in supplementation for depression.
c) SAMe exerts analgesic effects and stimulates the synthesis of proteoglycans (a protein with a high
polysaccharide content) by articular chondrocytes (cartilage cells), with minimal or absent side effects on
the gastrointestinal tract and other organs.
d) SAMe is involved in producing cartilage components such as glycosaminoglaycans (GAGS).
e) SAMe improves and normalizes liver function:
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In ethanol-fed baboons, SAMe prevents depletion of glutathione levels, normalizes mitochondrial
enzymes, and results in histological improvement of hepatic lesions.
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In healthy human volunteers it was demonstrated that, after ethanol ingestion, SAMe significantly
lowered plasma concentration of ethanol and acetaldehyde.
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SAMe was tested in patients with alcoholic cirrhosis. A 47-percent lower rate of death or need for liver
transplantation was noted compared to controls. Patients took 1,200 mg SAMe/ day. In people with less
severe cirrhosis, the results were even more impressive.
Sources
SAMe is naturally synthesized by the body from ATP and the amino acid methionine. SAMe is not found in food
however, it is manufacture as a nutritional supplement.
 Homocysteine (C4H9NO2S) – is a non-essential amino acid biosynthesized in the body from methionine via SAMe.
Functions
a) Homocysteine can be recycled back into methionine with the aid of Bvitamins thus creating additional methyl group donors.
b) Homocysteine can be converted into cysteine which is further used in the
detoxification of toxins.
Sources
Homocysteine is naturally synthesized in the body from methionine. Homocysteine is not obtained in the diet
from foods, nor is it manufactured as a nutritional supplement.
Cysteine, Cystine, N-Acetyl-Cysteine, Metallothionein
 Cysteine (C3H7NO2S) (THIOL) – is a non-essential amino acid biosynthesized in the body.
Functions
a) Cysteine has antioxidant properties which are typically expressed in the tripeptide
glutathione and is the rate-limiting precursor to the production of taurine as well
as glutathione.
b) Cysteine is critical to the metabolism of a number of essential biochemical
compounds such as biotin and coenzyme A.
c) The thiol group also has a high affinity for heavy metals and will tightly bind with metals such as mercury,
lead and cadmium.
d) Cysteine counteracts the poisonous effects of acetaldehyde by supporting the next step in metabolism,
which turns acetaldehyde into the relatively harmless acetic acid.
e) Cysteine also has the ability to breakdown proteins found in mucous that settles in the lungs. As a result it
may be useful in the treatment of bronchitis and other respiratory problems.
f)
Large amounts of cysteine are found in keratin, the protein that makes up fingernails, skin and hair. Human
hair is approximately 14% cysteine.
Sources
Cysteine naturally occurs in the body and is synthesized from homocysteine and serine (amino acid).
Cysteine is found in most high-protein foods such as pork, sausage meat, chicken, turkey, duck, eggs, milk, whey
protein, ricotta, cottage cheese, and yogurt. Non-protein sources include red peppers, garlic, onions, broccoli,
brussel sprouts, oats, granola, wheat germ.
Cysteine is also manufactured as a nutritional supplement.
CAUTION:
High levels of Cysteine are potentially toxic. Cysteine is a brain excito-toxin that can cause damage to brain cells in
susceptible individuals.
 Cystine (C6H12N2O4S2) (Disulfide) – is an amino acid formed by the linkage of two
cysteine molecules which covalently link to make a disulfide bond. The disulfide link is
readily reduced to make two corresponding cysteine molecules. In fact, both amino acids
can be converted into the other as needed.
For this reason, the nutritional benefits and sources of cystine are identical to those for the more common cysteine.
Cysteine is more easily absorbable than cystine, therefore most supplements contain cysteine.
CAUTION:
Too much cystine in the body can cause cystinosis, a rare disease that can cause cystine crystals to form in the body and
produce bladder or kidney stones. This side effect has not been associated with cysteine. However, cysteine is unstable
and is readily converted to cystine.
 N-Acetyl-Cysteine (NAC) (C5H9NO3S) (THIOL) – NAC is a metabolite of cysteine where an acetyl group is attached
to the nitrogen atom.
Functions
a) NAC is often used as a cough medicine because it breaks up the
disulfide bonds in the mucus and thus liquefies it, making it easier to
cough up. It is also this action of breaking disulfide bonds that makes it
useful in thinning the abnormally thick mucus in Cystic Fibrosis
patients.
b) NAC is also used as a specific antidote in cases of acetaminophen overdose.
c) NAC is rapidly metabolized to intracellular glutathione.
d) Heavy metals like lead, mercury and arsenic are detoxified and removed from the body by NAC. It also
increases the excretion of zinc and other essential minerals when taken over an extended period.
e) NAC has been shown to reduce the proliferation of certain cells lining the colon and may reduce the risk of
colon cancer in people with recurrent polyps in the colon. Its action as an antioxidant and a glutathione
precursor may also contribute to a protective effect against cancer.
Sources
NAC is naturally synthesized in the body from cysteine. Thought cysteine is found in a variety of foods, NAC is
not found in any foods. NAC is also manufactured as a nutritional supplement.
FURTHER RESEARCH:
There are conflicting reports that indicate NAC does not raise cysteine levels in the brain. This would be a way to obtain
additional cysteine while eliminating the neurotoxic effects in the brain. However, there are other reports indicating that
NAC does raise cysteine levels in the brain.
Additionally, there are reports that NAC may be a preferred delivery system for cysteine because cysteine readily
absorbs moisture and oxidizes. As well as being more stable and may be better absorbed. Yet other reports indicate NAC
is not an ideal source since it is catabolized (broken down) in the gut. Also, IV administration is preferable for poisoning,
since NAC may cause nausea and vomiting thereby reducing the effectiveness of oral therapy.
 Metallothionein (MT) – is a family of cysteine-rich low molecular weight proteins. Cysteine residues represent
about 30% of the amino acid content of MTs. MTs form complexes with heavy metal ions. The binding occurs via the
thiol groups of the cysteine residues.
Functions
a) MTs function is not clear, but experimental data suggest MTs may
provide protection against metal toxicity (cadmium, mercury, silver), be
involved in regulation of physiological metals (zinc, copper, selenium)
and provide protection against oxidative stress.
b) Other possible functions of MTs are: development and continued functioning of the immune system,
development and pruning of brain cells (neurons), prevention of yeast overgrowth in the intestines,
production of enzymes that break down casein and gluten, production of hydrochloric acid by stomach cells,
taste and texture discrimination by the tongue, behavior control and development of memory and social
skills.
Sources
Metallothionein is naturally synthesized primarily in the liver and kidneys. Its production is dependent on
availability of the dietary minerals – zinc, copper, selenium and the amino acids histidine and cysteine. MT is not
found in foods nor is it manufactured as a dietary supplement.
Alpha-Lipoic Acid, Glutathione, Taurine
 Alpha-Lipoic Acid (C8H14O2S2) (THIOL) – is a naturally occurring fatty acid found inside every cell in the body. Most
intracellular ALA is not “free” rather it is covalently bound to specific proteins. What free ALA that does exist is
converted to and exists in the reduced form as dihydrolipoic acid (DHLA), which is rapidly exported from the cell.
Functions
a) Reactive oxygen species (ROS) and reactive nitrogen species (RNS)
are highly reactive compounds (a.k.a. free radicals) with the
potential to damage DNA, proteins and lipids in cell membranes.
Both ALA and DHLA can directly scavenge (neutralize) physiologically
relevant ROS and RNS in the test tube. However, free ALA is rapidly
eliminated from cells, so any increases in direct radical scavenging
activity by DHLA are unlikely to be sustained.
b) In test tubes DHLA has been found to be a potent reducing agent with the capacity to reduce the oxidized
forms of several important antioxidants, including glutathione, CoQ10, vitamin C and E. In other words DHLA
recycles these antioxidants after they have been used thereby maintaining their levels.
c) ALA has been shown in cell culture experiments to increase cellular uptake of glucose by recruiting the
glucose transporter GLUT4 to the cell membrane, suggesting its use in diabetes.
d) ALA easily crosses the blood brain barrier and enters the brain producing protective effects on nerve tissue.
Studies of rat aging have suggested that the use of ALA results in improved memory performance and
delayed structural mitochondrial decay – suggesting its use for people with Alzheimer’s or Parkinson’s.
e) Owing to the presence of two thiol groups it is a chelating agent and has significantly enhance biliary
excretion of inorganic mercury in rat experiments.
f)
One of the most visible roles of ALA is as an essential cofactor for several mitochondrial enzyme complexes
that catalyze critical reactions related to energy production – specifically pyruvate dehydrogenase .
Sources
Alpha-Lipoic Acid is naturally synthesized in the body. It can also be found in small amounts in almost all foods,
but slightly more so in kidney, heart, liver, peas, spinach, broccoli, and yeast extract. However, naturally
occurring ALA is always covalently bound and not immediately available from dietary sources. This is probably
why consumption of ALA from foods has not yet been found to result in detectable increases of free ALA in
human plasma cell.
ALA is also manufactured as a nutritional supplement. And in contrast to foods, high oral doses of free ALA (50
mg or more) result in significant but transient increases in free ALA in plasma and cells. Studies in humans have
found that about 30-40% of an oral dose of ALA is absorbed. Oral ALA supplements are better absorbed on an
empty stomach than with food. Plasma ALA concentrations generally peak in one hour or less and decline
rapidly because free ALA is quickly reduced to DHLA and excreted.
CAUTION:
The chemical structure of biotin is similar to that of ALA and there is some evidence that high concentrations of ALA can
compete with biotin for transport across cell membranes.
 Glutathione (C10H17N3O6S) (THIOL) – is a tripeptide made up of the amino acids glycine, cysteine and glutamic acid
and is found inside every cell in the body.
Glutathione exists in reduced (GSH) and oxidized (GSSG) states. In the reduced state, the thiol group of cysteine is
able to donate a reducing equivalent to other unstable molecules, such as reactive oxygen species (free radicals). In
donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to
form glutathione disulfide (GSSG). Such a reaction is possible due to the relatively high concentration of glutathione
in cells (especially the liver). GSH can be regenerated from GSSG by the enzyme glutathione reductase.
In healthy cells and tissue, more than 90% of the total glutathione pool is in the reduced form (GSH) and less than
10% exists in the disulfide form (GSSG). An increased GSSG-to-GSH ratio is considered indicative of oxidative stress.
Functions
a) It is the major endogenous antioxidant produced by the
cell, participating directly in the neutralization of free
radicals / reactive oxygen compounds.
b)
Glutathione is a reducing agent which maintains exogenous
antioxidants such as vitamins C and E.
c) Through direct conjugation, it detoxifies xenobiotics (foreign compounds) and carcinogens, both organic and
inorganic. Unfortunately, hepatic (liver) glutathione can be depleted very quickly, resulting in less
glutathione being available for the conjugation of other toxic substances.
d) Glutathione is essential for the immune system to exert its full potential by:




Modulating antigen presentation to lymphocytes, thereby influencing cytokine production.
Enhancing proliferation of lymphocytes thereby increasing magnitude of response.
Enhancing killing activity of cytotoxic T cells and natural killer cells.
Regulating apoptosis, (cell death) thereby maintaining control of the immune response.
e) Glutathione plays a fundamental role in numerous metabolic and biochemical reactions such as DNA
synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport and enzyme
activation.
f)
Low GSH levels in elderly subjects have been theorized to accelerate the aging process.
Sources
Glutathione is naturally synthesized in the body from the amino acids -cysteine, glycine and glutamic acid.
Glutathione also occurs naturally in most foods, but occurs in highest amounts in fresh (uncooked) meats. It can
also be found in moderate amounts in certain raw fruits and vegetables and is absent or found only in small
amounts in grains and pasteurized dairy products. Dietary forms of glutathione are efficiently absorbed into the
blood, though heat or cooking greatly decreases glutathione concentrations.
Glutathione is also manufactured as a nutritional supplement.
FURTHER RESEARCH:
There is conflicting reports on glutathione’s absorbability. While some research suggests that glutathione taken orally, as
a supplement, is not well absorbed across the GI tract other research has shown administration of oral glutathione
increases hepatic GSH levels in rats. Though in the later, it is not completely clear whether the increase in GSH is from
direct absorption of the oral GSH or because GSH contains cysteine, the key precursor.
Regardless, plasma and liver glutathione concentrations maybe raised by oral administration of glutathione precursors SAMe, NAC, undenatured whey protein, and alpha lipoic acid. Melatonin (hormone) has been shown to stimulate a
related enzyme – glutathione peroxidase. And the herb silymarin or milk thistle has demonstrated an ability to
replenish glutathione levels.
Researchers also found that blood glutathione levels rose nearly 50% in healthy individuals taking 500 mg of vitamin C
daily. Vitamin C facilitates an increase in blood glutathione levels by supplying the body with a nutrient that is critical to
the manufacture of it.
 Taurine (C2H7NO3S) – Taurine often referred to as an amino acid, is not part
of the human body’s structural proteins. Instead, taurine remains free in the
tissues and bloodstream. In fact, taurine is one of the most abundant free
amino-acid-like compounds found in the heart, the skeletal muscles and the
nervous system.
Also, technically speaking, taurine is NOT an amino acid as it lacks a carboxyl group. Amino acids are molecules
containing an amine group (contain nitrogen –N) and a carboxylic acid group (organic acids/carbon - COOH)
attached to a side chain. However, taurine does contain a sulfonate group and may be called an amino sulfonic acid.
Functions
a) Taurine functions in electrically active tissues such as the brain and heart to help stabilize cell membranes.
This in turn can depress the firing of brain cells and cause a dampening of nerve cell action of the excitatory
amino acids - glutamate & aspartate. Thus protecting against excito-toxicity.
b) Taurine aids the movement of potassium, sodium, calcium, and magnesium in and out of cells and helps
generate nerve impulses. This has everything to do with the electrical activity of the cells and subsequent
communication between cells.
c) Taurine functions with glycine and GABA as an inhibitory neurotransmitter.
d) Taurine plays an important role in bile metabolism.
e) Taurine is involved in detoxification by conjugating with various toxins.
f)
Taurine acts as an important antioxidant – improving superoxide dismutase (SOD) and glutathione
peroxidase activities and improved mitochondrial membrane injury.
g) Taurine has been shown to boost white blood cell counts. Taurine is also known to re-invigorate the natural
killer cells of in the immune system.
h) Taurine plays a role in decreasing cataract development.
Sources
Taurine is naturally synthesized in the body from cysteine when adequate levels of vitamin B6 are available.
Taurine is found in high protein foods such as – dairy products, meat, poultry, eggs and fish. Taurine is also
manufactured as a nutritional supplement.
CAUTION:
Taurine affects the hypothalamus which regulates body temperature. High doses can decrease body temperature and
create chilliness.
Sulfite and Sulfate
 Sulfite (SO32-) – is an intermediate compound formed in the body during the metabolism of sulfur-containing amino
acids and other sulfur-containing compounds. This takes place via the detoxification pathway called – sulfoxidation.
Functions
The function of sulfites in the body is unknown other than as a toxic metabolite. Sulfites can react with a variety
of humoral (immune) and cellular components (i.e. proteins, lipids, DNA, etc.) potentially having neuro-toxic
effects on brain tissue. Sulfites can also inhibit 90% of lung ATP energy production, can impair liver cell ATP
energy production, and can deplete glutathione.
Because of sulfites potential damaging effect to cells (toxicity) it must be converted and detoxified via the
enzyme sulfite oxidase into the safer compound - sulfate. Sulfite oxidase is found in high concentrations in the
liver and lungs.
Mutations to the genes that code for sulfite oxidase are quite rare because they are usually fatal. A more
common problem has to do with one of the components of this enzyme, the molybdenum cofactor.
Molybdenum is a trace element that occurs in very low amounts in our soil and food supply. In fact, the
published minimum daily requirement for molybdenum is just 75 micrograms. Anything that disables the
molybdenum cofactor, such as lead and mercury can reduce a person’s ability to process sulfite.
Persons with a deficiency of or a poorly functioning sulfite oxidase are usually sensitive to sulfites. In such cases
measures need to be made to improve the conversion of sulfites to sulfates, as well as avoiding sources of
sulfites. The symptoms related to sulfite sensitivity are many, but the best documented cases report breathing
problems that lead to asthma attacks.
Sources
Sulfites are formed as a natural by-product of sulfur metabolism in the human body. Sulfites are also a naturally
occurring compound that nature uses to prevent microbial growth. They are found naturally on grapes, onions,
garlic, and on many other growing plants. Sulfites are also found naturally occurring in some foods undergoing
fermentation (i.e. beer and wine).
However, one of the main sources of sulfites in the human body comes from the addition of sulfites and sulfur
dioxide to many food products. This is done to preserve food and will be discussed below under man-made
sources of sulfur.
 Sulfate – (SO4) – a heavily oxidized sulfur compound, sulfate is an extremely important end product of sulfur
metabolism.
Functions
a) One of the important roles for sulfate is in the biosynthesis of 3′-phosphoadenosine-5′-phosphosulfate
(PAPS). Catalyzed by the enzyme PAPS synthetase (PAPSS), inorganic sulfate along with adenosine
triphosphate (ATP) is required in controlling the rate of PAPS formation. PAPS is also known as active sulfate.
Sulfate conjugation or sulfation (the addition of a sulfate group
to a substrate) is an important detoxification pathway in the
metabolism of many drugs, xenobiotics, neurotransmitters and
hormones. Sulfation also takes place in the formation of
glycosylaminoglycans (GAGs). PAPS is the high-energy sulfate
donor co-substrate for the sulfotransferase (SULT) enzymes that
catalyze these reactions.
The highest concentrations of PAPS is found in the liver, followed
by the kidney, then the lungs, intestines and brain.
b) Sulfate is also an essential component of key membrane-associated
macromolecules - glycosaminoglycans (GAGs). GAGs are long, unbranched
PAPS
heteropolysaccharide chains(long molecules composed of repeating carbohydrate/sugar structures). More
specifically, GAGs are composed of repeating disaccharide units (acidic sugar – amino sugar). The amino
sugar is either D-glucosamine or D-galactosamine. The acidic sugar is either D-glucuronic acid or L-iduronic
acid and together with sulfate give GAGs their strongly negative nature. GAGs are generally associated with
a small amount of protein, forming proteoglycans.
Sulfation of the carbohydrate chain occurs after the monosaccharide to be sulfated had been incorporated
into the growing carbohydrate chain. The source of the sulfate is 3’-phosphoadenosyl-5’-phosphosulfate
(PAPS). Sulfotransferases causes the sulfation of the carbohydrate chain at specific sites.
GAG synthesis occurs, in the endoplasmic reticulum and the goigi, rather than the cystosol. GAGs are then
transferred to and located on the surface of cells and in the extracellular matrix (ECM). The extracellular
matrix is the non-cellular component of connective tissues surrounding all cells. Cartilage is the primary
example of extracellular matrix in joints.
There are eight major classes of GAGs
1. Chondroitin 4- and 6- sulfates – are the most abundant GAGs in the body. Found in cartilage,
tendons, ligaments and aorta.
2.
Keratin sulfates I and II – KS I is found in cornea. KS II is found in loose connective tissue with
chondroitin sulfate.
3.
Dermatan sulfate – found in skin, blood vessels and heart valves.
4. Heparan sulfate – extracellular GAG, found in basement membrane (a thin, delicate layer of
connective tissue underlying the epithelium of many organs) and as a ubiquitous component of cell
surfaces.
5.
Heprin – unlike other GAGs that are extracellular compounds, heparin is an intracellular component
of mast cells that line arteries, liver, lungs and skin.
6. Hyaluronic acid – is different from other GAGs as it is unsulfated, not covalently attached to protein
and the only GAG not limited to animal tissue – also found in bacteria. Hyaluronic acid is found in
synovial fluid of joints, eyes, umbilical cord, loose connective tissue and cartilage.
With the exception of keratin sulfate, which has a half-life of greater than 120 days, the GAGs have a
relatively short half-life, ranging from about three days for hyaluronic acid to ten days for chondroitin and
dermatan sulfate.
The two main characteristics of sulfated GAGs is in their ability to maintain a negative charge on cell
membranes and serve also as hydration sites which maintain the properties of mucous membranes.
Meaning, GAGs have the special ability to bind large amounts of water, thereby producing the gel-like matrix
that forms the basis of the body’s ground substance or extracellular matrix.
Image: Glycsaminoglycans (GAGs)
Because of sulfated GAGs large number of negative charges they tend to be extended in solution. They repel
each other and are surrounded by a shell of water molecules. When brought together, they “slip” past each
other. This produces a “slippery” consistency of mucous secretions and synovial fluid. When a solution of
sulfated GAGs is compressed, the water is “squeezed out” and the sulfated GAGs are forced to occupy a
smaller volume. When the compression is released, the GAGs, spring back to their original hydrated volume.
These characteristics of sulfated GAGs allow them to be involved in numerous functions in the body such as:












Act as structural components of the extracellular membrane.
Act as a sieve in the extracellular membrane.
In cartilage, they bind collagen and hold fibres in a tight, strong network.
Are used to synthesize the chondroitin matrix of cartilage.
Have role in compressibility of cartilage by acting as lubricants and shock absorbers.
Contribute to the turgor (hydration) of various tissues.
In the eye they play a role in corneal transparency and have a structural role in the sclera (white part).
Act as anticoagulant.
Facilitate cell migration - tissue formation during embryonic development, wound healing and immune
responses all require the orchestrated movement of cells in particular directions to specific locations.
Are essential components of cell surfaces and play an important role in mediating cell- cell signalling and
adhesion.
Are components of synaptic vesicles.
Are widely distributed within the intestine.
Sources
The major source of sulfate (64%) is produced in the body from the conversion of organic sulfur to inorganic
sulfate. Methionine and cysteine in food proteins, glutathione in both animal and vegetable products, taurine in
animal-source foods and sulfated GAGs in both plant-and animal-derived foods are the primary contributors of
organosulfur compounds. Other organosulfur compounds, ingested for a variety of reasons, which are converted
and contribute to the inorganic sulfate pool are listed in this report (N-acetyl-L-cysteine, S-methylmethionine,
chondroitin sulfate, glucosamine sulfate, methylsulfonylmethane, etc.).
Approximately 19% of total sulfate comes from the direct ingestion of inorganic sulfate from foods. The
inorganic sulfate content of few foods is:
Food
Almonds
Bread (brown)
Bread (white)
Broccoli
Brussel sprouts
Cabbage
Cauliflower
Dates
Dried apples
Dried apricosts
Pasta, durum wheat
Peanuts
Prunes
Raisins
Sunflower seeds
Mean Sulfate Content (mg/g)
0.9
1.5
1.3
0.9
0.9
0.8
0.5
1.1
4.9
3.0
0.3
0.7
1.0
1.3
0.6
The inorganic sulfate contained in water and beverages, account for 17% of the sulfate found in the body. Most
public water supplies contain sulfate concentrations of less than 500 mg/L. Sulfate levels in water around 250
mg/L and above are detectable due to an off odor and taste, and this generally causes those exposed to water
with higher concentrations of sulfate to switch to bottled water sources for drinking. The inorganic sulfate
content of a few beverages is:
Beverage
Beer
Cider
Coconut milk
Cola
Juice, apple
Juice, grape
Juice, tomato
Milk, cow
Milk, human
Wine, red
Wine, white
Mean Sulfate Content (mg/L)
260
270
500
80
70
200
250
100
5
380
300
Sulfate ingestion from drinking water is highly variable and depends on the area of the country from which the
water is obtained. Some well water in rural areas of the United States has been known to contain upwards of
500 mg/L and some of the “mineral” waters sold with health claims have been reported to exceed this level.
Distilled water contains very little, if any, sulfate, and de-ionized water contains no sulfate.
Gastrointestinal absorption of sulfate can occur in the stomach, small intestine, and colon. Absorption is a
sodium-dependent active process. When soluble sulfate salts (e.g., potassium sulfate or sodium sulfate) are
consumed, more than 80 percent of oral sulfate doses are absorbed.
With insoluble sulfate salts, such as barium sulfate, almost no absorption occurs. When magnesium sulfate is
used what sulfate that is not absorbed in the upper gastrointestinal tract passes to the large intestine and colon,
where it is either excreted in the feces, reabsorbed or reduced by anaerobic bacteria to metabolites, such as
hydrogen sulfide.
The major pathway of excretion for sulfur consumed as both organic sulfur (amino acids, compounds) and as
inorganic sulfur (sulfites, sulfates) is via urine. A study found that fecal sulfate was not a major pathway of sulfur
excretion.
NOTE:
Sulfate is the rate limiting factor in the production of PAPS and GAGs. Meaning sulfate depletion inhibits PAPS and GAGs
synthesis. The depletion of sulfate is problematic because the extracellular sulfate pool in humans is among the smallest
of animal species.
Researchers have found that human cartilage – especially GAG – reproduction suffers significant deterioration with an
even slight decrease in serum sulfate. A reduction in the sulfate concentration from 0.3 mM to 0.2mM resulted in a 33%
reduction in human GAG synthesis. If the sulfate pool is depleted it will lead to a vicious cycle of degenerating
cartilage/extracellular matrix reproduction and eventually proceeding to effects of arthritis.
Unfortunately, there are several possible causes for sulfate depletion, some of which are:









Old age
Low protein or vegetarian diet – can lead to a deficient intake of dietary sulfur.
Mineral deficiency - molybdenum is needed for sulfite oxidase.
Poor sulfoxidizers – due to genetic weakness in sulfoxidation pathway.
Heavy metal toxicity (e.g. mercury).
Too much detoxification.
Infection – tumor necrosis factor (TNF) (a cytokine involved in systemic inflammation) blocks sulfite oxidase
which converts cysteine to sulfate.
Poor renal re-absorption – an important factor in the homeostasis of sulfate is its renal re-absorption. Chemicals
can have a direct effect on sulfate re-absorption. For example salicylic acid – found in many over-the-counter
medications as well as fruits and vegetables - increases the renal clearance of inorganic sulfate.
Use of sulfate reducing drugs – researchers have found that GAG synthesis in human cartilage appears to be
very sensitive to the potential sulfate-depleting effects of drugs used in the treatment of rheumatoid arthritis
and osteoarthritis, namely - non-steroidal anti-inflammatory drugs (NSAIDs ). It has been shown that NSAIDs
are detoxified via the sulfation pathway, thereby promptly reducing circulating sulfate concentrations for the
creation of PAPS. They also act by directly inhibiting GAG synthesis in human joint cartilage.
FURTHER RESEARCH:
There are conflicting reports on sulfates role in the gastrointestinal tract. There are some reports which make a
correlation between low levels of sulfated GAGs in the GI tract with irritable bowel diseases.
While other reports indicate that sulfate and undigested sulfur compounds are implicated in the etiology of ulcerative
colitis. The specific agent is thought to be the bacterial toxin - hydrogen sulfide, which is produced in the colon from
sulfate by sulfate-reducing bacteria. Sulfate-reducing bacteria convert either sulfate or sulfite to sulfide and release it
into the lumen (intestinal cavity) where it is further converted to hydrogen sulfide gas (H2S). Excess luminal sulfide is
thought to overburden mucosal detoxification systems, resulting in impaired butyrate oxidation and colonic epithelial
inflammation.
Also sodium sulfate supplementation has been demonstrated to stimulate the growth of sulfate-reducing bacteria in the
colon of humans.
Chondroitin Sulfate, Glucosamine Sulfate
 Chondroitin Sulfate – as mentioned above, chondroitin sulfate is a large molecule and a member of the
polysaccharides called glycosaminoglycans (GAGs). A chondroitin chain can have over 100 individual sugars, each of
which can be sulfated in variable positions and quantities. These chains consist of unbranched polysaccharides of
variable length containing two alternating monosaccharides: D-glucuronic acid (GlcA) and N-acetyl-D-galactosamine
(GalNAc).
Functions
a) Chondroitin sulfate is a major component of extracellular matrix –
cartilage, lumbar disc, bone, skin, cornea and the arterial wall and
is important in maintaining the structural integrity of these
tissues. When administered, chondroitin sulfate exhibits an
affinity for these sulfated GAG-rich tissues.
b) In cartilage, chondroitin sulfate provides structure by holding
water and nutrients and allowing other molecules to move
through cartilage—an important property, as there is no blood
supply to cartilage. The tightly packed and highly charged sulfate
groups of chondroitin sulfate generate electrostatic repulsion
that provides much of the resistance of cartilage to compression.
c) Chondroitin sulfate increases synovial fluid viscosity by increasing the amount of hyaluronic acid in the
joints. Hyaluronic acid, another GAG, is a protective fluid that keeps the joints lubricated.
d) Chondroitin sulfate inhibits extracellular proteases (enzymes) involved in cartilage degradation.
e) Chondroitin sulfate also blocks the TNF-alpha receptor - a cytokine involved in cartilage degradation.
f)
Chondroitin sulfate has an anti-inflammatory effect which protects cartilage matrix against damage from
free radicals.
g) In bones chondoitin sulfate increases the calcium pool and increases the rate of bone repair.
Sources
Chondrotin sulfate is naturally synthesized in the body. Chondroitin sulfate is not found in foods, but is
manufactured as a nutritional supplement from extracted animal cartilage, such as bovine tracheas or shark
cartilage. It can also be produced by synthetic means.
FURTHER RESEARCH:
Despite its use as a nutritional supplement only limited evidence supports its efficacy as a therapeutic supplement for
joint health. According to one authoritative study, pooled literature on chondroitin sulfate biochemistry offers enough
information to assert that chondroitin sulfate is not absorbed by the human gastrointestinal tract. Therefore, any direct
action of orally administered chondroitin sulfate on cartilage and chondrocytes is not possible.
However, in 1995 researchers found evidence that up to 15 percent of chondroitin is absorbed intact, even though it is a
large molecule with molecular weight ranging from 5,000 – 50,000 daltons. Lower molecular weight chondroitin (less
than 17,000 daltons) appear to be absorbed completely intact.
CAUTION:
Unfortunately, chondroitin sulfate appears to play a major role in cancer biology and using it may be risky. When the
joint is damaged (as it is in osteoarthritis), the joint cartilage responds by producing an array of chondroitin-containing
proteins in an attempt to heal. One of the proteins produced in the arthritic joint is the chondroitin binding protein
versican.
You can find versican on the surface of a wide range of cancer cell types. In general, the greater the amount of
chondroitin-containing versican bound to the cancer cell, the more likely it is that the cancer cell will be able to spread
widely throughout the body. There is sufficient documentation of this effect of versican for prostate cancer, melanoma,
some brain tumors, and a range of other cancers.
 Glucosamine Sulfate – is an amino acid-monosaccharide (a combination of glutamine and glucose) combined with
a sulfate group. Glucosamine is a natural compound that is found in healthy cartilage.
Functions
a) There are two main components of ligaments, cartilage, tendons and spinal discs tissues. The first is collagen
the second is sulfated glycosaminoglycans (GAGs). GAGs are the tissue frame work that collagen holds onto.
Glucosamine is concentrated in joint cartilage where it is a substrate for cartilage GAG synthesis.
b) Glucosamine sulfate decreases the catabolic activity of chondrocytes
by inhibiting the synthesis of protease enzymes and other
substances that contribute to the damage of the cartilage matrix.
c) Whereas glucosamine sulfate is thought to promote the formation
and repair of cartilage, chondroitin sulfate is beleived to promote
water retention and elasticity in cartilage.
Sources
Glucosamine sulfate is naturally synthesized by the body from glucose
and glutamine. Glucosamine sulfate is not found in foods, but is
manufactured as a nutritional supplement. Raw material for supplementation comes from the shells of shellfish
and animal bones and bone marrow. It can also be produced by synthetic means.
FURTHER RESEARCH:
Exactly how glucosamine works is not fully understood. About 90 percent of orally administered glucosamine gets
absorbed, although a significant portion is catabolized during first pass metabolism and free glucosamine is not
detectable in the serum after oral intake (possibly because it is bound to plasma proteins). This has led some researchers
to speculate it is the sulfate rather than the glucosamine that is the active constituent. This is one reason why
researchers believe that glucosamine sulfate might work better than other forms of glucosamine such as glucosamine
hydrochloride or N-acetyl glucosamine.
Methylsulfonylmethane (MSM), Methanethiol
 Methylsulfonylmethane (MSM) (C2H6O2S) (THIOL) – MSM is composed of 34% elemental sulfur and is one of the
least toxic substances in biology, similar in toxicity to water.
Functions
Because MSM provides such a high level of elemental sulfur, the claimed
attributes of MSM are similar to the functions listed for sulfur in the introduction
to this report.
Sources
MSM is not produced by the body but is found in small amounts in many foods such as - cow’s milk, meat,
seafood, fruits and alfalfa, corn, tomatoes and in human milk and urine. However, MSM is easily destroyed by
heat or processing. The half-life of MSM is only 12 hours when consumed within the body.
MSM is also manufactured as a nutritional supplement. According to research done at the MSM clinic at the
Oregon Health Sciences University, long-term use of MSM at a dose greater than 2 grams per day is well
tolerated, producing no adverse effects.
FURTHER RESEARCH:
There are conflicting reports about the utilization of MSM in humans. A 1975 study found recovery of MSM
administered orally to humans was only three percent, suggesting some type of utilization or modification in the gut or
liver. Yet another study (1986) of radio-labeled MSM was administered to guinea pigs and incorporation of sulfur into
methionine and cysteine was measured. One percent of the radioactivity was incorporated into serum methionine and
cysteine, none was found in the feces and most was excreted in the urine.
CAUTION:
MSM is sometimes incorrectly referred to as dimethyl sulfoxide (DMSO) (C2H6OS). Though MSM is structurally related to
DMSO due to it being an oxidized metabolite of DMSO, their behaviors differ. As a matter of fact when DMSO enters the
body approximately 15% is converted to MSM. The mistake comes from the fact that MSM is also known as DMSO2
because MSM/DMSO2 (C2H6O2S) has one more additional oxygen (O) molecule than DMSO. DMSO is described below.
 Methanethiol (CH4S) (THIOL) – also known as methyl mercaptan is a colorless gas
with a smell like rotten cabbage. It is a natural substance found in the blood, brain,
and other tissues of humans. Produced by bacteria, methyl mercaptan is always
present in your body and in your urine and feces. It is also one of the main
chemicals responsible for bad breath and the smell of flatus
Functions
a) Methyl mercaptan is a by-product of bacterial metabolism in the human gut and currently it is unknown if it
serves any biochemical function in humans.
b) Methyl mercaptan is manufactured for use in making the nutritional supplement - methionine. It is also
used in industry to produce pesticides, as a jet fuel additive and in the plastics industry.
c) It has also been approved for use as a food additive, but because of its unpleasant smell, very little can be
used.
Sources
Methyl mercaptan is naturally synthesized in the human body. Methyl mercaptan can be obtained through the diet
as it occurs naturally in certain foods such as some nuts (filberts) and cheese (Beaufort). Methyl mercaptan is not
manufactured as a nutritional supplement.
Methyl mercaptan is also released from decaying organic matter in marshes and in surface seawater, where it is the
primary breakdown product of algae. It also originates from man-made sources such as pulp mills and sewage
treatment plants. Therefore, methyl mercaptan can be inhaled through the lungs upon exposures to these sources.
Fibrinogen, Heparin, Insulin
 Fibrinogen – is a blood plasma protein produced by the liver.
Functions
Fibrinogen plays an important role in blood coagulation. Blood coagulation is a process in which several
components of the blood form a clot. When blood escapes from a rupture in a blood vessel several proteins,
called coagulation factors, go into action to produce thrombin. The thrombin then converts fibrinogen to fibrin.
Fibrin produced from fibrinogen is the main protein in a blood clot. It surrounds the cells in the blood and
plasma and helps form the clot.
Sources
Fibrinogen is found strictly as a synthesized protein in the body. Fibrinogen is not found in foods nor is it
manufactured as a nutritional supplement.
CAUTION: Increased levels of fibrinogen are a risk factor for heart disease and stroke.
 Heparin (C12H19NO20S3) – a highly sulfated glycosaminoglycan (GAG).
Functions
Heparin acts as an anticoagulant, preventing the
formation of clots and extension of existing clots within
the blood. While heparin does not break down clots that
have already formed, it allows the body's natural clot
mechanisms to work normally to break down clots that
have not yet formed.
Sources
Heparin is naturally synthesized in the body from basophiles and mast cells (immune cells). Heparin is not found
in foods nor is it manufactured as a nutritional supplement. However, heparin is produced by pharmaceutical
companies where it is derived from mucosal tissues of slaughtered meat animals such as porcine (pig) intestine
or bovine (cow) lung. Pharmaceutical grade heparin is administered via injection.
 Insulin – is a natural hormone and protein made by the pancreas.
Functions
Insulin controls the level of sugar glucose in the blood. Insulin permits cells to use
glucose for energy. Cells cannot utilize glucose without insulin.
Sources
Insulin is synthesized in the body by the pancreas. Insulin is not found in foods nor
is it manufactured as a nutritional supplement. However, insulin is produced by
pharmaceutical companies for the purpose of injections in treating diabetes.
Allicin, Acidophilus, Chlorella
 Allicin (C6H10OS2) – is an oily, yellow liquid, which gives garlic its characteristic odor. Allicin is produced when garlic
is crushed or bruised. The reaction is catalyzed by the enzyme allicinase.
Functions
Allicin is not bioavailable and will not get absorbed in the blood, even after
ingesting large amounts. However, the allicin remaining in the gut exhibits
antibacterial and anti-fungal properties. For example: studies have confirmed
that allicin has inhibitory activity on Helicobacter pylori - a bacteria
responsible for the development of gastric ulcers. The sensitivity might also
explain the lower risk of stomach cancer in people with high garlic intake.
Sources
Allicin is not synthesized by the body. Allicin is found primarily in garlic and onions. Allicin is also manufactured
as a nutritional supplement.
 Acidophilus (dairy) (THIOL) – also known as lactobacillus acidophilus is a probiotic. Probiotics (friendly bacteria)
are live microbial organisms that are naturally present in the digestive tract.
Functions
a) Acidophilus can help protect the body against harmful bacteria,
parasites, and other organisms. As it breaks down, it releases
hydrogen peroxide which creates a toxic environment for unhealthy
creatures in the body, helping to drive them out.
b) Acidophilus plays an important role in digestion, helping to produce a number of chemicals which aid in the
digestion process.
c) Acidophilus is thought to help boost the immune system and produce vitamin K.
Sources
Acidophilus is not synthesized by the body, rather acidophilus can be found in cultured dairy products such as
yogurt or kefir. Fermented foods such as sauerkraut also contain acidophilus. Acidophilus is also manufactured
as a nutritional supplement.
 Chlorella (THIOL) - is a single celled green algae. Chlorella contains the green photosynthetic pigments chlorophyll.
It is also an attractive food source because it is high in protein (SAA’s) and other essential nutrients.
Functions
Clinical studies on chlorella suggest effects including: detoxification of
dioxin (highly toxic chemicals in the environment that do not break
down), healing from radiation exposure, the ability to reduce high blood
pressure, lower serum cholesterol levels, accelerate wound healing, and
enhance immune functions in humans.
Sources
Chlorella is not synthesized by the body. Chlorella is grown in lake farms or outdoor ponds and then processed as a
nutritional supplement. However, studies have shown that chlorella actually loses most of its nutritional value when
altered or processed in any way.
Compiled Chart: Organosulfur Compounds
(both exogenous and endogenous, that the human body either inhales, ingest or biosynthesizes)
Organosulfur Compounds
Found in Food
(organic sulfur compounds)
Man-Made
Produced in Body
(supplements)
Biotin (C10H16N2O3S)
X
X
-
Thiamine(B1) (C12H17N4OS)
X
X
-
Pantethine (C22H42N4O8S2)
-
X
X
Coenzyme A (C23H38N7O17P3S)
-
X
X
Acetyl-CoA (C23H38N7O17P3S)
-
-
X
Methionine (C5H11NO2S)
X
X
-
S-Adenosylmethionine (C15H22N6O5S+)
-
X
X
Homocysteine (C4H9NO2S)
-
-
X
Cysteine (C3H7NO2S)
X
X
X
Cystine (C6H12N2O4S2)
X
-
X
N-Acetyl-Cysteine (C5H9NO3S)
-
X
X
Metallothionein
-
-
X
Alpha-Lipoic Acid (C8H14O2S2)
X
X
X
Glutathione (C10H17N3O6S)
X
X
X
Taurine (C2H7NO3S)
X
X
X
PAPS (C10H15N5O13P2S)
-
-
X
Chondroitin Sulfate
-
X
X
Glucosamine Sulfate
-
X
X
Methslsulfonylmethane (MSM) (C2H6O2S)
X
X
-
Methanethiol/Methyl Mercaptan (CH4S)
X
-
X
Fibrinogen
-
-
X
Heparin (C12H19NO20S3)
-
X
X
Insulin
-
X
X
Allicin (C6H10OS2)
X
X
-
Acidophilus
X
X
-
Chlorella
X
X
-
DMPS (C3H8O3S3)
-
X
-
DMSA (C4H6O4S2)
-
X
-
DMSO (C2H6OS)
-
X
-
“Man-Made” Sources of Sulfur and Sulfur Compounds in the Human Body
In the previous report – Sulfur and Sulfur Compounds in the Environment - the topic of man-made sources of sulfur is
discussed in detail. Below is a description of how some of them gain entry into the human body.
Elemental Sulfur (S)
Sulfur dust is used as a pesticide and can be inhaled, absorbed through contact with the skin, eyes or mucous
membranes and can be unintentionally swallowed. Additionally, people may be exposed to small amounts of sulfur
through the food supply as pesticide residue. However, EPA does not believe that the ingested sulfur is harmful in any
amount and therefore has not established limits for residues of sulfur in or on food.
Elemental sulfur is considered, by the EPA, to be non-toxic. However, many sulfur derivatives such as sulfur dioxide and
hydrogen sulfide are considered to be highly toxic.
Sulfur Dioxide (SO2)
Is a toxic, non-flammable, colorless gas that has a strong pungent, irritating odor familiar to the
smell of a just struck match. Sulfur dioxide is the result of sulfur being burned. When carbon is
burned the well known carbon dioxide (CO2) is produced. When sulfur is burned, sulfur dioxide
(SO2) is produced.
Sulfur dioxide is released into the atmosphere from a variety of natural sources such as hot springs, volcanoes, decay of
vegetation and forest fires. Man-made sources of sulfur dioxide result from the burning of sulfur and sulfur compounds
found in fossil fuels by way of - vehicle exhaust, power plants, pulp mills, homes burning oil for heat, etc.
In humans, sulfur dioxide irritates eyes and the respiratory systems. High concentrations are associated with a number
of lung problems, and even low concentrations can cause asthmatic subjects to experience severe bronchial constriction
during exercise. Sulfur dioxide can even react with moisture in the lungs to form sulfurous acid which in sufficient
quantities may harm the lungs, eyes or other tissues.
Inhalation of sulfur dioxide is dangerous however, “they” claim ingestion of sulfur dioxide and sulfites is harmless, hence
their use in the food industry as food preservatives.
Sulfite (SO32-)
It was determined earlier that sulfites are a naturally occurring compound in the human body. However, it was also
determined that they served no function and were toxic intermediates that need to be immediately detoxified.
Yet, a major source of sulfites to humans comes from the sulfite and sulfur dioxide additives found in many food
products. Sulfites and sulfur dioxide are strong antioxidants that are added to foods for the control of enzymatic and
non-enzymatic browning as well as for their antimicrobial action. For example:
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In 'fresh' food products sulfites prevent discoloration and oxidation (breakdown) of the food.
On grapes sulfites are used as a fungicide.
In wines sulfites kill certain unwanted bacteria and assist in the aging process.
In packaged processed food sulfites are a preservative.
Sulfites are used as a bleaching agent for food starches.
Sulfites are used as a strengthener in dough conditioners.
Sulfites can even be found in herbs because sulfur treatment is sometimes used to prevent herbs from deteriorating.
This is usually done by placing the herbs on a screen and having sulfur vapors (from burning sulfur) briefly flow from
below the screen, which could leave traces of sulfur dioxide. Sulfites are also frequently used in pharmaceutical drugs as
a preservative and stabilizer.
A list of the different types of sulfites used in foods and medicines are:
Sulfite
Sodium Bisulfite
Calcium Metabisulfite
Sulfur Dioxide
Sodium Metabisulfite
Potassium Bisulfite
Sodium Sulfite
Calcium Bisulfite
Potassium Metabisulfie
It should be noted sulfur dioxide (a gas), strictly speaking is not a sulfite. However, the human response to sulfur dioxide
mimics the response to sulfites, probably because it may be oxidized to become a sulfite. Sulfur dioxide gas is used to
prevent discoloration, for example in the drying of fruit. In the process, sulfur dioxide is trapped and bound to the fruit
and the concentration can be quite high. Since ancient times, burning sulfur has been used to temper the fermentation
of wine. Most modern wine makers today use the sulfite salts directly, but the result is the same.
Sulfur dioxide can also be dissolved in water to have a softening effect on fibers and other organic structures. This effect
is used in the corn refining process that produces corn starches and syrups. Since corn refining starts with a two day soak
in hot water laced with sulfur dioxide (called steeping), all corn starches and syrups wind up with a sulfur content. Corn
starches and syrups such as - baking powder, caramel, dextrin, maltodextrin, dextrose, fructose, etc. are the most
common sulfured ingredients in modern foods.
It should also be noted that sensitivity to sulfites is a different condition compared to a sulfa drug allergy. Some patients
will have allergic reactions to sulfur containing medications or sulfa antibiotics. This is a very different condition than
sulfite sensitivity. Those allergic to sulfites are often not at increased risk of sulfa drug allergy, and vice versa.
Hydrogen Sulfide (H2S)
Hydrogen sulfide is a colorless, flammable, extremely hazardous gas with a rotten egg smell which
occurs when water (H2O) mixes with sulfur(S). Natural sources come from – natural gas, hot
springs, swamps, shallow lakes, plumbing systems, water heaters, etc. Man-made sources of
hydrogen sulfide come from – pulp mills, waste water treatment plants, refineries, etc.
Hydrogen sulfide – is readily absorbed in the lung and by the alimentary canal (entire digestive system – mouth to
anus). At levels of only 5ppm hydrogen sulfide can cause irritation of the conjunctiva and bronchial mucus. At 100 ppm
it can cause asphyxia, nausea, cerebral excitement, narcosis and after an hour death. 1000 ppm leads to immediate
paralysis and death.
Though elemental sulfur is considered to be non-toxic, doses of over 10 grams will can cause headache, vomiting and
intestinal pain. These toxic effects are caused by sulfur mixing with water in the intestines to create hydrogen sulfide
which can be noticed on the breath.
Pharmaceutical Drugs
The amount of pharmaceutical drugs consumed in the US and worldwide is staggering. Many of these drugs are
manufactured with the element of sulfur and therefore must also be considered as a source of sulfur intake. The
chemical compounds found in pharmaceutical drugs are manufactured synthetic compounds. Below is a partial list of
the more common sulfur containing pharmaceutical drugs.
 2,3-Dimercapto-1-Propanesulfonic Acid (DMPS) (C3H8O3S3) (THIOL) – is a
chelating agent used as an antidote to heavy metals poisoning (mercury, arsenic,
lead). Chelating agents are chemical compounds that have the ability to bind
strongly with metal ions. DMPS is administered via injection.
 Dimercaptosuccinic Acid (DMSA) (C4H6O4S2)(Di-THIOL)– is a water-soluble,
sulfhydryl-containing organic compound that is FDA approved as a chelating agent
for the treatment of lead (Pb)and mercury (Hg) toxicity. DMSA is administered
orally and although it is sold as a prescription drug, it is also available as a
nutritional supplement.
Animal studies show DMSA to be almost 3 times more effective than DMPS in removing mercury from the brain.
DMSA has the added advantage that it is taken by mouth in capsule form, whereas DMPS must be given by injection.
DMPS is also 3 times more toxic than DMSA, based on its LD-50 (the dose at which 50 percent of lab animals die).
 Dimethyl Sulfoxide (DMSO) (C2H6OS) (THIOL) – is a by-product of the wood industry and has been in use as a
commercial solvent for decades.
In the medical field DMSO is predominantly used as a topical analgesic (relieves pain), a
vehicle for topical application of pharmaceuticals, as an anti-inflammatory and an
antioxidant.
Because DMSO passes through membranes easily it increases the rate of absorption of
some compounds through organic tissues including skin, it can be used as a drug
delivery system. It is frequently compounded with antifungal medications, enabling
them to penetrate not just skin but also toe and fingernails. It penetrates the skin so
rapidly one can taste it soon after it comes into contact with the skin. Additionally,
DMSO has demonstrated that it can exert a protective effect on the GAG - hyaluronic acid.
 Sulfonamides or Sulfa Drugs (H2NO2S) – in chemistry sulfonamide is another sulfur containing functional group
which is made up of a sulfonyl group S(=O)2 connected to an amine group (NH2). Attached to sulfonamide group is
an organic group which is produced by a pharmaceutical company.
There are several sulfonamide-based groups of drugs. The original sulfonamides (called sulfa
drugs) contained antibacterial/antimicrobial properties. These drugs have the marked ability to
halt the growth of bacteria in the body. Antibiotic sulfonamides were the first antibiotics used
to treat infections. However, today sulfa drugs are used much less frequently. Below is a partial
list of antibiotic/antimicrobial sulfonamides/sulfa drugs (generic names):
Antibiotic/Antimicrobial Sulfonamides
Sulfa-benzamide
Sulfa-diazine
Sulfa-doxine
Sulfa-isodimidine
Sulfa-methoxypyridazine
Sulfa-thiazole
Sulfa-cetamide
Sulfa-dimethoxine
Sulfa-methoxazole
Sulfa-nilamides
There are also non-antibiotic sulfonamides which are devoid of antibacterial activity. Most non-antibiotic
sulfonamides are prescribed as diuretics (increase the excretion of water from the body via urination) and
anticonvulsants (used for epileptic seizures by suppressing the rapid and excessive firing of neurons). Below is a
partial list of diuretic and anticonvulsant sulfonamide drugs (generic names):
Diuretic Sulfonamides
Acetazolamide
Furosemide
Metolazone
Ethoxzolamide
Hydrochlorothiazide
Xipamide
Chlorthalidone
Indapamide
Clopamide
Mefruside
Anticonvulsant Sulfonamides
Acetazolamide
Bumetanide
Sultiame
Zonisamide
Other non-antibiotic Sulfonamides
Celecoxib – a NSAID, brand name Celebrex or Celebra.
Sulfasalazine – another NSAID, brand name Azulfidine.
Darunavir – a protease inhibitor used to treat HIV infection, brand name – Prezista
Probenecid – increases uric acid excretion in urine for treatment of gout, brand name - Benuryl
Sumatriptan – used for the treatment of migraine headaches, brand name – Imitrex, Imigran.
 Other Sulfur-Containing Drugs
There are numerous drugs that are manufacture which contain elemental sulfur in its compound. Though these
drugs contain sulfur they are not considered to be sulfonamide drugs because the sulfur is not part of a “sulfur
functional group”.
CAUTION:
Approximately 3% of the general population has adverse reactions when treated with sulfonamide antimicrobials.
However, it is important to make a distinction between sulfur and other sulfur-containing compounds, which are
chemically unrelated to the sulfonamide group. A sulfonamide does contain sulfur, but the sulfur atoms are imbedded in
a complex molecule. The sulfur atom is not the allergenic agent and being allergic to sulfa drugs does not imply having a
propensity for an allergy to sulfur and other sulfur compounds. Rather, it is a unique property of the sulfonamide
molecule, which once in the body is capable of attaching to proteins and forming a larger molecule that could serve as
an allergen.
Also, a distinction must be made between an allergic reaction (i.e. to sulfa drugs, foods, pollens, etc) and the
physiological symptoms that present themselves due to the body’s inability to properly detoxify certain compounds such as sulfur and sulfur compounds listed in this report.
Compiled Chart: Inorganic Sulfur Compounds
(both exogenous and endogenous, that the human body either inhales, ingest or biosynthesizes)
Inorganic Sulfur Compounds
Naturally Occurring
In Environment
Man – Made
Produced in Body
Elemental Sulfur (S)
X
-
-
Sulfide (S2-)
X
-
X
Sulfur Dioxide (SO2)
X
X
-
Sulfur Trioxide (SO3)
X
X
-
Sulfate (SO4)
X
-
X
Hydrogen Sulfide (H2S)
X
X
X
Sulfurous Acid (H2SO3)
-
X
X
Sulfuric Acid (H2SO4)
X
X
-
Sulfite (SO32-)
X
X
X
Pharmaceuticals (sulfa) (H2NO2S)
-
X
-
(industry)
Conclusion
Sulfur and sulfur compounds are ubiquitous. The purpose of this report and the previous report was to identify the main
players - some of the more common sulfur compounds. In attempting to do so, distinctions were made between natural
sources of sulfur and man-made sources of sulfur. Between sulfur compounds found in the environment and those
found in the human body. And finally, between sulfur compounds that are vital nutrients and those that are potentially
harmful toxins.
Regardless of their distinctions, most sulfur and sulfur compounds do gain entry into the human body. Therefore, it is
imperative that the body properly metabolize, utilize and bio-transform (detoxify) them. Luckily, most people, though
not all, are able to do just that. Failure to do so will most likely result in illness with a wide range of symptomatology.
In the next report we will take on the complex subject of biotransformation (detoxification) in the human body. With a
concentration on the biotrasnformational processes of sulfur and sulfur compounds.
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 Encyclopedia Britannica
 Wikipedia
 Medpedia
 Arthritis Foundation
 The World’s Healhiest Foods
 Feingold Association of the United States
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Wilson Creek Winery and Vineyards
Oregon State University, Linus Pauling Institute
Florida State University
University of Florida IFAS Extension
University of Maryland Medical Center
University of Arizona, Department of Biochemistry and Molecular Biophysics
University of Illinois at Chicago