Methionine's role in heavy metal exposure
[Karl note: This page was taking from a page originally shown under "source" above. That web address was: http://www.talkinternational.com/redoxal/references.htm which, just several days later, was no longer available on the web.
[Subsequent to that experience someone from that company called me to inform me that there had been a change of servers and that the company was not out of business. Indeed, I find that the above link worked on January 17, 2003.]
The information on this page requires much more investigation. I have started that process. The page has an address that includes "redoxal," as shown above, and THAT name happens to be the name of a brand of "oral chelation" based only on the use of "Methionine."
One company selling this formula is Sunshine Herbs, with their web page below. This formula is based almost only on Methionine -- my research shows that it does combine with mercury, and it does cross the blood brain barrier -- thus Methionine is a suspect ingredient for the purposes of chelation.
Another distributor of "Redoxal" is apparently no longer in business. I would suggest that anyone taking Redoxal should insist on proof that it does not cause much more harm than good!]
Methionine's role in heavy metal exposure:Animal studies have shown that adding methionine to the drinking water of rats protected the animals from the toxic effects of lead(3). In a separate experiment it also protected the animals from the toxic effects of mercury and atrazine (an herbicide) (4).
This essential nutrient and its' metabolites help the body detoxify substances such as exhaust fumes, metals, chemicals, pesticides, herbicides, plastics and other hydrocarbons and xenobiotics. Methionine supports the body's natural detox pathways as well as offers protection from exposure to toxic and potentially toxic substances.
The medical literature reports that L- methionine has demonstrated the ability to inhibit toxic metals from crossing the blood-brain barrier.
Metal ions attached to other L form amino acids (such as L-cysteine and glutathione) can cross the blood brain barrier. (9,10).
L-cysteine bound to mercury
resembles the L-methionine molecule and can
cross the blood brain barrier. (9, 10) True
L-methionine inhibited the transport of the
methylmercury-L-cysteine complex into the
brain (9,10). The beneficial effects of
methionine may be attributed to its ability
to increase the bioavailability of
glutathione (GSH) (3). Most of the cysteine
required for the resynthesis of GSH must
originate from methionine and not from
cysteine generated by the catabolism of GSH.
(13) .
Additionally, chelating agents such
as DMSA (dimercaptosuccinic acid) and DMPS (dimercapto-
propane sulfonic acid) bind to cysteine for
excretion (11, 12). It would appear that
insuring adequate methionine/ cysteine levels
would enhance the chelating properties of
these drugs particularly if taken prior to
their administration. It may also inhibit the
transport of other thiol chelators already
bound to metal ions from entering the brain.
L-penicillamine, Dimercaptosuccinic acid, N-acetyl-L-cysteine and glutathione complexed with methylmercury were also transported across the blood brain barrier to varying degrees (10). (DMPS has never been demonstrated to enter the brain). (12)
Arthritis
Asthma and other lung conditions
Headaches
Migraines
Allergies
Acne
Diseases of immune dysfunction
Fibromyalgia
Supression of appetite
Detoxification from metals, pesticides, plastics, hydrocarbons
Protection from exposure to toxic metals, pesticides, plastics and hydrocarbons
Increased wound healing (surgical and accidental wounds)
Cholesterol lowering
Daily methionine and folic acid supplement
As a sulfhydral replacement for persons on daily aspirin or other NSAID treatments
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References:
(1) The Healing Nutrients Within , E. Braverman, MD and C. Pfeiffer, MD 1987, Keats Publishing (2) Methionine, The Missing Antioxidant, Gerald Hirsch, PhD 1996 (3 ) "Influence of Methionine Supplementation in Chelation of Lead in Rats" Kachru, D.N.; S. Khandelwal; and S. K. Tandon Biomed. Environ. Sci. 2:265-270, 1989 (4) "Effect of Dietary Methionine on Methyl Mercury and Atrazine Toxicity" Mohsen Meydani and J.N. Hathcock Drug Nurtrient Interactions 2:217-233, 1984 (5) "Regulation of Methionine Metabolism: Effects of Nitrous Oxide and Excess Dietary Methionine" M.S. Frontiera; S.P. Stabler, J.F. Kilhouse; R. H. Allen Department of Medicine and Department of Biochemistry, Biophysics and Genetics, University of Colorado Health Sciences Center, Denver, CO, USA. Journal of Nutritional Biochemistry, 1994 Vol 5, January 6) "The incorporation of Sulfur Amino Acids into the Proteins of Regenerating Wound Tissue" Williamson and From, Dept. of Biochemistry, Loyola University, Chicago. J. Biol. Chem. 2112:705-712, 1955 (7) "A Prospective Study of Plasma Homocyst(e)ine and Risk of Myocardial Infarction in US Physicians" M.J. Stampfer; R. Malinow; W.C. Willett; L.M. Newcomer; B. Upson; D. Ullmann; P.V. Tishler; C.H. Hennekens, JAMA, August 19, 1992-Vol 268, No. 7 (8) Healing Nutrients Within, Eric R. Braverman, MD, Revised Edition, 1997, Keats Publishing (9) "Methylmercury transport across the blood-brain barrier by an amino acid carrier" Kerper L.E.; Ballatori, N. ; Clarkson, TW, Department of Biophysics, University of Rochester School of Medicine, NY Am J Physiol 1992 May; 262 (5Pt 2) R761-5 Click Here For Abstract(10) "Methylmercury-thiol uptake into cultured brain capillary endothelial cells on amino acid system L" Mokrzan, E.M.; Kerper L.E. Ballatori, N. ; Clarkson, T.W.,Department of Environmental Medicine University of Rochester School of Medicine, NY J Pharmacol Exp Ther 1995 Mar; 272(3):1277 This title appears to be within a 368 page book which is for sale, but not available in electronic form. Click here for a one-page-at-a-time view of the book. Click here for a web page (published below) for Dr. Clarkson.11) Physicians’ Desk Reference 51Edition 1997 pp. 666-668, Bock Pharmacal Company Chemet ® ((DMSA) (12) Scientific Monograph 1997, Heyltex Corporation, Dimaval ® (DMPS) (13) " Glutathionine metabolism in activated human neutrophiles: stimulation of glutahione synthesis and consumption of glutathione by reactive oxygen species." Blizer, M ; Lauterburg, BH, Eur J Clin Invest 1991 Jun;21(3):316-22 |
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Redoxal HMF™The principal ingredients in Redoxal's formula are dl-Methionine and Betaine with additional nutrients required for metabolizing Methionine. The addition of Betaine makes this a methyl donor formula. Redoxal's formula contains all the nutrients required in the International Academy of Oral Medicine and Toxicology's (IAOMT) Standards of Care for oral Methionine use during mercury amalgam removal, increased wound healing and use of nitrous oxide gas for dental patients and personnel. Redoxal HMF™ is used by physicians and dentists throughout the USA and Europe for detoxification of toxic metals such as mercury, arsenic and lead, as an anti-inflammatory in arthritis, fibromyalgia, headaches, migraines and other chronic pain syndromes. Redoxal HMF™ is patented as an anti-inflammatory and antioxidant. Patent pending as a detoxification agent for heavy metals. Price: $29.95 (90 capsules) Order
This Item Each bottle contains 90 capsules. Suggested use is one capsule three times per day or as directed by a health care professional. Each capsule contains: dl-Methionine, 500 mg - Studies have shown the protective effects of Methionine in animal models against mercury, lead and atrazine (an herbicide). Methionine is an essential sulfur amino acid and is listed on the FDA's GRAS (generally regarded as safe) list. It was once used in soy bases baby formulas to provide adequate Methionine nutrition for infants. Methionine is a critical component of tissue development, growth and tissue repair for all humans - no mater what the age. Methionine functions as an anti-oxidant (free radical deactivator) and helps neutralize toxins. It is also important important in preventing disorders of the skin and nails and helps prevent hair loss. It serves as a principal source of sulfur that the body needs to replenish daily. Sulfur is used for mucous production and detoxification. Methionine helps prevent the accumulation of fat in the liver and is also anti-inflammatory. Betaine, 100 mg - Is a digestive aid and a folate-independent methyl donor. It can also cause the remethylation of homocysteine to Methionine and has been reported as an effective method of lowering blood homocysteine levels. l-Taurine, 50 mg - An important amino acid used by the heart muscle. It is also anti-arrhythmic, and is a potent, elective and long-lasting anti-convulsive agent. Pyridoxine (Vitamin B6), 0.8 mg - Essential is the synthesis and breakdown of amino acids and in the function of the neurotransmitters. It is also important in the production of red blood cells and supports immune cell function. Riboflavin (Vitamin B2), 0.6 mg - Is involved in the production of energy and the synthesis of fats and amino acids. It is also involved in cellular growth. Calcium Carbonate, 50 mg - Is critical to bone growth and health as well as the teeth. It is essential in the nerve impulse transmission and cell membrane permeability. It is often called nature's relaxant as it works on activating and relaxing smooth muscles. It is also involved in the blood clotting process, blood pressure regulation, heart rhythm and activation of digestive enzymes. Folic Acid, 0.4 mg - Prevents neural tube defects during pregnancy. It is essential for DNA and RNA synthesis, new cell growth in bone, gastrointestinal tract lining and in the production of red blood cells. It is essential in allowing methyl donor compounds such as Choline to be effective. Price: $29.95 (90 capsules) Order
This Item |
Sunrise Herb Shoppe
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This is a page reference to distributors of Redoxal -- but the link below does not work -- it appears that this distributor is not in business.
|
Preventhium International - Atlanta Georgia - Manufacturers & Distributors of Redoxal 1 (770) 831-8606 |
-
Methylmercury transport across the blood-brain barrier by an amino acid carrier.
Kerper LE, Ballatori N, Clarkson TW.
Department of Biophysics, University of Rochester School of Medicine, New York 14642.
The mechanism by which methylmercury (MeHg) crosses the blood-brain barrier was examined in the rat. Previous studies demonstrated that intravenous injection of L-cysteine with MeHg accelerates MeHg uptake into brain. Since the complex of MeHg with L-cysteine is structurally similar to L-methionine, a substrate for the L (leucine-preferring) amino acid transport system, this carrier may be involved in MeHg uptake. To examine this hypothesis, the rapid carotid infusion technique was used in the anesthetized rat. The concentration dependence of 203Hg uptake into brain after injection of Me203Hg-L-cysteine complex was nonlinear, exhibiting characteristics of saturable transport (apparent Michaelis constant 0.39 mM, vmax 33 nmol.min-1.g-1). A slower, nonsaturable uptake was seen after MeHg-L-cysteine uptake was inhibited by methionine and the amino acid analogue 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), an L system substrate, but not by alpha-methylaminoisobutyric acid, an alanine-preferring system substrate. Furthermore, L-[14C]methionine transport was inhibited by MeHg-L-cysteine but not by MeHgCl. There was a significant amount of uptake of 203Hg when injected as Me203Hg-glutathione, and this was inhibited by L-methionine and BCH but not D-methionine. S-ethylglutathione also inhibited 203Hg uptake after administration as Me203Hg-glutathione but had no effect on Me203Hg-L-cysteine uptake. These results suggest that MeHg may enter the brain as a cysteine complex via the L system and that plasma MeHg-glutathione serves as a source of MeHg-cysteine.
PMID: 1590471 [PubMed - indexed for MEDLINE]
| Am J Physiol 1992 May;262(5 Pt 2):R761-5 |
| Pharmacol Toxicol 1989 Jul;65(1):17-20 |
Brain, kidney and liver
203Hg-methyl mercury uptake in the rat:
relationship to the neutral amino acid
carrier.
Aschner M.
Department of Pharmacology and Toxicology,
Albany Medical College, NY 12208.
To investigate the effect of L-neutral amino
acids on tissue levels of methyl mercury in
the adult animal, rats were infused into the
external jugular vein with solutions
containing a) 0.05 mM 203Hg-MeHgCl and
saline, b) 0.05 mM 203Hg-MgHgCl-0.1 mM L-cysteine,
c) 0.05 mM 203Hg-MeHgCl-0.1 mM L-cysteine-0.1
mM L-cysteine-0.1 mM L-methionine, d) 0.05 mM
203Hg-MeHgCl-0.1 mM L-leucine, or e) 0.05 mM
203Hg-MeHgCl-0.1 mM L-cysteine-0.1 mM L-leucine,
Groups of animals were sacrificed at 3 min. 7
hr, and 96 hr. Brain, kidney, and liver 203Hg
radioactivity was measured by means of
gamma-scintillation spectrometry. Brain 203Hg
concentrations L-cysteine treated animals
were significantly higher compared with
saline treated animals (P less than 0.05) at
3 min., 7 hr and 96 hr. The coinjection or
coinfusion of methyl mercury with L-cysteine
and L-methionine abolished the L-cysteine-mediated
brain 203Hg uptake (P less than 0.05), at
each sacrifice time. Kidney and liver 203Hg
concentrations were not significantly
different in any of the treatment groups
compared with controls, irrespective of the
sacrifice time. Furthermore, the percentage
of diffusible 203Hg (non-protein bound) at
each sacrifice time was not statistically
different irrespective of the treatment
assigned. These results suggest that methyl
mercury L-cysteine conjugates in the plasma
may share a common transport step with the
L-neutral amino acid carrier transport system
and indicate the presence in brain
capillaries of a transport system capable of
selectively mediating methyl mercury uptake
across the capillary endothelial cell
membrane.
PMID: 2780503 [PubMed - indexed for MEDLINE]
| Pharmacol Toxicol 1989 Mar;64(3):293-7 | Related Articles, Books, LinkOut |
Methyl mercury uptake
across bovine brain capillary endothelial
cells in vitro: the role of amino acids.
Aschner M, Clarkson TW.
Environmental Health Sciences Center,
University of Rochester, School of Medicine
and Dentistry, New York 14642.
Previous studies in the rat in vivo have
demonstrated that co-injection of methyl
mercury (MeHg) with L-cysteine into the
common carotid artery enhances brain Hg
levels following a single capillary pass
through the CNS vasculature. In order to
elucidate the relationship between MeHg
transport and the neutral amino acid
transport carrier system, regulatory aspects
of MeHg transport across the bovine
blood-brain barrier were investigated in
isolated brain microvessel preparations.
Following 1 hour co-incubations of
203Hg-MeHgCl with 0.1 mM L-cysteine at 37
degrees, 203Hg uptake by suspended
microvessels was significantly increased (P
less than 0.05) compared with controls. This
enhanced capillary uptake of 203Hg was
abolished by co-incubations of microvessels
with 0.1 mM L-cysteine-L-methionine, or 0.1
mM L-cysteine plus AT-125 (alpha S,
5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazolacetic
acid), an irreversible inhibitor of gamma-glutamyl-transpeptidase.
One hr co-incubations of bovine capillaries
with 203Hg-MeHgCl and 0.1 mM D-cysteine at 37
degrees or 0.1 mM L-cysteine at 0 degrees did
not increase rat of 203Hg uptake compare with
controls. These results indicate that L-cysteine
enhances the rate of capillary MeHg uptake.
The accumulation of 203Hg in the bovine
microvessels appears to be a carrier-mediated
process. It is inhibited by L-methionine, a
competitive substrate for neutral amino acid
transport, and by AT-125. Capillary uptake of
203Hg is stereospecific to the L-enantiomorph
of cysteine, suggesting selective uptake of
MeHg across the blold-brain barrier. The data
emphasize the relationship between the L-enantiomorph
neutral amino acid carrier system and MeHg
transport across the capillaries.
PMID: 2498864 [PubMed - indexed for MEDLINE]
| 1: Acta Neurol Scand 1969;45(3):362-8 | Related Articles, Books, LinkOut |
Brain uptake of
Se75-selenomethionine after damage to
blood-brain barrier by mercuric ions.
Steinwall O.
PMID: 5807455 [PubMed - indexed for MEDLINE]
|
Graduate
Education in the Biomedical Sciences
University of Rochester Medical Center |
| Molecular Toxicology and Environmental Medicine |
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RESEARCH OVERVIEW
gradadm@urmc.rochester.edu
http://www.GEBS.rochester.edu/GEBS/mtem/Clarkson.htm
© 1998 All Rights Reserved
VTF
Last updated: 06/08/2002 08:07:27
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