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Augmenting glutathione in chronic fatigue syndrome (CFS)
January 10, 2006
I have recently become convinced that the genetic predisposition and
much of the biochemistry of CFS is similar to that of autism. In autism,
researchers associated with the DAN! (Defeat Autism Now!) project have
found that as a result of a combination of genetic variations and environmental factors there are blocks in the sulfur metabolism (including the
methylation cycle and/or the transsulfuration pathway) in many autistic
children. They have further found that lifting these blocks by means of
certain supplements allows the glutathione level to come up. I refer you
to the book "Autism: Effective Biomedical Treatments," by Jon Pangborn
and Sydney Baker (Sept. 2005, www.autismresearchinstitute.com) for the
details of these treatments. At present, I suspect that many PWCs will be
unable to raise their glutathione levels if these blocks are not first lifted.
Provided such blocks are not present or are not dominant in a given case,
there are several ways to augment one's glutathione in CFS. It is a good
idea to proceed slowly at first if glutathione has been depleted for an
extended period of time (months to years), because toxins and infections
may have been allowed to build up in the absence of sufficient glutathione to keep them under control. If glutathione is then brought up rapidly,
the mobilization of toxins can produce a Jarisch Herxheimer reaction,
which is an exacerbation of symptoms that can make a person feel very
unpleasant. Also, see the particular comments about mercury below.
Here are some approaches for building glutathione (Note that names of
products, laboratories and suppliers are given for information only, not
as recommendations. There may be others not mentioned that are satisfactory):
1. Oral supplements, such as the "nondenatured" or "native" whey protein
products (e.g. ImmunoPro Rx or RenewPro), the "undenatured" whey protein products (e.g. Immunocal, ImuPlus, etc.), such as from http.//www.
immunesupport.com or http://www.needs.com or http://www.iherb.com,
the fermented goat-milk-based version of whey protein, Goatein, available
from www.gardenoflifeusa.com, amino acid precursors including N-acetylcysteine, glycine and glutamic acid (such as from Jeff Clark at http://
www.cfsn.com), N-acetylcysteine together with dietary protein, or reduced
glutathione supplements per se, both available from health food stores.
One supplier of oral reduced glutathione is
http://www.theranaturals.com.
A relatively new type of oral glutathione supplement is liposomal glutathione, which is reduced glutathione encapsulated in tiny liposomes made from soy-based phosphatidylcholine. There are currently three of these products on the market of which I am aware: Essential GSH (http://
www.essentialgsh.com), Lipoceutical Glutathione (http://www.gshnow.
com), and LipoFlow Glutathione (http://www.lipoflow.com) The liposomal
form is relatively expensive, but more of the glutathione is absorbed
intact and appears to be carried to various cells of the body encapsulated
in the liposomes.
No prescription is required for the above oral supplements.
ImmunoPro Rx and RenewPro are actually "native" or "nondenatured,"
being made from whey that has not been heated to high temperatures or
treated with acid as in cheese making, which the "undenatured" products'
starting material have undergone, so that they have more cysteine present as actual cysteine per se rather than the oxidized form cystine, and
cysteine is more useable by the liver for making glutathione, probably
particularly in a person who is depleted in glutathione.
The "undenatured" and "nondenatured" whey protein products can be
problematical for those with allergies to whey proteins (or perhaps to casein, which may be present in small quantities in the whey protein products), and the goat-milk based version Goatein may be helpful in such
cases, even though the fermentation process likely converts much of the
cysteine to cystine.
The amino acid precursors should not present problems of allergic reactions, but should be taken with high quality dietary protein to ensure that
they are used effectively and that if mercury is present, its transport into
the brain is not encouraged. Some PWCs do not tolerate glutamic acid
well. In such cases, glutamine (or better yet, a product called Glutimmune, available from http://www.wellwisdom.com) can be substituted for
the glutamic acid, and taken together with N-acetylcysteine and glycine.
The reduced glutathione supplements are a more expensive approach
than the whey or NAC-based approaches. Free reduced glutathione appears to be largely broken down in the gut into amino acids, so there is
probably not an advantage to taking regular capsules of reduced glutathione per se except for the cells of the intestines themselves.
Liposomal glutathione is likely not significantly broken down in the gut
and is able to enter cells in its intact form more easily. Liposomal
glutathione may actually be absorbed through the wall of the stomach.
Oral supplements are probably the best way to raise the glutathione level
in the liver, since the liver gets first access to oral supplements via the
portal vein, and it is normally the main producer of glutathione in the
body and an exporter of glutathione to the systemic blood and the bile.
The liver is probably not able to take glutathione from the blood for its
own use, so approaches that put glutathione per se into the blood
probably are not very helpful in directly building glutathione in the liver.
If there is a high level of mercury in the body, such as can occur if glutathione has been low for an extended period of time (months to years) and
the person has silver amalgam fillings in their teeth or they have consumed a significant amount of large, predatory fish, including tuna, or they
are close to an environmental source of mercury, then caution should be
exercised by limiting the dosages of oral supplements that supply amino
acids to the liver for making glutathione. There are two reasons for this:
The first is that mercury can be moved into the brain from other parts of
the body by cysteine or N-acetylcysteine if the dosages are too high. Dr.
David Quig of Doctors Data Laboratories recommends limiting the dosage
of NAC to 300 mg per day and taking it with a high protein diet if heavy
metals are elevated. The ability of NAC to transport mercury into the
brain was confirmed in rats in recent experiments by Aposhian et al.
The second reason is that mercury can block the utilization of cysteine,
and if cysteine rises too high, it can act as a neurotoxin. (This last is also
the reason L-cysteine is not recommended as a supplement for building
glutathione.) It's a good idea to measure the blood plasma level of
cysteine periodically when building glutathione, to make sure it is not
rising too high.
If elevated mercury is suspected, it is a good idea to test for mercury and
detox it carefully if it is present, with the help of a doctor experienced in
doing this. The best test is a collection of urine for 6 hours, preceded by
a challenge with the chelator DMSA (succimer). A very small dosage of
DMSA should be tried first, to make sure there is not an allergic reaction
to it. A test of this type is offered by http://www.doctorsdata.com.
If there is elevated mercury, it may also be wise to begin building glutathione using one of the approaches below, which put glutathione per se
into the blood, rather than one of the oral approaches that help the liver
to make glutathione. This may help to remove the mercury more
"gently," starting with the kidneys, which absorb most of the glutathione
put directly into the blood.
2. Intramuscular injections, as pioneered by Dr. Patricia Salvato in Houston. She injects 100 mg of glutathione with 1 mg of ATP, intramuscularly, 2 times per week. One source of IM glutathione is McGuff Compounding Pharmacy in Santa Ana, CA (phone: (877)444-1133, fax: (877)4441155). This probably benefits most the muscle into which it is injected,
but it also has systemic effects.
3. Intravenous injections, and particularly fast I.V. pushes, as advocated
and used by Dr. Patricia Kane and her co-authors of The Detoxx Book
(www.detoxxbook.com) as part of their overall detox protocol. The book
says they do an I.V. push over 3 to 5 minutes starting with 1,500 mg of
glutathione in 12 cc of sterile water for adults, and going as high as
2,500 mg in 15 cc of sterile water, one to two time per week for 3 to 6
months or more. They suggest Wellness Health and Pharmaceuticals in
Birmingham, AL as the source for injectable reduced glutathione (phone:
(800)227-2627, fax: (205)879-6551).
Intravenous glutathione injections seem to be becoming more prevalent.
I think they were pioneered in the U.S. by Dr. David Perlmutter (after
initial work in Italy by Dr. Secchi) for the treatment of Parkinson's disease,
but they are being used in other disorders as well. Several cell types are
able to extract glutathione from the blood, break it down, import the
pieces, and resynthesize it inside the cell, via the gamma glutamyl cycle.
Other types of cells can import glutathione intact from the blood. This
approach requires a prescription and repeated visits to a doctor's office,
and it is relatively expensive to get these injections repeatedly.
4. Glutathione suppositories from a compounding pharmacy. One source
is Hopewell Pharmacy in New Jersey (phone: (800)792-6670). One person
told me they use suppositories containing 250 mg of glutathione.
Another told me that they are also available in 500 mg doses from
http://www.wellnesshealth.com. I don't know how much gets into the
blood with this method, but I suspect that it is substantial. This is a
relatively inexpensive way to put glutathione into the blood. I think a
prescription is required for this form.
5. Glutathione nasal spray. I've heard of people formulating their own by
mixing glutathione solution from compounding pharmacies with saline
solution. I don't know how much glutathione is absorbed into the blood
this way, but I suspect it is less than with the suppositories. It's
important to keep the solution refrigerated and to use it soon after it is
mixed, because the reduced glutathione undergoes chemical changes
over time in solution.
6. Glutathione transdermal skin creams (available from http://www.kirkmanlabs. com) (no prescription required). Lotions are also sold. These
may have a strong smell. A stabilized reduced glutathione transdermal
gel is available from http://www.leesilsby.com. I don't know how much
of the glutathione gets into the blood with these products.
7. Glutathione sublingual troches from a compounding pharmacy. One
source is Lionville Natural Pharmacy in Lionville, PA (phone: (877)3637474, fax: (610)363-5707) These are made in orange and blueberry
flavors, and are composed of a very firm gel. There are also hard troches
in orange flavor. I don't know how much gets into the blood.
8. Nebulizer application to the lungs, as pioneered by Dr. Buhl et al. at
the NIH and as described by Dr. Julian Whitaker in his newsletter Health
and Healing. Dr. Buhl used 600 mg in a few milliliters of water per application. Dr. Whitaker uses 300 mg, two times per day, applied over 5 to
10 minutes with a nebulizer, available from a medical supply company.
He recommends Wellness Health and Pharmaceuticals (numbers given above) and California Pharmacy and Compounding Center http://www.californiapharmacy.com) as sources for the glutathione. Nebulized glutathione is being used for a variety of lung diseases now, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, interstitial pulmonary
fibrosis and multiple chemical sensitivity. There are reports that blood
levels of glutathione rise when this method is used. Valerie Hudson, who
has helped to pioneer use of aerosol glutathione in cystic fibrosis, suggests L-Glutathione Plus capsules from http://www.theranaturals.com,
mixed with boiled water, applied with a nebulizer. No prescription is
required for the capsules, or to buy a nebulizer on the internet. Valerie
suggests one capsule containing 200 mg of reduced glutathione mixed
into 3 or 4 ml of boiled water. An important feature of this source of
glutathione (available without a prescription) is that it is buffered with
sodium bicarbonate. Clark Bishop, M.D., wrote me that this buffering is
important, because if the pH is too acid, it can lead to bronchospasm
when nebulizing. People who are subject to asthmatic attacks should not
use nebulized glutathione, as it can result in bronchospasm, thought to
be caused by the sulfites that form when glutathione is mixed with water.
It's also very important in nebulizing to use pure, boiled or sterile water,
and a clean nebulizer in order to prevent introducing infections or insoluble respirable particulates into the lungs. Because of these issues, nebulizing is best done under the supervision of a doctor or a respiratory
therapist.
9. Take turmeric (the yellow spice in mustard and in food eaten in India).
The curcumin in this spice has been shown to stimulate glutathione
production.
Some people are using more than one of these modes simultaneously.
My current opinion is that it is a good idea first to deal with possible
blocks in the sulfur metabolism, as discussed above, then to start at low
dosages of glutathione or precursors or protein supplements, to see how
well they are tolerated, and then work up as they are tolerated. I think
that a combination of an oral approach to build the liver's ability to make
glutathione combined with one or more of the approaches that puts
intact glutathione into the blood is probably the optimum way to build
glutathione, once the sulfur metabolism blocks, if present, have been
lifted.
It is a good idea to measure the glutathione level before starting to try to
build glutathione to see if it is low, and then, if it is low, to measure again
after trying to build it for a few months, to see how your approach is
working. There are several ways to do this. Probably the cheapest is to
measure the red blood cell glutathione. Two labs that offer this test are
Immunosciences Lab (www.immuno-sci-lab.com) and Amscot Medical
Labs ([email protected]). Great Smokies Diagnostic Lab (http://www.
gsdl.com) offers an assessment of the glutathione detoxification pathway
as well as plasma reduced glutathione in its Comprehensive Detox panel.
An analysis of urinary organic acids by either www.greatplainslaboratory.com or www.metametrix.com will give an indirect assessment of glutathione status, particularly in the skeletal muscles (via citric acid and
alpha ketoglutaric acid measurements) and the kidneys (via pyroglutamic
acid aka 5-oxo-proline measurement). A measurement of glutathione
function in the lymphocytes is offered by www.spectracell.com. I favor
the Spectracell test if a person can afford it, because the lymphocytes are
heavily affected in CFS. Otherwise, the red blood cell test is still useful.
It's also a good idea to measure the blood plasma level of cysteine periodically when building glutathione, to make sure it is not rising too high.
If a person is high in mercury, this can block the pathways that use
cysteine, and it can build up.
If anyone reading this finds errors or knows of things that have been left
out, please let me know at [email protected]. Thank you.
Rich Van Konynenburg