Tylenol depletes Glutathione (necessary for removal of mercury)

January 27, 2008

http://www.wellness.com/blogs/DrMarkham/51/what-every-user-of-acetamino

phen-needs-to-know/dr-laura-markham

" The danger is that there isn't much difference between a safe, effective

dose, and a toxic dose. Just a doubling of the maximum daily dose can be

enough to kill, warns Dr. Anne Larson of the University of Washington

Medical Center. The other problem is that if you have no food in your

stomach, or if you have alcohol in your system, or worse yet, both, (not

relevant for your kids unless they're teenagers, but think about that

tylenol you took for your hangover last month), the regular dosage can be

toxic because of the overload to the liver. "

COMMENT

" Glutathione is found in every one of the trillions of cells in the body.

It is most abundant in the liver and then the kidneys. These are the

detoxifying organs. NAC N-acetyl cystiene is provided to patients in every

hospital emergency situation in the USA for acetaminophen overdose. However

NAC has many side effects to the health of the individual, but the

alternative is certain death. So it is only administered in emergency room

situations. "

http://www.mercola.com/2005/may/17/tylenol_risk.htm

" Most experts believe Tylenol causes its damage by depleting glutathione.

If you keep your glutathione levels up, the damage from the Tylenol may be

largely preventable. Even conventional medicine recognizes this, as anyone

who overdoses on Tylenol receives large doses of NAC in the emergency room. "

http://www.sciencedaily.com/releases/2002/10/021014072451.htm

" An overdose of acetaminophen can cause depletion of glutathione and land a

person in the hospital. " Acetaminophen toxicity is the number one cause of

hospital admission for liver failure in the United States, " he said. "

http://www.benbest.com/nutrceut/NAC.html

" Glutathione detoxifies acetaminophen, but once glutathione is depleted

there can be significant cell death in the liver [THE AMERICAN JOURNAL OF

MEDICINE; Flanagan,RJ; 91(Suppl C):131S-139S (1991)]. AIDS victims can

suffer severe liver and kidney damage by using acetaminophen or alcohol,

which severely deplete glutatione [PROCEEDINGS OF THE NATIONAL ACADEMY OF

SCIENCES (USA); Herzenberg,LA; 94(5):1967-1972 (1997)]. "

http://www.ssafood.com/site/docsTopicsTips/Nourish%20Your%20Eyes.mht

" Glutathione, another antioxidant, also prevents cataracts. In fact, lenses

with cataracts contain one-fifteenth (1/15th) of the normal amount of

glutathione and one-tenth (1/10th) the normal level of vitamin C.

Glutathione is in asparagus, avocado, broccoli, garlic, onions, spinach,

tomatoes, watermelon, eggs and walnuts. Abel advises taking alpha lipoic

acid, N-acetyl cysteine and selenium, which contribute to glutathione

production. Abel notes that metabolizing and excreting acetaminophen

(Tylenol) depletes glutathione. “Tylenol is probably not the best long-term

pain reliever for anyone concerned with eye health.” He says. "

GOOGLE ON +glutathione+tylenol

http://www.gotdownsyndrome.net/glutathione & acetaminophen.html

Glutathione & The Acetaminophen (active ingredient in Tylenol) Issue:

Glutathione is commonly deficient in individuals with Down Syndrome, due to

the extra chromosome & overexpression of the SOD-1 gene. Glutathione is an

important antioxidant. It helps scavenge free radicals, deal with oxidative

stress & the pro-oxidant state of individuals withÂ Down Syndrome.

Acetaminophen (the active ingredient in Tylenol & many other OTC drugs),

depletes Glutathione levels in the liver (where it is made & stored).

Therefore, for a person with Down Syndrome, this situation is very

important. Since Acetaminophen depletes Glutathione (which is already

deficient in DS), it is a bad situation - a key antioxidant is being even

more depleted. It can then cause more oxidative damage, free radicals &

liver damage. Tylenol is known to possibly cause liver damage & failure. It

is best if Tylenol (and drugs containing Acetaminophen) be avoided, but if

it is necessary, they can be used at times. When you have to use them, just

make sure you give more Glutathione or N-acetyl-cysteine to help out!

Below, is alot of info on Glutathione & the Acetaminophen issue (since it

is an important issue that comes up fairly often on DS lists):

The following is a list of some of the drugs that contain Acetaminophen:

Actifed Plus

Anacin (all products)

Benadryl (Plus and Plus Nighttime)

Comtrex (all products)

Dristan (all products except Room Vaporizer)

Drixoral Plus

Excedrin (all products)

Nyquil Nighttime Cold Medicine

Pamprin (all products)

Panadol, Children's and Infant's

Percogesic

Sinutab (all products)

Sominex Pain Relief Formula 1 Tablets

TheraFlu (all products)

Tylenol (all products)

Paracetomal

from:

http://www.mdanderson.org/topics/paincontrol/display.cfm?id=34E2C00E-5D6A-44

A1-8317170F0DAB8D54 & method=displayFull

This article is one of the best articles I have seen on Glutathione. It

talks about the numerous things that Glutathione is involved with. It also

talks about Acetaminophen & Glutathione. The article also does not talk

with too many " big words " & things that are really hard to understand.

http://www.thorne.com/altmedrev/fulltext/glut.html

Here are a couple quotes from the above article about Acetaminophen (with a

few notes of mine):

" Many pharmaceutical products are oxidants capable of depleting GSH [my

note: Glutathione] from the liver, kidneys, heart, and other tissues.29 The

popular over-the-counter drug acetaminophen [my note: active ingredient inÂ

Tylenol] is a potent oxidant [my note: it creates oxidation - free

radicals]. It depletes GSH from the cells of the liver [my note: which is

where GSH is made & stored], and by so doing renders the liver more

vulnerable to toxic damage. "

" The consequences of sustained GSH depletion are grim. As cellular GSH is

depleted, first individual cells die in those areas most affected [my note:

we have lots of cell death already going on in DS]. Then zones of tissue

damage begin to appear; those tissues with the highest content of

polyunsaturated lipids and/or the most meager antioxidant defenses are

generally the most vulnerable. Localized free-radical damage [my note:

which is an issue in DS, due to low antioxidant levels & high oxidative

stress] spreads across the tissue in an ever-widening, self-propagating

wave. If this spreading wave of tissue degeneration is to be halted, the

antioxidant defenses must be augmented. "

This is an interesting abstract that says that Resveratrol helps against

the toxicity done by Acetaminophen. Resveratrol is a potent antioxidant -

it is from the skin of grapes. If you have to give Tylenol, it sounds like

it'd be very beneficial to give Resveratrol also:

Protective effects of resveratrol against acetaminophen-induced toxicity in

mice.

Marmara University, School of Pharmacy, Departments of Pharmacology,

Istanbul, Turkey.

This investigation elucidates the role of free radicals in acetaminophen

(AA)-induced toxicity and the possible protection by resveratrol (RVT).

BALB-c mice were injected with a single dose of 900mg/kg AA to induce

toxicity, while RVT administred in a dose of 30mg/kg i.p. following AA.

Mice were sacrificed 4h after AA injection to determine serum ALT, AST and

tumor necrosis factor-alpha (TNF-alpha) levels in blood, and glutathione

(GSH), malondialdehyde (MDA) levels, myeloperoxidase (MPO) activity and

collagen contents in liver tissues. Formation of reactive oxygen species in

hepatic tissue samples was monitored by using chemiluminescence (CL)

technique with luminol and lucigenin probe. ALT, AST levels and TNF-alpha

were increased significantly after AA treatment, and reduced with RVT. AA

caused a significant decrease in GSH levels while MDA levels and MPO

activity were increased in liver tissues. On the other hand when RVT

administered following AA, depletion of GSH and accumulation of MDA and

neutrophil infiltration were reversed back to control. Furthermore

increased luminol and lucigenin CL levels in the AA group reduced by RVT

treatment. Our results implicate that AA causes oxidative damage in hepatic

tissues and RVT, by its potent antioxidant effects protects the liver

tissue. These data suggest that RVT may be of therapeutic use in preventing

hepatic oxidative injury due to AA toxicity.

-----------------------

Someone asked for some articles/abstracts to take to their doctor to show

him the importance of Glutathione in Down Syndrome & the issue of

Acetaminophen. So, I figured it'd be good to compile a bunch of abstracts &

articles that show the AcetaminophenÂ issue, the pro-oxidant state already

present in an individual with Down Syndrome & their deficiency of

Glutathione. Below is that info:

Abstracts showing elevated oxidative stress, pro-oxidant state &

glutathione deficiency in DS -

Multiple evidence for an early age pro-oxidant state in Down Syndrome

patients.

Department of Physiology, University of Valencia, E-46010, Valencia, Spain.

Oxidative stress has been associated with Down syndrome (DS) and with its

major phenotypic features, such as early ageing. In order to evaluate an in

vivo pro-oxidant state, the following analytes were measured in a group of

DS patients aged 2 months to 57 years: (a) leukocyte

8-hydroxy-2'-deoxyguanosine (8-OHdG); ( blood glutathione; © plasma

levels of: glyoxal (Glx) and methylglyoxal (MGlx); some antioxidants (uric

acid, UA, ascorbic acid, AA and Vitamin E), and xanthine oxidase (XO)

activity. A significant 1.5-fold increase in 8-OHdG levels was observed in

28 DS patients vs. 63 controls, with a sharper increase in DS patients aged

up to 30 years. The GSSG:GSHx100 ratio was significantly higher in young DS

patients (< 15 years), in contrast to DS patients aged >/=15 years that

showed a significant decrease in the GSSG:GSHx100 ratio ratio vs. controls

of the respective age groups. Plasma Glx levels were significantly higher

in young DS patients, whereas no significant difference was detected in DS

patients aged >/=15 years. Unlike Glx, the plasma levels of MGlx were found

to be significantly lower in DS patients vs. controls. A significant

increase was observed in plasma levels of UA in DS patients that could be

related to an increased plasma XO activity in DS patients. The plasma

concentrations of AA were also increased in young (< 15 years) DS patients,

but not in older patients vs. controls in the same age range. The levels of

Vitamin E in DS patients did not differ from the values determined in

control donors. The evidence for a multiple pro-oxidant state in young DS

patients supports the role of oxidative stress in DS phenotype, with

relevant distinctions according to patients' ages.

Glutathione metabolism and antioxidant enzymes in children with Down syndrome.

Laboratory of Biochemistry, Molecular Medicine Unit, Children's Hospital

and Research Institute Bambino Gesu, Rome, Italy.

Oxidative stress has been proposed as a pathogenic mechanism of

atherosclerosis, cell aging, and neurologic disorders in Down syndrome.

This study demonstrates a systemic decrease of all glutathione forms,

including glutathionyl-hemoglobin, in the blood of children with Down

syndrome. Furthermore, we obtained a disequilibrium, in vivo, between the

antioxidant enzyme activities.

Diminished glutathione levels cause spontaneous and mitochondria-mediated

cell death in neurons from trisomy 16 mice: a model of Down's syndrome.

Institut fur Physiologie der Charite, Humboldt Universitat Berlin, Germany.

sebastian.schuchmann@...

It has been suggested that the increased neuronal death in cultures from

trisomy 16 (Ts16) mice, a model of Down's syndrome, might result from a

diminished concentration of reduced glutathione (GSH). In this study we

used microfluorometric techniques to investigate the effect of GSH levels

on neuronal survival in diploid and Ts16 cultures. Addition of the GSH

precursors cysteine and cystine and the antioxidant tocopherol to the

culture medium increased the GSH concentration up to 126.0% in diploid and

up to 111.9% in Ts16 neurons. Moreover, we observed a reduced spontaneous

neuronal death rate in diploid and Ts16 cultures. Following the application

of 50-100 microM glutamate to culture medium, we found a GSH increase in

the presence of cysteine, cystine, tocopherol, and cyclosporin A, an

inhibitor of mitochondrial permeability transition (diploid, 105.8-110.8%;

Ts16, 83.1-96.3%). However, only tocopherol and cyclosporin A had a

protective effect on glutamate-induced neuronal death. The results suggest

that reduced GSH levels affect the increase of a spontaneous and a

mitochondria-mediated, cyclosporin A-sensitive type of neuronal cell death.

Therefore, elevating intracellular GSH concentration may have

neuroprotective effects in Down's syndrome and Alzheimer's disease.

Glutathione levels and nerve cell loss in hippocampal cultures from trisomy

16 mouse--a model of Down syndrome.

Department of Neurophysiology, Humboldt University, Berlin, Germany.

The tripeptide glutathione (reduced state, GSH) is an important

intracellular free radical scavenger protecting cells against oxidative

stress. The trisomy 16 mouse is a model of the human trisomy 21 (Down

syndrome). Here we demonstrate that cultured hippocampal neurons from

trisomy 16 mouse exhibit decreased GSH levels and augmented cell death when

compared to diploid cells. Additional lowering of GSH levels led to

enhanced cell death in trisomy 16 cells. Based on these results we suggest

that a GSH level which is decreased under a specific threshold by increased

consumption, reduced synthesis or lack in precursor contributes to cell

loss and neurodegeneration in Down syndrome.

Evaluation of superoxide dismutase and glutathione peroxidase enzymes and

their cofactors in Egyptian children with Down's syndrome.

Department of Human Genetics, National Research Centre, Cairo, Egypt.

The present work investigated the activity of Cu/Zn superoxide dismutase

enzyme (SOD) in red blood cells and glutathione peroxidase enzyme (GPx) in

whole blood by spectrophotometric methods. Plasma levels of the cofactors

copper and zinc and whole-blood selenium were evaluated using atomic

absorption spectrophotometer. The study included a population of 18 Down's

syndrome (DS) patients with complete trisomy 21 (group 1), translocations

(group 2), and mosaicism (group 3), and their 15 matched controls. The

purpose of this work was to study the gene dosage effect of SOD and its

consequence on GPx enzyme and the various cofactors, and to find out

correlations with developmental fields. Our results showed that in the

population with complete trisomy 21 and translocations, SOD and GPx

activities were increased, whereas in cases with mosaicism, the enzymes

activities were within normal limits. Plasma copper concentrations were

increased, whereas whole-blood selenium concentrations were significantly

decreased in the three DS groups. Plasma zinc levels were within normal in

all patients. We concluded that changes in trace elements and enzyme

activities were not related to age or sex. Also, there was no correlation

between the enzyme levels and the developmental activities. Our results are

useful tools for identifying nutritional status and guiding antioxidant

intervention.

Correlations of glutathione peroxidase activity with memory impairment in

adults with Down syndrome.

Department of Neuroscience, University of California, San Diego, USA.

BACKGROUND: Down syndrome (DS) is a genetic disorder (trisomy 21 in 96% of

cases), associated with an excess of a key enzyme involved with free

radical metabolism (FRM), superoxide dismutase-1 (SOD-1), that is encoded

by a gene on chromosome 21. Consequently, SOD-1 activity is elevated in DS,

which also occurs in conditions of oxidative stress, and is associated with

a compensatory increase in glutathione peroxidase activity (GSHPx).

METHODS: This study examined the relationship of memory function with

erythrocyte SOD-1, GSHPx and catalase (CAT) activity in 22-51 year old

adults with DS. RESULTS: Mean erythrocyte SOD-1 (p < .02) and GSHPx (p <

..01), but not CAT (p = .76), activities were significantly greater in the

DS group than the controls. In the DS group, erythrocyte GSHPx, but not

SOD-1 or CAT activities, was significantly correlated with memory function

(r = .625, p < .025, df = 13 for savings score, r = .631, p < .01, df = 14

for intrusion errors) but not with intelligence quotients. CONCLUSIONS:

These observations suggest a possible relationship between altered FRM with

memory deficits among adults with DS within the age-range in that an

age-related increase in the prevalence for Alzheimer's neuropathology is

known to be robust before reaching a plateau of 100%.