Peripheral glutathione and elimination of organic mercury - quantiative reasoning

[Guest guest]

Dear ,

I don't play gin rummy with medline citations. I read the papers and as a

rule find few of them that have much useful in the way of interpretable data

- which is no different than when I was reading chemistry and chemical

engineering papers. When I find the useful data I indeed use it through some

form of quantitative reasoning which usually involves numbers and equations.

If you want me to respond positively to what you have to post about

glutathione you will have to present something I consider reasoning, which

includes at a minimum some quantitative discussions of mercury disposition

based on rates and equilibria with due consideration for the body's many

compartments, and the observed facts of what happens with mercury intoxicated

people and animals. Some of these facts are in journal papers, some can be

easily obtained by talking to people.

My quantitative reasoning to dismiss arguments that glutathione status at the

time of vaccination (thimerosal exposure) controls autism is as follows:

The liver is one compartment of the body, and is the one where all the

organic mercury that gets eliminated goes for excretion. There is no doubt

much mass transfer resistance involved so that as the liver speeds up

excretion of the mercury it has, total body clearance speeds up less. Thus

estimates of the liver clearance rate are upper bounds to the body clearance

rate.

While there is no clear reason to assume liver glutathione levels control the

rate of organomercury clearance and there IS evidence to the contrary (lipoic

acid increases liver glutathione dramatically yet slows organic mercury

clearance even as it accellerates inorganic mercury clearance - yet both are

excreted as glutathione conjugates) it is simple to work from the assumption

that organic mercury clearance is first order in glutathione and first order

in organic mercury. This would lead to apparent first order kinetics (as

observed) in organomercury for each individual if every person has their own

stable glutathione level.

So do we know anything about liver glutathione levels? Actually, we do. We

know how much variation there is in glutathione conjugation of assorted

xenobiotics due to the fact this is a common laboratory test, as run e. g.

by Great Smokies Labs. We also know what blood glutathione levels are, and

most blood glutathione is believed to be provided by the liver.

The normal range for blood glutathione is almost exactly a factor of 2 from

the upper to lower limit. The normal range for glutathione conjugation in

the liver is slightly less than a factor of two. Normal ranges are from the

geometric mean +1.96 sigma to -1.96 sigma in terms of the population if

whatever is being measured is log normal which we shall assume here for the

sake of argument.

et al. have directly determined the rate constants for excretion of

methylmercury in man and for its conversion to inorganic mercury. Even

though this is for adults and for methyl rather than ethyl mercury it is the

best data available so I will use it. If you propose a rational plausibility

argument for other numbers I will consider them.

The total rate of conversion of organic to inorganic mercury per day (in

fractional terms) is 0.0101. The rate of excretion into feces is 0.00475.

These are averages. So we know that the change in organic mercury with time

is

dM/dt = - (0.0101 + 0.00475) X M

where M is the amount of organic mercury present at a given time t following

a single exposure at time t=0.

M = Mo exp -[ (0.0101 + 0.00475) X t ]

Where Mo is the amount at time zero. These equations can be strung together

for the actual case of serial exposure via vaccination but the results below

come out the same either way so I will keep it simple.

The half life for decrease in blood content of organic mercury is 44 days.

This is to say that the organic mercury goes away much faster than it is

excreted - or that much of it is converted to inorganic mercury in the body.

In fact, the amount of organic mercury excreted before conversion is

0.00475

------------------ = 0.320

(0.0101 + 0.00475)

while the amount converted before excretion is

0.0101

------------------ = 0.680

(0.0101 + 0.00475)

The amount that is converted before excretion is the relevant quantity,

since that is where the brain mercury comes from. The organic mercury

converted to inorganic form in the brain stays there and is the source of

toxicity.

The 0.00475 is the average rate of organic mercury excretion as a glutathione

conjugate calculated from geometric means which are what one ought to use

with log-normally distributed quantities.

It is asserted that increasing or decreasing liver glutathione will

significantly affect mercury levels, which means it must change excretion

enough to change the amount of organic mercury converted to inorganic form in

the body significantly.

That factor of 2 from lower normal limit to upper normal limit gives a

multiplier of 1.1934 per sigma unit in the distribution. About 1 person in

1000 is 3 sigma below the mean and this serves as a reasonable estimate for

where problems should start given the incidence of autism. BTW, if people

have too low of glutathione in their liver they die quite promptly so there

is no real argument to be made that some people get sick and use up all their

glutathione...

Average person's excretion rate: 0.00475

3 sigma low person if first order in glutathione: (1.1934) ^ - 3 * 0/00475 =

0.00279

Fraction of organic mercury converted in the body to inorganic form by a 3

sigma low person:

0.0101

------------------ = 0.783

(0.0101 + 0.00279)

Increased conversion in the body due to low liver gutathione reducing

excretion rate:

0.783 / 0.680 = 1.152

or a 15% increase. 15% isn't going to make the difference between being

normal and autistic.

I have done you the courtesy of explaining in detail why I do not consider

the " low gutathione " hypothesis plausible. As you know I devote a large

amount of time to this list. I do so because it is full of people who,

despite substantial differences of opinion, earnestly seek truth using

whatever means of reasoning they are skilled in so that they can help people

who really do need help. If you do not wish to consider the " low

glutathione " hypothesis for causation of autism disproven at this point,

please do not phrase further postings on the list as if they were argument

directed at me unless they contain the type of quantitative reasoning I have

presented above. It is way too time consuming to do someone else's homework

for them, and way too disruptive of debate on the list to not address

apparently well phrased but subtly flawed arguments that are repeatedly

posted in minor variations.

Andy Cutler