Re: Rich Van Konynen's analysis of my medical history and genetics

[Guest guest]

Opps, Resending with medication and supplement list attached:

> Hi Rich, thanks for reviewing my case. Hi Dr. Amy, for your review and

> commnet regarding step 1. Hi , for your weekend reading (I hope).

> My comments and corrections are inserted into Rich's discussion as

> follows:

> rvankonynen wrote:

>

>> Hi, Joanee.

>>

>> I've studied your Detoxigenomic Profile, together with the other

>> information you sent me. I'm going to comment on all of it here, as

>> we've agreed. Thank you for allowing me to do this, because I think

>> that studying what you have gone through might be helpful to others

>> on the list as well.

>> As I wrote you earlier, I think you have a very interesting case. In

>> a nutshell, my hypothesis for your case is that the things that have

>> occurred in your health history have resulted to a large degree from

>> the genetic make-up you inherited. These genetics interacted with

>> your particular life choices as well as some things that occurred in

>> your life that you did not choose. Perhaps this can be said of

>> everyone, but in your case the genetics seem to have played a very

>> important role. This may seem to be true at least partly because you

>> have had so many important parts of your genetics characterized,

>> giving me an unusually large amount of data to work with. The result

>> of this interaction was that your glutathione level dropped, plunging

>> you into a vicious circle that you have not been able to climb back

>> out of. This led to a host of problems with toxins and pathogens,

>> because both your immune system and your detox system have been

>> unable to function normally.

>>

>> So let me start with the genetics with which you were born. We now

>> know that you have some important genetic variations in your detox

>> system, your HLA system, your methylation cycle, and your blood

>> coagulation system, though we don't yet have the Yasko panel results

>> on your methylation cycle, only some brief Labcorp results.

>>

>> In your Phase I detox system, you have SNPs in both CYP1A1 and

>> CYP1B1, and both are upregulators. In Phase II, you have COMT V158M

>> (+/-), which is a heterozygous downregulator, a null in your GSTM1,

>> and a GSTP1 I104V (+/-), which are effectively downregulators. You

>> also have an SOD2 A16V (+/-), which is a downregulator.

>>

>> Considering first the CYP1A1 and the CYP1B1, these enzymes are

>> particularly important for processing polycyclic aromatic

>> hydrocarbons (PAHs), which are toxic components found in all types of

>> smoke produced by the incomplete combustion of organic materials,

>> including cigarette smoke, engine exhaust, and barbecuing.

>> Charbroiled foods also contain PAHs. These two enzymes are also

>> important for the metabolism of the estrogens. They convert

>> estradiol into catechol estradiols, for example. Note that all these

>> reactions would occur more rapidly than normal in your body because

>> of these SNPs, so that the intermediate species would tend to build

>> up to higher levels, and they are more toxic than the original

>> substances.

>>

>> Normally, the intermediates produced by Phase I are conjugated by

>> Phase II pathways and are then eliminated from the body. However, in

>> your case you have some SNPs in Phase II enzymes that will hinder

>> this process and thus allow the toxic intermediates to build up even

>> higher. Consider first the downregulation of COMT (catechol-O-

>> methyltransferase). Normally COMT would add methyl groups from SAMe

>> to the catechol estrogens to detox them. However, in your case, this

>> process is slower than normal, so the catechol estrogens would be

>> allowed to build up. They are then able to react with oxygen to form

>> semiquinones and quinones. These reactions produce superoxide ions,

>> which are oxidizing free radicals. Going a step further, normally

>> semiquinones and quinones are conjugated with glutathione to detox

>> them, but in your case you have no M1 type glutathione transferase,

>> and you have a SNP in your P1 type. These will result in slower

>> conjugation of these substances to glutathione, allowing the quinones

>> and semiquinones to build up. They oscillate back and forth between

>> quinone and semiquinone, and these reactions produce more oxidizing

>> free radicals. In addition, your SNP in SOD2, which is the

>> mitochondrial (manganese-containing) form of superoxide dismutase,

>> will mean that superoxide ions will tend to build up to higher

>> concentrations.

>>

>> The results of this combination of SNPs were that you were born with

>> inherent difficulties in dealing with smoke of all sorts and with

>> metabolizing your own estrogens, and that you had a tendency to

>> develop oxidative stress, which would have placed higher than usual

>> demands on your glutathione.

>>

>> Moving now to your HLA system, you have a set of HLA alleles that Dr.

>> Shoemaker interprets as 13-3-52A and 15-6-51, which made you

>> mold-susceptible and post-Lyme susceptible, respectively. This meant

>> that you were born with an immune system that was unable to recognize

>> and eliminate mold toxins and Borrelia toxins and meant that you

>> would have problems if exposed to these toxins, because they would be

>> able to build up in your body.

>>

>> Considering next the methylation-cycle-related enzymes, we don't have

>> the complete results on these yet, but we do know that you were born

>> with an MTHFR A1298C (+/+). This means that at a minimum, you would

>> have had a tendency toward low levels of _tetrahydrobiopterin _

>> (BH4), which would have hindered your ability to synthesize serotonin

>> and dopamine.

>

> /(I found this information on Yasko's DVD, she mentions that persons

> with MTHFR A1298C (+/+)

> need to supplement BH4. Dr. Gordon wants to wait for Yasko's test

> results to confirm this as BH4 is very expensive. This also brings up

> the question of just how much supplementation to do at this point in

> time. Yasko has a very long list of " step 1 " supplements and strongly

> advises patients to spend sufficient time on step one prior to adding

> all the elements of " step 2 " which is methylation. Of course, she is

> used to treating children. I have already incorporated many of the

> " step 2 and 3 " supplements over the course of time, like glutathione

> and I am not sure how to proceed. I will attach a list of what I am

> taking and would apprecriate imput from you and the group on what to

> modify.)

> /

>

> This would have been opposed by your SNP in COMT, which would have

> slowed the metabolism of these neurotransmitters by methylation. I

> don't know how the balance of these two effects would have worked out,

> but I suspect that you would have experienced irregularities in your

> neurotransmitter metabolism in one direction or the other. The low

> BH4 would have impacted your nitric oxide synthase as well as your

> urea cycle and its ability to deal with ammonia.

>

> /(Dr. Yasko's intuition is that most CFSers have CBS upregulation and

> therefore have to deal with ammonia issues first. Dr. Gordon had a

> plasma ammonia level tsted for me last week and it was normal. She

> notes that blood testing should provide results related to urine

> testing, (blood testing is valid), so I am not sure if I need to start

> with dealing with the ammonia issues related to upregulated CBS or

> not. Do you have an idea?)

> /

> It would also have provided one more source of oxidizing free radicals

> and correspondingly one more

> demand on glutathione to deal with them. Another straw on the camel's

> back.

>

> Finally, your blood coagulation cascade had some hereditary issues as

> well, including elevated Protein C activity, elevated APC resistance

> factor II activity, and elevated PAI-1 activity. This would have made

> you susceptible to immune system activation of coagulation (ISAC).

>

> We don't know what SNPs you might have been born with in enzymes

> involving your immune system, but judging from the various immune

> issues you had subsequently, there may be some important ones there

> as well.

>

> So now that we have set the stage with some understanding of the

> genetic makeup with which you began your life, let's see how things

> played out. You reported that you were born in New York City in

> 1944 and had an early history of sinusitis and allergy. This suggests

> immune system issues from the beginning, and these problems may also

> have been partly a result of air pollution in the city and

> the inability of your detox system to deal properly with the toxins in

> smokes.

>

> You reported that you were perpetually overweight and cold. This

> suggests a hypothyroid condition, perhaps from birth, and sure enough,

> later on in your life, in your 30s, you were diagnosed with

> Hashimoto's autoimmune thyroiditis and began thyroid hormone replacement.

>

> In 1965 you had surgery to remove a fibroid from your breast, and in

> 1970 you had a dermoid cyst removed from your left ovary. I think it's

> possible that these were produced because of your detox

> system's inability to process the estrogens normally, since both the

> ovaries and the breast tissue are subject to effects of the estrogens

> and their metabolites.

>

> You began smoking cigarettes, and did so until the late 70s or early

> 80s. In view of your detox SNPs, this would have raised your toxic

> load considerably. I suspect that you would have had some respiratory

> problems from this, as a minimum.

> /(I did have allergies, and was always on a strict diet to control

> weight, but didn't really get sick. I did have bouts of depression.)/

>

> You moved to Los Angeles and began a demanding career as a partner in

> an advertising and design firm. You married, and you had a son in

> 1981. In the early 80s, you were diagnosed with degenerative

> disk disease, having extensive pain in your neck and shoulders.

> Perhaps this resulted partly from your overweight condition (perhaps

> at least partly secondary to hypothyroidism) and your sedentary and

> stressful job. I don't know how much exercise you were getting at this

> point.

> _

> _/(Actually I was running 3 miles a day and in great shape prior to

> the pregnancy. I was not over weight but had to work very hard to stay

> that way with diet and excercise.)//

> /

> In 1986 you had surgery for condyloma acuminatum of the vulva and

> removal of another dermoid cyst, this one from the right ovary. Again,

> the dermoid cyst may have resulted from the problems in

> metabolism of the estrogens stemming from your detox SNPs. Condyloma

> acuminatum sometimes resolves by itself in immunocompetent

> individuals, so this might have been an additional clue that your

> immune system was not functioning up to par.

>

> You then went through a very stressful period. You had a small child,

> a difficult relationship with your husband, and a stressful executive

> position in advertising. You filed for a divorce, underwent the

> surgery mentioned above, and had a business setback. I don't know

> whether this setback caused you to have to drop down to a job level

> where you did more hands-on work with art materials, including

> volatile solvents, but if so, this could have raised your body burdens

> of toxins, because of your detox system deficits.

>

> /(This is interesting because I guess no-one tests for our strengths.

> I come from a family that encourages positive thinking. I always rally

> after a setback. I founded the first health care division in an

> international advertising agency, brought in $12 million in billings

> annually after the business setback. I am bright, have talent, am good

> with managing people, have alot of intellectual curiousity; however I

> think the building that I worked in had some toxins.)

> /

> You rented out your bedroom and slept in the living room under a moldy

> air conditioner. The result was bronchitis for 18 months, which did

> not respond to antibiotics. Your immune system was definitely not

> functioning well at this point. You also had severe inflammation and

> pain in your hips, neck and shoulders. As you mentioned, your mold

> sensitivity was probably the cause of this, but no doubt the combined

> stress of the above life events played a role, and perhaps toxin

> exposures as well. It's as though all your

> gentetic deficits ganged up on you at this point and interacted with

> each other, multiplying the misery. You were diagnosed with

> fibromyalgia and given injections with steroids.

>

> I suspect that during this period your glutathione level started to

> drop under the influence of the combined stressors in combination with

> your detox, SOD2, and HLA genetic makeup, as described above,

> and that at a certain point, the glutathione level became low enough

> to interact with your SNPed methylation cycle enzymes and plunge you

> into a vicious circle involving your sulfur metabolism, which you have

> not been able to come back out of so far. I don't know the exact time

> when this occurred, but it appears to have been after 1985 but before

> 1988.

>

> You began to have prolonged episodes of fatigue and gastrointestinal

> distress, which was diagnosed as irritable bowel syndrome and reflux

> in 1988. You continued to suffer recurrent bronchitis and chronic

> low-grade enteritis with intermittent diarrhea, which drugs did not

> help. I think these symptoms and conditions resulted from glutathione

> depletion and the block in the methylation/folate/biopterin

> metabolism. I suspect that a lot of the gut problems, in particular,

> resulted from disruption of your serotonin metabolism, which depends

> on biopterin and methylation.

>

> In 1989 you changed positions, moved to Marin County, and began taking

> Sinequan for your G.I. tract and Prozac for depression. By March of

> 1990 you had become almost totally bedridden. You were

> found to have an active Epstein--Barr viral infection as well as

> antibodies to HHV-6, CMV and Candida as well as a number of allergies.

> You were diagnosed with CFIDS and found to have neuro-

> cognitive problems. You stopped working and went on disability,

> continuing to suffer from recurrent upper respiratory infection and

> inflammation. At this point it is clear that your glutathione was

> seriously depleted, since it is not possible to have an active

> Epstein--Barr infection unless glutathione is depleted. I suspect that

> the immune system's attempt to respond to the infection in the

> presence of your inherited blood coagulation abnormalities would

> likely have triggered immune system activation of coagulation at this

> point, also, though it was not tested for and detected until

> December of 2001.

>

> You were found to have a variety of problems with your immune system,

> and were given gamma globulin injections (/the gamma is intravenous

> /) and Zovirax. I suspect that the immune dysfunctions resulted from

> the depletion of glutathione as well as the associated block in your

> folate metabolism that prevented the synthesis of new RNA and DNA at

> fast enough rates to permit lymphocyte proliferation.

>

> In July of 1996 you started Phentermine for weight loss, which helped

> initially, but not over the longer term. (/It helped for about 5

> years, then the weight came back)./

>

> You were diagnosed with neurally mediated hypotension and also

> developed blood pooling in your legs and varicose veins. This may have

> resulted from your coagulation problem. You didn't mention

> diabetes insipidus related symptoms (high daily urine volume, constant

> thirst, high fluids consumption), so I don't know if a low total blood

> plasma volume was involved. /(No diabetes yet.)

>

> /Since you also didn't report having impedance cardiography or

> echocardiography run, I

> don't know whether you have low cardiac output (heart failure), or

> whether a viral cardiomyopathy or diastolic dysfunction might have

> developed. Both would have been possibilities, since you did have

> an active EBV infection, and I'm inferring that you did have

> glutathione depletion. /

> (I had a heart scan, and was told I had a small amount of calicum in

> the artery leading to my heart, but it would not build up to anything

> significant in my lifetime. Cardiac tissue looked excellent.)/

>

> You had more issues with Hashimoto's thyroiditis and switched to a

> natural, porcine-based thyroid hormone supplement. I suspect that the

> exacerbation of Hashimoto's was a result of glutathione

> depletion in the thyroid, allowing a rise of the endogenously produced

> hydrogen peroxide within the thyroid cells and reaction with

> thyroglobulin, leading to an elevated autoimmune response.

>

> Though UV blood irradiation helped temporarily, your immune system was

> unable to control infections by EBV, HHV-6, and mycoplasma over

> extended time periods. Again, I think the immune suppression

> resulted from the glutathione depletion--methylation/folate cycle

> block vicious circle. Sensitivities developed to a variety of molds,

> because of your hereditary HLA makeup./

>

> (Rich, this is far more than a sensitivity. Mold toxins make me very

> ill. It is not the same as having an allergy. Exposure to mold impacts

> me strongly, similar to being hit in the head, then thrown into an

> activation of flu like synthoms.) /

>

> You developed multiple chemical sensitivities after an exposure to

> sulfites. This was likely due to your detox system SNPs, but we don't

> yet know what your CBS and SUOX SNP picture looks like, so

> it's possible that there are issues there as well.

>

> You tested high for a variety of toxins that are normally taken out by

> glutathione. I suspect these buildups occurred because your

> glutathione was depleted, held down by the vicious circle involving

> the methylation cycle/folate metabolism/biopterin cycle.

>

> Your hereditary coagulation problem was detected, and treatment with

> nattokinase was begun.

>

> In the winter, the elevated mold counts exacerbate your viral

> infections. You were recently diagnosed with sackie B viral

> infection. I think that until your vicious circle is broken and the

> glutathione level and folate metabolism are restored, you will

> continue to have a suppressed cell-mediated immune response, and will

> continue to be subject to viral, intracellular bacterial and fungal

> infections.

>

> /(Rich, I have been on glutathione IV's since the mid to late 1990's.

> I think your theory about gluatathione is correct, however in my case,

> it's not sufficient. I have so many defects in my genes that I'm not

> sure my body can utilize all the benefits of glutathione replacement,

> because other things are missing as well.)

> /

> In 2003 you had an auto accident and sustained a head injury, which

> slowed your cognition. Provigil and Namenda have been helpful.

>

> After the auto accident you also had a fall, which caused a variety of

> additional problems with joints and connective tissue, involving a lot

> of chronic pain.

>

> You got a positive Lyme diagnosis in 2005, with antibiotics added for

> that. Of course, this would also have given you more problems with

> biotoxins, in view of your HLA genetics.

>

> A trip to San Diego in May 2006 resulted in major fatigue, weakness,

> inflammation and stiffness. You are currently at a low energy status,

> and I suspect that at the moment, you are trapped in the

> vicious circle I have described.

>

> Well, Joanee, that's my interpretation of what has gone on in your

> health history. I do think you are stuck in the

> glutathione--methylation--folate--biopterin vicious circle. I think

> the way out is to follow Dr. Yasko's program. I see that you have

> joined the autismanswer forum, and that should be helpful. I think you

> have also ordered the Yasko genetic variations panel, and it will be

> interesting, and I believe helpful, to see the results. You might also

> consider getting a red blood cell total glutathione test run by

> Immunosciences Lab, just to check on the glutathione level before you

> get very far into the treatment program. Then you will be able to

> compare and have a measure of the degree of improvement later on.

> /( I think Immunosciences no longer takes Medicare, is ther another

> lab doing this?)

> /

> I hope this is helpful.

> /(Thanks Rich, what would really help at this point is a review of

> what supplementation to do at this point to get me out of bed. I am

> attaching a list of what I am taking for comments from everyone

> familiar with the Yasko program, especially from Dr. Amy!).

> /

> Let me know what your thoughts are on it, especially if I said things

> that you know are not correct. Also, feel free to share this with

> whomever you would like.

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

>

[Guest guest]

Hi, Joanee.

The lists won't accept attachments. You could paste it in your

post, though.

Rich

>

> Opps, Resending with medication and supplement list attached:

>

[Guest guest]

I have pulled just one paragraph from Rich V.'s comments out of the entire

email. I have questions, but I will start with just one. (It is of interest

that Joannie has been on glutathione without improving, but I will leave

that to her and Rich to debate.)

Here is my paragraph/question.

" You got a positive Lyme diagnosis in 2005, with antibiotics added for

that. Of course, this would also have given you more problems with

biotoxins, in view of your HLA genetics. "

I have Shoemaker's genetic tests indicating I cannot deal with biotoxins

either. However, I have improved hugely on antibiotics. I don't have more

problems, I have far less.

I do, however, relapse as predicted by Shoemaker in cases like my genotype.

So the question then is, am I relapsing because my environment continues to

expose me to neurotoxins such as mold and ongoing borrelia infection? If it

is ongoing borrelia infection why not continue to take ongoing low dose,

appropriate antibiotics?

I cannot imagine my life without Zithromax. Has it cured me? No. Has it

given me some level of life back. YES.

I still want to see a nice simple list of what Amy Yasko recomments as

treatment - not all her tests. I want to save my money for a trip to Venice

and Nairobi not massive tests. Hey, when she gets funding for a research

study I will sign up.

a Carnes

[Guest guest]

>>>>>I still want to see a nice simple list of what Amy Yasko recomments as

treatment - not all her tests.<<<<

That seems reasonable, since we've been able to know that from other

Specialists/Specialties we discuss here.

The *specific* symptoms/improvements would be good too.

>>>I want to save my money for a trip to Venice

and Nairobi not massive tests.<<<<

Plus most CFS patients, especially long-term, haven't a chance in Hades of

getting them.

Does anyone here have a financial interest/gain from these tests/protcols? Just

asking, because we always have on this list.

>>> Hey, when she gets funding for a research

study I will sign up.

a Carne<<<<

That would make things clearer too!

>

> I have pulled just one paragraph from Rich V.'s comments out of the entire

> email. I have questions, but I will start with just one. (It is of interest

> that Joannie has been on glutathione without improving, but I will leave

> that to her and Rich to debate.)

>

>

>

> Here is my paragraph/question.

>

>

>

> " You got a positive Lyme diagnosis in 2005, with antibiotics added for

> that. Of course, this would also have given you more problems with

> biotoxins, in view of your HLA genetics. "

>

>

>

> I have Shoemaker's genetic tests indicating I cannot deal with biotoxins

> either. However, I have improved hugely on antibiotics. I don't have more

> problems, I have far less.

>

>

>

> I do, however, relapse as predicted by Shoemaker in cases like my genotype.

> So the question then is, am I relapsing because my environment continues to

> expose me to neurotoxins such as mold and ongoing borrelia infection? If it

> is ongoing borrelia infection why not continue to take ongoing low dose,

> appropriate antibiotics?

>

>

>

> I cannot imagine my life without Zithromax. Has it cured me? No. Has it

> given me some level of life back. YES.

>

>

>

> I still want to see a nice simple list of what Amy Yasko recomments as

> treatment - not all her tests. I want to save my money for a trip to Venice

> and Nairobi not massive tests. Hey, when she gets funding for a research

> study I will sign up.

>

>

>

> a Carnes

>

>

>

>

[Guest guest]

a, gluthione has helped, but not enough. I suspect that when I find

the other blocks in the methylation process, and supplent for them, the

glutathione will work even better. I find it helps clear reactions, Joanee

a Carnes wrote:

>I have pulled just one paragraph from Rich V.'s comments out of the entire

>email. I have questions, but I will start with just one. (It is of interest

>that Joannie has been on glutathione without improving, but I will leave

>that to her and Rich to debate.)

>

>

>

>Here is my paragraph/question.

>

>

>

> " You got a positive Lyme diagnosis in 2005, with antibiotics added for

>that. Of course, this would also have given you more problems with

>biotoxins, in view of your HLA genetics. "

>

>

>

>I have Shoemaker's genetic tests indicating I cannot deal with biotoxins

>either. However, I have improved hugely on antibiotics. I don't have more

>problems, I have far less.

>

>

>

>I do, however, relapse as predicted by Shoemaker in cases like my genotype.

>So the question then is, am I relapsing because my environment continues to

>expose me to neurotoxins such as mold and ongoing borrelia infection? If it

>is ongoing borrelia infection why not continue to take ongoing low dose,

>appropriate antibiotics?

>

>

>

>I cannot imagine my life without Zithromax. Has it cured me? No. Has it

>given me some level of life back. YES.

>

>

>

>I still want to see a nice simple list of what Amy Yasko recomments as

>treatment - not all her tests. I want to save my money for a trip to Venice

>and Nairobi not massive tests. Hey, when she gets funding for a research

>study I will sign up.

>

>

>

>a Carnes

>

>

>

>

>

>

>

[Guest guest]

a, I think Yasko is brilliant.

You shouldn't have to be on antibiotics the rest of your life.

Something is amiss. And it's not *just* the organism.

Did you have the dreaded combo HLA genes for both mold and lyme?

ly, I am ignoring all of Shoemaker's work. I have never been that

taken with it.

I think Yasko's work is much more pertinent.

>

> I have pulled just one paragraph from Rich V.'s comments out of the

entire

> email. I have questions, but I will start with just one. (It is of

interest

> that Joannie has been on glutathione without improving, but I will leave

> that to her and Rich to debate.)

>

>

>

> Here is my paragraph/question.

>

>

>

> " You got a positive Lyme diagnosis in 2005, with antibiotics added for

> that. Of course, this would also have given you more problems with

> biotoxins, in view of your HLA genetics. "

>

>

>

> I have Shoemaker's genetic tests indicating I cannot deal with biotoxins

> either. However, I have improved hugely on antibiotics. I don't have

more

> problems, I have far less.

>

>

>

> I do, however, relapse as predicted by Shoemaker in cases like my

genotype.

> So the question then is, am I relapsing because my environment

continues to

> expose me to neurotoxins such as mold and ongoing borrelia

infection? If it

> is ongoing borrelia infection why not continue to take ongoing low dose,

> appropriate antibiotics?

>

>

>

> I cannot imagine my life without Zithromax. Has it cured me? No. Has it

> given me some level of life back. YES.

>

>

>

> I still want to see a nice simple list of what Amy Yasko recomments as

> treatment - not all her tests. I want to save my money for a trip

to Venice

> and Nairobi not massive tests. Hey, when she gets funding for a research

> study I will sign up.

>

>

>

> a Carnes

>

>

>

>

[Guest guest]

> >

> > I have pulled just one paragraph from Rich V.'s comments out of

the entire

> > email. I have questions, but I will start with just one. (It is

of interest

> > that Joannie has been on glutathione without improving, but I

will leave

> > that to her and Rich to debate.)

> >

> >

> >

> > Here is my paragraph/question.

> >

> >

> >

> > " You got a positive Lyme diagnosis in 2005, with antibiotics

added for

> > that. Of course, this would also have given you more problems

with

> > biotoxins, in view of your HLA genetics. "

> >

> >

> >

> > I have Shoemaker's genetic tests indicating I cannot deal with

biotoxins

> > either. However, I have improved hugely on antibiotics. I don't

have more

> > problems, I have far less.

> >

> >

> >

> > I do, however, relapse as predicted by Shoemaker in cases like my

genotype.

> > So the question then is, am I relapsing because my environment

continues to

> > expose me to neurotoxins such as mold and ongoing borrelia

infection? If it

> > is ongoing borrelia infection why not continue to take ongoing

low dose,

> > appropriate antibiotics?

> >

> >

> >

> > I cannot imagine my life without Zithromax. Has it cured me? No.

Has it

> > given me some level of life back. YES.

> >

> >

> >

> > I still want to see a nice simple list of what Amy Yasko

recomments as

> > treatment - not all her tests. I want to save my money for a

trip to Venice

> > and Nairobi not massive tests. Hey, when she gets funding for a

research

> > study I will sign up.

> >

> >

> >

> > a Carnes

> >

> >

> >

> >

[Guest guest]

Hi, Joanee.

>

> Hi Rich, thanks for reviewing my case.

***You're welcome.

> >Considering next the methylation-cycle-related enzymes, we don't

> >have the complete results on these yet, but we do know that you

were

> >born with an MTHFR A1298C (+/+). This means that at a minimum,

you

> >would have had a tendency toward low levels of

_tetrahydrobiopterin _

> >(BH4), which would have hindered your ability to synthesize

> >serotonin and dopamine.

> >

> /(I found this information on Yasko's DVD, she mentions that

persons

> with MTHFR A1298C (+/+)

> need to supplement BH4. Dr. Gordon wants to wait for Yasko's test

> results to confirm this as BH4 is very expensive. This also brings

up

> the question of just how much supplementation to do at this point

in

> time. Yasko has a very long list of " step 1 " supplements and

strongly

> advises patients to spend sufficient time on step one prior to

adding

> all the elements of " step 2 " which is methylation. Of course, she

is

> used to treating children. I have already incorporated many of

the " step

> 2 and 3 " supplements over the course of time, like glutathione and

I am

> not sure how to proceed. I will attach a list of what I am taking

and

> would apprecriate imput from you and the group on what to modify.)

***I will of course defer to Dr. Yasko's advice on this, but it

would seem to me that going ahead with BH4 would be a good idea. As

I understand it, Dr. Yasko wants to see if you have CBS SNPs before

you start building up the methylation cycle to avoid increasing the

flow into the transsulfuration pathway, but I don't believe that

supplementing BH4 will affect that. On the other hand, it should

give you benefits with your neurotransmitter synthesis, your nitric

oxide synthase function/decrease in generation of oxidizing free

radicals, and improved handling of ammonia by the urea cycle. We

should know a lot more when your methylation SNPs panel comes back.

I don't know if you've ever gotten a urine amino acids test run, but

I would expect that your ratio of phenylalanine to tyrosine would

show up as being high, which would be another indicator of low BH4.

> /(Dr. Yasko's intuition is that most CFSers have CBS upregulation

and

> therefore have to deal with ammonia issues first. Dr. Gordon had a

> plasma ammonia level tsted for me last week and it was normal. She

notes

> that blood testing should provide results related to urine

testing,

> (blood testing is valid), so I am not sure if I need to start with

> dealing with the ammonia issues related to upregulated CBS or not.

Do

> you have an idea?)/

***Quite a few, but not all PWCs have CBS SNPs, based on my short

experience with this so far. If you don't have elevated ammonia (of

course you had to have been eating a fair amount of protein when you

tested for this, or you could be fooled), if you don't have problems

(such as headaches) from sulfur-containing supplements or foods, if

you don't have elevated cystathionine or taurine in a urine amino

acids test, if you don't smell ammonia in your perspiration, and if

you don't generate a lot of foul-smelling gas in your gut when you

eat foods containing a lot of sulfur, then I would guess that you

probably don't have a CBS upregulation. There's nothing like having

the SNP panel results to be sure, though!

> You began smoking cigarettes, and did so until the late 70s or

early

> 80s. In view of your detox SNPs, this would have raised your toxic

load

> considerably. I suspect that you would have had some respiratory

> problems from this, as a minimum.

> /(I did have allergies, and was always on a strict diet to

control

> weight, but didn't really get sick. I did have bouts of

depression.)/

***O.K. I can't imagine that you would have been able to smoke and

not have some problems, given your particular collection of detox

SNPs.

you were diagnosed with degenerative

> disk disease, having extensive pain in your neck and shoulders.

Perhaps

> this resulted partly from your overweight condition (perhaps at

least

> partly secondary to hypothyroidism) and your sedentary and

> stressful job. I don't know how much exercise you were getting at

this

> point.

> _

> _/(Actually I was running 3 miles a day and in great shape prior

to the

> pregnancy. I was not over weight but had to work very hard to stay

that

> way with diet and excercise.)//

***Sorry, I misinterpreted. You wrote me that you were always

overweight, but I guess you must have meant that you were always

overweight as a child. Were you doing exercises to strengthen your

back muscles at the time you were running 3 miles a day, also, or

only running? Also, running puts impact loads on your disks,

especially if your shoes aren't cushioned well, and especially if

you run on a hard surface, such as sidewalk or pavement. Another

factor is diet. The repair of the disks requires collagen

synthesis, which in turn needs protein, vitamin C and zinc. I think

that supplementing glutamine can help, too, because that's the main

substrate for the fibroblasts, the cells that make collagen. So

perhaps some of these factors came into play in the development of

your disk problems.

> You then went through a very stressful period. You had a small

child, a

> difficult relationship with your husband, and a stressful

executive

> position in advertising. You filed for a divorce, underwent the

surgery

> mentioned above, and had a business setback. I don't know whether

this

> setback caused you to have to drop down to a job level where you

did

> more hands-on work with art materials, including volatile

solvents, but

> if so, this could have raised your body burdens of toxins, because

of

> your detox system deficits.

>

> /(This is interesting because I guess no-one tests for our

strengths. I

> come from a family that encourages positive thinking. I always

rally

> after a setback. I founded the first health care division in an

> international advertising agency, brought in $12 million in

billings

> annually after the business setback. I am bright, have talent, am

good

> with managing people, have alot of intellectual curiousity;

however I

> think the building that I worked in had some toxins.)/

***Sorry, I guessed wrong! You mentioned that you suspected that

exposure to art materials had an impact on your developing multiple

chemical sensitivities. I didn't know when that occurred, and I

guessed that it was at this point. Did that occur earlier, or was

it later than this?

> In July of 1996 you started Phentermine for weight loss, which

helped

> initially, but not over the longer term. (/It helped for about 5

years,

> then the weight came back)./

***O.K. I looked into the pharmacology of phentermine, and learned

that it interferes with the reuptake of serotonin and

norepinephrine, and it also increases the release of dopamine. So

it appears that this drug was operating by making up for your low

BH4 status, resulting from your homozygous MTHFR A1298C SNP. I

think that's really interesting. Too bad we didn't know that a long

time ago! I don't know why this drug stopped working. Perhaps your

BH4 status got worse over time, or perhaps the receptors that

phentermine was binding to underwent adaptation or compensation over

time by becoming less abundant. I don't know.

>

> You were diagnosed with neurally mediated hypotension and also

developed

> blood pooling in your legs and varicose veins. This may have

resulted

> from your coagulation problem. You didn't mention

> diabetes insipidus related symptoms (high daily urine volume,

constant

> thirst, high fluids consumption), so I don't know if a low total

blood

> plasma volume was involved. /(No diabetes yet.)/

***O.K. You do realize that I don't mean the more common diabetes

mellitus that is involved with blood sugar and insulin, right? I

mean diabetes insipidus. Do you have any idea how much urine you

produce in 24 hours? The average is 1.5 liters, and if it gets

above about 2.5 liters, one has to consider the possibility of

diabetes insipidus.

>

> Since you also didn't report having impedance cardiography or

> echocardiography run, I

> don't know whether you have low cardiac output (heart failure), or

> whether a viral cardiomyopathy or diastolic dysfunction might have

> developed. Both would have been possibilities, since you did have

> an active EBV infection, and I'm inferring that you did have

glutathione

> depletion.

> /(I had a heart scan, and was told I had a small amount of calicum

in the

> artery leading to my heart, but it would not build up to anything

> significant in my lifetime. Cardiac tissue looked excellent.)/

***I'm not sure what kind of a scan this was. Did it involve a

radioisotope? Was it a CT scan? Or an MRI? These are beneficial

for some purposes, but I don't think they will tell you what your

cardiac output is, or tell you whether you have diastolic

dysfunction.

>

> You had more issues with Hashimoto's thyroiditis and switched to a

> natural, porcine-based thyroid hormone supplement. I suspect that

the

> exacerbation of Hashimoto's was a result of glutathione

> depletion in the thyroid, allowing a rise of the endogenously

produced

> hydrogen peroxide within the thyroid cells and reaction with

> thyroglobulin, leading to an elevated autoimmune response.

>

> Though UV blood irradiation helped temporarily, your immune system

was

> unable to control infections by EBV, HHV-6, and mycoplasma over

extended

> time periods. Again, I think the immune suppression

> resulted from the glutathione depletion--methylation/folate cycle

block

> vicious circle. Sensitivities developed to a variety of molds,

because

> of your hereditary HLA makeup.

>

> /(Rich, this is far more than a sensitivity. Mold toxins make me

very

> ill. It is not the same as having an allergy. Exposure to mold

impacts

> me strongly, similar to being hit in the head, then thrown into an

> activation of flu like synthoms.) /

***Right. I understand that. I get that it's far more serious than

hay fever! has been making that very clear to us on this list

for a long time. I guess I should have referred to it as mold

illness. That's what Dr. Shoemaker calls it in his book " Mold

Warriors. "

I think that until your vicious circle is broken and the

> glutathione level and folate metabolism are restored, you will

continue

> to have a suppressed cell-mediated immune response, and will

continue to

> be subject to viral, intracellular bacterial and fungal infections.

>

> /(Rich, I have been on glutathione IV's since the mid to late

1990's. I

> think your theory about gluatathione is correct, however in my

case,

> it's not sufficient. I have so many defects in my genes that I'm

not

> sure my body can utilize all the benefits of glutathione

replacement,

> because other things are missing as well.)/

***Right, I'm with you. What I meant was that you have to break the

vicious circle to be able to raise glutathione permanently. That's

what Dr. Yasko's program does. Quite a few other PWCs had had this

same experience, and that's what caused me to be so receptive to the

treatments used by DAN! and by Dr. Yasko in autism. This is

supported by the paper in late 2004 by S. Jill et al. That's

been the big breakthrough! Just pumping in more glutathione doesn't

do it if there is a stubborn vicious circle involving the earlier

part of the sulfur metabolism.

You might also consider

> getting a red blood cell total glutathione test run by

Immunosciences

> Lab, just to check on the glutathione level before you get very

far into

> the treatment program. Then you will be able to compare and have a

> measure of the degree of improvement later on.

> /( I think Immunosciences no longer takes Medicare, is ther

another lab

> doing this?)/

***Mayo Medical Labs offers an RBC total glutathione test, I think.

Genova Diagnostics offers a plasma reduced glutathione test as part

of its Comprehensive Detox panel. Spectracell offers a lymphocyte

functional test for glutathione as part of its panels. I don't know

if these labs take Medicare. I think the price at Immunosciences is

$85.

> I hope this is helpful.

> /(Thanks Rich, what would really help at this point is a review of

what

> supplementation to do at this point to get me out of bed. I am

attaching

> a list of what I am taking for comments from everyone familiar

with the

> Yasko program, especially from Dr. Amy!).

> /

***I can't guarantee that changing your supplements is going to

enable you to hop right out of bed, but I'll look at your list. I

think the program usually takes some time. Dr. Yasko is fond of

saying, " It's a marathon, not a sprint. "

***Rich

[Guest guest]

Hi a,

Please read her forum and you can get all the lists you want . . . lots of

info there. Start at the Welcome section at www.autismanswer.com/forum. A guess

what! . . .the reading of her forum is FREE.

Best Wishes, Sue T

a Carnes <pj7@...> wrote:

I have pulled just one paragraph from Rich V.'s comments out of the

entire

email. I have questions, but I will start with just one. (It is of interest

that Joannie has been on glutathione without improving, but I will leave

that to her and Rich to debate.)

Here is my paragraph/question.

" You got a positive Lyme diagnosis in 2005, with antibiotics added for

that. Of course, this would also have given you more problems with

biotoxins, in view of your HLA genetics. "

I have Shoemaker's genetic tests indicating I cannot deal with biotoxins

either. However, I have improved hugely on antibiotics. I don't have more

problems, I have far less.

I do, however, relapse as predicted by Shoemaker in cases like my genotype.

So the question then is, am I relapsing because my environment continues to

expose me to neurotoxins such as mold and ongoing borrelia infection? If it

is ongoing borrelia infection why not continue to take ongoing low dose,

appropriate antibiotics?

I cannot imagine my life without Zithromax. Has it cured me? No. Has it

given me some level of life back. YES.

I still want to see a nice simple list of what Amy Yasko recomments as

treatment - not all her tests. I want to save my money for a trip to Venice

and Nairobi not massive tests. Hey, when she gets funding for a research

study I will sign up.

a Carnes

[Guest guest]

Excuse me, this is not an either/or situation. Rich is correct,

glutathione is a great help. I am hoping that with Amy Yaskos' work,

other corrections will also help my methylation processes. In addition,

Shoemaker is correct. Mold neurotoxins nearly do me in. My biggest

challenge is to find a place to live that is clean enough (low ploution

levels) and mold free enough. Then with Dr. Amy's protocol, hopefully I

will begin washing away the build up of toxins and pathogens that have

stayed in my body making me ill. Joanee

jill1313 wrote:

>a, I think Yasko is brilliant.

>You shouldn't have to be on antibiotics the rest of your life.

>Something is amiss. And it's not *just* the organism.

>Did you have the dreaded combo HLA genes for both mold and lyme?

>ly, I am ignoring all of Shoemaker's work. I have never been that

>taken with it.

>I think Yasko's work is much more pertinent.

>

>

>

>

>

>

>>I have pulled just one paragraph from Rich V.'s comments out of the

>>

>>

>entire

>

>

>>email. I have questions, but I will start with just one. (It is of

>>

>>

>interest

>

>

>>that Joannie has been on glutathione without improving, but I will leave

>>that to her and Rich to debate.)

>>

>>

>>

>>Here is my paragraph/question.

>>

>>

>>

>> " You got a positive Lyme diagnosis in 2005, with antibiotics added for

>>that. Of course, this would also have given you more problems with

>>biotoxins, in view of your HLA genetics. "

>>

>>

>>

>>I have Shoemaker's genetic tests indicating I cannot deal with biotoxins

>>either. However, I have improved hugely on antibiotics. I don't have

>>

>>

>more

>

>

>>problems, I have far less.

>>

>>

>>

>>I do, however, relapse as predicted by Shoemaker in cases like my

>>

>>

>genotype.

>

>

>>So the question then is, am I relapsing because my environment

>>

>>

>continues to

>

>

>>expose me to neurotoxins such as mold and ongoing borrelia

>>

>>

>infection? If it

>

>

>>is ongoing borrelia infection why not continue to take ongoing low dose,

>>appropriate antibiotics?

>>

>>

>>

>>I cannot imagine my life without Zithromax. Has it cured me? No. Has it

>>given me some level of life back. YES.

>>

>>

>>

>>I still want to see a nice simple list of what Amy Yasko recomments as

>>treatment - not all her tests. I want to save my money for a trip

>>

>>

>to Venice

>

>

>>and Nairobi not massive tests. Hey, when she gets funding for a research

>>study I will sign up.

>>

>>

>>

>>a Carnes

>>

>>

>>

>>

[Guest guest]

Did mold toxins always do you in?

I think he makes too much of these HLA genetic variations.

If he were so correct, Cholestyramine would help many more

biotoxin-injured folks than it does. I'm also not convinced that the

body is so dumb that it circulates these toxins endlessly. I feel he's

making a leap from HLA subtypes to " clinical evidence " people can't

recognize the toxins.

HLA subtypes may predispose you to sensitivity but I suspect that is

only a predisposition, and I think he makes leaps that are not warranted.

Perhaps this is in part because I was on a list for a while, and then

delisted out of irritation, wherein he was clever enough to have been

the only one to think about the fact that babesia has an apicoplast,

which I asked about on the list, which is an organelle that is

devolved from cynoabacteria and therefore may 1) be vulnerable to

certain drugs not yet considered generally and 2) I wondered also if

babesia therefore released a toxin not unlike cigatuera...he had

already pondered this but some of his conclusions were incorrect, as I

found out when I contacted one of the major researchers into

apicoplasts in the world.

So I am skeptical that he is clever, but sloppy.

Sorry.

The visual contrast test--the guy who invented it said it is being

used improperly on the internet.

So anyway.

I'll shut my big mouth now!

> >

> >

> >>I have pulled just one paragraph from Rich V.'s comments out of the

> >>

> >>

> >entire

> >

> >

> >>email. I have questions, but I will start with just one. (It is of

> >>

> >>

> >interest

> >

> >

> >>that Joannie has been on glutathione without improving, but I will

leave

> >>that to her and Rich to debate.)

> >>

> >>

> >>

> >>Here is my paragraph/question.

> >>

> >>

> >>

> >> " You got a positive Lyme diagnosis in 2005, with antibiotics added

for

> >>that. Of course, this would also have given you more problems with

> >>biotoxins, in view of your HLA genetics. "

> >>

> >>

> >>

> >>I have Shoemaker's genetic tests indicating I cannot deal with

biotoxins

> >>either. However, I have improved hugely on antibiotics. I don't have

> >>

> >>

> >more

> >

> >

> >>problems, I have far less.

> >>

> >>

> >>

> >>I do, however, relapse as predicted by Shoemaker in cases like my

> >>

> >>

> >genotype.

> >

> >

> >>So the question then is, am I relapsing because my environment

> >>

> >>

> >continues to

> >

> >

> >>expose me to neurotoxins such as mold and ongoing borrelia

> >>

> >>

> >infection? If it

> >

> >

> >>is ongoing borrelia infection why not continue to take ongoing low

dose,

> >>appropriate antibiotics?

> >>

> >>

> >>

> >>I cannot imagine my life without Zithromax. Has it cured me? No.

Has it

> >>given me some level of life back. YES.

> >>

> >>

> >>

> >>I still want to see a nice simple list of what Amy Yasko recomments as

> >>treatment - not all her tests. I want to save my money for a trip

> >>

> >>

> >to Venice

> >

> >

> >>and Nairobi not massive tests. Hey, when she gets funding for a

research

> >>study I will sign up.

> >>

> >>

> >>

> >>a Carnes

> >>

> >>

> >>

> >>

[Guest guest]

Hi, a.

>

> I have pulled just one paragraph from Rich V.'s comments out of

the entire

> email. I have questions, but I will start with just one. (It is of

interest

> that Joannie has been on glutathione without improving, but I will

leave

> that to her and Rich to debate.)

>

***Well, I think I just covered that again in my response to Joanee,

but this seems to be a point that a lot of people haven't quite

grasped yet, though I've been posting about it since January and

before. Here it is again: Many (perhaps most) PWCs, though they

are depleted in glutathione, have not been able to raise it

permanently to a normal level by the direct, brute-force approach of

injecting or infusing glutathione, getting it in other ways, or

using whey protein products or NAC to help the liver to build it.

The big breakthrough in understanding this was the paper by S. Jill

and colleagues in late 2004. They found that in autism,

glutathione is also depleted, and that this depletion is coupled

with a block in the methylation cycle. If this block is lifted,

glutathione comes up! That's the basis for my application of the

autism treatments to CFS. The point is, a, this is something

new!

>

> Here is my paragraph/question.

>

> " You got a positive Lyme diagnosis in 2005, with antibiotics added

for

> that. Of course, this would also have given you more problems with

> biotoxins, in view of your HLA genetics. "

>

> I have Shoemaker's genetic tests indicating I cannot deal with

biotoxins

> either. However, I have improved hugely on antibiotics. I don't

have more

> problems, I have far less.

>

***Sorry, my wording was not clear here. What I meant was that the

Lyme borrelia produces biotoxins, and since her HLA genetics showed

that her immune system could not recognize and destroy Lyme

biotoxins, this would have caused her more biotoxin problems. I

didn't mean that the antibiotics would cause more biotoxin

problems. Yes, they should help, because if the bacteria are

knocked down some, there will be fewer of them to produce

biotoxins. In regard to Shoemaker's tests, your results are

somewhat different from Joanee's. You have the multisusceptible and

the low MSH HLA alleles, while Joanee has the mold-susceptible and

post-Lyme susceptible alleles. This might produce a somewhat

different response.

>

> I do, however, relapse as predicted by Shoemaker in cases like my

genotype.

> So the question then is, am I relapsing because my environment

continues to

> expose me to neurotoxins such as mold and ongoing borrelia

infection? If it

> is ongoing borrelia infection why not continue to take ongoing low

dose,

> appropriate antibiotics?

***I wish I could say for sure why you relapse, a. I do think

it's possible that there's an underlying immune suppression problem

going on. I realize that these tests are not cheap, but it would be

very interesting to know if your glutathione is depleted and what

your methylation-cycle-related SNPs look like. I think it's

possible that there are issues there that are preventing your immune

system from being able to mount a robust response to the Borrelia.

A satisfactory cell-mediated immune response requires both

glutathione and a robust folate metabolism to allow rapid

proliferation of lymphocytes. A methylation cycle block could be

interfering with both of these. I posted evidence from the

literature last January that Borrelia depletes glutathione. I think

that may be the connection between these things. A person starts

with the genetic makeup that sets them up for a methylation cycle

block if the glutathione level goes low enough. The Borrelia pushes

down the glutathione, trigerring the block, and the person is

trapped in a chronic illness. I think this is worth considering.

>

> I cannot imagine my life without Zithromax. Has it cured me? No.

Has it

> given me some level of life back. YES.

>

***I'm glad that you get some relief from the antibiotics, but it

would be just wonderful if we could get to the root of the problem,

instead of continually dealing with downstream effects that don't

give a complete solution.

>

> I still want to see a nice simple list of what Amy Yasko

recomments as

> treatment - not all her tests. I want to save my money for a trip

to Venice

> and Nairobi not massive tests. Hey, when she gets funding for a

research

> study I will sign up.

***Venice sounds pretty good, but I'm not so sure about Nairobi!

Unfortunately, I don't think it's going to be possible to come up

with a nice, simple, one size fits all list of treatments. The

problem is inherently complex because of genetic and biochemical

individuality. The genetic predisposition involves not just one

gene, but a set of them, and different people have different

combinations and permutations of them. A treatment that would be

great for one person will make another worse, for this reason. I

don't see an alternative to tailoring the treatment to the

individual. I wish I could, believe me. I do think that we may be

able to simplify it some, on the basis of other tests, symptoms,

history, and response to foods and pharmaceuticals. We may be able

to infer to some degree what the genetic variations are in a person

without having to characterize them, at least in a rough way. For

example, if we could just separate those who have CBS upregulations

or MTHFR A1298C SNPs from the rest, without expensive testing, that

would help a lot. I'm actually working along those lines, a.

It may turn out to be possible.

***As usual, I appreciate your comments and insights.

>

>

> a Carnes

>

***Rich

[Guest guest]

I suspect babesia is an even worse depleter of glutathione--its a red

blood cell parasite, and known to oxidize glutathione.

If you get both together, which many chronic lymies do, and you have

the vulnerable genetics, and you had mercury amalgams and THAT already

caused you problems, no wonder you can end up in a mess...

I am watching that Boyd Haley DVD again that I started watching months

ago. I am now doing a thorough immersion in all the autism literature.

It will be 24/7 DVD's. BTW Amy Yasko gave an interview on Autism One

last week and part two will be next week. I haven't listened to it but

I will and I think all of us here should do so, who are interested in

the methylation cycle issues.

Listening to Boyd Haley makes me want to jump up and down and go, " My

hero! " and at the same time sprint down to Atlanta with some boxing

gloves and knock the SHITE (EDY??! LOL) out of those officials, who so

eagerly allowed thimerosal into vaccines, and still insist that STARI

is not lyme and STILL insist on 5 bands for lyme and basically

perpetuate so much sickness in the interests of big pharma and other

lobbies.

> >

> > I have pulled just one paragraph from Rich V.'s comments out of

> the entire

> > email. I have questions, but I will start with just one. (It is of

> interest

> > that Joannie has been on glutathione without improving, but I will

> leave

> > that to her and Rich to debate.)

> >

> ***Well, I think I just covered that again in my response to Joanee,

> but this seems to be a point that a lot of people haven't quite

> grasped yet, though I've been posting about it since January and

> before. Here it is again: Many (perhaps most) PWCs, though they

> are depleted in glutathione, have not been able to raise it

> permanently to a normal level by the direct, brute-force approach of

> injecting or infusing glutathione, getting it in other ways, or

> using whey protein products or NAC to help the liver to build it.

> The big breakthrough in understanding this was the paper by S. Jill

> and colleagues in late 2004. They found that in autism,

> glutathione is also depleted, and that this depletion is coupled

> with a block in the methylation cycle. If this block is lifted,

> glutathione comes up! That's the basis for my application of the

> autism treatments to CFS. The point is, a, this is something

> new!

> >

> > Here is my paragraph/question.

> >

> > " You got a positive Lyme diagnosis in 2005, with antibiotics added

> for

> > that. Of course, this would also have given you more problems with

> > biotoxins, in view of your HLA genetics. "

> >

> > I have Shoemaker's genetic tests indicating I cannot deal with

> biotoxins

> > either. However, I have improved hugely on antibiotics. I don't

> have more

> > problems, I have far less.

> >

> ***Sorry, my wording was not clear here. What I meant was that the

> Lyme borrelia produces biotoxins, and since her HLA genetics showed

> that her immune system could not recognize and destroy Lyme

> biotoxins, this would have caused her more biotoxin problems. I

> didn't mean that the antibiotics would cause more biotoxin

> problems. Yes, they should help, because if the bacteria are

> knocked down some, there will be fewer of them to produce

> biotoxins. In regard to Shoemaker's tests, your results are

> somewhat different from Joanee's. You have the multisusceptible and

> the low MSH HLA alleles, while Joanee has the mold-susceptible and

> post-Lyme susceptible alleles. This might produce a somewhat

> different response.

> >

> > I do, however, relapse as predicted by Shoemaker in cases like my

> genotype.

> > So the question then is, am I relapsing because my environment

> continues to

> > expose me to neurotoxins such as mold and ongoing borrelia

> infection? If it

> > is ongoing borrelia infection why not continue to take ongoing low

> dose,

> > appropriate antibiotics?

>

> ***I wish I could say for sure why you relapse, a. I do think

> it's possible that there's an underlying immune suppression problem

> going on. I realize that these tests are not cheap, but it would be

> very interesting to know if your glutathione is depleted and what

> your methylation-cycle-related SNPs look like. I think it's

> possible that there are issues there that are preventing your immune

> system from being able to mount a robust response to the Borrelia.

> A satisfactory cell-mediated immune response requires both

> glutathione and a robust folate metabolism to allow rapid

> proliferation of lymphocytes. A methylation cycle block could be

> interfering with both of these. I posted evidence from the

> literature last January that Borrelia depletes glutathione. I think

> that may be the connection between these things. A person starts

> with the genetic makeup that sets them up for a methylation cycle

> block if the glutathione level goes low enough. The Borrelia pushes

> down the glutathione, trigerring the block, and the person is

> trapped in a chronic illness. I think this is worth considering.

> >

> > I cannot imagine my life without Zithromax. Has it cured me? No.

> Has it

> > given me some level of life back. YES.

> >

> ***I'm glad that you get some relief from the antibiotics, but it

> would be just wonderful if we could get to the root of the problem,

> instead of continually dealing with downstream effects that don't

> give a complete solution.

> >

> > I still want to see a nice simple list of what Amy Yasko

> recomments as

> > treatment - not all her tests. I want to save my money for a trip

> to Venice

> > and Nairobi not massive tests. Hey, when she gets funding for a

> research

> > study I will sign up.

>

> ***Venice sounds pretty good, but I'm not so sure about Nairobi!

> Unfortunately, I don't think it's going to be possible to come up

> with a nice, simple, one size fits all list of treatments. The

> problem is inherently complex because of genetic and biochemical

> individuality. The genetic predisposition involves not just one

> gene, but a set of them, and different people have different

> combinations and permutations of them. A treatment that would be

> great for one person will make another worse, for this reason. I

> don't see an alternative to tailoring the treatment to the

> individual. I wish I could, believe me. I do think that we may be

> able to simplify it some, on the basis of other tests, symptoms,

> history, and response to foods and pharmaceuticals. We may be able

> to infer to some degree what the genetic variations are in a person

> without having to characterize them, at least in a rough way. For

> example, if we could just separate those who have CBS upregulations

> or MTHFR A1298C SNPs from the rest, without expensive testing, that

> would help a lot. I'm actually working along those lines, a.

> It may turn out to be possible.

>

> ***As usual, I appreciate your comments and insights.

> >

> >

> > a Carnes

>

> >

> ***Rich

>

[Guest guest]

> >

> > Hi Rich, thanks for reviewing my case.

>

> ***You're welcome.

>

> > >Considering next the methylation-cycle-related enzymes, we don't

> > >have the complete results on these yet, but we do know that you

> were

> > >born with an MTHFR A1298C (+/+). This means that at a minimum,

> you

> > >would have had a tendency toward low levels of

> _tetrahydrobiopterin _

> > >(BH4), which would have hindered your ability to synthesize

> > >serotonin and dopamine.

> > >

> > /(I found this information on Yasko's DVD, she mentions that

> persons

> > with MTHFR A1298C (+/+)

> > need to supplement BH4. Dr. Gordon wants to wait for Yasko's test

> > results to confirm this as BH4 is very expensive. This also

brings

> up

> > the question of just how much supplementation to do at this point

> in

> > time. Yasko has a very long list of " step 1 " supplements and

> strongly

> > advises patients to spend sufficient time on step one prior to

> adding

> > all the elements of " step 2 " which is methylation. Of course, she

> is

> > used to treating children. I have already incorporated many of

> the " step

> > 2 and 3 " supplements over the course of time, like glutathione

and

> I am

> > not sure how to proceed. I will attach a list of what I am taking

> and

> > would apprecriate imput from you and the group on what to modify.)

>

> ***I will of course defer to Dr. Yasko's advice on this, but it

> would seem to me that going ahead with BH4 would be a good idea.

As

> I understand it, Dr. Yasko wants to see if you have CBS SNPs before

> you start building up the methylation cycle to avoid increasing the

> flow into the transsulfuration pathway, but I don't believe that

> supplementing BH4 will affect that. On the other hand, it should

> give you benefits with your neurotransmitter synthesis, your nitric

> oxide synthase function/decrease in generation of oxidizing free

> radicals, and improved handling of ammonia by the urea cycle. We

> should know a lot more when your methylation SNPs panel comes back.

> I don't know if you've ever gotten a urine amino acids test run,

but

> I would expect that your ratio of phenylalanine to tyrosine would

> show up as being high, which would be another indicator of low BH4.

>

>

> > /(Dr. Yasko's intuition is that most CFSers have CBS upregulation

> and

> > therefore have to deal with ammonia issues first. Dr. Gordon had

a

> > plasma ammonia level tsted for me last week and it was normal.

She

> notes

> > that blood testing should provide results related to urine

> testing,

> > (blood testing is valid), so I am not sure if I need to start

with

> > dealing with the ammonia issues related to upregulated CBS or

not.

> Do

> > you have an idea?)/

>

> ***Quite a few, but not all PWCs have CBS SNPs, based on my short

> experience with this so far. If you don't have elevated ammonia

(of

> course you had to have been eating a fair amount of protein when

you

> tested for this, or you could be fooled), if you don't have

problems

> (such as headaches) from sulfur-containing supplements or foods, if

> you don't have elevated cystathionine or taurine in a urine amino

> acids test, if you don't smell ammonia in your perspiration, and if

> you don't generate a lot of foul-smelling gas in your gut when you

> eat foods containing a lot of sulfur, then I would guess that you

> probably don't have a CBS upregulation. There's nothing like

having

> the SNP panel results to be sure, though!

>

>

> > You began smoking cigarettes, and did so until the late 70s or

> early

> > 80s. In view of your detox SNPs, this would have raised your

toxic

> load

> > considerably. I suspect that you would have had some respiratory

> > problems from this, as a minimum.

> > /(I did have allergies, and was always on a strict diet to

> control

> > weight, but didn't really get sick. I did have bouts of

> depression.)/

>

> ***O.K. I can't imagine that you would have been able to smoke and

> not have some problems, given your particular collection of detox

> SNPs.

>

>

> you were diagnosed with degenerative

> > disk disease, having extensive pain in your neck and shoulders.

> Perhaps

> > this resulted partly from your overweight condition (perhaps at

> least

> > partly secondary to hypothyroidism) and your sedentary and

> > stressful job. I don't know how much exercise you were getting at

> this

> > point.

> > _

> > _/(Actually I was running 3 miles a day and in great shape prior

> to the

> > pregnancy. I was not over weight but had to work very hard to

stay

> that

> > way with diet and excercise.)//

>

> ***Sorry, I misinterpreted. You wrote me that you were always

> overweight, but I guess you must have meant that you were always

> overweight as a child. Were you doing exercises to strengthen your

> back muscles at the time you were running 3 miles a day, also, or

> only running? Also, running puts impact loads on your disks,

> especially if your shoes aren't cushioned well, and especially if

> you run on a hard surface, such as sidewalk or pavement. Another

> factor is diet. The repair of the disks requires collagen

> synthesis, which in turn needs protein, vitamin C and zinc. I

think

> that supplementing glutamine can help, too, because that's the main

> substrate for the fibroblasts, the cells that make collagen. So

> perhaps some of these factors came into play in the development of

> your disk problems.

>

>

> > You then went through a very stressful period. You had a small

> child, a

> > difficult relationship with your husband, and a stressful

> executive

> > position in advertising. You filed for a divorce, underwent the

> surgery

> > mentioned above, and had a business setback. I don't know whether

> this

> > setback caused you to have to drop down to a job level where you

> did

> > more hands-on work with art materials, including volatile

> solvents, but

> > if so, this could have raised your body burdens of toxins,

because

> of

> > your detox system deficits.

> >

> > /(This is interesting because I guess no-one tests for our

> strengths. I

> > come from a family that encourages positive thinking. I always

> rally

> > after a setback. I founded the first health care division in an

> > international advertising agency, brought in $12 million in

> billings

> > annually after the business setback. I am bright, have talent, am

> good

> > with managing people, have alot of intellectual curiousity;

> however I

> > think the building that I worked in had some toxins.)/

>

> ***Sorry, I guessed wrong! You mentioned that you suspected that

> exposure to art materials had an impact on your developing multiple

> chemical sensitivities. I didn't know when that occurred, and I

> guessed that it was at this point. Did that occur earlier, or was

> it later than this?

>

> > In July of 1996 you started Phentermine for weight loss, which

> helped

> > initially, but not over the longer term. (/It helped for about 5

> years,

> > then the weight came back)./

>

> ***O.K. I looked into the pharmacology of phentermine, and learned

> that it interferes with the reuptake of serotonin and

> norepinephrine, and it also increases the release of dopamine. So

> it appears that this drug was operating by making up for your low

> BH4 status, resulting from your homozygous MTHFR A1298C SNP. I

> think that's really interesting. Too bad we didn't know that a

long

> time ago! I don't know why this drug stopped working. Perhaps

your

> BH4 status got worse over time, or perhaps the receptors that

> phentermine was binding to underwent adaptation or compensation

over

> time by becoming less abundant. I don't know.

> >

> > You were diagnosed with neurally mediated hypotension and also

> developed

> > blood pooling in your legs and varicose veins. This may have

> resulted

> > from your coagulation problem. You didn't mention

> > diabetes insipidus related symptoms (high daily urine volume,

> constant

> > thirst, high fluids consumption), so I don't know if a low total

> blood

> > plasma volume was involved. /(No diabetes yet.)/

>

> ***O.K. You do realize that I don't mean the more common diabetes

> mellitus that is involved with blood sugar and insulin, right? I

> mean diabetes insipidus. Do you have any idea how much urine you

> produce in 24 hours? The average is 1.5 liters, and if it gets

> above about 2.5 liters, one has to consider the possibility of

> diabetes insipidus.

> >

> > Since you also didn't report having impedance cardiography or

> > echocardiography run, I

> > don't know whether you have low cardiac output (heart failure),

or

> > whether a viral cardiomyopathy or diastolic dysfunction might

have

> > developed. Both would have been possibilities, since you did have

> > an active EBV infection, and I'm inferring that you did have

> glutathione

> > depletion.

> > /(I had a heart scan, and was told I had a small amount of

calicum

> in the

> > artery leading to my heart, but it would not build up to anything

> > significant in my lifetime. Cardiac tissue looked excellent.)/

>

> ***I'm not sure what kind of a scan this was. Did it involve a

> radioisotope? Was it a CT scan? Or an MRI? These are beneficial

> for some purposes, but I don't think they will tell you what your

> cardiac output is, or tell you whether you have diastolic

> dysfunction.

> >

> > You had more issues with Hashimoto's thyroiditis and switched to

a

> > natural, porcine-based thyroid hormone supplement. I suspect that

> the

> > exacerbation of Hashimoto's was a result of glutathione

> > depletion in the thyroid, allowing a rise of the endogenously

> produced

> > hydrogen peroxide within the thyroid cells and reaction with

> > thyroglobulin, leading to an elevated autoimmune response.

> >

> > Though UV blood irradiation helped temporarily, your immune

system

> was

> > unable to control infections by EBV, HHV-6, and mycoplasma over

> extended

> > time periods. Again, I think the immune suppression

> > resulted from the glutathione depletion--methylation/folate cycle

> block

> > vicious circle. Sensitivities developed to a variety of molds,

> because

> > of your hereditary HLA makeup.

> >

> > /(Rich, this is far more than a sensitivity. Mold toxins make me

> very

> > ill. It is not the same as having an allergy. Exposure to mold

> impacts

> > me strongly, similar to being hit in the head, then thrown into

an

> > activation of flu like synthoms.) /

>

> ***Right. I understand that. I get that it's far more serious

than

> hay fever! has been making that very clear to us on this list

> for a long time. I guess I should have referred to it as mold

> illness. That's what Dr. Shoemaker calls it in his book " Mold

> Warriors. "

>

> I think that until your vicious circle is broken and the

> > glutathione level and folate metabolism are restored, you will

> continue

> > to have a suppressed cell-mediated immune response, and will

> continue to

> > be subject to viral, intracellular bacterial and fungal

infections.

> >

> > /(Rich, I have been on glutathione IV's since the mid to late

> 1990's. I

> > think your theory about gluatathione is correct, however in my

> case,

> > it's not sufficient. I have so many defects in my genes that I'm

> not

> > sure my body can utilize all the benefits of glutathione

> replacement,

> > because other things are missing as well.)/

>

> ***Right, I'm with you. What I meant was that you have to break

the

> vicious circle to be able to raise glutathione permanently. That's

> what Dr. Yasko's program does. Quite a few other PWCs had had this

> same experience, and that's what caused me to be so receptive to

the

> treatments used by DAN! and by Dr. Yasko in autism. This is

> supported by the paper in late 2004 by S. Jill et al. That's

> been the big breakthrough! Just pumping in more glutathione

doesn't

> do it if there is a stubborn vicious circle involving the earlier

> part of the sulfur metabolism.

>

> You might also consider

> > getting a red blood cell total glutathione test run by

> Immunosciences

> > Lab, just to check on the glutathione level before you get very

> far into

> > the treatment program. Then you will be able to compare and have

a

> > measure of the degree of improvement later on.

> > /( I think Immunosciences no longer takes Medicare, is ther

> another lab

> > doing this?)/

>

> ***Mayo Medical Labs offers an RBC total glutathione test, I

think.

> Genova Diagnostics offers a plasma reduced glutathione test as part

> of its Comprehensive Detox panel. Spectracell offers a lymphocyte

> functional test for glutathione as part of its panels. I don't

know

> if these labs take Medicare. I think the price at Immunosciences

is

> $85.

>

> > I hope this is helpful.

> > /(Thanks Rich, what would really help at this point is a review

of

> what

> > supplementation to do at this point to get me out of bed. I am

> attaching

> > a list of what I am taking for comments from everyone familiar

> with the

> > Yasko program, especially from Dr. Amy!).

> > /

>

> ***I can't guarantee that changing your supplements is going to

> enable you to hop right out of bed, but I'll look at your list. I

> think the program usually takes some time. Dr. Yasko is fond of

> saying, " It's a marathon, not a sprint. "

>

> ***Rich

>

[Guest guest]

***Mayo Medical Labs offers an RBC total glutathione test, I think.

Not separately, if I correctly understood what I was looking at.

(They have a catalog of tests.)

Adrienne

[Guest guest]

>

> I suspect babesia is an even worse depleter of glutathione--its a red

> blood cell parasite, and known to oxidize glutathione.

>

> If you get both together, which many chronic lymies do, and you have

> the vulnerable genetics, and you had mercury amalgams and THAT already

> caused you problems, no wonder you can end up in a mess...

>

>

That is me in a " Nut Shell " . I have all of the above, with Mercury

coming out with Yasko's program.

Sue T