Female MS the Antithesis of Gout

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Bethr
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Re: Female MS the Antithesis of Gout

Post by Bethr »

search wrote:Hi Bethr,
Thanks for the info. Just remember that everytime you donate you not only dump excess Fe, but also many other elements, some of which were probably low even before your first donation.
I would like to know uric acid, urea creatinine, Na, Cl, Ca, P, ALP, AST, ALT, GGT, albumin, globulins, insulin, MCV, hgb, etc, for both of you.
If I can get some or all of these at some time, I will post them. It's simply not that easy to get tests done here. I know my liver test were all OK a couple of years ago. I will look for the MCV, no doubt high though prior to phlebs.
We are a family that reacts to foods and drugs as a norm. We have all been in hospital or at the Drs. for this at some time. Funnily enough we don't seem to get any common allergies, yet get such effects from ingesting things. My son had major reactions as a wee fellow, making schooling nearly impossible for a while. Salicylic acid was one major trigger for him, but has not effected others in the family, so we are indeed all individual. I suppose that MS is much like that. Many influences.
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Re: Female MS the Antithesis of Gout

Post by search »

1) Most of the damage in MS is caused by acrolein and ONOO-
2) Acrolein can be controlled by raising blood and cell pH and by taking 800 mg/d beta-alanine (from GNC, etc,). The best way to raise pH is a diet rich in low fat dairy, vegetables and fruits and to take 200 mg/d Mg as citrate, 800 IU vit D, 10 mg/d vit B6 (to enhance Mg uptake by the cell).
3) ONOO- can be neutralized directly and by reducing the levels of its precursors NO and O2-.
4) ONOO- can be scavenged by 5-hydroxyL-tryptophan, 5-HT (serotonin), epicatechin gallate (from tea), ebselen (GTS-peroxidase mimic), 10 mg/d PQQ (from tea, and which also neutralizes acrolein, O2-, etc, it is one of the most powerful antioxidants), etc, Uric acid prevents much of the damage casued by ONOO-.
5) Zn and TRP increase serotonin levels and reduce NO levels.
Green tea extract contains PQQ, epicatechin gallate, etc, but it inhibits iron absorption, so it is ideal for the minority of MS patients with iron accumulation, but should be avoided by young women with low Fe, who should take pure PQQ and catechin gallate.
Last edited by search on Thu Mar 29, 2012 9:45 pm, edited 1 time in total.
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Re: Female MS the Antithesis of Gout

Post by search »

Uric acid is the nnomal final product of purine metabolism in healthy cells. However, in MS the enzymes that produce uric acid from purines (XDH and XO) are damaged by ONOO- so that not only is uric acid low, but there is purine accumulation. Adenosin is a common purine in cells, which is produced when ATP, ADP and AMP are degraded. The build up of purines itsef also causes major damage as described in the article below. Whixh is why it is important to reestablish XDH and XO function, so as to prevent purine accumulation and produce protective uric acid. PQQ is not only a powerful antioxidant that reduces ONOO- damage, it is also an cofactor for the uric acid producing enzymes, so it can be quite beneficial in MS. Moreover, PQQ not only protects mitochondria, it also induces their proliferation.

The role of ecto-purines in inflammation leading to demyelination - new means for therapies against multiple sclerosis].
[Article in Polish]
Cieślak M, Komoszyński M.
SourceWojewódzki Szpital Zespolony, Oddział Neurologiczny,Toruñ. marcies@autograf.pl

Abstract
Nucleotides released from activated and/or injured cells activate P2 receptors. Extracellular nucleotides serve as danger signals or damage-associated molecular patterns (DAMPs) that trigger various immune responses. Indeed, P2 receptors are highly expressed in the astrocytes, microglia and other immune cells such as T and B lymphocytes that migrate to the central nervous system. The activation of P2 receptors triggers the secretion of proinflammatory cytokines and chemokines as well as immune cell migration and proliferation that contribute to demyelination and axonal damage. The activation of P2 receptors is controlled by the ectonucleotidases which hydrolyze extracellular nucleotides. Ecto-NTPDases and ecto-5'-nucleotidase are expressed in the astrocytes, oligodendrocytes, microglia, endothelial cells and activated T cells. The hydrolysis of extracellular ATP and ADP by enzymes results in the generation of extracellular adenosine. This nucleoside interacts with P1 receptors and activates anti-inflammatory and immunosuppressive responses in the cells involved in MS.
search
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Re: Female MS the Antithesis of Gout

Post by search »

Besides the suggested supplements and diet rich in dairy, vegetables and fruits, especially good foods for people with MS appear to be beets (beetroot), garlic, carrots, radishes, oatmeal (Si, TRP, etc,), dates (one of the best sources of Si). For young females with MS and ferritin <30 & serum Fe<60, red meat (the most absorbable source of iron) and vit C supplementation should be considered, since dairy are low in Fe.
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Re: Female MS the Antithesis of Gout

Post by search »

The Good Path and the Bad Path in Urate Synthesis
An enzyme is an organic catalyst that causes a reaction to take place. However, just as it causes the synthesis of a compound when there is plenty of substrate and little product, once there is a lot of product and little substrate, the reverse reaction takes place. Therefore, there is normally a built in mechanism that prevents accumulation of a given product.

Uric acid can be synthesized by two related enzymes:
a) Xanthine dehydrogenase (XDH) transforms xanthine into uric acid, without producing any harmful products. Once XDH has produced enough uric acid the reverse reaction begins to take place, establishing an equilibrium and rendering hyperuricemia unlikely.

b) Xanthine oxidase is made when amylase and proteases act on XDH or when (Fe+Mo+S)/(Cu+Mg) is very high. Xanthine oxidase produces noxious superoxide (O2-) along with uric acid. Unfortunately, O2- rapidly reacts with nitric oxide (NO) in the cell to form the extremely harmful peroxinitrite (ONOO-) which in turn damages XO and all other Fe-Mo-S proteins and releases iron from ferritin, causing oxidative damage. Accordingly once uric acid levels are very high the damaged XO cannot catalyze the reverse reaction, causing hyperuricemia.

Therefore, XDH protects from gout, while XO increases the risk of a gout attack by raising urate and by releasing Fe from ferritin, which induces Na-urate crystallization

Another cofactor that plays an important role in XDH function, but appears no to be required for XO is PQQ, the last vitamin B to be discovered. PQQ is also one of the best antioxidants. PQQ can be bought as a pure supplement or is present in green tea (if you don't like tea, take green tea extract capsules).
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Re: Female MS the Antithesis of Gout

Post by search »

Scott1 wrote:Maybe you should stay with Gout.

I've had both which makes me fairly rare.
Sorry Scott1, I hadn't seen your post, I only saw the following one by Bethr.

Your case is precisely why I was addressing female MS and why I consider it a separate disease from male MS and from female MS with hemochromatosis.

Did you take allopurinol for several years to reduce urate when you developed gout?

How close is your case to this one?
56 year old male who drank heavily and smoked and had gout at age 43 and then developed MS at age 49.
He started out with uric acid of 9.1, homocysteine fo 11.3, ferritin of 237, serum Fe of 144.
He had hyperuricemia and homocysteinemia because of high Fe, S & Mo or Pb and low Cu, Mg, Zn, vit D. He also had high Cd because of 24 years of smoking.
After taking allopurinol to reduce urate for 6 years he developed MS.
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Re: Female MS the Antithesis of Gout

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The crucial role of lipoic acid deficiency in MS.
Vit A reacts with free radicals forming toxic products that must be deactivated by vit E, forming again toxic products, which are finally neutralized by vit C. Unfortunately, vit C cannot cross the blood brain barrier (BBB), except in the oxidized form. Lipoic acid is produced by mitochondria and it reduces (recycles) oxidized vits C, E and A. Unfortunately, in MS ONOO- causes considerable damage to mitochondria by destroying MnSOD, aconitase, cytochrome C, etc, and acrolein damages the mitochondrial membrane, etc, so that lipoic acid production is impaired and the oxidative damage to the cell exacerbated. Moreover mitochondrial damage also results in low levels of heme, which is required for many enzymes. Finally when ONOO- damages aconitase (another name for IBP-1), the enzyme that metabolized citrate when it is bound to Fe, it interferes with cellular Fe uptake and Fe sequestration in ferritin, causing major damage that leads to cell death and Fe deposits. Coenzyme Q10 (Co Q10) is also produces in the healthy mitochondrion and also plays a crucial role in checking oxidative damge and is also low in MS. Glutamine and Zn play an important role BBB repair and the latter displaces noxious Cd.

Therefore, simultaneous supplementation with lipoic acid, PQQ, Co Q 10, beta-alanine (which neutralizes acrolein), Zn, 5-HT, glutamine, Mg, vits C, D, K, B6 and B12, folate, niacin and a good diet which maintains 7.4<blood pH<7.44 can reduce considerably the rate of damage and provide a respite for repair.
Last edited by search on Tue Apr 03, 2012 2:46 pm, edited 1 time in total.
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Re: Female MS the Antithesis of Gout

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Perhaps the best form of niacin is picamilon (20 mg/d), developed in Russia, which is a compound of niacin and GABA and which increases blood flow to the brain, which according to the CCSVI theory is a major problem is MS. Similarly, perhaps the best form of vit B6 is not the usual pyridoxine, but pyridoxamine, which neutralizes acrolein (10 mg/d).
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Re: Female MS the Antithesis of Gout

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Hormone receptors are an often neglected aspect of formone function. Vit D is a steroidal hormone that binds to the same receptors as estrogen, TH and other hormones, so that if the other hormones are high and vit D is low, the deficiency will be exacerbated by displacing vit D from the receptors. Moreover, Zn is required for receptors synthesis, so that low Zn levels may result in low receptor count and impaired vit D function, even in the presence of adequate levels of vit D.
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Re: Female MS the Antithesis of Gout

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Another way in which excess copper in young women can contribute to MS is through histapenia (histamine below 44 mg/l). Cu causes histapenia by directly binding to histamine and by accelerating histamine elimination through the copper enzyme diamine oxidase. Histamine is made from histidine, an essential amino acid abundant in animal meat, but less abundant in most vegetable protein (which often contains more Cu than animal protein). Histidine is also used to make carnosine (histidine+beta-alanine), which neutralizes the harmful acrolein in MS. Histamine is made by histidine decarboxylase using vit B6. Histamine plays an important role in myelinization and regulating autoimmunity and in brain irrigation by causing vasodilation. Histamine is also an important neurotransmitter that regulates dopamine, norepi, epi and serotonin release, so it plays a crucial role in mood. Histamine also boosts mitochondrial production of creatine phosphate, used to recycle ADP into ATP throughout the cell, so it can lessen fatigue. Ideally 44<histamine<65
Last edited by search on Thu Apr 19, 2012 2:44 pm, edited 1 time in total.
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Scott1
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Re: Female MS the Antithesis of Gout

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Hi Search,

I haven't been paying attention for a while and just noticed you asked if I was like the case you mentioned. The answer is I was nothing like it.
The allopurinol I took contraindicated with the Valtrex because Valtrex is a Purine Nucleotide analogue and allopurinol is an "anti purine"in effect. When I worked that out and showed my doctor we agreed to drop the full gout treatment which was the old fashioned combination of Allopurinol, Procid and Colgout. I was only on it for a very short time.
In the end I backed off from everything and then played around a bit to see what worked. I detailed most of this under the Regimens section under the title "Avonex and Valtrex".
The bottom line is I elevated my purine levels by taking 500mg of Valtrex twice a day for 10 years. The gout wasn't from the usual background. It was the breakthrough of noting that MS and gout are regarded as mutually exclusive that set me on the path of finding out why. I went back over all my medical records and noted what the trends in data were as opposed to just looking at single observations. What really stood out back in the early days was the extremely low readings of non essential amino acids. I then spent some time drawing maps for myself of the citric acid (Krebs)cycle till I started to understand what needs to be active at each stage to lead to the next. At that point I learned about the role of ATP and the cycle involved its production. The deeper I dug the more implicated Peroxynitite became particularly as the EBV infected B cell is a well documented source of superoxide.
My doctor was running along the Vitamin D path. By this time I was quite cautious about understanding what is a marker of something being disabled as opposed to being the problem itself. That lead me on to looking at nuclear receptors and in particular the RXR. Once you get to that point, the amount of literature pointing to EBV and to some degree peroxynitrite grows quite dramatically but it tends to be at the cutting edge of research. I'm sure the good researchers are circling around the point but not quite pulling it together. The fact the some MS strategies have used Rituximab tells me that the focus is very much on knocking out the B cells and the only reason to do that is to destroy the EBV as it can't persist without B cells.
I went back onto Valtrex this week as I could sense the peroxynitrite starting build up and it was leaving me a bit tired. After four days I felt much more energetic again. The effect is always the same with me.
My regime is now Valtrex twice daily, Coenezyme Q10 at bedtime, Avonex weekly and carrot juice daily. The gout is not troubling me as I have avoided the Valtrex for a while. When it starts to impact I'll just cut it out for a while and continue the rest.
I still have to disagree about this gender divide you are using. Being different genders may lead to different paths but the cause isn't an issue of gender.

Regards
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Re: Female MS the Antithesis of Gout

Post by search »

¿So apparently you develped MS before gout? It would be more useful to have your medical history than a few isolated bits that don't make much sense.
It may not even be gout, but pseudogout (Ca pyrophosphate crystals), etc, The only way to diagnose gout with certaintly is to extract fluid from the joint and to look at it under the microscope, gout crystals are pointed needles and pseudogout crystals are blunt needles. ¿did your doctor do this?

You may disagree all you want about different gender and age chemistry, the fact is that the high estrogen in young women increases Cu & Cd half life considerably and high estrogen displaces vit D, cortisol and T3 from their recpetor and when there is excess Cu, the Cu protein hepcidin inhibits Fe absorption and Cu displaces Mo. With low Mo and Fe and high Cu XDH, XO, aldehyde oxidase, etc, perform poorly. This and menstrual losses explain why millions of young women are anemic due to Fe deficiency, have low uric acid and histamine, tolerate ethanol and even small amounts of methanol and sulfites poorly. Those who also have high Cd (from smoking, eating produce grown in soils contaminated with Cd, etc,) have low vit C (Cd catalyzes its convertion to oxalate) and vit D and Zn is displaced from MgCuZnSOD, etc, when both Cu and Cd are high and catalase and other heme enzymes don't work propelry, there is considerable oxidative damage, which elevates acrolein, ONOO-, H2O2, etc, and if the wrong genes are there and there is limited exposure to sunlight in childhood, MS may ensue. In your case and inmenopausal women the path may be quite different (unless there is Wilson's disease, which involves Cu accumulation in liver and brain).
The chemistry of a young woman is so different from that of a 70 year old woman that the latter is much more likely to experience the same diseases as a 50 year old man (cardiovascular and kidney disease, diabetes, gout, osteoarthritis, etc, the diseases of excess Fe, low Cu, etc,), than those of a young girl (the problems of excess Cu & Cd and low Fe, Mo, Zn, etc,)
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Re: Female MS the Antithesis of Gout

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Here's something that may be of potential interest. High levels of uric acid can lead to high blood pressure as uric acid inhibits endothelial nitric oxide synthase (eNOS) leading to lower levels of nitric oxide and reduced vasodilation.

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Bethr
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Re: Female MS the Antithesis of Gout

Post by Bethr »

Search, I'm enjoying your posts, although I must admit I don't understand a lot of it, there is just so many paths and influences. I'm quite sure I had the psuedo-gout. My knees and hips ached and were very bad when I was at my worst. X-rays showed nothing (a rheumatologist looked at them), but if the only way to truly see the crystals is by biopsy then how would they really know.

All I know is when I had blood drawn off in the beginning the effects were almost immediate, I felt light and my joints moved freely. My fatigue melted, I felt quite high. I'd slowly go downhill until the next blood draw (or having a menstrual period :?: also helped, always has).
I have always had trouble consuming alcohol, especially wine & spirits (beer is sort of OK in moderation). I get violently sick at times after maybe two glasses, so I just gave up alcohol years ago , there was no point as The chance of being ill was about 50/50 and it spoils the party!.

Anyway, I'm confused as to whether the improvements in my monthly episodes were due to the hormones or the blood loss, or a combination. To complicate things I'm more than likely entering menopause now.

The proof has been that now I have my iron levels (especially transferrin saturation) down, I'm
feeling better than I have in years and years, it's like getting the iron down stopped the hormones affecting me so much. Joints good, monthly cycle moods under control, debilitating fatigue gone (I used to pass out every day for hours). And of course no more brain events. I even had an attack of chorea two weeks after my first blood draw. I still have the hyperpigmentation on my arms that showed up when my iron got high. It's really blotchy and looks a bit like liver spots. I think my liver is OK, but how do you really know.

This is the only tests I've ever had for my liver in 2010

Total protein 70 g/l
Albumin (serum) 44 g/l
Globulins (serum) 26 g/l
Bilirubin (total) 11 umol/L
GGTP: 19 IU/L
Alkaline Phosphatase 64 IU/L
ALT: 16 IU/L

All normal from the looks of it.

On the other hand this is my CBC in 2010
Hb 163 High
HCT .485 High
Red Cell 5.17
MCV 93.8 fL
MCH 31.5 pg
Platelets 402 x 10*9/L
White cell 15.4 High
Neutrophils 6.9
Lymphocytes 6.9 High
Monocytes 1.4 High
Eosinophils 0.2
Basophils 0.0
Comment: occasional acanthocyte present

I had a nasty rash come up not too long after this blood test.
I had it biopsied and it was called Pityriasis Lichenoides where lymphocytes
come out of your skin in blisters and leave brown marks.
It cleared up fast and I haven't had it back, a couple of months after
that I sweated blue under my armpits for a week, and felt heaps better all round.
Very weird stuff you must admit. I think they call it lipofuscin.
My stained clothes were sent to a lab in Australia.
The brightest blue you ever saw!

My latest CBC in Jan 2012 (after 5 more pints of blood taken)

Hb 150 g/L
HCT .447
Red Cell 4.92
MCV 90.9
MCH 30.5
MCHC 336 g/L
Platelets 499 HIGH
White cell 9.7
Neutrophils 3.7
Lymphocytes 4.9 HIGH
Monocytes 0.9
Eosinophils 0.2
Basophils 0.1
Comments: Red cells show hyposplenic changes

PS: I have no spleen because of a car accident as a youngster.

I really do feel I'm out the other side, but press trying to find out what the hell happened to me, in case I can help my sister in some way. I'm even starting to think she may be better off than she could have been BECAUSE of her good iron supplies. She has had MS for so long and she's still functioning, working, walking and living a reasonably good life. But at what point does iron become toxic. At lower levels than most Dr's think I believe.
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Re: Female MS the Antithesis of Gout

Post by search »

Hi Bethr,
Iron can cause joint pain by other mechanisms besides hyperuricemia, so its no wonder than you feel better.
Did your doctor ever consider Mc Leod's syndrome because of the acanthocytes, etc,? It usually presents with hemolytic anemia, but since you don't have a spleen, this may have prevented the anemia.
Your liver was OK in 2010.
Like I've said a few times, the reference values are useless because they are obtained by forcing 95% of patients analyzed in the lab to fall within them, so they are too wide. Here are some of the ideal ranges I use.
3.8<white cells<5.2, 240<platelets<290 so you were very high on both of these.
Take care
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