uric acid

[karldeleeuw]

During pregnancy MS women excrete uric acid more than normal and there is evidence that show that increased progesterone hormone levels make this happen. It seems to be that MS women improve during pregnancy. Is the key not therefore that during MS pregnancy more uric acid goes out of the body and is not trapped in the body. Therefore that normally the uric acid levels in the body (not the blood) is very high and is it not this uric acid that is eating away at the myelin sheaths in MS people ?

With Huntington’s (HD) that is more a male condition HD people's testosterone is low and uric acid is high. Again it seems that hormones linked to uric acid could be the cause with HD as well

[jimmylegs]

1) please observe forum rules re advertising and
2) oh my goodness no. uric acid tends to be low in ms patients. have you read the wikipedia uric acid entry wrt MS? http://en.wikipedia.org/wiki/Uric_acid# ... _sclerosis

in my experience, this uric acid problem is associated with the low zinc levels also typically seen in ms patients.

for years my serum uric acid was dead-on or below the ms average of 194. then i suspected and confirmed a zinc deficiency.

i corrected the zinc deficiency, then realized the zinc/uric acid connection and started testing serum Zn and UA together.

at that time i had successfully raised my zinc levels to 16.1 (which approaches the healthy controls average of 18.2). after years of unsuccessfully trying to elevate my serum uric acid via high purine foods (likely skyrocketing my serum ammonia due to broken urea cycle, greeaaat), the zinc therapy finally resulted in a serum uric acid jump to 278 umol/L (approaching the healthy controls range of 290-300).

although it's not the only relevant nutrient where myelin health is concerned, zinc is critical to membrane integrity throughout the human body. the myelin sheath is no exception:

Specificity of zinc binding to myelin basic protein (1995)
http://www.springerlink.com/content/k4621j762u623l22/
Abstract

Z2+ appears to stabilize the myelin sheath but the mechanism of this effect is unknown. In a previous report we have shown that zinc binds to CNS myelin basic protein (MBP) in the presence of phosphate and this results in MBP aggregation. For this paper we used a solid phase zinc blotting assay to identify which myelin proteins bind zinc. MBP and a 58 kDa band were found to be the major targets of65Zn binding. Moreover, using fluorescence, light scattering and electron microscopy we investigated the binding of zinc and other cations to purified MBP in solution. Among the cations tested for their ability to interfere with the binding of zinc, the most effective were cadmium, mercury and copper, but only cadmium and mercury increased the scattering intensity, whereas MBP aggregation was not inhibited by copper ions. Thus, the effect of zinc on the formation of MBP clusters seems to be specific.

Myelin Basic Protein Is a Zinc-Binding Protein in Brain: Possible Role in Myelin Compaction (1997)
http://www.springerlink.com/content/g11684506347u682/
Abstract

The zinc-binding proteins (ZnBPs) in porcine brain were characterized by the radioactive zinc-blot technique. Three ZnBPs of molecular weights about 53 kDa, 42 kDa, and 21 kDa were identified. The 53 kDa and 42 kDa ZnBPs were found in all subcellular fractions while the 21 kDa ZnBP was mainly associated with particulate fractions. This 21 kDa ZnBP was identified by internal protein sequence data as the myelin basic protein. Further characterization of its electrophoretic properties and cyanogen bromide cleavage pattern with the authentic protein confirmed its identity. The zinc binding properties of myelin basic protein are metal specific, concentration dependent and pH dependent. The zinc binding property is conferred by the histidine residues since modification of these residues by diethyl-pyrocarbonate would abolish this activity. Furthermore, zinc ion was found to potentiate myelin basic protein-induced phospholipid vesicle aggregation. It is likely that zinc plays an important role in myelin compaction by interacting with myelin basic protein.

low zinc consequences are hypothesized to go beyond the structural integrity of the myelin sheath:

The possible role of gradual accumulation of copper, cadmium, lead and iron and gradual depletion of zinc, magnesium, selenium, vitamins B2, B6, D, and E and essential fatty acids in multiple sclerosis (2000)

...low Zn levels result in deficient CuZnSuperoxide dismutase (CuZnSOD), which in turn leads to increased levels of superoxide. ... Vitamin B6 moderates intracellular nitric oxide (NO) production and extracellular Mg is required for NO release from the cell, so that a deficiency of these nutrients results in increased NO production in the cell and reduced release from the cell. The trapped NO combines with superoxide to form peroxinitrite, an extremely powerful free radical that leads to the myelin damage of MS. ...

prenatal vitamin supplementation may be in part responsible for some of the improvement seen in ms patients during pregnancy. there are also some steroid hormone changes (with zinc connections of their own) in the third trimester that affect the immune system. links to '06 discussion
http://www.thisisms.com/forum/general-d ... tml#p20496
http://www.thisisms.com/forum/general-d ... tml#p20560

[CureOrBust]

I saw one of my neuro's today, and while he was looking at my blood results (I am on Gilenya) I quickly explained to him that my Uric Acid reading was so high (0.60 mmol/L), because I was taking inosine. He had NEVER heard of the association between Uric acid and MS He then went on-line and read a meta-analysis article that said it was more associated with PPMS and not RRMS. Either way, he should of been interested to have learned something new about a disease he has been studying/researching for so many years. I have slowly been losing respect for this guy every time I see him.

[jimmylegs]

it's ceased to amaze me what docs don't know :S

as for ppms vs rrms, yes you can see that low Ua would have a stronger association with more serious disease, duhhhh 7:|

however, we do have research showing Ua fluctuates in rrms, lower in relapse, higher in remission, and averaging 194umol/L in ms patients, about 100 units lower than your average healthy controls.

i was just posting on another topic re zinc supplementation normalizing uric acid status (just one of zinc's vastly diverse beneficial effects)

[DIM]

Wife's uric acid (RRMS) is at the upper normal level along with her zinc so we reduced daily inosine dose to 500mg and zinc to 4-5 days per week, although phosphorus calcium magnesium are also quite high in her recent blood tests probably due to been 5 years on supplements!
Thanks god she has Remitting Remitting MS now...

[jimmylegs]

good to hear! i still have never taken inosine.. for me zinc definitely does the trick to correct low uric acid

[Jimpsull]

Ian - we appreciate your concern - but I would not be too quick to rain on people's parade. Many of the approaches people are pursuing on this site are supported by quite a bit of research. The Swank diet, in particular, found most adherents walking after 31 years. By contrast members of the study that did not stick with the program were dead or severely disabled over the same time frame.

In addition to the benefits of the therapies themselves there is a placebo effect that should not be undervalued. Placebo effect demonstrates the healthy effects of the feeling of hope and empowerment we get from doing something (even if the thing had no merit in and of itself).

Many of the things Jimmy mentioned have sound theoretical basis and empirical data to back them up. Inosine definitely falls into this category. It is also cheap - but drink lots of water.

[jimmylegs]

"Many of the things Jimmy mentioned have sound theoretical basis and empirical data to back them up."
i should hope so. my professors will slap me otherwise

[zjac020]

Hi all,

As someone how has received Inosine in the post (yet im still not taking it), would you only base the decision to take inosine going on UA serum levels?

In my last test my level was at 5.2 mg/dl (ref 2.5 - 7). Maybe I should take some inosine to try and push the level to the upper limit? Having said that my dad has problems with uric acid (and takes meds to keep it down) and brother is also slightly on the high side although he has been warned to monitor his level, with no needs for meds yet.

Your thoughts...?

cheers,
zjac

[ribeye]

I take inosine for UA and for the possible neuroprotection. Cost is low so just another way to keep what I have. No gout, but do watch for it.

[jimmylegs]

heya, healthy control serum UA levels are 290-300 umol/L (4.8 - 5.0). gout risk increases above 340 umol/L (6.1). i'd fix the zinc level and recheck UA before i bothered with inosine, personally..

[zjac020]

sounds reasonable jimmy. let me saw how levels are after next check up.

I think the study I read on MS and Inosine had slightly higher serum levels than 6 if I recall correctly.

[pawel96]

Did anyone here try to do some experiments with NOT drinking enough water (fluids)? The other way round what is usually recommended? I tried to drink only a small amount of water (less then a half glass + some fruits) at work, during 8-9 hours. Guess what? I found that my symptoms were significantly reduced. I suppose this has something to do with levels of uric acid raising and scavenging peroxynitrate, which could act antiinflammatory? I repeated this a few times so I am pretty sure this works for me.

I know that long term this might be unsafe, but short term - just another trick for managing MS?

P.

[zjac020]

Unfortunately that really is hard on your kidneys. Water isnkey for too many things...

[jimmylegs]

Low serum uric acid levels in patients with multiple sclerosis and neuromyelitis optica: An updated meta-analysis
http://www.sciencedirect.com/science/ar ... 4816300608
Highlights
• We performed a meta-analysis to evaluate the association between serum uric acid levels and patients with MS and NMO.
• We found the serum uric acid levels of MS and NMO patients were significantly lower compared to those of healthy controls.
• We speculated that serum uric acid might be a potential diagnostic biomarker for MS and NMO.

Abstract
Objectives
To evaluate the association between serum uric acid (UA) levels and patients with MS and NMO.
Methods
The PubMed, Web of Science and Cochrane Library database were searched for relevant studies. Pooled standardized mean difference (SMD) and 95% confidence interval (CI) were used as effect size. Subgroup analysis was performed by gender, country, disease durations, scores of EDSS, detection method and clinical classification.
Results
A total of 10 case-control studies involving 1537 patients (1308 MS patients, 229 NMO patients) and 908 healthy controls were included. We found the serum UA levels of patients with MS and NMO were significantly lower compared to those of healthy controls (SMD=−0.52, 95%CI,−0.81 to −0.24). In the subgroup analysis, there was no significant difference between serum UA levels in patients and healthy controls in European subgroup (SMD=−0.32, 95%CI,−0.78 to 0.14). Additionally, we found that serum UA levels were higher in MS and NMO patients than in healthy controls in EDSS>3.5 subgroup (SMD=−0.38, 95%CI,−0.58 to −0.19), but not in EDSS≤3.5 subgroup (SMD=−0.35, 95%CI,−0.97 to 0.27). Patients of relapsing group had significant lower serum UA levels than patients of remitting group (SMD=0.70, 95%CI, 0.19-1.21).
Conclusion
Patients with MS and NMO showed lower serum UA levels when compared with healthy controls. Serum UA might be a potential diagnostic biomarker for MS and NMO.


the higher se UA in the >3.5 EDSS subgroup is a bit of a twist, wonder what is going on there... in the full text table 1 seems a bit rough but it will be interesting to check out the studies in the analysis more closely. it's been a long time since i sorted out my low uric acid. have never seen half of the studies in this analysis before; they've all been done since i sorted out my own low level. (recall http://www.thisisms.com/forum/natural-a ... tml#p53615 worked for me!)