Sunday, 15 February 2015

Uric acid and MS

Should we be treating MS with anti-oxidants? #MSBlog #MSResearch

"It has been known for sometime that uric acid is a weak anti-oxidant and is reduced in condition associated with the production of oxygen free radicals. In Parkinson's disease low uric acid levels are associated with a poor outcome. This study although small hints at a similar observation in MS. The findings clearly needs to be confirmed, but the study hints at a potential biomarker that can be included in longitudinal studies of outcome in MS. Based on this study it appears that uric acid is unlikely to be useful in individual MSers, but could be used for hypothesis testing in large groups of subjects. I would be very interested to know if DMTs affect uric acid levels and whether of not UA levels correlate with disease activity. I would predict that MSers with NEDA would have higher levels than those with ongoing disease activity. This study also shows that MS is a systemic disease and affects metabolism in general; another reasons for us to take a systems biology approach to the disease when thinking about it. For those of you who don't know about uric acid; it is a breakdown product of DNA metabolism and is excreted in the urine. Too much uric acid can lead to gout. I wonder if MSers are lower risk of getting gout?"



Epub: Moccia et al. Uric acid in relapsing-remitting multiple sclerosis: a 2-year longitudinal study. J Neurol. 2015.

Background: Uric acid (UA) is reduced in MS, and possibly relates to MS outcomes, with lower UA levels in subjects experiencing a relapse or presenting higher disability scores. 

Methods: The present retrospective longitudinal study evaluated UA variations in MS, in relation to clinical relapses, disability progression, and cognitive functions. We included 141 subjects with relapsing-remitting MS (RRMS) and performed expanded disability status scale (EDSS), symbol digit modalities test (SDMT) and UA evaluation at baseline visit and after 2-year follow-up. 

Results: Paired t test showed significantly lower UA levels after 2-year follow-up than at baseline (3.987 ± 1.135 and 4.167 ± 1.207 mg/dL, respectively) (p = 0.001). The difference in UA levels between 2-year follow-up and baseline related to EDSS sustained progression (p < 0.001; OR = 0.099), and presented a trend for clinical relapses at logistic regression (p = 0.211; OR = 0.711) and for the time to relapse at Cox regression (p = 0.236; HR = 0.792). Analysis of variance showed reduced baseline UA levels in subjects with impaired SDMT at baseline (p = 0.045; adjusted R 2 = 0.473) and after 2-year follow-up (p = 0.034; adjusted R 2 = 0.470). 

Conclusion: This is the first study showing a progressive reduction of UA levels during the course of RRMS, suggesting a progressive decrease of antioxidant reserves, in relation to relapse risk, disability progression and cognitive function.

9 comments:

  1. Interesting article. Too much uric acid can also cause hypertension (high blood pressure) is that correct? My blood pressure is often on the higher end. I've been on Tec for a few weeks now (my first DMT) and wonder how that is effecting the level.

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  2. Isn't this a classic in overintepretation of data on the part of the authors of this paper? Drawing a conclusion like that from an observational retrospective study? :-)
    How about an easier alternative explanation: people with more disease activity and more progression are more likely to implement diatary changes ( less red meat, more vagetables, less sugar and processed foods with HFCS etc - that is less purines in their diet and hence lower uric acid) and are much less likely to go to the pub and drink beer and spirits that raise uric acid levels.

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  3. I can make a solid statement about my uric acid levels because I have had them checked regularly for many years: before diagnosis, during DMT and after I stopped taking DMTs.

    The uric acid levels before my diagnosis of RRMS were high but within the norm - I know that at that time I must have had a relapse but that did NOT lower the uric acid levels.

    While I was taking DMTs (Tecfidera) the uric acid dropped considerably to the lower end of the normal range.

    After I stopped taking DMTs the levels returned to be normal but quite high (and much higher than on DMTs).

    So I hope that helps somehow.

    If you test your patients you need to understand that their levels may be unnaturally low due to MS medication - that could muddle the predictive value of your research in regards to progression.

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    Replies
    1. Prof G, are uric acid levels taken as standard/ included when blood tests are done for Tec? I'm having blood tests and urine test taken for Tec every three months so I would be interested to know my uric acid levels. thanks

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  4. See some early studies with inosine to raise uric acid levels in MS. These were conducted many years ago such as this http://www.ncbi.nlm.nih.gov/pubmed/15493114 and reached phase 2 but haven't heard anything since https://clinicaltrials.gov/ct2/show/NCT00067327. As I recall there was some research into using inosine as an adjunct to copaxone. Again no idea what happened with this. Here is another one with inosine and beta interferon http://www.pubfacts.com/detail/25313094/Associated-Inosine-to-interferon:-results-of-a-clinical-trial-in-multiple-sclerosis.

    Re: gout and MS, it is pretty unlikely.

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  5. I have come across a couple of studies which found that gout was rare in people with MS - but I can't find them right now to post the links. If I can track them down again, I'll put the links up.

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  6. The observation about Parkinson's and uric acid is interesting and would point to a link with neurodegeneration - that sounds quite promising and could indeed be a measure of progressive loss of neurons - more studies needed but a good start..

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  7. Our anti-oxidant levels decrease as we get older.Free radicals therefore are able therefore to do more damage. This is why we are more likely to get cancers etc. Also arthritis is very prone to appear in joints were there has been previous inflammation. In our CNS neurons that have been exposed due to inflammation/demyelination are more likely to be weaker and therefore more likely not being able to with stand damage from free-radicals.


    In 1990 I had inflammation of cervical spinal cord following radiation treatment for hodgkins lymphoma. My symptoms at time were l'hermittes which lasted several months. I was tested for MS at the time which was ruled out. I was fine until 2010 when foot drop foot began to appear and has got progressively worse since (right foot only). Progressive MS has been suspected thistime but I dont satisfy the McDonald criteria so they think it might be the radiation. I dont think I will ever know.

    Anyway I have been taking anti-oxidants for the last 18 months and my mobility has not got any worse. My energy levels are good and I attend the gym and walk dog most days.

    I take green tea, resveratrol, astaxanthin, ubiquinol (coQ10). Glutathione is the mother of all anti-oxidants and I take a product to help my body produce more.

    There are many people who have progressive neurological issues who have had CNS inflammation in the past. So maybe the MS doesnt actually kill the nerves - they only die because of a combination of free-radicals and demyelination.

    Anti-oxidants are a key to neuro protection. They are needed to protect vulnerable cells/neurones that have exposed by the attacks on the myelin.

    That is my theory anyway.

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  8. I have had my diagnosis of MS for 19 years. I started Avonex and continued taking it until last year switched to Tec. I had one relapse on Avonex. I was just diagnosed with Gout. I am a female 55 years old I don't drink and 130 lbs. I can't figure out why I have gout.. But I do. I just wonder if the Tec .could have contributed?

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