on causality vs correlation..
low zinc intakes or diets/regimens/meds that are hard on zinc absorption can lead to poor zinc status and consequently low uric acid.
I've had this question before re correlation vs causation (that was in relation to nutrient status and disease state, after a presentation on applying restoration practice to human illness) and my out loud answer was, it can be both - but everything I have seen leads me to believe that nutrient status can certainly be causal. my less diplomatic facetious answer might have been that we can decide that scurvy causes vit c deficiency or is perhaps correlated with low vit c, or that rickets causes vit d deficiency or is merely correlated with low vit d. when of course we know that these conditions are caused by nutrient deficits.
anyway back on the zinc/ua track. I fought low uric acid for years with no success until identifying and correcting zinc deficiency. after working on zinc, I later made the zinc-uric acid connection. it's not the easiest thing in the world to sniff out a causal link in the literature, but this was my first hint -
in this study they put women (no disease process) on a low zinc diet and watched the uric acid levels fall, whether or not they were taking oral contraceptive drugs:
Effect of Low Zinc Intake and Oral Contraceptive Agents on Nitrogen Utilization and Clinical Findings in Young Women
jn.nutrition.org/content/107/12/2219.full.pdf
"
Serum uric acid, «-2-and /8-glob- ulin changed significantly in both groups. Clinical problems developed in all the subjects with serum zinc levels below 50 ug/dl during the study; three of the six with serum zinc levels above 50 ug/dl also complained of clinical symptoms. The results suggest that zinc deficiency through depletion of accessible body zinc stores developed during the 35-day study."
after reading that study I started measuring zinc and ua together. finally with improved zinc status my urea cycle had begun to function properly, the zinc levels and the uric acid levels were both up. I shudder to think what my ammonia levels must have been when my zinc was deficient - research on zinc levels and their inverse relationship with ammonia makes me wish I had known enough at the time to ask for ammonia testing. certainly my cognitive function at the time was a disaster. if we found a case where uric acid was low and zinc replete, then we'd be looking for something else. but when uric acid marches in lockstep with zinc status AND intake, as supported in research and in personal practice, you start to gain certainty re causality.
check out these patient results.. by sept 2012 you can really see the zinc ua connection:
https://sites.google.com/site/brmnutrients/ the vit d3 connection is visible too.
across the board I prefer to ensure optimal status of essential nutrients before looking to non-essential products such as inosine (by non-essential i mean it is synthesized endogenously in humans if the biochemistry is functioning properly). unfortunately the pathway is complex enough that I can't name the specific nutrients involved off the top of my head.. on that subject, I am having trouble getting a handle on the difference between adenosine deaminase, which appears to be zinc-dependent, and adenosine deaminidase.. i digress.
the
relevant action of inosine in ms appears (if murine eae studies can be considered applicable)
to be via conversion to ua..
Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC138606/
"We have assessed the effects of inosine, as well as inosinic acid, on parameters relevant to the chemical reactivity of peroxynitrite and the pathogenesis of EAE. Both had no effect on chemical reactions associated with peroxynitrite, such as tyrosine nitration, or on the activation of inflammatory cells in vitro. ...
the mode of action of inosine and inosinic acid in EAE is via their metabolism to UA."
leaving aside whether inosine does one or two or ten different things, and really regardless of whether these eae research conclusions are in fact transferable to human ms, i would definitely come down on the side of optimizing zinc first and letting it do its hundreds if not thousands of jobs - known and documented jobs.. (which definitely include
virus-fighting, ensuring membrane (
eg endothelium, intestinal, BBB) impermeability, being a requirement for the
utilization of vitamin A, and possibly including supporting endogenous inosine synthesis)- rather than choosing an inosine supplement to do one or even several of zinc's many jobs (i may not have been looking in the right places, but i have yet to see any hint that inosine is specifically antiviral).
another issue i have with inosine is the lack of information on reference or target serum inosine levels. my full text access is still pending and there don't appear to be any easily accessible abstracts that actually give numbers and units for healthy control vs patient inosine levels. here's one study i came across the other day, in which inosine levels seem to have been in excess:
Purine metabolites in fibromyalgia syndrome.
http://www.ncbi.nlm.nih.gov/pubmed/23000315
"Significantly higher serum inosine, hypoxanthine and xanthine levels (p<0.001) and significantly lower serum adenosine (p<0.05) were detected in the FMS patients vs healthy controls... purines, in particular adenosine and
inosine, may be involved in pain transmission in fibromyalgia"
that 2013 study was actually done in humans, but doesn't seem to have anything to do with supplementation. there's just not enough data :S
anyway. excess can be a danger for anything, but with zinc we can research what those numbers are quite easily. with inosine i am not finding this to be the case. we also have a pretty decent handle on how zinc supplementation can affect other nutrients. i have yet to see research on how inosine supplementation might affect internal balance of related systems. we're seeing the outcome of action without full comprehension of interactions, with the increase in mortality after years (decades?) of being urged to supplement calcium without considering impacts on magnesium balance... or zinc status for that matter.