Opinion

... in response to Caffeine Pharmacology
  1. Kari Luoto Kari Luoto Finland says:

    Caffeine is metabolized mostly to uric acids.
    www.genome.jp/dbget-bin/www_bget?pathway+hsa00232

    Caffeine accumulates in the body and if you use it on daily basis, you have caffeine and its active metabolites in the blood 24/7.
    35% of caffeine binds to proteins and is not in the blood circulation.
    http://www.ncbi.nlm.nih.gov/pubmed/2060564

    Because caffeine is metabolized mostly to uric acids and caffeine accumulates in the body, it is safe to assume that caffeine accumulates in the body as different caffeine uric acids.

    Why is it then that these caffeine uric acids are not being removed from the blood to urine? Isn't that what kidneys are supposed to do? What can stop kidneys from secreting uric acids from blood to urine?

    "Physiologically, the major factors that affect urate excretion are the tubular fluid pH, the tubular fluid flow rate, and renal blood flow. The first 2 factors primarily diminish uric acid and urate precipitation in the collecting ducts, while the third is important in urate secretion. In disorders such as sickle cell disease, hypertension, and eclampsia, hyperuricemia out of proportion with decreases in glomerular filtration result from decreased renal blood flow. Organic acids, such as lactic acid and ketoacids, also can impair the proximal secretion of uric acid."
    emedicine.medscape.com/.../244255-overview#a0104
    http://www.ncbi.nlm.nih.gov/pubmed/3721778

    The major factor is the effect of caffeine to blood circulation. Caffeine inhibits adenosine which is the most important neurotransmitter that dilates the blood vessels. Caffeine releases stress hormones that constrict blood vessels and reduce renal blood flow, inhibiting the secretion of uric acids to urine. The fact that caffeine's pharmacodynamic effects are mainly based on chronic elevation of stress hormones, makes it a systemic toxin that alters the chemical balance of every cell, and can thereby cause drastic changes in body's processes and organ functions.
    http://www.ncbi.nlm.nih.gov/pubmed/11815511

    Uric acids are poorly water soluble. When they enter tissues with reduced water flow, the concentration elevates locally and the acids start to crystallize. Such tissues are bone, connective tissue between skeletal muscles and bones and fat. When blood UA concentration gets too high, blood can no longer melt crystallized acids. It is known that caffeine lowers the blood uric acid concentration, but reason to this is not known.
    http://www.ncbi.nlm.nih.gov/pubmed/17530681

    This video shows two different modes of accumulation in big toe. First between the bone and soft tissue starting from the second joint to both directions. The second view is from the side of the toe, where uric acids have started to crystallize downward from the joint, forming a large blister under the toe. This is same mechanism applies in the whole body.
    http://www.youtube.com/watch?v=TB1un6xzlRI


    Caffeine metabolites stored in the body have very similar sympathomimetic effects with caffeine.
    http://www.ncbi.nlm.nih.gov/pubmed/8529334

    Crystallized uric acids are not stable. They can start melting from one point or another for various reasons, creating an acute caffeine poisoning that can be lethal. The problem with diagnosing the symptoms caused by these toxins is that they can cause systemic symptoms with high concentration and local peripheral symptoms close to an infected deposit, and central nervous system symptoms with two different mechanisms; generally elevated UA concentration, and locally elevated concentration in brain due to local melting in small scale. The latter one can create extremely bizarre physical symptoms depending on the location of meltdown.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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