Keizman D, Ish-Shalom M, Berliner S, Maimon N, Vered Y, Artamonov I, Tsehori J, Nefussy B, Drory VE.
Low uric acid levels in serum of patients with ALS: further evidence for oxidative stress?.
J Neurol Sci. 2009 Oct 15;285(1-2):95-9.
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Uric Acid: Not Just for Gout Anymore
The major flaw of the antioxidant theory of aging is the lack of efficacy of antioxidant supplements against diseases of aging. A patchwork of experimental demonstrations show that oxidative stress is involved in several degenerative diseases, and diet, but not supplements, protects people from those diseases. Dissecting diet from a lifetime of exposure has always raised more questions than it has solved.
New evidence is establishing a direct link between oxidant balance and disease, demonstrating that increased uric acid, one of the body’s most effective antioxidants, is correlated with reduced risk of amyotrophic lateral sclerosis. Uric acid, a metabolite of purine metabolism, is maintained in the body rather than broken down by uricase, as it is in most animals. Interestingly, save humans, most animals that excrete uric acid do so to reduce water loss through urine. Could it be that human antioxidant needs were the major drive for retention of a uricase mutation in humans that blocks activity and allows high urate levels?
The contrast of disease reduction caused by urate and diet versus lack of efficacy of supplements should be seen in the context of a strong evolutionary pressure to maintain critical central nervous system functions through strong responses. The metabolic reorganization and stress responses (Martins et al., 1986; Smith et al., 1994) and urate increase may be the best indicators of the primacy of oxidative stress and response in human disease and aging. Seen in this light, gout is not just for big toes anymore.
Martins RN, Harper CG, Stokes GB, Masters CL.
Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer's disease may reflect oxidative stress.
J Neurochem. 1986 Apr;46(4):1042-5.
Smith MA, Kutty RK, Richey PL, Yan SD, Stern D, Chader GJ, Wiggert B, Petersen RB, Perry G.
Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease.
Am J Pathol. 1994 Jul;145(1):42-7.