The silicon link between aluminium and Alzheimer's disease

Abstract

Christopher Exley and colleagues report in this issue of JAD [15] the results of a clinical study showing that drinking silicic acid (Si(OH)4)-rich mineral water for five days significantly reduces the urinary excretion of aluminium, but not iron in Alzheimer disease (AD) patients. The authors argue that the long-term dietary supplementation of Si(OH)4 might qualify as a non-invasive therapy for reducing the body burden of aluminium in AD. This study opens a new chapter of the investigations of J. Derek Birchall’s hypothesis of a silicon link between aluminium and AD, for it offers a direct demonstration of the efficacy of dietary silica supplementation in increasing the excretion of aluminium in AD. But what can we expect in terms of therapeutic effects from stimulating the aluminium urinary excretion in AD? We will briefly discuss here the context and implications of this study. The systematic interest for the utilization of silicon in medicine can be traced back to the late nineteenth century, when the emulation of physiologists for research on this element led Luis Pasteur to predict that silicon reserved important therapeutic applications in many human diseases. However, the recognition of silicon as an essential trace element came only in 1972 when two reports showed that dietary silicon deprivation in chicks and rats was associated with retarded growth and bone deformities [6,28]. Subsequent research has established that silicon is indeed important for the calcification of bone and cartilage, and it may be thus involved in disorders characterized by an imbalance between bone formation and resorption (e.g., osteoporosis), joint disorders (e.g., osteoarthritis), and even heart disease and aging (for review see [27]). In contrast to the rather straightforward demonstrations of the roles of silicon in bone and connective tissue homeostasis, the link between silicon and neuropathology and particularly AD was put forward via the aluminium hypothesis in AD. Taking account of the high chemical affinity of silicon for aluminium, and the typical inverse relation between the concentrations of aluminium and silicon in water supplies, the British chemist J.D. Birchall suggested that silicon might mediate the effect of aluminium from drinking water on AD incidence [2,3]. This suggestion was partly based on an earlier finding reported by Birchall, Exley and coworkers that Si(OH)4 in water protected salmon against fatal ionoregulatory, osmoregulatory and respiratory dysfunctions caused by toxic aluminium binding to the gill epithelium [4,14]. Following Birchall’s suggestion, several epidemiological studies reviewed in [19] (see also [20]) indicated that the protective effect of silicon from drinking water against AD was only modest. Nonetheless, in spite of this apparent rebuttal of Birchall’s hypothesis, the silicon link between aluminium and AD continued to be supported on other lines of research. For instance, silicon, more specifically as silica oligomers [21], reduced by several folds the gastrointestinal absorption of aluminium in humans [11] and increased its urinary excretion [1], as originally suggested [2]; high serum silicon was shown