Article

Silicon-Rich Mineral Water as a Non-Invasive Test of the 'Aluminum Hypothesis' in Alzheimer's Disease

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Abstract

There has been a plausible link between human exposure to aluminum and Alzheimer's disease for several decades. We contend that the only direct and ethically acceptable experimental test of the 'aluminum hypothesis', which would provide unequivocal data specific to the link, is to test the null hypothesis that a reduction in the body burden of aluminum to its lowest practical limit would have no influence upon the incidence, progression, or severity of Alzheimer's disease. Herein we are testing the hypothesis that silicon-rich mineral waters can be used as non-invasive methods to reduce the body burden of aluminum in individuals with Alzheimer's disease and a control group consisting of their carers and partners. We have shown that drinking up to 1 L of a silicon-rich mineral water each day for 12 weeks facilitated the removal of aluminum via the urine in both patient and control groups without any concomitant affect upon the urinary excretion of the essential metals, iron and copper. We have provided preliminary evidence that over 12 weeks of silicon-rich mineral water therapy the body burden of aluminum fell in individuals with Alzheimer's disease and, concomitantly, cognitive performance showed clinically relevant improvements in at least 3 out of 15 individuals. This is a first step in a much needed rigorous test of the 'aluminum hypothesis of Alzheimer's disease' and a longer term study involving many more individuals is now warranted.

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... Also, silicon in the form of silicic acid is regarded as a natural antagonist of aluminum toxicity in biota and in humans. It reduces aluminum uptake across the gut and simplifies the excretion of systemic aluminum via kidneys (Exley 2009a;Davenward et al. 2013). Moreover, the studies presented an evidence that long-term drinking of silicon-rich mineral water significantly reduces the body burden of Al (Exley et al. 2006;Davenward et al. 2013). ...
... It reduces aluminum uptake across the gut and simplifies the excretion of systemic aluminum via kidneys (Exley 2009a;Davenward et al. 2013). Moreover, the studies presented an evidence that long-term drinking of silicon-rich mineral water significantly reduces the body burden of Al (Exley et al. 2006;Davenward et al. 2013). Silicon is also important for the immune system and prevents arteriosclerosis. ...
... It is worth noticing that our research, for the first time, confirmed the similarity between Si and Al for human intervertebral disc tissue. Our observations are in compliance with those which show a strong relationship of silicon and aluminum, both in humans and in biota (Exley 2009a, b;Davenward et al. 2013). Birchall et al. (1996) suggested that deficiency of silicon and its influence on collagen and osteogenesis may be due to low copper utilization. ...
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There is a growing body of evidence concerning the significant role of silicon in development and composition of both connective and bone tissue. Bio-essential silicon shows strong chemical and biological affinity to aluminum, which is toxic and biologically inessential element. The presence of silicon was confirmed in a variety of tissues; however, it has never been examined in intervertebral disc tissue, neither in healthy nor in degenerated one. In this paper, for the first time in the literature, we present the content of silicon in the degenerated intervertebral disc tissue. We also compared the results of silicon analysis with aluminum values in degenerated intervertebral disc tissue in humans. We used chemometric methods to find correlations and similarities between silicon, aluminum, and elements associated with tissue metabolism (Mg) and degenerative processes (Zn and Cu). The presence of silicon was confirmed in all 30 samples harvested from 22 patients operated on due to degenerative changes. Its concentration was within the range of 5.37–12.8 μg g⁻¹ d.w., with the mean concentration of 7.82 μg g⁻¹ d.w. The analysis showed significant correlation between Si and both Al and Mg and weak or negative correlation with Zn and Cu, where the latter was probably the result of degenerative processes. Although silicon is considered essential in glycosaminoglycan and collagen synthesis in connective tissue, it did not show any correlation nor similarities with elements reflecting changes associated with the degenerative process of the intervertebral disc. Silicon showed significant correlation with aluminum, similar to those observed in other human tissues.
... We have pioneered silicon-rich mineral waters as non-invasive methods to facilitate the urinary excretion of aluminium in both health and disease (Exley et al., 2006b). Individuals have been shown to excrete significant amounts of aluminium following regular drinking of 1.0-1.5 L of a silicon-rich mineral water and in individuals with Alzheimer's disease (AD) this resulted in a lowering of their body burden of aluminium over only 12 weeks (Davenward et al., 2013). Herein we have recruited individuals with SPMS and used urinary excretion of aluminium to establish their body burdens of aluminium both before and after regular drinking of a silicon-rich mineral water for 12 weeks. ...
... Upon arrival in the Bioinorganic Chemistry Laboratory the total volumes of the 24 h samples were measured and thereafter all urine samples were thoroughly mixed and sampled for subsequent creatinine analyses using the Jaffe reaction. Further sub-samples were then stored frozen prior to their microwave-assisted acid digestion and analysis of total aluminium and silicon by transversely heated graphite furnace atomic absorption spectrometry (TH GFAAS) (Davenward et al., 2013). ...
... A longer study over months and years would help to test the validity of this hypothesis. It is of note that the median urinary excretion of aluminium in week 12 of the previous AD study (Davenward et al., 2013) was 64.8 nmol/mmol Crt compared to 389.9 nmol/mmol Crt in SPMS. This may be further evidence that the body burden of aluminium in MS may be significantly higher than it is in AD and as such it may take considerably longer to lower the body burden of aluminium in MS through regular drinking of a silicon-rich mineral water. ...
Article
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Background: Progressive multiple sclerosis is a chronic autoimmune condition of unknown aetiology and few therapeutic options. Human exposure to aluminium has been linked with multiple sclerosis and affected individuals are known to excrete unusually high amounts of aluminium in their urine. Silicon-rich mineral waters facilitate the removal of aluminium from the body in urine and herein we have tested their efficacy in affecting urinary excretion of aluminium in individuals diagnosed with secondary progressive multiple sclerosis (SPMS). Methods: Urinary excretion of aluminium and silicon, measured using transversely-heated graphite furnace atomic absorption spectrometry, was determined in 15 individuals diagnosed with SPMS over 24weeks, a 12week baseline period (control) followed by a 12week treatment period, during which individuals consumed up to 1.5L of a silicon-rich mineral water every day. Findings: Individuals with SPMS excreted high amounts of aluminium during the baseline period (135.2nmol/mmol Crt (70.3-222.2, n=180) and females excreted significantly more aluminium than males. Regular drinking of a silicon-rich mineral water increased the urinary excretion of aluminium significantly (349.0nmol/mmol Crt (231.7-524.7, n=180; three-way ANOVA, F1,13=59.17, p-value=0.000003) relative to the baseline period. The majority of individuals, 14 out of 15, excreted more aluminium (μmol/24h) following drinking of a silicon-rich mineral water (independent-test, p<0.05). Silicon-rich mineral waters may be an effective and non-invasive therapy for the removal of aluminium from the body of individuals with SPMS.
... [25] Studies have shown a correlation between improvements in Alzheimer's disease and hair loss with ingestion of fruits and vegetables with high Si content. [26,27] Chromium is considered to be an important microelement for normal carbohydrate, lipid and protein metabolism in humans. [28] The consumption of 10 g of fruits exceeds the RDA for this element (1342%). ...
... However, high intake of Cr is not linked to adverse health effects therefore the Institute of Medicine has not established a tolerable upper intake level (UL) for this element. [26] Soil propertiessoil pH, SOM and CEC ...
Article
In this study, the elemental distribution of essential and toxic elements in the soil and fruits of the indigenous plant species, Mimusops caffra, from ten sites along the KwaZulu-Natal east coast was investigated using inductively coupled plasma-optical emission spectrometry. This was done to determine the nutritional value of the fruits as well as to evaluate the impact of soil quality on elemental uptake by the plant. The elemental concentrations in the fruits (in descending order) were found to be K > Na > Ca > Mg > Si > Al > Fe > Zn > Mn > Ni > Cr > Cu > Pb > Mo > Sb > As > Se > V > Cd > Co. The results show that approximately 10?g of fruit would contribute more than 85% towards the recommended dietary allowance for Fe and Si for most adults. The proximate chemical composition revealed the fruits to contain approximately 84% moisture, 4.7% ash, 6.9% protein, 1.7% oil and 2.7% carbohydrates. The study indicates that the fruits of this indigenous plant species are a good source of essential elements with low levels of potentially toxic elements (Pb, As and Cd) which makes the plant a good indigenous food source especially for vulnerable communities that need food security.
... However, research has shown a significant protective effect of silicon in drinking water, irrespective of the aluminum content, with higher silicon reducing the incidence of Alzheimer's disease [23]. In addition, clinical trials involving only a small number of participants have shown that regular drinking of a silicon-rich mineral water helps to remove aluminum from the body of individuals with Alzheimer's disease [24,25]. For 20% of such individuals, the lowering of the body burden of aluminum following drinking a silicon-rich mineral water for just 12 weeks produced clinically significant improvements in their cognitive function [25]. ...
... In addition, clinical trials involving only a small number of participants have shown that regular drinking of a silicon-rich mineral water helps to remove aluminum from the body of individuals with Alzheimer's disease [24,25]. For 20% of such individuals, the lowering of the body burden of aluminum following drinking a silicon-rich mineral water for just 12 weeks produced clinically significant improvements in their cognitive function [25]. The potential benefits of silicon in Alzheimer's disease can only be explained if aluminum has a role to play in the disease. ...
Article
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In this paper, I have summarized the experimental and largely clinical evidence that implicates aluminum as a primary etiological factor in Alzheimer’s disease. The unequivocal neurotoxicity of aluminum must mean that when brain burdens of aluminum exceed toxic thresholds that it is inevitable that aluminum contributes toward disease. Aluminum acts as a catalyst for an earlier onset of Alzheimer’s disease in individuals with or without concomitant predispositions, genetic or otherwise. Alzheimer’s disease is not an inevitable consequence of aging in the absence of a brain burden of aluminum.
... These nanoparticles have demonstrated promising results when in previous in-vitro studies. For example, both boron nitride nanotubes and molybdenum disulfide nanoparticles have been used in the treatment of brain diseases (Ciofani et al. (2011);Han et al. (2017)), and recent clinical trials have also found that silica based materials may reduce cognitive impairment associated with AD (Davenward et al. (2013)). Based on this information, we selected three biocompatible monolayers and tested their chelation potential. ...
... Silicene was initially selected as its high surface area is suitable for metal adsorption, and its buckled structure points towards reactivity that may allow copper binding. Recent clinical trials have also revealed that silica particles may reduce the cognitive impairment associated with AD (Davenward et al. (2013)). Analysis of copper coordination to silicene revealed that copper displayed a preference for the hollow site. ...
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Alzheimer's disease is a neurodegenerative disorder that results in the death of neurons and impaired cognitive function. One of the pathological hallmarks of Alzheimer's is the formation of senile plaques which originate from the aggregation of the Amyloid-β protein. Recent research has found that the overabundance of certain metal-ions in the brain may contribute to this problem, and that chelation therapy may be an effective tool to solve it. In this study, we conducted Density Functional Theory calculations to investigate the interaction of metal ions to the Amyloid-β protein, as well as the adsorption of the copper-ion by potential chelation materials. We conducted binding energy calculations and plotted the charge transfer between the metals and the substrates in order to evaluate bond strength. Binding energy calculations revealed that the binding affinities followed the order of Cu > Al > Zn, proving copper to retain the strongest affinity compared to other metal ions of biological significance. Due to copper's strong affinity, binding energies were also evaluated for its interaction with potential chelators: monolayer boron nitride, monolayer molybdenum disulfide, and monolayer silicene. Silicene produced the highest binding energies to copper, and the evidence of charge transfer between copper and the monolayers proves that there is a strong ionic bond present. Although our three monolayers did not directly present chelation potential, the absolute differences between the binding energies of the silicene binding sites and the Amyloid-β binding sites were minimal proving that further research in silicene chelators will open doors for therapy in Alzheimer's disease.
... The LS water extract used in this study is an exogenous antioxidant rich in the silicon that chelates with different silicon compounds such as propanoic acid, and proline. Proline-rich polypeptides (PRPs) have a high potency for hydroxyl acid scavenger (Davenward, Bentham, & Wright, 2013;Nićiforović & Abramovič, 2014;Raouf, Gashlan, Khedr, & Al-Jabbri, 2015). However, PRPs have been shown to produce cognitive improvement in an experimental model and in patients with AD. ...
... Propionic acid (Trimethylsilyl) can bind to β (12-28) that is a central fragment of the 40-42-residue Alzheimer's-associated Aβ peptide, and causes dissociation of these peptide aggregates (Jayawickrama & Larive, 1999). Thus, silicon when reduces the accumulation of Al in brain in the Cure and Prot groups, reduces for that reason its above mentioned effects that mediated with AD (Davenward et al., 2013). ...
... [4,6,7] Some studies have suggested that silicon (Si) is a natural antidote to the Al 3+ that may decrease the bioavailability of Al by hindering its uptake through the gastrointestinal tract and by impeding its reabsorption. [8][9][10] The main sources of Si via foods are cereal products, unrefined grains, and root vegetables; however, its availability in meat, milk, and beer is higher than the others. [11] Studies have suggested that Si is essential in rats and chicks' diet, and its insufficiency is associated with growth defects, especially with bone and cartilage formation, whereas, a study in human has shown that ingestion of a Si supplement resulted in an increase in bone mass. ...
... Moreover, the negative correlation is an emphasis on the study of Davenward et al., where they suggested that Si rich mineral water could be a treatment for Alzheimer disease as it may eliminate the aggregated Al in tissues by urinary excretion. [8] Comparison between Figure 2a and b and fewer fluctuations in Al concentrations, and in Figure 2c and d with a different pattern in Si concentrations gives the impression that other sources of water was fed into the distribution system. Nevertheless, it should be emphasized that the correlation between Al and Si is clear in the two studied seasons. ...
Article
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Background: High concentrations of elements such as aluminum (Al) and silicon (Si) in drinking water can affect human health. It is suggested that high daily intake of Al is associated with increased risk of neurodegenerative disorders. Si, as an antidote of Al, may decrease Al bioavailability. The study was conducted to estimate Al and Si concentration and correlation in water and evaluate their health risk. Methods: In this cross-sectional study, water samples were collected from 20 points of water distribution system and the water treatment plant of Isfahan in spring and summer. Samples were analyzed using DR-5000. The health risk was evaluated via calculating chronic daily intake (CDI) and hazard index (HI). Results: Significant negative correlation was documented between Al and Si (R = -0.482, P = 0.037 in spring, and R = -0.452, P = 0.049 in summer). These values were approximately similar in all types of Al and Si. The amounts of CDI for Al in spring and summer were 6.67E-04 and 0.002 mg/kg/day, respectively. The Al HI values were below 1 in both seasons. Conclusions: The significant correlation between Al and Si concentrations suggests that Si can eliminate Al in water, and probably it might do the same in the body. The health risk of Al intake from tap water was negligible, it was assessed in an acceptable range with an HI value of less than the standard levels. The health risk of Si remained unknown due to lack of information regarding its toxicity and adverse health effects.
... While it is important that we obtain such data our default position on this is that to achieve maximum protection against everyday human exposure to aluminum the consumption of a silicon-rich mineral water should become a normal part of an individual's diet and lifestyle. In a small cohort of individuals with Alzheimer's disease, we were able to demonstrate a statistically significant reduction in their body burdens of aluminum over 12 weeks of treatment while in their age and gender-matched control population the reductions in body burden of aluminum did not reach statistical significance in the same period (39). We do not, of course, know if aluminum is being removed from all of the body, for example, if it is being purged from the brain. ...
... The assumption, which is as good as we can make at the moment, is that all body stores of aluminum will be in some sort of dynamic equilibrium with the blood and so the removal of aluminum from the blood via the kidney will drive the removal of aluminum from other tissues including the brain. Tentative support for the removal of aluminum from the brain comes from our recent study on Alzheimer's disease where 3 out of 15 individuals with the disease showed clinically relevant improvements in cognitive performance by the end of the study (39). Up until very recently, we assumed that the major route of elimination of systemic aluminum was in urine. ...
Article
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In the aluminum age, it is clearly unpalatable for aluminum, the globe's most successful metal, to be implicated in human disease. It is unpalatable because for approximately 100 years human beings have reaped the rewards of the most abundant metal of the Earth's crust without seriously considering the potential consequences for human health. The aluminum industry is a pillar of the developed and developing world and irrespective of the tyranny of human exposure to aluminum it cannot be challenged without significant consequences for businesses, economies, and governments. However, no matter how deep the dependency or unthinkable the withdrawal, science continues to document, if not too slowly, a burgeoning body burden of aluminum in human beings. Herein, I will make the case that it is inevitable both today and in the future that an individual's exposure to aluminum is impacting upon their health and is already contributing to, if not causing, chronic diseases such as Alzheimer's disease. This is the logical, if uncomfortable, consequence of living in the aluminum age.
... The use of silicic acid has also been suggested to have a protective affect against the development of dementia [26][27][28]. As previously mentioned, the bioavailability of aluminium in drinking water is, for instance, co-dependent on its silica content: large amounts of silicic acid in drinking water reduce the uptake of aluminium and vice versa [6,10]. ...
... As previously described, one such method utilising silica-enriched water has thus far yielded promising results and has been shown to reduce the human body burden of aluminium. Currently, this method has been shown to reduce the body burden of aluminium in Alzheimer's patients, and release systemic aluminium in urine [26,28]. Its application in other contexts such as in patients undergoing long-term SCIT treatment could be similarly applied. ...
Article
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We are living in an “aluminium age” with increasing bioavailability of the metal for approximately 125 years, contributing significantly to the aluminium body burden of humans. Over the course of life, aluminium accumulates and is stored predominantly in the lungs, bones, liver, kidneys and brain. The toxicity of aluminium in humans is briefly summarised, highlighting links and possible causal relationships between a high aluminium body burden and a number of neurological disorders and disease states. Aluminium salts have been used as depot-adjuvants successfully in essential prophylactic vaccinations for almost 100 years, with a convincing positive benefit-risk assessment which remains unchanged. However, allergen-specific immunotherapy commonly consists of administering a long-course programme of subcutaneous injections using preparations of relevant allergens. Regulatory authorities currently set aluminium limits for vaccines per dose, rather than per treatment course. Unlike prophylactic vaccinations, numerous injections with higher proportions of aluminium-adjuvant per injection are applied in SCIT and will significantly contribute to a higher cumulative life dose of aluminium. While the human body may cope robustly with a daily aluminium overload from the environment, regulatory cumulative threshold values in immunotherapy need further addressing. Based on the current literature, predisposing an individual to an unusually high level of aluminium, such as through subcutaneous immunotherapy, has the potential to form focal accumulations in the body with the propensity to exert forms of toxicity. Particularly in relation to longer-term health effects, the safety of aluminium adjuvants in immunotherapy remains unchallenged by health authorities. The possibility of providing an effective means of measuring aluminium accumulation in patients undergoing long-term SCIT treatment as well as reducing their aluminium body burden, is discussed.
... In particular humans are experiencing a burgeoning exposure to aluminium in everyday life 26 and such is implicated in a number of chronic diseases including neurological conditions such as Alzheimer's disease 27 . The formation of HAS has been shown to protect against the toxicity of aluminium 3,28 and is believed to underlie the mechanism whereby silicon-rich mineral waters facilitate the removal of aluminium from the human body 25 . The therapeutic potential of Si(OH) 4 was recently reviewed 9 but it was Louis Pasteur (June 13 th 1878) who is attributed as saying that "effects of silicic acid are destined to play a great and major role in therapy" and the formation of HAS may well be the mechanism. ...
Article
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The formation of hydroxyaluminosilicates is integral to the biogeochemical cycles of aluminium and silicon. The unique inorganic chemistry which underlies their formation explains the non-essentiality in biota of both of these elements. However, the first steps in the formation of hydroxyaluminosilicates were hitherto only theoretical and plausibly only accessible in silico. Herein we have used computational chemistry to identify and define for the first time these unique and ultimately critically important reaction steps. We have used density-functional theory combined with solvent continuum models to confirm first, the nature of the reactants, an aluminium hydroxide dimer and silicic acid, second, the reaction products, two distinct hydroxyaluminosilicates A and B and finally, how these are the precursors to highly insoluble hydroxyaluminosilicates the role of which has been and continues to be to keep inimical aluminium out of biota.
... Reduction of dietary sources of aluminum, lead and fluoride via filtration or replacement with silica-rich waters should be studied as a way to prevent total aluminum exposure. A study of silicic acid-rich mineral waters found reduction of total aluminum body burden and increase in cognitive performance in some study participants [190]. Other participants showed no change, and some show continued decline. ...
Article
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Neurodevelopmental disorders, including Autism Spectrum Disorders, have a complex biological and medical basis involving diverse genetic risk and myriad environmental exposures. Teasing apart the role of specific stressors is made challenging due to the large number of apparently contributing associations, gene X environment interactions and phenomimicry [1]. Historically, these conditions have been rare, making causality assessment at the population level infeasible. Only a few vaccines have been tested for association with autism, and it has been shown that improved diagnosis only explains a percentage of the increase in diagnosis. Now, the rates are so high in some countries that public school programs cannot handle the large numbers of special needs students, and professionals are quitting their jobs due to security concerns. Here, I review evidence of the pathophysiology of autism that reconciles the apparent paradox between the high degree of causal heterogeneity in environmental toxins, the absence of common "autism gene," and the high degree of genetic concordance (heritability) of ASD and ASD-like traits. In brief, the sampling of environmental toxins, and thus the environmental toxin sampling liability for ASD varies among families involving different local exposures following injury to normal cellular endoplasmic detoxification and mitochondrial processes from toxic metals. The literature strongly supports that autism is most accurately seen as an acquired cellular detoxification deficiency syndrome with heterogeneous genetic predisposition that manifests pathophysiologic consequences of accumulated, run-away cellular toxicity. At a more general level, it is a form of a toxicant-induced loss of tolerance of toxins, and of chronic and sustained ER overload (ER hyper stress), contributing to neuronal and glial apoptosis via the unfolded-protein response (UPR). Inherited risk of impaired cellular detoxification and circulating metal retoxification in neurons and glial cells accompanied by chronic UPR is key. This model explains the aberrant protein disorder observed in ASD; the great diversity of genes that are found to have low, but real contributions to ASD risk and the sensitivity of individuals with ASD to environmental toxins. The hindrance of detoxification and loss of cellular energetics leads to apoptosis, release of cytokines and chronic neuroinflammation and microglial activation, all observed hallmarks of ASD. Interference with the development of normal complex (redundant) synapses leads to a pathological variation in neuronal differentiation, axon and dendrite outgrowth, and synaptic protein expression. The most general outcomes are overall simplification of gross synaptic anatomy and, neurofunctionally, a loss of inhibitory feedback and aberrations in long-term connections between distant regions of the brain. Failed resolution of the ER stress response leads to re-distribution of neurotoxic metals, and the impaired neurocellular processes lead to subsequent accumulation of a variety of additional types of toxins with secondary, sometime life-threatening comorbidities such as seizures, with overlapping (not mutually exclusive) causality. Reduction of exposure to toxins known to cause mitopathy (mercury) and endoplasmic reticulum dysfunction (mercury and aluminum) during pregnancy and during the early years of development will reduce the risk of ER overload and ER hyper stress, and of ASD diagnosis. This knowledge has immediate clinical translational relevance: post-vaccination symptoms should be heeded as a sign of susceptibility to toxin; Vitamin D can be increased to drive the healthy early phases of the UPR, and mutations in ASD genes encoding proteins with high intrinsic disorder may contraindicate the use of aluminum and mercury for carriers of risk alleles. Clinicians should be alert to a patient’s Vitamin D receptor (BSM) mutational status prior to recommending increased doses. Approaches to improving overall brain health in autistics must be de-stigmatized and given high priority. Reduction of lifetime exposures of industrial and agricultural toxins will improve brain health for the entire human population. Purely genetic studies of ASD, and studies that do not include vaccination as an environmental exposure with potential liability and interactions with genes, are unethical. To qualify as science, studies must test plausible hypotheses, and the absence of association from poorly designed, unethically executed, and underpowered and unsound whole-population association studies have been harmful distractions in the quest for understanding. Skilled paediatricians and ob/gyns will seek evidence of genetic predisposition to environmental susceptibility in the form of non-synonymous substitutions in brain proteins that require ER-folding, and they will provide informed cautions on exposures (from all sources) to environmental toxins to patients and parents of patients with signs of metal and chemical sensitivity. To aid in this, a list of ASD environmental susceptibility protein-encoded genes is presented. A clinical Exome sequence test, followed by loss of function prediction analysis, would point to individuals most susceptible to vaccine metal-induced ER hyper stress leading to failed cellular detoxification.
... Davenward et al. [20] showed that Si-rich mineral waters can be used as a non-invasive method to reduce the body burden of Al in both Alzheimer's patients and a control group by facilitating the removal of Al via the urine without any other concomitant effect. Si has also been shown to induce clinically relevant cognitive improvements in a pilot study with 3 of 15 patients with Alzheimer's disease [20][21][22]. This suggests a possible use for ortho-silicic acid as long-term non-invasive therapy for Al reduction in Alzheimer's disease patients. ...
Article
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Background Hydrogen peroxide (H2O2) is a toxic agent that induces oxidative stress and cell death. Silicon (Si) is a biological element involved in limiting aluminium (Al) absorption with possible preventive effects in Alzheimer’s disease. However, Si has not yet been associated with other neuroprotective mechanisms. Methods The present experiments evaluated in the SH-SY5Y human neuroblastoma cell line the possible role of different Si G5 (50-1000 ng/mL) concentrations in preventing cellular death induced by H2O2 (400 μM, 24 hours). Results Our findings showed that H2O2 promoted cell death in the human SH-SY5Y cell cultures and this could be prevented by Si treatment. The loss in cell viability mediated by H2O2 was due to an apoptotic and necrotic process. Apoptotic death was incurred by regulating caspase-8 activity in the extrinsic pathway. The apoptotic and necrotic cell death induced by H2O2 was almost totally reversed by Si (50-500 ng/mL), indicating that it down-regulates both processes in H2O2 treated cells. Conclusions According to our data, Si is able to increase SH-SY5Y cell survival throughout partially blocking cellular damage related to oxidative stress through a mechanism that would affect H2O2/ROS elimination.
... We have also been investigating non-invasive ways to reduce the uptake of aluminium into the body and, importantly, to facilitate the excretion of aluminium from the body. We were successful in lowering the body burden of aluminium in individuals with moderateto-severe AD and concomitantly we were able to demonstrate clinically significant improvements in cognitive performance in some individuals [14]. These experiments offer some hope that the aluminium hypothesis of AD, and indeed other neurodegenerative diseases, might be tested by lowering the body burden of aluminium in affected individuals. ...
Article
Aluminium is neurotoxic. Its free ion, Al(3+) (aq), is highly biologically reactive and uniquely equipped to do damage to essential cellular (neuronal) biochemistry. This unequivocal fact must be the starting point in examining the risk posed by aluminium as a neurotoxin in humans. Aluminium is present in the human brain and it accumulates with age. The most recent research demonstrates that a significant proportion of individuals older than 70 years of age have a potentially pathological accumulation of aluminium somewhere in their brain. What are the symptoms of chronic aluminium intoxication in humans? What if neurodegenerative diseases such as Alzheimer's disease are the manifestation of the risk of aluminium as a neurotoxin? How might such an (outrageous) hypothesis be tested?
... Based on the knowledge that silicon is the natural antagonist to Al 3+ , some researchers have shown that silicon-rich mineral waters can be used to reduce the body burden of Al 3+ in individuals with Alzheimer's disease, macrophagic myofasciitis, and chronic fatigue syndrome. [61,211] Pogue and Lukiw [229] reported that drinking up to 1 L of a silicon-rich mineral water each day for 12 weeks facilitate the removal of Al 3+ via the urine without any concomitant affect upon the urinary secretion of iron and copper. [194] There is some evidence that silicone could act either as a neuroprotector, since low doses increased cell viability and reduced TNF-α levels, or as a neurotoxic agent at higher concentrations. ...
Article
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Our review suggests that most autism spectrum disorder (ASD) risk factors are connected, either directly or indirectly, to immunoexcitotoxicity. Chronic brain inflammation is known to enhance the sensitivity of glutamate receptors and interfere with glutamate removal from the extraneuronal space, where it can trigger excitotoxicity over a prolonged period. Neuroscience studies have clearly shown that sequential systemic immune stimulation can activate the brain’s immune system, microglia and astrocytes, and that with initial immune stimulation, there occurs CNS microglial priming. Children are exposed to such sequential immune stimulation via a growing number of environmental excitotoxins, vaccines, and persistent viral infections. We demonstrate that fluoride and aluminum (Al3+) can exacerbate the pathological problems by worsening excitotoxicity and inflammation. While Al3+ appears among the key suspicious factors of ASD, fluoride is rarely recognized as a causative culprit. A long-term burden of these ubiquitous toxins has several health effects with a striking resemblance to the symptoms of ASD. In addition, their synergistic action in molecules of aluminofluoride complexes can affect cell signaling, neurodevelopment, and CNS functions at several times lower concentrations than either Al3+ or fluoride acting alone. Our review opens the door to a number of new treatment modes that naturally reduce excitotoxicity and microglial priming.
... The effect of aluminium on the human body and human health as well as aluminium intake through cosmetic preparations and pharmaceutical preparations, particularly in childhood vaccines [15,16,17,18,19], is still being discussed. Aluminium has a potential neurotoxic effect, and its intake by the human organism is connected with, for example, Alzheimer's disease, autism and breast cancer [15,20,21,23,24]. Therefore, the determination of aluminium in environmental, pharmaceutical and cosmetic preparations is very important and greatly needed [25]. ...
... Silica is pivotal in calcium phosphate nucleation, determinant in bone mineralization, growth and self-healing during dislocations and fractures [59]. Aluminum absorption and (eventual) intoxication in human body (particularly important in Alzheimer's disease) may be prevented by silica ingestion, through the bonding to Al in the gastrointestinal tract [60,61]. Maintenance of health in the immune system and reduction of the risk of atherosclerosis are other of silica attributes [62]. ...
Article
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Silica is one of the most abundant minerals in the Earth’s crust, and over time it has been introduced first into human life and later into engineering. Silica is present in the food chain and in the human body. As a biomaterial, silica is widely used in dentistry, orthopedics, and dermatology. Recently amorphous sol-gel SiO2 nanoparticles (NPs) have appeared as nanocarriers in a wide range of medical applications, namely in drug/gene target delivery and imaging diagnosis, where they stand out for their high biocompatibility, hydrophilicity, enormous flexibility for surface modification with a high payload capacity, and prolonged blood circulation time. The sol-gel process is an extremely versatile bottom-up methodology used in the synthesis of silica NPs, offering a great variety of chemical possibilities, such as high homogeneity and purity, along with full scale pH processing. By introducing organic functional groups or surfactants during the sol-gel process, ORMOSIL NPs or mesoporous NPs are produced. Colloidal route, biomimetic synthesis, solution route and template synthesis (the main sol-gel methods to produce monosized silica nanoparticles) are compared and discussed. This short review goes over some of the emerging approaches in the field of non-porous sol-gel silica NPs aiming at medical applications, centered on the syntheses processes used.
... Насколько нам известно, на сегодняшний день нет данных об изменении уровня кремния в биосубстратах при синдроме Дауна. Кремний известен своим антагонизмом с алюминием [30], и употребление богатой кремнием воды приводило к значительному выделению алюминия у пациентов с болезнью Альцгеймера [31]. ...
Article
The objective of the present study was to assess gender effects on the levels of essential and toxic chemical elements in hair of children with Down’s syndrome. It has been revealed that hair phosphorus in boys and girls with Down’s syndrome exceeded the con-trol values by 36% (p < 0,001) and 30% (p < 0,001), respectively. Boys were also characterized by increased hair magnesium con-tent. At the same time, hair zinc in boys and girls suffering from Down’s syndrome was 54% (p = 0,021) and 109% (p = 0,085) high-er as compared to the control levels. Girls with the syndrome were characterized by higher hair chromium and silicon levels. In con-trast to other metals, in boys and girls with Down’s syndrome hair mercury levels were decreased by a factor of more than 2 (p = 0,088) and 3 (p = 0,031), whereas hair content of lead and arsenic was elevated in boys and girls, respectively. Two-way ANOVA demonstrated a significant factorial interaction (gender*syndrome) only in the case of Cr (p = 0,030) and Hg (p = 0,031). Therefore, the results of the study indicate a possible pathogenic role of trace element imbalance in Down’s syndrome.
... Reduction of dietary sources of aluminum, lead and fluoride via filtration or replacement with silica-rich waters should be studied as a way to prevent total aluminum exposure. A study of silicic acid-rich mineral waters found reduction of total aluminum body burden and increase in cognitive performance in some study participants [190]. Other participants showed no change, and some show continued decline. ...
... In this context, combined strategies aiming to increase the removal of Al from the human body and to prevent the effects of the remaining Al could be an alternative to reduce the impact of the overall chronic Al intoxication. Drinking silicon-rich mineral water (30 mg/L, 1 L/ day) appears to facilitate the excretion of Al from the body and improve cognitive function in Alzheimer's patients [70]. In the reproductive system, the natural active product found in crucifers, such as broccoli sprouts and sulforaphane, showed the potential to lower AlCl 3 -induced testicular toxicity in rats [71]. ...
Article
Full-text available
Aluminum (Al) is a non-essential metal omnipresent in human life and is considered an environmental toxicant. Al increases reactive oxygen production and triggers immune responses, contributing to chronic systemic inflammation development. Here, we have tested whether an egg white hydrolysate (EWH) with potential bioactive properties can protect against changes in reproductive function in rats exposed to long-term Al dietary levels at high and low doses. Male Wistar rats received orally: low aluminum level group—AlCl3 at 8.3 mg/kg b.w. for 60 days with or without EWH (1 g/kg/day); high aluminum level group—AlCl3 at 100 mg/kg b.w. for 42 days with or without EWH (1 g/kg/day). The co-administration of EWH prevented the increased Al deposition surrounding the germinative cells, reducing inflammation and oxidative stress in the reproductive organs. Furthermore, the daily supplementation with EWH maintained sperm production and sperm quality similar to those found in control animals, even after Al exposure at a high dietary contamination level. Altogether, our results suggest that EWH could be used as a protective agent against impairment in the reproductive system produced after long-term exposure to Al at low or high human dietary levels.
... On the contrary, aluminum reduction was actually correlated directly to the consumption of M-OSA and MMST. This effect is in accordance with the literature: epidemiological studies already suggested that silicon can prevent the absorption of aluminum and/or increase its excretion [31][32][33][34]. Indeed, in nature, silicon readily forms complexes with aluminum and therefore, aluminosilicates are the most prevalent form of silicates [3]. ...
Article
Full-text available
Chemical form of silicon determines its absorption and bioavailability: particulate and polymerized forms exhibit minimal oral bioavailability, while monomers (maltodextrin-stabilized orthosilicic acid, M-OSA) and organic compounds (monomethylsilanetriol, MMST) may hypothetically be highly absorbed. This study aimed to investigate the dermatological effects of oral ingestion of silicon, either solid (M-OSA-SiliciuMax® Powder) or liquid (MMST, SiliciuMax® Liquid) on the skin, hair and nails of healthy volunteers, through a clinical trial (Registry number 2,032,724. Full protocol at Plataforma Brasil website). Patients were randomized to receive 5 mg of elemental Si, either M-OSA or MMST (group 1 and 2, n = 17 each) or placebo (group 3, n = 17) twice a day for 150 days. Clinical and patients' subjective evaluations were conducted. Multispectral face imaging and hair mineral analysis were also performed. Use of M-OSA and MMST provided significant (p < 0.05) betterment of facial wrinkles and UV spots. Changes were also observed at the end of the study in skin texture and length of eyelashes. Hair aluminum levels decrease with the treatments. Self-reported questionnaire indicated good satisfaction with both M-OSA and MMST. Continuous use of both M-OSA and MMST can provide improvements on skin parameters, as well as act as a detox agent for aluminum.
... In particular, silicon administration significantly reduces aluminum absorption and retention [62]. In addition, drinking silicon-rich water resulted in a significant aluminum excretion in Alzheimer patients [63]. Aluminum was proposed to be the one of the key etiological factors in Alzheimer's disease [64], although certain studies demonstrate that hair Al levels may be normal [65] or reduced in AD. ...
Article
Full-text available
The objective of the present study was to assess the level of minerals and trace elements in 40 children with Down’s syndrome and 40 controls aged 1–2 years old. Hair mineral and trace element analysis was performed using inductively coupled plasma mass spectrometry. The obtained data demonstrate that hair levels of Mg, P, I, Cr, Si, Zn, and Pb in Down’s syndrome patients exceeded the respective control values by 36, 36, 93, 57, 45, 28, and 54%, whereas hair mercury was more than twofold lower in children with Down’s syndrome. The observed difference in the levels of trace elements was age-dependent. In particular, in 1-year-olds, major differences were observed for essential elements (Cr, Si, Zn), whereas in 2-year-olds—for toxic elements (Hg, Pb). At the same time, hair P levels in Down’s syndrome patients were 14 and 35% higher at the age of 1 and 2 years in comparison to the respective controls. Multiple regression analysis demonstrated that a model incorporating all elements, being characterized by a significant group difference, accounted for 42.5% of status variability. At the same time, only hair phosphorus was significantly interrelated with Down’s syndrome status (β = 0.478; p < 0.001). Principal component analysis (PCA) used As, Ca, Cr, Fe, Hg, I, Mg, P, Pb, Se, Si, Sn, and Zn as predictors, with the resulting R² = 0.559. The OPLS-DA models also separated between Down’s and health control groups. Therefore, 1–2-year-old patients with Down’s syndrome are characterized by significant alterations of mineral and trace element status.
... A number of previous studies have investigated associations between aluminum in drinking water and AD (Rondeau et al., 2000;2009;Martyn et al., 1989;Forbes and McLachlan, 1996;Jacqmin-Gadda et al., 1996;McLachlan et al., 1996;Frecker, 1991;Neri and Hewitt, 1991;Wood et al., 1988;Wettstein et al., 1991;Forster et al., 1995;Sohn et al., 1996;Gillette-Guyonnet et al., 2005;Flaten, 1990;2001). Davenward et al. (2013) found that administration of silicon-rich water for 12 weeks reduced the aluminum body burden in 3 of 15 AD patients, and that these patients had clinically relevant improvements in cognition, suggesting a possible role of aluminum in AD. Two large prospective studies (Rondeau et al., 2000;2009) included relevant socio-demographic and water quality covariates: the most recent examined a 15 year follow-up of the PAQUID cohort where individual intakes of aluminum and silica based on daily consumption of tap and bottled water were assessed (Rondeau et al., 2009). ...
Article
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Epidemiological evidence linking aluminum in drinking water and Alzheimer’s disease (AD) has been inconsistent, with previous studies often limited by small sample sizes. The present study addresses this issue using data from the Canadian Study of Health and Aging (CSHA), a prospective cohort of 10,263 subjects followed-up from 1991-1992 through 2001-2002. Participants’ residential histories were linked to municipal drinking water sources in 35 Canadian municipalities to obtain ecologic pH, aluminum, fluoride, iron and silica concentrations in drinking water. Cox proportional hazards models were used to examine associations between aluminum and incident AD [Hazard Ratios (HRs), 95% confidence intervals (CIs)], adjusting for age, gender, history of stroke, education, and high blood pressure. A total of 240 incident AD cases were identified during follow-up of 3, 638 subjects derived from the CSHA cohort with complete data on all covariates. With categorical aluminum measurements, there was an increasing, but not statistically significant, exposure-response relationship (HR = 1.34, 95% CI 0.88-2.04, in the highest aluminum exposure category; p = 0.13 for linear trend). Similar results were observed using continuous aluminum measurements (HR=1.21, 95% CI 0.97-1.52, at the interquartile range of 333.8 μg/L; p = 0.09 for linear trend). In a subsample genotyped for ApoE-ε4, there was some evidence of an association between aluminum and AD (p=0.03 for linear trend). Although a clear association between aluminum in drinking water and AD was not found, the linear trend observed in ApoE-ε4 subsample warrants further examination.
... Datorita acestor efecte au apărut floculanții și coagulanții cu structură complexă, care conțin siliciu. Cercetări apărute recent arată rolul pozitiv al siliciului în tratamentul maladiei Alzheimer [42]. ...
Book
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Studiile efectuate la nivel monsial au arătat că utilizarea reactivilor de coagulare-floculare asigură reducerea aldehidelor, fenolilor și aminoacizilor. Substanțele organice cu masa moleculară mare sunt ușor îndepărtate, în timp ce zaharurile și hidrații de carbon sunt relativ puțin reduși. Faza de coagulare este capabilă de a reduce 30-50% din concentrația de carbon organic biodegradabil (BDOC) și între 50-80% a carbonului organic asimilabil (AOC). Apariția coagulanților prehidrolizați și apoi a celor bicomponenți a crescut eficiența în reducerea conținutului mineral, organic şi biobacteriologic al apelor de suprafață folosite pentru potabilizare, concomitent cu obținerea unor concentrații minime de metal rezidual Într-un proces convențional de tratare a apei, coagularea și flocularea reprezintă etapele cheie ce determină destabilizarea particulelor și aglomerarea lor, care pot fi apoi eliminate prin procese de sedimentare și filtrare. Utilizarea eficientă a acestor procese ca parte a unei strategii de bariere multiple pentru reducerea materiei organice naturale și microbiene reprezintă o abordare operațională pentru producătorii de apă în asigurarea biostabilității apei livrate. Datorită complexității conceptului de biostabilitate a apei, este necesară definirea unui set de indicatori şi a unor limite acceptabile la nivel internațional. Determinările privind indicatorii de biostabilitate din punct de vedere al tehnicii de laborator trebuie să fie simple şi rapide, astfel încât să asigure implementarea de măsuri corective şi preventive.
... Epidemiological studies demonstrated that increased silicon intake may prevent adverse neurological effects of Al (Davenward et al., 2013;Nielsen, 2014) through its direct interaction with Al ion forming aluminosilicate thus reducing Al bioavailability and toxicity (Domingo et al., 2011). Particularly, increased Si intake was shown to reduce brain Al accumulation in mice (Granero et al., 2004). ...
Chapter
Recent studies have demonstrated that brain may be considered as the target for aluminium (Al) toxicity, resulting in development of neurodegenerative and neurodevelopmental disorders. However, the particular mechanisms of Al neurotoxicity and their role in Al-associated neurological disorders are still debatable. The neurotoxic effect of Al exposure is mediated by its common toxic properties including prooxidant, proinflammatory, proapoptotic activity that are reported for a variety of cell lines and tissues, as well as more specific “neurotropic” effects namely interference with neurotransmitter metabolism and neuronal cytoskeleton. Although specific treatment of Al toxicity is not developed, Al chelation as well as compounds targeting molecular mechanisms of Al neurotoxicity (trace elements, polyphenols, phytoextracts, etc.) may be considered as therapeutic strategies to counteract Al neurotoxicity. However, further studies are required to unravel the particular role of Al in neurological diseases and specific treatment agents.
... However, the downregulation of Nrf2 and loss from the hippocampal neural nuclei of AD patients is emblematic of the fact that this normal state of affairs can be subverted in diseases [216,303,305]. As mentioned, two examples of the inhaled and ingested toxins that accumulate in AD patients' brains are iron and aluminum [144,145,578,583,584,586,591,592,595,603,[609][610][611]900,901]. ...
Thesis
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Abstract. Consistent with the numerous Aβ-targeting clinical trials that failed to meet their primary endpoints, Aβ does not correlate spatiotemporally with oxidative stress (OS), oxygen/glucose hypometabolism, or other AD hallmarks in sporadic Alzheimer’s disease (AD) patients, suggesting it is a compensatory response and an amplifying signal in sporadic AD, not the distal or primary cause of sporadic AD as some still believe. Diverse bacteria, fungi, and DNA viruses accumulate in AD patients’ brains. OS occurs in the preclinical AD (PCAD) medial temporal lobe (MTL), but not the PCAD neocortex. However, oxidatively damaged DNA (oxoDNA) accumulates in the MTLs and neocortices of PCAD, mild cognitive impairment (MCI), and AD patients. DNA-oxidizing iron and aluminum accumulate in AD patients’ hippocampal neuron chromatin. OS, pathogens, and cytokines drive Aβ42 deposition. At the intersection of OS and poly-microbial infections in AD, we hypothesize oxoDNA drives multiple AD hallmarks at all stages of AD pathogenesis. OxoDNA appears to drive Aβ42 deposition via <cGAS/cGAMP/STING/IFN/AIM2>, <MYD88→NFκB→BACE1>, <MAP4K4→JNK→AP1>, and <CK2→pSer529-p65-NFκB→BACE1>. OxoDNA appears to spread OS via Nrf2 mislocalization. OxoDNA appears to drive tau hyperphosphorylation via mitochondrial OS induction. OxoDNA appears to drive oxygen hypo-metabolism, ATP depletion, and mitochondrial OS via <PARP1→PAR→PARG→ADPR→TPRM2→AMP→ANT→ADP→ATP synthase inhibition>. OxoDNA appears to drive neurotoxicity via <PARP1→PAR→mPTP→AIF→parthanatos>, <ROS,ADPR,Ca2+→TRPM2→Ca2+,Zn2+→(Zn2+/LKB1/pThr172-AMPKα2)→p-FOXO3→Bim→oxytosis/ferroptosis>, <CK2→pSer529-p65→Noxa+Bim>, <ATM→p53→caspase9+BAX+APAF1→apoptosis>, <AIM2→caspase1→gasderminD→pyroptosis>. OxoDNA appears to drive synaptoxicity via PARP1, <ADPR→TRPM2→Ca2+>, p53, NFκB, IL-6, <AIM2→caspase1→IL-1β>. OxoDNA appears to drive immunosuppression via IFNs+IL-6→SOCS1/3, and <AIM2+(Ca2+/CaMKKβ/pThr183-AMPKα1)+EB1+LC3→IL-1β>. Via <ROS,ADPR,Ca2+→TRPM2→Ca2+,Zn2+→ZnT6→S-SMase→ceramide> and possibly <AIM2+(Ca2+/CaMKKβ/pThr183-AMPKα1)+EB1→LC3>, oxygen-hypometabolic and partially immortalized medial temporal lobe pyramidal neurons excite each other, neocortical neurons with trans-synaptic extracellular vesicles bearing Aβ42, Zn2+, p-tau, ceramides, IL-1β, RNA, and oxoDNA, promoting synaptotoxicity. The multi-dsDNA repair factor depletion/suppression in AD neurons appears to have been selected for to evade viral integration, e.g. HHV-6A telomere integration. The ATM and BRCA1 loss in AD neurons appears to have been selected for to evade chromosomal fusions at telomeres deprotected by Ku80 downregulation and triaging to dsDNA breaks. BRCA1 and sporadic-AD-specific BMI1 loss derepress heterochromatin. Tau-associated derepressed endogenous retroviruses induce immunodeficiency. In the hippocampus, oxoDNA/IFN/IL-6-induced SOCS1 and oxoDNA/IFN- plus oxoDNA/IL-6-induced SOCS3 promote JAK/STAT suppression. oxoDNA/IFNs may drive IL-1 resistance. Hippocampal <LPS→TLR4→NFκB→pro-IL-1β> + <oxoDNA→cGAS→IFNs→AIM2> + <AIM2+(Ca2+/CaMKKβ/pThr183-AMPKα1)+EB1+LC3>-mediated IL-1β secretion suppresses neocortex IFN immunity, enabling opportunistic herpesvirus-6A and herpesvirus-7, and drives glucose hypo-metabolism, evading parthanatos and sepsis. Stress-associated glucocorticoids also drive immunodeficiency. AD is an inflammatory/autoimmune/immunosuppressive/pseudo-cancerous brain acquired immunodeficiency meta-syndrome (AIDS) driven by chronic oxidative DNA damage, dsDNA repair factor depletion/suppression, endogenous retrovirus derepression, cytokines, and poly-pathogen dysbiosis.
... Interestingly, oral aluminum bioavailability is known to be increased by acidic pH, such as the pH in the human intestine, but in case of clinoptilolite tuff, it may be decreased, as this is a silicon-containing compound that releases certain amounts of dissolved silica (Jurkić et al., 2013). Data has been provided on the ability of silicon-rich mineral water or silicic acid to remove Al from the human organism (Buffoli et al., 2013;Davenward et al., 2013), and this Si and Al relation has been recognized as the main evolutionary mechanism for fighting ecotoxicity of aluminum in living organisms. Water-soluble silica forms may thus be acknowledged as important contributors to fighting aluminum detrimental effects on human and animal health, especially nowadays when the exposure to bioavailable free aluminum cation poses a serious problem due to industrial development (Exley, 2009;Beardmore et al., 2016;Exley, 2016). ...
Article
Full-text available
Unique and outstanding physical and chemical properties of zeolite materials make them extremely useful in a variety of applications including agronomy, ecology, manufacturing, and industrial processes. Recently, a more specific application of one naturally occurring zeolite material, clinoptilolite, has been widely studied in veterinary and human medicine. Due to a number of positive effects on health, including detoxification properties, the usage of clinoptilolite-based products in vivo has increased enormously. However, concerns have been raised in the public about the safety of clinoptilolite materials for in vivo applications. Here, we review the scientific literature on the health effects and safety in medical applications of different clinoptilolite-based materials and propose some comprehensive, scientifically-based hypotheses on possible biological mechanisms underlying the observed effects on the health and body homeostasis. We focus on the safety of the clinoptilolite material and the positive medical effects related to detoxification, immune response, and the general health status.
... Despite the substantial evidence available to accentuate the role of Al in AD [85] , it has been controversial for a few decades [1,58,86,87] . ...
Article
Full-text available
Aluminium (Al) has long been implicated in the etiology of the neurodegenerative diseases like Alzheimer’s disease (AD). Although abundant studies substantiated its potential role in inducing neurotoxic effects, yet this subject has been a controversy of profound importance. This article summarizes the various ways in which Al induces oxidative stress, eventually leading to cell death. It also gives a brief account of manifold epidemiological studies that relate the abundant occurrence of Al in soil and water and the prevalence of AD. Al carriers, their role in AD, Al in neurofibrillary tangles, biochemical reactions altered by Al influx in mitochondria have been briefly discussed.
... A change in the diet was introduced, replacing as much as possible tap water with silica-rich mineral water, based on positive results with this type of mineral water on various neurological diseases. 1,2 The mineral waters used for this case were first the commercially available brand Carrefour Eau d'Auvergne, that is no longer available, and second Volvic, both with a content of 32 mg/l of silica (SiO2). Family members administered the silicon-rich water as much as possible, however when the child was at pre-school or school (about 9 hours per day, on normal school days) he continued drinking tap water. ...
... Given the new view on the biological role of many micronutrients (which also include silicon and boron), which were previously considered only in terms of health risks or not taken into account as factors necessary for human life, now they should be considered as important factors, which correct the course and intensity of many metabolic processes [2][3][4][5][6][7]. According to the latest literature data, the presence of biologically active components, compounds and substances (silicon, boron, organic matter, etc.), which are xenobiotics by their nature, when it enters the body in mineral water, causes the development of a general adaptive reaction and an increase in nonspecific resistance [8][9][10][11][12][13][14][15]. ...
... While silicon is not an essential element in humans, myriad examples suggest health benefits, perhaps first postulated by Pasteur in the mid-nineteenth century (Dobrzyński and Exley, 2010;Exley, 2012). Relatively recent research demonstrates that silicic acid helps to lower the body burden of aluminium, primarily by facilitating its excretion from the body (Davenward et al., 2013;Jones et al., 2017). The health benefits of silicic acid in humans, like Chlorella, emanate from its antagonism of aluminium toxicity. ...
Article
We contend that silicic acid is a much under-valued molecule and specifically in the context of its role in establishing and maintaining life on Earth. Silicic acid can also be an ill-understood molecule with its chemistry all too often confused with that of either silicates or silica. Herein we (i) provide a working definition for silicic acid; (ii) identify its omnipresent role in biochemical evolution in excluding aluminium from biota and providing adventitious benefits through biological silicification and (iii) explain how the silicic acid cycle is intrinsic to climate change.
... Some additional factors, such as excessive consumption of ethanol, have been suggested to increase Al bioavailability due to increased permeability of the intestinal mucosa [33]. However, experimental studies have shown that silicon (Si) may be protective against aluminum accumulation in the brain [34,35]. It has been previously hypothesized that alcoholic amnesia and dementia may also arise from increased Al exposures in individuals through the excessive consumption of ethanol beverages [33] and that Al accumulation may be regulated by Si availability. ...
Article
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Introduction: Alcohol overuse may be related to increased aluminum (Al) exposure, the brain accumulation of which contributes to dementia. However, some reports indicate that silicon (Si) may have a protective role over Al-induced toxicity. Still, no study has ever explored the brain content of Al and Si in alcoholic use disorder (AUD). Materials and methods: To fill this gap, the present study employed inductively coupled plasma optical emission spectrometry to investigate levels of Al and Si in 10 brain regions and in the liver of AUD patients (n = 31) and control (n = 32) post-mortem. Results: Al content was detected only in AUD patients at mean ± SD total brain content of 1.59 ± 1.19 mg/kg, with the highest levels in the thalamus (4.05 ± 12.7 mg/kg, FTH), inferior longitudinal fasciculus (3.48 ± 9.67 mg/kg, ILF), insula (2.41 ± 4.10 mg/kg) and superior longitudinal fasciculus (1.08 ± 2.30 mg/kg). Si content displayed no difference between AUD and control, except for FTH. Positive inter-region correlations between the content of both elements were identified in the cingulate cortex, hippocampus, and ILF. Conclusions: The findings of this study suggest that AUD patients may potentially be prone to Al-induced neurodegeneration in their brain-although this hypothesis requires further exploration.
... Some additional factors, such as excessive consumption of ethanol, have been suggested to increase Al bioavailability due to increased permeability of the intestinal mucosa [33]. However, experimental studies have shown that silicon (Si) may be protective against aluminum accumulation in the brain [34,35]. It has been previously hypothesized that alcoholic amnesia and dementia may also arise from increased Al exposures in individuals through the excessive consumption of ethanol beverages [33] and that Al accumulation may be regulated by Si availability. ...
Article
Full-text available
Introduction: Alcohol overuse may be related to increased aluminum (Al) exposure, the brain accumulation of which contributes to dementia. However, some reports indicate that silicon (Si) may have a protective role over Al-induced toxicity. Still, no study has ever explored the brain content of Al and Si in alcoholic use disorder (AUD). Materials and methods: To fill this gap, the present study employed inductively coupled plasma optical emission spectrometry to investigate levels of Al and Si in 10 brain regions and in the liver of AUD patients (n = 31) and control (n = 32) post-mortem. Results: Al content was detected only in AUD patients at mean ± SD total brain content of 1.59 ± 1.19 mg/kg, with the highest levels in the thalamus (4.05 ± 12.7 mg/kg, FTH), inferior longitudinal fasciculus (3.48 ± 9.67 mg/kg, ILF), insula (2.41 ± 4.10 mg/kg) and superior longitudinal fasciculus (1.08 ± 2.30 mg/kg). Si content displayed no difference between AUD and control, except for FTH. Positive inter-region correlations between the content of both elements were identified in the cingulate cortex, hippocampus, and ILF. Conclusions: The findings of this study suggest that AUD patients may potentially be prone to Al-induced neurodegeneration in their brain-although this hypothesis requires further exploration.
Chapter
Abstract Alzheimer's disease (AD) is an important public health problem which affects millions of people worldwide. The major pathological hallmarks associated with AD are the accumulation of amyloid beta (Aβ) in senile plaques and neurofibrillary tangles (NFT) made up of hyperphosphorylated tau proteins. New findings suggest that oligomeric Aβ is a more toxic species than fibrillar Aβ relevant to AD pathology. Although the molecular mechanism (s) underlying the disease is not identified completely, various factors have been ...
Article
Silicon is the second most abundant element in nature behind oxygen. As a metalloid, silicon has been used in many industrial applications including use as an additive in the food and beverage industry. As a result, humans come into contact with silicon through both environmental exposures but also as a dietary component. Moreover, many forms of silicon, that is, Si bound to oxygen, are water-soluble, absorbable, and potentially bioavailable to humans presumably with biological activity. However, the specific biochemical or physiological functions of silicon, if any, are largely unknown although generally thought to exist. As a result, there is growing interest in the potential therapeutic effects of water-soluble silica on human health. For example, silicon has been suggested to exhibit roles in the structural integrity of nails, hair, and skin, overall collagen synthesis, bone mineralization, and bone health and reduced metal accumulation in Alzheimer's disease, immune system health, and reduction of the risk for atherosclerosis. Although emerging research is promising, much additional, corroborative research is needed particularly regarding speciation of health-promoting forms of silicon and its relative bioavailability. Orthosilicic acid is the major form of bioavailable silicon whereas thin fibrous crystalline asbestos is a health hazard promoting asbestosis and significant impairment of lung function and increased cancer risk. It has been proposed that relatively insoluble forms of silica can also release small but meaningful quantities of silicon into biological compartments. For example, colloidal silicic acid, silica gel, and zeolites, although relatively insoluble in water, can increase concentrations of water-soluble silica and are thought to rely on specific structural physicochemical characteristics. Collectively, the food supply contributes enough silicon in the forms aforementioned that could be absorbed and significantly improve overall human health despite the negative perception of silica as a health hazard. This review discusses the possible biological potential of the metalloid silicon as bioavailable orthosilicic acid and the potential beneficial effects on human health.
Article
A deterioration of human semen quality has been observed over recent decades. A possible explanation could be an increased exposure to environmental pollutants, including aluminum. Our aim was to measure the aluminum concentration in the semen of 62 patients and to carry out a preliminary evaluation on its impact on specific semen parameters. For each patient, semen analyses were performed according to WHO guidelines. A graphite furnace atomic absorption spectrometry method was used to determine semen aluminum concentration. A cytological analysis using an aluminum-specific fluor, lumogallion, was also performed. The mean aluminum concentration in human semen was 339μg/L. Patients with oligozoospermia had a statistically higher aluminum concentration than others. No significant difference was observed for other semen parameters. Cytological analysis showed the presence of aluminum in spermatozoa. This study provided unequivocal evidence of high concentrations of aluminum in human semen and suggested possible implications for spermatogenesis and sperm count. Copyright © 2014 Elsevier Inc. All rights reserved.
Article
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The Treignac water is a natural mineral water containing mainly orthosilicic acid. On inert substrates, it forms a silica film with fractal structures which cannot be reproduced in laboratory-reconstituted water. These structures form by condensation of orthosilicic acid monomers, following the Witten–Sander model of diffusion-limited aggregation. On biological surfaces, such as tomato leaves, the Treignac water forms a silica film with a different morphology and devoid of fractal structures. The filmogenic properties of this natural mineral water are here discussed in the context of crop protection, as the silica film can provide a barrier and a platform for the immobilization of elicitors of plant defense responses.
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Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by loss of memory and other cognitive functions. AD can be classified into familial AD (FAD) and sporadic AD (SAD) based on heritability and into early onset AD (EOAD) and late onset AD (LOAD) based on age of onset. LOAD cases are more prevalent with genetically complex architecture. In spite of significant research focused on understanding the etiological mechanisms, search for diagnostic biomarker(s) and disease-modifying therapy is still on. In this article, we aim to comprehensively review AD literature on established etiological mechanisms including role of beta-amyloid and apolipoprotein E (APOE) along with promising newer etiological factors such as epigenetic modifications that have been associated with AD suggesting its multifactorial nature. As genomic studies have recently played a significant role in elucidating AD pathophysiology, a systematic review of findings from genome-wide linkage (GWL), genome-wide association (GWA), genome-wide expression (GWE), and epigenome-wide association studies (EWAS) was conducted. The availability of multi-dimensional genomic data has further coincided with the advent of computational and network biology approaches in recent years. Our review highlights the importance of integrative approaches involving genomics and systems biology perspective in elucidating AD pathophysiology. The promising newer approaches may provide reliable means of early and more specific diagnosis and help identify therapeutic interventions for LOAD.
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The aim of this study was to investigate the in vitro effect of Silicon, in the soluble form of sodium orthosilicate, combined and not with the Concentrated Growth Factors (CGF), a platelet rich preparation, on three different human cell lines of fibroblasts (NHDF), endothelial cells (HUVEC) and osteoblasts (HOBs). Each cell type, was treated with sodium orthosilicate at the final concentration of 0,5 mM and 1 mM, CGF, and sodium orthosilicate combined with CGF, for 72 hours. At the end of the experimental period, the in vitro effect on cell growth, proliferation and metabolic activity was evaluated by performing a simple cell count, using an automated cell counter and by evaluating the expression of the intracellular proliferation marker Ki-67, using Fluorescence-activated cell sorting (FACS) analysis. Moreover, the expression of other cell markers and active molecules such as Collagen type I, Osteopontin, Vascular Endothelial Growth Factor and endothelial Nitric Oxide Synthase, was evaluated, through immunohistochemistry. Results obtained showed that the combined use of CGF and sodium orthosilicate, stimulates cell growth, proliferation and metabolic activity, suggesting that this treatment could be effective in tissue regeneration.
We are living in the 'aluminium age'. Human exposure to aluminium is inevitable and, perhaps, inestimable. Aluminium's free metal cation, Alaq(3+), is highly biologically reactive and biologically available aluminium is non-essential and essentially toxic. Biologically reactive aluminium is present throughout the human body and while, rarely, it can be acutely toxic, much less is understood about chronic aluminium intoxication. Herein the question is asked as to how to diagnose aluminium toxicity in an individual. While there are as yet, no unequivocal answers to this problem, there are procedures to follow to ascertain the nature of human exposure to aluminium. It is also important to recognise critical factors in exposure regimes and specifically that not all forms of aluminium are toxicologically equivalent and not all routes of exposure are equivalent in their delivery of aluminium to target sites. To ascertain if Alzheimer's disease is a symptom of chronic aluminium intoxication over decades or breast cancer is aggravated by the topical application of an aluminium salt or if autism could result from an immune cascade initiated by an aluminium adjuvant requires that each of these is considered independently and in the light of the most up to date scientific evidence. The aluminium age has taught us that there are no inevitabilities where chronic aluminium toxicity is concerned though there are clear possibilities and these require proving or discounting but not simply ignored.
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A nutritional-based strategy has been proposed in order to improve cognitive performance of Alzheimer’s disease (AD) patients. The strategy requires daily dietary supplementation with magnesium (Mg), folic acid, and vitamins B6 and B12, daily consumption of silicic acid-rich mineral water in order to lower the body burden of Al, and several plasma exchange procedures in order to replace Aβ-bound albumin with fresh albumin. Evidence suggests that the deteriorating cognitive performance associated with AD may be improved by supplementation with either Mg alone or with the combination of the above three B vitamins (B vitamin combo), or by drinking silicic acid-rich mineral water, or by undergoing plasma exchange. However, for the following reasons the combination of all four therapeutic approaches may have a synergistic effect on improving cognitive performance of AD patients. 1. Various studies suggest that AD represents a form of diabetes of the brain, otherwise known as Type 3 diabetes. Proper functioning of carbohydrate metabolism requires both Mg and the B vitamin combo. 2. High levels of homocysteine associated with gray matter atrophy found in AD patients can be lowered by the B vitamin combo, which has also been found to prevent loss of intracellular Mg induced by homocysteine. 3. Consumption of silicic acid-rich mineral water not only removes Al, but lowering the body burden of Al enables more Mg to access the brain and regulate neurochemical processes that would otherwise be disrupted by Al. 4. As a result of plasma exchange, fresh albumin, not bound to the amyloid-β (Aβ) peptide that is associated with AD and which binds extensively to albumin, replaces Aβ-bound albumin. Compared to Aβ-bound albumin, the fresh albumin has an increased affinity for Mg, thereby facilitating the distribution of Mg across the blood–brain barrier (BBB) and into brain tissue.
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Stress or stress-induced intestinal disturbances, especially diarrhea, are the main triggers for inflammatory bowel disease and irritable bowel syndrome. Diarrhea and intestinal inflammatory disease afflict patients around the world, and it has become a huge burden on the global health care system. Drinking sodium metasilicate-based alkaline mineral water (SM-based AMW) exerts a potential therapeutic effect in gastrointestinal disorders, including gut inflammation, and diarrhea, but the supportive evidence on animal studies and mechanism involved remain unreported. The maternally separated (MS) piglet (Newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infant. This study aims to determine whether drinking SM-based AMW confers diarrhea resistance in maternally separated (MS) piglets under weaning stress and what the underlying mechanisms are involved. 240 newly weaned piglets were randomly divided into the Control group and the sodium metasilicate pentahydrate (SMP) group. A decreased diarrhea incidence was observed in SMP treatment piglets. The intestine injury and activated stress hormones (COR and ACTH) induced by weaning was alleviated by SM-based AMW. This may be related to the improvement of intestinal microflora structure and function by SMP, especially the increase of s_copri abundance. Meanwhile, SMP maintained the integrity of the duodenal mucus barrier in MS piglets. Importantly, by targeting NF-kB inhibition via the microbiota-gut interaction, SM-based AMW alleviated intestinal inflammation, maintained fluid homeostasis by modulating aquaporins and fluid transporter expression, and enhanced barrier integrity by suppressing MLCK/p-MLC signaling. Therefore, drinking metasilicate-based alkaline mineral water confers diarrhea resistance in MS piglets via the microbiota-gut interaction.
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Embryos at shield stage and larvae at protruding mouth stage were exposed to different concentrations of aluminium chloride (AlCl3) for 72 h with the purpose to analyse their phenotype and lethality. After 24, 48 and 72 h of treatment, higher toxicity of the metal was observed on larvae with minimal lethal concentration of 0.25, 0.20 and 0.08 mm, respectively, while for embryos the corresponding values were 40, 25 and 16 mm. We observed pericardial oedema and alteration of heart rate in 50% of larvae after 48 h of exposure to 100 μm. In larvae exposed to the same concentration, there was also a neurological injury at the level of glial cells, with the number of glial fibrillary acidic protein-positive cells being significantly reduced. This study confirms the toxic nature of this metal and shows that aluminium could also interestingly represent a cardiotoxin in addition to its neurotoxic ability.
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This chapter will focus on organic metal species of environmental concern that can exercise some influence on neurological disorders. A variety of organic metal species were identified in the last couple of years and their concentrations in the environment are rising. Moreover cases of overnutrition are increasing and due to the fortification of various organic metallic compounds in our diet there are growing anxieties that food ingredients may inadvertently be contributing to neurological disorders. This chapter provides a summary of organic metal species that have been linked with neurological disorders including its exposure pathways (especially diet), and a possible risk in the context of consumers safety pointing out gaps in the actual research. The list includes agents which have no known biological role in humans as organic species of mercury, tin, lead and arsenic. Besides the classical organometals also aluminium is illuminated. Additionally those, such as iron and manganese which are essential for life but can be toxic when absorbed in excess amounts will be discussed.
Chapter
Reproduction is one of the most basic biological processes, but it is also among the most mysterious. The fusion of two haploid gametes to form a diploid zygote, which divides and grows to eventually create a human infant, requires coordination of immense complexity. As a result, the clinical intervention in reproductive issues may require a detailed examination of the web of biological and environmental systems. Interventions can then be targeted to individual circumstances. In this chapter, we illustrate some of the complexities of systems-based biological interactions and help the reader develop an appreciation for the intricacies involved in reproduction. We will also suggest nutritional and other strategies that can be considered for intervention. While not a comprehensive catalogue of nutritional influences on reproduction, this chapter illustrates methodologies for solving reproductive issues that have broad applicability.
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In this study, we conducted density functional theory calculations comparing the binding energy of the copper-amyloid-β complex to the binding energies of potential chelation materials. We used the first-coordination sphere of the truncated high-pH amyloid-β protein subject to computational limits. Binding energy and charge transfer calculations were evaluated for copper’s interaction with potential chelators: monolayer boron nitride, monolayer molybdenum disulfide, and monolayer silicene. Silicene produced the highest binding energies to copper, and the evidence of charge transfer between copper and the monolayer proves that a strong ionic bond is present. Although our three monolayers did not directly present chelation potential, the absolute differences between the binding energies of the silicene binding sites and the amyloid-β binding sites were minimal, proving that further research in silicene chelators may be useful for therapy in Alzheimer’s disease.
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Alzheimer’s disease (AD) is a type of neurodegenerative malady that is associated with the accumulation of amyloid plaques. Metal ions are critical for the development and upkeep of brain activity, but metal dyshomeostasis can contribute to the development of neurodegenerative diseases, including AD. This review highlights the association between metal dyshomeostasis and AD pathology, the feasibility of rebalancing metal homeostasis as a therapeutic strategy for AD, and a survey of current drugs that action via rebalancing metal homeostasis. Finally, we discuss the challenges that should be overcome by researchers in the future to enable the practical use of metal homeostasis rebalancing agents for clinical application.
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This paper describes a hydrochemical study focusing spas groundwaters occurring at São Paulo and Minas Gerais states, Brazil, that are extensively used for drinking in public places, bottling and bathing purposes, among other. The water samples (75) for this study were taken from springs and pumped tubular wells drilled at different aquifer systems that are inserted in Paraná and Southeastern Shield hydrogeological provinces. The data acquisition for temperature, electrical conductivity (EC), pH, redox potential (Eh), dissolved gases (O2, CO2 and H2S) and alkalinity was in situ performed for avoiding losses and modification due to transportation. The total dissolved solids (TDS) concentration was evaluated by gravimetry, the major cations and anions, iron and silica by colorimetry/atomic absorption spectrophotometry (AAS), and fluoride by potentiometry. The acquired database allowed establish the principal trends among the parameters analyzed after assuring its consistence from expected relationships found in hydrogeochemical surveys. The groundwaters are reducing (from pH and Eh data), there is a direct TDS-EC relationship, implying on a significant correlation between their ionic strength (IS) and EC. The major ions justifying such trends were sodium, (bi)carbonate, chloride, sulfate and phosphate that also correlated positively with the IS. The spas groundwaters were classified according to the guidelines of the Brazilian Code of Mineral Waters (BCMW) and EU directive for mineral waters. The major hydrochemical facies were also determined, as well the main sources influencing the groundwater composition and possible subsurface temperatures.
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The brain is a highly compartmentalized organ exceptionally susceptible to accumulation of metabolic errors. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the elderly and is characterized by regional specificity of neural aberrations associated with higher cognitive functions. Aluminum (Al) is the most abundant neurotoxic metal on earth, widely bioavailable to humans and repeatedly shown to accumulate in AD-susceptible neuronal foci. In spite of this, the role of Al in AD has been heavily disputed based on the following claims: 1) bioavailable Al cannot enter the brain in sufficient amounts to cause damage, 2) excess Al is efficiently excreted from the body, and 3) Al accumulation in neurons is a consequence rather than a cause of neuronal loss. Research, however, reveals that: 1) very small amounts of Al are needed to produce neurotoxicity and this criterion is satisfied through dietary Al intake, 2) Al sequesters different transport mechanisms to actively traverse brain barriers, 3) incremental acquisition of small amounts of Al over a lifetime favors its selective accumulation in brain tissues, and 4) since 1911, experimental evidence has repeatedly demonstrated that chronic Al intoxication reproduces neuropathological hallmarks of AD. Misconceptions about Al bioavailability may have misled scientists regarding the significance of Al in the pathogenesis of AD. The hypothesis that Al significantly contributes to AD is built upon very solid experimental evidence and should not be dismissed. Immediate steps should be taken to lessen human exposure to Al, which may be the single most aggravating and avoidable factor related to AD.
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AN increased level of aluminium in acidified natural waters is a primary cause of fish death from damage to gill epithelia and loss of osmoregulatory capacity1-4. Aluminium toxicity depends on the species of aluminium present (cationic, neutral or anionic) and hence is affected by pH and the presence of complexing ligands, such as fluoride, and organic material, such as humic acid, which may ameliorate aluminium toxicity5,6. But silicic acid, Si(OH) 4, present in natural waters as a consequence of the weathering of the aluminosilicates of rocks and soil minerals, has a strong and unique affinity for aluminium7, although its influence on toxicity has not been investigated. Here we show that, with an excess of Si over Al and with the formation of hydroxy-aluminosilicate species, the bioavailability of aluminium at pH 5 is reduced and acute toxicity is eliminated. Silicic acid concentration should therefore be considered as a key parameter in toxicity studies and could be important for the treatment of vulnerable waters.
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A new rating instrument, the Alzheimer's Disease Assessment Scale, was designed specifically to evaluate the severity of cognitive and noncognitive behavioral dysfunctions characteristic of persons with Alzheimer's disease. Item descriptions, administration procedures, and scoring are outlined. Twenty-seven subjects with Alzheimer's disease and 28 normal elderly subjects were rated on 40 items. Twenty-one items with significant intraclass correlation coefficients for interrater reliability (range, .650-.989) and significant Spearman rank-order correlation coefficients for test-retest reliability (range, .514-1) constitute the final scale. Subjects with Alzheimer's disease had significantly more cognitive and noncognitive dysfunction than the normal elderly subjects.
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The chemistry of mono or ortho silicic acid (Si(OH)4) is barely considered in most chemistry texts. Mention is usually only made of its autocondensation in forming hydrated amorphous silica and its reaction with ammonium molybdate in forming the molybdosilicic acid complex. Reference should now be made to its unique inorganic chemistry with aluminium (Al) and specifically aluminium hydroxide (Al(OH)3(s)) in forming hydroxyaluminosilicates (HAS(s)). The competitive condensation or substitution of Si(OH)4 into a framework of Al(OH)3(s) results in the formation of either HASA or HASB. Which type of HAS(s) predominates depends upon the ratio of Si:Al in preparative solutions with the formation of HASB requiring a two-fold excess of Si(OH)4 over Al. The Si:Al ratio of HASA is 0.5 and the existence of HASA is a prerequisite to the formation of HASB in which the ratio of Si:Al is 1.0. HASA is composed of only octahedrally co-ordinated Al, AlVI, whereas HASB is composed of equal quantities of AlVI and tetrahedrally coordinated Al, AlIV, and is formed by a Si(OH)4-fuelled dehydroxylation reaction. HAS(s) are significantly more ‘kinetically’ stable than Al(OH)3(amorphous) with HASB predicted to predominate at pH>4.0 and [Si(OH)4]>0.1mmol/L. HAS(s) are critical secondary mineral phases in the biogeochemical cycle of Al and Si(OH)4 and the formation of HAS(s) have played a major role in precluding Al3+(aq) from biochemical evolution. In the future Si(OH)4 and the formation of HAS(s) are predicted to be of significant importance in providing protection for humans against a potentially burgeoning exposure to biologically available Al.
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An inevitable consequence of humans living in the Aluminium Age is the presence of aluminium in the brain. This non-essential, neurotoxic metal gains entry to the brain throughout all stages of human development, from the foetus through to old age. Human exposure to myriad forms of this ubiquitous and omnipresent metal makes its presence in the brain inevitable, while the structure and physiology of the brain makes it particularly susceptible to the accumulation of aluminium with age. In spite of aluminium’s complete lack of biological essentiality, it actually participates avidly in brain biochemistry and substitutes for essential metals in critical biochemical processes. The degree to which such substitutions are disruptive and are manifested as biological effects will depend upon the biological availability of aluminium in any particular physical or chemical compartment, and will under all circumstances be exerting an energy load on the brain. In short, the brain must expend energy in its ‘unconscious’ response to an exposure to biologically available aluminium. There are many examples where ‘biological effect’ has resulted in aluminium-induced neurotoxicity and most potently in conditions that have resulted in an aluminium-associated encephalopathy. However, since aluminium is non-essential and not required by the brain, its biological availability will only rarely achieve such levels of acuity, and it is more pertinent to consider and investigate the brain’s response to much lower though sustained levels of biologically reactive aluminium. This is the level of exposure that defines the putative role of aluminium in chronic neurodegenerative disease and, though thoroughly investigated in numerous animal models, the chronic toxicity of aluminium has yet to be addressed experimentally in humans. A feasible test of the ‘aluminium hypothesis’, whereby aluminium in the human brain is implicated in chronic neurodegenerative disease, would be to reduce the brain’s aluminium load to the lowest possible level by non-invasive means. The simplest way that this aim can be fulfilled in a significant and relevant population is by facilitating the urinary excretion of aluminium through the regular drinking of a silicic acid-rich mineral water over an extended time period. This will lower the body and brain burden of aluminium, and by doing so will test whether brain aluminium contributes significantly to chronic neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Graphical Abstract The co-localisation of aluminium (purple) and amyloid (red) in human brain tissue
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Attention is devoted to the role of chelating agents in the treatment of aluminium related diseases. In fact, in spite of the actions that have drastically reduced the occurrence of dialysis diseases, they so far constitute a cause of great medical concern. Being aluminium chelators strictly related to iron chelators, a comparison is made of the complex formation properties of these two hard metal ions towards ligands characterized by charged oxygen donor groups. Empirical correlations between aluminium(III) and iron(III) complex formation constants, and their behavior are discussed in terms of structural and thermodynamic stabilities. Insertion of proper substituents to enhance the chelator binding capacity is debated on the bases of substituent effects on protonation and complex formation constants.
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In 1991, treatment with low dose intramuscular desferrioxamine (DFO), a trivalent chelator that can remove excessive iron and/or aluminum from the body, was reported to slow the progression of Alzheimer's disease (AD) by a factor of two. Twenty years later this promising trial has not been followed up and why this treatment worked still is not clear. In this critical interdisciplinary review, we provide an overview of the complexities of AD and involvement of metal ions, and revisit the neglected DFO trial. We discuss research done by us and others that is helping to explain involvement of metal ion catalyzed production of reactive oxygen species in the pathogenesis of AD, and emerging strategies for inhibition of metal-ion toxicity. Highlighted are insights to be considered in the quests to prevent potentially toxic effects of aluminum toxicity and prevention and intervention in AD.
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Aluminium, iron and copper are all implicated in the aetiology of neurodegenerative diseases including Alzheimer's disease. However, there are very few large cohort studies of the content of these metals in aged human brains. We have used microwave digestion and TH GFAAS to measure aluminium, iron and copper in the temporal, frontal, occipital and parietal lobes of 60 brains donated to the Cognitive Function and Ageing Study. Every precaution was taken to reduce contamination of samples and acid digests to a minimum. Actual contamination was estimated by preparing a large number of (170+) method blanks which were interspersed within the full set of 700+ tissue digests. Subtraction of method blank values (MBV) from tissue digest values resulted in metal contents in all tissues in the range, MBV to 33 μg g(-1) dry wt. for aluminium, 112 to 8305 μg g(-1) dry wt. for iron and MBV to 384 μg g(-1) dry wt. for copper. While the median aluminium content for all tissues was 1.02 μg g(-1) dry wt. it was informative that 41 brains out of 60 included at least one tissue with an aluminium content which could be considered as potentially pathological (> 3.50 μg g(-1) dry wt.). The median content for iron was 286.16 μg g(-1) dry wt. and overall tissue iron contents were generally high which possibly reflected increased brain iron in ageing and in neurodegenerative disease. The median content for copper was 17.41 μg g(-1) dry wt. and overall tissue copper contents were lower than expected for aged brains but they were commensurate with aged brains showing signs of neurodegenerative disease. In this study we have shown, in particular, the value of carrying out significant numbers of method blanks to identify unknown sources of contamination. When these values are subtracted from tissue digest values the absolute metal contents could be considered as conservative and yet they may still reflect aspects of ageing and neurodegenerative disease in individual brains.
Article
To establish the minimal clinically relevant change (MCRC) on the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) for patients with mild Alzheimer's disease (AD). Cohort study. 59 recruiting sites for the Alzheimer's Disease Neuroimaging Initiative. Outpatients with AD in the Alzheimer's Disease Neuroimaging Initiative. The authors applied anchor-based MCRC methodology comparing ADAS-Cog change against clinicians' judgement of clinically relevant worsening between baseline and 6 months in four domains: memory and non-memory cognitive performance; Clinical Dementia Rating Scale; and Functional Assessment Questionnaire. The analysis was repeated for the 6-12-month interval. To support these findings, the authors calculated distribution-based measures including half-baseline SD (1/2 SD) and SEM. 181 patients (baseline ADAS-Cog score 18.5±6.4) had ADAS-Cog data at 0 and 6 months. Those undergoing clinically significant worsening on any of the four anchor questions (n=41-47) had an average ADAS-Cog change of 3.1-3.8 points. Similar results were found for the 177 patients with 6-12-month data. The average 1/2 SD for the baseline ADAS-Cog score was 3.2, and the SEM was 3.7. 3 points decline on the ADAS-Cog may be an appropriate MCRC for clinical trials of patients with early AD. However, further studies assessing the MCRC for improvement on the ADAS-Cog, using patient-based judgement as an anchor, and determining the minimal clinically relevant difference between change on two treatments are required. http://clinicalTrials.gov Identifier: NCT00106899.
Article
Evidence for the neurotoxicity of extended exposure to low levels of aluminum salts is described using an animal model treated with aluminum at low levels reflecting those found in some water supplies. Emphasis is given to the potential role of aluminum in acceleration and promotion of some indices characteristic of brain aging. These hallmarks include the appearance of excess levels of inflammation in specific brain areas. Aluminum salts can increase levels of glial activation, inflammatory cytokines and amyloid precursor protein within the brain. Both normal brain aging and to a greater extent, Alzheimer's disease are associated with elevated basal levels of markers for inflammation. These are not attributable to obvious exogenous stimuli and may reflect the lifespan history of the organism's immune responses. It is possible that aluminum salts can act as a subtle promoter of such apparently unprovoked responses.
Article
Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.
Article
Although epidemiological and biochemical evidence suggests that aluminium may be associated with Alzheimer's disease (AD), there is no convincing proof of a causal link for aluminium in disease progression. We have completed a two year, single-blind study to investigate whether the progression of dementia could be slowed by the trivalent ion chelator, desferrioxamine. 48 patients with probable AD were randomly assigned to receive desferrioxamine (125 mg intramuscularly twice daily, 5 days per week, for 24 months), oral placebo (lecithin), or no treatment. No significant differences in baseline measures of intelligence, memory, or speech ability existed between groups. Activities of daily living were assessed and videorecorded at 6, 12, 18, and 24 month intervals. There were no differences in the rate of deterioration of patients receiving either placebo or no treatment. Desferrioxamine treatment led to significant reduction in the rate of decline of daily living skills as assessed by both group means (p = 0.03) and variances (p less than 0.04). The mean rate of decline was twice as rapid for the no-treatment group. Appetite (n = 4) and weight (n = 1) loss were the only reported side-effects. We conclude that sustained administration of desferrioxamine may slow the clinical progression of the dementia associated with AD.
Article
Data from studies of dementia prevalence between 1945 to 1985 were analyzed statistically. Prevalence rates were found to vary as a function of methodological differences between studies. However, despite these differences, the relationship between prevalence and age was found to be consistent across studies, with rates doubling every 5.1 years. Across studies, Alzheimer's disease (AD) was found to be more common in women, with a tendency for multi-infarct dementia (MID) to be more common in men. There were also national differences in the relative prevalence of AD and MID, with MID being more common in Japanese and Russian studies, no difference in Finnish and American studies, and an excess of AD in other Western European countries.
Article
The reported geographical association between Alzheimer's disease and levels of aluminium (Al) in water supplies may reflect the inverse relation between Al and silicon (Si) concentrations in water, and the potential for Si to reduce the bioavailability of the metal. We tested this hypothesis using isotopic 26Al tracer administered orally to five healthy volunteers in the presence and absence of Si. Dissolved Si, at a concentration found in some water supplies (100 mumol/L), reduced the peak plasma 26Al concentration to 15% of the value obtained in the absence of Si. The results indicate that dissolved Si is an important factor in limiting the absorption of dietary Al.
Article
Silicon is possibly important in human physiology in protecting against the toxic effects of aluminium, but the kinetics of uptake and excretion of silicic acid, the bioavailable form, are not well characterised. We have used 32Si as a tracer in a human uptake experiment to determine a gastrointestinal uptake factor for silicic acid, and to elucidate the kinetics of renal elimination. Urine collections were made for extending intervals from 2 to 12 h over 2 days following ingestion by a single human subject of a neutral silicic acid solution containing tracer levels of 32Si (t1/2 approximately 150 y). Silicon was isolated as SiO2 and the 32Si content determined by accelerator mass spectrometry (AMS), using a gas-filled magnet technique to eliminate a prolific isobaric interference from 32S. Silicon uptake appears to have been essentially complete within 2 h of ingestion. Elimination occurred by two simultaneous first-order processes with half-lives of 2.7 and 11.3 h, representing around 90% and 10%, respectively, of the total output. The rapidly eliminated 32Si was probably retained in the extracellular fluid volume, whilst the slower component may represent intracellular uptake and release. Elimination of absorbed 32Si was essentially complete after 48 h and was equivalent to 36% of the ingested dose. This establishes only a lower limit for gastrointestinal absorption as, although there was no evidence for longer term retention of additional 32Si, the possibility could not be excluded by these results.
Article
The elaboration of biogeochemical cycles for elements which are known to be essential for life has enabled a broad appreciation of the homeostatic mechanisms which underlie element essentiality. In particular they can be used effectively to identify any part played by human activities in element cycling and to predict how such activities might impact upon the lithospheric and biospheric availability of an element in the future. The same criteria were the driving force behind the construction of a biogeochemical cycle for aluminium, a non-essential element which is a known ecotoxicant and a suspected health risk in humans. The purpose of this exercise was to examine the concept of a biogeochemical cycle for aluminium and not to review the biogeochemistry of this element. The cycle as presented is rudimentary and qualitative though, even in this nascent form, it is informative and predictive and, for these reasons alone, it is deserving of future quantification. A fully fledged biogeochemical cycle for aluminium should explain the biospheric abundance of this element and whether we should expect its (continued) active involvement in biochemical evolution.
Article
There are unexplained links between human exposure to aluminium and the incidence, progression and aetiology of Alzheimer's disease. The null hypothesis which underlies any link is that there would be no Alzheimer's disease in the effective absence of a body burden of aluminium. To test this the latter would have to be reduced to and retained at a level that was commensurate with an Alzheimer's disease-free population. In the absence of recent human interference in the biogeochemical cycle of aluminium the reaction of silicic acid with aluminium has acted as a geochemical control of the biological availability of aluminium. This same mechanism might now be applied to both the removal of aluminium from the body and the reduced entry of aluminium into the body while ensuring that essential metals, such as iron, are unaffected. Based upon the premise that urinary aluminium is the best non-invasive estimate of body burden of aluminium patients with Alzheimer's disease were asked to drink 1.5 L of a silicic acid-rich mineral water each day for five days and, by comparison of their urinary excretion of aluminium pre-and post this simple procedure, the influence upon their body burden of aluminium was determined. Drinking the mineral water increased significantly (P<0.001) their urinary excretion of silicic acid (34.3 +/- 15.2 to 55.7 +/- 14.2 micromol/mmol creatinine) and concomitantly reduced significantly P=0.037) their urinary excretion of aluminium (86.0 +/- 24.3 to 62.2 +/- 23.2 nmol/mmol creatinine). The latter was achieved without any significant (P>0.05) influence upon the urinary excretion of iron (20.7 +/- 9.5 to 21.7 +/- 13.8 nmol/mmol creatinine). The reduction in urinary aluminium supported the future longer-term use of silicic acid as non-invasive therapy for reducing the body burden of aluminium in Alzheimer's disease.
Silicic acid-rich mineral water as a non-invasive method of reducing aluminium body burden in healthy individuals, Alzheimer's and Parkinson's disease
  • Davenward
Davenward S (2012) Silicic acid-rich mineral water as a non-invasive method of reducing aluminium body burden in healthy individuals, Alzheimer's and Parkinson's disease, PhD Thesis, Keele University.