Updated 14 July 2005

By Colin Meyer

The epidemiological features of both diseases can be explained using the hypothesis that the initiating factor is the precipitation of aluminosilicates in the brain. The combination of solubilized aluminum and the only water-soluble form of silicon, silicic acid, to form insoluble aluminosilicates is a peculiar and unique reaction in inorganic chemistry. An evaluation of the uptake and distribution of these compounds provides an explanation for the development of plaques and tangles and a rationale for the findings of the collective epidemiological studies.

The premise of this hypothesis is that both AD and ALS/PD are forms of aluminosilicate neurotoxicity. I emphasize that the etiology of these diseases is aluminosilicate toxicity, not aluminum toxicity. I'll begin with a summary of the epidemiology of AD.

During the 1980s Perl et al. (1) and Edwardson et al. (2), among others, identified aluminosilicate deposits within plaques and tangles. The aluminosilicate deposits seen within plaques were localized in the cores of the lesions, suggesting that this was the initiating factor. Aluminum was a known neurotoxin, so these findings led to a flurry of epidemiological studies that were uniform in one aspect: They focused solely on aluminum exposure and ignored the role of silicon. I will summarize these epidemiological findings.

ANTACIDS—Many epidemiological studies during the 1980s assessed the incidence of AD among heartburn sufferers who consumed aluminum-containing antacids. No correlation was identified.

ALUMINUM TOXICITY—Several epidemiological studies assessed the incidence of AD among those afflicted with overt aluminum toxicity to include workers in aluminum foundries, renal patients treated with aluminum-containing dialysates, etc. No correlation was identified.

ANTIPERSPIRANTS—Amy Graves' 1990 study (3) assessed the incidence of AD among users of two aluminum-containing products, antacids and antiperspirants. No association was found with aluminum-containing antacids, just as none was identified in the previous antacid studies. But antiperspirant users were found to have a statistically significant correlation with AD risk that was dose-related, with a higher incidence among the most frequent users.

WATER—As summarized by Flaten (4), 13 epidemiological studies have assessed the incidence of AD in relation to aluminum levels in local drinking water. Nine of these studies identified a statistically significant correlation.

LEAVENING AGENTS—In 1999 Rogers and Simon (5) published a preliminary study that sought to determine a relationship between consumers of aluminum-containing food additives and AD. Their sample size was only 22 cohort pairs. They identified a non-significant trend (p=0.19) that frequent aluminum consumers were more than eight times as likely to incur AD as controls. They further identified a statistically significant association (p=0.025, OR infinite) among consumers of aluminum-containing leavening agents. It wasn't mentioned in the Rogers-Simon publication, but please note that two-thirds of Americans' dietary aluminum is from leavening agents.

WINE—Consumption of red wine is reported to reduce the incidence of AD (6).

GENDER—Women incur AD more frequently than do men.

Collectively, these findings appear to be inconclusive and even contradictory. But I believe that these findings are valid and represent reality just as virtually all other well-designed epidemiological studies do. I'll begin by reviewing aluminosilicate formation.

Perl et al. and Edwardson et al. identified aluminosilicates within AD lesions, not simply aluminum deposits. Aluminosilicates are little chunks of rock, totally insoluble. How did they get into brain tissue? They cannot be carried across the blood-brain barrier by any known mechanism. Let's then consider that they were formed within the brain.

Ralph Iler has written a text entitled The Chemistry of Silica (7). Much of that text is dedicated to descriptions of aluminosilicate formation. A review of these various reactions leads to this conclusion: Under physiological conditions (in a solution of water, at a temperature where water is in the liquid phase and at a pH between 5 and 9) there is one and only one way that aluminosilicates can form. That is the combination of silicic acid, H₄SiO₄, and solubilized aluminum. Silicic acid is the only water-soluble form of silicon, and at pH 7.4, the species of solubilized aluminum that occurs is Al(OH)_4-, a negative ion. These two compounds combine readily to precipitate aluminosilicate particulates.

Iler describes aluminosilicate precipitation as a unique reaction in inorganic chemistry, one for which there is greater propensity than any other. This reaction proceeds even with minuscule concentrations of both silicic acid and hydroxyl-aluminum. The resulting aluminosilicates can form in a bewildering array of lattice structures and all of these formations are highly insoluble. And there is more than enough activation energy at body temperature for the reaction to proceed spontaneously.

Iler also discusses the uptake, distribution and excretion of silicic acid. In mammalian tissue it is readily absorbed from the gut and is subsequently excreted by the kidney unchanged. Silicic acid passes through all membranes and tissues including the CNS. It reacts with nothing whatsoever except aluminum that may be present. And as previously mentioned, this will result in a precipitation reaction that occurs with greater propensity than any other chemical reaction that is known.

Let's then consider the fate of these precipitates. Within 95 percent of the body's tissues these tiny aluminosilicate particulates present no problem. They are carried to the kidney by the blood and lymph and excreted. But any particles that form in the brain have no means for leaving the CNS. Silicic acid readily transits the blood-brain barrier as does aluminum, the latter carried by transferrin. Thus, both reagents can enter the brain but the specialized endothelium of the blood-brain barrier has no pores, nor does the brain have any other mechanism to eliminate an insoluble particulate.

I, therefore, hypothesize that these trapped particulates serve as nidi for plaque formation, and as charged particles they are also toxic to neurons, inducing tangles. Note that this hypothesis of pathogenesis provides an explanation for the concentration of AD lesions around blood vessels.

With this reaction in mind, let's consider what happens in the body. A person with high blood levels of silicic acid, usually a result of drinking water with high silicon content, will precipitate any aluminum that is absorbed into blood before it can be carried across the blood-brain barrier. Thus, no aluminum enters the brain and no aluminosilicate formation will occur in the brain. This, then, explains why those suffering from aluminum toxicity are not at higher risk for AD.

Likewise a person with high blood levels of aluminum such as a dialysis patient will precipitate any absorbed silicic acid before it can cross the blood-brain barrier. Again, no aluminosilicate formation will occur in the brain.

So the stage is set for the disastrous precipitation event when a person with low blood levels of silicic acid has a surge of aluminum uptake, say from an application of an antiperspirant or a pancake breakfast. The ingested aluminum will first combine with any available silicic acid in the blood, but the excess aluminum will be available to be carried into the brain by transferrin. After crossing the blood-brain barrier, it will then precipitate any silicic acid that is encountered in the brain with most encounters being near the site where the aluminum entered, the blood vessel. Note that some plaques actually form within the walls of blood vessels. Multiple episodes of this event over decades will eventually result in AD. Those who use antiperspirants or frequently consume aluminum-containing leavening agents can be expected to be at greater risk.

Why didn't the antacid studies of the 1980s demonstrate a positive association? Well, a review of the composition of aluminum-containing antacids during the 1950-1980 era reveals that the most common formulation was a combination of aluminum hydroxide and magnesium trisilicate (see the Handbook of Non-Prescription Drugs, First Edition, 1969). Both compounds were cheap, both neutralized stomach acid and the constipating tendency of the former was countered by the laxative properties of the latter. And when magnesium trisilicate neutralizes HCl, silicic acid is formed.

Absorbable aluminum and silicic acid are both created when these antacids neutralized stomach acid, but both are not equally bioavailable. Silicic acid is readily absorbed but aluminum is not. Aluminum uptake occurs only through the gastric mucosa and only in the totally ionized Al+++ form. The totally ionized form of the metal exists when the pH is below 3, and a single dose of virtually any antacid elevates the stomach contents to a pH in the 4-5 range. Thus, the administration of an antacid in itself creates a gastric environment in which aluminum cannot be absorbed.

The antacid studies of the 1980s were confounded. Antacids are a trivial source of bioavailable aluminum and those formulated with magnesium trisilicate are actually a good source of aluminum's "antidote," silicic acid. Accordingly, the findings of the various AD-antacid studies must be regarded as meaningless.

Regarding the drinking water studies, it is logical that aluminum and silicic acid are mutually exclusive in water. If both are present, precipitation will occur until a surplus of one or the other remains. Water is a trivial source of dietary aluminum but a primary source of silicic acid. The collective drinking water studies did indicate a direct relationship with aluminum levels and AD incidence, but this could actually be regarded as an inverse relationship between silicic acid levels and AD occurrence.

Concerning wine, small thin-skinned fruits such as grapes will concentrate silicic acid. Grapevines uptake silicic acid in ground water through the roots. Grapes have a thin epidermis and a high surface-to-volume ratio, and will evaporate a good deal of this water. Silicic acid does not evaporate, and therefore concentrates in the fruit. Wine is a rich source of silicic acid, and it is reasonable to expect wine drinkers to have higher blood levels of protective silicic acid than non-drinkers and a correspondingly lower incidence of AD.

I believe that there are two reasons for the gender disparity of AD incidence. The first entails the brain-mass-to-body-mass ratio of men and women. In women 2.22 percent of the body is brain tissue compared to 1.89 percent in men. As a result women have a 17.5 percent greater brain-mass-to-body-mass ratio.

Is there any reason this should make a difference? Well, consider the fate of aluminum that is absorbed from the gut. If silicic acid or aluminosilicate particulates are abundant in the blood, the aluminum will form covalent bonds with either and will then be circulated until excreted by the kidney. But if it is not precipitated, it will be carried by transferrin around the circulatory system.

On each circuit there is some chance that it will be excreted by the kidney, let's say 20 percent. The probability of renal excretion should be the same for men and women. Also, on each circuit some aluminum will enter the carotid artery and may then be carried across the blood-brain barrier. The probability for this is greater for women than men simply due to the dynamics of blood distribution to the tissues. In women there is a greater probability that the aluminum will be diverted to the brain on each transit of the circulatory system prior to excretion.

The second reason concerns use of aluminum-containing antiperspirants. Women are literally more thin-skinned than men and it is logical that females will absorb more of anything that is applied topically. Accordingly, women who use antiperspirants will have higher blood levels of aluminum versus men. And kindly forgive me if this sounds sexist, but I also believe that women are more inclined to use antiperspirants than are men.

The other half of the story concerns ALS/PD in the western Pacific. The epidemiological studies and pathological features discussed in the following narrative are referenced to Ralph Garruto's extensive summary (8) concerning this condition.

The plaques and tangles of ALS/PD victims are indistinguishable from those of AD victims. The lesions are concentrated near blood vessels. I will again begin with a review of epidemiological findings.

ALS/PD occurs 2-3 times more commonly in males than females. The disease strikes victims 2-4 decades earlier than AD. The incidence has decreased over the past half-century as the societies where the disease occurs have become westernized.

ALS/PD occurs only at a few distinct locations: the Kii Peninsula on the main body of Japan, some islands of the Mariana archipelago, some villages on southern Guam and some villages in the New Guinea lowlands. Within the New Guinea lowlands it has long been noted that villages on rivers with headwaters in the lowlands are endemic foci of the disease, but those on rivers with headwaters in the mountains are not. We should also note that villages on rivers with co-mingled water are not endemic areas.

As you might imagine, the drinking water at these various sites has been tested for every element and toxin imaginable. It is somewhat high in aluminum but not at toxic levels. Similarly, no toxic fauna or dietary factors have been incriminated.

Can aluminosilicate precipitation account for this? Well, I'll begin with the thesis outlined above by which I've suggested that AD incurs in people with low silicic acid levels who periodically have a surge of aluminum uptake. If this is true, then we could expect a similar fate for a group of people whose baseline is zero blood level of silicic acid and low blood levels of solubilized aluminum. If such a person were to occasionally ingest a substantial quantity of silicic acid, we would expect to see aluminosilicate precipitation in the brain by the same mechanism described above for AD. The ingested silicic acid would readily diffuse throughout all tissues, including the brain, and would precipitate any aluminum that is encountered.

Well, this would then account for the negative findings for toxins in all of the water testing. No one thought to test water for a deficiency, but I propose that the drinking water at the endemic sites may be totally deficient in silicic acid. This is suggested by the analysis of a soil sample taken from an endemic site on Guam in which the aluminum-silicon ratio was 40:1.

We can further hypothesize that the mountain waters of New Guinea contain dissolved silicates, while the lowland waters do not. This would account for the distribution of the disease along the waterways.

Regarding the gender disparity seen with ALS/PD, the villages where this disease has occurred were generally tribal societies in which the males were typically the hunters/gatherers and the females remained in the villages throughout the day to care for children and other domestic chores. The males would then be the most likely to venture away from the village to a location where the water would contain some silicic acid. If some were ingested, the silicic acid would be readily absorbed and would in turn initiate the cascade of events leading to aluminosilicate precipitation in the brain.

Then why is ALS/PD vanishing as the various sites become westernized? It appears that the availability of imported foods and drinks such as canned goods provides sources of silicic acid that generally eliminates the precarious condition of zero blood levels among the indigenous people in endemic areas..

In summary, I suggest the three studies to confirm or refute this hypothesis. (1) A follow-up to Graves' 1990 epidemiological study of AD incidence among users of aluminum-containing antiperspirants, (2) a follow-up to Rogers and Simon's 1999 preliminary study of AD incidence among those who frequently consume aluminum-containing leavening agents, and (3) testing of water at ALS/PD foci for silicic acid levels.

References
1. Perl DP, Brody AR. Alzheimer's disease: X-ray spectrometric evidence of aluminum accumulation in neurofibrillary tangle-bearing neurons. Science. 1980 Apr 18;208(4441):297-9. Abstract

2. Edwardson JA, Klinowski J, Oakley AE, Perry RH, Candy JM. Aluminosilicates and the ageing brain: implications for the pathogenesis of Alzheimer's disease. Ciba Found Symp. 1986;121:160-79. Abstract

3. Graves AB, White E, Koepsell TD, Reifler BV, van Belle G, Larson EB. The association between aluminum-containing products and Alzheimer's disease. J Clin Epidemiol. 1990;43(1):35-44. Abstract

4. Flaten TP. Aluminium as a risk factor in Alzheimer's disease, with emphasis on drinking water. Brain Res Bull. 2001 May 15;55(2):187-96. Review. Abstract

5. Rogers MA, Simon DG. A preliminary study of dietary aluminium intake and risk of Alzheimer's disease. Age Ageing. 1999 Mar;28(2):205-9. Abstract

6. McDowell I. Alzheimer's disease: insights from epidemiology. Aging (Milano). 2001 Jun;13(3):143-62. Review. Abstract

7. Ralph K. Iler. The Chemistry of Silica: Solubility, Polymerization, Colloid and Surface Properties and Biochemistry of Silica. New York: Wiley, ©1979.

8. Garruto RM. Pacific paradigms of environmentally-induced neurological disorders: clinical, epidemiological and molecular perspectives. Neurotoxicology. 1991 Fall;12(3):347-77. Review. Abstract

Colin Meyer's 'hypothesis' concerning the precipitation of aluminosilicates and AD is, of course, by no means new (eg., Evans et al., 1992). In addition, while it is true that silicic acid will react with aluminium to form an hydroxyaluminosilicate (Exley et al., 2002), there is no evidence to date that such a reaction could occur in vivo. What is more, recent research demonstrates a protective influence of silicic acid acid in drinking water and the incidence of AD (Rondeau et al, 2000). Clearly there is much more to this issue than is included here.

In response to my posted aluminosilicate precipitation hypothesis, Chris Exley has noted that this suggestion is not original to me and that there is no evidence that aluminosilicates will precipitate in vivo. I'll respond to both issues.

I make no claim that I am the first to propose aluminosilicate precipitation as the initiating event in AD. However, the foremost reason that this thesis is not regarded as credible is the failure of the 1980s era epidemiological studies to demonstrate an association between use of aluminum-containing antacids and AD incidence. I have pointed out that over half of the aluminum-containing antacids produced during the preceding decades were formulated with magnesium trisilicate and that this is a logical reason that these negative findings. I've further noted that antacids elevate the gastric pH such that aluminum is not bioavailable.

I have also explained that aluminosilicate precipitation can account for the etiology of not only AD but also ALS/PD of the western Pacific. I don't believe that this has been suggested previously.

Bilinski H, Horvath L, Trbojevic-Cepe M. Precipitation and characterization of an aluminosilicate from AlCl3-Na2SiO3-HCl in serum, of interest for Alzheimer disease. Clin Chem. 1992 Oct;38(10):2019-24. Abstract

Additional Reference—Posted 14 July 2005

Gillette-Guyonnet S, Andrieu S, Nourhashemi F, de La Guéronnière V, Grandjean H, Vellas B. Cognitive impairment and composition of drinking water in women: findings of the EPIDOS Study. Am J Clin Nutr. 2005 Apr 1 ; 81(4):897-902. Abstract