Entropy2012, 14, 2227-2253; doi:10.3390/e14112227entropyISSN 1099-4300 www.mdpi.com/journal/entropy
Review Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure Stephanie Seneff 1,*, Robert M. Davidson 2 and Jingjing Liu 11 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; E-Mail: jingl@csail.mit.edu (J.L.) 2 Internal Medicine Group Practice, PhyNet, Inc., Longview, TX 75604, USA; E-Mail: patrons99@yahoo.com (R.M.D.) * Author to whom correspondence should be addressed; E-Mail: seneff@csail.mit.edu; Tel.: +1-617-253-0451.
Received: 24 September 2012; in revised form: 16 October 2012 / Accepted: 5 November 2012 / Published: 7 November 2012
Abstract: Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.
Keywords: autism; vaccines; MMR; HEP-B; glutathione; sulfate; cholesterol sulfate; aluminum; mercury; acetaminophen OPEN ACCESSEntropy 2012, 14 2228 PACS Codes: 87.19.xm; 87.19.xt; 87.19.xw; 87.18.Vf; 87.18.Sn; 87.19.lk; 87.19.lv; 87.19.um; 87.19.uj 1.
Introduction Autism, and, more broadly, autism spectrum disorder (ASD), is a condition characterized by impaired cognitive and social skills [1], along with a compromised immune function [2–5]. It can now no longer be denied that the incidence of ASD is alarmingly on the rise in the U.S. [6]. While it has been suggested that the observed increase in rates may be due mainly to a change in diagnosis criteria, the actual criteria have changed very little from 1943 to DSM-IV-TR [7–9]. Despite considerable research efforts devoted to trying to uncover the cause(s) of autism, thus far no definitive answer seems available from the research literature. However, the fact that ASD rates have been rapidly increasing over the last two decades strongly points to an environmental component. Indeed, autism is recently being reframed from being a strictly genetic disease to representing a complex interaction between genetics and environmental factors, suggesting that we should focus our attention more on “environmentally responsive genes” [10]. The ASD community has maintained a long-standing conviction that vaccination plays a causative role in ASD [11], an idea that has been vehemently denied by the vaccine industry [12], but nonetheless is still hotly debated [13]. A study published in 2011 has confirmed a positive correlation between the proportion of children who received vaccinations in each state over the interval from 2001 to 2007 and the incidence of autism or speech and language impairment [14]. For each 1% increase in vaccination rate, 680 additional children were diagnosed with autism or speech delay. In [15], we proposed that a causative factor in autism is an inadequate supply of cholesterol sulfate, both in utero and postnatally. Cholesterol sulfate synthesis in the skin is catalyzed by sun exposure [16]. We hypothesized that autism may be induced by a combination of inadequate dietary sulfur and insufficient sun exposure to the skin, for both the mother and the child. A meta-study involving oxidative-stress related biomarkers present in association with autism identified a consistent deficiency in reduced glutathione [17], an important sulfur-based antioxidant that also plays a role in detoxifying aluminum. We proposed that cysteine, the rate-limiting amino acid involved in the synthesis of glutathione [18], is depleted through redirection into an alternative pathway to produce sulfate, due to the impaired sulfate synthesis from thiosulfate in the skin. A recent study of biomarkers for 28 individuals with an ASD diagnosis showed reduced glutathione, cysteine, and sulfate compared to controls, and the authors proposed that a reduced detoxification capacity might impede mercury excretion [19]. These same authors observed a marked reduction in serum sulfate in association with ASD in another paper [20]. In particular, the level of free sulfate in the blood stream was only 33% of the level found in control subjects. We hypothesize that sulfate deficiency results in insufficient ionic buffering in the vasculature, with grossly inadequate sulfation of the extracellular matrix proteins that are essential for proper colloidal suspension of particles and cells [21,22]. Entropy 2012, 14 2229 Glutathione [23] and sulfate [24] are also essential for the detoxification of xenobiotics and commonly administered drugs like acetaminophen in the liver. Selenium, a trace metal in the same column of the periodic table as oxygen and sulfur, has been shown to protect against acetaminophen toxicity [25], and it has also been shown to be severely depleted in hair and nail samples from individuals on the autism spectrum [26]. A possible link has been found between acetaminophen and both autism and asthma [27]. The association of both asthma [28] and eczema [29] with ASD can be explained as an inadequate supply of filaggrin, due to the fact that cholesterol sulfate in the epidermis stimulates the production of profilaggrin, its precursor [30]. Filaggrin plays an essential role in maintaining the epithelial barrier [31], and its impairment leads to increased risk of both asthma [32] and eczema [33,34]. Thus cholesterol sulfate deficiency provides an explanation for the multiple links among autism, acetaminophen, asthma, and eczema. It has been demonstrated that chronic aluminum exposure in rats induces depletion of glutathione in the liver as well as a significant reduction in the synthesis of bile acids [35], which are conjugated with taurine, the only sulfonic amino acid [36]. Taurine administration in conjunction with aluminum greatly ameliorates the adverse effects of aluminum on the liver, and this was explained as possibly due to the ability of the sulfonate group in taurine to bind with heavy metals such as aluminum [37]. These results suggest that glutathione and taurine are both involved in aluminum detoxification in the liver. Many children with autism have a low amount of serum glutathione, with a larger fraction of it oxidized to GSSG [38]. Furthermore, increased use of antibiotics leads to an alteration in gut flora which impairs the ability to detoxify toxic metals like mercury. Dimercaptosuccinic acid (DMSA), an organosulfur compound with two thiol groups, has been found to be effective in ameliorating the symptoms of autism in placebo controlled studies [39], likely through its ability to enable the excretion of toxic metals such as lead and mercury [40]. It also led to a normalization of glutathione levels in red blood cells [40]. Vitamin D deficiency has been hypothesized to be a risk factor for autism [41]. The over-zealous application of sunscreen is strongly implicated in autism, not only because sunscreen interferes with the production of vitamin D3 and cholesterol sulfate but also because it often contains aluminum, particularly the high Sun Protection Factor (SPF) sunblock products. Aluminum, due in part to its +3 ionic charge, is highly toxic to biological systems [42,43] as will be described more fully in Section 2.1. Indeed, there are no known life forms that utilize aluminum in any biological systems. The poorly developed barrier function of the autistic child’s epidermis would likely lead to an increased penetration of aluminum through the skin. Furthermore, their serum sulfate deficiency leads to an impaired ability to dispose of aluminum. Aluminum would therefore be expected to accumulate over time, and, due to increased permeability of the blood brain barrier associated with autism [44], would almost certainly interfere with neuron function. In the next section, we examine the evidence from the literature that aluminum toxicity may play a role in vaccine adverse reactions, and we describe available theories for the mode of toxicity of aluminum and other toxic metals. Entropy 2012, 14 2230 2.
Aluminum and Mercury in Vaccines It has recently been proposed that aluminum, commonly used in vaccines as an adjuvant, may be the most significant factor in adverse reactions, and, furthermore, that the nervous system is especially vulnerable to aluminum toxicity [45]. Vaccine clinical trials often include aluminum in the placebo, at the same or greater concentrations than the amount found in the vaccine [46–49]. A comparable number of adverse reactions between vaccine and placebo in these trials suggests that aluminum is an important source of toxicity in the vaccine. Indeed, intraperitoneal injection of aluminum-adsorbed vaccine in mice caused a transient rise in aluminum in brain tissues [50]. The Food and Drug Administration (FDA) has set an upper limit of 5 micrograms Al/kg/day for neonates and individuals with impaired kidney function [51]. A highly informative recent review of a possible relationship between aluminum toxicity and Alzheimer's disease [52] also discussed issues related to the aluminum burden in children's vaccines. There, it was pointed out that children today receive a cumulative aluminum burden from vaccines that may exceed the FDA limit by a factor of 50. The vaccine industry has a difficult task in designing vaccines that are both safe and effective [53]. The use of weakened but live pathogens can lead to vaccine-induced disease in children with an impaired immune system, yet debris from dead pathogens may not always cause a sufficient reaction to induce the production of antigen-specific memory CD8 T-cells, required for protection against future exposure. The industry widely reports success in creating vaccines with dead pathogens by adding adjuvants such as aluminum, lipopolysaccharide (LPS) from E. coli, and polycationic surfactants, to further stimulate the immune response [54]. It remains unclear exactly how aluminum achieves its effect of enhancing the immune reaction, but aluminum adjuvants are now thought to impact on humoral systems via their positive influence on the inflammasome complexes [55]. Another industry-claimed basis for adding aluminum or mercury to vaccines is to increase the stability of the antigen in long-term storage. It has been shown that the rate of acid-catalyzed hydrolysis of glucose-1-phosphate is significantly slower when the molecule is adsorbed to aluminum hydroxide adjuvant, increasing the effective pH of the environment by 2 pH units [56]. This effect would however also interfere with the human body’s ability to break down the antigen from the vaccine, which may partially explain the heightened immune reaction. Based on concerns that the mercury (49.6% by weight) in thimerosal might be contributing to autism [57], the industry made an effort to significantly reduce the amount of mercury present in vaccines beginning in the late 1990’s [58]. In parallel, they began storing the vaccines in individualized glass vials—to avoid the ostensible need for a preservative to reduce the danger of contaminating repeated invasions of multidose vials. However, this raises another concern, as aluminum can be leached out of the glass vial and the rubber stopper during storage [59]. This same issue can also affect premature infants given serum albumin infusions, resulting in an inadvertent exposure to aluminum very early in life [60]. Glass contains aluminum oxide at levels ranging from 1.9% to 5.8% [61]. Leaching from a container is an ongoing process until the product is used. Storage containers contribute significantly to aluminum contamination in human serum albumin products. Because of impaired renal function, dialysis patients are at risk to developing encephalopathy and a severe form of dementia due to their inability to dispose of the small amounts of aluminum that could be present in the dialysis water base [62],
Review Empirical Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen Exposure Stephanie Seneff 1,*, Robert M. Davidson 2 and Jingjing Liu 11 Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; E-Mail: jingl@csail.mit.edu (J.L.) 2 Internal Medicine Group Practice, PhyNet, Inc., Longview, TX 75604, USA; E-Mail: patrons99@yahoo.com (R.M.D.) * Author to whom correspondence should be addressed; E-Mail: seneff@csail.mit.edu; Tel.: +1-617-253-0451.
Received: 24 September 2012; in revised form: 16 October 2012 / Accepted: 5 November 2012 / Published: 7 November 2012
Abstract: Autism is a condition characterized by impaired cognitive and social skills, associated with compromised immune function. The incidence is alarmingly on the rise, and environmental factors are increasingly suspected to play a role. This paper investigates word frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting System (VAERS) database. Our results provide strong evidence supporting a link between autism and the aluminum in vaccines. A literature review showing toxicity of aluminum in human physiology offers further support. Mentions of autism in VAERS increased steadily at the end of the last century, during a period when mercury was being phased out, while aluminum adjuvant burden was being increased. Using standard log-likelihood ratio techniques, we identify several signs and symptoms that are significantly more prevalent in vaccine reports after 2000, including cellulitis, seizure, depression, fatigue, pain and death, which are also significantly associated with aluminum-containing vaccines. We propose that children with the autism diagnosis are especially vulnerable to toxic metals such as aluminum and mercury due to insufficient serum sulfate and glutathione. A strong correlation between autism and the MMR (Measles, Mumps, Rubella) vaccine is also observed, which may be partially explained via an increased sensitivity to acetaminophen administered to control fever.
Keywords: autism; vaccines; MMR; HEP-B; glutathione; sulfate; cholesterol sulfate; aluminum; mercury; acetaminophen OPEN ACCESSEntropy 2012, 14 2228 PACS Codes: 87.19.xm; 87.19.xt; 87.19.xw; 87.18.Vf; 87.18.Sn; 87.19.lk; 87.19.lv; 87.19.um; 87.19.uj 1.
Introduction Autism, and, more broadly, autism spectrum disorder (ASD), is a condition characterized by impaired cognitive and social skills [1], along with a compromised immune function [2–5]. It can now no longer be denied that the incidence of ASD is alarmingly on the rise in the U.S. [6]. While it has been suggested that the observed increase in rates may be due mainly to a change in diagnosis criteria, the actual criteria have changed very little from 1943 to DSM-IV-TR [7–9]. Despite considerable research efforts devoted to trying to uncover the cause(s) of autism, thus far no definitive answer seems available from the research literature. However, the fact that ASD rates have been rapidly increasing over the last two decades strongly points to an environmental component. Indeed, autism is recently being reframed from being a strictly genetic disease to representing a complex interaction between genetics and environmental factors, suggesting that we should focus our attention more on “environmentally responsive genes” [10]. The ASD community has maintained a long-standing conviction that vaccination plays a causative role in ASD [11], an idea that has been vehemently denied by the vaccine industry [12], but nonetheless is still hotly debated [13]. A study published in 2011 has confirmed a positive correlation between the proportion of children who received vaccinations in each state over the interval from 2001 to 2007 and the incidence of autism or speech and language impairment [14]. For each 1% increase in vaccination rate, 680 additional children were diagnosed with autism or speech delay. In [15], we proposed that a causative factor in autism is an inadequate supply of cholesterol sulfate, both in utero and postnatally. Cholesterol sulfate synthesis in the skin is catalyzed by sun exposure [16]. We hypothesized that autism may be induced by a combination of inadequate dietary sulfur and insufficient sun exposure to the skin, for both the mother and the child. A meta-study involving oxidative-stress related biomarkers present in association with autism identified a consistent deficiency in reduced glutathione [17], an important sulfur-based antioxidant that also plays a role in detoxifying aluminum. We proposed that cysteine, the rate-limiting amino acid involved in the synthesis of glutathione [18], is depleted through redirection into an alternative pathway to produce sulfate, due to the impaired sulfate synthesis from thiosulfate in the skin. A recent study of biomarkers for 28 individuals with an ASD diagnosis showed reduced glutathione, cysteine, and sulfate compared to controls, and the authors proposed that a reduced detoxification capacity might impede mercury excretion [19]. These same authors observed a marked reduction in serum sulfate in association with ASD in another paper [20]. In particular, the level of free sulfate in the blood stream was only 33% of the level found in control subjects. We hypothesize that sulfate deficiency results in insufficient ionic buffering in the vasculature, with grossly inadequate sulfation of the extracellular matrix proteins that are essential for proper colloidal suspension of particles and cells [21,22]. Entropy 2012, 14 2229 Glutathione [23] and sulfate [24] are also essential for the detoxification of xenobiotics and commonly administered drugs like acetaminophen in the liver. Selenium, a trace metal in the same column of the periodic table as oxygen and sulfur, has been shown to protect against acetaminophen toxicity [25], and it has also been shown to be severely depleted in hair and nail samples from individuals on the autism spectrum [26]. A possible link has been found between acetaminophen and both autism and asthma [27]. The association of both asthma [28] and eczema [29] with ASD can be explained as an inadequate supply of filaggrin, due to the fact that cholesterol sulfate in the epidermis stimulates the production of profilaggrin, its precursor [30]. Filaggrin plays an essential role in maintaining the epithelial barrier [31], and its impairment leads to increased risk of both asthma [32] and eczema [33,34]. Thus cholesterol sulfate deficiency provides an explanation for the multiple links among autism, acetaminophen, asthma, and eczema. It has been demonstrated that chronic aluminum exposure in rats induces depletion of glutathione in the liver as well as a significant reduction in the synthesis of bile acids [35], which are conjugated with taurine, the only sulfonic amino acid [36]. Taurine administration in conjunction with aluminum greatly ameliorates the adverse effects of aluminum on the liver, and this was explained as possibly due to the ability of the sulfonate group in taurine to bind with heavy metals such as aluminum [37]. These results suggest that glutathione and taurine are both involved in aluminum detoxification in the liver. Many children with autism have a low amount of serum glutathione, with a larger fraction of it oxidized to GSSG [38]. Furthermore, increased use of antibiotics leads to an alteration in gut flora which impairs the ability to detoxify toxic metals like mercury. Dimercaptosuccinic acid (DMSA), an organosulfur compound with two thiol groups, has been found to be effective in ameliorating the symptoms of autism in placebo controlled studies [39], likely through its ability to enable the excretion of toxic metals such as lead and mercury [40]. It also led to a normalization of glutathione levels in red blood cells [40]. Vitamin D deficiency has been hypothesized to be a risk factor for autism [41]. The over-zealous application of sunscreen is strongly implicated in autism, not only because sunscreen interferes with the production of vitamin D3 and cholesterol sulfate but also because it often contains aluminum, particularly the high Sun Protection Factor (SPF) sunblock products. Aluminum, due in part to its +3 ionic charge, is highly toxic to biological systems [42,43] as will be described more fully in Section 2.1. Indeed, there are no known life forms that utilize aluminum in any biological systems. The poorly developed barrier function of the autistic child’s epidermis would likely lead to an increased penetration of aluminum through the skin. Furthermore, their serum sulfate deficiency leads to an impaired ability to dispose of aluminum. Aluminum would therefore be expected to accumulate over time, and, due to increased permeability of the blood brain barrier associated with autism [44], would almost certainly interfere with neuron function. In the next section, we examine the evidence from the literature that aluminum toxicity may play a role in vaccine adverse reactions, and we describe available theories for the mode of toxicity of aluminum and other toxic metals. Entropy 2012, 14 2230 2.
Aluminum and Mercury in Vaccines It has recently been proposed that aluminum, commonly used in vaccines as an adjuvant, may be the most significant factor in adverse reactions, and, furthermore, that the nervous system is especially vulnerable to aluminum toxicity [45]. Vaccine clinical trials often include aluminum in the placebo, at the same or greater concentrations than the amount found in the vaccine [46–49]. A comparable number of adverse reactions between vaccine and placebo in these trials suggests that aluminum is an important source of toxicity in the vaccine. Indeed, intraperitoneal injection of aluminum-adsorbed vaccine in mice caused a transient rise in aluminum in brain tissues [50]. The Food and Drug Administration (FDA) has set an upper limit of 5 micrograms Al/kg/day for neonates and individuals with impaired kidney function [51]. A highly informative recent review of a possible relationship between aluminum toxicity and Alzheimer's disease [52] also discussed issues related to the aluminum burden in children's vaccines. There, it was pointed out that children today receive a cumulative aluminum burden from vaccines that may exceed the FDA limit by a factor of 50. The vaccine industry has a difficult task in designing vaccines that are both safe and effective [53]. The use of weakened but live pathogens can lead to vaccine-induced disease in children with an impaired immune system, yet debris from dead pathogens may not always cause a sufficient reaction to induce the production of antigen-specific memory CD8 T-cells, required for protection against future exposure. The industry widely reports success in creating vaccines with dead pathogens by adding adjuvants such as aluminum, lipopolysaccharide (LPS) from E. coli, and polycationic surfactants, to further stimulate the immune response [54]. It remains unclear exactly how aluminum achieves its effect of enhancing the immune reaction, but aluminum adjuvants are now thought to impact on humoral systems via their positive influence on the inflammasome complexes [55]. Another industry-claimed basis for adding aluminum or mercury to vaccines is to increase the stability of the antigen in long-term storage. It has been shown that the rate of acid-catalyzed hydrolysis of glucose-1-phosphate is significantly slower when the molecule is adsorbed to aluminum hydroxide adjuvant, increasing the effective pH of the environment by 2 pH units [56]. This effect would however also interfere with the human body’s ability to break down the antigen from the vaccine, which may partially explain the heightened immune reaction. Based on concerns that the mercury (49.6% by weight) in thimerosal might be contributing to autism [57], the industry made an effort to significantly reduce the amount of mercury present in vaccines beginning in the late 1990’s [58]. In parallel, they began storing the vaccines in individualized glass vials—to avoid the ostensible need for a preservative to reduce the danger of contaminating repeated invasions of multidose vials. However, this raises another concern, as aluminum can be leached out of the glass vial and the rubber stopper during storage [59]. This same issue can also affect premature infants given serum albumin infusions, resulting in an inadvertent exposure to aluminum very early in life [60]. Glass contains aluminum oxide at levels ranging from 1.9% to 5.8% [61]. Leaching from a container is an ongoing process until the product is used. Storage containers contribute significantly to aluminum contamination in human serum albumin products. Because of impaired renal function, dialysis patients are at risk to developing encephalopathy and a severe form of dementia due to their inability to dispose of the small amounts of aluminum that could be present in the dialysis water base [62],
Pharmacol Toxicol. 1992 Apr;70(4):278-80.
Aluminium-adjuvanted vaccines transiently increase aluminium levels in murine brain tissue.Redhead K, Quinlan GJ, Das RG, Gutteridge JM.
SourceDivision of Bacteriology, National Institute for Biological Standards and Control, Herts., UK.
AbstractAluminium is widely used as an adjuvant in human vaccines, and children can often receive up to 3.75 mg of parenteral aluminium during the first six months of life. We show that intraperitoneal injection of aluminium adsorbed vaccines into mice causes a transient rise in brain tissue aluminium levels peaking around the second and third day after injection. This rise is not seen in the saline control group of animals or with vaccine not containing aluminium. It is likely that aluminium is transported to the brain by the iron-binding protein transferrin and enters the brain via specific transferrin receptors.
PMID: 1608913 [PubMed - indexed for MEDLINE]
Curr Med Chem. 2011;18(17):2630-7.
Aluminum vaccine adjuvants: are they safe?Tomljenovic L, Shaw CA.
SourceNeural Dynamics Research Group, Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, V5Z 1L8, Canada. lucijat77@gmail.com
Abstract
Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue.
PMID:21568886[PubMed - indexed for MEDLINE]
http://www.mothering.com/articles/growing_child/vaccines/aluminum-new-thimerosal.html
Is Aluminum the New Thimerosal?
By Robert W. Sears Issue 146, January/February 2008
Vaccines have become the most controversial parenting topic of the decade. When parents are considering whether or not to vaccinate their children, one of the things that must be considered is aluminum toxicity. Aluminum is added to a number of vaccines to help them work better. Normally, one wouldn't consider aluminum to be a problem. It's a naturally occurring element that is present everywhere in our environment—in food, water, air, and soil. It's also a main ingredient in over-the-counter antacids. And because the body doesn't absorb aluminum, it's harmless when swallowed.
I didn't think much about aluminum when, 13 years ago, I began researching vaccines. In fact, the early seminars on vaccine education that I offered to parents included a brief statement that aluminum was nothing to worry about. But as I read each product insert and saw the number of micrograms (mcg) of aluminum contained in several vaccines, I wondered, "Has anyone determined what a safe level of injected aluminum actually is?" I didn't have to wonder for long, because the answer is easy to find; go to www.fda.gov, search on "aluminum toxicity," and you'll find several documents about aluminum.
The first document I came across discusses the labeling of aluminum content in injected dextrose solutions (the sugar solutions added to intravenous fluids in hospitals): "Aluminum may reach toxic levels with prolonged parenteral administration [i.e., injected into the body] if kidney function is impaired. . . . Research indicates that patients with impaired kidney function, including premature neonates [i.e., babies], who received parenteral levels of aluminum at greater than 4 to 5 micrograms per kilogram of body weight per day, accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading [i.e., toxic buildup in certain body tissues] may occur at even lower rates of administration."1 For a tiny newborn, this toxic dose would be 10 to 20 mcg; for an adult, it would be about 350 mcg.
The second document discusses aluminum content in IV feeding solutions, or Total Parenteral Nutrition (TPN) solutions. The FDA requires these solutions to contain no more than 25 mcg of aluminum per liter of solution. A typical adult in the hospital would get around 1 liter of TPN each day, thus about 25 mcg of aluminum. The FDA document also states, "Aluminum content in parenteral drug products could result in a toxic accumulation of aluminum in individuals receiving TPN therapy. Research indicates that neonates and patient populations with impaired kidney function may be at high risk of exposure to unsafe amounts of aluminum. Studies show that aluminum may accumulate in the bone, urine, and plasma of infants receiving TPN. Many drug products used routinely in parenteral therapy may contain levels of aluminum sufficiently high to cause clinical manifestations [i.e., symptoms]. . . Aluminum toxicity is difficult to identify in infants because few reliable techniques are available to evaluate bone metabolism in premature infants. . . Although aluminum toxicity is not commonly detected clinically, it can be serious in selected patient populations, such as neonates, and may be more common than is recognized."2
Elsewhere, I found a relevant 2004 statement by the American Society for Parenteral and Enteral Nutrition (ASPEN), a group that monitors oral and injectable nutritional products for safety and side effects. It reiterated the cited FDA warnings to the letter, and recommended that doctors purchase IV products with the lowest aluminum content possible, "and should monitor changes in the pharmaceutical market that may affect aluminum concentrations."3
The source of the daily limit of 4 to 5 mcg of aluminum per kilogram of body weight quoted by the ASPEN statement seems to be a study that compared the neurologic development of about 100 premature babies who were fed a standard IV solution that contained aluminum, with the development of 100 premature babies who were fed the same solution with almost all aluminum filtered out. The study was prompted by a number of established facts: that injected aluminum can build up to toxic levels in the bloodstream, bones, and brain; that preemies have decreased kidney function and thus a higher risk of toxicity; that an autopsy performed on one preemie whose sudden death was otherwise unexplained revealed high aluminum concentrations in the brain; and that aluminum toxicity can cause progressive dementia. The infants who were given IV solutions containing aluminum showed impaired neurologic and mental development at 18 months, compared to the babies who were fed much lower amounts of aluminum. Those who got aluminum received an average of 500 mcg of the metal over a period of 10 days, or about 50 mcg per day. The other group received only about 10 mcg of aluminum daily—4 to 5 mcg per kilogram of body weight per day.4 This seems to be the source of this safety level.
However, none of these documents or studies mentions vaccines; they look only at IV solutions and injectable medications. Nor does the FDA require labels on vaccines warning about the dangers of aluminum toxicity, although such labels are required for all other injectable medications.
All of these studies and label warnings seem to apply mainly to premature babies and kidney patients. What about larger, full-term babies with healthy kidneys? Using the 5 mcg/kg/day criterion from the first document as a minimum amount we know a healthy baby could handle, a 12-pound, two-month-old baby could safely receive at least 30 mcg of aluminum per day. A 22-pound one-year-old could receive at least 50 mcg safely. Babies with healthy kidneys could probably handle much more than this, but we at least know that they can handle this much. However, these documents don't tell us what the maximum safe dose would be for a healthy baby or child, and I can't find such information anywhere. This is probably why the ASPEN group suggests, and the FDA requires, that all injectable solutions be limited to 25 mcg; we at least know that that level is safe.
Calculating Aluminum in Vaccines
Here are the current levels of aluminum per shot of the following vaccines, as listed on each vaccine's packaging:
* DTaP (for Diphtheria, Tetanus, and Pertussis): 170-625 mcg, depending on manufacturer
* Hepatitis A: 250 mcg
* Hepatitis B: 250 mcg
* HIB (for meningitis; PedVaxHib brand only): 225 mcg
* HPV: 225 mcg
* Pediarix (DTaP Hepatitis B Polio combination): 850 mcg
* Pentacel (DTaP HIB Polio combination): 1500 mcg
* Pneumococcus: 125 mcg
In other words, a newborn who gets a Hepatitis B injection on day one of life would receive 250 mcg of aluminum. This would be repeated at one month with the next Hep B shot. When, at two months, a baby gets its first big round of shots, the total dose of aluminum could vary from 295 mcg (if a non-aluminum HIB and the lowest-aluminum brand of DTaP are used) to a whopping 1225 mcg (if the Hep B vaccine is given along with the brands with the highest aluminum contents). If the Pentacel combo vaccine is given along with the Hep B and Pneumococcus vaccines, the total aluminum dose could be as high as 1875 mcg. These doses are repeated at four and six months. With most subsequent rounds of shots, a child would continue to get some aluminum throughout the first two years. But the FDA recommends that premature babies, and anyone with impaired kidney function, receive no more than 10 to 25 mcg of injected aluminum at any one time.
As a medical doctor, my first instinct was to worry that these aluminum levels far exceed what may be safe for babies. My second instinct was to assume that the issue had been properly researched, and that studies had been done on healthy infants to determine their ability to rapidly excrete aluminum. My third instinct was to search for these studies. So far, I have found none. It's likely the FDA thinks that the kidneys of healthy infants work well enough to excrete aluminum before it can circulate through the body, accumulate in the brain, and cause toxic effects. However, I can find no references in FDA documents that show that using aluminum in vaccines has been tested and found to be safe.
So I did what any pediatrician would do. I turned to the American Academy of Pediatrics (AAP), who in 1996 published a policy statement, "Aluminum Toxicity in Infants and Children," that made the following points:
* Aluminum can cause neurologic harm.
* A study from 30 years ago showed that human adults increase their urine excretion of aluminum when exposed to higher levels of the metal, which suggests that adults can clear out excess aluminum.
* Adults taking aluminum-containing antacids don't build up high levels of aluminum in their bodies.
* Reports of infants with healthy kidneys show elevated blood levels of aluminum from taking antacids.
* People with kidney disease who build up bloodstream levels of aluminum greater than 100 mcg per liter are at risk of toxicity.
* The toxic threshold of aluminum in the bloodstream may be lower than 100 mcg per liter.
* The buildup of aluminum in tissues has been seen even in patients with healthy kidneys who receive IV solutions containing aluminum over
extended periods.5
However, nowhere in this paper was there any mention of aluminum in vaccines.
To put this in perspective: Because the body of the average adult contains about 5 liters of blood, receiving more than 500 mcg of aluminum in the bloodstream all at once will be toxic if the kidneys aren't working well. (Toxicity has also been seen in patients with healthy kidneys.) Because a newborn's body contains about a liter (300 milliliters) of blood, more than 30 mcg of aluminum floating around in the bloodstream could be toxic if the baby's kidneys aren't working well. The body of a toddler or preschool-age child contains about 1 liter of blood, so more than 100 mcg in his system could be toxic—and, as we've seen, babies can receive more than 1000 mcg of injected aluminum all at one time. Fortunately, this amount doesn't all go into the blood at once, but is slowly diffused into the bloodstream over a period of time from the muscle or skin where it was injected.
But that is the main point of this article. No one has measured the levels of aluminum absorption by the bloodstream when it is injected into the skin and muscle of infants, or the levels of excretion from the body via urination. All of the FDA and AAP documents that I've read state that aluminum might be a problem, but that they haven't studied it yet, so we should limit the amount of aluminum included in injectable solutions. But,
again, no one is talking about the levels of aluminum in vaccines.
What I think may have happened is that because aluminum used to be found in only one vaccine—DTP, an older version of the current DTaP vaccine—no one
thought much about it. Then, in the 1980s, the PedVaxHib brand of HIB meningitis vaccine was released, which also included aluminum; but other brands of HIB vaccine did not, so again, no one thought much about it. In the 1990s, the Hepatitis B vaccine began to be widely used; in the 2000s, the Pneumococcus vaccine; and, more recently, the Hepatitis A vaccine. Administering one aluminum-containing vaccine at a time involves only a small amount of the metal; administering four such vaccines simultaneously is a different story. It seems this issue has simply escaped everyone's attention. Or has it?
Limited Studies limit thinking
Several years ago, some suspected cases of aluminum toxicity resulted in various neurologic and degenerative problems. The Cochrane Collaboration, a group that studies health-care issues around the world, wanted to look at a very large study group to see if there was a real correlation between neurologic problems and the aluminum in vaccines. They investigated all the reported side effects of one aluminum-containing vaccine, DTP (no longer used), and looked for any evidence that such vaccines caused more side effects than non-aluminum vaccines. Other than more redness, swelling, and pain at the injection site, they found no indication that an aluminum-containing vaccine caused any more problems, and concluded that no further research should be undertaken on this topic.6 That is a very bold statement. Most researchers will draw conclusions from the findings of their own research; it's unusual to say that no one else should do any more research into the matter.
This is especially surprising because of the limitations of the Cochrane Collaboration's study. They looked at the effects of only one standard aluminum-containing vaccine, rather than the effects of all four being administered at once. They didn't study aluminum metabolism itself. They didn't test aluminum levels in children after vaccination, nor did they explore whether or not the amount of aluminum in vaccines builds up in the brain or bone tissues. They looked only for evidence of external symptoms of aluminum toxicity, not internal effects. Nor did they do their own research; instead, they reviewed all available studies conducted by other investigators. Despite all this, the Cochrane Collaboration study essentially closed the book on investigating aluminum toxicity from vaccines, without really having opened it in the first place.
The most obvious way to study this matter would be to inject various amounts of aluminum into children and see what happens to them internally. We know from the FDA documents that aluminum toxicity does occur from other types of injectable treatments; that it accumulates in the brain and bones in toxic amounts; that this may occur more commonly than is recognized; and that aluminum toxicity is hard to detect by looking for external symptoms. The question remains: What happens when these amounts of aluminum are injected via vaccines? Vaccine manufacturers may have begun to wonder about the same thing; I found some interesting research in the product insert of the new HPV vaccine, Gardasil. In researching the safety of Gardasil, Merck & Co., Inc., the vaccine's developer and manufacturer, added a step to their testing procedure by injecting aluminum into a separate group of test subjects used as a safety control group. They then compared the side effects of the Gardasil vaccine with a saline placebo that contained neither Gardasil nor aluminum, as well as with the placebo containing no Gardasil but the same amount of aluminum as the vaccine. They found that the placebo containing aluminum was much more painful than the saline placebo, and about as painful as the full HPV shot. The aluminum placebo also caused much more redness, swelling, and itching than the saline
placebo, though not quite as much as the full HPV shot.
Unfortunately, Merck looked only at the effects of aluminum at the injection site. Nor did they state in the Gardasil product insert what role the aluminum placebo played in all the other standard side effects, such as fever and flu-like symptoms. Nor did they study the body's internal metabolism of aluminum. However, their research did show how irritating aluminum can be when injected into the muscles. It was a good first step. If aluminum can be toxic, why not just remove it from vaccines, as is being done with the preservative thimerosal, which contains the neurotoxin mercury? It's not that simple. Aluminum is an adjuvant; in other words, it helps vaccines work more effectively. When the metal is mixed with a vaccine, the body's immune system more easily recognizes the vaccine and creates antibodies against the disease. Thimerosal was easy to omit, because it has nothing to do with the efficacy of the vaccine itself. But the pharmaceutical companies would need good evidence that aluminum is harmful before they would invest in coming up with new, aluminum-free vaccines. (The Cochrane Collaboration report pointed out that removing aluminum from vaccines would then require extensive trials of the reformulated vaccines.7)
What, exactly, does a toxic level of aluminum do to the brain? While no one has studied healthy babies to see how much, if any, aluminum builds up in the brain from the amounts of aluminum used in vaccines, the study on IV feeding solutions in premature babies mentioned above revealed that aluminum impaired their neurologic and mental development.8 But that was in premature babies, not healthy, full-term infants. I found several animal studies involving aluminum and/or aluminum-containing vaccines that did show neurologic harm. Not only did aluminum build up in the brain and cause damage, but some of the damage looked similar to what is seen in the brains of Alzheimer's patients.9-1314 However, it's hard to draw conclusions about aluminum's effects on humans from studies of animals. What we need are more studies of human infants.
A Call for Better Research
There is good evidence that large amounts of aluminum are harmful to humans. Because no meaningful research has specifically been done on aluminum in vaccines, there is no existing evidence that the amount in vaccines is harmful to infants and children. However, no one has actually studied aluminum levels in healthy human infants after vaccination to make sure it is safe. Should we now stop and research this matter? Or should we just go on, continuing to hope that it is safe to use aluminum as an adjuvant in vaccines?
Vaccine policy makers and advocates may read this article, review my perspective, and initiate research studies to explore the risks of aluminum. I would hope that those researchers do not conduct a retrospective review of all the old vaccine safety studies and journal articles to look for the side effects of aluminum. As the FDA, AAP, and others have stated, aluminum toxicity can't be detected by external observation alone. It would be a waste of time, and a grave disservice to
the health of America's children, to have several such reports show up in the medical literature. The only way the issue of aluminum safety can be put to rest is to conduct real-time studies on thousands of infants and measure aluminum levels after vaccination.
In such a study, the researchers should look not only at blood levels. They should also find out whether or not aluminum accumulates in the body, where it accumulates, how the body eliminates it, and at what rate. Once I see such research, and have determined to my satisfaction that aluminum has been proven safe, I will post an update on www.thevaccinebook.com, and revise future editions of the book accordingly. If such research finds that aluminum may not be safe, then I would expect a new vaccine schedule to be adopted in which the administering of vaccines is spread out to minimize the amount of aluminum a child receives at any given time. I would also expect vaccine manufacturers to begin finding ways to reduce or remove aluminum from vaccines without compromising their effectiveness. We need to know the answers to many questions: Why does one brand of HIB vaccine require aluminum to make it work while another brand does not? Why does one brand of DTaP vaccine contain four times as much aluminum as another? Why does one brand of combination vaccine contain three times as much aluminum as the sum of its parts?
Learning from the Past
I worry that aluminum may end up being another thimerosal. I am relieved that, as of 2002, the mercury-containing preservative had been removed from most vaccines. But according to an article in the Los Angeles Times, Merck & Co., the makers of several vaccines, knew in 1991 that the cumulative amount of mercury in vaccines given to infants by six months of age was about 87 times the level then thought to be safe.14 The article includes a copy of an internal memo, written by one of Merck's research doctors and sent to the president of Merck's vaccine division, clearly stating the doctor's worry about mercury overload. What was done with that information back in 1991? We'll never know. What we do know is that vaccine manufacturers knew that we were overdosing babies, but that the mercury wasn't removed from vaccines until 10 years later. This was because few paid attention to the potential problems with mercury. When we did find out, we hoped it wasn't harmful, we did extensive research to try to show that it wasn't, and we slowly removed it from most vaccines.
The issue of mercury toxicity from vaccines is moot for infants receiving vaccines today, as long as doctors and parents choose a flu shot without mercury, know which brands of vaccines still contain barely detectable traces of mercury, and are aware that some plain Tetanus and Diphtheria-Tetanus vaccines still contain mercury (though these last vaccines are not parts of the routine vaccine schedule). [For a current list of vaccines and their thimerosal contents, go to www.vaccine safety.edu/thi-table.htm.—Ed.]
What isn't moot is the question of aluminum toxicity. As doctors, we can choose certain vaccine brands that contain less or no aluminum. We can be careful about giving only one aluminum-containing vaccine at a time. And we can talk about it instead of sweeping the issue under the rug. I pray that my fears about aluminum are unfounded, and that objective studies performed by completely independent groups with no ties to vaccine manufacturers or political organizations show that it is safe. If not, I would hope that manufacturers would start to reduce or eliminate the aluminum content of their vaccines as soon as possible. I know this won't be an easy task, but our children are worth it.
Excerpted from The Vaccine Book © 2007 by Robert Sears, MD. Reprinted by
permission of Little, Brown and Company. New York, NY. All rights reserved.
For more information, see www.thevaccinebook.com. For the notes to this
article, see www.mothering.com/
articles/growing_child/vaccines/aluminum-new-thimerosal-notes.html.
Michael Wagnitz: Aluminum in our vaccines: Is it safe?
Michael Wagnitz
February 9, 2009
With the vaccines available in the U.S. today, parents can avoid vaccines preserved with thimerosal (50% mercury) for their newborns and infants. This is not the case with aluminum, which has been linked to impaired neurological development in children. Aluminum has not replaced thimerosal as a vaccine preservative; it has always been used in vaccines. Its purpose is to generate an immune response, thus providing a person the ability to produce adequate levels of antibodies to the vaccine being administered. Unlike thimerosal, if aluminum is removed, the vaccine will not work.
In the recent past, most kids got exposed to both thimerosal and aluminum simultaneously with the hepatitis B, Hib, DTaP (diphtheria, tetanus and pertussis) and pneumococcal vaccines. Combining mercury with aluminum increases the likelihood that the mercury will damage human tissue. While aluminum is in the food we eat at much higher levels, it is not absorbed well through the gastrointestinal tract. When this protective gastrointestinal mechanism is bypassed, aluminum toxicity can cause serious problems.
There are currently eight childhood vaccines that contain aluminum ranging from 125 to 850 micrograms (mcg). These vaccines are administered 17 times in the first 18 months of life, an almost six-fold increase compared to the vaccine schedule of the 1980s. According to the American Society for Parenteral and Enteral Nutrition, based on IV feeding solutions, a child should not exceed a maximum daily dose of 5 mcg of aluminum per kilogram of weight per day. That means if a child weighs 11 pounds, the child should not exceed 25 mcg in a day. This level was determined to be the maximum safety limit based on a study published in the New England Journal of Medicine titled "Aluminum Neurotoxicity in Preterm Infants Receiving Intravenous Feeding Solutions."
The hepatitis B vaccine, administered at birth, contains 250 mcg.
In a 1996 policy statement, "Aluminum Toxicity in Infants and Children," the American Academy of Pediatrics states, "Aluminum can cause neurological harm. People with kidney disease who build up bloodstream levels of aluminum greater than 100 mcg per liter are at risk of toxicity. The toxic threshold of aluminum in the bloodstream may be lower than 100 mcg per liter."
So let's say an infant receives 1,250 micrograms at 2 months of age (three vaccines). Assuming a child's body contains a half liter of blood, this would put the blood level 25 times higher than the above mentioned levels.
Now people will argue whether an intramuscular injection (such as vaccines) would introduce aluminum into the bloodstream at the same level as an IV feeding solution. Unfortunately, the purpose of direct intramuscular injection is to provide rapid access to the bloodstream. This provides direct access to all target organs such as the brain.
The real eye-opener is a recently published paper where the authors investigated Gulf War syndrome based on the fact that soldiers were getting sick without deployment to the Persian Gulf region. They eventually focused on aluminum used in the anthrax vaccine. Injecting mice with aluminum at levels equal to what the soldiers received induced motor neuron death. The dose, per body weight, given to children easily exceeds what the soldiers received.
One must question whether exposing newborns to aluminum is worth the risk to protect them against a sexually transmitted disease (hepatitis B). If aluminum can cause injury to an adult, combat-ready soldier, what is it doing to newborns?
Michael Wagnitz of Madison is a chemist.
madison.com is operated by Capital Newspapers, publishers of the Wisconsin State Journal, The Capital Times, Agri-View and Apartment Showcase. All contents Copyright ©2009, Capital Newspapers. All rights reserved.
Aluminum adjuvant linked to gulf war illness induces motor neuron death in mice.
Neuromolecular Medicine
February 2007, Volume 9, Issue 1
http://journals.humanapress.com/index.php?option=com_opbookdetails&task=articledetails&category=humanajournals&article_code=NMM:9:1:83
Petrik MS, Wong MC, Tabata RC, Garry RF, Shaw CA.
Department of Ophthalmology and Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, Canada.
Gulf War illness (GWI) affects a significant percentage of veterans of the 1991 conflict, but its origin remains unknown. Associated with some cases of GWI are increased incidences of amyotrophic lateral sclerosis and other neurological disorders. Whereas many environmental factors have been linked to GWI, the role of the anthrax vaccine has come under increasing scrutiny. Among the vaccine's potentially toxic components are the adjuvants aluminum hydroxide and squalene.
To examine whether these compounds might contribute to neuronal deficits associated with GWI, an animal model for examining the potential neurological impact of aluminum hydroxide, squalene, or aluminum hydroxide combined with squalene was developed. Young, male colony CD-1 mice were injected with the adjuvants at doses equivalent to those given to US military service personnel. All mice were subjected to a battery of motor and cognitive- behaviora l tests over a 6-mo period postinjections.
Following sacrifice, central nervous system tissues were examined using immunohistochemistr y for evidence of inflammation and cell death. Behavioral testing showed motor deficits in the aluminum treatment group that expressed as a progressive decrease in strength measured by the wire-mesh hang test (final deficit at 24 wk; about 50%). Significant cognitive deficits in water-maze learning were observed in the combined aluminum and squalene group (4.3 errors per trial) compared with the controls (0.2 errors per trial) after 20 wk.
Apoptotic neurons were identified in aluminum- injected animals that showed significantly increased activated caspase-3 labeling in lumbar spinal cord (255%) and primary motor cortex (192%) compared with the controls. Aluminum-treated groups also showed significant motor neuron loss (35%) and increased numbers of astrocytes (350%) in the lumbar spinal cord.
The findings suggest a possible role for the aluminum adjuvant in some neurological features associated with GWI and possibly an additional role for the combination of adjuvants.
Neuromolecular Med. 2007; 9(1); 83-100.
http://brain.oupjournals.org/cgi/content/full/124/9/1821 (Full text article)
Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminum hydroxide in muscle
Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminum hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminum hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 396 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminum hydroxide-containing vaccines, shows both long-term persistence of aluminum hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.
One of the more entertaining (scientifically entertaining) experiences I had in the year past was attendance at a workshop on aluminum-containing adjuvants in vaccines. The workshop was held in the felicitous environment of San Juan, Puerto Rico, last May, and was sponsored by the National Vaccine Program Office, a Health and Human Services-based office charged with coordination of the major federal players in the vaccine arena, namely, the National Institutes of Health, the Food and Drug Administration and the Centers for Disease Control and Prevention (CDC).
It was the second in a series of workshops that examined additives to vaccines. The first workshop, held the previous year, dealt with thimerosal, and exposed a great deal of scientific uncertainty extending in some areas to ignorance about the distribution and the behavior of the active compound, ethyl mercury. The same pervasive uncertainty, bordering in some instances on ignorance, characterized the aluminum-containing adjuvants workshop.
Mechanism of action uncertain
There are three basic aluminum salts used as vaccine adjuvants: aluminum hydroxide, aluminum phosphate and potassium-aluminum sulfate, or alum. Each has different chemical properties and isoelectric points, and they are not simply interchangeable when used in vaccine formulations. The mechanism of action of these adjuvants represents an area of scientific uncertainty, but they are believed to form a repository of antigen in tissue, to facilitate presentation of particulate antigen to immune cells, and perhaps, to activate complement and other immune enhancers.
The goal of adjuvant use in vaccines is to enhance immune contact, to increase the height of the antibody response, and to prolong the immune response - all this, of course, with total safety and freedom from adverse effects. The aluminum-containing adjuvants have certainly succeeded as immune enhancers, and this is amply documented in the literature of the 1930s-1960s. The enhancement effect is most marked during the primary immunization series; there is little incremental benefit of aluminum adjuvants in booster doses. The adjuvants appear to facilitate a type 2 immunologic response and do not induce cytotoxic T cells and cell-mediated immune mechanisms. These adjuvants are, however, not totally free of adverse effects; sterile abscesses, erythema, swelling, subcutaneous nodules, granulomatous inflammation and contact hypersensitivity have been reported with variable frequency and severity.
U.S. licensed vaccines that contain aluminum salts include DTP, DTaP, some but not all Hib vaccines, and HepA and HepB, Lyme disease, anthrax and rabies vaccines. Among inactivated vaccines, only inactivated poliovirus and influenza vaccines do not contain aluminum salts used as adjuvants. This is true not only for U.S. licensed vaccines, but also is true around the entire world. The World Health Organization's Enhanced Program in Immunization (EPI) is highly reliant on vaccines containing aluminum adjuvants, and these vaccines have an established track record of safety extending over almost half a century.
Controversial data
By far the most controversial (scientifically entertaining) part of the workshop was presented by a French investigator, Romain Gherardi, pathologist at the Henri Mondor University in Creteil. He had published an article in The Lancet two years previously (1998;352: 347-52) describing a clinica and pathologic entity he called macrophagic myofasciitis (MMF), an unusual "new inflammatory muscle disorder of unknown cause." Based on additional work done in the two years since that publication, he presented his data at the workshop and argued that the cause of this entity is actually the aluminum in vaccines given in France.
More than 100 patients have been identified to date, and the analysis he presented was confined to the first 50 patients. The entity itself has been identified in deltoid muscle biopsies of patients with a variety of complaints, including diffuse myalgia, arthralgia, and fatigue; some but not all of these patients met the CDC definition for chronic fatigue syndrome. Biopsies revealed extensive infiltration of macrophages around, but not inside muscle fibers, with a few CD8+ T cells. Typically, there was no tissue necrosis and little evidence of muscle damage. Many of the macrophages contained para-aminosalicylic acid (PAS)-positive crystalline structures, subsequently identified as aluminum. Laboratory evidence of inflammation was variable; most patients had a normal white blood cell count and creatine phosphokinase; about half had some serum autoantibodies present. In addition, levels of certain cytokines seemed to be increased, especially interleukin (IL)-1 receptor antagonist and IL-6.
The patients were mostly middle-age adults with males and females about equally represented. All had received aluminum-containing vaccines, mostly HepB vaccine, in the biopsied deltoid muscle; a mean of 36 months had elapsed between vaccination and muscle biopsy. A high proportion of patients were health care workers, had a sports affiliation, or had traveled extensively. There was a seemingly higher than expected proportion of patients with concurrent autoimmune disease (34%). In fact, six of the 50 patients in an epidemiologic analysis had multiple sclerosis. Most patients responded to treatment with steroids and/or antibiotics.
Why only France? Dr. Gherardi related that there had been an extensive campaign there in the preceding five years to immunize adults with HepB vaccine. Also, the French typically do a deltoid biopsy whenever muscle biopsy is indicated; elsewhere, including the U.S., calf muscles such as the gastrocnemius are preferred.
Participants remained unconvinced Most workshop participants were frankly skeptical. Many were unconvinced that MMF really represented a new entity, and all doubted that the argument that it was caused by aluminum could be sustained. In particular, his argument was faulted for a lack of controls, for there were no data on unvaccinated patients, or on patients who had been vaccinated but were asymptomatic. For that reason, many participants suggested that this was simply an epiphenomenon, or represented an epidemic of recognition, which is now feeding in France on its own publicity. To quote that most overused concluding comment, "further investigation is warranted," and indeed many additional in vitro and in vivo studies are already underway to elucidate the etiology and significance of MMF.
All the scientific uncertainties notwithstanding, most participants left the workshop reassured about the safety of aluminum adjuvants. Yet, the most relevant question - "Do we really need them?"- was never really answered.
Lessons from Macrophagic Myofasciitis: Towards a Definition of a Vaccine Adjuvant-Related Syndrome [Chronic Fatigue Syndrome news]
ImmuneSupport.com
04-02-2003
Source: Rev Neurol (Paris) 2003 Feb;159(2):162-4
[original article published in French]
Gherardi RK.
Groupe Nerf-Muscle, Departement de Pathologie, Hopital Henri Mondor, Creteil.
Macrophagic myofasciitis is a condition first reported in 1998, and the cause remained obscure until 2001. Over 200 definite cases have been identified in France, and isolated cases have been recorded in other countries. The condition manifests by diffuse myalgias and chronic fatigue, forming a syndrome that meets both Center for Disease Control and Oxford criteria for the so-called Chronic Fatigue Syndrome in about half of patients.
One third of patients develop an autoimmune disease, such as multiple sclerosis. Even in the absence of overt autoimmune disease they commonly show subtle signs of chronic immune stimulation, and most of them are of the HLADRB1*01 group, a phenotype at risk to develop polymyalgia rheumatica and rheumatoid arthritis. Macrophagic myofasciitis is characterized by a stereotyped and immunologically active lesion at deltoid muscle biopsy.
Electron microscopy, microanalytical studies, experimental procedures, and an epidemiological study recently demonstrated that the lesion is due to persistence for years at site of injection of an aluminum adjuvant [auxiliary substance] used in vaccines against hepatitis B virus, hepatitis A virus, and tetanus toxoid. Aluminum hydroxide is known to potently stimulate the immune system and to shift immune responses towards a Th-2 profile.
It is plausible that persistent systemic immune activation that fails to switch off represents the pathophysiologic basis of Chronic Fatigue Syndrome associated with macrophagic myofasciitis, similarly to what happens in patients with post-infectious chronic fatigue and possibly idiopathic Chronic Fatigue Syndrome.
Therefore, the WHO recommended an epidemiological survey, currently conducted by the French agency AFSSAPS, aimed at substantiating the possible link between the focal macrophagic myofasciitis lesion (or previous immunization with aluminum-containing vaccines) and systemic symptoms. Interestingly, special emphasis has been put on Th-2 biased immune responses as a possible explanation of chronic fatigue and associated manifestations known as the Gulf War Syndrome. Results concerning macrophagic myofasciitis may well open new avenues for etiologic investigation of this syndrome.
Indeed, both type and structure of symptoms are strikingly similar in Gulf War veterans and patients with macrophagic myofasciitis. Multiple vaccinations performed over a short period of time in the Persian gulf area have been recognized as the main risk factor for Gulf War Syndrome.
Moreover, the war vaccine against anthrax, which is administered in a 6-shot regimen and seems to be crucially involved, is adjuvanted by aluminum hydroxide and, possibly, squalene, another Th-2 adjuvant. If safety concerns about long-term effects of aluminum hydroxide are confirmed, it will become mandatory to propose novel and alternative vaccine adjuvants to rescue vaccine-based strategies and the enormous benefit for public health they provide worldwide.
http://books.nap.edu/books/0309044995/html/347.html#pagetop
Adverse Effects of Pertussis and Rubella Vaccines (1991)
Institute of Medicine (IOM)
The following text is provided to enhance readability. Many aspects of typography translate only awkwardly to HTML. Please use the page image as the authoritative form to ensure accuracy. Page 347E Possible Involvement of Aluminum Salts in Erythema Multiforme, Encephalopathy, or Other Adverse Events After Pertussis Immunization
DPT vaccine preparations regularly contain aluminum salts (aluminum hydroxide, aluminum potassium sulfate, or aluminum phosphate) that are intended to serve as adjuvants (British National Formulary, 1988; Physicians' Desk Reference, 1989). Orlans and Verbov (1982) suggested that DPT-associated rashes could be due to aluminum hydroxide. Other more significant local reactions including nodules at the site of injection, itching, eczema, and circumscribed hypertrichosis over nodules have been observed more frequently following administration of aluminum hydroxide-adsorbed DPT vaccine than after administration of unadsorbed DPT vaccine (Pembroke and Marten, 1979).Interest has developed recently in the potential health effects of aluminum, particularly in the setting of chronic renal failure, in which aluminum is not excreted from the body normally (Alfrey, 1984; Monteagudo et al., 1989). A severe, often fatal encephalopathy found in patients undergoing long-term dialysis was attributed to aluminum deposition in the brain (Alfrey et al., 1976). Reduction of aluminum in dialysate has largely eliminated this condition, but dialysis patients may still have subtle psychomotor defects that may be due to aluminum toxicity (Altmann et al., 1989). Animal studies have shown that aluminum can increase the rate of transmembrane diffusion across the blood—brain barrier (Banks and Kastin, 1989), which could possibly permit greater access of toxins to the brain. Patients receiving long-term injections of aluminum-containing allergenic
Aluminum-Alzheimer's link Date: Sun, 20 Apr 2003 14:45:39 -0400
http://www.nlm.nih.gov/medlineplus/news/fullstory_12359.html
Aluminum in Drinking Water Tied to Alzheimer's
Reuters Health
By Jacqueline Stenson
Monday, April 14, 2003
SAN DIEGO (Reuters Health) - Adding support to a controversial theory linking aluminum with Alzheimer's disease, new research indicates the disease is more common in regions of northwest Italy where levels of aluminum in drinking water are highest.
And when the investigators studied the effects of one form of the metal on two types of human cells in the lab, they found it hastened cell death."We were absolutely surprised by these results," said study author Dr.Paolo Prolo, a researcher at the University of California at Los Angeles. "I did not expect any effect from aluminum." In findings released here Monday at the annual Experimental Biology meeting, Prolo and colleagues focused on monomeric -- single molecule --aluminum. This is the type that can be most easily absorbed by human cells, he said.
While there have been suggestions that aluminum cookware might pose a risk for Alzheimer's, the type of aluminum used in pots and pans consists of multiple molecules and does not appear to affect human cells, according to Prolo. "There is almost no evidence that the cookware is dangerous," he said. When the researchers tested water in regions of northwest Italy in 1998, they found that total aluminum levels -- including monomeric and other types of aluminum -- ranged from 5 to 1,220 micrograms per liter, while monomeric aluminum levels alone ranged from 5 to 300 micrograms per liter.
Environmental officials generally recommended that total aluminum levels be below 200 micrograms per liter, Prolo noted.After comparing this data to death rates from Alzheimer's in those regions, the researchers found that the disease was more common in areas with the highest levels of monomeric aluminum.
Back in the lab, Prolo and colleagues then tested the effects of monomeric aluminum on human immune-system cells and bone cancer cells. Ideally, human brain cells would be tested but these are not readily available because a biopsy of a patient's brain is necessary to acquire them, he said. "We found that a very low quantity of aluminum added to our cell cultures was modifying cellular processes" like normal cell death, Prolo told Reuters Health.
When the aluminum was paired with beta-amyloid, a protein found in the brains of Alzheimer's patients, the combination killed off even more cells. Because aluminum could kill both types of human cells, these findings raise the question of whether aluminum is potentially involved in other diseases, Prolo said.
But much more research is needed to understand how the metal does or does not affect people, he added.
Related News:
Related MEDLINEplus Pages:
http://www.healthwell.com/hnbreakthroughs/mar98/aluminum.cfm
April 19, 2003 Can Aluminum Cause Alzheimer's Disease? by Melvyn R. Werbach, M.D.
Senile dementia is a progressive degenerative brain disease associated with old age. Its symptoms include short-term memory loss, slowness in thought and movement, confusion, disorientation, depression, difficulty communicating, and loss of physical function. Alzheimer's disease accounts for about half of all senile dementia cases. Although there are many theories about what causes Alzheimer's, the fact is, its origins remain poorly understood.
One theory proposed that the common occurrence of being exposed to aluminum could cause Alzheimer's dementia. Aluminum, the theory postulated, becomes concentrated in the characteristic lesions (senile plaques and neurofibrillary tangles) that develop in the brain during the course of the disease. At first, medical scientists thought this theory was absurd. Aluminum, they believed, accumulated merely as a result of a destructive process caused by some other factor.
In recent years, however, the aluminum hypothesis has been gaining respect. For example, studies have discovered a direct association between the level of aluminum in municipal drinking water and the risk of Alzheimer's dementia. One study found aluminum in drinking water was related to only this specific type of dementia;1 another found that the probability of the association being due to chance was only 1 in 24, with a 46 percent increased risk for people drinking water with the highest aluminum levels.2
The use of aluminum-containing antiperspirants--but not the use of antiperspirants and deodorants in general--has also been associated with a risk of Alzheimer's dementia, with a trend toward a higher risk corresponding with increasing frequency of use.3 This relationship does not extend to aluminum-containing antacids,4 which may simply be evidence that the aluminum in antacids is not absorbed--the process of absorption through the gut mucosa is quite different from absorption through the skin.
We also know that serum aluminum concentrations increase with age. Aluminum may accumulate slowly over our lifetimes or we may absorb it more easily as we age. Moreover, there is evidence that people with probable Alzheimer's disease have serum aluminum levels that are often significantly higher than those of people with other types of dementia, as well healthy people of similar ages.5
Further evidence that aluminum fosters the development of Alzheimer's dementia comes from a scientific (placebo-controlled) trial of desferrioxamine, a drug that removes aluminum from the body by binding with it. While regular administration of the drug failed to stop the disease from progressing, desferrioxamine did significantly reduce the rate of decline in the ability of a group of people with Alzheimer's dementia to care for themselves.6
Although the aluminum/Alzheimer's link remains unproven, I believe that waiting for definitive proof before taking a few easy and protective measures is foolhardy--and more scientists are starting to agree.7,8 Perhaps one person in 10 age 65 or older suffers from dementia; by age 80 that figure rises to one in five. This is too common an illness to ignore preventive measures until we can know for certain why it develops.
Ways To Avoid Aluminum Here are my suggestions for minimizing your exposure to aluminum.
* Drinking water should be low in aluminum. Some bottled-water companies provide an analysis of the aluminum content of their water. You might also find out from your public water company what the aluminum level is in the local drinking water.
* Aluminum-containing antiperspirants can easily be avoided, as can aluminum utensils and even, to play it safe, aluminum-containing antacids.
* Commercially processed foods such as cake and pancake mixes, frozen doughs and self-rising flour are sources of dietary aluminum, so their ingestion should be minimized. Watch for and avoid sodium aluminum phosphate, an ingredient in baking powder. Pickles and cheese should also be avoided.
* There is a close relationship between silicon and aluminum in Alzheimer brain lesions, as the two substances bind together to form aluminosilicates.9 High levels of silica in drinking water in the form of silicic acid do seem to protect against the adverse effects of aluminum ingestion, and silicic acid ingestion increases urinary aluminum excretion.10,11 Whether silica supplements protect against the development of dementia has yet to be determined.
* Besides minimizing aluminum exposure, taking the Recommended Dietary Allowance (RDA) of calcium, magnesium and zinc should help to protect against aluminum accumulation.12-14 Deficiencies of these important minerals are common among the elderly.15 Yet, unless there is laboratory evidence of a zinc deficiency, I would not recommend zinc supplementation to help prevent Alzheimer's disease, for two reasons. First, beta-amyloid protein, the major substance found in the brain lesions (usually in a liquid form), binds with zinc. At concentrations only slightly higher than those normally found in the brain, excess zinc may convert the protein to the solid form that is found in Alzheimer lesions.16 This suggests that, at least in theory, excess zinc could actually promote the development of the disease. Second, there is a lack of adequate research demonstrating the efficacy of zinc supplementation in preventing Alzheimer's, although in one study all six relatively young dementia victims had some memory improvement following supplementation with zinc aspartate.17
References
1. Martyn, C.N., et al. Lancet, 1: 59-62, 1989.
2. Neri, L.C., & Hewitt, D. Letter. Lancet, 338: 390, 1991.
3. Graves, A.B., et al. J Clin Epidemio,l 43(1): 35-44, 1990.
4. Ibid.
5. Zapatero, M.D. Biol Trace Elem Res, 47: 235-40, 1995.
6. McLachlan, D.R., et al. Lancet, 337: 1304-8, 1991.
7. Lukiw, W.J. Mineral and Metal Neurotoxicology. 113-26. CRC Press, 1997.
8. McLachlan, D.R., et al. Can Med Assoc J, 145(7): 793-804, 1991.
9. Candy, J.M., et al. Lancet, i: 354-57, 1986.
10. Jacqmin-Gadda, H., et al. Epidemiology 7(3): 281-85, 1996.
11. Bellia, J.P., et al. Ann Clin Lab Sci, 26: 227-33, 1996.
12. Foster, H.D. Health, Disease and the Environment. 311-16. Boca Raton,Fla.: CRC Press, 1992:
13. Durlach, J. Magnes Res, 3(3): 217-18, 1990.
14. Wenk, G.L., & Stemmer, K.L. Brain Res 288: 393-95, 1983.
15. Werbach, M.R. Foundations of Nutritional Medicine: Common nutritional deficiencies. Tarzana, Calif.: Third Line Press, 1997.
16. Bush, A.I., et al. Science, 265: 1464-67, 1994.
17. Constantinidis, J. Schweiz Arch Neurol Neurochir Psychiatr, 141(6):523-56, 1990.
Melvyn R. Werbach, M.D., is a faculty member at the UCLA School of Medicine and the author of Nutritional Influences on Illness (Third Line Press Inc.,1993).
http://www.bio.unipd.it/~zatta/alumin.htm
CNR NATIONAL RESEARCH COUNCIL OF ITALY INSTITUTE FOR BIOMEDICAL TECHNOLOGIES
Padova Unit "Metalloproteins" University of Padova Department of Biology Via G. Colombo 3, 35121 Padova, Italy
An International Aluminum Network was established in 1995 open to all scientists interested to a better understanding of the aluminum impact on biological systems from different point of views: Physiological, Pathological, Toxicological, Biochemical in humans as well as in vitro and in vivo experimentation.
This network is devoted to exchanging proposals and scientific data (relevant papers, experimental data etc.) as well as to inform on various activities around the world: workshops, round tables, symposia etc. where relevant issues on Chemistry or Biology related to the Physiopathology of aluminum could be discussed.
Besides, being the most abundant metal and the third most abundant element on the Earth's crust, aluminum has been implicated as an etiological factor in some pathologies related to long-term dialysis treatment of uremic patients and as a potential factor or cofactor in the Alzheimer's syndrome, as well as in the etiopathogenesis of other neurodegenerative diseases, Parkinsonism, Amyotrophic Lateral Sclerosis and other diseases.
Al(III) SPECIATION
Tamas Kiss
ALUMINUM DETERMINATION IN BIOLOGICAL SPECIMENS
Andrew Taylor
ALUMINUM WITH SILICIC ACID
Christopher Exley
TRANSFERRIN AS A METAL ION CARRIER
Peter Sadler and Hongyan Li
BINDING SPECIFICITY OF ANTI-ALUMINUM ANTIBODIES
R. Levy and B. Solomon
ALUMINIUM AND THE NEURONAL GLUTAMATE-NITRIC OXIDE-CYCLIC GMP PATHWAY
Vicente Felipo
ALUMINUM AND GENE EXPRESSION
Walter J. Lukiw
ALUMINUM AND NEUROFILAMENT ASSEMBLY
Thomas B. Shea
ALUMINUM INDUCED ALTERATIONS IN THE NEURONAL CYTOSKELETON
Nancy Muma
Al(III)AND FREE RADICALS
Patricia I. Oteiza
EFFECT OF IRON STATUS ON ALUMINIUM SPECIATION, ABSORPTION AND DISTRIBUTION
Christian Steinhausen
ALUMINUM AND HEPATOPOIETIC SYSTEM
Khalequz Zaman
INTERACTIONS OF ALUMINUM WITH NEURONAL PLASTICITY, SYNAPTIC TRASMISSION AND MEMBRANE PORES
Dietrich Busselberg and Bettina Platt
PROCESS OF ACCUMULATION OF ALUMINIUM IN HUMAN BRAIN
Satoshi Tokutake
ALUMINUM AND ALZHEIMER'S AMYLOID BETA-PROTEIN
Masahiro Kawahara ALUMINUM AND BLOOD-BRAIN BARRIER PERMEABILITY
William A. Banks NEUROFIBRILLARY PATHOLOGY AND ALUMINUM IN ALZHEIMER'S DISEASE
J. Q. Trojanowski
Ryong-Woon Shin
ALUMINUM AND THE PRECURSOR PROTEIN OF THE NON-A COMPONENT OF ALZHEIMER'S
DISEASE AMYLOID (NACP)
Seung R. Paik and Ju-hyun Lee
First International Conference on METALS AND THE BRAIN: From Neurochemistry to Neurodegeneration (University of Padova, Italy: 20-23 September 2000)
ALUMINUM AND HEALTH
RECOMMENDATIONS
Aluminum is an environmentally abundant element to which we are all exposed. The neurotoxicity of this metal has been known for more than a century. More recently, it has been implicated as an etiological factor in some pathologies (including encephalopathy, bone disease, anemia) related to dialysis treatment . In addition, it has been hypothesized to be a cofactor in the etiopathogenesis of some neurodegenerative diseases, including Alzheimer's disease (AD), although, despite many studies in several laboratories in different countries, direct evidence is still, so far controversial. Thus, examples of aluminum neurotoxicity are well recognized-in experimental animals and in individuals with renal failure (consequent upon aging, intoxication or renal disease) - and there are grounds to link neurodegenerative disorders to aluminum exposure. Furthermore, an increased concentration of Al in infant formulas and in solutions for home parenteral nutrition has been associated with neurological consequences and metabolic bone disease, characterized by low-bone formation rate, respectively.
For all these reasons and on the basis of our many years of scientific experience in this field, we propose the following recommendations as guidelines to avoid risks due to aluminum accumulation and potential intoxication. These recommendations are not rigid and will be updated when relevant new scientific data is available.
GENERAL RECOMMENDATIONS
1. It would be valuable to define as completely as possible which patient groups are at risk for iatrogenic aluminum loading, and under which conditions aluminum represents a health hazard. The more complete knowledge we have for the clinical, iatrogenic setting, the better basis we will have to judge whether different types of aluminum exposure are hazardous to the general population or to susceptible subgroups.
2. A provisional list of patients groups at risk of iatrogenic aluminum loading should include, at least, people with impaired renal function, infants, old people and patients on total home parenteral nutrition. Where such exposure occurs, serum aluminum concentrations should be less than 30 µg/l and possibly lower. However, further studies are necessary.
3. Urinary aluminum is also an indicator of aluminum absorption, the excreted Al/retained Al ratio depends on the integrity of the renal function.
4. Al may enter human body by mouth, intravenous infusions and by environment. Specific controls have to be adopted in order to reduce each risk of exposure.
Oral exposure
5. Aluminum in drinking water should be less than 50 µg L-1. Silicon is relevant to aluminum toxicity and, therefore, the water silicon concentrations should be monitored in parallel.
6. The aluminum content should be declared in all food preparations and pharmacological products.
7. Citrate-containing compounds appear to increase the bioavailability of ingested aluminum. Therefore, particular care should be taken to avoid these compounds in combination with Al-containing drugs. With citric acid, the enhanced gastrointestinal absorption may by compensated for by a parallel increase in urinary Al excretion, where there is good renal function. However, it is strongly suspected from recent simulation studies that other dietary acids (e.g., succinic and tartaric acids) also increase Al-bioavailability but do not cause any compensatory increase in urinary excretion. Ascorbate and lactate also significantly enhance gastrointestinal absorption of Al, as was recently demonstrated in animal studies.
8. It is recommended that acidic food, e.g., acid cabbage, tomato, etc. should not be cooked or stored in aluminum ware. In this connection, it has been demonstrated that in the juice of acidic cabbage, cooked in aluminum, the metal ion content is up to 20 mg/ L.
9. Individual susceptibility to aluminum has been reported by the scientific literature. Thus, special efforts should be taken to prevent contamination of food and beverages etc. with aluminum either directly or during preparation, with special regard to infants, old people or individuals with suboptimal renal functionality.
10. Magnesium depletion is considered a high risk for aluminum accumulation especially during pregnancy and in the neonate with possible consequent problems for normal development and growth. Magnesium depletion is also common with aging.
11. Iron depletion is considered a high risk for aluminium accumulation, as iron and Al share common carriers.
Parenteral exposure:
12. Aluminum in all intravenous (i.v.) fluids should be controlled monitored and labeled. There is a general consensus that the aluminum content of i.v. fluids used in children and adults with renal failure or undergoing dialysis, should be as low as possible and in any case no higher than 10 µg/L.
13. The use of parenteral nutrition fluids that are high in aluminum should be eliminated or significantly reduced.
CONTRIBUTORS (Provisional list)
P. Zatta, CNR Center on Metalloproteins. University of Padova, Italy.
Coordinator of the Project: Interdisciplinary Approach to The Study of
Aluminum Toxicity. E.C.COST D8 "Metals in Medicine".
* C. Canavese, (On the behalf of the Italian Nephrological Society) Le Molinette Hospital, Torino, Italy.
* S. Costantini, Istituto Superiore di Sanità, Roma, Italy.
* M. Gallieni, Dept. of Nephrology, San Paolo Hospital, University of Milano, Italy.
M. Andriani, +Chief Nephrologist, Dolo General Hospital, Venice, Italy (On the behalf of the SIN-Italian Nephrological Society).
* G. Berthon, CNRS FR1744, Université Paul Sabatier, Toulouse, France.
* D. Boggio - Bertinet, on the behalf of the Italian Society of Parenteral and Enteral Nutrition
* J. Domingo, Faculty of Medicine, Rovira I Virgili University, Reus, Spain.
* T. Flaten, Dept. of Chemistry, Norwegian University of Science and Technology, Trondheim, Norway.
* M. Golub, Dept. Internal medicine. University of California, Davis, USA.
N. Goto, Laboratory of General Toxicology, Dept. Safety Research on Biologics, National Institute of Infectious Diseases, Tokyo, Japan.
* M. Kawahara, Metropolitan Institute for Neuroscience, Tokyo, Japan.
* T. Kiss, Dept. of Inorganic and Analytical Chemistry, University of Szeged, Hungary.
* W. Lukiw, LSU Neuroscience Center, New Orleans, LA, USA.
W. Markesbery, University of Kentucky Alzheimer's Disease Research Center, Lexington, KY, USA.
* R. Milacic, Josef Stefan Institute, Ljubljana, Slovenia.
C. Ronco, Director of the Renal Research Laboratory, Beth Israel Med. Ctr, New York, NY, USA.
H.H. Sandstead, University of Texas, Med. Branch, Galveston, TX, USA.
A. Taylor, Center for Clinical Sciences and Measurement, School of Biological Sciences, University of Surrey, Guilford, U.K.
This document will be published in relevant scientific journals, and will be sent to all Health Ministers of the European Community as well as to other Public Health Authorities. (FDA, WHO etc.). For further information, please contact Prof. P. Zatta: zatta@civ.bio.unipd.it
Padova 20-23 September 2000
ALZHEIMERS/ALUMINUM STUDIES YEAR HEAD INVESTIGATOR AFFILIATED INSTITUTION FINDINGS
1965 Klatzo NIH Injection of animal salts produced changes in the animal brains. J.Neuropathol Exp Neurol 24:187-199, 1965.
1970 Wisniewski Einstein Medical Center Changes in animal brains different from those in Alzheimer's Disease. J.Neuropathol Exp Neurol 29: 163-176, 1970.
1973 McLachlan University of Toronto Brains of Alzheimer's Disease victims have higher Aluminum content.
1976 Alfrey Denver V.A. Hospital Dialysis dementia attributed to Aluminum. NEngl J Med 294: 184-188, 1976.
1979 Ellis University of Sheffield Aluminum affects bones of dialysis patients
1980 Perl University of Vermont Aluminum in Alzheimer's Disease "tangles" in brain. Science 208: 297-299, 1980; Neurotoxicoloy 1: 133-137, 1980.
1981 Markesbery University of Kentucky Aluminum not elevated in Alzheimer's Disease brains. Ann Neurol 10: 511-516, 1981
1982 Perl University of Vermont ALS and Parkinson dementia on Guam associated with Aluminum. Science 217: 1053-1055, 1982.
1985 Greger University of Wisconsin Metallic Aluminum contributes very little to dietary intake
1986 Edwardson Newcastle General Hospital Aluminum in core of senile patient plaques 1986 Drezner Duke University Aluminum may not cause bone disease
1987 Perl Mt.Sinai Hospital Route of entry of Aluminum into body may be inhalation. Lancet1987: 1028
1988 Wisniewski N.Y. State Institute for Basic Research Aluminum not found in cores of senile patient plaques
1989 Martyn University of Southhampton Frequency of Alzheimer's Disease related to Aluminum in drinking water
1990 McLachlan University of Toronto Loss of cognitive function from exposure to McIntyre powder
1990 McLachlan University of Toronto Aluminum can be chemically extracted from brains of Alzheimer's Disease patients, clinical results being evaluated
B.Ghetti and O Bugiani. "Aluminum's Disease" and Alzheimer's Disease. Indiana Medical Center, Department of Pathology
Z. S. Khachaturian. Aluminum Toxicity Among Other Views on the Etiology of Alzheimer's Disease. Office of Alzheimer Disease Research, National Institute on Aging, National Institutes of Health, Bethesda, MD.
Jay W. Pettegrew. Aluminum and Alzheimer's Disease: An Evolving Understanding. Neurophysics Laboratory, University of Pittsburg, School of Medicine.
Richard S. Jope. Aluminum Toxicity: Transport and Sites of Action. Department of Pharmacology and euroscience Program, University of Alabama.
Allen C. Alfrey. Systemic Toxicity of Aluminum in Man. Renal Section, Denver Veterans Administration Hospital.
Daniel P Perl. The Aluminum Hypothesis of Alzheimer's Disease: A Personal View Based on Microprobe Analysis. Neuropathology Division, Mount Sinai Medical Center NY.
S.S. Krishnan, D.R. McLachlan, B. Krishnan, S.S.A. Fenton, and J.E. Harrison. Aluminum Toxicity to the Brain Toronto General Hospital and Departments of Physiology and Medicine, University of Toronto. Copyright 1988. Elsevier Science Publishers B.V. Reprint requests: S.S. Krishnan, Toronto General Hospital, Medical Physical Department, Room ccrw-g-803, 200 Elizabeth Street, Toronto, Ontario, Canada.
G. M. Zemansky, Ph.D Aluminum in Drinking Water , an assessment document. Scientific/Technical Section, Illinois Pollution Control Board, Nov. 12, 1985.
S.G. Epstein, 1984, Aluminum in nature, in the body, and it's relationship to human health. In: Trace Substances in Environmental Health - XVIII. Proceeding of thew 18th Annual Conference on Enviromantal Health held at the University of Missouri, June 4-7, 1984, D.D. Hemphill, ed., University Of Missouri, Columbia, MO pp. 139-148.
USEPA, 1985, Proposed Phase I and II recommended maximum contaminant levels under the Safe Drinking Water Act. Office of Drinking Water USEPA, Washington, D.C., pp. 119 - 121a.
D.R. Crapper and U. DeBoni. 1980, Aluminum. In: Experimental and Clinical Neurotoxicology. P. S. Spencer and H.H. Schaumburg, eds., Williams and Wilkins, Baltimore, MD. pp. 326 - 335.
Yoshimasu, F., M. Yasui, H. Yoshida, S. Yoshida, Y. Lebayashi, Y. Yase, D.C. Gajdusek, K.I.M. Chen. Aluminum in Alzheimer's disease in Japan and Parkinsonism dementia in Guam. XII World Congress of Neurology - 1985. (Abstr 15.07.02).
Aluminum - Journal Articles
Campbell, A; Bondy, S. Aluminum induced oxidative events and its relation to inflammation: a role for the metal in Alzheimer's disease. Cellular and Molecular Biology. (Noisy-le-grand) June 2000; vol. 46(4), pp.721-730.
Christen, Y. Oxidative stress and Alzheimer disease. American Journal of Clinical Nutrition. February 2000; vol. 71(2), pp. 621S-629S.
Crapper-McLachlan, D; Dalton, A; Kruck, T; et al. Intramuscular desferrioxamine in patients with Alzheimer's disease. Lancet. August 3, 1991; vol. 337(8753), pp. 1304-1308.
Flaten, T. Aluminum as a risk factor in Alzheimer's disease, with an emphasis on drinking water. Brain Research Bulletin. May 15, 2001; vol. 55(2), pp. 187-196.
Forbes, W; Hill, G. Is exposure to aluminum a risk factor for the development of Alzheimer disease?--Yes. Archives of Neurology. May 1998; vol. 55(5), pp. 740-741.
Gauthier, E; Fortier, I; Courchesne, F; et al. Aluminum forms in drinking water and risk of Alzheimer's disease. Environmental Research. November 2000; vol. 84(3), pp. 234-246.
Good, P; Perl, D; Bierer, L; et al. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Annals of Neurology. March 1992; vol. 31(3), pp. 286-292.
Graves, A; Rosner, D; Echeverria, D; et al. Occupational exposures to solvents and aluminum and estimated risk of Alzheimer's disease. Occupational and Environmental Medicine. September 1998; vol. 55(9), pp. 627-633.
Hachinski, V. Aluminum exposure and risk of Alzheimer disease. Archives of Neurology. May 1998; vol. 55(5), pp. 742.
Jansson, E. Aluminum exposure and Alzheimer disease. Journal of Alzheimer's Disease. December 2001; vol. 3(6), pp. 541-549.
Kiss, T. Interaction of aluminum with biomolecules -- any relevance to Alzheimer's disease? Archives of Gerontology and Geriatrics. July-August 1995; vol. 21(1), pp. 99-112.
Lovell, M; Ehmann, W; Markesbery W; et al. Standardization in biological analyses of aluminum: What are the needs? Journal of Toxicology and Environmental Health. August 30, 1996; 48(6), pp. 637-648.
Makjanic, J; McDonald, B; Li-Hsian C; et al. Absence of aluminum in neurofibrillary tangles in Alzheimer's disease. Neuroscience Letters. January 16, 1998; vol. 240(3), pp. 123-126.
Munoz, D. Causes of Alzheimer's disease. Canadian Medical Association Journal. January 2000; vol. 162(1), pp. 65-72.
Munoz, D. Is exposure to aluminum a risk factor for the development of Alzheimer disease? -- No. Archives of Neurology. May 1998; vol. 55(5), pp.737-739.
Newman, P. Alzheimer's disease revisited. Medical Hypotheses. May 2000; vol. 54(5), pp. 774-776.
Rao, J; Katsetos, C; Herman, M; et al. Experimental aluminum encephalomyelopathy. Relationship to human neurodegenerative disease. Clinics in Laboratory Medicine. December 1998; vol. 18(4), pp. 687-698.
Roberts, N; Clough, A; Bellia, J; et al. Increased absorption of aluminum from a normal dietary intake in dementia. Journal of Inorganic Biochemistry. February 15, 1998; vol. 69(3), pp. 171-176.
Rogers, M; Simon, D. A preliminary study of dietary aluminum intake and risk of Alzheimer's disease. Age & Ageing. March 1999; vol. 28(2), pp. 205-209.
Rondeau, V; Commenges, D; Jacqmin-Gadda, H; et al. Relation between aluminum concentrations in drinking water and Alzheimer's disease: an 8-year follow-up study. American Journal of Epidemiology. July 1, 2000; vol. 152(1), pp. 59-66.
Savory, J; Garruto, R. Aluminum, tau protein, and Alzheimer's disease: an important link? Nutrition. March 1998; vol. 14(3), pp. 313-314.
Savory, J; Exley, C; Forbes, W; et al. Can the controversy of the role of aluminum in Alzheimer's disease be resolved? What are the suggested approaches to this controversy and methodological issues to be considered? Journal of Toxicology and Environmental Health. August 30, 1996; vol.
48(6), pp. 615-636.
Smith, M; Perry, G. What are the facts and artifacts of the pathogenesis and etiology of Alzheimer disease? Journal of Chemical Neuroanatomy. December 1998; vol. 16(1), pp. 35-41.
Soni, M; White, S; Flamm W; et al. Safety evaluation of dietary aluminum. Regulatory Toxicology and Pharmacology. February 2001; vol. 33(1), pp. 66-79.
Study linking fluoride and Alzheimer's under scrutiny (Health Media Watch). Journal of the American Dental Association. Sept 1998; vol. 129(9), pp. 1216-1218.
Werbach, M. Healing foods: does aluminum exposure promote Alzheimer's? Nutrition Science News. January 1998; vol. 3(1), pp. 16.
Yokel, R. The toxicology of aluminum in the brain: a review. Neurotoxicology. October 2000, vol. 21(5), pp. 813-828.
Yokel, R; Ackrill, P; Burgess, E; et al. Prevention and treatment of aluminum toxicity including chelation therapy: status and researchneeds. Journal of Toxicology and Environmental Health. August 30, 1996; vol. 48(6), pp. 667-684.
For more information on Alzheimer's Disease (AD) see: * Alzheimer's Disease Education and Referral (ADEAR) http://www.alzheimers.org/index.html * Alzheimer's Association
http://www.realsalt.com/totalhealth.html
"Two of the most common anticaking agents used in the mass production of salt are sodium alumino-silicate and alumino-calcium silicate. These are both sources of aluminum, a toxic metal that has been implicated in the development of Alzheimer's disease and that certainly does not belong in a healthy diet. To make matters worse, the aluminum used in salt production leaves a bitter taste in salt, so manufacturers usually add sugar in the form of dextrose to hide the taste of aluminum. Refined sugaras I explained in my previous book, Get the Sugar Out (Harmony Books, 1996)severely disrupts the equilibrium of the body and is associated with the development of more than 60 diseases."
Oshiro S. [A new inducible transferrin-independent iron uptake system involved with aluminum accumulation in the brain of patients with Alzheimer's disease].
Tanpakushitsu Kakusan Koso. 1995 Aug;40(11):1738-43. Review. Japanese. PubMed PMID: 7676035.
Is Hidden True Cause Of Alzheimer's Your Toothpaste?
From Paul Kuhlman
5-3-3
Hello Jeff...
I am a truck driver, and have hauled just about everything over the past 13 years. I read your site's article postulating that naturally occurring aluminum found in water might be the key to Alzheimer's disease. I'll go one better than that.
I once picked up a 44,000 pound load of aluminum dioxide powder in the aptly-named town of Bauxite, Arkansas. Noting that the destination for the load was not a processing plant or a mill, I enquired as to why this load was destined for the Colgate-Palmolive Company. The shipping agent said that the quality of bauxite (Aluminum dioxide) found in Arkansas was too low grade for manufacturing purposes, but was fine for toothpaste.
"Toothpaste?" I enquired. He then went on to explain that common white toothpaste is made largely from Aluminum Dioxide, which is a mildly abrasive, brilliantly white powder. They'll simply add a sudsing agent to make the bubbles, a flavoring agent to make it palatable, perhaps a food coloring agent, some water, and presto - toothpaste. Go read the ingredients on your tube of toothpaste. It'll list one or two 'active ingredients'...notice the combined total amounts of 'active ingredients' is usually less than 1%. What about the other 99%?
* Were you aware that every day of your life, you are filling your mouth with a gob of nearly pure aluminum dioxide?
* Can you imagine the possible health effects?
* Do you see how this is the number one entry point for aluminum to enter the body?
* Can you guess why the inactive ingredients aren't listed?
* Imagine the outcry from all the millions of health conscious Americans who suddenly discovered that they are being poisoned!
*Yes, that's why they aren't listed.
So, if you and your vast readership are concerned about getting too much aluminum in their diets, you can all relax about naturally occurring aluminum in the water, or cooking with pots and pans. These are trivial sources of aluminum compared with the several pounds of aluminum directly swallowed or absorbed through the tissues while brushing our teeth.
On the bright side, we can all still have a beautiful smile in our old age, if only we can remember how to smile.
From KT Feller
5-4-3
Toxicity, AluminumLast Updated: November 26, 2002
Synonyms and related keywords: hyperaluminosis, aluminum-related illness, aluminum concentration, aluminum intoxication, peritoneal dialysis, impaired renal function, renal insufficiency, aluminum clearance, aluminum-related disease, osteomalacia, osteoid mineralization, dialysis encephalopathy, aluminum deposition, uremic pruritus, microcytic anemia, anisocytosis, poikilocytosis, chromophilic cells, basophilic stippling, deferoxamine therapy
Author: Barbara Barnett, MD, Associate Program Director, Assistant Professor, Departments of Internal Medicine and Emergency Medicine, Albert Einstein College of Medicine
Coauthor(s): Michael R Edwards, MD, Staff Physician, Department of Emergency Medicine, Long Island Jewish Medical Center, Jacobi Medical Center
Barbara Barnett, MD, is a member of the following medical societies:
American Academy of Emergency Medicine, American Medical Association, and
Society for Academic Emergency Medicine
Editor(s): Lisa Kirkland, MD, Senior Associate Consultant, Department of Internal Medicine, Division of Area Internal Medicine, Mayo Clinic, Rochester; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; Harold L Manning, MD, Associate Professor, Departments of Medicine, Anesthesiology, and Physio, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School; Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University; and Michael R Pinsky, MD, Research Fellowship Program Director, Professor, Department of Critical Care Medicine, University of Pittsburgh School of Medicine
Background: Aluminum is a trivalent cation found in its ionic form in most kinds of animal and plant tissues and in natural waters everywhere. It is the third most prevalent element and the most abundant metal in the earth’s crust. Dietary aluminum is ubiquitous, but in such small quantities that it is not a significant source of concern in persons with normal elimination capacity. Urban water supplies may contain a greater concentration because water is usually treated with the element before becoming part of the supply. Subsequent purification processes that remove organic compounds take away many of the same compounds that bind the element in its free state, further increasing aluminum concentration.
All metals can cause disease through excess, deficiency, or imbalance. Malabsorption through diarrheal states can result in essential metal and trace element deficiencies. Toxic effects are dependent upon the amount of metal ingested, entry rate, tissue distribution, concentration achieved, and excretion rate. Mechanisms of toxicity include inhibition of enzyme activity and protein synthesis, alterations in nucleic acid function, and changes in cell membrane permeability.
No known physiologic need exists for aluminum; however, because of its atomic size and electric charge (0.051 nm and 3+, respectively), it is sometimes a competitive inhibitor of several essential elements of similar characteristics, such as magnesium (0.066 nm, 2+), calcium (0.099 nm, 2+), and iron (0.064 nm, 3+). Approximately 95% of an aluminum load becomes bound to transferrin and albumin intravascularly and is then eliminated renally.
Aluminum is absorbed from the GI tract in the form of oral phosphate-binding agents (aluminum hydroxide) and parenterally via dialysate or total parenteral nutrition (TPN) contamination. It is also absorbed during peritoneal dialysis. Lactate, citrate, and ascorbate all facilitate GI absorption. If a significant load exceeds the body's excretory capacity, the excess is deposited in various tissues, including bone, brain, liver, heart, spleen, and muscle. This accumulation causes morbidity and mortality through various mechanisms.
Pathophysiology: Aluminum toxicity is usually found in patients with impaired renal function. Acute intoxication is extremely rare; however, in persons in whom aluminum clearance is impaired, it can be a significant source of pathology. Aluminum toxicity was originally described in the mid-to-late 1970s in a series of patients in Newcastle, England, through an associated osteomalacic dialysis osteodystrophy that appeared to reverse itself upon changing of the dialysate water to deionized water (ie, aluminum-depleted water). Previously, the only known dialysis-associated bone disease was osteitis fibrosa cystica, which was the result of abnormalities in vitamin D production that resulted in a secondary hyperparathyroidism, increased bone turnover, and subsequent peritrabecular fibrosis. In aluminum-related disease, the predominant features are defective mineralization and osteomalacia that result from excessive deposits at the site of osteoid mineralization.
Since the role of aluminum in disease has been identified, more attention has been paid to the element, leading to its recognition in several other processes. For example, among patients with osteomalacia, there has been a closely associated dialysis encephalopathy, which is thought to be caused by aluminum deposition in the brain. Aluminum causes an oxidative stress within brain tissue, leading to the formation of Alzheimerlike neurofibrillary tangles.
Aluminum also has a direct effect on hematopoiesis. Excess aluminum has been shown to induce anemia. Daily injections of aluminum into rabbits produced severe anemia within 2-3 weeks. The findings were very similar to those found in patients suffering from lead poisoning. Aluminum may cause anemia through decreased heme synthesis, decreased globulin synthesis, and increased hemolysis. Aluminum may also have a direct effect on iron metabolism. Patients with anemia from aluminum toxicity often have increased reticulocyte counts.
Other organic manifestations of aluminum intoxication have been proposed, but the mechanism by which it exerts its effect is complex and multifactorial.
Frequency:
In the US: The actual incidence of toxicity is unknown. The greatest incidence is observed in patients with any degree of renal insufficiency. A higher incidence is observed in populations who have aluminum-contaminated dialysate or who are taking daily oral phosphate-binding agents. Patients who require long-term TPN are at increased risk as well. Recent case reports have implicated the use of oral aluminum-containing antacids during pregnancy as a possible cause for abnormal fetal neurologic development.
Internationally: No evidence indicates a preponderance of aluminum toxicity in any one geographic region or country.
Mortality/Morbidity: The mortality rate may be as high as 100% in patients in whom the condition goes unrecognized. Today, however, recognition by nephrologists is the norm, and increased awareness by all practitioners has led to earlier detection and overall avoidance of the syndrome. Morbidity and mortality have been diminished significantly. Prior to this, bone pain, multiple fractures, proximal myopathy, and the sequelae of dementia have been the main sources of morbidity.
Race: Aluminum toxicity has no predilection for any race.
Sex: Aluminum toxicity has no predilection for either sex.
Age: Aluminum toxicity is observed in all age groups.
History: The signs and symptoms of aluminum toxicity are usually nonspecific.
In patients on long-term hemodialysis, osteomalacia is associated with the accumulation of aluminum in bone. Most evidence to support skeletal toxicity is from animal studies.
Studies have also shown that hemodialysis patients exposed to dialysate containing high aluminum concentrations are at increased risk of osteomalacia.
Some of the clinical symptoms of the disease entity reflect the chief complaint. An ED physician will rarely consider aluminum toxicity as a possible diagnosis in a dialysis patient who presents with an acute mental status change; however, these patients are the specific group most closely associated with the syndrome.
Typical presentations may include proximal muscle weakness, bone pain, multiple nonhealing fractures, acute or subacute alteration in mental status, and premature osteoporosis.
These patients almost always have some degree of renal disease. Most patients are on hemodialysis or peritoneal dialysis.
