In 2011 researchers from the FDA’s Center for Biologics Evaluation and Research published a paper on the toxicity of aluminum adjuvant (Mitkus et al 2011). Vaccine promoters cite Mitkus 2011 more often than any other paper when defending the safety of Al adjuvant. Mitkus is a mathematical modeling study of the Al3+ ions released by slowly dissolving Al adjuvant nanoparticles. Mitkus calculates where the dissolved Al3+ ions travel in the body and how fast they are eliminated as the Al adjuvant slowly dissolves in body fluids. Mitkus 2011 analyzed the two most common Al adjuvants: Al hydroxide and Al phosphate.
Mitkus 2011 paper: Updated aluminum pharmacokinetics following infant exposures through diet and vaccination
The Oxford Vaccine Group cites Mitkus 2011 here: http://vk.ovg.ox.ac.uk/vaccine-ingredients#aluminium
The FDA had a dedicated page for promoting Mitkus 2011, but it was removed in 2017. Even the CDC linked to this page to support their claims about Al adjuvant safety. Fortunately, I saved the FDAs webpage about Mitkus 2011: FDA’s webpage about Mitkus 2011
Today, The FDA no longer cites Mitkus 2011, which is perhaps surprising because Mitkus 2011 was the FDA’s own research. Why did they decide to stop citing it? Did the FDA lose confidence in Mitkus 2011? Today, this is all the FDA website says about aluminum adjuvant:
Above: The FDA website’s only statement about the safety of aluminum adjuvant, as of June 2018. Mitkus 2011 is not mentioned. Link: https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/VaccineSafety/ucm187810.htm
The Mitkus 2011 study is very important to the debate about the safety of Al adjuvant. Vaccine promoters continue to rely on it, because they dont have much else.
What is the Mitkus 2011 Study?
The Mitkus analysis goes like this:
1) Obtain a “Minimal Risk Level” (MRL) for ingested aluminum. The MRL is a dosage that can be consumed for long periods without any negative health effects. Mitkus uses an MRL of 1mg/kg/day, from a 2008 report by the Agency for Toxic Substances and Disease Registry (ATSDR) : ATSDR: Toxicological Profile for Aluminum. As explained below, the 1mg/kg/day MRL is wrong for two reasons.
2) Calculate aluminum body burden from vaccines. The body burden is calculated from the dissolution and excretion rates of Al adjuvant. Aluminum adjuvant is not considered part of the “body burden” as long as it is in solid (particulate) form. Only dissolved Al3+ ions released by slowly dissolving Al adjuvant is included in Mitkus’s body burden. Ignoring the solid Al adjuvant particles is a critical error, as explained below.
3) Compare the “body burden” of Al from vaccines with calculated body accumulation resulting from consuming Al at the MRL. If the body burden is always less than the amount accumulated at the MRL dosage, then the aluminum adjuvant is safe!
The Mitkus analysis is a reasonable way to estimate the toxicity and retention of water-soluble aluminum (Al3+ ions). But it cannot establish safety of low-solubility, persistent aluminum adjuvant particles. More on this below.
Mitkus has some pretty graphs showing that the Al body burden from vaccines is lower than the MRL. The Al adjuvant body burden is not even close to the MRL, implying a large margin of safety. Aluminum adjuvant is extremely safe! What a relief!
So for example, the chart below shows Mitkus’s minimal risk level (MRL) and Al body burden for vaccine exposure in the first year of life, assuming all the Al adjuvant comprises Al phosphate. The pink shaded area indicates the alleged margin of safety.
Above: “Minimal risk levels” (MRL) are calculated from a “no-observed adverse effects level” (NOAEL) from a mouse experiment of ingested aluminum salts. The NOAEL is divided by a safety factor of 30 for application to humans. 30 is a reasonable safety factor for translating from mice to humans. The aluminum adjuvant “body burden” curve (gray) indicates the amount of aluminum dissolved from the aluminum adjuvant and retained in the body. Al adjuvant is considered safe if the Al adjuvant body burden curve remains below the MRL. The Al adjuvant curve does not include undissolved adjuvant particles, which Mitkus erroneously assumes to be harmless. The 2-, 4-, 6-, and 12-month vaccination dates are shown.
The Mitkus analysis has three fatal flaws:
1) The MRL is derived from feeding experiments with water-soluble aluminum salts, not injected aluminum adjuvant. The safety of injected aluminum adjuvant can only be proven by experiments with injected aluminum adjuvant (insoluble and persistent), not ingested, water-soluble aluminum. Scientific studies have established that injected aluminum adjuvant has unique toxic properties and ways of moving around the body (“kinetics”) that are not the same as ingested water-soluble aluminum. Studies demonstrating the unique toxicity and kinetics of aluminum adjuvant are described in these articles:
Al Adjuvant Causes Brain Inflammation and Behavioral Abnormalities; Low Dose Is More Harmful
UPDATE: Adjuvant Transport Gets Complicated
Aluminum Adjuvant Injection Experiment #1: 100mcg/kg
Aluminum Adjuvant Injection Experiment #2: 300mcg/kg
Aluminum Adjuvant Injection Experiment #3: 550mcg/kg
Vaccine Aluminum Travels Into The Brain
Therefore, Mitkus’s MRL curve does not represent a true safe upper limit for injected aluminum adjuvant nanoparticles (AANs). Mitkus’s MRL can only be used to estimate the safety of ingested, water-soluble aluminum.
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2) The MRL is based on outdated and wrong science. The MRL is derived from a “No Observed Adverse Effects Level” (NOAEL). The NOAEL is the highest known ingested dosage that causes no adverse effects in experimental animals. The 1mg/kg/day MRL is based on a single study (Golub 2001) that reported no adverse effects from mice ingesting 26mg/kg/day aluminum.
The 2008 ATSDR report explains how the 1mg/kg/day MRL is derived:
Using a NOAEL/LOAEL approach, the NOAEL of 26 mg Al/kg/day identified in the Golub and Germann (2001) study was selected as the point of departure for the MRL. An MRL based on this NOAEL should be protective for neurological effects, neurodevelopmental effects, and for delays in maturation. Dividing the NOAEL by an uncertainty factor of 100 (10 to account for the extrapolation from mice to humans and 10 for human variability) and a modifying factor of 0.3 to account for possible differences in the bioavailability of the aluminum lactate used in the Golub and Germann (2001) study and the bioavailability of aluminum from drinking water and a typical U.S. diet results in an MRL of 1 mg Al/kg/day.
–2008 ATSDR Report “Toxicological Profile For Aluminum”, page 24 ATSDR: Toxicological Profile for Aluminum
However, there is a big problem: 26 mg/kg/day is not a NOAEL (safe dosage) for animals. The “no-observed adverse effects level” (NOAEL) of 26mg/kg/day (ingested) is the foundation for the Mitkus analysis, and it is wrong. Scientific studies report adverse effects (e.g., brain injury, cognitive impairment, and brain inflammation) from ingested aluminum dosages of 3.4, 4, 5.6, 6, 10 and 20 mg/kg/day. This is important and based on many citations, so it is covered in a separate article:
Mitkus’s MRL curve is therefore too high. Since 3.4 mg/kg/day is the lowest dosage (so far) discovered to cause adverse effects, the MRL is too high by a factor of at least 26/3.4 = 7.6. Thats a large error. I say “at least” because 3.4 mg/kg/day is not a NOAEL; adverse effects were observed at this dosage. The NOAEL is definitely less than 3.4 mg/kg/day.
What does Mitkus’s graph look like when the MRL is based on a NOAEL of 3.4mg/kg/day? To find out, I scaled the MRL down by a factor of 7.6. With this correction, the body burden curve (for AlPO4 adjuvant) exceeds the corrected MRL for months.
Above: The Mitkus graph for AlPO4 corrected in accordance with the new discovery that ingestion of 3.4 mg/kg/day Al causes adverse effects. Now, the body burden exceeds the MRL for almost the entire first year of life, indicating toxicity from Al3+ released by dissolving AlPO4 adjuvant. This is for AlPO4 adjuvant, not AlOH. The toxicity of Al adjuvant particles is a separate, additional issue.
And here is a redrawn graph for AlOH adjuvant.
Above: The Mitkus graph for AlOH corrected in accordance with the new discovery that ingestion of 3.4 mg/kg/day Al causes adverse effects. Now, the body burden overlaps the MRL for almost the entire first year of life, indicating threshold toxicity from Al3+ released by dissolving AlOH adjuvant. The margin of safety is gone. The body burden from AlOH is lower than that for AlPO4 because it dissolves more slowly. The toxicity of Al adjuvant particles is a separate, additional issue.
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3) Mitkus assumes that aluminum adjuvant has zero toxicity while in particulate form. The “body burden” of Mitkus does not include the AANs. In Mitkus’s analysis, only Al3+ ions (released by dissolving adjuvant particles) are toxic. This is why the Al adjuvant curve has an upward slope after each vaccination date.
Above: The “body burden” increases over time after each vaccination. This is because Mitkus’s body burden only includes Al3+ released by dissolving Al adjuvant particles. Undissolved aluminum adjuvant nanoparticles (AANs) are not included in the body burden, which means that the particle toxicity is ignored. In other words, Mitkus erroneously assumes the AANs are completely harmless. There is no evidence for this assumption, and much evidence that it is wrong.
But here is the problem: AANs are not harmless or inert. They are biologically active, and stimulate inflammation. AANs cause inflammation and immune system activation. Thats why they are used in vaccines. Also, AANs travel to parts of the body (like the brain) that can be injured by inflammation. The citations in #1 above clearly prove that AANs are toxic at vaccine dosages.
Also, it is now known that nanoparticle toxicity depends greatly on the particle size, shape, surface chemistry and other properties. Particle toxicity is not merely a function of released ions. Nanoparticle surfaces are chemically reactive and catalytic, and can produce mechanisms of toxicity unrelated to the toxicity of dissolved constituents. For example, asbestos comprises nano-fibers made of magnesium, silicon and oxygen, which are all nontoxic elements and essential nutrients. But asbestos is carcinogenic and inflammatory. Nanoparticle toxicity is reviewed here: Toxicity of Nanomatertials
This paper states:
“Particle size and surface area are crucial material characteristics from a toxicological point of view, as interactions between nanomaterials and biological organisms typically take place at the surface of the NP. As the particles’ size decreases, the surface area exponentially increases and a greater proportion of the particles’ atoms or molecules will be displayed on the surface rather than within the bulk of the material. Thus, the nanomaterial surface becomes more reactive toward itself or surrounding biological components with decreasing size, and the potential catalytic surface for chemical reactions increases.”
AND
“The nature of the interface between nanomaterials and biological systems affects the in vivo biocompatibility and toxicity of NPs.”
AND
“Particle shapes and aspect ratios are two additional key factors that determine the toxicity of NPs. Nanomaterials can have very different shapes including fibers, spheres, tubes, rings, and planes.”
AND
“Surface charge also plays a role in toxicity, as it influences the adsorption of ions and biomolecules that may change organism or cellular responses toward particles.”
NPs = nanoparticles
(Emphasis added)
Clearly, it is wrong to only consider the dissolved aluminum ions, as Mitkus did. The Mitkus study completely ignores the toxicity of the AANs, and this is a fatal error.
Above: Injected Al adjuvant nanoparticles (AANs) travel to distant organs where they remain for years, causing inflammation. Mitkus assumes the AANs have zero toxicity, even when present in sensitive organs like the brain. Mitkus assumes only the dissolved Al3+ ions released by the AANs are toxic. There is no evidence for this assumption, and conclusive evidence from animal experiments that it is wrong (see links in #1, above).
Final Word
Mitkus 2011 is the best scientific evidence vaccine promoters have for defending Al adjuvant safety. It is fatally flawed and incredibly bad. It is not based on any toxicity experiments with actual Al adjuvant. It ignores key studies that contradict the assumptions it is based on. And yet, government agencies (FDA, CDC) and vaccine promoters cite it as powerful and conclusive evidence of safety.
Aluminum adjuvant nanoparticles are very different from dissolved aluminum ions. Consequently, the only scientifically-valid way to establish the safety of injected aluminum adjuvant, is by experiments with injected aluminum adjuvant. Studies of ingested, soluble aluminum salts cannot establish the safety of Al adjuvant. Models of only dissolved aluminum cannot be used to determine the toxicity of the particles. Ignoring the toxicity of Al adjuvant particles is scientifically indefensible.
Why do the vaccine promoters rely on oral-ingestion studies to defend Al adjuvant safety? It is because they have no experimental research showing that injecting Al adjuvant is safe! They are empty-handed.
************************2018 UPDATE************************
Dr Romain Gherardi’s research group in collaboration with Dr Chris Exley have published a detailed paper (Masson 2018) explaining the flaws and failures in the Mitkus 2011 study. The Masson 2018 papers makes the same arguments I do, in more detail, and has additional reasons for why the Mitkus 2011 study is fatally flawed. Full text is here:
Masson et al 2018 Full Text: Critical analysis of reference studies on the toxicokinetics of aluminum- based adjuvants
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- Mitkus cites a 2008 report on aluminum from the Agency for Toxic Substances and Disease Registry (ATSDR), which cites Golub 2001 for the 26mg/kg/day NOAE. So, Mitkus indirectly cites Golub 2001.
Papers in this post:
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Mitkus, Robert J. King, David B. Hess, Maureen A. Forshee, Richard A. Walderhaug, Mark O. Vaccine 2011; 29(51):9538-43
PubMed Link
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Keith, L S. Jones, D E. Chou, C H S J. Vaccine 2002; 20 Suppl 3():S13-7
PubMed Link