Clinical Concerns Over Cerebrovascular Leakage Caused by Chronic Aluminum Exposure are Warranted

Cell death caused by aluminum likely opens the blood-brain barrier. In childhood, this can potentially lead to unsafe levels of exposures to aluminum, pharmaceuticals and other environmental toxins.

The blood-brain barrier exists in the network of blood vessels that bring oxygen and nutrients to the brain. This network, made up of a network of cerebrovascular cells, can usually prevent a wide array of compounds from entering the brain. It is so effective that pharmaceutical companies have spent millions to identify drug additives that can help their product better cross the blood-brain barrier to allow them to save money in the production of pharmaceuticals that target the brain.

A recent study (Garcia et al., 2022) performed single-cell RNA-sequencing on more than 16,000 cerebrovascular cells. Using the cells’ gene-expression patterns, the researchers were able to classify them into 11 different subtypes, including endothelial cells, which line the blood vessels; mural cells, which include pericytes, found in the walls of capillaries, and smooth muscle cells, which help regulate blood pressure and flow; and fibroblasts, a type of structural cell.

All of these cells types are subject to endoplasmic reticulum stress - and for some, the resulting cell death - due to aluminum exposure. This causes cerebrovascular leaking, allowing both aluminum, pharmaceuticals, and environmental toxins to enter the brain more readily. It has been known for a long time that aluminum in various forms can attack the blood-brain barrier in a manner that is synergistic with sodium-fluoride (Varner et al., 1998). The breakdown of the BBB was identified by Gherardi et al. (2015) as a "Trojan Horse" mechanism for infectious particles, but the general mechanism as a route for increased exposure to environmental toxins is now more apparent.

Abnormalities of the blood-brain barrier are seen in renal failure and high-dose aluminum exposure, leading to a high brain burden of aluminum hydroxide and cerebral aluminum hydroxide toxicity (Arieff et al., 1979).

Once in the brain, aluminum is locally persistent and deadly; Mold et al. (2019), recently reported that aluminum was found in microglia, astrocytes, lymphocytes, and cells lining the choroid plexus. Aluminum-induced brain cell death elicits macrophages responsible for clearing cellular debris (microglia), analogous to those who perform cellular clean-up in the periphery (macrophages). These dual-purpose macrophages also play a key role in learning, and when they are chronically activated - as they are in people with autism from age 5 to 25 - they are not available to perform the pruning and synaptic connection formation roles needed for proper learning.

Claims of low-dose safety of aluminum are not reassuring; Crépeaux et al. (2017) found that the lowest dose of chronic exposure to aluminum hydroxide was associated with the highest brain uptake, leading to altered neurobehaviors, including decreased activity levels and altered anxiety-like behavior. My own research (funded by the public via IPAK) has led to the discovery that FDA has never provided a pediatric dose limit (PDL) for aluminum from vaccines, and that when a PDL is estimated, infants under one year of age are in aluminum whole-body toxicity every day of their first year of life (Lyons-Weiler et al., 2020; McFarland et al., 2020).

In my deep dive into the literature on aluminum safety in vaccines, and in preparing materials for my comprehensive 16-week online course on Environmental Toxicology, I see a pattern of science denialism and warping of the “science” that alleges that the dosing in aluminum is “safe”. In reality, CDC and FDA have used no studies at all designed to determine the dosage safety of injected forms of aluminum in the pediatric population. For example, FDA has conducted and NIH have funded no dose-varying studies on newborn animals animal studies. This is in spite of the fact that FDA has conducted those very same studies on alternative vaccine adjuvants.

Aluminum and Brain Dysfunction

According to Medical News Today, acetylcholine is a chemical messenger, or neurotransmitter, that plays an important role in brain and muscle function. Imbalances in acetylcholine are linked with chronic conditions, such as Alzheimer’s disease and Parkinson’s disease. Low-dose aluminum exposures leads to decreased whole brain acetylcholine (Willhite et al., 2016).

The extracellular signal-regulated kinase (ERK) pathway is essential for neuronal differentiation, survival, regeneration, and structural and functional plasticity. Researchers have found that lithium and valproate, commonly used mood stabilizers for the treatment of manic-depressive illness, stimulated the ERK pathway in the rat hippocampus and frontal cortex (Einat et al., 2003). This means the harm from aluminum can contribute to the risk of depression in one of the most significant ways that impairs mental wellness.

Sebaiti et al., (2018) found that high aluminum burden in aluminum hydroxide-induced macrophagic myofasciitis was associated with cognitive impairment that mainly affected executive functions and selective attention, and that even patients without measurable cognitive deficits displayed weakness in attention.

Pediatric patients that formed subcutaneous pseudolymphoma following vaccination showed delayed motor milestones, instability, dysarthria, and involuntary movement (Kim et al., 2020). A mini-review cites other studies that have found motor deficits, motor degeneration and neuroinflammation associated with aluminum exposures (Warfving et al., 2017).

Observations of association of high aluminum with neurodegenerative diseases have been made for decades (at least since 1981), including Alzheimer disease, Huntington disease, Parkinson disease, amyotrophic lateral sclerosis (ALS), progressive supranuclear palsy, acoustic neuroma, and cerebrovascular disease itself. It’s been known since 2006 that aluminum interactions with amyloid beta protein - a protein key to formation of plaques in Alzheimer’s disease - enhances protein penetration of blood-brain barrier (Banks 2006). The fact that the blood-brain barrier loses integrity in neurodegenerative diseases is widely known; the idea that aluminum may be a contributing factor is heresy. Prior debates involved denial that aluminum could “cross” the blood-brain barrier, a futile argument since aluminum kills the very cells that make up this layer of protection. The recent work of Exley and colleagues reporting high amounts of aluminum in the brains of patients with autism, multiple sclerosis, epilepsy, and confirming its presence in Alzheimer’s disease is confirmatory - aluminum is actually part of amyloid plaque, a fact known since 1985 (see 31 related studies on Pubmed).

Lack of Studies on Aluminum in Vaccines and Pharmaceutical Dose Effects

Given that aluminum likely destroys cells responsible for maintaining the integrity of the blood-brain barrier, and that drug studies determined efficacy on safety on animals and people who have not been recently vaccinated, a clinical concern is warranted on dose effects of drugs and vaccines given before and after aluminum-containing vaccines. Concerns over giving easy access to the brain to the slurry of environmental toxins we have added to our lives via aluminum injections are well-founded (e.g., Kennedy et al., 2016).

Aluminum hydroxide is used routinely to induce autoimmunity in mice and rats to provide pharmaceutical companies with the opportunity to test drugs to treat autoimmune conditions such as asthma, allergic rhinitis, food allergies, and lupus. The mouse models that combine a genetic risk of the condition use body-weight adjusted amounts of aluminum that overlap the dose exposures that children experience on the CDC-recommended vaccine schedule.

Mitigation?

Supplements that help with vascular health, such as Omega fatty acids, might reasonably be expected to mitigate these effects, and evidence that silicic acid (Exley et al., 2008) - and for unknown reasons, beer (Gonzalez-Muñoz, 2008) - might reduce the negative effects of acute aluminum exposure, chronic protection against aluminum from vaccines would require constant consumption for silicic acid and chronic beer consumption - the latter not recommended for most people, especially those under the age of 21.

The most remarkable processes of brain development occur between the ages of conception and 25 years of age. With the exception of a few hold-out denialists, nearly all of the scientific literature reports that aluminum is a neurotoxin.

Perhaps it would be most rational and ethical if we were to act on these concerns. It’s time to revisit the use of aluminum in vaccines in people, especially those under the age of 21, as well.

For information on my course on Environmental Toxicology, visit ipak-edu.org.

CITATIONS

Aluminum and Brain Dysfunction

Aoun Sebaiti M, Kauv P, Charles-Nelson A, Van Der Gucht A, Blanc-Durand P, Itti E, Gherardi RK, Bachoud-Levi AC, Authier FJ. Cognitive dysfunction associated with aluminum hydroxide-induced macrophagic myofasciitis: A reappraisal of neuropsychological profile. J Inorg Biochem. 2018 Apr;181:132-138. doi: 10.1016/j.jinorgbio.2017.09.019. Epub 2017 Oct 6. PMID: 29079320.

Einat H, Yuan P, Gould TD, Li J, Du J, Zhang L, Manji HK, Chen G. The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci. 2003 Aug 13;23(19):7311-6. doi: 10.1523/JNEUROSCI.23-19-07311.2003. PMID: 12917364; PMCID: PMC6740453.

Crépeaux G, Eidi H, David MO, Baba-Amer Y, Tzavara E, Giros B, Authier FJ, Exley C, Shaw CA, Cadusseau J, Gherardi RK. Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity. Toxicology. 2017 Jan 15;375:48-57. doi: 10.1016/j.tox.2016.11.018. Epub 2016 Nov 28. PMID: 27908630.

Mold M, Cottle J, King A, Exley C. Intracellular Aluminium in Inflammatory and Glial Cells in Cerebral Amyloid Angiopathy: A Case Report. Int J Environ Res Public Health. 2019 Apr 24;16(8):1459. doi: 10.3390/ijerph16081459. PMID: 31022962; PMCID: PMC6518255.

Acute, Chronic and Low-Dose Exposure

Arieff AI, Cooper JD, Armstrong D, Lazarowitz VC. Dementia, renal failure, and brain aluminum. Ann Intern Med. 1979 May;90(5):741-7. doi: 10.7326/0003-4819-90-5-741. PMID: 434672.

Lyons-Weiler J, McFarland G, La Joie E. Impact of catch-up vaccination on aluminum exposure due to new laws and post social distancing. J Trace Elem Med Biol. 2020 Dec;62:126649. doi: 10.1016/j.jtemb.2020.126649. Epub 2020 Sep 21. PMID: 32980768; PMCID: PMC7505097.

McFarland G, La Joie E, Thomas P, Lyons-Weiler J. Acute exposure and chronic retention of aluminum in three vaccine schedules and effects of genetic and environmental variation. J Trace Elem Med Biol. 2020 Mar;58:126444. doi: 10.1016/j.jtemb.2019.126444. Epub 2019 Dec 5. Erratum in: J Trace Elem Med Biol. 2021 May;65:126727. PMID: 31846784.

Varner JA, Jensen KF, Horvath W, Isaacson RL. Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity. Brain Res. 1998 Feb 16;784(1-2):284-98. doi: 10.1016/s0006-8993(97)01336-x. PMID: 9518651.

BBB Breakdown as Trojan Horse

Gherardi RK, Eidi H, Crépeaux G, Authier FJ, Cadusseau J. Biopersistence and brain translocation of aluminum adjuvants of vaccines. Front Neurol. 2015 Feb 5;6:4. doi: 10.3389/fneur.2015.00004. PMID: 25699008; PMCID: PMC4318414.

BBB Cerebrovasculature

“Single-cell dissection of the human brain vasculature” by Francisco J. Garcia, Na Sun, Hyeseung Lee, Brianna Godlewski, Kyriaki Galani, Blake Zhou, Julio Mantero, David A. Bennett, Mustafa Sahin, Manolis Kellis and Myriam Heiman, 14 February 2022, Nature.
DOI: 10.1038/s41586-022-04521-7

Varner JA, Jensen KF, Horvath W, Isaacson RL. Chronic administration of aluminum-fluoride or sodium-fluoride to rats in drinking water: alterations in neuronal and cerebrovascular integrity. Brain Res. 1998 Feb 16;784(1-2):284-98. doi: 10.1016/s0006-8993(97)01336-x. PMID: 9518651.

Al Impairs Brain Function

Li H, Campbell A, Ali SF, Cong P, Bondy SC. Chronic exposure to low levels of aluminum alters cerebral cell signaling in response to acute MPTP administration. Toxicol Ind Health. 2007 Oct;23(9):515-24. doi: 10.1177/0748233708089027. PMID: 18681236.

Kim H, Lim KY, Kang J, Park JW, Park SH. Macrophagic myofasciitis and subcutaneous pseudolymphoma caused by aluminium adjuvants. Sci Rep. 2020 Jul 16;10(1):11834. doi: 10.1038/s41598-020-68849-8. PMID: 32678281; PMCID: PMC7366910.

Warfving, N, J Laufs and K Weber 2017 Short Review of Aluminum Hydroxide Related Lesions in Preclinical Studies and their Relevance Journal of Vaccines and Vaccination. DOI:10.15406/ijvv.2017.04.00076Corpus ID: 196486570

Willhite CC, Karyakina NA, Yokel RA, Yenugadhati N, Wisniewski TM, Arnold IM, Momoli F, Krewski D. Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts. Crit Rev Toxicol. 2014 Oct;44 Suppl 4(Suppl 4):1-80. doi: 10.3109/10408444.2014.934439. PMID: 25233067; PMCID: PMC4997813.

Alzheimer’s

Banks WA, Niehoff ML, Drago D, Zatta P. Aluminum complexing enhances amyloid beta protein penetration of blood-brain barrier. Brain Res. 2006 Oct 20;1116(1):215-21. doi: 10.1016/j.brainres.2006.07.112. Epub 2006 Aug 30. PMID: 16942756.

Bhattacharjee S, Zhao Y, Hill JM, Culicchia F, Kruck TP, Percy ME, Pogue AI, Walton JR, Lukiw WJ. Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD). J Inorg Biochem. 2013 Sep;126:35-7. doi: 10.1016/j.jinorgbio.2013.05.007. Epub 2013 May 21. PMID: 23764827; PMCID: PMC3720708.

Bondy SC. Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration. Neurotoxicology. 2016 Jan;52:222-9. doi: 10.1016/j.neuro.2015.12.002. Epub 2015 Dec 12. PMID: 26687397.

Senitz D, Blüthner K. Uber das Vorkommen von Aluminium in Hirngefässen bei Alzheimer-Krankheit [The presence of aluminum in cerebral vessels in Alzheimer's disease]. Zentralbl Allg Pathol. 1990;136(4):329-35. German. PMID: 2402958.

Lin WT, Chen RC, Lu WW, Liu SH, Yang FY. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer's disease rat model. Sci Rep. 2015 Apr 15;5:9671. doi: 10.1038/srep09671. PMID: 25873429; PMCID: PMC4397698.

Mitigation/Protection

Exley C, Korchazhkina O, Job D, Strekopytov S, Polwart A, Crome P. Non-invasive therapy to reduce the body burden of aluminium in Alzheimer's disease. J Alzheimers Dis. 2006 Sep;10(1):17-24; discussion 29-31. doi: 10.3233/jad-2006-10103. PMID: 16988476.

Gonzalez-Muñoz MJ, Meseguer I, Sanchez-Reus MI, Schultz A, Olivero R, Benedí J, Sánchez-Muniz FJ. Beer consumption reduces cerebral oxidation caused by aluminum toxicity by normalizing gene expression of tumor necrotic factor alpha and several antioxidant enzymes. Food Chem Toxicol. 2008 Mar;46(3):1111-8. doi: 10.1016/j.fct.2007.11.006. Epub 2007 Nov 17. PMID: 18096288.

Exley C, Korchazhkina O, Job D, Strekopytov S, Polwart A, Crome P. Non-invasive therapy to reduce the body burden of aluminium in Alzheimer's disease. J Alzheimers Dis. 2006 Sep;10(1):17-24; discussion 29-31. doi: 10.3233/jad-2006-10103. PMID: 16988476.

Synergistic Toxicity

Kennedy D, Seneff S, Davidson RM, Oller Jr JW, Haley BE, et al. (2016) Environmental Toxicants and Infant Mortality in the USA. Open J Biol Sci 1(1): 036-061. DOI: https://dx.doi.org/10.17352/ojbs.000005