Systematic Reviews of Neurotoxins

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BOTULINUM TOXIN

  • “The cellular mechanism of action of the large majority of bacterial protein exotoxins with intracellular targets, including the BoNTs, can be conveniently divided into four subsequent steps: a) cell binding, b) internalization/endocytosis; c) membrane translocation of the enzymatic moiety into the cytosol and d) intracellular target modification of a selected target (Montecucco et al., 1994).”
  • Top Sources: Root canals, injections, rotten anaerobic food

Rossetto O, Megighian A, Scorzeto M, Montecucco C. Botulinum neurotoxins. Toxicon. 2013 Jun 1;67:31-6. doi: 10.1016/j.toxicon.2013.01.017. Epub 2013 Feb 19. PMID: 23435262. (Accessed 11/20/2024)

BPA (Bisphenol-A)

  • “…the brain has consistently emerged as one of the most sensitive organs disrupted by BPA, even at doses below those considered safe by regulatory agencies such as the European Food Safety Authority (EFSA).”
  • Top Sources: Water bottles, packaged food, thermal paper receipts, canned goods, waterproof lining

Mustieles, V., Fernández, M.F. Bisphenol A shapes children’s brain and behavior: towards an integrated neurotoxicity assessment including human data. Environ Health 19, 66 (2020). https://doi.org/10.1186/s12940-020-00620-y

  • Apoptosis (programmed cell death)
  • Cell damage
  • Hippocampal targeting

Pang Q, Li Y, Meng L, Li G, Luo Z, Fan R. Neurotoxicity of BPA, BPS, and BPB for the hippocampal cell line (HT-22): An implication for the replacement of BPA in plastics. Chemosphere. 2019 Jul;226:545-552. doi: 10.1016/j.chemosphere.2019.03.177. Epub 2019 Mar 30. PMID: 30953899. https://pubmed.ncbi.nlm.nih.gov/30953899/ (Accessed 11/20/2024)

COVID-19 VACCINE

  • Guillain-Barre syndrome (GBS)
  • Bell’s palsy
  • Seizures
  • Encephalitis
  • Acute transverse myelitis
  • Acute disseminated encephalomyelitis (ADEM)
  • Stroke
  • Cerebral venous sinus thrombosis
  • Top Sources: USA, Germany, UK, EU, Canada, Norway, Singapore, China*****

Ostovan VR, Sahraian MA, Karazhian N, Rostamihosseinkhani M, Salimi M, Marbooti H. Clinical characteristics, radiological features and prognostic factors of transverse myelitis following COVID-19 vaccination: A systematic review. Mult Scler Relat Disord. 2022 Oct;66:104032. doi: 10.1016/j.msard.2022.104032. Epub 2022 Jul 6. PMID: 35858499; PMCID: PMC9258415. (Accessed 11/20/2024)

FLUORIDE

  • Headache
  • Insomnia
  • Lethargy
  • Polydipsia
  • Polyuria
  • Top Sources: Tap water, dental products, infant formulas, fluoridated salt

Miranda, G.H.N., Alvarenga, M.O.P., Ferreira, M.K.M. et al. A systematic review and meta-analysis of the association between fluoride exposure and neurological disorders. Sci Rep 11, 22659 (2021). https://doi.org/10.1038/s41598-021-99688-w (accessed 10/8/24).

  • Cognitive deficits during testing
  • Intellectual disability

Grandjean P. Developmental fluoride neurotoxicity: an updated review. Environ Health. 2019 Dec 19;18(1):110. doi: 10.1186/s12940-019-0551-x. PMID: 31856837; PMCID: PMC6923889. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6923889/ (accessed 10/8/24).

GLYPHOSATE (RoundUpTM)

  • Disrupts normal cellular development – changes to cell differentiation
  • Neuronal growth
  • Myelination
  • Toxic effect on neurotransmission
  • Induces oxidative stress
  • Neuroinflammation
  • Mitochondrial dysfunction
  • Starts processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. 
  • Top Sources: RoundUpTM weed killer, corn, soybeans, chickpeas, wheat, oats

Costas-Ferreira C, Durán R, Faro LRF. Toxic Effects of Glyphosate on the Nervous System: A Systematic Review. Int J Mol Sci. 2022 Apr 21;23(9):4605. doi: 10.3390/ijms23094605. PMID: 35562999; PMCID: PMC9101768. (Accessed 11/20/2024).

HEAVY METALS

  • “Significant correlation between exposure to cadmium (Cd) and mercury (Hg) and deleterious neurocognitive outcomes in the adult population.”
  • Top Sources: Rice, fish, seafood, e-cigarettes, motor vehicle emissions, industrial, fertilizers, pesticides, glassworking, incinerators, aging water supply infrastructure

Althomali, R.H., Abbood, M.A., Saleh, E.A.M. et al. Exposure to heavy metals and neurocognitive function in adults: a systematic review. Environ Sci Eur 36, 18 (2024). https://doi.org/10.1186/s12302-024-00843-7 (Accessed 11/20/2024)

PARABENS

  • Linked to mitochondrial failure dependent on initiation of membrane permeability transition accompanied by the mitochondrial depolarization and exhaustion of cellular ATP through uncoupling of oxidative phosphorylation
  • Skin irritation and breakdown
  • Methylparaben damages skin esterase metabolism leading to sunlight irradiation
  • Top Sources: Cosmetics, food and drink preservatives, pharmaceuticals (wound care, skin creams, ointments), personal care products (shaving creams, razors, antiperspirants, sunscreens, lip balms)

Safety and Toxicity Assessment of Parabens in Pharmaceutical and Food Products, Rahul Tade. 2018. DO – 10.13140/RG.2.2.23621.40161. (accessed 11/20/2024).

PFAS

  • “Numerous studies have demonstrated toxicity in a variety of domains, including hepatotoxicity, nephrotoxicity, developmental toxicity, immunotoxicity, and endocrine toxicity, which has led to further scrutiny of this chemical class as a whole (Lau et al., 2004, 2007; Cousins et al., 2020; Kwiatkowski et al., 2020).”
  • Top Sources: Water supply, Teflon coatings, Firefighting foams, industrial processes, landfills, military bases (Hundreds of military bases across the U.S. and around the world have used AFFF containing high levels of PFAS for fire training drills and fighting fires, contributing to widespread contamination.)

A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior, Hannah M. Starnes, Kylie D. Rock, Thomas W. Jackson, and Scott M. Belcher. Center for Environmental and Health Effects of PFAS, Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States. Front. Toxicol., 10 April 2022, Sec. Neurotoxicology. Volume 4 – 2022 | https://doi.org/10.3389/ftox.2022.881584 (accessed 10/8/24).

  • “Disruption of neurotransmission, particularly the dopamine and glutamate systems, which are implicated in age-related psychiatric illnesses and neurodegenerative diseases.”

Brown-Leung JM, Cannon JR. Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes. Chem Res Toxicol. 2022 Aug 15;35(8):1312-1333. doi: 10.1021/acs.chemrestox.2c00072. Epub 2022 Aug 3. PMID: 35921496; PMCID: PMC10446502. Brown-Leung JM, Cannon JR. https://pmc.ncbi.nlm.nih.gov/articles/PMC10446502/ (Accessed 11/20/2024)