Pesticide exposure link to ME/CFS

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

Pesticides are chemicals that kill or harm pests. Pesticides include insecticides (which control insects) and herbicides (which control weeds). The main classes of insecticides are: organophosphates, carbamates, pyrethroids, neonicotinoids and organochlorines. Common organophosphate pesticides include malathion, parathion and chlorpyrifos.

Pesticide link to ME/CFS[edit | edit source]

Organophosphates[edit | edit source]

In one study, Scottish sheep farmers using organophosphate-based sheep dip to protect their sheep against parasites were found to suffer much higher rates of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS): the prevalence of ME/CFS in these farmers was 4 times the national UK average, implicating organophosphates as a probable causal factor in ME/CFS.[1][2] Farmers who used organophosphate-based sheep dip were also found to be 10,000 times more likely to suffer from mental health disorders.[3]

Across the UK, at least 500 farmers were left with debilitating health problems after using organophosphate sheep dip, and the Countess of Mar, a life peer in the House of Lords who developed ME/CFS after coming into contact with sheep dip on her farm, has spent the past decades campaigning on the organophosphate issue.[4]

ME/CFS researcher Professor Peter Behan studied the organophosphate link to ME/CFS, and talks about it in this 1997 newspaper article.

In Gulf War Illness (some types of which resemble ME/CFS), most of the toxic exposures and vaccinations that soldiers were exposed to have been ruled out as playing a causal role in GWI. Except for organophosphates, which the studies found strong evidence of playing a role. 

Organochlorines[edit | edit source]

Another class of pesticides called organochlorines (which includes DDT and dieldrin) have also been linked to ME/CFS.[5][6] However most organochlorines were banned in the 1980s, with some exceptions such as dicofol which is banned in Europe but still used on cotton and fruit crops in the US, and DDT which is still used for malaria control in Africa and parts of Asia.

Pyrethroids[edit | edit source]

Pyrethroids are synthetic compounds similar to the pyrethrins produced by Chrysanthemum flowers. Pyrethroids are considered less toxic to human than organophosphates, but nevertheless are also linked to ME/CFS.[7]

Broad range of diseases linked to pesticides[edit | edit source]

An article in The Herald[8] summarizes the wide range of diseases that are associated with pesticide exposure:[9]

  • Asthma — 41 studies linking pesticides to asthma. Studies show that pesticides not only trigger asthma attacks, but are also a root cause of asthma.
  • Birth defects — 19 studies linking pesticides to fetal and birth defects.
  • Cancer — 260 studies linking pesticides to various forms of cancer: 30 studies linking pesticides to brain cancer, 11 studies linking pesticides to breast cancer, 40 studies linking pesticides to leukemia, 46 studies linking pesticides to lymphoma, 23 studies linking pesticides to prostate cancer, 7 studies linking pesticides to soft tissue sarcoma.
  • Learning and developmental disorders — 26 studies linking pesticides to these disorders: 8 studies linking pesticides to ADHD, 5 studies linking pesticides to autism.
  • Diabetes — 6 studies linking pesticides to diabetes.
  • Parkinson’s disease — 65 studies linking pesticides to Parkinson’s.
  • Reproductive health effects — 22 studies linking pesticides to reproductive health issues. These include decreased fertility in both males and females, an androgenic (demasculinizing) effects, increased rates of miscarriage, altered sex ratios and altered maturity.

Pesticides are associated with autoimmune disease: a study of nearly 77,000 women found that those who personally mixed or applied insecticides for 20 years had double the rate of the autoimmune conditions rheumatoid arthritis and systemic lupus erythematosus.[10]

Organophosphate pesticide exposure is linked to psychiatric changes that result in suicidal thoughts and suicidal ideation (suicidality), and may lead to suicide.[11][12][13][14]

Organophosphate exposure during pregnancy causes a 7-point IQ drop in children[edit | edit source]

A large study in an agricultural community in California found that children who were exposed to organophosphate pesticides during pregnancy had poorer scores for working memory, processing speed, verbal comprehension, perceptual reasoning and intelligence quotient (IQ). Children with the highest prenatal exposures to organophosphates had an IQ which was 7 points lower on average compared to children with the lowest prenatal organophosphate exposures. Organophosphate exposure was determined by measuring organophosphate metabolites in the urine. In this study postnatal exposure to organophosphates was not correlated to poorer intellectual development, only prenatal exposure.[15]

Another large study in New York City found that inner-city children whose mothers had the highest organophosphate exposures during pregnancy (as measured by organophosphate metabolites in the mother's urine) had an IQ which was on average 6.7 points lower compared to children whose mother's had the lowest exposure.[16]

In a study in a farming valley in Mexico employing pesticides agriculturally, the researchers asked children in the valley to draw a person using pencil and paper. The children from the valley were unable to do draw a person: their drawings looked unintelligible, nothing like the human subjects they were asked to draw. But when the researchers asked children of similar age in an adjacent foothills region which did not use pesticides to draw a person, the children from the foothills were quite capable of producing intelligible drawings of a person.[17] The image shows a representative example of the children's drawings from the study.

Intelligible drawings by children in the foothills who were not exposed to pesticides (left), compared to the unintelligible drawings made by children in the valley who were exposed to pesticides from agriculture (right)

Biological effects of pesticides[edit | edit source]

Pesticides cause structural changes in the basal ganglia of the brain[edit | edit source]

Studies on asymptomatic agricultural workers exposed to pesticides found micro-structural changes in their substantia nigra, a region in the basal ganglia of the brain.[18][19]  Basal ganglia injury was also found in Gulf War illness patients.[20]

Organophosphates cause immunosuppression[edit | edit source]

A study in sheep found that the organophosphate pesticide parathion suppressed both the IgM and IgG immune antibody responses, which is thought to be due to the  cholinergic stimulation caused by organophosphates.[21]  This may in part explain why organophosphate exposure is a risk factor for ME/CFS, as this disease is usually precipitated by a viral infection, and immunosuppression during the acute phase of infection may allow the virus to breach into tissues compartments such as the brain which it would normally not reach. Exposure to immunosuppressive corticosteroids during acute viral infection is also a risk factor for developing ME/CFS from the infection (see corticosteroids given during acute viral infection may trigger myalgic encephalomyelitis).

Routes of human exposure to pesticides[edit | edit source]

Pesticides can enter the body through the mouth, skin, eyes or lungs. Sources of pesticide exposure include garden pesticide sprays used by you or your neighbor, which can be tracked into the house on shoes. Agricultural exposure may occur in rural areas through crop spraying. Pesticide exposure can also occur through treating wood with preservatives, and treating livestock with anti-parastitic preparations, such as sheep dip.

The pesticide malathion multiplies its toxicity 1000-fold indoors[edit | edit source]

The household organophosphate pesticide malathion is particularly dangerous if a significant quantity is spilt in an indoor environment (in a house, workplace, garage or barn): although malathion itself is rated as "class III slightly toxic" in its pesticide toxicity class, the breakdown product of malathion called malaoxon is 33 times more toxic than malathion,[22] and 1,000 times more toxic than malathion in terms of its acetylcholinesterase activity.[23] Thus when malathion is spilt indoors, because it is not dispersed by the wind or rain, it will remain indoors, and as it breaks down into malaoxon, the toxicty is increased by 1000 times, thereby becoming highly toxic to the inhabitants. Absorption or ingestion of malathion into the human body also results in its metabolism to malaoxon.

The oxon breakdown products of malathion, parathion and chlorpyrifos (malaoxon, paraoxon and chloroxon) have also been shown to be 10 to 100 times more toxic than their parent compound to amphibians.[24]

Detoxification of pesticides[edit | edit source]

Organophosphate pesticides are detoxified from the body by an enzyme called paraoxonase, whose gene is PON1. Mutations in the PON1 gene greatly reduce the ability of paraoxonase to detoxify organophosphates.[25][26]  The person-to-person variation in the ability of paraoxonase to detoxify organophosphate is in the range of 10- to 40-fold, and is determined in part by four SNP mutations in the PON1 gene.[27] Individuals who have PON1 mutations which make paraoxonase less active are much more susceptible to the damage caused by organophosphates. The hormone leptin markedly decreases plasma PON1 activity.[28] High leptin is found in obesity.

Organophosphate and carbamates pesticides do not bioaccumulate to a great degree, and so are removed from the body quickly (the metabolic half-live of organophosphates in the body is in the range of hours to days).[29] They also have low environmental persistence. Organochlorines pesticides on the other hand are environmentally persistent and bioaccumulate in the body fat tissues, so can remain in the body for years or decades (this is the reason organochlorines were banned and largely replaced by organophosphates and carbamates).

One study found organochlorines are expelled during sweating in a sauna.[30] Some ME/CFS patients with high blood levels of organochlorines achieved remission from their symptoms after a detoxification regimen comprising choline and ascorbic acid.[31]

Call to ban all organophosphate pesticides[edit | edit source]

A systematic review in PLOS Medicine is calling for a blanket ban of all organophosphate pesticides.[32] The paper says that widespread use of organophosphate pesticides to control insects has resulted in ubiquitous human exposures, and that compelling evidence indicates that prenatal organophosphate exposure at low levels is putting children at risk for cognitive and behavioral deficits and for neurodevelopmental disorders. The authors point out that there is no safe level of exposure to any organophosphate pesticide for pregnant women, whose babies suffer disorders ranging from impaired mental and motor skills and memory loss to autism and attention-deficit hyperactivity disorder.

The paper also describes how high exposures to organophosphate pesticides are responsible for poisonings and deaths, particularly in developing countries. The United Nations estimates that 200,000 people die each year from pesticide poisonings, about 99% of them in the developing world.[33]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. "Health - Report raises sheep dip health fears". BBC News. 1999. Two years ago 60 sheep dippers in the Western Isles were found to be suffering from the chronic fatigue syndrome ME - four times the national average. Farmers who say exposure to the dips has affected their health complain of symptoms including excessive tiredness, headaches, limb pains, disturbed sleep, poor concentration, mood changes, and thoughts of suicide.
  2. "Inquiry into sheep dip 'sickness'". BBC News. 2000.
  3. "Controversial sheep dip withdrawn". BBC News. 1999.
  4. "Revealed: government knew of farm poisoning risk but failed to act". The Guardian. 2015.
  5. Dunstan, R. H.; Donohoe, M.; Taylor, W.; Roberts, T.K.; Murdoch, R.N.; Watkins, J.A.; McGregor, N.R. (September 18, 1995). "A preliminary investigation of chlorinated hydrocarbons and chronic fatigue syndrome". The Medical Journal of Australia. 163 (6): 294–297. ISSN 0025-729X. PMID 7565234.
  6. Dunstan, R. H.; Roberts, T.K.; Donohoe, M.; McGregor, N.R.; Hope, D.; Taylor, W.G.; Watkins, J.A.; Murdoch, R.N.; Butt, H.L. (June 1996). "Bioaccumulated chlorinated hydrocarbons and red/white blood cell parameters". Biochemical and Molecular Medicine. 58 (1): 77–84. ISSN 1077-3150. PMID 8809349.
  7. Nacul, Luis Carlos; Lacerda, Eliana Mattos; Sakellariou, Dikaios (2009). "Is there an association between exposure to chemicals and chronic fatigue syndrome? Review of the evidence. Bulletin of International Association for CFS/ME" (PDF).
  8. "Symptoms of a wider malaise". The Herald Scotland. March 2, 1997. Retrieved October 7, 2019.
  9. Owens, Kagan; Feldman, Jay; Kepner, John (2010). "Wide Range of Diseases Linked to Pesticides" (PDF).
  10. Parks, Christine G.; Walitt, Brian T.; Pettinger, Mary; Chen, Jiu-Chiuan; de Roos, Anneclaire J.; Hunt, Julie; Sarto, Gloria; Howard, Barbara V. (February 2011). "Insecticide use and risk of rheumatoid arthritis and systemic lupus erythematosus in the Women's Health Initiative Observational Study". Arthritis Care & Research. 63 (2): 184–194. doi:10.1002/acr.20335. ISSN 2151-4658. PMC 3593584. PMID 20740609.
  11. Wesseling, Catharina; Joode, Berna van Wendel de; Keifer, Matthew; London, Leslie; Mergler, Donna; Stallones, Lorann (November 1, 2010). "Symptoms of psychological distress and suicidal ideation among banana workers with a history of poisoning by organophosphate or n-methyl carbamate pesticides". Occupational and Environmental Medicine. 67 (11): 778–784. doi:10.1136/oem.2009.047266. ISSN 1351-0711. PMID 20798019.
  12. London, L.; Flisher, A.J.; Wesseling, C.; Mergler, D.; Kromhout, H. (April 2005). "Suicide and exposure to organophosphate insecticides: cause or effect?". American Journal of Industrial Medicine. 47 (4): 308–321. doi:10.1002/ajim.20147. ISSN 0271-3586. PMID 15776467.
  13. Jaga, Kushik; Dharmani, Chandrabhan (January 2007). "The interrelation between organophosphate toxicity and the epidemiology of depression and suicide". Reviews on Environmental Health. 22 (1): 57–73. ISSN 0048-7554. PMID 17508698.
  14. Ghimire, Shree Ram; Parajuli, Sarita (February 4, 2016). "Chronic organophosphate-induced neuropsychiatric disorder: a case report". Neuropsychiatric Disease and Treatment. 12: 275–277. doi:10.2147/NDT.S91673. ISSN 1176-6328. PMC 4745950. PMID 26893566.
  15. Bouchard, Maryse F.; Chevrier, Jonathan; Harley, Kim G.; Kogut, Katherine; Vedar, Michelle; Calderon, Norma; Trujillo, Celina; Johnson, Caroline; Bradman, Asa (August 2011). "Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children". Environmental Health Perspectives. 119 (8): 1189–1195. doi:10.1289/ehp.1003185. ISSN 1552-9924. PMC 3237357. PMID 21507776.
  16. Factor-Litvak, Pam; Insel, Beverly; Calafat, Antonia M.; Liu, Xinhua; Perera, Frederica; Rauh, Virginia A.; Whyatt, Robin M. (December 10, 2014). "Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years". PLoS ONE. 9 (12). doi:10.1371/journal.pone.0114003. ISSN 1932-6203. PMC 4262205. PMID 25493564.
  17. Guillette, E A; Meza, M M; Aquilar, M G; Soto, A D; Garcia, I E (June 1998). "An anthropological approach to the evaluation of preschool children exposed to pesticides in Mexico". Environmental Health Perspectives. 106 (6): 347–353. ISSN 0091-6765. PMC 1533004. PMID 9618351.
  18. Du, Guangwei; Lewis, Mechelle M.; Sterling, Nicholas W.; Kong, Lan; Chen, Honglei; Mailman, Richard B.; Huang, Xuemei (January 2014). "Microstructural changes in the substantia nigra of asymptomatic agricultural workers". Neurotoxicology and Teratology. 41: 60–64. doi:10.1016/ ISSN 1872-9738. PMC 3943901. PMID 24334261.
  19. Lewis, Mechelle M.; Sterling, Nicholas W.; Du, Guangwei; Lee, Eun-Young; Shyu, Grace; Goldenberg, Michael; Allen, Thomas; Stetter, Christy; Kong, Lan (September 2017). "Lateralized Basal Ganglia Vulnerability to Pesticide Exposure in Asymptomatic Agricultural Workers". Toxicological Sciences: An Official Journal of the Society of Toxicology. 159 (1): 170–178. doi:10.1093/toxsci/kfx126. ISSN 1096-0929. PMC 5837257. PMID 28633499.
  20. Haley, R. W.; Fleckenstein, J.L.; Marshall, W.W.; McDonald, G.G.; Kramer, G.L.; Petty, F. (September 2000). "Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels". Archives of Neurology. 57 (9): 1280–1285. doi:10.1001/archneur.57.9.1280. ISSN 0003-9942. PMID 10987894.
  21. Casale, G. P.; Cohen, S. D.; DiCapua, R.A. (April 1983). "The effects of organophosphate-induced cholinergic stimulation on the antibody response to sheep erythrocytes in inbred mice". Toxicology and Applied Pharmacology. 68 (2): 198–205. doi:10.1016/0041-008x(83)90004-2. ISSN 0041-008X. PMID 6857660.
  22. "Malathion — Technical Fact Sheet. National Pesticide Information Center".
  23. Rodriguez, O. P.; Muth, G.W.; Berkman, C.E.; Kim, K.; Thompson, C.M. (February 1997). "Inhibition of various cholinesterases with the enantiomers of malaoxon". Bulletin of Environmental Contamination and Toxicology. 58 (2): 171–176. doi:10.1007/s001289900316. ISSN 0007-4861. PMID 8975790.
  24. Sparling, D. W.; Fellers, G. (June 2007). "Comparative toxicity of chlorpyrifos, diazinon, malathion and their oxon derivatives to larval Rana boylii". Environmental Pollution (Barking, Essex: 1987). 147 (3): 535–539. doi:10.1016/j.envpol.2006.10.036. ISSN 0269-7491. PMID 17218044.
  25. Mackness, Bharti; Durrington, Paul; Povey, Andrew; Thomson, Stuart; Dippnall, Martin; Mackness, Mike; Smith, Ted; Cherry, Nicola (February 2003). "Paraoxonase and susceptibility to organophosphorus poisoning in farmers dipping sheep". Pharmacogenetics. 13 (2): 81–88. doi:10.1097/01.fpc.0000054058.98065.38. ISSN 0960-314X. PMID 12563177.
  26. Costa, Lucio G.; Richter, Rebecca J.; Li, Wan-Fen; Cole, Toby; Guizzetti, Marina; Furlong, Clement E. (January 2003). "Paraoxonase (PON 1) as a biomarker of susceptibility for organophosphate toxicity". Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals. 8 (1): 1–12. doi:10.1080/13547500210148315. ISSN 1354-750X. PMID 12519632.
  27. Rozek, Laura S.; Hatsukami, Thomas S.; Richter, Rebecca J.; Ranchalis, Jane; Nakayama, Karen; McKinstry, Laura A.; Gortner, David A.; Boyko, Edward; Schellenberg, Gerard D. (September 1, 2005). "The correlation of paraoxonase (PON1) activity with lipid and lipoprotein levels differs with vascular disease status". Journal of Lipid Research. 46 (9): 1888–1895. doi:10.1194/jlr.M400489-JLR200. ISSN 0022-2275. PMID 15995178.
  28. Bełtowski, Jerzy; Wójcicka, Grazyna; Jamroz, Anna (September 2003). "Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia". Atherosclerosis. 170 (1): 21–29. doi:10.1016/s0021-9150(03)00236-3. ISSN 0021-9150. PMID 12957679.
  29. "Organophosphorus pesticides". INCHEM.
  30. Genuis, Stephen J.; Lane, Kevin; Birkholz, Detlef (2016). "Human Elimination of Organochlorine Pesticides: Blood, Urine, and Sweat Study". BioMed Research International. doi:10.1155/2016/1624643. ISSN 2314-6133. PMC 5069380. PMID 27800487.
  31. Richardson, John (January 1, 2000). "Four Cases of Pesticide Poisoning, Presenting as "ME," Treated with a Choline and Ascorbic Acid Mixture". Journal of Chronic Fatigue Syndrome. 6 (2): 11–21. doi:10.1300/J092v06n02_03. ISSN 1057-3321.
  32. Hertz-Picciotto, Irva; Sass, Jennifer B.; Engel, Stephanie; Bennett, Deborah H.; Bradman, Asa; Eskenazi, Brenda; Lanphear, Bruce; Whyatt, Robin (October 24, 2018). "Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms". PLOS Medicine. 15 (10): e1002671. doi:10.1371/journal.pmed.1002671. ISSN 1549-1676. PMC 6200179. PMID 30356230.
  33. "Ban entire pesticide class to protect children's health, experts say". The Guardian. 2018. 200,000 people still die each year from pesticide poisonings, according to UN estimates, about 99% of them in the developing world. A further 110,000 suicides using pesticides take place each year.