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Pesticides and a wide variety of other chemicals persist in the environment and make their way into our everyday lives. While the concept that toxicants accumulate in the body and are the cause of various health problems has long been a fundamental tenet of traditional healthcare systems around the world, researchers have learned a great deal in recent years about how toxicants affect the human population, where they originate, and how to improve our ability to detoxify in a toxic world. How can we help patients manage the health risks of exposure to these ubiquitous substances?

Pesticides

In the last half of the last century, worldwide pesticide production increased at a rate of about 11% per year, from 0.2 million tons in the 1950s to more than five million tons in 2000.¹ In 2020, the global production of pesticide reached 3.5 million tons.² What’s more, it is estimated that only 0.1% of applied pesticides reach the target pests, leaving the vast majority of the chemicals (99.9%) to linger in the environment.¹

Organophosphate pesticides are one of the most extensively applied insecticides in the field of agriculture.³ Approximately 40% of all pesticides produced and used commercially belong to this category.³ Pesticides have been associated with short- and long-term effects on human health, including elevated cancer risks and potential disruption of the body’s metabolic functioning⁴ as well as the reproductive, immune, endocrine, and nervous systems.^5,6 A 2022 systematic review and meta-analysis suggests that pesticide exposure is a major risk factor for metabolic syndrome.² The analysis included 12 studies for a total of 6,789 participants, in which 1,981 (29.1%) had metabolic syndrome; overall exposure to pesticides and their contaminants increased the risk of metabolic syndrome by 42%.²

Exposure to pesticides predominantly comes from dermal absorption or through ingestion,³ particularly through food—either on or within fruits and vegetables or in the tissues of fish and other animals we eat—through contaminated drinking water, or in the air we breathe.⁵

Respiratory pathologies are also related to occupational exposure to pesticides, including asthma, chronic obstructive pulmonary disease (COPD), and lung cancer.⁷ One interesting study found associations between agricultural crops and the risk of lung cancer in agricultural workers; winegrowers were at a higher risk of adenocarcinoma, pea growers were at a higher risk of small-cell lung cancer, and the risk of squamous cell carcinoma was increased by sunflower growing, fruit tree pruning, and pesticide use on beets.⁸

Neonicotinoid pesticides are members of a relatively new class of chemicals registered in 120 countries for their use on crops like corn, canola, soybeans, and the majority of fruits and vegetables.⁹ In addition to being toxic to birds and mammals, neonicotinoids have been associated with colony collapse disorder in honey bees. Studies suggest that in humans, these neonicotinoids (and atrazine as well) are effective inducers of aromatase in human adrenocortical carcinoma cells. A 2016 study published in Toxicological Sciences for the first time demonstrated in vitro that neonicotinoids may stimulate a change in the enzyme aromatase (CYP19) in a promoter-specific manner similar to that observed in patients with hormone-dependent breast cancer.⁹

Insecticides & Herbicides

Organophosphates (carbon- and phosphate-containing molecules) are also the most commonly used components of insecticides and herbicides in the US in all market sectors (i.e., agriculture, home and garden, industrial, commercial, and government).¹⁰ The International Agency for Research on Cancer classifies malathion and diazinon as probably carcinogenic to humans and dichlorvos, parathion, and tetrachlorvinphos as possibly carcinogenic to humans. The US Environmental Protection Agency also classifies parathion as a possible human carcinogen. Increased cancer risk has been associated with several organophosphate insecticides in epidemiological studies in the US, Canada, and Italy.^10,11 In addition to cancer, studies suggest that organophosphates may be tied to a wide variety of other negative health effects, including ADHD,¹⁰ muscle weakness, and numbness.¹²

Glyphosate

Use of the herbicide glyphosate began in the 1970s, and the chemical swiftly attained widespread use in modern agriculture, becoming the most commercially successful and widely used herbicide of all time as of 2016.¹² Total worldwide glyphosate use (agricultural plus non-agricultural) rose more than 12-fold from about 67 million kg in 1995 to 826 million kg in 2014 (0.15-1.8 billion pounds).¹³ Levels of glyphosate and its primary metabolite, aminomethylphosphonic acid (AMPA), have been detected in the air, soil, water,¹³ and food.¹⁴

A number of studies suggest that glyphosate stimulates breast cancer growth via estrogen receptors.¹⁵ A 2018 study published in Food and Chemical Toxicology investigated the effect of glyphosate on the estrogen signaling pathway involved in the induction of cholangiocarcinoma (CCA) cell growth, cell cycle, and molecular signaling pathways. The data suggest that glyphosate can induce cell growth in estrogen receptor-alpha–positive CCA cells through the non-genomic estrogen receptor/ERK1/2 signaling pathway.¹⁵

A formal review of glyphosate by the Department of Health and Human Services and the Agency for Toxic Substances and Disease Registry was published in 2020, finding some statistically significant links to some cancers like non-Hodgkin’s lymphoma.¹⁶ More recently, Bayer, the company behind Roundup weed killer, which contains glyphosate, settled most of the current and possible future lawsuits brought against it by plaintiffs alleging that glyphosate causes cancer. The press reports that non-Hodgkin’s lymphoma patients started suing in 2015 when the World Health Organization report suggested glyphosate might cause cancer. Monsanto, the company that developed glyphosate and is now owned by Bayer, has long maintained that Roundup does not cause cancer, citing some studies that suggest glyphosate may be safe.¹⁷ Even so, in July 2021, Bayer said it would remove all glyphosate-based herbicides from the US consumer market by 2023 due to tens of thousands of lawsuits brought by people alleging they developed non-Hodgkin’s lymphoma from exposure.

In addition to glyphosate, malathion, parathion, and dimethoate are known for their endocrine-disrupting potential.⁵ They have been associated with effects on the function of cholinesterase enzymes; a decrease in insulin secretion; disruption of normal cellular metabolism of proteins, carbohydrates, and fats; genotoxic effects; and effects on mitochondrial function, which can lead to cellular oxidative stress and problems with the nervous and endocrine systems.⁵

Clinical Considerations

A large part of reducing a patient’s total toxic burden is through education—bringing the patient into a level of awareness regarding different sources of toxins so they can avoid potential exposures. From here, many functional medicine strategies for detoxification have a nutritional focus. Clinical evidence demonstrates the importance of matching the patient’s unique genotype to the appropriate diet, food preparation, and eating patterns in order to induce the appropriate phase I and phase II enzymes responsible for balanced detoxification of exogenous molecules and biotransformation of endogenous metabolic by-products.

In addition to the vegetables that aid detoxification, eating more phytonutrient-dense and diverse food aids the detoxification process. The bottom line is that while green, non-starchy vegetables are essential for detoxification, it is important to eat a rainbow of colors every day. In addition to healthy greens, red beets, peppers, and radishes; orange carrots, yams, sweet potatoes, peppers, and winter squash; yellow summer squash and peppers; and white onions and garlic should be consumed regularly.

Training in functional medicine teaches clinicians how to develop personalized dietary treatments using the IFM Elimination Diet and Detox Food Plan suites, as well as how to apply various nutraceuticals, botanicals, pharmaceuticals, and lifestyle interventions to increase the mobilization, biotransformation, and elimination of toxic compounds in the body.

Related Articles

Talking to patients about toxins

Toxins and toxicants as drivers of disease

Toxin exposures at home

References

1. Carvalho FP. Pesticides, environment, and food safety. Food Energy Secur. 2017;(6)2:48-60. doi:1002/fes3.108
2. Lamat H, Sauvant-Rochat MP, Tauveron I, et al. Metabolic syndrome and pesticides: a systematic review and meta-analysis. Environ Pollut. 2022;305:119288. doi:1016/j.envpol.2022.119288
3. Kaushal J, Khatri M, Arya SK. A treatise on organophosphate pesticide pollution: current strategies and advancements in their environmental degradation and elimination. Ecotoxicol Environ Saf. 2021;207:111483. doi:1016/j.ecoenv.2020.111483
4. Lamat H, Sauvant-Rochat MP, Tauveron I, et al. Metabolic syndrome and pesticides: a systematic review and meta-analysis. Environ Pollut. 2022;305:119288. doi:1016/j.envpol.2022.119288
5. Nicolopoulou-Stamati P, Maipas S, Kotampasi C, Stamatis P, Hens L. Chemical pesticides and human health: the urgent need for a new concept in agriculture. Front Public Health. 2016;4:148. doi:3389/fpubh.2016.00148
6. Sturm ET, Castro C, Mendez-Colmenares A, et al. Risk factors for brain health in agricultural work: a systematic review. Int J Environ Res Public Health. 2022;19(6):3373. doi:3390/ijerph19063373
7. Tarmure S, Alexescu TG, Orasan O, et al. Influence of pesticides on respiratory pathology – a literature review. Ann Agric Environ Med. 2020;27(2):194-200. doi:26444/aaem/121899
8. Boulanger M, Tual S, Lemarchand C, et al. Lung cancer risk and occupational exposures in crop farming: results from the AGRIculture and CANcer (AGRICAN) cohort. Occup Environ Med. 2018;75(11):776-785. doi:1136/oemed-2017-104976
9. Caron-Beaudoin É, Denison MS, Sanderson JT. Effects of neonicotinoids on promoter-specific expression and activity of aromatase (CYP19) in human adrenocortical carcinoma (H295R) and primary umbilical vein endothelial (HUVEC) cells. Toxicol Sci. 2016;149(1):134-144. doi:1093/toxsci/kfv220
10.  Lerro CC, Koutros S, Andreotti G, et al. Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study. Occup Environ Med. 2015;72(10):736-744. doi:1136/oemed-2014-102798
11.  Bastos PL, Bastos AFTL, Gurgel ADM, Gurgel IGD. Carcinogenicity and mutagenicity of malathion and its two analogues: a systematic review. Carcinogenicidade e mutagenicidade do malathion e seus dois análogos: uma revisão sistemática. Cien Saude Colet. 2020;25(8):3273-3298. doi:1590/1413-81232020258.10672018
12.  Hongsibsong S, Sittitoon N, Sapbamrer R. Association of health symptoms with low-level exposure to organophosphates, DNA damage, AChE activity, and occupational knowledge and practice among rice, corn, and double-crop farmers. J Occup Health. 2017;59(2):165-176. doi:1539/joh.16-0107-OA
13.  Benbrook CM. Trends in glyphosate herbicide use in the United States and globally. Environ Sci Eur. 2016;28(1):3. doi:1186/s12302-016-0070-0
14.  Myers JP, Antoniou MN, Blumberg B, et al. Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement. Environ Health. 2016;15:19. doi:1186/s12940-016-0117-0
15.  Sritana N, Suriyo T, Kanitwithayanun J, Songvasin BH, Thiantanawat A, Satayavivad J. Glyphosate induces growth of estrogen receptor alpha positive cholangiocarcinoma cells via non-genomic estrogen receptor/ERK1/2 signaling pathway. Food Chem Toxicol. 2018;118:595-607. doi:1016/j.fct.2018.06.014
16.  Agency for Toxic Substances and Disease Registry. Toxicological Profile for Glyphosate. US Department of Health and Human Services; 2020. Accessed September 15, 2023. https://www.atsdr.cdc.gov/toxprofiles/tp214.pdf
17.  Yan H. Bayer settles lawsuits from cancer patients over Roundup weed killer in $10 billion agreement. CNN Health. Published June 24, 2020. Accessed September 15, 2023. https://www.cnn.com/2020/06/24/health/bayer-monsanto-roundup-settlement/index.html