Detoxifying Phthalates: Genes and Diet

Plastics are everywhere – and a source of the chemicals we are exposed to daily. One component of plastics is a class of compounds called phthalates, which can act as an endocrine disruptor and mimic estrogen.

Amid all the scary headlines these days, are phthalates worth worrying about? It may depend, in part, on your genetic variants. Some people are genetically more susceptible to the harmful effects of phthalates and may want to prioritize changes in order to avoid exposure. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

What are phthalates?

Phthalates (pronounced THAL-eights) are a type of chemical used as a plasticizer, which makes plastics more pliable. Because they are not bonded to plastic, phthalates can leak out of plastic items when exposed to heat or solvents.

As one research study puts it: “…phthalates have been found to leach or migrate from PVC-containing items into the air, dust, water, soils, and sediment. ”[ref] In other words, phthalates are ubiquitous in our environment.

Phthalates are classified under the umbrella of “endocrine disrupting chemicals”, linked to reproductive harms such as decreased fertility and pregnancy loss.[ref][ref]

Where do we find phthalates?

Phthalates are commonly found in:[ref]

  • adhesives
  • caulk
  • vinyl products
  • flooring
  • coatings on pharmaceuticals
  • flexible coatings on extension cords and appliance cords
  • medical devices
  • nail polish
  • food and other packaging
  • fragrances
  • personal care products
  • carpet backing
  • faux leather
  • printing inks
  • and in boxed mac and cheese.

Several types of phthalates are banned in the US and the EU for use in toys and other objects, such as teething rings that can fit in a child’s mouth.[ref]

Packaged food can contain phthalates due to processing or packaging. Additionally, prescription and OTC medicines can contain phthalates as excipients.[ref](2012)

In 2010, the FDA created a list of products that they had tested for phthalatesfragrances topped the list as a huge source of phthalates in the tested products.

Are phthalates really a problem?

It depends on how you define ‘a problem’…

Phthalate exposure is not going to kill you outright. Many toxicity tests dating back to the 1970s used rats as a model and showed that phthalates are not immediately toxic.

A recent (2021) study found that phthalate exposure increases all-cause mortality, in part due to cardiovascular disease increases. The study found that the impact on people aged 55-64 caused >90,000 attributable deaths/year. The increase in deaths is not a sudden occurrence, though. Instead, it is due to a lifetime  of exposure.[ref]

US government toxicology studies in 1995 on rats showed that exposure to phthalates didn’t kill adult rats in 13 weeks. However, the doses used did kill the baby rats.

Important to know:

  • Animal studies using rats and mice may not be good models for the human metabolism of phthalates. Newer studies indicate rats do not metabolize phthalates the same way humans do.[ref]
  • Based on mouse studies, the exposure limits are set fairly high, at around 100 mg/kg/day for tumorigenesis (tumor formation).

Exposure to phthalates may be even more harmful to infants and children than  to adults. Over the past couple of decades, the FDA and EU have required the removal of some types of phthalates from teething rings and bottle nipples. In 2009, the US banned the use of certain phthalates in children’s toys.

California does include six types of phthalates on its list of possible carcinogens in its Prop 65 regulations.

What do studies show about chronic, low-dose exposure?

Evidence showing the effect of low, chronic exposure to phthalates on people and animals includes:

  1. Phthalates act as an endocrine disruptor.[ref]
  2. As an endocrine disruptor, phthalates may increase the risk of fibroids, obesity, asthma, ADHD, IVF problems, and reproductive problems in men.[ref][ref]
  3. Higher exposure to phthalates is associated with decreased cognition (most studies were done in children).[ref]
  4. In women, higher phthalate levels are linked to obesity and metabolic syndrome.[ref]
  5. Chronic exposure to phthalates increases allergies.[ref]
  6. Researchers think that environmental phthalates may lead to a global decrease in amphibians. Phthalates at very, very low, chronic levels affect frogs’ sperm.[ref]

How are we exposed to phthalates?

Phthalate contamination exists literally everywhere in our food supply.

For example, a 2014 Norwegian study found:[ref]

  • Phthalates were present in ALL foods and beverages commonly consumed (and BPA was in 54%).
  • Exposure levels were highest in meat and grains. However, average levels were less than European maximum exposure level limits.

Can eating organic save you from phthalate exposure? Probably not. A study found that phthalate levels in people eating junk food were the same as those eating a controlled organic diet with food stored in glass containers instead of plastic.[ref]

How do phthalates get into our bodies?

Phthalates are pervasive in the food supply due to leaching out of packaging and processing materials.

One study sums up the routes of exposure well:
“phthalates can migrate into food from plasticized PVC materials such as tubing typically used in the milking process, lid gaskets, food-packaging films, gloves used in the preparation of foods, and conveyor belts [19,20]. These compounds are also found in printing inks and adhesives on food wrappers as well as coatings on cookware that have been contaminated by packaging [20-22]. Foods high in fat are contaminated by higher-weight phthalates that are more lipophilic such as DEHP [19].”[ref]

In the US, phthalates are allowed by the FDA in food packaging and processing materials. In contrast, the EU has limited the use of phthalates in materials that are in contact with food since 2009.[ref]

Finally, if you aren’t eating phthalates or inhaling phthalates (in artificial fragrances), you may be swallowing them in your medications.

Some pharmaceuticals also use phthalates as plasticizers in their drug capsules or coatings. Even if not deliberately added to drugs, a recent study in China found phthalates at varying levels in all of the medications they tested.[ref][ref]

What do studies show about phthalates in humans?

Below are a few of the thousands of studies on phthalates. As with most environmental factors, phthalates likely affect people differently based on their genetic susceptibility.[ref]

  • ADHD: “In particular, recent evidence supports the existence of an association between urine phthalate metabolite levels, attention-deficit/hyperactivity disorder (ADHD), and executive functioning.”[ref]
  • Infertility: Lower odds of in vitro fertilization working for those with higher phthalate levels. This study found that those in the top quartile for phthalate metabolites had about half the chance of IVF working.[ref]
  • Lower Testosterone: Low-dose, long-term exposure may decrease males’ reproduction and testosterone levels.[ref][ref]
  • Endocrine (thyroid, uterine) disruptors: The main problem with phthalates stems from their role as endocrine disruptors, which could cause obesity, thyroid function, and uterine issues.

Obesity and weight gain:

  • Weight gain: Contaminated dust containing phthalates (found in all of the household dust sampled) was found to cause human cells to create triglycerides and cause mice to get fat.
  • Fat accumulation: Previous studies in cells have similar findings for phthalates promoting fat accumulation.[ref]
  • Obesity and diabetes: Sometimes, the best way to figure out the impact of a substance on a population as a whole is to put a price on it. It is especially true in countries with government-provided healthcare, and a recent European study calculated the cost of obesity caused by phthalates. “The panel also identified a 40% to 69% probability of phthalate exposure causing 53 900 cases of obesity in older women and €15.6 billion in associated costs. Phthalate exposure was also found to have a 40% to 69% probability of causing 20 500 new-onset cases of diabetes in older women with €607 million in associated costs.”[ref]
  • A March 2017 study says “Most data support the effects of bisphenol A and some phthalates … on the development of obesity and type 2 diabetes mellitus.”[ref]

Thyroid function affected by phthalates:

  • Depressed thyroid function: Several studies link urinary phthalate levels to depressed thyroid hormone levels.[ref]
  • Subclinical hypothyroidism: A Korean study found phthalate metabolite levels correlate to lower FT4, FT3, and slightly higher TSH levels.[ref]
  • Not showing up in common thyroid tests: Rat study shows that phthalates decrease T4, T3, and TRH but not TSH.[ref]
  • Most doctors prescribe thyroid medications based on TSH, so if phthalates are messing with Free T3 and Free T4 but not TSH, there could be a lot of people with lower thyroid function that doctors are missing. Check out Stop the Thyroid Madness for more information on FT4, FT3, and all the other thyroid hormones.
  • Circling back to obesity: Another study explains how this depression of thyroid hormones links back to obesity: “Another possible mechanism by which phthalates might promote obesity is through the disruption of thyroid function, which plays a key role in the regulation of energy balance and metabolism. … In rodent studies, exposure to DEHP lowered plasma thyroxine and decreased iodide uptake of thyroid follicular cells26,27). Recent human studies have also demonstrated possible effects of phthalate exposure on thyroid function in children and adults”.[ref]

Uterine fibroids:

  • Several studies link phthalates and other endocrine disruptors to fibroids and uterine problems. Although most of the studies seem to be small or else reliant on self-reported cases of fibroids, the studies all seem to point to the same thing – a link between endocrine-disrupting phthalate metabolites and fibroids.[ref]
  • Again, putting a price on the issue may give a bigger picture of what is happening. A 2016 study estimated the cost of this endocrine disruptor caused fibroids at 1.3 billion euros in the EU.[ref]
  • The truth may lie in the fact that not everyone is affected the same way by phthalates. A study showed that women with certain CYP17A1 and ESR1 variants had higher phthalate levels and a greater risk of uterine fibroids.[ref]

Histamine / Mast Cell / Allergy connection:

  • Histamine release: Phthalates increase histamine release from IgE in Mast cells.[ref]
  • There are atopic dermatitis and FLG gene polymorphism connections and interactions.[ref]
  • Itchy skin: Another study found that higher phthalate exposure more than doubled the risk of atopic dermatitis.[ref]
  • Dust allergies: A known connection has existed between phthalates in dust and allergies for more than ten years, with good studies backing it up.[ref]
  • One more study replicated the finding that higher phthalate levels (flooring, dust, etc.) correlate with higher allergy levels.[ref]

How can we get rid of (detoxify) phthalates?

Phthalates metabolize rapidly and are excreted in urine and feces.

It is a two-step process –

  • first making the molecules more water-soluble
  • then attaching other chaperones for elimination from the body.

Phase I metabolism involves hydrolysis by lipases, which are enzymes produced in the pancreas and stomach. 

Next, the phthalates must be further metabolized by oxidation. The oxidative metabolites can then go through glucuronidation reactions in phase II metabolism.[ref]

This second phase of detoxification is where genetic variants come into play. It is common to have variants that impact the specific phase II detoxification genes, and understanding these variants can help you to improve detoxification.


Phthalate Detoxification Genotype Report

Your genes impact how well you eliminate phthalates from your body. The genetic variants listed below have been shown in studies to impact phthalate metabolism (detoxification) directly.

Members: Log in to see your data below.
Not a member? Join here. Membership lets you see your data right in each article and also gives you access to the member’s only information in the Lifehacks sections.

 

GSTP1 gene: encodes the glutathione S-transferase pi enzyme, which is a phase II detoxification enzyme

Check your genetic data for rs1695 (23andMe v4, v5; AncestryDNA):

  • A/A: most common genotype; higher phthalate metabolite levels[ref]
  • A/G: somewhat reduced function
  • G/G: reduced function[ref]

Members: Your genotype for rs1695 is .

SOD2 gene: Superoxide dismutase 2 is a manganese-dependent antioxidant enzyme responsible for breaking down toxins and eliminating reactive oxygen species in the cell.

Check your genetic data for rs5746136 (AncestryDNA):

  • T/T: higher phthalate metabolite levels, almost 3-fold increased risk of asthma[ref]
  • C/T: somewhat increased asthma risk
  • C/C: typical

Members: Your genotype for rs5746136 is .

CYP2B6 gene: This gene codes for a phase I detoxification enzyme important for the metabolism of various toxins, including phthalates.[ref][ref]

Check your genetic data for rs3745274 (23andMe v4; AncestryDNA):

  • G/G: typical
  • G/T: typical
  • T/T: decreased CYP2B6 enzyme[ref]

Members: Your genotype for rs3745274 is .

GSTM1 Gene: The GSTM1 gene codes for glutathione S-transferase Mu 1, an important enzyme in phase II detoxification.

Check your genetic data for rs366631 (23andMe v4 only):

  • A/A: deletion (null) GSTM1 gene. GSTM1 deletion is associated with a 2x increased risk of breast cancer,[ref] women with phthalate exposure are at a 5-fold increased risk of fibroids.[ref]
  • A/G: GSTM1 present
  • G/G: GSTM1 present

Members: Your genotype for rs366631 is .

HSPA1L gene encodes part of the HSP70 protein.

Check your genetic data for rs2227956 T2437C (23andMe v4, v5; AncestryDNA):

  • A/A: most common genotype, more likely to develop insulin resistance with phthalate exposure[ref]
  • A/G: more likely to develop insulin resistance with phthalate exposure
  • G/G: decreased HSP70[ref]

Members: Your genotype for rs2227956 is .


Lifehacks for detoxifying phthalates:

Tips for avoiding phthalate exposure:

The rest of this article is for Genetic Lifehacks members only.  Consider joining today to see the rest of this article.

Member Content:

An active subscription is required to access this content.

Join Here for full access to this article, genotype reports, and much more!


Already a member? Log in below.


Related Articles and Genes:

Detoxification: Phase I and Phase II metabolism
Learn how the different genetic variants in the phase I and phase II detoxification genes impact how you react to medications and break down various toxins.

Lithium Orotate + B12: Boosting mood and decreasing anxiety for some people…
For some people, low-dose, supplemental lithium orotate is a game-changer for mood issues when combined with vitamin B12. But other people may have little to no response. The difference may be in your genes.

Top 10 Genes to Check in Your Genetic Raw Data
It can be overwhelming when you are getting started with learning how your genes affect your health. Let me help you cut through some of the confusion with my list of what is important. These are 10 genes with important variants that can greatly impact health.

Detoxifying organophosphate pesticides: Genetics and resilience
Is buying organic worth the extra cost? There isn’t a one-size-fits-all answer to that question. Pesticides that are sprayed on conventionally grown foods affect people differently. Some people carry genetic variants that decrease their ability to detoxify specific pesticides; others may be more resilient.

 

References:

Ait Bamai, Yu, et al. “Exposure to Phthalates in House Dust and Associated Allergies in Children Aged 6-12years.” Environment International, vol. 96, Nov. 2016, pp. 16–23. PubMed, https://doi.org/10.1016/j.envint.2016.08.025.

Benjamin, Sailas, et al. “Phthalates Impact Human Health: Epidemiological Evidences and Plausible Mechanism of Action.” Journal of Hazardous Materials, vol. 340, Oct. 2017, pp. 360–83. PubMed, https://doi.org/10.1016/j.jhazmat.2017.06.036.

Bølling, Anette Kocbach, et al. “Phthalate Exposure and Allergic Diseases: Review of Epidemiological and Experimental Evidence.” Environment International, vol. 139, June 2020, p. 105706. PubMed, https://doi.org/10.1016/j.envint.2020.105706.

DeKeyser, Joshua G., et al. “Selective Phthalate Activation of Naturally Occurring Human Constitutive Androstane Receptor Splice Variants and the Pregnane X Receptor.” Toxicological Sciences: An Official Journal of the Society of Toxicology, vol. 120, no. 2, Apr. 2011, pp. 381–91. PubMed, https://doi.org/10.1093/toxsci/kfq394.

Genuis, Stephen J., et al. “Human Elimination of Phthalate Compounds: Blood, Urine, and Sweat (BUS) Study.” The Scientific World Journal, vol. 2012, Nov. 2012, p. e615068. www.hindawi.com, https://doi.org/10.1100/2012/615068.

Grindler, N. M., et al. “Exposure to Phthalate, an Endocrine Disrupting Chemical, Alters the First Trimester Placental Methylome and Transcriptome in Women.” Scientific Reports, vol. 8, no. 1, Apr. 2018, p. 6086. www.nature.com, https://doi.org/10.1038/s41598-018-24505-w.

Huang, Po-Chin, Eing-Mei Tsai, et al. “Association between Phthalate Exposure and Glutathione S-Transferase M1 Polymorphism in Adenomyosis, Leiomyoma and Endometriosis.” Human Reproduction (Oxford, England), vol. 25, no. 4, Apr. 2010, pp. 986–94. PubMed, https://doi.org/10.1093/humrep/deq015.

Huang, Po-Chin, Wan-Fen Li, et al. “Risk for Estrogen-Dependent Diseases in Relation to Phthalate Exposure and Polymorphisms of CYP17A1 and Estrogen Receptor Genes.” Environmental Science and Pollution Research International, vol. 21, no. 24, Dec. 2014, pp. 13964–73. PubMed, https://doi.org/10.1007/s11356-014-3260-6.

Jaramillo-Rangel, G., et al. “Polymorphisms in GSTM1, GSTT1, GSTP1, and GSTM3 Genes and Breast Cancer Risk in Northeastern Mexico.” Genetics and Molecular Research: GMR, vol. 14, no. 2, June 2015, pp. 6465–71. PubMed, https://doi.org/10.4238/2015.June.11.22.

Jia, Lu-Lu, et al. “Occurrence of Phthalate Esters in Over-the-Counter Medicines from China and Its Implications for Human Exposure.” Environment International, vol. 98, Jan. 2017, pp. 137–42. PubMed, https://doi.org/10.1016/j.envint.2016.10.025.

Kim, Jin Hee, and Yun-Chul Hong. “HSP70-Hom Gene Polymorphisms Modify the Association of Diethylhexyl Phthalates with Insulin Resistance.” Environmental and Molecular Mutagenesis, vol. 55, no. 9, Dec. 2014, pp. 727–34. PubMed, https://doi.org/10.1002/em.21884.

Legler, Juliette, et al. “Obesity, Diabetes, and Associated Costs of Exposure to Endocrine-Disrupting Chemicals in the European Union.” The Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 4, Apr. 2015, pp. 1278–88. PubMed, https://doi.org/10.1210/jc.2014-4326.

Nutrition, Center for Food Safety and Applied. “Phthalates in Cosmetics.” FDA, May 2022. www.fda.gov, https://www.fda.gov/cosmetics/cosmetic-ingredients/phthalates-cosmetics.

Park, Choonghee, et al. “Associations between Urinary Phthalate Metabolites and Bisphenol A Levels, and Serum Thyroid Hormones among the Korean Adult Population – Korean National Environmental Health Survey (KoNEHS) 2012-2014.” The Science of the Total Environment, vol. 584–585, Apr. 2017, pp. 950–57. PubMed, https://doi.org/10.1016/j.scitotenv.2017.01.144.

“Phthalates Business Guidance & Small Entity Compliance Guide.” U.S. Consumer Product Safety Commission, https://www.cpsc.gov/Business–Manufacturing/Business-Education/Business-Guidance/Phthalates-Information. Accessed 14 July 2022.

“Phthalates Hard To Avoid In Food: Junk Food No Worse Than Healthful Food For These Potentially Harmful Substances.” ScienceDaily, https://www.sciencedaily.com/releases/2009/09/090927154823.htm. Accessed 14 July 2022.

Radke, Elizabeth G., et al. “Phthalate Exposure and Male Reproductive Outcomes: A Systematic Review of the Human Epidemiological Evidence.” Environment International, vol. 121, no. Pt 1, Dec. 2018, pp. 764–93. PubMed, https://doi.org/10.1016/j.envint.2018.07.029.

Rudel, Ruthann A., et al. “Phthalates, Alkylphenols, Pesticides, Polybrominated Diphenyl Ethers, and Other Endocrine-Disrupting Compounds in Indoor Air and Dust.” Environmental Science & Technology, vol. 37, no. 20, Oct. 2003, pp. 4543–53. DOI.org (Crossref), https://doi.org/10.1021/es0264596.

Sakhi, Amrit K., et al. “Concentrations of Phthalates and Bisphenol A in Norwegian Foods and Beverages and Estimated Dietary Exposure in Adults.” Environment International, vol. 73, Dec. 2014, pp. 259–69. PubMed, https://doi.org/10.1016/j.envint.2014.08.005.

Seckin, Elcim, et al. “Determination of Total and Free Mono-n-Butyl Phthalate in Human Urine Samples after Medication of a Di-n-Butyl Phthalate Containing Capsule.” Toxicology Letters, vol. 188, no. 1, July 2009, pp. 33–37. PubMed, https://doi.org/10.1016/j.toxlet.2009.03.002.

Sedha, Sapna, et al. “Role of Oxidative Stress in Male Reproductive Dysfunctions with Reference to Phthalate Compounds.” Urology Journal, vol. 12, no. 5, Nov. 2015, pp. 2304–16.

Stojanoska, Milica Medic, et al. “The Influence of Phthalates and Bisphenol A on the Obesity Development and Glucose Metabolism Disorders.” Endocrine, vol. 55, no. 3, Mar. 2017, pp. 666–81. PubMed, https://doi.org/10.1007/s12020-016-1158-4.

Sun, Jing, et al. “Phthalate Monoesters in Association with Uterine Leiomyomata in Shanghai.” International Journal of Environmental Health Research, vol. 26, no. 3, 2016, pp. 306–16. PubMed, https://doi.org/10.1080/09603123.2015.1111310.

Tordjman, Karen, et al. “Exposure to Endocrine Disrupting Chemicals among Residents of a Rural Vegetarian/Vegan Community.” Environment International, vol. 97, Dec. 2016, pp. 68–75. PubMed, https://doi.org/10.1016/j.envint.2016.10.018.

Trasande, Leonardo, et al. “Phthalates and Attributable Mortality: A Population-Based Longitudinal Cohort Study and Cost Analysis.” Environmental Pollution, vol. 292, Jan. 2022, p. 118021. ScienceDirect, https://doi.org/10.1016/j.envpol.2021.118021.

Wang, I.-Jen, and Wilfried Joachim Jurgen Karmaus. “The Effect of Phthalate Exposure and Filaggrin Gene Variants on Atopic Dermatitis.” Environmental Research, vol. 136, Jan. 2015, pp. 213–18. PubMed, https://doi.org/10.1016/j.envres.2014.09.032.

Yin, Lei, et al. “Benzyl Butyl Phthalate Promotes Adipogenesis in 3T3-L1 Preadipocytes: A High Content Cellomics and Metabolomic Analysis.” Toxicology in Vitro: An International Journal Published in Association with BIBRA, vol. 32, Apr. 2016, pp. 297–309. PubMed, https://doi.org/10.1016/j.tiv.2016.01.010.
.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.