Detoxifying Phthalates:  Genes and Diet

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

Amidst all of the scary headlines these days, are phthalates really worth worrying about?  It may depend, in part, on your genetic variants. Some people are genetically going to be more susceptible to the negative effects of phthalates.

What are phthalates?

Phthalates are a type of chemical used as a plasticizer, which makes plastics more pliable. Because they are not bonded to the plastic, phthalates can come out of plastic products 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]

Where do we find phthalates?
Phthalates are commonly found in:

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

Several types of phthalates are banned in the US and the EU now 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 of the products they tested.

Are phthalates really a problem?

It depends on how you define ‘a problem’.

Phthalate exposure is probably not going to kill you outright. There were quite a few toxicity tests done dating back to the 1970s using rats as a model. US government toxicology studies in 1995 on rats showed that exposure to phthalates didn’t kill adult rats in 13 weeks (but the doses used did kill the baby rats).

Animal studies using rats and mice may not be a good models for human metabolism of phthalates.  Newer studies indicate rats do not metabolize phthalates the same way that humans do.[ref]

Based on mouse studies, the exposure limits are set fairly high, at around 100 mg/kg/day for tumorigenesis (tumor formation).

California does include 6 types of phthalates on their list of possible carcinogens in their Prop 65 regulations.

Exposure to phthalates may be 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 certain phthalates from use in children’s toys.

Evidence showing the effect of low, chronic exposure of 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. Researchers think that phthalates in the environment may be leading to a global decrease in amphibians. Phthalates at very, very low, chronic levels are affecting frogs’ sperm.[ref]

If low, chronic doses of phthalates are a problem, how are we exposed?

It turns out that phthalates are ubiquitous – literally everywhere – in our food supply.  For example, the 2014 Norwegian study found phthalates in all foods and beverages commonly consumed (and BPA in 54%).[ref]

Exposure was highest in meat and grains, but levels were on average less than European maximum exposure level limits.

Phthalates are even a problem for people who eat organic and don’t store their food in plastic. 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?

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 or breathing phthalates (in artificial fragrances), you may be swallowing them in medications that you take.  Some pharmaceuticals also use phthalates as plasticizers 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]

phthalate-linkedHow do phthalates affect the body?

Below are a few of the thousands of studies on phthalates. As with most environmental factors, it is likely that phthalates affect different people in different ways 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]
    • Low T: Low dose, long-term exposure may decrease reproduction in males and decreased testosterone levels.[ref][ref]
    • Endocrine (thyroid, uterine) disruptors: The main problem with phthalates stems from their role as endocrine disruptors, which could cause problems with obesity, thyroid function, and uterine issues.

Obesity and weight gain:

      • Weight gain: Contaminated dust containing phthalates (which was found in all of the household dust sampled) was found to cause human cells to create triglycerides and also to 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. This 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 levels.[ref]
    • Subclinical hypothyroidism: A Korean study found phthalate metabolite levels to correlate to lower FT4, FT3, and just slightly higher TSH levels.[ref]
    • Rat study showing 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 are being missed by doctors.  Check out Stop the Thyroid Madness for more information on FT4, FT3, and all the other thyroid hormones.
    • Another study explains how this links 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:

      • There are quite a few studies linking phthalates and other endocrine disruptors to fibroids and other 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 going on.  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 both higher phthalate levels and 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 that replicated the finding that higher phthalate levels (flooring, dust, etc) correlate with higher allergy levels.[ref]

What happens to phthalates in your body?

According to this study, phthalates metabolize rapidly and are excreted in urine and feces.  Phase I metabolism involves hydrolysis by lipases; the enzymes produced in the pancreas and stomach.  Depending on whether the phthalates are high or low molecular weight, they can also be further metabolized the oxidation. The oxidative metabolites can then go through glucuronidation in phase II metabolism.[ref]


Genetic Variants:

GSTP1 gene:

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:

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 that is 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 enzyme that is important in phase II detoxification.

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

  • A/A: deletion (null) GSTM1 gene. GSTM1 deletion is associated with 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 .

 


Lifehacks for detoxifying phthalates:

  • Avoid storing and heating food in plastics
  • Studies have shown that almost all packaged and processed food contains low levels of phthalates. Buying fresh foods from local farmers should help to decrease phthalate exposure
  • Many artificial fragrances have phthalates in them, so avoiding air fresheners (or switching to essential oils) may help.
  • Vegans eating only organic do have slightly lower levels of phthalates.[ref] This is probably due to eating more fresh fruits and vegetables.
  • Dusting frequently decreases phthalates in the air at home. But make sure you aren’t using furniture polish or spray that contains phthalates.[ref]
  • Studies show that phthalates can be excreted in sweat; saunas and exercise may be a good way to get rid of phthalates.[ref][ref]
  • If you have a GSTM1 null gene type (see above), eating a lot of fruits and vegetables should help.[ref]
  • Supplementing with the antioxidants vitamin E and C may help with GSTM1 null. [ref]

 


Related Genes and Topics:

SHOULD YOU EAT ORGANIC? DETOXIFYING ORGANOPHOSPHATES
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.

GLUCURONIDATION: UGT GENETIC VARIANTS, PHASE II DETOXIFICATION
The UGT family of enzymes are responsible for an important part of phase II detoxification. In this article, I’ll explain what the UGT enzymes do in the body, how your genes impact this part of detoxification, and lifestyle factors that can increase or decrease this detox process.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.