Phthalates: Genes, Detoxification, and Diet

Key Takeaways:
~ Phthalates are a class of compounds that add flexibility to plastics and vinyl. They are also found in artificial fragrances.
~ We are all regularly exposed to phthalates through food, inhalation of fragrances, and the degradation of vinyls and plastics in the home. Studies show that almost all of us have phthalates in our bodies.
~ Genetic variants play a role in how well we break down phthalates and how quickly we eliminate them.
~ Research on human exposure to phthalates now shows significant long-term health effects from these ubiquitous compounds.

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What are phthalates?

Phthalates (pronounced THAL-eights) are a class of chemicals used as plasticizers to make plastics more pliable. They are also used as solvents and fixatives in artificial fragrances. Because they are not covalently bonded to plastic polymers, phthalates can leach from plastic items when exposed to heat or solvents. Phthalates can leach from PVC-containing items (plastics, pipes, vinyl flooring, etc.) and become airborne or part of soil and water.[ref][ref]

Phthalates are classified as “endocrine disruptors.” They have been linked to reproductive harm, such as decreased fertility and pregnancy loss.[ref][ref][ref]

Where do we find phthalates?

Phthalates are commonly found in:[ref][ref]

Artificial fragrances (fabric softener, candles, air freshener, body spray)
Personal care products (shampoo, lotions, cosmetics, hair care products)
Nail polish (inhaled vapors, absorbed through the nails)
Vinyl products (PVC, vinyl tubing, flooring)
Food and food packaging
Coatings on pharmaceuticals
Flexible coatings on extension cords and appliance cords
Medical devices
Carpet backing
Faux leather, such as in furniture
Printing inks
Added to boxed mac and cheese!

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

Packaged foods may contain phthalates due to processing or packaging. In addition, prescription and over-the-counter medicines can contain phthalates as excipients.[ref] In 2010, the FDA created a list of products it had tested for phthalates – fragrances topped the list as a major source of phthalates in the products tested.

Are phthalates really a problem?

You may wonder if this is just another scary “sky is falling” type of headline-grabbing chemical.

Let’s look at the latest research and put it in context.

Phthalate exposure will not kill you outright. Many toxicity tests dating back to the 1970s used rats as a model, showing that phthalates were not immediately toxic. For example, a 1995 U.S. government toxicology study on rats showed that exposure to phthalates didn’t kill adult rats after 13 weeks. (However, the doses used did kill the baby rats.)[ref] When you read about phthalate exposure, the effect on frogs is often mentioned. And research shows that phthalate pollution in the environment could lead to a global decline in amphibians because phthalates affect frog sperm at very, very low levels.[ref]

When looking at research studies, it is important to know:

Animal studies using rats and mice may not be good models for the human metabolism of phthalates. Recent studies suggest that rats do not metabolize phthalates in the same way as humans.[ref]
Based on mouse studies, the exposure limits are set relatively high, at about 100 mg/kg/day for tumor formation.

A lifetime of phthalate exposure at low levels likely has an effect on mortality. A recent study (2021) found that phthalate exposure increases all-cause mortality, in part due to an increase in cardiovascular disease. The study estimated the impact on people aged 55-64 caused >90,000 attributable deaths/year in the U.S.[ref]

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

Let me set the stage with a sampling of recent human studies:

12 Effects of chronic, low-dose phthalate exposure in humans:

Evidence of the effects of low-level, daily exposure to phthalates in humans and animals includes:

Phthalates act as endocrine disruptors.[ref]
As endocrine disruptors, phthalates may increase the risk of fibroids, obesity, asthma, ADHD, IVF problems, and reproductive problems in men.[ref][ref]
Higher exposure to phthalates has been linked to decreased cognition (studies in children).[ref]
In women, higher phthalate levels are linked to obesity and metabolic syndrome.[ref]
Chronic exposure to phthalates increases allergies.[ref]
Phthalate exposure correlates with the size of uterine fibroids – more phthalates, larger fibroids.[ref]
Higher prenatal exposure to phthalates is linked to eczema in children.[ref]
Higher phthalates exposure in children is strongly associated with subclinical atherosclerosis.[ref]
Phthalate metabolite levels are also linked to higher blood pressure profiles in teenagers.[ref]
Metabolites are associated with a 200% increased relative risk of asthma in boys.[ref]
Ovarian oxidative stress increases in women exposed to higher phthalate levels.[ref][ref]
Phthalates have been linked to testicular dysgenesis syndrome.[ref]

How are we exposed to phthalates?

Phthalate contamination exists literally everywhere in our food supply, from packaging to the equipment used to process foods and dairy products.

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

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

Can eating organic protect you from phthalate exposure from food? Probably not.

One study found that phthalate levels in people who ate junk food were the same as those who ate a controlled organic diet with food stored in glass containers instead of plastic.[ref] This is likely due to phthalate contamination throughout food processing, storage, and shipping.

I mentioned above that phthalates are also a component of many artificial fragrances. Thus, shampoos, lotions, cosmetics, and other personal care products often contain fragrances – and phthalates.

Phthalates can pass through the skin and be absorbed transdermally or inhaled.[ref]

Kids spend a lot of time on the floor, playing, and tend to have more “hand-to-mouth” behavior. Vinyl flooring in homes is linked to a 15-fold higher phthalate level in children compared to kids living in homes with other flooring materials.[ref]

Phthalate exposure is also higher in certain workplaces. For example, phthalates are used as a plasticizer in nail polish, and inhaling nail polish fumes by nail salon workers is linked to high phthalate levels in their urine.[ref]

Routes of exposure:

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

One study summarizes 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 restricted the use of phthalates in materials in contact with food since 2009.[ref]

Phthalates are also found in face masks and can be absorbed through skin contact as well as inhalation.[ref]

Finally, if you are not eating phthalates or inhaling phthalates from artificial fragrances, you may be swallowing them in your medications. Some drugs use phthalates as plasticizers in their capsules or coatings. Even if they were not intentionally added to drugs, a recent study in China found varying levels of phthalates in all of the medications they tested.[ref][ref]

Going in-depth on phthalate research in humans:

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

ADHD:

A review article summarizes the link between ADHD and phthalates: “Recent evidence supports the existence of an association between urine phthalate metabolite levels, attention-deficit/hyperactivity disorder (ADHD), and executive functioning.”[ref]
Higher levels of phthalates in mothers are linked to a threefold increased relative risk of ADHD diagnosis in their children at age 3.[ref]

Infertility:

Research shows 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]
Women with phthalate metabolite levels in the second and third quartiles had twice the risk of infertility compared to women with lower phthalate levels.[ref]

Lower Testosterone:

Low-dose, long-term exposure may decrease male fertility and testosterone levels.[ref][ref]
Higher levels of phthalate metabolites during late puberty are associated with poorer semen quality. The highest quintile had “30% lower sperm concentration, 32% lower count and 30% lower progressive motile count, compared to men in the lowest quintile”.[ref]

Obesity and weight gain:

Weight gain: Contaminated dust containing phthalates (found in all of the household dust samples) was found to cause human cells to produce triglycerides and cause mice to become fat.[ref]
Fat accumulation: Previous studies in cells have found similar results for phthalates promoting fat accumulation.[ref]
Obesity and diabetes: Sometimes, the best way to understand the impact of a substance on a whole population is to put a price on it. 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][ref]
A large study looked at phthalate metabolite levels in over 2,000 women in relation to sex hormones and BMI. The results showed that higher levels of phthalates were associated with obesity and metabolic syndrome. In addition, the researchers found that SHBG levels were lower in women with higher levels of phthalate metabolites. [ref]

Thyroid function affected by phthalates:

Depressed thyroid function: Several studies link urinary phthalate levels to depressed thyroid hormone levels.[ref][ref]
Subclinical hypothyroidism: A Korean study found phthalate metabolite levels correlated with lower FT4, FT3, and slightly higher TSH levels.[ref]
In pregnant women, higher phthalate metabolite levels are associated with lower free T4 levels as well as altered TSH/FT4 ratios. The conclusion was that “exposure to phthalates may interfere with the thyroid system during pregnancy.”[ref]
May not be showing up in common thyroid tests: Animal studies show 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.

Uterine fibroids:

Several studies have linked phthalates and other endocrine disruptors to fibroids and uterine problems. Although most of the studies seem to be small or rely 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 tag on the problem can give a bigger picture of what is happening. A 2016 study estimated that the cost of fibroids due to this endocrine disruptor was 1.3 billion euros in the EU.[ref]
Not everyone is at the same risk: One study found that women with certain CYP17A1 and ESR1 variants had higher phthalate levels and a higher risk of 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]

Mental Health and Phthalate Exposure:

A study of more than 11,000 participants found that higher levels of metabolites were associated with an increased relative risk of depression in adults.[ref]
In adults over the age of 60, higher levels of phthalates were linked to a more than twofold increase in the relative risk of depression.[ref]
Higher maternal phthalate levels correspond with higher rates of mental health diagnoses in their children.[ref]
Elevated phthalate levels are also linked to the risk of postpartum depression.[ref]

How can we get rid of (detoxify) phthalates?

Phthalates are metabolized fairly quickly and are excreted in urine, sweat, and feces. Research shows us that the half-life of phthalates can range from hours to several days. [ref]

Phthalate detoxification is a two-step process:

Phase I: making the molecules more water-soluble
Phase II: attaching other chaperone compounds for elimination from the body.

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

Phthalates must then be further metabolized by oxidation. The oxidative metabolites can then undergo 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 find ways to eliminate phthalates from the body more quickly.

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.

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Phase I detoxification:

CYP2B6 gene: This gene codes for a phase I detoxification enzyme important for metabolizing various toxins, including phthalates.[ref][ref] Decreased enzyme function may decrease the rate at which phthalates are metabolized.

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 —.

Phase II detoxification:

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 —.

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], and 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 (heat shock 70) protein. Learn more about heat shock proteins here.

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; insulin resistance not tied to phthalate exposure[ref]

Members: Your genotype for rs2227956 is —.

Lifehacks for detoxifying phthalates:

Lifestyle changes for avoiding phthalate exposure:

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