PhthalateGeneticsThere have been several recent studies about phthalates that have piqued my interest lately.  I decided that it was time to look into the science behind the stories and see if there really is anything to the scare-tactic type headlines about phthalates.  Below are my notes with links to studies.  I encourage you to check out the research and come to your own conclusions about whether phthalates are something to worry about for your body — and whether there is really anything you can do…

What are phthalates?
Phthalates are a type of chemical used as plasticizers to make plastics more pliable. They are not bonded with the plastic, thus allowing them to come out of plastic products when exposed to heat or solvents. “Because they are not covalently bound into plastic when used as plasticizers, phthalates have been found to leach or migrate from PVC-containing items into air, dust, water, soils, and sediment ” [study]

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, paints, carpet backing, faux leather, printing inks, and apparently 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.

In addition to food containing phthalates due to processing or packaging, prescription and over the counter medicines (2012) can contain phthalates as excipients. [study]  In 2010 the FDA created a list of products that they had tested for phthalates – fragrances were a huge source of phthalates of the products they tested.

Are phthalates really a problem?
I guess to answer that question, you would have to define ‘problem’.  Phthalate exposure is probably not going to kill you outright. They are not a new substance, and there have been quite a few toxicity tests dating back to the 1970’s using rats as a model.  US government toxicology studies in 1995 on rats showed that it didn’t kill adult rats in 13 weeks, but the doses used did kill baby rats.

There is some question, though, as to whether rodent studies are good models for human metabolism of phthalates, and newer studies now indicated that rats do not metabolize phthalates the same way that humans do.  [study] Exposure limits based on mouse studies are set fairly high, at around 100 mg/kg/day, as far as tumorigenesis. But California does include 6 types of phthalates on their list of possible carcinogens in their Prop 65 regulations.

Even though they probably aren’t going to kill you and probably won’t give you cancer, some of the harms of phthalates have been clearly shown, especially with infant and child exposures. Some types of phthalates have been removed over the past 15 years or so from teething rings and bottle nipples (EU and FDA regulations) and in 2009 US banned certain phthalates from use in children’s toys.

Some of the evidence showing that phthalates do have an effect on people and animals in low, chronic doses includes:

  1. Phthalates act as an endocrine disruptor
  2. As an endocrine disruptor, phthalates may increase the risk of fibroids, obesity, asthma, ADHD, IVF problems, and reproductive problems in men.
  3. It may be leading to a global decrease in amphibians – phthalates at very, very low, chronic levels are affecting frogs’ sperm.

So if low, chronic doses of phthalates are a problem, where are they coming from?
It turns out that phthalates are ubiquitous – literally everywhere – in our food supply.  For example, 2014 Norwegian study found phthalates in all foods and beverages commonly consumed (and BPA in 54%).  Exposure was highest in meat and grains, but levels were on average less than European max exposure levels.  Phthalates are even a problem for those trying to eat clean, organic food which is stored in glass. A study found that levels in junk food were the same as for those eating a controlled organic diet with food stored in glass containers instead of plastic.

How do phthalates get into our body?
One study sums up the routes of exposure well: “According to a review by Cao, 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].”

Another study notes: “In the United States, phthalates have been approved by the Food and Drug Administration (FDA) as plasticizers in food packaging materials and food contact substances used during processing and storage while the European Commission and Chinese authorities have limited phthalates in food contact materials made of plastic since 2008–2009”

Finally, if you aren’t eating or breathing phthalates, they may be 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 medications that they tested.

phthalate-linkedWhat are the effects of phthalates on the body?
Below are just some of the studies that show different effects of phthalates.  This is not a comprehensive list, so I hope you will do some researching on your own if you are interested in other effects of phthalates.  As with most environmental factors, it is likely that phthalates affect different people in different ways based on their genetic susceptibility.

  • ADHD “Consistent with previous studies [18], we found a significant correlation between the urine phthalate metabolite concentrations and the poor attentional performance” [study]
  • 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.
  • Low dose, long term study (mice) found decreased reproduction in males and decreased testosterone levels
  • 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:
    • Contaminated dust containing phthalates (which was found in all the household dust sampled) was found to cause human cells to create triglycerides and also cause mice to get fat.
    • Previous studies in cells have similar findings for phthalates promoting fat accumulation.
    • 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.”
    • A March 2017 study says “Most data support the effects of bisphenol A and some phthalates … on the development obesity and type 2 diabetes mellitus.”
  • Thyroid function is also affected by phthalates:
    • Several studies link urinary phthalate levels to depressed thyroid levels.
    • A Korean study found phthalate metabolite levels to correlate to lower FT4, FT3 and just slightly higher TSH levels.
    • Rat study showing that phthalates decrease T4, T3 and TRH but not TSH
    • 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”
  • 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.
    • Again, putting a price on the issue may give a bigger picture to what is going on.   A 2016 study estimated the cost of endocrine disruptor caused fibroids at 1.3 billion euros in the EU.
    • 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.
  • Histamine / Mast Cell / Allergy connection:

What happens to phthalates in your body?
According to this study, phthalates are metabolized rapidly and excreted in urine and feces.  Phase I metabolism involves hydrolysis by lipases, which are 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.

So which genes are involved in breaking down and getting rid of phthalates?

  • A GSTP1 polymorphism, rs1695 AA, is associated with increased risk of asthma with phthalate exposure
  • “Humans are mainly exposed to DEHP via ingestion of food. Once absorbed into the body, DEHP is rapidly hydrolyzed to mono(2-ethylhexyl)phthalate (MEHP) and 2-ethylhexanol (2-EH) by the catalytic action of lipase [2, 3]. A part of MEHP is further oxidized by various cytochrome P450s (CYPs), followed by alcohol dehydrogenase (ADH) or aldehyde dehydrogenase (ALDH), to produce dicarboxylic acid or ketones. The remaining MEHP is excreted in the urine directly or in the conjugation form by the catalytic action of UDP-glucuronocyltransferase (UGT). 2-EH is metabolized mainly to carboxylic acid [mainly 2-ethylhexanoic acid, 2-EHA] via 2-ethylhexanal by the catalytic action of ADH and ALDH [2]. The 2-EHA formed is further oxidized to a dicarboxylic acid in a way similar to MEHP oxidation.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3944035/
  • Phase 1 detoxification is thought to be mainly through hydrolysis by lipases. Lipases are a type of enzyme produced in the pancreas, saliva, and bile.  They are what break down the fats that you eat.
    I found one EPA report that implies that the PNLIP and LIPF genes code for the pancreatic and gastric lipases that break down phthalates, but I couldn’t find any other studies to confirm this.
  • Some phthalate metabolites also induce CYP450 genes including CYP2B6.
  • While I didn’t find any specific studies on CYP2B6 polymorphisms and phthalates, there are a couple of polymorphisms that cause impaired metabolism by CYP2B6.
  • UGT enzymes involved in the glucuronidation (phase II metabolism) of phthalates include UGT1A9, UGT1A3, UGT1A7, UGT1A10, UGT2B7  — check out my article on UGT genes
  • GSTM1 (Glutathione S-Transferase Mu 1) has been shown in several studies to interact with phthalates.  The main variant of GSTM1 is known as GSTM1 null, meaning it is absent.
    • A small study, but one that has been replicated and cited by quite a few other studies, found that for those with GSTM1 null genotypes and phthalate exposure, the risk of fibroids was about 5 times greater.
    • Check your genetic data for rs366631.  It is a proxy for GSTM1 null with the AA genotype corresponding to null.  About 50% of the population is null.

So what can you do about phthalates, especially if you genetically may not be detoxifying them well?

  • First, while avoiding plastics and not heating your food up wrapped in plastic wrap may help a bit overall, I think that studies have shown that almost all food these days contains low levels of phthalates. A lot of fragrances have phthalates in them, so removing air fresheners (or switching to essential oils) may help as well.
  • Vegans eating only organic do have slightly lower levels of phthalates.   I’m not sure that switching to an organic, vegan diet is worth it just for the slight decrease in phthalate levels.
  • High frequency of dusting does decrease phthalates in the air at home. But make sure you aren’t using a furniture polish or spray that contains phthalates.
  • While I have read mixed results before about sweating out toxins, studies do show that phthalates can be excreted in sweat, thus saunas and exercise may be a good way to get rid of phthalates.
  • If you have a GSTM1 null gene type (see above), high fruit and vegetable consumption should help out.
  • Supplementing with the antioxidants vitamin E and C may help with GSTM1 null. Especially vitamin C.
  • If you have UGT polymorphisms (and even if you don’t), one way to boost the power of these phase II enzymes is to inhibit beta-glucuronidase, an enzyme produced by gut bacteria that basically reverses the glucuronidation of toxins by UGT enzymes. Calcium D-glucarate supplements are one way to inhibit beta-glucuronidase.  Bifidobacteria longum, l. plantarum, and l. acidophilus also inhibit the bacteria that produce beta-glucuronidase.

Personal Plan of Action:
A lot of the above problems and genetic variants apply to me personally.  My personal plan of action includes:

More to read:

 


2 Comments

Kate · September 27, 2017 at 7:33 pm

You write wonderfully! I understood most of what you were disseminating and teaching. Thank you for all of your hard work for those of us who just want to be ‘fed’ the information before passing it along to others.

    genelife · September 29, 2017 at 10:35 pm

    Thanks so much for the kind words!

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