Common environmental hormone disruptors and WALL-E
For those of you who haven’t watched WALL-E (weirdos), the film follows a solitary robot called WALL-E on a future inhabitable, deserted Earth in the year 2805. WALL-E is left to clean the garbage-strewn Earth caused by years of rampant consumerism and corporate greed.
Humanity in this animation has been evacuated to live on starliners in space. And through years of evolutionary regression have become morbidly obese and totally reliant on machines for everything.
Back on Earth, whilst cleaning humanity’s garbage, WALL-E finds a seedling. There is no biological life on Earth remember, so the discovery of this seedling is revolutionary and transforms WALL-E’s life forever. I won’t spoil the rest.
What’s a Pixar film got to do with anything? Well currently nearly a third of the world’s population are obese and the worldwide obesity rate has tripled since 1975. It looks like this health-disaster freight train is only getting quicker, and sooner than later we might be treating the film ‘WALL-E’ as a prophecy.
In the film, the deteriorated health of humanity is put down to unhealthy diets, physical inactivity and genetics. However, I believe the artificial environment on the spaceship combined with previous decades of pollutant-filled living on the later inhabitable Earth may have played a big part too.
Our environment is not as clean as it once used to be. To keep humanity afloat and ticking, we have cut corners at the expense of quality. The use of fertilisers is rampant. Microplastics continue to litter the ocean. Other plastics, manufacturing pollutants and medical chemicals leach into our drinking water. Shampoos, deodorants and personal care products are laced with unnatural chemicals. And in cities, the air is smog and smoke-ridden too. And I’m telling you that these pollutants make us fat. Yes, there are things other than food that can make you fat.
Don’t believe me? Well, we have already learnt that words written on food packaging can alter one's hormones, so it shouldn’t be difficult to appreciate that there are chemicals in our environment that can disrupt our hormones and cause belly fat in the process too. Plus evidence from research studies has shown that a variety of environmental chemicals can influence the formation of fat cells and obesity. Today, there are more than 1000 chemicals reported to have hormonal effects.
These chemicals, also known as ‘obesogens’ or ‘endocrine disruptors’ (endocrine being the scientific term for hormone-secreting organs) are everywhere and slowly becoming more recognised as a contributor to obesity and weight gain in the scientific community.
One of the first studies exploring the link between industrial chemicals and the rise in obesity occurred 20 years ago and suggested these so-called obesogens could have damaged many of the body’s natural weight-control mechanisms. The graph from their study (which I have placed below) demonstrates their potential link better I think.
Since then, further studies have been performed on animals, and human population studies have been undertaken too. And the results from these and emerging studies continue to strengthen the link between environmental pollutants and obesity every day.
The link will however only ever remain a ‘link’ because randomised controlled trials (RCTs) will never be performed studying the role of obesogens directly on human health. RCTs are a type of study design where participants are either given intervention or not whilst other factors are controlled for. This is done to study the effects of the intervention without other factors interfering with the results. RCTs are revered within the scientific community because they can provide us with high-quality evidence.
Whilst RTCs would be optimal for determining causality between obesogens and obesity, ethical concerns, practical limitations, including the importance of developmental time of exposures, the long lag between exposure and effect, and the nonlinear relationship (I’ll explain what this means below) between environmental hormones and its effects, limit the feasibility of the standard RCTs in evaluating environmental contaminants as obesogens.
For this reason, many hardline scientists may disregard the importance of obesogens and population health. This may be one reason why you may not have heard of obesogens before now. But there are no RTCs on humans to associate smoking with cancers. Does this mean we lack evidence associating the two?
What I mean by ‘nonlinear (or non-monotonic) relationship’ is that interestingly, a lot of endocrine disruptors work in an inverted U-shaped dose-response manner. This means that extremely high and low doses of hormone disruptors have minimal biological effects, whilst mid-range doses are enough to activate receptors. More of a certain chemical doesn’t always translate to more problems. But remember that this doesn’t apply to all obesogens. So it all gets a bit complicated.
Also due to this non-monotonic-dose-response-relationship that some obesogens have, problems fester, and seem harmless at first, until circulating levels of pollutants increase in concentration enough to cause disease states. This may be another reason why the scientific community at large hasn't taken serious note of them…yet.
One more thing to note is that environmental hormone disruptors do not affect everyone equally. It has been noted that there are likely specific development time windows and organs where endocrine disruptors have the most effect. E.g. during foetal development and to reproductive organs. Adults require longer exposure to obesogens for the effect to take shape. Whereas if a pregnant mother were to be exposed in those important 9 months, the child born may have major biological consequences as a result.
Obesogens have been shown to cause weight gain following two mechanisms. One, they increase the number and size of fat cells and storage of fat per cell. And secondly, they disrupt all our wonderful metabolic hormones, messing up appetite regulation, fullness, food preferences, metabolism and insulin sensitivity in the process.
There are several environmental chemicals which have been shown to act as hormone disruptors. Here is a list of some of the more common ones:
Bisphenol A
Bisphenol A (BPA) is primarily used in the production of polycarbonate plastics and epoxy resins. It is an activator of an oestrogen-sensitive membrane receptor (GPR30) and steroid (glucocorticoid) receptors and it mimics the structure and function of oestrogen. And through this mechanism it alters the way sugars are metabolised, impairs the proper formation of fat cells causing fat cell dysfunction. Studies have demonstrated a positive association between urinary BPA levels and obesity and diabetes in adults, children, and adolescents.
Phthalates
Phthalates are plasticizers which are chemicals used to turn hard plastics into soft plastics. It has anti-male-hormone and pro-oestrogenic properties and influences obesity through various mechanisms such as acting against thyroid hormone and activating peroxisome proliferator-activated receptors (PPARs). PPARs are receptors involved in the regulation of glucose and fat balance via the modulation of our genetics. Maternal phthalates have shown to negatively interfere with the genetics of the placenta (the birthing sac) during the first three months of pregnancy in women, suggesting that changes to modifiable areas of our DNA (called epigenetic changes) may link phthalate exposure to changes in placental function and adverse pregnancy outcomes.
Atrazine
Atrazine (ATZ) is the second most extensively used herbicide in the United States and Australian agriculture, and is a potent hormone disruptor, inhibiting male sex hormones and having weak oestrogenic effects. ATZ is also capable of causing dysfunction within the battery of our cells - the mitochondria. 94% of US drinking water contains atrazine as a contaminant and approximately seven million people were exposed to atrazine between 1998 and 2003. Long-term exposure to ATZ in animal studies has been shown to contribute to the development of insulin resistance and obesity, especially when the animals were also given a high-fat diet. Furthermore, the Agricultural Health Study in 11,273 pregnant mothers showed that women who reported agricultural exposure to herbicide, ATZ, during pregnancy had a risk of developing gestational diabetes.
Organotins
Organotins are chemicals used as polyvinyl chloride stabilisers, biocides, and antifouling paints. Tributyltin (TBT) a type of organotins, might be known to those clued-up eco-warriors out there, as it is used in antifouling paint formulations, especially for external marine applications, and thus is released into water causing inexplicable effects on aquatic animals. Organotins are also used in plastics, silicone and foams, and so they are found almost everywhere in clothes, wallpaper, medical devices, household piping, food containers and toys. You’re probably inhaling them right now. Organotins stimulate the formation and accumulation of fat cells, may cause thyroid dysfunction and can be classed as carcinogens.
Organophosphates
Organophosphates are used as insecticides, ophthalmic agents, herbicides and industrial chemicals, and exposure to them commonly occurs through accidental inhalation or ingestion of these compounds in fish, dairy products, and other fatty foods that are contaminated. Early-life exposure to organophosphates in neonatal rats has shown the subsequent emergence of biological states resembling prediabetes (the condition that arrives before type 2 diabetes). And a recent mice study showed that long-term exposure to organophosphates alters the gut microbiome leading to weight gain and reduced insulin sensitivity. Besides animal studies, one human cohort study noted that patients with acute poisoning from organophosphates had higher incidence rates of cardiovascular diseases compared with that in the non-organophosphate poisoning cohort.
Monosodium glutamate
MSG is the sodium salt of glutamic acid and is found naturally in algae, mushrooms, tomatoes and grapes. You’ll find MSG in other processed foods too, as it is artificially manufactured by the large-scale fermentation of starch for flavouring purposes. In the lab MSG has shown to impair glucagon-like peptide 1 (GLP-1) - which as we know is involved in satiety responses and insulin release. A cross-sectional study involving 752 healthy Chinese, aged 40–59 years, has shown that the users in the highest tertile of MSG intake had 2.75 times increased risk of being overweight compared to non-users. Another study, this time in Thai individuals, demonstrated that there were 1.16 times increased risk of being overweight for every 1 g increase in MSG intake.
Clozapine (antipsychotics)
Clozapine is an antipsychotic usually reserved for treatment-resistant Schizophrenia. All antipsychotics are associated with substantially increased appetite and weight gain, as well as increased risk for obesity and metabolic abnormalities, but due to its strength, clozapine may be more metabolically harmful than its counterparts. Prolonged use of clozapine has been found to cause a drug-induced metabolic syndrome in mammals that gave rise to adverse metabolic side effects such as obesity. Clozapine has been shown to inhibit GLP-1 secretion, cause mitochondrial dysfunction, and induces a preference for high-fat/high-sugar foods in humans.
Polychlorinated biphenyls
Polychlorinated biphenyls (PCBs) are heavily used in various commercial applications such as plasticizers in paints, plastics and rubber products, in pigments, dyes and carbonless copy paper and in electrical, heat transfer and hydraulic equipment. They are non-flammable, chemically stable, insulating with high boiling points. And due to their durability, they can be leached into the environment and bioaccumulate via entering the food chains. PCBs are mainly stored in human fat cells and liver with elimination half-lives of around 10-15 years. One animal study showed significantly increased body weight in mice that were fed a high fat diet along with PCB exposure, suggesting that certain PCBs are diet-dependent obesogens. Researchers hypothesised that this was due to the production of abnormal fat cell hormones and the altering of liver fat metabolism by PCBs.
Organobromines
Organobromines are used as flame retardants and have shown to disrupt a whole range of hormones including thyroid function and testosterone metabolism, and it is by this mechanism that we think organobromines disrupt metabolism. Other studies have shown that on exposure to certain organobromines, the formation of fat cells and the burning of sugar were both increased and decreased respectively.
Perfluorooctanoic acid
Perfluorooctanoic acid (PFOA) is a surfactant (a type of wetting agent), which is used in non-stick cookware, waterproof clothing and stain repellent on carpets, mattresses and microwaveable food items. Evidence shows that PFOA tends to accumulate in the liver and kidneys with a half-life in the blood of four years. This is likely due to its structure which resembles natural fatty acids. And due to this, it has been found to activate PPAR-α. Mice exposed to PFOA before birth have been shown to be more likely to become obese than controls when they reach adulthood. And exposure to PFOA during mice development has been shown to increase insulin, leptin and body weight during mid-life. Human studies are required.
Heavy metals
Heavy metals are metals that are high in density or weight and are toxic at relatively low concentrations. Some heavy metals like iron, cobalt and zinc are essential nutrients, but the dose makes the poison. You will find heavy metals everywhere as they belong to many aspects of modern human life plastics, mobile phones, solar panels, antiseptics, and many more) and pose a serious threat to human health.
Arsenic, commonly found in alloys of lead (for example, in car batteries and ammunition) has been shown to cause metabolic dysfunction with exposure. Human studies have shown that consuming arsenic-contaminated water significantly increased leptin levels in the blood of children of pregnant women, in placental tissue and in placental cord blood. Population studies have shown that individuals living in areas of high arsenic exposure have an increased risk of diabetes. It is thought that arsenic has the ability to impair glucose-stimulated insulin secretion by the pancreas, and increase pancreatic inflammation and insulin resistance in muscles too. The main source of arsenic found in fish, called arsenobetaine, can accumulate in the human body or transform into toxic inorganic arsenic in the gastrointestinal tract by microorganisms. Arsenobetaine is significantly associated with pancreatic dysfunction.
Cadmium and lead are both highly toxic and carcinogenic heavy metals. It has been demonstrated that exposure to both cadmium and lead heavy metals, particularly during the prenatal period, is linked to decreased birth weight and gestational age in humans. Animal studies have shown that exposure to both heavy metals early after being born is linked to increased body weight, fat mass or food intake in adulthood.
Dichloro-diphenyl-trichloroethane
Dichloro-diphenyl-trichloroethane (DDT) is an insecticide and has been shown to cause transgenerational obesity in part by inducing pro-obesity epigenetic changes. In plain English, exposure to DDT in one generation can cause modifiable changes to the genetics of offspring to make them fatter. DDT has also been shown to impair fat cell function, decrease response to eating more than needed, and increase fat cell numbers and size.
Nicotine
Found in tobacco plants, nicotine has been used as medicine and stimulant for at least 2000 years now. Population studies indicate that pregnant mothers who smoke increase the chances of obesity in the child, even when exposure is limited only to the early pregnancy stage. Studies have shown that exposure to nicotine in children still in the womb prevents the flight-or-fight responsiveness from working properly and this, in turn, may increase appetite and decrease the usage of fat from fat cells.
As you can see, there are a lot of things other than food that can cause or worsen obesity. And unfortunately our food and water quality are plummeting which will only further increase the rates of disease within the population.
It can be a little overwhelming learning about obesogens, simply because they are everywhere and hard to run away from. My mantra has always been “do what you can with what you have.”. For example, if you can grow your own vegetables organically, do that. If you can invest in a water filter system, do that. But if you can’t do either of those things or leave your job at the plastic factory, then don’t beat yourself about it.
Most of these chemicals preferentially affect the unborn baby as it sleeps in its mother's womb. So if you’re currently pregnant or looking to start a family, you may want to pay special emphasis with regards to reducing your exposure to these pollutants.
Will industrial and farming practices change fast enough to help reduce the accumulation of hormone-disrupting chemicals in the environment? Will the scientific community take the association between obesogens and obesity seriously? Will government policies be introduced to protect us? Will a rogue robot stumble up a seedling on a pollutant-filled inhospitable Earth in the future? Will humanity continue to degrade?
We will see.
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