Links Between Flame Retardants and Diabetes/Obesity
Over 100 peer-reviewed studies published since 2006 in scientific journals have examined the relationship between flame retardants and diabetes or obesity.
The findings from human epidemiological studies are mixed. Some have found that exposure to flame retardants is not associated with the risk of diabetes or obesity, and some have found associations.
Laboratory studies on animals or cells, however, show that flame retardants can cause biological effects related to diabetes/obesity.
About Flame Retardants
Flame retardants are chemicals added to furniture and electronics. Brominated flame retardants (BFRs) include compounds such as polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), and hexabromocyclododecane (HBCD). PBDEs are present in consumer products such as furniture and electronics, and exposure is largely through house dust. PBDEs have been banned or are being phased out throughout much of Europe and North America. One substitute is Firemaster 550, added to furniture foams and children's products, also found in house dust. HBCD is used in textiles and polystyrene foam, such as in automobile interiors. PBBs were banned in the U.S. in the 1970s, and current exposure is largely through diet. In general, flame retardant chemicals can accumulate in body tissues. BFRs are a type of persistent organic pollutants.
Type 2 Diabetes, Metabolic Syndrome, and Body Weight
Longitudinal Studies in Humans
The strongest evidence for the ability for environmental exposures to contribute to the development of diabetes comes from longitudinal studies. These are studies that take place over a period of time, where the exposure is measured before the disease develops.
A long-term study from Michigan found that levels of PBBs were not associated with diabetes risk. The people in this study were exposed to very high levels of PBBs for about eight months during the 1970s (Vasiliu et al. 2006). A long-term study from France found that dietary exposure to the flame retardants HBCD and PBDEs were associated with type 2 diabetes development (Ongono et al. 2018).
U.S. adolescents with higher PBDE levels have higher blood glucose levels (Baumert et al. 2022).
Exposure During Development
Evidence is growing that exposure to pollution during critical developmental periods, such as in utero or during childhood, may have effects later in life. A long-term study from California found that mothers' PBDE levels during pregnancy were associated with a higher body mass index (BMI) in their sons, but a lower BMI in their daughters at age 7. Also, the child's PBDE levels were associated with a lower BMI at age 7 (Erkin-Cakmak et al. 2015).
In Cincinnati, Ohio, prenatal PBDE levels generally were not associated with height or weight in children, although a few were associated with lower weight-related measures in childhood (Vuong et al. 2016). A further study by these authors found that BDE-153 levels during childhood were associated with lower weight-related measurements, especially in boys. The associations were stronger with PBDE levels measured later in childhood, and could be due to the greater storage of PBDEs in the fatty tissue of heavier children (Vuong et al. 2018).
A large European study found PBDE-153 exposure levels were associated with a lower childhood BMI; prenatal PBDE and other PBDE levels were not associated (Vrijheid et al. 2020).
Toddlers and Children Have High Levels of Flame Retardants In Their Bodies
In this family of four, the toddler (18 months) has the highest levels of BDE flame retardants in their body, followed by the child (age 5), and their parents have the lowest.
Source: Fischer et al. 2006, EHP.
A long-term Spanish study of 27 different endocrine disrupting chemicals found that in utero levels of various persistent organic pollutants were associated with overweight/higher BMI at age 7, while other chemical levels (flame retardants, arsenic, BPA, phthalates, lead, and cadmium) were not associated (Agay-Shay et al. 2015).
In North Carolina, PBDE levels in breastmilk were not associated overall with growth in children through age 3. However in boys, PBDE levels were associated with a lower weight-to-height ration, while in girls they were associated with higher weight-to-height (with the exception of BDE-153, which showed the opposite association) (Hoffman et al. 2016).
In Baltimore, Maryland, higher levels of the organophosphate flame retardant BDCIPP during pregnancy was associated with lower insulin and leptin levels in umbilical cord blood (Kuiper et al. 2020).
In China, umbilical cord levels of various PBDEs were associated with lower weight-related measures at age 7 (Guo et al. 2020).
PBDE exposures in the mother have been associated with lower birth weight of the baby (Chao et al. 2007 Harley et al. 2011; Lignell et al. 2013), and with epigenetic changes related to fetal growth (Zhao et al. 2019; Zhao et al. 2016). Maternal levels of organophosphate flame retardants are also linked to low birth weight (Luo et al. 2020; Luo et al. 2021) as well as growth and feeding behavior during infancy (Crawford et al. 2020).
Cross-Sectional Studies in Humans
Cross-sectional studies are studies that measure exposure and disease at one point in time. These provide weaker evidence than longitudinal studies, since the disease may potentially affect the exposure, and not vice versa.
Lim et al. (2008) studied exposure to BFRs using the U.S. National Health and Nutrition Examination Survey (NHANES) dataset, a U.S.-wide survey of chemical exposures, nutrition, and health conditions. They found that two of six flame retardants (PBB-153 and PBDE-153) were associated with both diabetes and metabolic syndrome (a cluster of conditions that are common in people with diabetes). The two chemicals had different dose response curves. PBB-153 was positively associated with diabetes, in that the risk increased as the levels of exposure increased. PBDE-153 was also associated with diabetes, but in the highest exposure group, the trend decreased slightly. Similar trends were seen in the associations with metabolic syndrome: steadily increasing for PBB-153, and increasing then decreasing for PBDE-153. These unusual dose-response relationships have been seen in animal studies of endocrine disrupting compounds. It may be that the effects of PBBs show up at lower doses, and at higher exposure levels, the risk would level off or even decrease (Lim et al. 2008).
Also using NHANES, exposure levels of organophosphate esters were positively associated with a higher risk of metabolic syndrome and its individual components in men, especially among those under 60. In women there was less of an association, except for the consistent positive association of a mixture of these flame retardants with obesity (Luo et al. 2020).
In North Carolina, pregnant women with higher BMIs had higher levels of various organophosphate flame retardant metabolites than those with lower BMIs (Hoffman et al. 2017). In NHANES, organophosphate levels were variously associated with either lower or greater body size, depending on the specific chemical, age, and sometimes sex (Boyle et al. 2019).
Among Cree people in northern Canada, higher fasting glucose levels were associated with higher PBDE levels, and beta cell function was lower in people with higher levels of PBDEs (Cordier et al. 2020).
In Finland, PBDE-47 and PBDE-153 were not associated with type 2 diabetes in elderly adults (Airaksinen et al. 2011).
In China, PBDE-47 were associated with diabetes in two independent community-based studies (Zhang et al. 2016). In Qatar, accumulation of PBDEs in human fat tissue was associated with insulin resistance in obese people (Helaleh et al. 2018). In Chinese people with high blood pressure, diastolic blood pressure was associated with organophosphate flame retardant levels (Li et al. 2020). In Chinese adults, levels of BBOEP, BDCPP, and DPHP were higher in people with type 2 diabetes than in people without diabetes. Higher levels of each of these flame retardants was associated with higher levels of cortisol and cortisone, which may impact energy metabolism (Ji et al. 2020).
Rats exposed to PBDE-47 for 8 weeks developed high blood glucose levels (Zhang et al. 2016). Male rats exposed to various flame retardants developed high glucose levels, plus had other metabolic effects that varied by chemical and sex of the rat (Krumm et al. 2018). Diet is also important; BDE-47 caused numerous obesogenic effects in mice fed a high-fat diet, but not in those fed a low-fat diet (Yang et al. 2021).
Mice exposed to HBCD gained more weight and had higher blood sugar and insulin levels (similar to type 2 diabetes) than unexposed mice. These effects were strongest in the mice fed a high-fat diet, as opposed to a normal diet (Yanagisawa et al. 2014). Additional mouse studies also show weight gain after exposure to HBCD (Xie et al. 2020). In rats, HBCD altered gene transcripts which were involved in the metabolism of chemicals, oxidative stress, the immune response, and the metabolism of glucose and lipids (Farmahin et al. 2018).
Chronic exposure to the PBDE known as penta-BDE disturbs glucose and insulin metabolism in fatty tissue of rats, characteristics associated with type 2 diabetes, insulin resistance, and obesity (Hoppe and Carey 2007). DE-71, a mixture of PBDEs, also disturbs whole-body glucose and insulin metabolism in rats, and may influence whole-body insulin resistance levels (Nash et al. 2013). Exposure to the flame retardant DecaBDE led to higher blood glucose levels in mice (Yanagisawa et al. 2018).
In mice and rats, BDE-209 causes increased glucose levels, affects cholesterol and triglyceride levels, and damages the the liver and the fatty tissue (Zhu et al. 2022; Zhu et al. 2021; Zhu et al. 2019). Another mouse study also found that BDE-209 increased body weight, fat and liver tissue weight, total and LDL cholesterol and triglycerides, reduced HDL cholesterol, and caused insulin resistance (Alimu et al. 2021). In rats, BDE-209 and DBDPE caused inflammation and oxidative stress, and led to cardiovascular damage as well (Jing et al. 2019).
How Are We Exposed to Flame Retardants?
Furniture labels that state that the item met California's flammability requirement technical bulletin 117 likely contained high levels of chemical flame retardants. Thanks to the work of many, including the Green Science Policy Institute, this law was updated in 2013 to longer require the use of chemical flame retardants. Furniture labelled with the newer "TB 117-2013" tag might or might not contain chemical flame retardants.
A rat study shows that PBDEs alters fat metabolism in the liver and increases blood ketone levels (Cowens et al. 2015).
Zebrafish exposed to natural mixtures of PBDEs and other persistent organic pollutants from Norwegian lakes showed increased body weight, as well as changes in the regulation of a variety of genes associated with body weight and insulin signalling (Lyche et al. 2010; Lyche et al. 2011).
Another type of flame retardant, triphenyl phosphate (TPhP), which is being used as a replacement for brominated flame retardants, causes changes in glucose levels, and carbohydrate and lipid metabolism in zebrafish, an animal used to test chemical exposure effects (Du et al. 2016). It also affects cholesterol levels in rats (National Toxicology Program, 2018). The flame retardant TMCP increased total cholesterol and triglyceride levels in fish (Cocci et al. 2019). In mice, TPhP inhibited levels of adiponectin, the insulin-sensitizing hormone, in females and stimulated it in males, leading to increased insulin resistance and glucose intolerance in females (Wang et al. 2019). In mice, TPhP (combined with high fat diet or alone) caused kidney structural damage and gut microbiota disorders (Cui et al. 2020). These and other organophosphorus flame retardants disrupt metabolism, and scientists are figuring out how (e.g., Wang et al. 2021). They can also affect fat cells and cause inflammation in these cells (Liu et al. 2022).
Adult organophosphate flame retardant exposure influences and exacerbates the effects of diet-induced obesity in adult mice by altering activity, feeding behavior, and metabolism (Vail et al. 2020). These organophosphate flame retardants affect feeding behavior controls in the mouse neurons (Vail and Roepke 2020). These authors are working to identify the mechanisms involved (Vail et al. 2022).
Exposure to low, environmentally relevant doses of the flame retardant and PBDE replacement Dechlorane Plus promoted glucose intolerance in mice fed a high fat diet, even without weight gain. Dechlorane Plus also affected fat tissue, and some of these effects occurred even when the mice were fed a regular diet. It also inhibited insulin signaling in fat cells (Peshdary et al. 2020).
Exposure to the flame retardant tetrabromobisphenol A (TBBPA) (and BPA) at concentrations commonly found in the environment led to obesity, increased appetite, and fat accumulation in the liver in adult male zebrafish (Tian et al. 2021).
In adult female zebrafish, chronic exposure to Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, lead to significant weight gain, fat accumulation, changes to the gut microbiome, and more, which were enhanced by a high-fat diet (Zhou et al. 2021).
A review of mechanisms of flame retardant toxicity involving inflammation and immune system dysfunction finds that flame retardants may also be able to contribute to Non-Alcoholic Fatty Liver Disease (NAFLD) (Negi et al. 2021a), and several flame retardants (e.g., tricresyl phosphate (TMPP), triphenyl phosphate (TPHP), tris(1,3-dichloropropyl) phosphate (TDCIPP), and 2-ethylhexyl diphenyl phosphate (EHDPP)) have been identified as potential contributors to this disease (Negi et al. 2021b). Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH), a novel brominated flame retardant, also enhanced diet-induced NAFLD progression in zebrafish (Guo et al. 2021).
A PBDE replacement, decabromodiphenyl ethane (DBDPE), increases blood glucose levels and causes liver damage in mice (Sun et al. 2018). And another replacement, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH) is also under suspicion as an obesogen (Marteinson and Fernie, 2019). This is a common problem, when replacements for toxic chemicals end up being toxic themselves.
Exposure During Development
Pregnant and lactating rats were exposed to the flame-retardant mixture Firemaster 550. The offspring developed signs of metabolic syndrome, including weight gain. Like other flame retardant chemicals, the chemicals used in Firemaster 550 accumulated in the body tissues of mothers as well as offspring, and had effects that suggested they disrupt the endocrine system (Patisaul et al. 2013). The flame retardant triphenyl phosphate, a component of Firemaster 550 and also found in consumer products such as nail polish, causes increased body fat mass in rodents exposed during gestation until weaning. It also accelerates the development of diabetes in the males (Green et al. 2017). In adult male mice, early life exposure to triphenyl phosphate led to increased body weight, fat mass, impaired glucose homeostasis, insulin resistance, and modulated gut microbiome composition (Wang et al. 2018).
Rats exposed to the flame retardant mixture DE-71 during development also weighed more than unexposed controls (Bondy et al. 2013). And mice exposed to deca-BDE had lipid abnormalities in the mothers, inhibiting fetal growth and development (Chi et al. 2011). Another study, of zebrafish, also found that developmental exposure to these compounds promotes fat accumulation in larvae and weight gain in the juvenile fish (Riu et al. 2014).
The offspring of pregnant rats exposed to a mixture of flame retardants had higher cholesterol levels, although lower fat pad weight, and no change in glucose or insulin levels (Tung et al. 2017).
Low doses of BDE-47, the PBDE that is most abundant in human tissues, was given to female mice while pregnant and lactating. Pups had increased body weight and body length during the first few months of life. Exposure also increased glucose uptake in male pups (Suvorov et al. 2009).
Four days after a single developmental exposure to the flame retardant HBCD, mice developed different metabolite levels that included metabolites involved in glycolysis, gluconeogenesis, and lipid metabolism (Szabo et al. 2017).
Exposure to flame retardants (BDE-47) in early life (but after weaning) led mice to develop insulin resistance-- but only if those mice were genetically susceptible (McIntyre et al. 2015). Perinatal exposure to the same chemical affects gene expression in a number of genes related to obesity and metabolism (Abrha and Suvorov, 2018). Environmentally relevant developmental exposures to BDE-47 permanently altered lipid uptake and accumulation in the liver of mice (Khalil et al. 2018). Exposure to BDE-47 exposure before conception and through weaning caused increased adult body weight in male but not in female offspring rats (Gao et al. 2019). Exposure to BDE-47 in the womb and via milk worsened the obesity caused by a high-fat diet, impaired glucose levels, and affected the gut microbiome as well (Wang et al. 2018). In rats, early exposure to BDE-47 led to epigenetic changes in the liver that are related to metabolism, insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (Suvorov et al. 2019).
Exposure to DE-71, a mixture of PBDEs, caused high fasting blood sugar and glucose intolerance in offspring mice, with more minor effects on the mother mice (Kozlova et al. 2020).
In pregnant rats, exposure to Dechlorane Plus caused long-term changes to the gut microbiota and metabolic function in offspring (Zhang et al. 2020). Maternal exposure to BDE-47 and TBBPA also affected the gut microbiota of offspring mice as adults (Gomez et al. 2020), as did BDE-99 (Lim et al. 2021). PBDE-209 injured the colon of mice and was toxic to intestinal cells (Li et al. 2022).
The flame retardant (and plasticizer) triphenyl phosphate (TPhP) disrupts the metabolism of both mothers and fetuses when exposure occurs during pregnancy (Philbrook et al. 2018).
Perinatal exposure to decabromodiphenyl ethane (DBDPE), a kind of new brominated flame retardant, and a replacement for decaBDE, increased the risk of obesity in mouse offspring and affected triglyceride synthesis, mitochondrial function, and glucose metabolism; the effects were exacerbated by a high-fat diet (Yan et al. 2018).
Early life exposure to 2-ethylhexyl diphenyl phosphate (EHDPHP), a new type of organophosphate flame retardant, resulted in weight changes in male mice offspring, altered glucose tolerance, and caused liver damage, depending on dose and diet (Yan et al. 2020).
In mice, although maternal exposure to organophosphate flame retardants did not alter body weight, exposure did affect other things. Flame retardants increased systolic and diastolic blood pressure in male offspring, and interacted with a high fat diet to increase fasting glucose in females and alter glucose and insulin tolerance in male offspring (Walley et al. 2020a). These authors also found that developmental exposure to flame retardants did not affect adult body weight in mice, but exposed males fed a high-fat diet consumed more food and had lower activity than those unexposed, and there were other behavioral effects as well (Walley et al. 2020b).
Exposing zebrafish and their larvae to the flame retardant TCPP caused obesity, fatty liver, inflammation, oxidative stress, and potentially increased the risk of cancer (Yan et al. 2022).
In placental cells, the flame retardant triphenyl phosphate affects triglyceride levels and cause fat accumulation, among other things (Wang et al. 2021).
In Vitro Studies on Cells
Flame retardants can affect the insulin-producing beta cells in the pancreas. For example, BDE-47 and BDE-85 stimulate insulin secretion in beta cells (Karandrea et al. 2017).
The liver cells of fish exposed to various PBDEs and PBDE mixtures showed metabolic disturbances related to blood glucose control pathways (Søfteland et al. 2011).
In liver cells, organophosphorus flame retardants caused fat accumulation, linked to effects on mitochondria (Le et al. 2021).
In liver cells, the replacement chemicals TBBPS and TCBPA are more likely to disrupt liver function than the original flame retardant TBBPA (Yu et al. 2022).
BDE-99, the second most abundant PBDE flame retardant congener in human adipose tissue, increased fat levels in differentiating fat cells (Armstrong et al. 2020).
TBBPA promotes fat cell development (Chappell et al. 2018; Kakutani et al. 2018; Woeller et al. 2017). TBBPA as well as its derivatives and by-products, also promote fat cell changes that are linked to obesity (Liu et al. 2020).
Dechlorane Plus causes pre-fat cells to accumulate fat (Peshdary et al. 2018).
Firemaster 550 induces obesity in rodents. In human cells, it causes stem cells to turn into fat cells instead of bone cells (Pillai et al. 2014). For an article about this study, see More fat, less bone? Flame retardant may deliver a one-two punch, published in Environmental Health Perspectives (Nicole 2014). A further study found that Firemaster and two of its specific components can induce fat cell development in pre-fat cells (Tung et al. 2017).
Triphenyl phosphate (which is also used in nail polish), as well as its metabolite, enhance the differentiation of fat cells and affect the glucose uptake of fat cells (Cano-Sancho et al. 2017). Numerous organophosphorous flame retardants (which are used as replacements for PBDEs) promote cholesterol and triglyceride accumulation in human liver cells (Hao et al. 2019). BDE-47 and BDE-99 affect the expression of genes related to carbohydrate and lipid metabolism in liver cells (Zhang et al. 2020). Another organophosphate flame retardant/plasticizer, 2-Ethylhexyl diphenyl phosphate (EHDPP), induced fat cell formation in pre-fat cells (Sun et al. 2019 ).
New replacement flame retardants cause fat to accumulate in fat and liver cells (Maia et al. 2021).
According to a study of cells, some flame retardants can activate PPARγ (peroxisome proliferator-activated gamma receptor), which play a role in glucose metabolism as well as fat storage Riu et al. 2011). For an article on this study, see Warm reception? Halogenated BPA flame retardants and PPARγ activation, published by Environmental Health Perspectives (Barrett 2011). Additional flame retardants also activate PPARγ and may be obesogens, including PBDE 99 (Wen et al. 2019). In fact, most types of tested flame retardants (including PBDEs, phthalates, and phenols) have been shown to activate PPARγ -- as does house dust, which is high in flame retardant chemicals (Fang et al. 2015). Firemaster 550, a type of flame retardant mixture, also activates the PPARγ receptor, which may explain its potential to cause weight gain (Belcher et al. 2014).
Mixtures of flame retardants from house dust promoted fat development in vitro. There was also a positive association between dust-induced triglyceride accumulation and people's BMI (Kassotis et al. 2019).
Flame retardants released from waste water treatment plants have been linked to metabolic problems in fish living downstream (Dépatie et al. 2020).
Type 1 Diabetes
Could flame retardants affect the risk of type 1 diabetes? We don't know.
One animal study has found that treating adult male rats with the flame retardant BDE-209 for 8 weeks caused high blood sugar in those rats. A genetic analysis showed that BDE-209 induced changes in gene expression, including changes to some genes that are involved in type 1 diabetes, and some involved in autoimmune thyroid disease (common in people with type 1 diabetes). The link to type 1 was supported by a decrease in insulin levels in the rats. They also found immune system changes similar to type 1, as well as inflammation and oxidative stress (Zhang et al. 2013).
Animal studies confirm that PBDEs affect the immune system (e.g., Lv et al. 2015; Zheng et al. 2014), including immune stimulation (Koike et al. 2013), during development (Liu et al. 2012), and at low levels of exposure (Fair et al. 2012). One study found that mice exposed to PBDEs had lower levels of the immune cells (cytokines) important in the defense of coxsackie virus (Lundgren et al. 2009). (Coxsackie virus is one of the viruses linked to type 1 diabetes; see the viruses page). These authors have also found that PBDEs affect the course of a virus in mice, and that the virus caused a higher accumulation of PBDEs in the liver (Lundgren et al. 2013). PBDEs also affect the gut microbiota of mice (Li et al. 2018) and zebrafish (Chen et al. 2018) and the human microbiome in the lab (Cruz et al. 2020); changes to the gut microbiota are linked to type 1 diabetes (see the Diet and the Gut page). Now in fact a human study from Quebec, Canada, shows that mid-pregnancy levels of PBDEs in the mothers are linked to a child's gut microbiota composition in childhood (Laue et al. 2019). And New York boys with higher blood levels of BDE-153 had a higher risk of celiac disease, an autoimmune disease common in people with type 1 diabetes (Gaylord et al. 2020).
Tris exposure affected the gut microbiome community structure, microbial species, gut microbe associated gene expression and gut metabolites in mice (Yan et al. 2020).
There have been no human studies on type 1 diabetes and PBDEs, although I have met at least one person who found his child had high levels of PBDEs in blood after diagnosis with type 1. In Sweden, PBDEs were banned in the 1990s, and by the end of that decade, levels in Swedish women's breastmilk began to decline. (Overall, PBDE levels in the US are much higher than in Sweden). Curiously, Swedish children born beginning in the year 2000 show slightly lower risks of type 1 diabetes than those born earlier. (The incidence is still increasing in Swedish children, but not as rapidly). I wonder if these two trends could be related? (Howard 2011).
U.S. women with higher levels of BDE-47 and BDE-153 had a higher risk of gestational diabetes (Rahman et al. 2019). Another U.S. study found that pre-conception levels of PBDE-153 (but not other chemicals) were indeed linked to an increased risk of developing gestational diabetes (Smarr et al. 2016). Another study, from Iran, found that total PBDE levels were associated with gestational diabetes as well (Eslami et al. 2016). A study from China found that PBDE levels were associated with the development of gestational diabetes (Liu et al. 2018). A very small study of pregnant women in Shanghai, China, found that newer, organophosphate flame retardants were present in 100% of women, but were not associated with health effects, including gestational diabetes (Feng et al. 2016). I expect a larger sample size would be needed to show some associations.
A U.S. study from Cincinnati, Ohio, found that PBDEs were linked to higher glucose and cholesterol levels during pregnancy (Vuong et al. 2021).
In pregnant overweight or obese Californian women, PBDE levels were associated with lower fasting glucose and insulin levels, and lower insulin resistance (Mehta et al. 2020).