Weight gain is multifactorial, influenced by genetics, nutrition, behavior, socioeconomic factors, and a person’s environment. While it is widely accepted that weight gain involves more than just "calories in versus calories out", its etiology remains widely misunderstood. In recent research, the role of toxin exposure in weight gain is being brought to the forefront. 

Industrialization has introduced persistent organic pollutants (POPs) and heavy metals into the air, water, and food chain. Chronic exposure, ingestion, and inhalation of these pollutants have been associated with the development of obesity, diabetes, cardiovascular disease, and chronic respiratory disease. Moreover, lipophilic (fat-soluble) environmental pollutants, such as POPs, pesticides, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), have been shown to accumulate in adipose tissue after exposure. 

Endocrine-disrupting chemicals (EDCs) are aptly named as they disrupt endocrine function and interfere with endogenous hormone receptors and programming. Synthetic EDCs are found in pesticides, fungicides, flame retardants, plastic, food wrappers, solvents, and metals. In vitro and in vivo studies suggest synthetic EDCs affect multiple bodily systems, including the reproductive, immune, and central nervous systems.

“Obesogens” are a subset of EDCs — chemicals shown to disrupt lipid homeostasis and hormone receptors through epigenetic, structural, and functional mechanisms. Obesogens may disturb the normal functioning of energy homeostasis, lipid metabolism, appetite regulation, and adipogenesis. Thus, the obesogen hypothesis proposes that obesogenic EDC chemicals may lead to increased lipid storage and greater susceptibility to weight gain. Systemic exposure to certain EDCs may also be potentially associated with adverse obesity-related health outcomes, such as metabolic syndrome, insulin resistance, prediabetes, diabetes, oxidative stress, and hypertension.

The total number of obesogen EDCs is unknown. However, ones that have been identified as possible obesogens include diethylstilbestrol (DES), bisphenol A (BPA), phthalates, organotins, PBDEs, polyfluoroalkyl chemicals (PFCs), organochlorine pesticides (OCs), and PCBs, and some heavy metals like arsenic and cadmium.

Current research is investigating the influence of obesogens on disrupting the gut microbiome, modifying neurotransmitter signaling and sensitivity, and altering sympathetic nervous system activity. It is proposed that exposure to these chemicals during fetal or infancy periods may have long-lasting effects throughout adulthood. However, more research is needed on this subject. 

Many obesogen EDCs also fall under the category of POPs. POPs are known to accumulate in adipose tissue, and their concentration has been found to be higher in obese individuals than in lean subjects. Examples of POPs include dioxins, OCs, PBDEs, and PCBs. They are referred to as “persistent” because once released in the environment, they resist degradation and persist in the air, water, soil, and living organisms.

Rapid, extreme weight loss has been shown to increase POP levels in the bloodstream, as weight loss may potentially liberate POPs from fatty tissue into circulation. This may help explain why rapid weight loss can be associated with adverse health effects in certain individuals. 

While there is the risk of increasing lipophilic toxins from adipose tissue into the bloodstream during any weight loss journey, obesity is a major risk factor in non-communicable diseases, such as diabetes and cardiovascular disease. Moreover, extreme, rapid weight loss may only be necessary for some and should be performed under medical supervision. A clinical study with 401 overweight and obese adults observed that weight loss between 5% and 10% of initial body weight significantly improved cardiometabolic risk factors, such as fasting glucose, triglycerides, and total cholesterol. 

Hence, gradual weight loss may be more clinically beneficial in limiting toxin release from adipose tissue. Furthermore, optimally functioning detoxification involving the liver, kidney, and gastrointestinal system is necessary to help mitigate the reabsorption of POPs and other toxins during an individual’s weight loss journey. 

Further research is needed to explore the role of toxins in weight gain, particularly around obesogenic EDCs. Limiting exposure to obesogenic EDCs and other potentially harmful toxins is the first step to helping reduce the overall toxic burden in patients. Additionally, a holistic plan for sustainable weight management must promote optimal detoxification to support the mobilization and elimination of lipophilic toxins from the body. Patients should work with their healthcare practitioner to create a sustained, individualized weight loss plan considering potential toxin exposure and optimal detoxification pathways.   

By Danielle Moyer Male, MS, CNS LDN