DDT and Obesity in Humans: Exploring the Evidence in a New Way.

Although conventional wisdom holds that overeating and a sedentary lifestyle are the main causes of obesity, increasing evidence indicates that additional risk may be conferred by exposure to obesogens, environmental chemicals suspected of influencing the development and maintenance of adipose (fat) tissue.1,2,3,4 The insecticide dichlorodiphenyltrichloroethane (DDT) and its breakdown products are among many such suspected obesogens.2,5 A systematic review and meta-analysis in Environmental Health Perspectives now concludes that the collective evidence supports the presumption that DDT is a human obesogen.5

The excess accumulation of body fat can cause adverse health effects including diabetes, cardiovascular disease, and cancer.2,6 Obesogens are thought to disrupt the molecular mechanisms controlling the development and maintenance of adipose tissue. This disruption has the potential to produce larger and more numerous fat cells, which could in turn lead to obesity and related complications.1,6 Obesogens can also alter programing of metabolic set points, appetite, and satiety.6

From the 1940s to the 1970s, DDT was used widely to control mosquitoes and the diseases they transmit.7,8 As a result of concerns about its adverse effects on wildlife and humans and its persistence in the environment, its use was largely banned,7,8 although it is still used in some countries to fight mosquito-borne diseases.9 Despite the relatively limited use today, DDT is highly persistent in the human body, and most people throughout the world carry at least traces of it and its metabolites in their bodies.5,8

U.S. Marines dust their clothing with DDT shortly before landing on Iwo Jima in February 1945. For several decades DDT was widely used to fight mosquitoes. Although the insecticide has been largely banned around the world, it is still used in some Asian and African countries to control malaria. Image: U.S. National Archives.

The current review evaluated the body of research on DDT as an obesogen using what is known as the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The authors applied this approach with guidance from two sources: the Handbook for Conducting a Literature-Based Health Assessment published by the National Toxicology Program Office of Health Assessment and Translation (OHAT),10 and the Navigation Guide developed by a work group of nearly two dozen environmental health experts.11

The GRADE approach originated as a means of methodically and rigorously assessing human studies in clinical medicine and public health. The OHAT Handbook and Navigation Guide adapt this approach to integrate lines of evidence from epidemiological, animal, and in vitro studies. Investigators can then systematically assess the findings of various studies and conclude how strongly they collectively support a particular conclusion.

“This kind of hazard identification that integrates across experimental systems and human systems has not been done for an obesogen before,” says review coauthor Michele A. La Merrill, an assistant professor of environmental toxicology at the University of California, Davis. “I think it is important, because as the first study to really do this for obesogens, it adds legitimacy to this new and emerging field that not everyone is familiar with or necessarily believes has real scientific merit,” she says.

For the current review, La Merrill and colleagues searched for literature related to whether exposure to DDT may increase obesity in humans, following a protocol they developed prior to conducting this review. The researchers first identified studies pertaining to DDT and obesity, markers of obesity, or underlying mechanisms of obesity in human epidemiological research, animal experiments, and in vitro investigations. Human evidence and in vivo assessments of adiposity in animals made up the primary evidence for evaluating the DDT–obesity relationship. In vitro assessment of adipocyte development and in vivo studies of energy balance, lipids, and molecular markers were considered supporting evidence potentially informing the biological plausibility of findings in the primary evidence.

The authors graded each category of evidence based on factors such as risk of bias in study design, inconsistency among studies, and imprecision. They judged that both the relevant human epidemiology and the primary in vivo toxicology constituted a moderate level of evidence, which along with a moderate level of supporting evidence led to the overall conclusion that DDT can be presumed to be a hazard to humans, namely by increasing the risk of obesity.5

The researchers also identified epidemiological and experimental research needs for refining understanding of the DDT–obesity relationship and protecting public health. Gaps in current research, such as the limited assessment of dose–response relationships and a dearth of prospective epidemiological data, prevent more definitive conclusions.

“I think the authors made reasonable conclusions and evaluated the strengths and weaknesses of their study appropriately,” says Bruce Blumberg, a professor of developmental and cell biology at the University of California, Irvine, and a pioneer in the study of obesogens. “This paper is notable for the thoroughness of the analysis and the transparency of the methodology.” Blumberg was not involved in the review.

The study serves as a model for deriving conclusions from research on other obesogens, notes Blumberg. For him, the current paper is proof of principle for the impact that such analyses will have once additional prospective cohort studies have been conducted on known obesogens.