Science Selection is available at conformant HTML version ... · says Bruce Blumberg, a professor...
2
DDT and Obesity in Humans: Exploring the Evidence in a New Way Julia R. Barrett https://doi.org/10.1289/EHP2545 Although conventional wisdom holds that overeating and a sed- entary lifestyle are the main causes of obesity, increasing evi- dence 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 con- trolling 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 compli- cations. 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 persist- ence 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 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 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 mosqui- toes. 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. Environmental Health Perspectives 024003-1 A Section 508–conformant HTML version of this article is available at https://doi.org/10.1289/EHP2545. Science Selection
Transcript of Science Selection is available at conformant HTML version ... · says Bruce Blumberg, a professor...
DDT and Obesity in Humans: Exploring the Evidence in a New WayJulia R. Barrett
https://doi.org/10.1289/EHP2545
Although conventional wisdom holds that overeating and a sed-entary lifestyle are the main causes of obesity, increasing evi-dence indicates that additional risk may be conferred by exposureto obesogens, environmental chemicals suspected of influencingthe development and maintenance of adipose (fat) tissue.1,2,3,4
The insecticide dichlorodiphenyltrichloroethane (DDT) and itsbreakdown products are among many such suspected obesogens.2,5
A systematic review and meta-analysis in Environmental HealthPerspectives now concludes that the collective evidence supportsthe presumption that DDT is a human obesogen.5
The excess accumulation of body fat can cause adverse healtheffects including diabetes, cardiovascular disease, and cancer.2,6
Obesogens are thought to disrupt the molecular mechanisms con-trolling the development and maintenance of adipose tissue. Thisdisruption has the potential to produce larger and more numerousfat cells, which could in turn lead to obesity and related compli-cations.1,6 Obesogens can also alter programing of metabolic setpoints, appetite, and satiety.6
From the 1940s to the 1970s, DDT was used widely to controlmosquitoes and the diseases they transmit.7,8 As a result of concerns
about its adverse effects on wildlife and humans and its persist-ence in the environment, its use was largely banned,7,8 althoughit is still used in some countries to fight mosquito-borne diseases.9
Despite the relatively limited use today, DDT is highly persistent inthe human body, and most people throughout the world carry atleast traces of it and its metabolites in their bodies.5,8
The current review evaluated the body of research on DDT as anobesogen using what is known as the Grading of RecommendationsAssessment, Development, and Evaluation (GRADE) approach. Theauthors applied this approach with guidance from two sources: theHandbook for Conducting a Literature-Based Health Assessmentpublished by the National Toxicology Program Office of HealthAssessment and Translation (OHAT),10 and the Navigation Guidedeveloped by a work group of nearly two dozen environmentalhealth experts.11
The GRADE approach originated as a means of methodicallyand rigorously assessing human studies in clinical medicine andpublic health. The OHAT Handbook and Navigation Guide adaptthis approach to integrate lines of evidence from epidemiological,animal, and in vitro studies. Investigators can then systematically
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 mosqui-toes. 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.
Environmental Health Perspectives 024003-1
A Section 508–conformant HTML version of this articleis available at https://doi.org/10.1289/EHP2545.Science Selection
assess the findings of various studies and conclude how stronglythey collectively support a particular conclusion.
“This kind of hazard identification that integrates across ex-perimental systems and human systems has not been done for anobesogen before,” says review coauthor Michele A. La Merrill,an assistant professor of environmental toxicology at the Universityof California, Davis. “I think it is important, because as the firststudy to really do this for obesogens, it adds legitimacy to this newand emerging field that not everyone is familiar with or necessarilybelieves has real scientific merit,” she says.
For the current review, La Merrill and colleagues searchedfor literature related to whether exposure to DDT may increaseobesity in humans, following a protocol they developed prior toconducting this review. The researchers first identified studiespertaining to DDT and obesity, markers of obesity, or underlyingmechanisms of obesity in human epidemiological research, ani-mal experiments, and in vitro investigations. Human evidenceand in vivo assessments of adiposity in animals made up the pri-mary evidence for evaluating the DDT–obesity relationship. Invitro assessment of adipocyte development and in vivo studies ofenergy balance, lipids, and molecular markers were consideredsupporting evidence potentially informing the biological plausi-bility of findings in the primary evidence.
The authors graded each category of evidence based on fac-tors such as risk of bias in study design, inconsistency amongstudies, and imprecision. They judged that both the relevanthuman epidemiology and the primary in vivo toxicology consti-tuted a moderate level of evidence, which along with a moderatelevel of supporting evidence led to the overall conclusion thatDDT can be presumed to be a hazard to humans, namely byincreasing the risk of obesity.5
The researchers also identified epidemiological and experi-mental research needs for refining understanding of the DDT–obesity relationship and protecting public health. Gaps in currentresearch, such as the limited assessment of dose–response rela-tionships and a dearth of prospective epidemiological data, pre-vent more definitive conclusions.
“I think the authors made reasonable conclusions and eval-uated the strengths and weaknesses of their study appropriately,”says Bruce Blumberg, a professor of developmental and cell biol-ogy at the University of California, Irvine, and a pioneer in thestudy of obesogens. “This paper is notable for the thoroughnessof the analysis and the transparency of the methodology.” Blumbergwas not involved in the review.
The study serves as a model for deriving conclusions fromresearch on other obesogens, notes Blumberg. For him, the cur-rent paper is proof of principle for the impact that such analyseswill have once additional prospective cohort studies have beenconducted on known obesogens.
Julia R. Barrett, MS, ELS, a Madison, Wisconsin–based science writer and editor, isa member of the National Association of Science Writers and the Board of Editors inthe Life Sciences.
References1. Janesick AS, Blumberg B. 2016. Obesogens: an emerging threat to public
health. Am J Obstet Gynecol 214(5):559–565, PMID: 26829510, https://doi.org/10.1016/j.ajog.2016.01.182.
2. Heindel JJ, Newbold R, Schug TT. 2015. Endocrine disruptors and obesity. NatRev Endocrinol 11(11):653–661, PMID: 26391979, https://doi.org/10.1038/nrendo.2015.163.
3. Brown RE, Sharma AM, Ardern CI, Mirdamadi P, Mirdamadi P, Kuk JL. Seculardifferences in the association between caloric intake, macronutrient intake,and physical activity with obesity. Obes Res Clin Pract 10(3):243–255, PMID:26383959, https://doi.org/10.1016/j.orcp.2015.08.007.
4. Klimentidis YC, Beasley TM, Lin H-Y, Murati G, Glass GE, Guyton M, et al. 2011.Canaries in the coal mine: a cross-species analysis of the plurality of obesityepidemics. Proc Biol Sci 278(1712):1626–1632, PMID: 21106594, https://doi.org/10.1098/rspb.2010.1890.
5. Cano-Sancho G, Salmon AG, La Merrill MA. 2017. Association between expo-sure to p,p0-DDT and its metabolite p,p 0-DDE with obesity: integrated system-atic review and meta-analysis. Environ Health Perspect 125(9):096002, PMID:28934091, https://doi.org/10.1289/EHP527.
6. Levian C, Ruiz E, Yang X. 2014. The pathogenesis of obesity from a genomic andsystems biology perspective. Yale J Biol Med 87(2):113–126, PMID: 24910557.
7. Bouwman H, van den Berg H, Kylin H. 2011. DDT and malaria prevention:addressing the paradox. Environ Health Perspect 119(6):744–747, PMID: 21245017,https://doi.org/10.1289/ehp.1002127.
8. Eskenazi B, Chevrier J, Rosas LG, Anderson HA, Bornman MS, Bouwman H,et al. 2009. The Pine River statement: human health consequences of DDT use.Environ Health Perspect 117(9):1359–1367, PMID: 19750098, https://doi.org/10.1289/ehp.11748.
9. van den Berg H, Manuweera G, Konradsen F. 2017. Global trends in the pro-duction and use of DDT for control of malaria and other vector-borne diseases.Malaria J 16:401, PMID: 28982359, https://doi.org/10.1186/s12936-017-2050-2.
10. OHAT (Office of Health Assessment and Translation). 2015. Handbook forConducting a Literature-Based Health Assessment Using OHAT Approachfor Systematic Review and Evidence Integration. Washington, DC:NationalToxicology Program. https://ntp.niehs.nih.gov/ntp/ohat/pubs/handbookjan2015_508.pdf [accessed 12 January 2018].
11. Woodruff TJ, Sutton P. Navigation Guide Work Group. 2011. An evidence-based medicine methodology to bridge the gap between clinical and environ-mental health sciences. Health Aff (Millwood) 30(5):931–937, PMID: 21555477,https://doi.org/10.1377/hlthaff.2010.1219.
Environmental Health Perspectives 024003-2
