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Nutritional and Environmental Contaminant Exposure: A Tale of
Two Co-Existing Factors for Disease Risks
Yichao Huang and Mingliang Fang*
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I n the quest to understand factors contributing to the
etiology of noncommunicable diseases such as diabetes,
heart disease and obesity, it is increasingly apparent that the
consideration of nutrition, diet and lifestyle alongside exposure
to environmental contaminants should be investigated
collectively. On the one hand, nutritional epidemiology
explores how an imbalanced diet, compounded by disease-
promoting lifestyles, is contributing to the substantial epidemic
of many metabolic syndromes. On the other hand, environ-
mental epidemiology seeks to understand how exposure to
environmental contaminants may impact human health.
Environmental toxicants of concern include particulate
matters, persistent organic pollutants such as organochlorine
pesticides, perfluoroalkyl and polyfluoroalkyl substances
(PFASs), brominated fire retardants, plasticizers, heavy metals,
and other emerging contaminants. The individual and totality
of these pollutant exposures further complicates the study of
adverse health consequences, and the study of individual health
risks particularly challenging. In this viewpoint, we propose
that both dietary nutrition and environmental contaminant
exposure are two factors that are intertwined intrinsically in
health outcomes, and synergistic and confounding effects of
© 2020 American Chemical Society
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nutritional and environmental exposure, on chronic disease
etiology should be researched together.
Previous research has investigated the contribution of
“exposome”, or nongenetic, long-term exposure to different
environments as risk factors in the onset of noncommunicable
diseases.1 Despite this concept of holistic understanding of
exposome and disease risk exists,2,3 current epidemiological
studies of nutritional and environmental factors as two key
components in disease risks continue to be investigated
separately rather than collectively. It has been well documented
in literature that high-fat, high-sugar, high-protein diets alone
or in combination could induce inflammation and oxidative
stress in animal studies.4 Elevated levels of oxidative stress have
also been demonstrated to be critical in the pathogenesis of
metabolic disorders including obesity5 and type 2 diabetes
mellitus.6 Concurrently and independently, research on the
environmental exposure of toxicants in humans has increased
substantially over the last three decades, as shown in Figure 1.
Food has consistently been shown to be a dominant source of
exposure to the majority of environmental contaminants of
health concern including bisphenol analogues,7 phthalates,8
PFASs,9 polychlorinated biphenyl (PCBs),10 particulate
matter,11 parabens,12 heavy metals,13 as well as other emerging
contaminants, although other exposure conduits including via
air, soil and dust, water, and dermal adsorption may also
constitute significant contributions. Many studies14−16 includ-
ing our own work17 have demonstrated significant correlations
between exposure levels of environmental pollutants and
significantly elevated levels of oxidative stress. The over-
whelming number of studies in this area (Figure 1) have all
suggested compromised immune responses to exogenous
stimuli, and increased free radicals. One should acknowledge
that these studies have laid solid mechanistic foundations for
the understanding of exogenous stressors and disease etiology
in humans. These research works also suggest differing health
risks of each pollutant toward different population groups, and
offer recommendations for authorities and policy makers
Received: August 22, 2020
Published: November 12, 2020
https://dx.doi.org/10.1021/acs.est.0c05658
Environ. Sci. Technol. 2020, 54, 14793−14796
Environmental Science & Technology
Figure 1. Number of papers on each topic relating to environmental exposure and oxidative stress recorded from Pubmed (pubmed.ncbi.nlm.nih.
gov) between 1975 and 2020. Data was retrieved on July 19, 2020. BW, body weight. OS, oxidative stress.
regarding restrictions and safety doses. Being able to adjust for
the additional “matrix effect” from nutrition, diet and lifestyle
becomes essential in understanding the real relative risks of
environmental pollutants residing in food matrices leading to
oxidative stress in human cohort studies.
Another common feature in the occurrence and develop-
ment of these noncommunicable diseases is chronic subclinical
inflammation, which is manifested with long-term alterations
of systemic levels of immune mediators (i.e., higher level of
proinflammatory cytokines).18 An imbalanced diet, for
example, can lead to significantly increased ratios of omega-6
to omega-3 fatty acids in the diet, that has been shown to
increase pro-inflammatory eicosanoid mediators in the body,
and may cause prolonged elevation in inflammatory
cytokines.19 Meanwhile, environmental contaminants includ-
ing phthalates and bisphenols may also cause continuous
upregulation of inflammatory immune responses toward these
xenobiotic substances, resulting in eventual chronic diseases.20
Among other mechanisms, these nutrients and metabolites
may both partially share similar molecular targets such as
peroxisome proliferator-activated receptors (PPARs) that can
regulate inflammation.21
In addition to oxidative stress and subclinical inflammation,
the obesogenic characteristics of endocrine disrupting
chemicals (EDCs) by both environmental exposure as well
as overnutrition further suggests the probability of shared
contribution to noncommunicable diseases. A wide range of
EDCs particularly the “environmental obesogens” such as
bisphenol A, phthalates, and PFASs22 have been suggested to
be able to interfere with endocrine signaling pathway and
disrupt sensitive metabolic processes and eventually lead to
obesity, type 2 diabetes and other metabolic syndromes.23
These environmental obesogens may predispose individuals to
enhanced weight gain via the promotion of fat storage and
alteration of basal metabolic rate,22 although they can also
partially act through induction of oxidative stress. Despite the
prominent contribution to obesity and type 2 diabetes by
excessive calorie intake, obesogenic effect by these chemicals
may still persist even with restricted diet and improved
lifestyles.22
An additional consideration is that many of the environ-
mental toxicants listed above tend to accumulate in fats during
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food processing and consequently in the fatty tissues of animal
bodies due to their hydrophobicity.24 Thus, variations in food-
type consumption and resultant exposure to additional levels of
contaminant toxicants may become a significant confounding
factor, particularly in ‘western diets” which contains high
protein and fat. The overconsumption of calories via fat may
result in increased exposures to toxicants and an increased
body-exposure burden and related metabolic disorders. A
significant challenge is estimating total food/energy (i.e., fats,
carbohydrates, and proteins) intake, which directly correlates
to increased energy storage and adiposity. Optimized food
frequency questionnaires (FFQs) have been developed and
applied in many epidemiological studies;25 however, the
obvious difficulty in collecting these data limits their wider
applications. Objective assessment of dietary factors is a rapidly
evolving area where environment and nutrition methodologies
can help, such as using liquid chromatography−mass
spectrometry (LC-MS) to quantify nutrient intake from food
biomarkers.26 Future work is needed to establish streamlined
and validated methodologies to estimate the entire food-bound
exposome, for comprehensive epidemiological research.
■
RECOMMENDATIONS
In summary, we propose it is essential to conduct
epidemiological investigations on chronic disease etiology by
considering both environmental exposure of toxicants in
conjunction with dietary nutrition and lifestyle investigations,
using appropriate statistical considerations and methodology.
The concept is that the whole food exposome, nutrition, and
environmental contaminants, may collectively exert perturba-
tions to humans, via combined or confounding effects, rather
than merely by nutrient or food contaminant intake alone. In
epidemiological studies, the ideal statistical model necessitates
the inclusion of covariates with ample sample size for achieving
sufficient statistical power. We believe that epidemiologists
from these two fields should aim to consolidate these exposure
covariates, that is, the totality of exposome, in search of true
disease risk factors (Figure 2). It is with this indivisible nature
of both confounding factors that we recommend for more
comprehensive consideration of the entire food exposome in
association with disease risks.
https://dx.doi.org/10.1021/acs.est.0c05658
Environ. Sci. Technol. 2020, 54, 14793−14796
Environmental Science & Technology
Figure 2. Proposed research workflow for consideration of the totality
of food exposome in environmental health research in humans.
■ AUTHOR INFORMATION
Corresponding Author
Mingliang Fang − School of Civil and Environmental
Engineering, Nanyang Technological University, Singapore
639798; orcid.org/0000-0002-2204-9783; Phone: +65
6790 5331; Email: mlfang@ntu.edu.sg
Author
Yichao Huang − School of Environment, Jinan University,
Guangdong, Guangzhou, P. R. China 511443; orcid.org/
0000-0003-1186-1300
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.est.0c05658
Notes
The authors declare no competing financial interest.
■
ACKNOWLEDGMENTS
We thank the Editors of ES&T, Julie Beth Zimmerman and
Margaret Mills, for excellent suggestions, feedback, and input
on this Viewpoint. We thank Dr Xiongfei Pan from Vanderbilt
University Medical Center and Professor Heather Stapleton
from Nicholas School of the Environment, Duke University for
helpful comments. YH was funded by Guangdong Basic and
Applied Basic Research Foundation, China (No.
2019A1515110317), and MF was funded by the Singapore
Ministry of Education Academic Research Fund Tier 1
(04MNP000567C120).
■
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