Heavy Metal Exposure and Metabolic Syndrome: Evidence from Human and Model System Studies

Abstract

Data from 36 epidemiological studies involving 17 unique countries/regions and 13 studies leveraging model systems are included in this review. Epidemiological and model system studies support a possible association between heavy metal exposure and MS or comorbid conditions; however, results remain conflicting. Epidemiological studies were predominantly cross-sectional and collectively, they highlight a global interest in this question and reveal evidence of differential susceptibility by sex and age to heavy metal exposures. In vivo studies in rats and mice and in vitro cell-based assays provide insights into potential mechanisms of action relevant to MS including altered regulation of lipid and glucose homeostasis, adipogenesis, and oxidative stress. Heavy metal exposure may contribute to MS or comorbid conditions; however, available data are conflicting. Causal inference remains challenging as epidemiological data are largely cross-sectional; and variation in study design, including samples used for heavy metal measurements, age of subjects at which MS outcomes are measured; the scope and treatment of confounding factors; and the population demographics vary widely. Prospective studies, standardization or increased consistency across study designs and reporting, and consideration of molecular mechanisms informed by model system studies are needed to better assess potential causal links between heavy metal exposure and MS.

RW‐2018—Research Workshop: The Effect of Nutrition on Epigenetic Status, Growth, and Health

“…These are markers for metabolic syndrome (type 2 diabetes mellitus, hypertension, obesity, and cardiovascular disease). However, human clinical studies have been inconsistent in demonstrating a clear link between cardiometabolic impairment/metabolic syndrome and cadmium exposure …”

“…Lead was associated with lower birth weight, accelerated growth in early childhood, and prehypertension. These are all early indicators of cardiometabolic syndrome in childhood …”

“…Unlike low doses of radiation, which appear to stimulate hormesis in the agouti mouse model, lead and cadmium even at low levels of exposure are associated with lower birth weight, increased preterm births, and accelerated catchup growth. 40,41 In vivo and in vitro models indicate increased adipocyte numbers and decreased insulin-dependent glucose uptake. These are markers for metabolic syndrome (type 2 diabetes mellitus, hypertension, obesity, and cardiovascular disease).…”

“…However, human clinical studies have been inconsistent in demonstrating a clear link between cardiometabolic impairment/metabolic syndrome and cadmium exposure. [40][41][42] Unlike in the situations of massive exposures and poisonings, strategies to reduce the risk of low-level exposures through supplementation with essential metals and nutrients such as iron, selenium, calcium, and folate are of minimal benefit. Furthermore, the presence of other micronutrients that are part of a multivitamin regimen, such as zinc, copper, magnesium, and manganese, can increase serum levels of both cadmium and lead.…”

“…These are all early indicators of cardiometabolic syndrome in childhood. 39,40,42 So what do you do when you have association results? The possibility of confounding by difficult-to-measure, nonchemical stressors that co-occur with poverty and ethnic minority status makes it very difficult to advocate for a policy to reduce exposure, since cause and effect is difficult to infer.…”