Researchers find significant association between phthalate levels and chronic disease in men

In men, a positive association may exist between total phthalate levels and cardiovascular disease, type 2 diabetes, hypertension, and increased levels of biomarkers of chronic low-grade inflammation, according to Australian researchers, who published their results in the international journal Environmental Research.

"We found that the prevalence of cardiovascular disease, type-2 diabetes, and high blood pressure increased among those men with higher total phthalate levels," said senior author Zumin Shi, associate professor, senior research fellow, Adelaide Medical School, and the Freemasons Foundation Centre for Men's Health, School of Medicine, University of Adelaide, Adelaide, South Australia, Australia, and member, SAHMRI's Nutrition & Metabolism theme. "In addition to chronic diseases, higher phthalate levels were associated with increased levels of a range of inflammatory biomarkers in the body," he added.

Phthalate concentrations are directly associated with both age and Western diets; and in previous studies, men who ate less fresh fruit and vegetables, more processed, packaged foods, and drank more carbonated soft drinks had higher urinary phthalate levels.

"While we still don't understand the exact reasons why phthalates are independently linked to disease, we do know the chemicals impact on the human endocrine system, which controls hormone release that regulates the body’s growth, metabolism, and sexual development and function,” noted Shi.

To that end, Shi and colleagues undertook this study to assess any associations between urinary total phthalate concentrations, chronic low-grade inflammation, and non-communicable diseases. They included 1,504 South Australian men, aged 39 to 84, who supplied a urinary sample during a follow-up visit for the Men's Androgen Inflammation Lifestyle Environment and Stress (MAILES) study. Subjects were randomly-selected, urban-dwelling, community-based men living in Adelaide, Australia (N=2,038).

In fasting morning urine samples, these researchers quantified total phthalate concentration, and assessed chronic diseases via self-reported questionnaire or via standard clinical and laboratory procedures. Finally, they assayed inflammatory biomarkers by ELISA or spectroscopy.

In 99.6% of urinary samples, total phthalates were detectable in men aged 35 and older, with a mean of 114.1 µg/g creatinine (95% CI: 109.5-118.9). Researchers found that higher total phthalate levels were associated with higher levels of high-sensitivity C-reactive protein (hs-CRP), IL-6 (all P < 0.05), and TNF-?, but not myeloperoxidase (MPO), all markers of inflammation, and oxidative processes.

They also found a positive association between urinary total phthalate concentrations and cardiovascular disease, type 2 diabetes, and hypertension.

In comparisons of extreme quartiles of total phthalate, the prevalence ratios were 1.78 for cardiovascular disease (95% CI: 1.17-2.71; P-trend=0.001); 1.84 for type 2 diabetes (95% CI: 1.34-2.51; P-trend=0.001); and 1.14 for hypertension (95% CI: 1.01-1.29; P-trend=0.013). They found no significant associations between total phthalates and asthma and depression.

"Importantly, while 82% of the men we tested were overweight or obese – conditions known to be associated with chronic diseases – when we adjusted for this in our study, the significant association between high levels of phthalates and disease was not substantially altered," said Shi. "In addition, when we adjusted for socio-economic and lifestyle factors such as smoking and alcohol, the association between high levels of phthalates and disease was unchanged."

Shi added that while this study was conducted in men, the findings are also likely to be relevant to women.

"While further research is required, reducing environmental phthalates exposure where possible, along with the adoption of healthier lifestyles, may help to reduce the risk of chronic disease," Shi concluded.

This research was supported by the National Health and Medical Research Council (NHMRC).