title: Is dietary nitrate/nitrite exposure a risk factor for development of thyroid abnormality? A systematic review and meta-analysis.
abstract: The potential effects of inorganic nitrate/nitrite on global health are a much debated issue. In addition to possible methemoglobinemia and carcinogenic properties, anti-thyroid effects of nitrate/nitrite have been suggested. Considering the growing significance of nitrate/nitrite and since there is no comprehensive review in data available, clarifying the effect of nitrate/nitrite on thyroid disorder outcomes is essential. Therefore, we conducted this systematic review of experimental and clinical studies, and a meta-analysis of relevant cohort and cross-sectional studies investigating the association of nitrate/nitrite exposure and thyroid function. Most animal studies show that high exposure (~10-600 times of acceptable daily intake) to nitrate/nitrite induces anti-thyroid effects, including decreased serum level of thyroid hormones and histomorphological changes in thyroid gland; however no similar observations have been documented in humans. Based on our meta-analysis, no significant association was observed between nitrate exposure and the risk of thyroid cancer, hyper- and hypothyroidism; findings from three cohort studies however showed a significant association between higher exposure to nitrite and the risk of thyroid cancer (risk = 1.48, 95% confidence interval = 1.09-2.02, P = 0.012). Additional research is needed to clarify the association between nitrate/nitrite exposures and both thyroid function and cancer.
authors.affiliation: Nutrition and Endocrine Research Center, Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Bahadoran
authors.affiliation: Department of Clinical Nutrition and Dietetics, Faculty of Nutrition Sciences and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Parvin
authors.initials: P
authors.lastname: Mirmiran
authors.affiliation: Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Ghasemi@endocrine.ac.ir.
authors.forename: Asghar
authors.initials: A
authors.lastname: Ghasemi
authors.affiliation: Minimally Invasive Surgery Research Center; Iran University of Medical Sciences, Tehran, Iran; Department of Epidemiology, School of Public Health, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Kabir
authors.affiliation: Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fereidoun
authors.initials: F
authors.lastname: Azizi
authors.affiliation: Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Farzad
authors.initials: F
authors.lastname: Hadaegh
mesh_terms: D000818:Animals; D003430:Cross-Sectional Studies; D004032:Diet / Q000009:adverse effects*; D006801:Humans; D009566:Nitrates / Q000008:administration & dosage / Q000009:adverse effects*; D009573:Nitrites / Q000008:administration & dosage / Q000009:adverse effects*; D012307:Risk Factors; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*
chemical_list: D009566:Nitrates; D009573:Nitrites
keywords: Goiter; Nitrate; Nitrite; Thyroid cancer; Thyroid function