Contents lists available at ScienceDirect Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb Dietary phosphorus enhances inflammatory response: A study of human gingivitis J. Max Goodson a , Ping Shi a , Mohammed S. Razzaque a,b,c, ⁎ a Department of Applied Oral Sciences, Forsyth Institute, Harvard School of Dental Medicine Affiliate, Cambridge, MA, USA b College of Advancing & Professional Studies (CAPS), University of Massachusetts Boston (UMB), Boston, MA, USA c Department of Pathology, Lake Erie College of Osteopathic Medicine, Erie, PA, USA ARTICLE INFO Keywords: Phosphate Cytokines Inflammation Sweetened beverages ABSTRACT Phosphates are associated with numerous disorders, ranging from vascular calcification to premature aging, possibly because of an increased inflammatory response. We therefore investigated the association of dietary phosphorus with gingivitis. We analyzed consumption of both phosphorus and sugar and related it to the concentrations of inflammatory biomarkers in saliva samples collected from 8314 children (mean age, 9.99 ± 0.68 years). About 64% of the children consumed more than 1250 mg phosphorus daily, and 34% consumed more than 82 g of sugar daily. Gingivitis was prevalent, with an average of 74% of possible gingival sites considered red. Quantile regression analysis revealed a statistically significant correlation between the occurrence of gingivitis and calorie-adjusted phosphorus intake and between gingivitis and calorie-adjusted sugar intake (both significant either as a linear trend or a categorical variable). In a subset (n = 744) in- vestigation of nutrient consumption related to salivary biomarkers, we found that elevated calorie-adjusted phosphorus intake was directly associated with salivary IL-1β concentration (OR1.40, 95% CI 1.04–1.89), and inversely associated with salivary IL-4 concentration (OR0.62, 95% CI 0.46–0.84). Sugar intake was not sig- nificantly associated with either biomarker. Thus, elevated dietary phosphorus consumption may influence in- flammatory disease by altering cytokine levels. 1. Introduction Gingivitis is the most common human gum disease, causing swel- ling, redness, and bleeding of tissues surrounding the teeth [1]. Without treatment, it can contribute to the development of more serious peri- odontal diseases and tooth loss [2]. Importantly, gingivitis is not just a disease seen in adults and the elderly. In large, international studies of dental health, the vast majority of children and adolescents are reported to have signs of mild-to-moderate gingival inflammation [3], making management and prevention an important public health concern. The exact pathogenesis is not fully understood [4]. It is recognized that many factors, including smoking or using chewing tobacco, certain medications (oral contraceptives, steroids, anticonvulsants, calcium channel blockers, chemotherapy, etc.), and bacterial infection, can in- teract to trigger oral inflammatory events which facilitate the devel- opment of gingivitis [5,6]. Genetic, environmental, and nutritional predisposing factors can also contribute to the intensity of oral in- flammation following an insult [7–9]. For example, numerous studies have shown a positive association between the consumption of sugar- sweetened beverages (SSBs) and oral diseases in children and adoles- cents, including gingivitis [10–15]. In a study of 100 healthy primary school children in Australia who consumed sweetened foods and bev- erages, around 50% showed visible plaque/gingivitis upon clinical dental examination [15]. While such an association has historically been thought to be due to the high sugar content of the SSBs and/or sweetened foods, these items (particularly SSBs) also often contain very high levels of phosphate [16]. Because elevated dietary phosphorus consumption can induce an inflammatory microenvironment [17,18], it is reasonable to consider that excessive phosphorus intake might propagate and aggravate gin- givitis. Indeed, excessive phosphorus intake is very common [19–21]. Of clinical significance, inorganic phosphate is absorbed at a higher rate than the organic phosphate, and is more likely to induce more in- flammatory responses. In the United States, the recommended dietary allowance (RDA) of phosphorus is 1250 mg per day for children be- tween the ages of 9 to 18 years, and 700 mg per day for adults and the https://doi.org/10.1016/j.jsbmb.2019.01.023 Received 9 November 2018; Received in revised form 29 January 2019; Accepted 31 January 2019 Abbreviations: BMI, body mass index; RDA, recommended dietary allowance; SSBs, sugar-sweetened beverages ⁎ Corresponding author at: Department of Pathology, Lake Erie College of Osteopathic Medicine, 1858 West Grandview Boulevard, Erie, PA 16509, USA. E-mail addresses: mrazzaque@lecom.edu, mohammed.razzaque@umb.edu (M.S. Razzaque). Journal of Steroid Biochemistry and Molecular Biology 188 (2019) 166–171 Available online 08 February 2019 0960-0760/ © 2019 Elsevier Ltd. All rights reserved. T