Elsevier

Clinical Nutrition

Volume 37, Issue 5, October 2018, Pages 1625-1630
Clinical Nutrition

Original article
High dietary phosphorus intake is associated with an increased risk of type 2 diabetes in the large prospective E3N cohort study

https://doi.org/10.1016/j.clnu.2017.07.025Get rights and content

Summary

Phosphorus is an essential nutrient; the adult recommended daily intake ranges from 550 to 700 mg/day, with a tolerated upper limit of 4000 mg/day. Phosphorus intake has increased in the general population in recent years, and simultaneously an alarming rise of type 2 diabetes incidences has been observed. No study has investigated the relationship between phosphorus intake and the risk of type 2 diabetes.

To evaluate the association between phosphorus intake and incidence of type 2 diabetes.

Among 71,270 women from the French E3N-EPIC cohort, 1845 cases of incident type 2 diabetes were validated during follow-up (1993–2011). Adjusted Cox proportional hazards regression models were used to calculate hazard ratios and 95% confidence intervals (95% CI) for the associations between phosphorus intake and type 2 diabetes risk, adjusted on potential confounders.

The overall mean (±SD) phosphorus intake was 1477 mg/day (±391 mg/day). High phosphorus intake was associated with risk of type 2 diabetes. In multivariate models, compared with women in the 1st quartile of phosphorus intake (<1203 mg/day), those included in the 2nd (1203–1434.0 mg/day), 3rd (1434–1700 mg/day), and 4th (>1700 mg/day) were at a higher risk of type 2 diabetes, with a hazards ratios (95% CI) of 1.18 (1.00–1.38), 1.41 (1.20–1.66) and 1.54 (1.25–1.90), respectively.

Our results may have important public health implications for dietary recommendations in the prevention of type 2 diabetes. More studies are warranted to better understand the biological mechanisms underlying this positive association.

Introduction

Phosphorus is an essential mineral and plays a crucial role in several biological processes. Indeed phosphorus is structural component of cell membranes and nucleic acids; moreover, phosphorus is also implicated in several biological processes, such as bone mineralization, energy production, cell signaling through phosphorylation reactions, and regulation of acid-base homeostasis [1]. In adults, 55–80% of phosphorus intake is absorbed in the intestine and the rest is excreted in the feces [2]. The European Food Safety Authority established an Adequate Intake (AI) for adults of 550 mg/day, while the Food and Nutrition Board of the Institute of Medicine of the American National Academy of Sciences set a Recommended Dietary Allowance (RDA) of 700 mg/d and a tolerable upper limit of 4000 mg/d for adults [3], [4]. In European Union countries, the mean phosphorus intake in adults ranges from 1000 to 1767 mg/day. Foods rich in protein content, such as milk and dairy products followed by meat, poultry and fish, grain products, and legumes are the principal dietary contributors to phosphorus intake [3]. Several food additives commonly used in food processing have Phosphorus as main component, moreover soft drinks can contribute to the phosphorus intake due to the use of phosphoric acid. Food nutrient composition databases do not always include phosphorus derived from food, thus it has been estimated that the total amount of phosphorus intake may be underestimated by more than 20% [5].

Even though it has been suggested that the population dietary intake of phosphorus has increased due to the growing consumption of foods processed with phosphate additives, reports on the long-term health risks associated with high dietary phosphorus intake are scarce and contradictory. Previous studies reported that the intake of phosphorus is inversely associated with hypertension and with bladder cancer incidence [6], [7], [8]. Long-term high dietary phosphorus intake, even without leading to hyperphosphatemia, has been described as a risk factor for cardiovascular disease, and osteoporosis and bone fracture [9], [10], [11]. Finally, Chang et al. (2014) [12] reported that high phosphorus intake was associated with increased mortality in a healthy US population.

The alarming rise of type 2 diabetes (T2D) incidence that has been observed worldwide in the last decades [13], in parallel with the increasing consumption of processed foods which is also associated to an increase of dietary intake of phosphorus [14], led us to investigate the association between dietary intake of phosphorus and T2D risk in the E3N-EPIC study, a large French cohort.

Section snippets

E3N cohort

The E3N cohort is a prospective study involving 98,995 women born in 1925–1950, living in metropolitan France at inclusion and insured by the Mutuelle Générale de l’Education Nationale, a national teachers' health insurance plan. Details of the cohort have been previously reported [15]. All women enrolled returned a baseline self-administered questionnaire on their lifestyle and medical history from February 1st, 1989, through November 30th, 1991, and, since then, answered follow-up

Phosphorus intake and baseline characteristics

The overall mean (±SD) dietary phosphorus intake was 1477 mg (±391). We describe the participants' characteristics at baseline according to the absolute phosphorus intake quartiles in Table 1. Women with higher phosphorus intake were younger than those with low dietary phosphorus intake. They were also characterized by a higher BMI and more physical activity, more frequently reporting a family history of diabetes, with a higher education level; fewer had hypercholesterolemia and they were less

Discussion

In this cohort of middle-aged women, a higher intake of phosphorus was associated with increased T2D risk. To the best of our knowledge, the present study represents the first prospective study to investigate the risk of T2D associated with dietary intake of phosphorus. The relationship between increasing dietary phosphorus intake and T2D appeared to be linear and the increased risk was observed already from the 2nd quartile of phosphorus intake. The association between high phosphorus intake

Contribution statement

FRM and GF conceived and designed the study. FCC collected the data. FRM, MCB and GF performed the statistical analysis. FRM drafted the original manuscript. All authors contributed to the interpretation of data discussed in the manuscript, revised the manuscript and approved its final version.

Conflict of interest

The authors declare that they have no conflict of interest associated with this manuscript.

Acknowledgments

The authors are grateful to all participants for providing the data used in the E3N Study. This present work was supported by grant from the World Cancer Research Fund (WCRF) (Grant number: 2015/1389), the French Research Agency (ANR, Agence Nationale de la Recherche) via an “Investissement d’Avenir” grant (investment for the future grant, ANR-10-COHO-0006) that supports the E4N study, and the Nutriperso IDEX Paris Saclay University funding. The validation of potential diabetes cases was

References (29)

  • D.S. Michaud et al.

    Prospective study of dietary supplements, macronutrients, micronutrients, and risk of bladder cancer in US men

    Am J Epidemiol

    (2000 15)
  • A. Alonso et al.

    Dietary phosphorus, blood pressure and incidence of hypertension in the atherosclerosis risk in communities (ARIC) Study and the multi-ethnic study of atherosclerosis (MESA)

    Hypertension

    (2010)
  • P. Elliott et al.

    Dietary phosphorus and blood pressure: international study of macro- and micro-nutrients and blood pressure

    Hypertension

    (2008)
  • E. Takeda et al.

    Dietary phosphorus in bone health and quality of life

    Nutr Rev

    (2012)
  • Cited by (26)

    • Association between ultrapocessed food and chronic kidney disease

      2021, Nefrologia
      Citation Excerpt :

      The Framingham and CARE studies show an increase in vascular risk associated with the phosphate increase in plasma, which is why some authors suggest that the term “new cholesterol”.56,57 It has been described a correlation between serum phosphorus levels, mortality and the risk of developing diabetes in a population without CKD58,59 and the development of CKD is more frequent in diabetic patients depending on the phosphorus levels.60 Studies in children, adolescents and premenopausal women relate high phosphate levels with hypocalcemia, hyperparathyroidism and increase in fractures.61,62

    View all citing articles on Scopus
    View full text