Public health impact of dietary phosphorus excess on bone and cardiovascular health in the general population

Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Department of Health and Human Services, Laurel, MD.
American Journal of Clinical Nutrition (Impact Factor: 6.5). 05/2013; 98(1). DOI: 10.3945/ajcn.112.053934
Source: PubMed

ABSTRACT This review explores the potential adverse impact of the increasing phosphorus content in the American diet on renal, cardiovascular, and bone health of the general population. Increasingly, studies show that phosphorus intakes in excess of the nutrient needs of a healthy population may significantly disrupt the hormonal regulation of phosphate, calcium, and vitamin D, which contributes to disordered mineral metabolism, vascular calcification, impaired kidney function, and bone loss. Moreover, large epidemiologic studies suggest that mild elevations of serum phosphate within the normal range are associated with cardiovascular disease (CVD) risk in healthy populations without evidence of kidney disease. However, few studies linked high dietary phosphorus intake to mild changes in serum phosphate because of the nature of the study design and inaccuracies in the nutrient composition databases. Although phosphorus is an essential nutrient, in excess it could be linked to tissue damage by a variety of mechanisms involved in the endocrine regulation of extracellular phosphate, specifically the secretion and action of fibroblast growth factor 23 and parathyroid hormone. Disordered regulation of these hormones by high dietary phosphorus may be key factors contributing to renal failure, CVD, and osteoporosis. Although systematically underestimated in national surveys, phosphorus intake seemingly continues to increase as a result of the growing consumption of highly processed foods, especially restaurant meals, fast foods, and convenience foods. The increased cumulative use of ingredients containing phosphorus in food processing merits further study given what is now being shown about the potential toxicity of phosphorus intake when it exceeds nutrient needs.

  • [Show abstract] [Hide abstract]
    ABSTRACT: High calcium intake has been associated with an increased risk of advanced-stage and high-grade prostate cancer. Several studies have found a positive association between phosphorus intake and prostate cancer risk. We investigated the joint association between calcium and phosphorus and risk of prostate cancer in the Health Professionals Follow-Up Study, with a focus on lethal and high-grade disease. In total, 47,885 men in the cohort reported diet data in 1986 and every 4 y thereafter. From 1986 to 2010, 5861 cases of prostate cancer were identified, including 789 lethal cancers (fatal or metastatic). We used Cox proportional hazards models to assess the association between calcium and phosphorus intake and prostate cancer, with adjustment for potential confounding. Calcium intakes >2000 mg/d were associated with greater risk of total prostate cancer and lethal and high-grade cancers. These associations were attenuated and no longer statistically significant when phosphorus intake was adjusted for. Phosphorus intake was associated with greater risk of total, lethal, and high-grade cancers, independent of calcium and intakes of red meat, white meat, dairy, and fish. In latency analysis, calcium and phosphorus had independent effects for different time periods between exposure and diagnosis. Calcium intake was associated with an increased risk of advanced-stage and high-grade disease 12-16 y after exposure, whereas high phosphorus was associated with increased risk of advanced-stage and high-grade disease 0-8 y after exposure. Phosphorus is independently associated with risk of lethal and high-grade prostate cancer. Calcium may not have a strong independent effect on prostate cancer risk except with long latency periods. © 2015 American Society for Nutrition.
    American Journal of Clinical Nutrition 01/2015; 101(1):173-83. DOI:10.3945/ajcn.114.088716 · 6.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality. Double-blind, placebo-controlled, randomized trial. 149 patients with estimated glomerular filtration rates < 60mL/min/1.73m(2), iron deficiency anemia (hemoglobin, 9.0-12.0g/dL; transferrin saturation [TSAT]≤30%, serum ferritin ≤ 300ng/mL), and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. Coprimary end points were change in TSAT and serum phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary phosphate excretion, and estimated glomerular filtration rate. Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum phosphate levels from 4.5±0.6 to 3.9±0.6mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum phosphate level (4.7±0.6 to 4.4±0.8mg/dL; between-group P<0.001 for each). Ferric citrate increased hemoglobin levels (from 10.5±0.8 to 11.0±1.0g/dL; P<0.001 vs placebo), reduced urinary phosphate excretion 39% (P<0.001 vs placebo), and reduced serum intact FGF-23 levels from a median of 159 (IQR, 102-289) to 105 (IQR, 65-187) pg/mL (P=0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms. The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes. Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum phosphate, urinary phosphate excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5. Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
    American Journal of Kidney Diseases 11/2014; DOI:10.1053/j.ajkd.2014.10.014 · 5.76 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Migraine is an incompletely understood, debilitating disorder that lacks a universally effective treatment. Magnesium participates in a variety of biochemical processes related to migraine pathophysiology, and a deficiency could contribute to migraine development. A review of the literature from 1990 to the present on magnesium and migraine was conducted. The authors identified 16 studies aimed at magnesium status assessment in migraine, and four intervention trials assessing the efficacy of oral magnesium supplementation, independent of other therapies, in the prevention of migraine. The strength of evidence supporting oral magnesium supplementation is limited at this time. With such limited evidence, a more advantageous alternative to magnesium supplementation, in patients willing to make lifestyle changes, may be to focus on increasing dietary magnesium intake. © International Headache Society 2014 Reprints and permissions:
    Cephalalgia 12/2014; DOI:10.1177/0333102414564891 · 4.12 Impact Factor