Public health impact of dietary phosphorus excess on bone and cardiovascular health in the general population.
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.
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ABSTRACT: Phosphorus intake in excess of the nutrient needs of healthy adults is thought to disrupt hormonal regulation of phosphorus (P), calcium (Ca), and vitamin D, contributing to impaired peak bone mass, bone resorption, and greater risk of fracture. Elevation of extracellular phosphorus due to excessive intake is thought to be the main stimulus disrupting phosphorus homeostasis in healthy individuals, as it is in renal disease even when intake is modest. If high serum phosphorus is the critical link to the effect of high phosphorus intake on bone health, the issue could be addressed through epidemiologic or dietary studies. However, several confounding factors, including problems estimating accurate phosphorus intake, the influence of a low dietary Ca:P ratio, the acidic nature of phosphorus, the rapid rate of absorption and greater phosphorus bioavailability from processed food such as cola drinks, and circadian fluctuation in serum phosphorus, make this question difficult to address using conventional study designs. These confounding factors are considered in this review, exploring whether phosphorus intake exceeding nutrient needs in healthy individuals disrupts phosphorus regulation and negatively affects bone accretion or loss. Specific attention is given to phosphorus intake from processed foods rich in phosphorus additives, which significantly contribute to phosphorus intake.Annals of the New York Academy of Sciences 10/2013; 1301(1):29-35. · 4.38 Impact Factor
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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; · 5.29 Impact Factor
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ABSTRACT: Even within accepted normal ranges, higher serum phosphorus, dietary phosphorus density, parathyroid hormone (PTH) and alkaline phosphatase (ALP) are independent predictors of cardiovascular mortality. Lower serum 25-hydroxy vitamin D (25(OH)D) also predicts adverse cardiovascular outcomes. We hypothesized that vascular dysfunction accompanying subtle disturbances of these bone metabolism parameters would result in associations with increased low grade albuminuria. We examined participants in the National Health and Nutrition Examination Surveys 1999-2010 (N = 19,383) with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m(2) and without severe albuminuria (urine albumin:creatinine ratio (ACR) <300 mg/g). Albuminuria was quantified as ACR and fractional albumin excretion (FEalb). Increasing quintiles of dietary phosphorus density, serum phosphorus and ALP were not associated with higher ACR or FEalb. The lowest versus highest quintile of 25(OH)D was associated with greater albuminuria, but not after adjustment for other covariates including cardiovascular risk factors. An association between the highest versus lowest quintile of bone-specific ALP and greater ACR persisted after covariate adjustment, but was not accompanied by an independent association with FEalb. Increasing quintiles of PTH demonstrated associations with both higher ACR and FEalb that were not abolished by adjusting for covariates including age, gender, race, body mass index, diabetes, blood pressure, history of cardiovascular disease, smoking, eGFR, 25(OH)D, season of measurement, lipids, hemoglobin and C-reactive protein. Adjusted increases in ACR and FEalb associated with the highest versus lowest quintile of PTH were 19% (95% confidence interval 7-28% p<0.001) and 17% (8-31% p = 0.001) respectively. In this population, of the bone mineral parameters associated with cardiovascular outcomes, only PTH is independently associated with ACR and FEalb.PLoS ONE 01/2014; 9(2):e88388. · 3.53 Impact Factor