Circulating phosphorus level and risk of prostate cancer: a Mendelian randomization study

Background Recent observational studies have suggested that circulating phosphorus levels are positively associated with risk of prostate cancer. However, little is known about the causal direction of the association. Objective To explore the potential causal relationship between circulating phosphorus and risk of prostate cancer, we conducted a Mendelian randomization (MR) study. Design Summary statistics of prostate cancer were obtained from a meta-analysis of genome-wide association studies (GWAS) consisting of 79,148 cases and 61,106 controls. Single nucleotide polymorphisms (SNP) associated with serum phosphorus level were selected from a GWAS of 291,408 individuals from the UK Biobank. MR analysis was performed using the inverse-variance weighted (IVW) method, supplemented with simple-median, weighted-median, maximum likelihood-based, MR-Egger regression and MR-PRESSO test. We also performed a meta-analysis of observational studies to assess the associations of dietary phosphorus intake and serum phosphorus level with risk of prostate cancer. Results In the MR analysis, a total of 125 independent SNPs associated with serum phosphorus levels were used as instrumental variables. Genetically predicted serum phosphorus levels were associated with a 19% increased risk of prostate cancer (95% confidence interval (CI): 9%, 31%) per one SD increment of serum phosphorus by IVW (P = 1.82 × 10–4). Sensitivity analyses using alternative MR methods produced similar positive associations, and no evidence of pleiotropy was detected by MR-Egger regression (P = 0.422). For meta-analysis, eight studies for dietary phosphorus intake and four for serum phosphorus levels were included involving a total of 669,080 participants. Consistently, high dietary phosphorus intake and serum phosphorus levels were associated with an 8% (95% CI: 4%, 12%) and 7% (95% CI: 1%, 14%) increase in prostate cancer risk, respectively. Conclusions Our study suggested a potential causal relationship between circulating phosphorus and risk of prostate cancer. Further studies are warranted to elucidate the underlying mechanism of phosphorus in the development of prostate cancer.

Trends in Total, Added, and Natural Phosphorus Intake in Adult Americans, NHANES 1988–1994 to NHANES 2015–2016

Dietary phosphorus intake in the USA has been consistently greater than the Recommended Daily Allowance (RDA) with several studies reporting associations between intake and health risks as well as all-cause mortality within healthy subjects and patients with chronic kidney disease (CKD). The current study utilized a novel approach to calculate added phosphorus content in foods to determine sources (National Health and Nutrition Examination Survey, NHANES 2001–2016, n = 39,796) and trends in consumption (NHANES 1988–1994, 2001–2016, n = 55,744) of total, naturally occurring, and added phosphorus. Among adults (19+ years), the mean intake of total and natural phosphorus (mg/day) in 1988–1994 as compared with 2015–2016 increased (total: 1292 ± SE 11 vs. 1398 ± SE 17; natural: 1113 ± SE 10 vs. 1243 ± SE 16 mg/day); in contrast, added phosphorus intake decreased during this time (178 ± SE 2.9 vs. 155 ± SE 4.1 mg/day). Added phosphorus as a percent of total ranged from about 14.6% in 1988–1994 to about 11.6% in 2015–2016. The top five sources of total and naturally occurring phosphorus, representing approximately 20% of intake, were cheese, pizza, chicken (whole pieces), reduced-fat milk, and eggs/omelets. The top five sources of added phosphorus were cheese, soft drinks, cakes/pies, rolls/buns, and cookies/brownies, representing 45% of added phosphorus in the diet. Consumption of added phosphorus has decreased over the past few decades, possibly due to increased demand for foods with less additives/ingredients but may also be due to inaccurate phosphorus values in nutrition databases. Further studies are needed to validate the added phosphorus calculations utilized in this study and nutrition databases should consider providing added phosphorus content.

MO593CONTROLLING DIETARY PHOSPHORUS IN CHRONIC KIDNEY DISEASE STAGES 1 AND 2 DECREASES PROTEINURIA AND PREVENTS DECLINE IN RENAL FUNCTION

Background and Aims High phosphorus intake is known to cause renal and vascular calcification and renal tubular injury and albuminuria. Dietary phosphorus restriction is therapeutic for controlling disordered phosphorus homeostasis and for improving cardiovascular outcomes in CKD. However, early restriction of dietary phosphorus is not advocated Aim: To evaluate if early control of dietary phosphorus ameliorates proteinuria, prevents decline in glomerular filtration rate and prevents increase in FGF-23 Method One year longitudinal study on 79 CKD patients in stages 1 and 2. eGFR, serum creatinine , phosphorus, calcium, FGF-23, soluble α-Klotho iPTH FGF 23, blood pressure, were evaluated and compared with 35 controls. 3 days dietary intake was taken using standard methodology on first visit, 6 and 12 months. CKD patients were grouped based on dietary phosphorus intake: Group 1 (n 42): normal phosphorous intake (<1000mg/day) and Group 2 (n=37; 17 in CKD 1; 20 CKD 2): high phosphorous intake (>1000mg/d). Patients in Group 2 were educated on high and low phosphorus foods and counselled to avoid fresh and frozen and processed meat, eggs, nuts and seeds, chocolates, packaged food, phosphorus-containing food additives and counselled to adopt a plant-based diet, for low phosphorus availability/absorption diet with directed diet plan. Lentils and pulses, milk and milk products (hard cheese, ice-creams, custards, cottage cheese, pudding, yoghurt), bran and whole wheat cereals were restricted up to 1-2 servings a day Data were analysed using SPSS. Results At baseline there was no significant difference in the GFR (group1 85.00±18.64 ml/min vs group 2 82.53±16.30ml/min), serum creatinine between groups. In group2 ; GFR, sKlotho, serum phosphorus and FGF-23 correlated significantly with dietary phosphorus intake. In group 2, FGF-23, Serum phosphorus, dietary protein and phosphorus intake were significantly higher and sKlotho was significantly lower than group 1. There was significant difference in serum phosphorus (p 0.000), iPTH, (p 0.004), FGF23 (p0.000), Klotho (p0.000), urinary protein (p0.000), dietary protein (Group 1 37.57±3.40; Group 248.79±5.86 p 0.000) and phosphorus (Group 1868.96±69.99 mg/d and Group 2 1312.26±137.57 mg/d p 0.000) intake and dietary phosphorous to protein ratio (p 0.000) between groups 1 and 2.. After dietary intervention in group 2 GFR increased from 80.93±15.34 to 84.11±15.38 in six months and to 87.43±18.27 ml/min at 12 months p 0.012, and urinary protein declined to 22.01±3.39 mg/mL. FGF 23 declined from 60.67±6.26 to 58.00±7.07 to 53.29±9.48 pg/mL at 12 months. Urinary phosphorus excretion increased from 574.37±214.22 to 624.64±137.67 at 12 months. Dietary phosphorus protein to ratio reduced from 27.16±4.35 to24.75±4.34 p 0.000 at 12 months Conclusion CKD patients should be cautioned and counselled on their first visit on the impact of dietary phosphorus intake on the progression of CKD and development of CVD.

The Percentage of Dietary Phosphorus Excreted in the Urine Varies by Dietary Pattern in a Randomized Feeding Study in Adults

ABSTRACTBackgroundUrinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors.ObjectiveWe assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial.MethodsDASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test.ResultsAt the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P = 0.74 control vs. FV, P < 0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons).ConclusionsThese findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054.

Dietary phosphorus intake and blood pressure in adults: a systematic review of randomized trials and prospective observational studies

ABSTRACT Background Elevated blood pressure (BP) is a major cause of preventable disease in the United States and around the world. It has been postulated that phosphorus intake may affect BP, with some studies suggesting a direct and others an inverse association. Objectives We systematically reviewed the literature on the association of dietary phosphorus with BP in adults and performed a qualitative synthesis. Methods We included randomized and nonrandomized behavioral intervention and feeding studies (intervention studies) and prospective observational studies that measured dietary phosphorus intake or urinary phosphorus excretion and BP. We excluded studies of supplements, children, or individuals with major medical conditions. We searched PubMed, Embase, Cochrane Trials, and clinicaltrials.gov on 1 June, 2017 and 22 August, 2018. We assessed studies’ risk of bias in their assessment of phosphorus exposure and BP. Results We reviewed 4759 publications and included 14 intervention studies (2497 participants), 3 prospective observational cohorts (17,795 participants), and 2 ongoing trials. No included intervention studies were designed specifically to achieve a phosphorus contrast. Two studies found a significant positive association of dietary phosphorus with systolic BP, 4 a significant inverse association, and 8 no significant association. Four studies found a significant inverse association with diastolic BP and 10 no significant associations. Two cohorts found lower risk of incident hypertension comparing the highest with the lowest quintiles of phosphorus intake and 1 found no significant difference: HR: 0.86 (95% CI: 0.75, 0.98); HR: 0.83 (95% CI: 0.68, 1.02); and HR: 0.75 (95% CI: 0.45, 1.27), respectively. Conclusions We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association. This trial was registered at www.crd.york.ac.uk/prospero/ as CRD42017062489.

Phosphorus Consumption Within 1 Hour Prior to Blood Work and Associated Serum Levels of Phosphate, Calcium, and PTH in Adult Patients Receiving Hemodialysis Treatment

Background: While dietary intake is known to influence serum markers of chronic kidney disease–mineral and bone disorder (CKD-MBD), the effects of recent food and beverage intake, particularly phosphorus consumption on these serum markers (phosphate, calcium, and parathyroid hormone [PTH]), are unknown in hemodialysis patients. An understanding of these effects could have direct and important implications on the management of CKD-MBD. Objective: To determine whether serum phosphate, calcium, and PTH levels were higher in hemodialysis patients who had consumed dietary phosphorus within 1 hour prior to their routine dialysis-related blood work (non–phosphorus-fasted) compared with patients who did not (phosphorus-fasted). Design: Observational, cross-sectional study. Setting: Kingston Health Sciences Center—Kingston General Hospital Site and its affiliated satellite hemodialysis units. Patients: Two hundred fifty-four adult patients receiving outpatient hemodialysis treatment for end-stage kidney disease were recruited. Measurements: The main measurements for this study included an assessment of dietary phosphorus intake as well as serum phosphate, calcium, PTH, albumin, Kt/V, and urea reduction ratio. Methods: A direct patient interview was performed to assess dietary phosphorus intake within 1 hour prior to routine dialysis-related blood work. The Canadian Nutrient File was then used to estimate dietary phosphorus based on the specific foods and beverages (including portion sizes and brands where applicable) identified in the interview. Serum measures of phosphate, PTH, calcium, albumin, and dialysis adequacy (Kt/V and urea reduction ratio) were obtained from participants’ routine dialysis-related blood work. Results: Non–phosphorus-fasted participants had nonsignificantly higher serum PTH levels compared to phosphorus-fasted participants (61.2 ± 64.7 vs 47.9 ± 39.7, P = .05). Non–phosphorus-fasted participants with PTH levels at the Kidney Disease Improving Global Outcomes (KDIGO) “target” (between 15 and 60 pmol/L) had significantly higher serum phosphate levels relative to phosphorus-fasted participants (1.6 ± 0.3 vs 1.4 ± 0.4, P = .006). In non–phosphorus-fasted participants, there was a nonsignificant association between the number of items containing inorganic phosphate additives and higher levels of serum phosphate and lower levels of serum calcium. Limitations: Some limitations include the cross-sectional nature of this study, self-reporting biases and estimates (as opposed to direct measurements) related to the dietary assessment, and the use of single (and not serial) assessments of serum measures. Conclusions: Dietary phosphorus intake in close proximity to blood work may contribute to subtle alterations in some key serum CKD-MBD parameters in adult outpatient hemodialysis patients but may not meaningfully alter CKD-MBD management.