High phosphorus intake and gut-related parameters - results of a randomized placebo-controlled human intervention study

Ulrike Trautvetter, Amélia Camarinha-Silva, Gerhard Jahreis, Stefan Lorkowski, Michael Glei, Ulrike Trautvetter, Amélia Camarinha-Silva, Gerhard Jahreis, Stefan Lorkowski, Michael Glei

Abstract

Background: In recent years, high phosphate intakes were discussed critically. In the small intestine, a part of the ingested phosphate and calcium precipitates to amorphous calcium phosphate (ACP), which in turn can precipitate other intestinal substances, thus leading to a beneficial modulation of the intestinal environment. Therefore, we analysed faecal samples obtained from a human intervention study regarding gut-related parameters.

Methods: Sixty-two healthy subjects (men, n = 30; women, n = 32) completed the double-blind, placebo-controlled and parallel designed study (mean age: 29 ± 7 years; mean BMI: 24 ± 3 kg/m2). Supplements were monosodium phosphate and calcium carbonate. During the first 2 weeks, all groups consumed a placebo sherbet powder, and afterwards a sherbet powder for 8 weeks according to the intervention group: P1000/Ca0 (1000 mg/d phosphorus), P1000/Ca500 (1000 mg/d phosphorus and 500 mg/d calcium) and P1000/Ca1000 (1000 mg/d phosphorus and 1000 mg/d calcium). After the placebo period and after 8 weeks of intervention faecal collections took place. We determined in faeces: short-chain fatty acids (SCFA) and fat as well as the composition of the microbiome (subgroup) and cyto- and genotoxicity of faecal water (FW). By questionnaire evaluation we examined tolerability of the used phosphorus supplement.

Results: Faecal fat concentrations did not change significantly due to the interventions. Concentrations of faecal total SCFA and acetate were significantly higher after 8 weeks of P1000/Ca500 supplementation compared to the P1000/Ca0 supplementation. In men, faecal total SCFA and acetate concentrations were significantly higher after 8 weeks in the P1000/Ca1000 group compared to the P1000/Ca0 one. None of the interventions markedly affected cyto- and genotoxic activity of FW. Men of the P1000/Ca1000 intervention had a significantly different gut microbial community compared to the men of the P1000/Ca0 and P1000/Ca500 ones. The genus Clostridium XVIII was significantly more abundant in men of the P1000/Ca1000 intervention group compared to the other groups. Supplementations did not cause increased intestinal distress.

Conclusions: The used high phosphorus diet did not influence cyto- and genotoxicity of FW and the concentrations of faecal fat independent of calcium intake. Our study provides first hints for a potential phosphorus-induced modulation of the gut community and the faecal total SCFA content.

Trial registration: The trial is registered at ClinicalTrials.gov as NCT02095392 .

Keywords: Calcium intake; Cytotoxicity; Faecal water; Genotoxicity; Human study; Phosphate intake; Phosphorus intake; Short-chain fatty acids.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Ethical Committee of the Friedrich Schiller University Jena (no.: 3987-01/14). Written informed consent was obtained from all subjects. The trial is registered at Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flow chart of the study concept. P1000/Ca0: 1000 mg phosphorus; P1000/Ca500: 1000 mg phosphorus/500 mg calcium; P1000/Ca1000: 1000 mg phosphorus/1000 mg calcium; SCFA: short-chain fatty acids; FW: faecal water
Fig. 2
Fig. 2
Overview of intestinal disturbances after supplementation with phosphorus and calcium. a: Proportional (y-axis) and absolute (numbers in the bars) distribution of subjects reporting problems with gut health or not; b: proportional (y-axis) and absolute (numbers in the bars) distribution of reported associations with the test product, when subjects reported complaints; c proportional (y-axis) and absolute (numbers in the bars) distribution of types of reported problems; P1000/Ca0: 1000 mg phosphorus/0 mg calcium; P1000/Ca500: 1000 mg phosphorus/500 mg calcium; P1000/Ca1000: 1000 mg phosphorus/1000 mg calcium
Fig. 3
Fig. 3
Faecal concentrations of short-chain fatty acids after supplementation with phosphorus and calcium. P1000/Ca0: n = 16; P1000/Ca500: n = 19; P1000/Ca1000: n = 19; data are expressed as means + standard deviations; #, * mean values with similar symbols are significantly different (p ≤ 0.05); effect of supplementation was tested using univariate analysis of variance followed by Bonferroni post-hoc test; P1000/Ca0: 1000 mg phosphorus; P1000/Ca500: 1000 mg phosphorus/500 mg calcium; P1000/Ca1000: 1000 mg phosphorus/1000 mg calcium; SCFA: short-chain fatty acids
Fig. 4
Fig. 4
Cell vitality (a) and tail intensity (b) of HT29 cells. a P1000/Ca0: n = 15; P1000/Ca500: n = 19; P1000/Ca1000: n = 17; b P1000/Ca0: n = 10; P1000/Ca500: n = 8; P1000/Ca1000: n = 15; cell vitality and tail intensity after treatment of HT29 cells with faecal water collected following supplementation with phosphorus and calcium; data are expressed as means + standard deviations; #, * mean values with similar symbols are significantly different (p ≤ 0.05); effect of time was tested with paired Students t-test, effect of supplementation was tested using univariate analysis of variance followed by Bonferroni post-hoc test; P1000/Ca0: 1000 mg phosphorus; P1000/Ca500: 1000 mg phosphorus/500 mg calcium; P1000/Ca1000: 1000 mg phosphorus/1000 mg calcium; PBS: phosphate buffered saline
Fig. 5
Fig. 5
Global bacterial community structure of men after eight weeks of intervention with phosphorus and calcium. Sequencing data were standardized prior to the use of Bray-Curtis similarity algorithm, the symbols represent a unique sample comprising all OTUs and its abundance information, the data of the red symbols (P1000/Ca1000) are significantly different from the grey (P1000/Ca0, R = 0.778, p = 0.01) and blue (P1000/Ca500, R = 0.593, p = 0.01) ones, P1000/Ca0: 1000 mg phosphorus; P1000/Ca500: 1000 mg phosphorus/500 mg calcium; P1000/Ca1000: 1000 mg phosphorus/1000 mg calcium, n = 9; ns: not significant, OTU: operational taxonomic unit
Fig. 6
Fig. 6
Principal coordinate analysis ordination of the global microbial community structure of men. a Data of men after eight weeks of P1000/Ca1000 vs. P1000/Ca500 intervention; b data of men after eight weeks of P1000/Ca1000 vs. P1000/Ca0 intervention, n = 6; bubbles were superimposed to visualise the relative abundance of the most relevant OTUs; P1000/Ca0: 1000 mg phosphorus; P1000/Ca500: 1000 mg phosphorus/500 mg calcium; P1000/Ca1000: 1000 mg phosphorus/1000 mg calcium, ns: not significant, OTU: operational taxonomic unit; PCO: principal coordinate

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