Phytate and Kidney Health: The Roles of Dietary Phytate in Inhibiting Intestinal Phosphorus Absorption and Intravenous Phytate in Decreasing Soft Tissue Calcification

There is currently much interest in diets which provide a large proportion of protein from plant foods.1Mariotti F. Animal and plant protein sources and cardiometabolic health.Adv Nutr. 2019; 10: S351-S366Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar Epidemiological studies indicate people who commonly ingest these diets have reduced cardiovascular disease mortality and all-cause mortality,1Mariotti F. Animal and plant protein sources and cardiometabolic health.Adv Nutr. 2019; 10: S351-S366Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, 2Aune D. Plant foods, antioxidant biomarkers, and the risk of cardiovascular disease, cancer, and mortality: a review of the evidence.Adv Nutr. 2019; 10: S404-S421Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 3Herpich C. Muller-Werdan U. Norman K. Role of plant-based diets in promoting health and longevity.Maturitas. 2022 Nov; 165: 47-51Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar a lower prevalence of obesity,3Herpich C. Muller-Werdan U. Norman K. Role of plant-based diets in promoting health and longevity.Maturitas. 2022 Nov; 165: 47-51Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar,4Magkos F. Tetens I. Bugel S.G. et al.A perspective on the transition to plant-based diets: a diet change may attenuate climate change, but can it also attenuate obesity and chronic disease risk?.Adv Nutr. 2020; 11: 1-9Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar hypertension,3Herpich C. Muller-Werdan U. Norman K. Role of plant-based diets in promoting health and longevity.Maturitas. 2022 Nov; 165: 47-51Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar constipation5Bellini M. Tonarelli S. Barracca F. et al.Chronic constipation: is a nutritional approach reasonable?.Nutrients. 2021; 13: 3386Crossref PubMed Scopus (5) Google Scholar and other gastrointestinal disorders,3Herpich C. Muller-Werdan U. Norman K. Role of plant-based diets in promoting health and longevity.Maturitas. 2022 Nov; 165: 47-51Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar less chronic kidney disease (CKD),6Joshi S. McMacken M. Kalantar-Zadeh K. Plant-based diets for kidney disease: a guide for clinicians.Am J kidney Dis. 2021; 77: 287-296Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar and slower rates of CKD progression.6Joshi S. McMacken M. Kalantar-Zadeh K. Plant-based diets for kidney disease: a guide for clinicians.Am J kidney Dis. 2021; 77: 287-296Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar,7Joshi S. Moore L.W. Kalantar-Zadeh K. The future of nutrition in kidney disease: plant-based diets, gut microbiome, and beyond.J Ren Nutr. 2021; 31: 97-99Abstract Full Text Full Text PDF PubMed Google Scholar There are a number of characteristics of these diets that may be responsible for these potential benefits. These include the lower content of saturated fatty acids and cholesterol, the particular chemical constituents of some fruits and vegetables, for example, higher nitrite, fiber, carotenoids, and potassium content and lower sodium.3Herpich C. Muller-Werdan U. Norman K. Role of plant-based diets in promoting health and longevity.Maturitas. 2022 Nov; 165: 47-51Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The alkalizing properties and propensity to reduce intestinal phosphorus absorption due to the binding of phosphorus to phytate from plant foods in the intestinal tract may be therapeutic for CKD patients.8Kalantar-Zadeh K. Joshi S. Schlueter R. et al.Plant-dominant low-protein diet for conservative management of chronic kidney disease.Nutrients. 2020; 12: 1931Crossref PubMed Scopus (76) Google Scholar Although many dietitians and nephrologists recommend a “plant-based diet” for nondialyzed CKD patients and chronic dialysis patients because of these latter properties,9Betz M.V. Nemec K.B. Zisman A.L. Plant-based diets in kidney disease: Nephrology professionals' perspective.J Ren Nutr. 2022; 32: 552-559Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar there may not be general understanding of what phytate is and that phytate content, and hence, the ability to bind phosphorus can vary greatly among different plants and plant-based foods. Phytic acid is also called myo-inositol-1,2,3,4,5,6-hexakis dihydrogen phosphate, inositol hexakisphosphate, or inositol polyphosphate (Figure 1).10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Inositol, or more precisely the myo-isomer, myo-inositol, is a sugar alcohol made naturally in the human body from glucose.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Phytic acid is a six-fold dihydrogenphosphate ester of inositol (specifically, of the myo-isomer) and the phosphates are partially ionized at physiological pH (pH∼ 6-7) producing the phytate anion.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Phytate, the salt of phytic acid, is considered a storage form of phosphorus and minerals in plants.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar At physiological pH, phytate is highly negatively charged.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Phytate inhibits the intestinal absorption of essential minerals and trace elements such as calcium, phosphorus, iron, and zinc11Gibson R.S. Raboy V. King J.C. Implications of phytate in plant-based foods for iron and zinc bioavailability, setting dietary requirements, and formulating programs and policies.Nutr Rev. 2018; 76: 793-804Crossref PubMed Scopus (115) Google Scholar and also serves as an antioxidant and anticancer agent.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Phytate is mainly present in unprocessed plant foods but it can be hydrolyzed to a broad range of inositol phosphates with food processing.12Calvo M.S. Uribarri J. Perspective: plant-based whole-grain foods for chronic kidney disease: the phytate-phosphorus conundrum.Adv Nutr. 2021; 12: 2056-2067Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar The main sources of phytate in the diet are in the seeds, grains, and fruit of plants, especially cereals, legumes, oil seeds, and nuts.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Other parts of plant anatomy generally have much lower phytate content.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar The amount of phytate in these foods varies considerably, depending on the variety of the plant and the food processing.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar It is not uncommon in these foods for the phytic acid content to be about 2.0 g per 100 g dry weight.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar In walnuts, almonds, and soy concentrate, the phytic acid content can be 6.7%, 9.4%, and 10.7% dry weight.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar The reduced intestinal phosphorus absorption shown with diets very high in plant foods is considered to be due to the higher phytate content of plant foods.12Calvo M.S. Uribarri J. Perspective: plant-based whole-grain foods for chronic kidney disease: the phytate-phosphorus conundrum.Adv Nutr. 2021; 12: 2056-2067Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Phytate can be degraded during food processing and possibly upon cooking.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Phytases ingested with foods are responsible for most of the phytate degradation that occurs in the stomach.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar Little phytate is degraded in the small intestine because there is little endogenous phytase, and phytate is precipitated in the intestinal chyme.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar The colon is very high in bacterial phytases and little phytate is detectable in feces.12Calvo M.S. Uribarri J. Perspective: plant-based whole-grain foods for chronic kidney disease: the phytate-phosphorus conundrum.Adv Nutr. 2021; 12: 2056-2067Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Some phytate is absorbed from the intestinal tract and excreted in urine.10Schlemmer U. Frolich W. Prieto R.M. Grases F. Phytate in foods and significance for humans: food sources, intake, processing, bioavailability, protective role and analysis.Mol Nutr Food Res. 2009; 53: S330-S375Crossref PubMed Scopus (549) Google Scholar,12Calvo M.S. Uribarri J. Perspective: plant-based whole-grain foods for chronic kidney disease: the phytate-phosphorus conundrum.Adv Nutr. 2021; 12: 2056-2067Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar Although this has not been well studied, possible changes in the microbiota of CKD patients13Hobby G.P. Karaduta O. Dusio G.F. et al.Chronic kidney disease and the gut microbiome.Am J Physiol Ren Physiol. 2019; 316: F1211-F1217Crossref PubMed Scopus (88) Google Scholar might affect the amount of phytase and degree of phytate degradation in the gastrointestinal tract. The foregoing data raise the question of whether phytate or phytic acid could be fed to CKD and chronic dialysis patients to reduce intestinal phosphorus absorption. Recent clinical trials have explored whether intravenously infused phytate may treat cardiovascular calcification and calciphylaxis in chronic hemodialysis patients. The results of these early studies suggest that intravenously infused phytate may reduce cardiovascular calcification. Elsewhere in this issue, Hegbrant et al14Hegbrant J. Bernat A. Del Castillo D. et al.Residual renal phosphate clearance in patients receiving hemodialysis or hemodiafiltration.J Ren Nutr. 2023; 33: 326-331Abstract Full Text Full Text PDF Scopus (1) Google Scholar report on a prospective study that examined the phosphorus clearance of patients with residual renal function who were treated with hemodialysis or hemodiafiltration. They found that residual renal clearance of phosphorus in patients undergoing these types of treatment could be estimated by knowing their urea clearance, a solute more commonly assessed than renal phosphorus. Four additional reports in this issue relate to plant-based diets.15Chen Y. Wu J. Yu D. Liu M. Plant or animal-based or plado diets: which should chronic kidney disease patients choose?.J Ren Nutr. 2023; 33: 228-235Abstract Full Text Full Text PDF Google Scholar,17Betz M.V. Nemec K.B. Zisman A.L. Patient perception of plant based diets for kidney disease.J Ren Nutr. 2023; 33: 243-248Abstract Full Text Full Text PDF Google Scholar, 18Praditpornsilpa K. Garneata L. Lin Y.C. et al.Economic analysis of a ketoanalogue-supplemented very low-protein diet in patients with chronic kidney disease in taiwan and Thailand.J Ren Nutr. 2023; 33: 269-277Abstract Full Text Full Text PDF Scopus (0) Google Scholar, 19Slagle C.L. Riddle S.L. McNelis K. Claes D. Single-center experience on growth in infants born with end-stage kidney disease.J Ren Nutr. 2023; 33: 236-242Abstract Full Text Full Text PDF Google Scholar Chen et al15Chen Y. Wu J. Yu D. Liu M. Plant or animal-based or plado diets: which should chronic kidney disease patients choose?.J Ren Nutr. 2023; 33: 228-235Abstract Full Text Full Text PDF Google Scholar provide a review of articles published regarding the use of plant-based foods as protein sources for patients with CKD. Tallman et al16Tallman D.A. Khor B.H. Karupaiah T. et al.Nutritional adequacy of essential nutrients in low protein animal- and plant-based diets in the United States for chronic kidney disease patients.J Ren Nutr. 2023; 33: 249-260Abstract Full Text Full Text PDF Google Scholar provide data from analysis of theoretical menus using animal-based, lacto-ovo-based, and plant-based diets for low-protein dietary approaches for CKD. Their study reports on the adequacy of each protein source for amino acids and other vitamins and minerals at varying levels of dietary protein ranging from 0.5 to 1.2 g per day. Betz et al17Betz M.V. Nemec K.B. Zisman A.L. Patient perception of plant based diets for kidney disease.J Ren Nutr. 2023; 33: 243-248Abstract Full Text Full Text PDF Google Scholar report on a survey of patients with CKD regarding their thoughts on plant-based diets. Praditpornsilpa et al18Praditpornsilpa K. Garneata L. Lin Y.C. et al.Economic analysis of a ketoanalogue-supplemented very low-protein diet in patients with chronic kidney disease in taiwan and Thailand.J Ren Nutr. 2023; 33: 269-277Abstract Full Text Full Text PDF Scopus (0) Google Scholar report on the economics, including quality-adjusted life years, of using ketoanalog supplements with a very low-protein diet for patients with CKD. These reports are timely, in keeping with the current interest in plant-based foods, and demonstrate a need for additional research in this area. This issue of the Journal includes a report by Slagle et al19Slagle C.L. Riddle S.L. McNelis K. Claes D. Single-center experience on growth in infants born with end-stage kidney disease.J Ren Nutr. 2023; 33: 236-242Abstract Full Text Full Text PDF Google Scholar regarding the pattern of growth of infants born with congenital anomalies of the kidneys, compares infants receiving dialysis to infants not receiving dialysis, and urges the need for more research to understand the nutritional needs of this highly vulnerable population. Another special population report is a study from Pereira et al20Pereira R.A. Alvarenga M.D.S. de Andrade L.S. et al.Effect of a nutritional behavioral intervention on intuitive eating in overweight women with chronic kidney disease.J Ren Nutr. 2023; 33: 289-297Abstract Full Text Full Text PDF Scopus (3) Google Scholar who examined a behavioral intervention focused on intuitive eating for women who are overweight and have CKD. Two studies report on eating patterns; one of patients with CKD and diabetes21Real Rodrigues C.C. Riboldi B.P. Rodrigues T.D.C. et al.Association of eating patterns and diabetic kidney disease in type 2 diabetes: a cross-sectional study.J Ren Nutr. 2023; 33: 261-268Abstract Full Text Full Text PDF Google Scholar and one of patients requiring hemodialysis.22Muniz G.A.S. Ramos C.I. Claudino G. Cuppari L. Development and validation of a food frequency questionnaire to assess potassium intake of patients on hemodialysis.J Ren Nutr. 2023; 33: 386-392Abstract Full Text Full Text PDF Scopus (0) Google Scholar Real Rodrigues et al21Real Rodrigues C.C. Riboldi B.P. Rodrigues T.D.C. et al.Association of eating patterns and diabetic kidney disease in type 2 diabetes: a cross-sectional study.J Ren Nutr. 2023; 33: 261-268Abstract Full Text Full Text PDF Google Scholar correlated eating patterns (specifically snack eaters and red meat eaters) to markers of diabetes using a food frequency questionnaire. Muniz et al22Muniz G.A.S. Ramos C.I. Claudino G. Cuppari L. Development and validation of a food frequency questionnaire to assess potassium intake of patients on hemodialysis.J Ren Nutr. 2023; 33: 386-392Abstract Full Text Full Text PDF Scopus (0) Google Scholar developed a food frequency questionnaire for assessing potassium intake in patients receiving hemodialysis. Several reports in this issue assess malnutrition or markers of malnutrition. Two reports on serum albumin are included in this issue.23Rami Arab L. Dabernat S. Boutin J. et al.Impact of albumin assays in the diagnosis of malnutrition in hemodialysis patients: a cohort study.J Ren Nutr. 2023; 33: 332-336Abstract Full Text Full Text PDF Google Scholar,24Suzuki Y. Harada M. Matsuzawa R. et al.Trajectory of serum albumin prior to death in patients receiving hemodialysis.J Ren Nutr. 2023; 33: 368-375Abstract Full Text Full Text PDF Scopus (1) Google Scholar Rami Arab et al23Rami Arab L. Dabernat S. Boutin J. et al.Impact of albumin assays in the diagnosis of malnutrition in hemodialysis patients: a cohort study.J Ren Nutr. 2023; 33: 332-336Abstract Full Text Full Text PDF Google Scholar performed a study examining four analytic methods of measuring plasma albumin concentration (bromocresol green, bromocresol purple, immunonephelometry, and immunoturbidimetry) and report on the false positive rates using the cut point of 3.5 g/dL for each assay. Suzuki et al24Suzuki Y. Harada M. Matsuzawa R. et al.Trajectory of serum albumin prior to death in patients receiving hemodialysis.J Ren Nutr. 2023; 33: 368-375Abstract Full Text Full Text PDF Scopus (1) Google Scholar report on the pattern of change in serum albumin associated with death of patients receiving chronic hemodialysis. Also associated with death of patients with CKD is a low concentration of plasma insulin-like growth factor when muscle strength is low, as per a report by Chen et al.25Chen Z. Nilsson E. Lindholm B. et al.Low-plasma insulin-like growth factor-1 associates with increased mortality in chronic kidney disease patients with reduced muscle strength.J Ren Nutr. 2023; 33: 298-306Abstract Full Text Full Text PDF Scopus (1) Google Scholar Rodrigues et al26Rodrigues R.G. Dalboni M.A. Correia M.A. et al.Calf circumference predicts falls in older adults on hemodialysis.J Ren Nutr. 2023; 33: 363-367Abstract Full Text Full Text PDF Scopus (0) Google Scholar report on the association of calf circumference and falls in older adults requiring hemodialysis. Takahashi et al27Takahashi R. Yabe H. Hibino T. et al.Influence of malnutrition on the improvement of physical function by intradialytic resistance exercise in patients undergoing hemodialysis.J Ren Nutr. 2023; 33: 346-354Abstract Full Text Full Text PDF Google Scholar report that malnutrition may not prevent patients requiring hemodialysis from successful intradialytic exercise and physical function improvements. Exercise was also examined by Hendriks et al,28Hendriks F.K. Kuijpers J.H.W. van Kranenburg J.M.X. et al.Intradialytic protein ingestion and exercise do not compromise uremic toxin removal throughout hemodialysis.J Ren Nutr. 2023; 33: 376-385Abstract Full Text Full Text PDF Scopus (0) Google Scholar who describe a crossover study where intradialytic protein supplements versus placebo and exercise versus no exercise were assessed for their influence on uremic toxin removal during hemodialysis. In a secondary analysis of the Rutgers Nutrition and Kidney Disease database, Brown et al29Brown T. Brody R. Sackey J. et al.Dietary intake correlated to waist-to-hip ratio in patients on maintenance hemodialysis.J Ren Nutr. 2023; 33: 355-362Abstract Full Text Full Text PDF Scopus (0) Google Scholar report on the relationship of waist-to-hip ratio and dietary intake in patients receiving chronic hemodialysis. Liver fibrosis was examined in patients receiving hemodialysis who exhibited liver siderosis related to intravenous iron supplementation in a report from Ibrahim et al.30Ibrahim W.H. Abokresha M.M. Nigm D.A. et al.Relation of liver siderosis to liver fibrosis in hemodialysis patients with severe hyperferritinemia secondary to high doses of intravenous iron supplementation.J Ren Nutr. 2023; 33: 337-345Abstract Full Text Full Text PDF Google Scholar Long-term follow-up of participants in the Tehran Lipid and Glucose Study demonstrated that a dietary pattern with high-fat dairy was associated with a lower risk of CKD.31Gaeini Z. Bahadoran Z. Mirmiran P. Feyzi Z. Azizi F. High-fat dairy products may decrease the risk of chronic kidney disease incidence: a long-term prospective cohort study.J Ren Nutr. 2023; 33: 307-315Abstract Full Text Full Text PDF Google Scholar The plasma metabolome of patients with CKD was correlated to oral glucose tolerance testing response and compared to healthy controls in a study examined by Ahmadi et al.32Ahmadi A. Huda M.N. Bennett B.J. et al.Chronic kidney disease is associated with attenuated plasma metabolome response to oral glucose tolerance testing.J Ren Nutr. 2023; 33: 316-325Abstract Full Text Full Text PDF Google Scholar Twelve weeks of a synbiotic supplement demonstrated a reduction in indoxyl sulfate and high sensitive C-reactive protein compared to placebo in patients with CKD in a study from Mitrovic et al.33Mitrović M. Stanković-Popović V. Tolinački M. et al.The impact of synbiotic treatment on the levels of gut-derived uremic toxins, inflammation, and gut microbiome of chronic kidney disease patients- a randomized trial.J Ren Nutr. 2023; 33: 278-288Abstract Full Text Full Text PDF Scopus (1) Google Scholar This issue of the Journal of Renal Nutrition contributes to the knowledge base for nutrition and dietary aspects of treating and preventing kidney disease. We hope our readers are encouraged to examine and further query the topics presented.