Seminars in nephrologyOct 24, 2026

Intestinal Phosphate Absorption and Phosphate Metabolism in Chronic Kidney Disease: Direct and Indirect Toxicity of Phosphate Additives in Ultra-processed Diets.

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 25, 2026

Abstract

Chronic kidney disease is associated with constant intestinal phosphate absorption despite decreased kidney excretion capacity.

Rising levels of fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) help maintain normal serum phosphate until advanced stages of chronic kidney disease.
Ultra-processed foods contain phosphate additives that are absorbed more readily than natural food phosphates, leading to underestimation of true phosphorus exposure.
The direct pathway of harm from phosphate additives includes activation of PTH and FGF23, vascular and soft-tissue calcification, and faster chronic kidney disease progression.
The indirect pathway involves combinations of phosphate additives with other ingredients that may contribute to gut dysbiosis, inflammation, and the formation of harmful toxins.
Current understanding suggests the need for more comprehensive safety evaluations of additive mixtures and better phosphorus labeling to assess long-term health impacts.

Simplified

In chronic kidney disease (CKD), intestinal phosphate absorption stays largely constant even as the kidneys lose the ability to excrete phosphate, creating a tendency toward positive phosphate balance. Rising fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) keep serum phosphate near normal until advanced CKD, but these same adaptations can cause systemic harm long before overt hyperphosphatemia develops. Ultra-processed foods worsen this burden through phosphate additives (Pi-additives) used as preservatives, emulsifiers, stabilizers, leavening agents, and moisture retainers. These additives are absorbed more readily than natural food phosphate and are poorly captured by nutrient databases. Therefore, true phosphorus exposure is easily underestimated. This perspective outlines 2 pathways of harm. The direct pathway involves PTH and FGF23 activation, vascular and soft-tissue calcification, endothelial dysfunction, disordered bone remodeling, faster CKD progression, and cellular senescence-effects documented in CKD and possibly relevant even with preserved kidney function. The indirect pathway reflects that Pi-additives rarely occur alone: they accompany added sugars, non-nutritive sweeteners, nitrites, emulsifiers, and preservatives in ultra-processed foods, combinations that may drive gut dysbiosis, intestinal barrier dysfunction, oxidative stress, inflammation, and the formation of advanced glycation endproducts and other gut-derived toxins. We synthesize current understanding of phosphate homeostasis with mechanistic and epidemiologic evidence linking Pi-additives-alone and combined with other additives-to cardiovascular, skeletal, renal, and metabolic disease. Future research should move beyond single-additive safety testing toward evaluating additive mixtures, cumulative exposure, and food-matrix interactions. Better exposure assessment and transparent phosphorus labeling are essential to clarify the long-term health effects of these ubiquitous additives.

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Intestinal Phosphate Absorption and Phosphate Metabolism in Chronic Kidney Disease: Direct and Indirect Toxicity of Phosphate Additives in Ultra-processed Diets.

Abstract

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