Stress, inflammation, depression, and dementia associated with phosphate toxicity
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REVIEW
Stress, inflammation, depression, and dementia associated with phosphate toxicity Ronald B. Brown1 Received: 9 July 2020 / Accepted: 13 November 2020 © Springer Nature B.V. 2020
Abstract Depression and dementia are predicted to increase within aging global populations. Pathophysiological effects of phosphate toxicity, dysregulated amounts of accumulated phosphorus in body tissue, are under-investigated in association with stress, inflammation, depression, and dementia. A comparative analysis of concepts in cited sources from the research literature was used to synthesize novel themes exploring the disease-oriented neuroscience effects of phosphate toxicity. Phosphate toxicity is associated with activation of cellular stress response systems and inflammation. Cortisol released by the hypothalamicpituitary-adrenal axis responds to stress and inflammation associated with phosphate toxicity and depression. In a reciprocal interaction, phosphate toxicity is capable of harming adrenal gland function, possibly leading to adrenal insufficiency and depression. Furthermore, Alzheimer’s disease is associated with hyperphosphorylated tau which self-assembles into neurofibrillary tangles from excessive amounts of phosphate in the brain and central nervous system. Future research should investigate dietary phosphate modification to reduce potential pathophysiological effects of phosphate toxicity in stress, inflammation, depression, and cognitive decline which affects global populations. Keywords Phosphate toxicity · Cortisol · Stress · Inflammation · Depression · Dementia · Alzheimer’s disease · Cognitive decline
Introduction Phosphorus, an essential dietary micronutrient, plays a major role in many structural and metabolic functions in the body, and phosphate toxicity, the excessive cellular accumulation of inorganic phosphate (Pi) caused by dysregulated phosphate metabolism, can adversely affect the body’s major organ systems [1]. Similarly, chronic stress can adversely affect major systems of the body such as the immune system, cardiovascular system, central nervous system, and neuroendocrine system [2]. In the neuroendocrine system, secretion of the glucocorticoid cortisol from the adrenal cortex is activated by the hypothalamic-pituitary-adrenal (HPA) axis in response to stress [3]. This review synthesizes evidence from research findings investigating pathophysiological effects of phosphate toxicity associated with stress, inflammation, depression, and dementia including Alzheimer’s disease. * Ronald B. Brown [email protected] 1
School of Public Health and Health Systems, University of Waterloo, Waterloo, ON N2L 3G1, Canada
Phosphate toxicity is under-investigated in disease-oriented neuroscience research. Innovative findings in this review could stimulate future research that prevents diseases and conditions of stress, inflammation, depression, and cognitive decline in populations around the globe by regulating dietary phosphate consumption and reducing phosphate toxicity.
Phosphate toxicity and cell
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