Vitamin D, phosphate, and vasculotoxicity

Brown, Ronald B.; Haq, Afrozul; Stanford, Charles; Razzaque, Mohammed S.

doi:10.1139/cjpp-2015-0083

Cited by 32 publications

(18 citation statements)

References 98 publications

(79 reference statements)

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“…Vitamin D helps regulate calcium and phosphate balance to maintain healthy bone functions. [1][2][3][4][5][6] Skeletal muscles, heart, teeth, bones, and many other organs require magnesium to sustain their physiologic functions. Furthermore, magnesium is needed to activate vitamin D. Abnormal levels in either of these nutrients can lead to serious organ dysfunctions.…”

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confidence: 99%

Role of Magnesium in Vitamin D Activation and Function

Uwitonze¹,

Razzaque²

2018

J Am Osteopath Assoc

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273

207

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Nutrients usually act in a coordinated manner in the body. Intestinal absorption and subsequent metabolism of a particular nutrient, to a certain extent, is dependent on the availability of other nutrients. Magnesium and vitamin D are 2 essential nutrients that are necessary for the physiologic functions of various organs. Magnesium assists in the activation of vitamin D, which helps regulate calcium and phosphate homeostasis to influence the growth and maintenance of bones. All of the enzymes that metabolize vitamin D seem to require magnesium, which acts as a cofactor in the enzymatic reactions in the liver and kidneys. Deficiency in either of these nutrients is reported to be associated with various disorders, such as skeletal deformities, cardiovascular diseases, and metabolic syndrome. It is therefore essential to ensure that the recommended amount of magnesium is consumed to obtain the optimal benefits of vitamin D.

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mentioning

confidence: 99%

Role of Magnesium in Vitamin D Activation and Function

Uwitonze¹,

Razzaque²

2018

J Am Osteopath Assoc

Self Cite

273

207

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“…2,3 However, physiologic phosphate regulation cannot be fully explained by the actions of these hormones alone, [4][5][6][7][8] and the identification of fibroblast growth factor 23 (FGF23), which can influence both vitamin D and PTH functions, helped us gain further insights into the physiologic regulation of phosphate homeostasis. Skeletal-derived FGF23 exerts phosphate-lowering effects in the kidney via a complex endocrine network; studies have identified osteoblasts and osteocytes as the main FGF23-producing cells.…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity

Brown

2015

BoneKEy Reports

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Phosphate homeostasis is coordinated and regulated by complex cross-organ talk through delicate hormonal networks. Parathyroid hormone (PTH), secreted in response to low serum calcium, has an important role in maintaining phosphate homeostasis by influencing renal synthesis of 1,25-dihydroxyvitamin D, thereby increasing intestinal phosphate absorption. Moreover, PTH can increase phosphate efflux from bone and contribute to renal phosphate homeostasis through phosphaturic effects. In addition, PTH can induce skeletal synthesis of another potent phosphaturic hormone, fibroblast growth factor 23 (FGF23), which is able to inhibit renal tubular phosphate reabsorption, thereby increasing urinary phosphate excretion. FGF23 can also fine-tune vitamin D homeostasis by suppressing renal expression of 1-alpha hydroxylase (1a(OH)ase). This review briefly discusses how FGF23, by forming a bone-kidney axis, regulates phosphate homeostasis, and how its dysregulation can lead to phosphate toxicity that induces widespread tissue injury. We also provide evidence to explain how phosphate toxicity related to dietary phosphorus overload may facilitate incidence of noncommunicable diseases including kidney disease, cardiovascular disease, cancers and skeletal disorders.

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“…In the first phase, biochemical investigations into the physiology of phosphate metabolism, the healthful effects of its regulation, and the harmful consequences of its dysregulation must generate a scientific consensus about the dangers of phosphate toxicity. However, as important as biochemical discoveries are, it is also essential that research findings are translated into preventive applications and public health interventions that allow the public to benefit healthwise [32,33].…”

Section: Discussionmentioning

confidence: 99%

Phosphate toxicity: a stealth biochemical stress factor?

Brown

2015

Med Mol Morphol

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Phosphate is an essential mineral component of the human body, and therefore, its dysregulation can affect the functionality of almost all the organ systems. Both organic and inorganic forms of phosphate are routinely consumed through meats, fish, eggs, milk/dairy products, and vegetables. The amount of total phosphate ingestion is significantly increased by the consumption of processed food and drinks in which phosphate metabolites are used as additives. Of clinical significance, phosphate additives are almost entirely absorbed in the intestine, whereas about 60 % is absorbed from naturally available sources [1]. Normal phosphate homeostasis is tightly controlled by numerous endocrine factors, including fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), vitamin D and klotho [2][3][4][5][6][7][8][9]. FGF23, through the activation of FGF receptors, acts as a counter regulatory hormone to suppress renal 1a-hydroxylase and activities of sodium-phosphate cotransporters (NaPi2a and NaPi2c) which influence systemic phosphate balance [7]; such receptor activation by FGF23 needs klotho, as a cofactor to generate downstream signaling events [10]. Moreover, PTH can induce FGF23 transcription in bone cells to influence systemic phosphate balance [11].In an average healthy 70 kg adult individual, the total body phosphorus content is around 700 g, more than 80 % of which is present in the bone and tooth (calcium-phosphate hydroxyapatite), about 9 % in the skeletal muscle, around 10 % in various internal organs, and less than 1 % in the extracellular fluid [12]. In general, serum inorganic phosphate is actively transported through the cellular membrane, often against a molecular concentration gradient and involving glucose metabolism. Type III sodium-phosphate cotransporters (SLC20 family; also called Pit-1 and Pit-2), alongside Type I (SLC17 family) and Type II (SLC34 family) are believed to be involved in cellular phosphate transport in various organs. Pit-1 and Pit-2 are mostly expressed on the basolateral membranes of the epithelial cells, where these transporters are likely to be involved in cellular phosphate transport. Although measuring extracellular serum phosphate is the gold standard to estimate the overall phosphate status of the body, the amount of intracellular phosphate distribution or phosphate storage or the amount of phosphate uptake is not taken into consideration in such traditional methods of serum measurement. Moreover, lack of public awareness of getting too much dietary phosphorus [13,14], which might not always be reflected by serum phosphate levels, is gradually becoming a public health concern as dietary phosphate burden from consumption of an unhealthy diet is linked to various non-communicable diseases and eventual mortality [15].

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Vitamin D, phosphate, and vasculotoxicity

Cited by 32 publications

References 98 publications

Role of Magnesium in Vitamin D Activation and Function

Role of Magnesium in Vitamin D Activation and Function

Dysregulation of phosphate metabolism and conditions associated with phosphate toxicity

Phosphate toxicity: a stealth biochemical stress factor?

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