Big Macs and Heart Attacks; Would you like some inorganic phosphate additives with that?

TMED Blog

| 23 March 2024

Written by Lindsay Jefferson, MSc 25' (Candidate)

On Thursday, February 15th, the Department of Medicine had the privilege of hearing from Dr. Rachel Holden and Dr. Mandy Turner (PhD) about the ongoing epidemic of inorganic phosphate additives in food.

Dr. Holden and Dr. Turner’s presentation discussed inorganic phosphates, their addition to food, potential health harms, and phosphate homeostasis, before finishing off by discussing areas of ongoing research they are undertaking. They began by discussing the prevalence of inorganic phosphates, primarily the lack of labelling in foods as to how much phosphate has been added. This occurs as inorganic phosphates were shown to be ‘safe’, despite more recently discovered potential harms.1

Surprisingly, while phosphates are added to items such as baked goods to help with preservation, they are also highly prevalent in food typically viewed as ‘healthy’, such as non-dairy milks, and are even found in many prescription tablets.1-4 This can all be cause for concern particularly for patients with chronic kidney disease (CKD), where they are instructed to avoid these inorganic phosphates.1

Dr. Turner was then able to describe phosphate homeostasis and discuss these potential harms. She described the increasing medial vascular calcification with an increase in calcium and phosphate deposits into blood vessels.5 This can cause arteries to become stiffer, decreases arterial elasticity, and can cause ischemia (low blood supply).5 All of this is accelerated by conditions such as CKD and diabetes, highlighting the importance for these patients to avoid phosphates.5 The build-up of calcium and phosphate deposits are seemingly causing bone-like structures and calcification.5

Typically, phosphate is absorbed through the small intestine.6 Once in the blood stream, it is distributed to bone, soft tissue, and extra-circulatory spaces, before being eliminated in the kidney.6 However, as kidney function declines, the body appears to compensate, allowing serum (circulating) phosphate levels to remain normal.6

To study this compensation, Dr. Holden’s group devised a test based on the oral glucose tolerance test, where they gave patients a drink with highly bioavailable phosphate, and baseline and hourly blood and urine collections were done.6 This allowed them to measure individual’s levels to excrete phosphate in urine.6 This was followed up with animal studies where phosphate was radiolabeled in a CKD model, which showed phosphates going primarily into bone, heart, and kidney tissues.7 Phosphates were also found going to arteries only in animals with medial calcification, meaning phosphates were depositing into already calcified vessels.7

Dr. Turner then described another player in phosphate homeostasis, calciprotein particles (CPPs).7 These are protein-mineral colloids, where calcium and phosphates in circulation can bind to make CPP-I.8 CPP-I is not crystallized, small enough to get cleared by the kidney, and can perform important duties such as shuttling calcium and phosphate to bones.8 However, at a certain point, CPPs reach a stage where they crystallize, the protein gets bigger, and makes CPP-II, crystalline and sharp, and unable to be cleared by the kidneys.8 The transition time from CPP-I to CPP-II can be measured in serum, and the longer it resists this change under pressure is a measure of resiliency of this system.8 A shorter transition time is associated with adverse outcomes such as negative outcomes in CKD and increased cardiovascular disease (CVD) mortality.8

Dr. Holden finished off by touching on sex differences in CVD potentially linked to phosphate levels in females,9 the further lack of regulation on phosphates in pet food, and the political aspect to inorganic phosphate food additives.

Afterwards, Dr. Holden and Dr. Turner offered their time to the TMED 801 class where students were able to ask questions about how their research directly impacts patients, such as the difficulties with food labelling. Dr. Holden emphasized the importance of interdisciplinary work with inorganic phosphate management, highlighting the role dietitians and pharmacists play in helping patients avoid phosphates. We further discussed research and policy changes surrounding inorganic phosphates and how this has shifted over time in patient, researcher, and public perspectives. They highlighted difficulties with testing phosphate levels and homeostasis in patients, particularly due to inaccuracies of the serum blood test, the currently accepted methodology for phosphate testing. The latter part of our discussion focused on Dr. Holden and Dr. Turner’s career paths, where they emphasized the importance of supervisor-student mentorship, give us advice as we move through academia and beyond, and highlighted the importance of collaboration.

On behalf of the Department of Medicine and the TMED 801 class, I would like to thank Dr. Holden and Dr. Turner for taking the time to teach and inspire us.

References:

1. Olanbiwonnu T, Holden RM. Inorganic phosphate as a potential risk factor for chronic disease. Canadian Medical Association journal (CMAJ). 2018;190:E784-E785. doi: 10.1503/cmaj.180525

2. Lim R, How P, Lee C, Yong XN, Wong WK, Lo E. Phosphorus Content of Commonly Prescribed Medications Among Patients With Chronic Kidney Disease. Journal of renal nutrition. 2022;32:22-29. doi: 10.1053/j.jrn.2021.08.010

3. Tarantola J, Wujastyk L. Alternative Milk Beverages. Journal of renal nutrition. 2009;19:e1-e10. doi: 10.1053/j.jrn.2008.12.002

4. Antle L. Is Your Milk Kidney Friendly? Kidney Nutrition Institute. https://kidneynutritioninstitute.org/is-your-milk-kidney-friendly/. September, 2023. Accessed February 18, 2024.

5. Kim TI, Guzman RJ. Medial artery calcification in peripheral artery disease. Frontiers in cardiovascular medicine. 2023;10:1093355-1093355. doi: 10.3389/fcvm.2023.1093355

6. Turner ME, White CA, Hopman WM, Ward EC, Jeronimo PS, Adams MA, Holden RM. Impaired Phosphate Tolerance Revealed With an Acute Oral Challenge. Journal of bone and mineral research. 2018;33:113-122. doi: 10.1002/jbmr.3294

7. Turner ME, Rowsell TS, Lansing AP, Jeronimo PS, Lee LH, Svajger BA, Zelt JGE, Forster CM, Petkovich MP, Holden RM, Adams MA. Vascular calcification maladaptively participates in acute phosphate homeostasis. Cardiovascular research. 2023;119:1077-1091. doi: 10.1093/cvr/cvac162

8. Silaghi CN, Ilyés T, Van Ballegooijen AJ, Crăciun AM. Calciprotein particles and serum calcification propensity: Hallmarks of vascular calcifications in patients with chronic kidney disease. Journal of clinical medicine. 2020;9:1287. doi: 10.3390/jcm9051287

9. Turner ME, Paynter AS, White CA, Mazzetti T, Ward EC, Norman PA, Munroe J, Adams MA, Holden RM. Sex Differences in Phosphate Homeostasis: Females Excrete More Phosphate and Calcium After an Oral Phosphate Challenge. The journal of clinical endocrinology and metabolism. 2023;108:909-919. doi: 10.1210/clinem/dgac616

Big Macs and Heart Attacks; Would you like some inorganic phosphate additives with that?

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Big Macs and Heart Attacks; Would you like some inorganic phosphate additives with that?

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