Dietary Phosphate Impact on Phosphate Overload

Overseen By John Giacona, PA-C

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Antihypertensives, Vasoactive agents

Disqualifiers: Diabetes, Chronic kidney disease, Cardiopulmonary, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

124 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on antihypertensive medications or any vasoactive agents that affect cardiovascular responses to exercise.

What evidence supports the effectiveness of the treatment for phosphate overload?

Research shows that oral phosphate therapy can reduce certain blood markers in patients with primary hyperparathyroidism, suggesting it may help manage phosphate levels. However, oral sodium phosphate has been effective as a colon cleansing agent, but it can cause shifts in blood volume and other side effects, indicating the need for careful use. ^{1 2 3 4 5}

Is sodium phosphate safe for human use?

Sodium phosphate is often used for bowel cleansing, but it can cause serious side effects like high phosphate levels in the blood, low calcium levels, and kidney problems, especially in people with certain health conditions or when used in high doses. ^{1 6 7 8 9}

How does the drug Sodium Phosphate differ from other treatments for phosphate overload?

Sodium Phosphate is unique because it directly affects appetite and organ growth by altering dietary phosphate levels, which may influence how the body handles phosphate, unlike other treatments that primarily focus on reducing phosphate intake or absorption. ^{3 7 10 11 12}

What is the purpose of this trial?

Studies in mice demonstrated that dietary phosphate (Pi) loading that mimic the level of US adult consumption leads to reduced spontaneous locomotor activity, exercise capacity, and reduced resting metabolic rate when in normal mice by impairing skeletal muscle mitochondrial function and fat oxidation. However, relevance of this findings in humans remains unknown.

Research Team

Wanpen Vongpatanasin, MD

Principal Investigator

[e-mail]

Eligibility Criteria

This trial is for healthy adults without diabetes, chronic kidney disease, heart disease, or those on blood pressure medications. Participants should not be pregnant, have normal phosphate levels in their blood, and no history of psychiatric illness, active cancer or substance abuse including smoking.

Inclusion Criteria

I am healthy without diabetes, kidney disease, heart disease, or taking heart-related meds.

Exclusion Criteria

Any history of substance abuse or current cigarette use

I have a history of cancer.

Serum phosphorus < 2.4 or > 4.5 mg/dL.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Run-in and Washout

Participants undergo a run-in and washout phase to stabilize dietary phosphate intake, estimated by food recall for 2 consecutive days

2 days

Low Phosphate Phase

Participants receive a low phosphate diet (700 mg/d) and Sodium Chloride capsules for 4 weeks

4 weeks

Bi-weekly visits for serum electrolytes and Pi monitoring

High Phosphate Phase

Participants receive a high phosphate diet (1,200 mg/d) and Sodium Phosphate capsules for 4 weeks

4 weeks

Bi-weekly visits for serum electrolytes and Pi monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sodium Chloride
• Sodium Phosphate

Trial Overview The study tests the effects of dietary phosphate (found in many foods) on exercise ability and belly fat. It compares taking sodium phosphate to sodium chloride (table salt), looking at how these supplements might affect physical activity and metabolism.

Participant Groups

Group I: Sodium Phosphate (NaPO4) then sodium chloride (NaCl) Experimental Treatment 2 Interventions

Participants will be asked to take 2 capsules daily of Sodium Phosphate (containing a total of 500 mg of Pi, 372mg of sodium) ) for 4 weeks during the high Pi phase (total Pi intake 1,200 mg/d). Then, participants will be asked to take 2 capsules of Sodium Chloride (NaCl, containing a total of 372mg of sodium) to match Na content to Sodium Phosphate without extra Pi daily for 4 weeks during the low Pi phase (total Pi intake = 700 mg/d).

Group II: NaCl then NaPO4 Experimental Treatment 2 Interventions

Participants will be asked to take 2 capsules daily of Sodium Chloride (NaCl, containing a total of 372mg of sodium) for 4 weeks during the low Pi phase (total Pi intake = 700 mg/d). Then, participants will be asked to take 2 capsules of Sodium Phosphate daily for 4 weeks Sodium Phosphate (containing a total of 500 mg of Pi, 372mg of sodium) for 4 weeks during the high Pi phase (total Pi intake 1,200 mg/d).

Sodium Phosphate is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Sodium Phosphate for:

• Electrolyte imbalance
• Acidosis
• Urinary acidification

Approved in European Union as Sodium Phosphate for:

• Electrolyte disturbances
• Metabolic acidosis

Approved in Canada as Sodium Phosphate for:

• Electrolyte imbalance
• Acidosis

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Findings from Research

Oral sodium phosphate is an effective and well-tolerated agent for colonic cleansing, as shown in multiple clinical trials, but it can cause shifts in intravascular volume and lead to hyperphosphatemia, which may result in hypocalcemia.

A review of cases at the authors' institution found four patients with adverse events related to oral sodium phosphate, primarily in those with pre-existing health conditions or who received higher doses than recommended, highlighting the need for careful patient selection and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognizing the clinical contraindications to the use of oral sodium phosphate for colon cleansing: a case study. Hookey, LC., Vanner, S.[2019]

In a study of 311 patients undergoing colonoscopy, oral sodium phosphate solution (OSPS) caused a slight increase in serum creatinine levels, indicating a minor impact on renal function, but this change was not clinically significant.

The proportion of patients experiencing a significant increase (50% or more) in serum creatinine was similar between those using OSPS and those using polyethylene glycol (PEG), suggesting that OSPS has minimal renal toxicity in patients with baseline creatinine levels below 1.5 mg/dL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol. Singal, AK., Rosman, AS., Post, JB., et al.[2018]

Dietary phosphate influences food intake and appetite, as changes in phosphate load corresponded with variations in digestive system distention, indicating a direct effect on appetite.

Rats receiving phosphate showed specific growth effects in the liver and fat tissue, and their serum contained a factor that inhibits sodium-dependent phosphate transport in kidney cells, suggesting a complex interaction between dietary phosphate and renal function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinctive features of dietary phosphate supply. Landsman, A., Lichtstein, D., Ilani, A.[2013]

A systematic screening of 3763 medications revealed that 12.5% contained phosphorus as an excipient, with the highest prevalence found in oral antidiabetic (23.8%) and antidepressant (19.2%) medications.

While the overall prevalence of phosphate-containing medications is low, calcium hydrogen phosphate, the most common form found, has a lower intestinal absorption rate compared to sodium phosphate, suggesting that the extra phosphate load from medications is generally minimal and mainly a concern in specific cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The extra-phosphate intestinal load from medications: is it a real concern? Cupisti, A., Moriconi, D., D'Alessandro, C., et al.[2018]

In a study of 10 patients with primary hyperparathyroidism, oral phosphate treatment significantly reduced levels of 1,25-dihydroxyvitamin D and calcium excretion, indicating a potential therapeutic effect on hypercalciuria and renal stone formation.

While phosphate therapy showed promise in managing symptoms, it also led to increased biochemical hyperparathyroidism, suggesting that the treatment's long-term impact on bone health and overall metabolic balance needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. Broadus, AE., Magee, JS., Mallette, LE., et al.[2015]

Smaller individuals (weighing <55 kg) experience significantly higher serum phosphate levels after consuming sodium phosphate preparations compared to larger individuals (weighing >100 kg), indicating a potential risk for complications.

The study suggests that lower body weight may increase the risk of calcium-phosphate nephropathy due to elevated phosphate levels, even when hydration is carefully monitored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased serum phosphate levels and calcium fluxes are seen in smaller individuals after a single dose of sodium phosphate colon cleansing solution: a pharmacokinetic analysis. Ehrenpreis, ED.[2013]

Most healthy adults in the U.S. consume nearly double the Recommended Dietary Allowance (RDA) of phosphate, which is set at 700 mg/day, leading to potential health risks.

Excessive phosphate intake is linked to serious health issues such as cardiovascular diseases, kidney diseases, and tumor formation, highlighting the need for better nutritional education and clearer labeling on food products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Dietary Sources of Natural and Artificial Phosphate in Food. Miyamoto, KI., Oh, J., Razzaque, MS.[2022]

Sodium phosphate, commonly used for bowel cleansing, can lead to serious side effects such as hypocalcemia, hyperphosphatemia, and renal failure, as demonstrated in a case involving a 75-year-old woman.

The patient's hypocalcemic tetany and renal failure were linked to asymptomatic hypoparathyroidism, highlighting the importance of considering underlying health conditions when using sodium phosphate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Symptomatic hypocalcemia after sodium phosphate preparation in an adult with asymptomatic hypoparathyroidism. Niemeijer, ND., Rijk, MC., van Guldener, C.[2013]

Sodium phosphate is an effective bowel preparation agent that is generally safe and better tolerated by patients due to its smaller volume requirements.

However, there are significant risks associated with its use, particularly in patients with advanced age, impaired renal function, or colonic motility issues, as evidenced by six reported cases of severe electrolyte imbalances and life-threatening complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe hyperphosphataemia and associated electrolyte and metabolic derangement following the administration of sodium phosphate for bowel preparation. Tan, HL., Liew, QY., Loo, S., et al.[2022]

Regular consumption of ready-to-eat meals is linked to obesity and various health issues, including cardiovascular diseases and diabetes, due to their high calorie content and unhealthy additives.

Excessive intake of phosphate preservatives in processed foods can lead to phosphate toxicity, which may contribute to kidney disease and vascular problems, highlighting a need for better awareness among health professionals and the public.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity, Diabetes Mellitus, and Vascular Impediment as Consequences of Excess Processed Food Consumption. Sinha, S., Haque, M.[2022]

A survey of 190 medical and nursing students revealed that only 6.9% were aware of phosphate in soda drinks and 11.6% in processed foods, highlighting a significant lack of awareness about phosphate toxicity in chronic kidney disease (CKD) patients.

After learning about the risks of high phosphate consumption, 40.5% of students expressed a desire to reduce their intake of phosphate-rich fast foods and sodas, indicating a need for better education on dietary phosphate management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of awareness among future medical professionals about the risk of consuming hidden phosphate-containing processed food and drinks. Shutto, Y., Shimada, M., Kitajima, M., et al.[2021]

Elevated serum phosphorus is a significant risk factor for cardiovascular issues in dialysis patients, making dietary phosphorus restriction crucial for managing hyperphosphatemia.

The average daily phosphorus intake is around 1550 mg for males and 1000 mg for females, but this can be underestimated due to the addition of phosphates in processed foods, which can increase intake by up to 1 g/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? Uribarri, J., Calvo, MS.[2022]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Recognizing the clinical contraindications to the use of oral sodium phosphate for colon cleansing: a case study. [2019]

2. England pubmed.ncbi.nlm.nih.gov

The renal safety of bowel preparations for colonoscopy: a comparative study of oral sodium phosphate solution and polyethylene glycol. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Distinctive features of dietary phosphate supply. [2013]

4. Italy pubmed.ncbi.nlm.nih.gov

The extra-phosphate intestinal load from medications: is it a real concern? [2018]

5. United States pubmed.ncbi.nlm.nih.gov

A detailed evaluation of oral phosphate therapy in selected patients with primary hyperparathyroidism. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Increased serum phosphate levels and calcium fluxes are seen in smaller individuals after a single dose of sodium phosphate colon cleansing solution: a pharmacokinetic analysis. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Common Dietary Sources of Natural and Artificial Phosphate in Food. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Symptomatic hypocalcemia after sodium phosphate preparation in an adult with asymptomatic hypoparathyroidism. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Severe hyperphosphataemia and associated electrolyte and metabolic derangement following the administration of sodium phosphate for bowel preparation. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Obesity, Diabetes Mellitus, and Vascular Impediment as Consequences of Excess Processed Food Consumption. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Lack of awareness among future medical professionals about the risk of consuming hidden phosphate-containing processed food and drinks. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Hidden sources of phosphorus in the typical American diet: does it matter in nephrology? [2022]