Vitamin C's Impact on Kidney Stones

Overseen By Demond Wiley

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must be taking: Thiazides, Citrate supplementation

Disqualifiers: Diabetes, Hypertension, Gout, others

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

Compensation: Varies

Number of Visits: 6

Duration: 4 days

136 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how vitamin C (ascorbic acid) affects kidney stone formation, focusing on the body's conversion of this vitamin into oxalate, which can contribute to stones. Participants will follow a specific diet low in oxalate and vitamin C, take a vitamin C supplement (Carbon-13 Ascorbic Acid Oral Load), and provide blood and urine samples for analysis. It is ideal for adults who have had calcium oxalate kidney stones within the past three years and are willing to adjust their diet and medication as needed for the study.

As an unphased trial, this study offers a unique opportunity to contribute to scientific understanding and potentially benefit future patients with kidney stones.

Will I have to stop taking my current medications?

The trial requires participants to stop taking supplements like vitamins, calcium, and other minerals for 2 weeks before and during the study. If you are on medications for stone prevention, you must have been on a stable dose for at least 8 weeks before the study, and if you take allopurinol, you need to stop it 2 weeks before the study.

What prior data suggests that this method is safe?

Research shows that vitamin C is generally safe for most people. Earlier studies used special forms of vitamin C to examine its absorption, and these studies reported no serious side effects.

However, some research has found that vitamin C can alter urine, potentially making it more acidic and increasing the risk of certain kidney stones. Despite this, the studies did not identify major safety concerns with its use.

Overall, vitamin C is usually well-tolerated, but awareness of its possible effects on urine and kidney stone risk is important. Always consult a healthcare provider before starting a new supplement or treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for kidney stones, which often focus on pain management or surgical removal, the use of Carbon-13 Ascorbic Acid aims to understand how vitamin C can influence stone formation. This approach is unique because it involves a controlled dietary study that carefully monitors vitamin C intake, allowing researchers to track its metabolism and effects on kidney stone risk. Researchers are excited about this trial as it could reveal new insights into preventing kidney stones by managing dietary factors, potentially offering a non-invasive and preventive strategy.

What evidence suggests that Carbon-13 Ascorbic Acid Oral Load might be an effective treatment for kidney stones?

Research has shown that vitamin C can influence the risk of developing kidney stones, particularly in men. One study found that moderate vitamin C intake slightly increased urinary oxalate, a substance linked to kidney stones. Another study discovered that high vitamin C intake might raise the risk of kidney stones in men, but not in women. This trial will investigate the impact of a controlled dietary study, where participants will consume a low oxalate and ascorbic acid diet, followed by an oral load of ascorbic acid. Overall, these findings suggest that vitamin C can affect kidney stone risk, depending on the individual and their consumption levels. ^{1 3 6 7 8}

Who Is on the Research Team?

John Knight

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for adults with normal BMI or obese, non-stone formers and calcium oxalate stone formers who haven't had certain health conditions like diabetes, hypertension, or severe kidney issues. Participants must not be on specific medications that could affect the study results and should agree to follow a controlled diet without supplements or vigorous exercise during the study.

Inclusion Criteria

Able to provide informed consent

Your fasting blood test results are normal for a comprehensive metabolic panel (CMP).

Willingness to not undertake vigorous exercise during the study

Exclusion Criteria

Your kidney function is too low (eGFR less than 60ml/min/1.73m2).

I have been diagnosed with primary hyperoxaluria.

I have high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Dietary Equilibration

Participants consume a controlled diet low in oxalate and ascorbic acid for two days to equilibrate

2 days

1 visit (in-person)

Treatment

Participants ingest an oral load of carbon-13 ascorbic acid and undergo serial blood and urine collections

4 days

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carbon-13 Ascorbic Acid Oral Load
• Low Oxalate Diet

Trial Overview

The study aims to understand how much vitamin C (ascorbic acid) from our diet turns into oxalate in the urine, which can contribute to kidney stones. It involves following a special low-oxalate diet and taking a stable isotope of ascorbic acid orally while researchers measure its turnover using advanced techniques.

How Is the Trial Designed?

Group I: Controlled Dietary Study Experimental Treatment 2 Interventions

Subjects will consume a controlled diet (low in oxalate and ascorbic acid) for six days. After two days of equilibration, subjects will provide a blood sample and ingest an oral load of ascorbic acid (1 mg/kg) with breakfast on Day 3. The following day (Day 4), serial blood and urine collections will occur. On Days 5 through 7, subjects will complete a 24-hr urine collection and blood draw.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

Ascorbic acid (AA) supplements are associated with a significantly higher risk of kidney stones in men, with an odds ratio of 1.62, indicating that men taking AA supplements may be more likely to develop kidney stones compared to women.

In contrast, AA supplements do not show a significant correlation with kidney stone risk in women, suggesting that the effects of AA may differ by gender and highlighting the need for further research to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic Acid Supplements and Kidney Stones Incidence Among Men and Women: A systematic review and meta-analysis. Jiang, K., Tang, K., Liu, H., et al.[2020]

In a study involving 156,735 women and 40,536 men over a median follow-up of 11.3 to 11.7 years, high total and supplemental vitamin C intake was linked to an increased risk of kidney stones in men, particularly at doses of 1,000 mg/day or more.

Conversely, no significant association was found between vitamin C intake and kidney stones in women, suggesting that the effects of vitamin C on kidney stone risk may differ by sex.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total, Dietary, and Supplemental Vitamin C Intake and Risk of Incident Kidney Stones. Ferraro, PM., Curhan, GC., Gambaro, G., et al.[2018]

Ascorbic acid (AA) supplementation significantly lowered urinary pH in stone-forming patients, from 7.6 to 6.9, which may influence the formation of certain types of kidney stones.

Despite the reduction in urinary pH, 33.3% of patients developed new kidney stones, indicating that while AA may alter urine acidity, it does not necessarily prevent stone formation and could lead to complications like hyperoxaluria in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is it safe to prescribe ascorbic acid for urinary acidification in stone-forming patients with alkaline urine? Noureldin, YA., da Silva, A., Fahmy, N., et al.[2020]

A male subject who consumed large doses of vitamin C for 8 days experienced a 350% increase in oxalate excretion, leading to calcium oxalate crystalluria and haematuria, indicating a significant risk associated with high vitamin C intake.

The study highlights that high doses of vitamin C can lead to increased calcium oxalate supersaturation in urine, suggesting that clinicians should be cautious about recommending large doses of vitamin C due to the potential for kidney stone formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C. Auer, BL., Auer, D., Rodgers, AL.[2019]

High doses of vitamin C do not increase the risk of calcium oxalate kidney stones due to the body's ability to regulate absorption and metabolism of ascorbic acid, which limits oxalate production.

In a large study, individuals consuming more than 1,500 mg of vitamin C daily actually had a lower risk of developing kidney stones compared to those with lower intakes, suggesting a protective effect in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No contribution of ascorbic acid to renal calcium oxalate stones. Gerster, H.[2022]

In a study involving 47 calcium stone-forming patients and 20 healthy subjects, vitamin C supplementation (1 g or 2 g) significantly increased urinary oxalate levels, suggesting a potential risk for calcium oxalate stone formation.

Despite the increase in urinary oxalate, urinary pH remained unchanged after vitamin C supplementation, indicating that the mechanism of increased oxalate excretion does not involve changes in urine acidity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of vitamin C supplements on urinary oxalate and pH in calcium stone-forming patients. Baxmann, AC., De O G Mendonça, C., Heilberg, IP.[2016]

In a study involving guinea pigs, ascorbic acid supplementation at doses of 10, 40, and 60 mg per 100g body weight per day for 105 days did not lead to crystalluria, calcification, or stone formation, confirming its safety in the doses typically used by clinicians.

However, when ascorbic acid was given to animals with induced hypercalciuria and hyperoxaluria for 45 days, it worsened calcification in renal and bladder tissues, suggesting caution in its use under certain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic acid is an abettor in calcium urolithiasis: an experimental study. Singh, PP., Kiran, R., Pendse, AK., et al.[2013]

Ingesting large doses of vitamin C (ascorbic acid) does not appear to cause significant adverse health effects in healthy individuals, despite concerns about issues like kidney stones and vitamin B12 destruction.

However, high doses of ascorbic acid should be avoided in people with certain health conditions, such as renal insufficiency or those prone to kidney stones, indicating the need for caution in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of high-level vitamin C ingestion. Rivers, JM.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4769668/

Total, Dietary, and Supplemental Vitamin C Intake and Risk ...

Total and supplemental intake of vitamin C was significantly associated with a higher risk of incident kidney stones in men, but not among women.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4946963/

Ascorbic Acid Intake and Oxalate Synthesis - PMC

In humans approximately 60 mg of ascorbic acid (AA) breaks down in the body each day and has to be replaced by a dietary intake of 70 mg in females and 90 mg ...

3.

auajournals.org

auajournals.org/doi/10.1097/01.ju.0000076001.21606.53

Effect of Ascorbic Acid Consumption On Urinary Stone Risk ...

Ingestion of moderate doses of vitamin C results in a modest but statistically significant increase in urinary oxalate in normal subjects (20%) and in stone ...

4.

researchgate.net

researchgate.net/publication/376281246_Effect_of_Ascorbic_Acid_on_the_Kidneys

(PDF) Effect of Ascorbic Acid on the Kidneys

Results Data revealed that vitamin C therapy was associated with increases in AKI (OR = 2.07 95% CI [1.46–2.93]) and in-hospital mortality (OR = 1.67 95% CI ...

5.

mdpi.com

mdpi.com/2072-6643/15/4/877

Kidney Stone Prevention: Is There a Role for ...

The overall results suggested that high intake of vitamin C can be a risk factor for kidney stones in males, whereas high dietary vitamin B6 ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5503439/

Is it safe to prescribe ascorbic acid for urinary acidification ...

AA supplementation resulted in significantly lower urinary pH in patients with recurrent urolithiasis and alkaline urine pH.

7.

mdpi.com

mdpi.com/2072-6643/13/6/1917

Nutrition and Kidney Stone Disease

The association between ascorbic acid intake and the risk of urinary stone formation has been noted in several large cohort studies [146,147]. A study under ...

8.

urologyresearchandpractice.org

urologyresearchandpractice.org/content/files/sayilar/166/buyuk/183-8.pdf

Is it safe to prescribe ascorbic acid for urinary acidification ...

Exclusion criteria consisted of over-the-counter use of AA without prescription, no history of urolithiasis and missing data about urine.