This article was published on July 7, 2022. It was last edited on July 9, 2022.
In recent years, there has been great enthusiasm—maybe, too much enthusiasm?—for recommending vitamin D supplementation. That is why we have many articles on this website about the evaluation and treatment of vitamin D insufficiency or deficiency; please see Related Pages below.
Of course, vitamin D supplementation in reasonable doses is generally safe and well-tolerated. It is only with the consumption of massive doses of vitamin D that vitamin D toxicity occurs. On this page, we won’t discuss vitamin D toxicity due to massive doses.
Instead, before we assume that vitamin D supplementation at recommended doses is completely benign, let’s ask the question of whether vitamin D supplementation at commonly used doses increases calcium excretion in the urine leading to hypercalciuria and, so, to an increased risk of kidney stone formation.
Why increased urinary calcium excretion increases the risk of kidney stones
Kidney stones develop due to a combination of many factors—genetics, diet, fluid intake, and so on. The most common type of kidney stones, by far, are those that contain calcium oxalate. And, the second most common ones are those that contain calcium phosphate. Together, these two types of stones that contain calcium compounds (by themselves or mixed with other compounds) account for roughly 85% of all kidney stones (Bargagli et al., 2021; Schulster and Goldfarb, 2020).
This explains why a major risk factor for the formation of kidney stones is excessive excretion of calcium in the urine—hypercalciuria.
Vitamin D levels in persons with kidney stones/ hypercalciuria
When clinicians order a vitamin D level, we get the levels for 25-hydroxy vitamin D (calcidiol) and not for calcitriol even though calcitriol is the main active form of vitamin D. Why is that? Because calcitriol has a very short half-life in the blood, only a few hours, while in adults the half-life of 25-hydroxy vitamin D is about two weeks (Bouillon and Carmeliet, 2018).
Here are two findings about kidney stones, hypercalciuria, and vitamin D (Bargagli et al., 2021):
– Patients who tend to form kidney stones, also tend to have higher levels of the main biologically active form of vitamin D—calcitriol (1, 25-dihydroxy vitamin D).
– Persons with hypercalciuria tend to have higher levels of plasma 25-hydroxycholecalciferol (25-hydroxy vitamin D or calcidiol).
But such studies can’t show that the higher levels of calcitriol or calcidiol were the cause of kidney stones or hypercalciuria. To evaluate whether or not vitamin D supplementation is causally related to kidney stones/ hypercalciuria, we need prospective follow-up studies and, preferably, ones in which patients were randomized to receive either vitamin D or placebo.
What do prospective follow-up studies show?
– A meta-analysis of studies found that vitamin D supplementation did increase the risk of hypercalcemia and hypercalciuria (Malihi et al., 2016).
– But in that meta-analysis, vitamin D supplementation did not increase the risk of kidney stones (Malihi et al., 2016).
– A large prospective study published after the meta-analysis mentioned above did not find a relationship between vitamin D intake and the risk of developing kidney stones (Ferraro et al., 2017).
Supplementation with BOTH calcium and vitamin D
Data from three randomized, controlled clinical trials with a total of nearly 40,000 participants show that supplementation with BOTH vitamin D and calcium for 4 to 7 years did increase the incidence of kidney stones (US Preventive Services Task Force, 2018). Their report categorically concluded: “The USPSTF found adequate evidence that supplementation with vitamin D and calcium increases the incidence of kidney stones” (US Preventive Services Task Force, 2018).
Just to clarify, we are not talking about supplementation with high doses of vitamin D and calcium. For example, in one of the 3 clinical trials, a large, well-known study, women randomized to receive just 1000 mg/day of elemental calcium (in the form of calcium carbonate) and a relatively small amount of vitamin D3 (400 IU/day) were found to have an increased risk of kidney stones (Jackson et al., 2004).
1. Vitamin D supplementation does seem to increase the risk of hypercalciuria. This could be very serious because hypercalciuria is one of the main risk factors for developing calcium-containing kidney stones.
2. Vitamin D supplementation alone has not been directly linked to an increased risk of kidney stones. But, my thought is that the risk of kidney stones may be underestimated because:
– Kidney stones take time to form, and
– Kidney stones may be missed while they are still small.
3. Supplementation with both vitamin D and calcium, even at modest doses, does increase the risk of developing kidney stones.
4. It has been hypothesized that, due to genetic mutations, some persons with a history of kidney stones may be at increased risk of recurrence of kidney stones if given vitamin D supplementation, which are known to be a risk factor for stone formation (Schulster and Goldfarb, 2020).
Here I won’t go into the controversies related to checking vitamin D levels and the limited benefits of vitamin D supplementation (despite the hype). I’ll just share a summary statement from a review article: “…routine screening and supplementation in asymptomatic patients likely has little benefit and may present a theoretical harm in some genetically predisposed stone formers” (Schulster and Goldfarb, 2020).
Let me first share with two statistics that shocked me and convinced me that all clinicians should be concerned about kidney stones:
– Since 1980, the prevalence of kidney stones in the USA has nearly TRIPLED!
– In the USA, the lifetime prevalence of kidney stones is nearly 9%.
Vitamin D supplementation at reasonable doses is usually safe and has not been shown to increase the risk of kidney stones. But, in some situations, we may need to be concerned about a possible increased risk of kidney stones with vitamin D supplementation:
1. Patients who are known to already have hypercalciuria. In these patients, giving vitamin D supplementation could further increase the risk of kidney stone formation (Bargagli et al., 2021).
2. Patients who have previously developed a calcium-containing urinary stone.
3. Patients who have other risk factors for developing calcium-containing stones.
What could be done in persons like those described above to not increase their risk of developing kidney stones?
1. In these patients, supplementation with both calcium and vitamin D should probably be avoided.
2. If vitamin D supplementation is needed, only modest doses of vitamin D should be given. Presumably, the risk of kidney stones would be expected to go up with higher doses of vitamin D.
3. These high-risk patients could be screened for possible hypercalciuria.
What test should be ordered to screen for hypercalciuria?
The definitive test for hypercalciuria is 24-hour urinary calcium excretion. But, collection of a 24-hour urine sample is quite inconvenient. So, instead, to screen for hypercalciuria, clinicians often check the calcium to creatinine ratio in a random urine sample.
We can see this test on the websites of large laboratory chains in the US—Labcorp and Quest Diagnostics. For Labcorp, the test can be ordered as “urine calcium: creatinine ratio” and for Quest Diagnostics as “Calcium, Random Urine with Creatinine”.
Optional to read: The ratio of urine calcium (mg/dL) to creatinine (mg/dL) ratio is normally 0.14 or less. If the ratio is clearly above this cut-off, say, more than 0.20, this suggests that hypercalciuria is present (source).
1. The calcium: creatinine ratio in a random urine sample may not correlate well with 24-hour urinary calcium excretion (Song and Maalouf, 2017). So, in case of doubt or greater concern, measurement of 24-hour urinary calcium excretion should be ordered.
2. There is no specific cut-off for urinary calcium excretion or calcium: creatinine ratio that identifies the presence or absence of increased risk of stone formation. Rather, the risk of stone formation goes up with progressively higher levels of urinary calcium excretion.
Optional to read: Causes of increased urinary calcium excretion
(in no particular order)
Vitamin D overdose
Bone destruction due to multiple myeloma, metastasis of cancer to bone
Primary (idiopathic) hypercalciuria.
Articles published in 2019 or later
Bargagli M, Ferraro PM, Vittori M, Lombardi G, Gambaro G, Somani B. Calcium and Vitamin D Supplementation and Their Association with Kidney Stone Disease: A Narrative Review. Nutrients. 2021 Dec 4;13(12):4363. doi: 10.3390/nu13124363. PMID: 34959915; PMCID: PMC8707627.
Malihi Z, Lawes CMM, Wu Z, Huang Y, Waayer D, Toop L, Khaw KT, Camargo CA, Scragg R. Monthly high-dose vitamin D supplementation does not increase kidney stone risk or serum calcium: results from a randomized controlled trial. Am J Clin Nutr. 2019 Jun 1;109(6):1578-1587. doi: 10.1093/ajcn/nqy378. PMID: 31005969.
Malihi Z, Wu Z, Lawes CMM, Scragg R. Adverse events from large dose vitamin D supplementation taken for one year or longer. J Steroid Biochem Mol Biol. 2019 Apr;188:29-37. doi: 10.1016/j.jsbmb.2018.12.002. Epub 2018 Dec 6. PMID: 30529281.
Schulster ML, Goldfarb DS. Vitamin D and Kidney Stones. Urology. 2020 May;139:1-7. doi: 10.1016/j.urology.2020.01.030. Epub 2020 Feb 4. PMID: 32032687.
Smith LM, Gallagher JC. Reference range for 24-h urine calcium, calcium/creatinine ratio, and correlations with calcium absorption and serum vitamin D metabolites in normal women. Osteoporos Int. 2021 Mar;32(3):539-547. doi: 10.1007/s00198-020-05615-6. Epub 2020 Sep 4. PMID: 32886188; PMCID: PMC8451703. This reference was not used in the article on this webpage.
Taheri M, Tavasoli S, Shokrzadeh F, Amiri FB, Basiri A. Effect of vitamin D supplementation on 24-hour urine calcium in patients with calcium Urolithiasis and vitamin D deficiency. Int Braz J Urol. 2019 Mar-Apr;45(2):340-346. doi: 10.1590/S1677-5538.IBJU.2018.0522. PMID: 30735332; PMCID: PMC6541149. This reference was not used in the article on this webpage.
Articles published earlier than 2019
Bouillon R, Carmeliet G. Vitamin D insufficiency: Definition, diagnosis and management. Best Pract Res Clin Endocrinol Metab. 2018 Oct;32(5):669-684. doi: 10.1016/j.beem.2018.09.014. Epub 2018 Oct 3. PMID: 30449548.
Eisner BH, Thavaseelan S, Sheth S, Haleblian G, Pareek G. Relationship between serum vitamin D and 24-hour urine calcium in patients with nephrolithiasis. Urology. 2012 Nov;80(5):1007-10. doi: 10.1016/j.urology.2012.04.041. Epub 2012 Jun 13. PMID: 22698470. This reference was not used in the article on this webpage.
Ferraro PM, Taylor EN, Gambaro G, Curhan GC. Vitamin D Intake and the Risk of Incident Kidney Stones. J Urol. 2017 Feb;197(2):405-410. doi: 10.1016/j.juro.2016.08.084. Epub 2016 Aug 18. PMID: 27545576; PMCID: PMC5241241.
Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D; Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med. 2006 Feb 16;354(7):669-83. doi: 10.1056/NEJMoa055218. Erratum in: N Engl J Med. 2006 Mar 9;354(10):1102. PMID: 16481635.
Letavernier E, Daudon M. Vitamin D, Hypercalciuria and Kidney Stones. Nutrients. 2018 Mar 17;10(3):366. doi: 10.3390/nu10030366. PMID: 29562593; PMCID: PMC5872784.
Malihi Z, Wu Z, Stewart AW, Lawes CM, Scragg R. Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis. Am J Clin Nutr. 2016 Oct;104(4):1039-1051. doi: 10.3945/ajcn.116.134981. Epub 2016 Sep 7. PMID: 27604776.
Song L, Maalouf NM. 24-Hour Urine Calcium in the Evaluation and Management of Nephrolithiasis. JAMA. 2017 Aug 1;318(5):474-475. doi: 10.1001/jama.2017.7085. PMID: 28763529.
Taylor PN, Davies JS. A review of the growing risk of vitamin D toxicity from inappropriate practice. Br J Clin Pharmacol. 2018 Jun;84(6):1121-1127. doi: 10.1111/bcp.13573. Epub 2018 Apr 16. PMID: 29498758; PMCID: PMC5980613.
US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Barry MJ, Caughey AB, Davidson KW, Doubeni CA, Epling JW Jr, Kemper AR, Krist AH, Kubik M, Landefeld S, Mangione CM, Silverstein M, Simon MA, Tseng CW. Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 Apr 17;319(15):1592-1599. doi: 10.1001/jama.2018.3185. PMID: 29677309.
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