Vitamin C with Metabolites Reduce Oxalate Levels Compared to Ascorbic Acid: A Pre l i m i n a ry and Novel Clinical Urologic Finding Mark A. Moyad Joshua E. Baisley Angelica S. Vr a b l i c Maile A. Combs Prachi Sharm a Malkanthi Evans David C. Crowley e p h rolithiasis, or form a- The incidence and prevalence of kidney stones are notable and are tion of kidney stones, p rojected to increase over the next decade. Risk factors for kidney is a worldwide issue stones abound, but a prominent risk factor is hy p e rox a l u r i a , w h i ch impacting all racial, eth- has nu m e rous etiologies, i n cluding vitamin C (ascorbic acid) dietary Nnic, cultural, and geographic supplement intake. This randomize d , d o u bl e - bl i n d , c ro s s over study g roups (Wo r cester & Coe, 2008). examined the effects of two different vitamin C fo r mulations and Past incidence and prevalence of found that vitamin C with metabolites (Ester- C ®) significantly reduced kidney stones in men and women urine oxalate levels compared to ascorbic acid. This is a potential was previously notable at 5% to n ovel finding that requires further clinical eva l u a t i o n . 1 0 %, but has increased over the last 2 decades and is predicted to © 2009 Society of Urologic Nurses and Associates f u rther increase over the next U rologic Nurs i n g , p p . 9 5 - 1 0 2 . decade (Moe, 2006). The lifetime risk is currently 10% to 15% Key Wo rd s : Vitamin C, ascorbic acid, Ester-C®, hyperoxaluria, (Pak, 1998), but the risk of re c u r- rence after diagnosis appro a c h e s oxalate, nephrolithiasis, kidney stones. 50% within 5 to 10 years ( Trinchieri et al., 1999). The inter- val between relapses becomes The financial impact of kidney Four types of kidney stones pri- s h o rter with each uro l i t h i a s i s stones on the U.S. health care sys- marily diagnosed are calcium (cal- event. tem alone is approximately $2 bil- cium oxalate or calcium phos- lion per year (Clark, Thompson, & phate), struvite (infection), uric O p t e n b e rg, 1995; Pearle, Calhoun, acid, and cystine (Hall, 2002). & Curhan, 2005). The cost, fre- A p p r oximately 75% to 80% of q u e n c y, and re c u rrence rates high- kidney stones diagnosed consist Mark A. M oya d , M D, is the Jenkins/ p r edominantly of calcium oxalate Po kempner Director, Preve n t i ve and light the demand for ongoing pre- A l t e rn a t i ve Medicine, University of Michigan ventive re s e a rch and education. ( Wo rcester & Coe, 2008). These Medical Center, Department of Urology, The estimated economic savings solutes may precipitate from Ann Arbor, MI. D r. M oyad is also a paid in preventing kidney stones has supersaturated urine and form a research consultant for NBTY, Inc. been calculated to be $2500 dol- stone depending on the risk fac- Maile A. C o m b s , B S c , is Associate lars per patient per year (Parks & tors harbored by each individual. D i r e c t o r, Scientific Affa i r s, The Ester C Coe, 1996). Risk factors for calcium stones C o m p a ny (a subsidiary of NBTY, Inc.), Prescott, AZ. D avid C. C row l ey, M D, is Pri n c i p l e I nve s t i g a t o r, KGK Synergize Inc., L o n d o n , P r a chi Sharma, M S c , is a Clinical Research Associate, KGK Synergize, Inc., London, O n t a ri o, Canada. O n t a ri o, Canada. Joshua E. B a i s l ey, B S c , is Regulatory A n gelica S. V r a bl i c , P h D, is Manager, Nutrition Research, NBTY, Inc., Boca Raton, FL. A f fairs & QA Manager, KGK Synergize, Inc., London, Ontari o, Canada. Malkanthi Eva n s , P h D, is Scientific Director, KGK Synergize Inc., London, Ontari o, Canada. UROLOGIC NURSING / March-April 2009 / Volume 29 Number 2 95 Objective I n t ro d u c t i o n R e s u l t s The incidence and prevalence of There was a significant change in This randomized, double-blind, urolithiasis continue to increase. O n e 24-hour urine oxalate levels among c rossover trial is the largest to date risk fa c t o r, hy p e r ox a l u ria, is related to subjects when comparing the two to evaluate the impact of supple- i n t a ke of vitamin C supplements. H i g h treatments (p = 0.04), with a decrease mentation with vitamin C with vitamin C intake (1000 to 2000 of urine oxalate levels in the vitamin C metabolites compared to ascorbic m g / d ay) correlates with higher uri n a ry with metabolites group and an acid with re g a rd to two separate, oxalate levels because a pri m a ry by - increase in urine oxalate in the ascor- product of ascorbic acid catabolism is bic acid gr o u p. A p p r oximately 25% 10-day oxalate production peri- ox a l a t e. A patented fo rm of vitamin C more subjects ex p e rienced a reduction ods in healthy individuals with- k n own as vitamin C with metabolites in 24-hour oxalate (59% to 34%) and out a history of kidney stones. The ( E s t e r - C ®), contains seve ral metabo- oxalate concentration (72% to 46%) objective of this study was to com- lites and is bound to calcium to create over the 10-day period when taking p a r e the effect of this buff e re d a non-acidic fo rmu l a t i o n . vitamin C with metabolites compared vitamin C supplement containing to ascorbic acid, despite higher plas- m e t a b o l i t e s versus ascorbic acid O b j e c t i v e ma, white blood cell, and urine vitamin on numerous health-related end- To determine if intake of vitamin C C levels in the vitamin C with metabo- points when administered as two with metabolites (Ester-C) has the lites gr o u p. i n c reasing doses over 10 days to capacity to reduce urine oxalate leve l s when compared to vitamin C (ascorbic C o n cl u s i o n s healthy volunteers. The primary acid) in previously non-stone fo rm i n g Due to the crossover design, it is outcome was the impact on gas- s u b j e c t s. p l a u s i ble that vitamin C with metabo- t rointestinal symptoms and qual- lites reduces urine oxalate levels com- ity of life (data submitted else- M e t h o d pared to ascorbic acid, which is a nove l w h e re), whereas a variety of sec- A ra n d o m i zed, doubl e - bl i n d , finding that requires further clinical o n d a ry outcomes were assessed, c r o s s over trial of vitamin C with eva l u a t i o n . including the impact of these two metabolites was compared to ascorbic f o rmulations on urinary oxalate L evel of Evidence – II acid in 50 healthy adults. Subjects (n = levels. This was a pertinent sec- 25 in each arm) on a controlled diet ( M e l nyk & Fineout-Overholt, 2005) ondary endpoint because the ingested 1000 mg/day for 5 days and 2000 mg/day for an additional 5 day s, dosages utilized in this trial are and urine oxalate was measured. A f t e r well known for potentially pro- a 7-day washout, participants repeated ducing hyperoxaluria when the same protocol (crossed over) with ascorbic acid is utilized by itself the alternate fo rm of vitamin C. in stone-forming and non-stone- f o rming subjects (Baxmann, De, Mendonca, & Heilberg, 2003; M a s s e y, Liebman, & Kynast-Gales, 2005; Tr a x e r, Huet, Poindexter, Pak, & Pearle, 2003). include low fluid intake, low uri- for less binding of oxalate). The impact of vitamin C with n a ry citrate, high salt or pro t e i n Another often-cited pro m i n e n t metabolites on oxalate levels has intake, low calcium intake, high s o u rce of hyperoxaluria is vita- not been thoroughly quantified, u r i n a ry calcium, and higher lev- min C (ascorbic acid) dietary but a past study found the poten- els of urinary oxalate (hypero x- supplements, where incre a s i n g tial for oxalate reduction (Wr i g h t , aluria) (Hall, 2002; Moe, 2006). dosages are directly corre l a t e d Suen, & Kirk, 1990). Vitamin C is An increased concentration of with increases in urinary oxalate one of the most utilized dietary oxalate can be due to numero u s because this is one primary supplements in the U.S.