Abstract
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It Is Known Which Foods Have High Oxalate Content
Oxalate is found in foods of plant origin, whereas it is found in negligible quantities in foods of animal origin. A list of oxalate-containing foods is found at the Harvard T.H. Chan School of Public Health website, 4 with oxalate content categorized from “little to none” to “very high.” In addition, an example of a low-oxalate diet is provided, as well as a list of low-oxalate alternatives to high-oxalate foods. There are several other online databases and smartphone applications listing food oxalate content, and some variation has been reported in these values for particular foods. 5 Differences in the reported oxalate content of particular foods can be caused by biological variation, growing conditions, and analytical differences. 6 Furthermore, the method of food preparation introduces variation (e.g., 1 cup of raw spinach contains 656 mg oxalate, whereas ½ cup of cooked spinach contains 755 mg; 1 ounce of raw peanuts contains 27 mg, whereas 1 tablespoon of peanut butter contains 13 mg 4 ). However, it is reasonably clear which foods are high in oxalate, as well as which foods are low in oxalate and admissible in a low-oxalate diet. Furthermore, one study utilizing food frequency questionnaires established that spinach and potatoes together accounted for more than half of total oxalate intake in a large cohort, 7 suggesting that curtailing intake of several key high-oxalate foods may be a practical strategy.
Carefully Controlled Dietary Studies Have Quantified Dietary Oxalate's Contribution to Urinary Oxalate
In a small study of subjects on self-selected diets, daily oxalate intake ranged from 44 to 352 mg, 8 suggesting that diet-derived urinary oxalate can vary substantially between individuals without dietary control. A few studies have assessed the influence of dietary oxalate intake on urinary oxalate excretion using diets controlled in their nutrient content. Holmes and colleagues demonstrated that the contribution of dietary oxalate to urinary oxalate was between 25% and 42% for patients receiving 10 mg vs 250 mg dietary oxalate per day. 9 The influence of dietary calcium on the bioavailability of ingested oxalate cannot be overstated; subjects on the 250 mg dietary oxalate diet had an absolute increase in urinary oxalate excretion of 28% when dietary calcium was reduced from 1002 to 391 mg. 9 Similar controlled dietary studies have demonstrated that intestinal handling and renal handling have key roles. 10,11 Importantly, the urinary oxalate excretion of kidney stone formers appears to be more sensitive to dietary oxalate compared with normal controls, 12,13 supporting the limitation of oxalate-rich foods in the diet for stone formers.
Large Epidemiologic Studies Established the Contribution of Urinary Oxalate to Calcium Oxalate Stone Disease
The importance of urinary oxalate excretion in kidney stone formation was illustrated in a study of the urine of 2237 stone formers compared with matched healthy controls from the Nurses' Health Study I-II and Health Professionals Follow-up Study cohorts. 14 The relative risk of forming a stone increased ∼2.5- to 3.5-fold in each of the cohorts studied as urinary oxalate excretion increased from 20 to 40 mg/day. These results also demonstrated that small changes in the amount of oxalate excreted each day, as little as 4 mg/day, could increase kidney stone risk by 60% to 100%. 14 Most commercial laboratories utilize >40 mg/day as the threshold to define hyperoxaluria. However, the data suggest that urinary oxalate should be interpreted as a continuum, as small increases within the normal range can impose a significant increase in stone risk.
Urinary Oxalate May Be the Most Important Constituent of Calcium Oxalate Supersaturation
The supersaturation of urine with calcium oxalate markedly increases the risk of stone formation, 15 and supersaturation is the driving force behind crystal precipitation. 16 Although the daily excretion of oxalate is an order of magnitude less than that of calcium (by number of milligrams and number of moles), the contribution of urinary oxalate to calcium oxalate supersaturation is at least as important, or potentially more important, than that of urinary calcium. In one study by Pak and colleagues, among calcium oxalate stone formers, urinary calcium and urinary oxalate were equally effective in increasing the supersaturation of calcium oxalate. 17 An earlier study by Rodgers demonstrated that urinary oxalate was 23 times more potent than urinary calcium in its effect on calcium oxalate supersaturation in healthy volunteers. 18 These findings confirm on a biochemical level that even minor increases in urinary oxalate may have a substantial impact on stone formation.
Beyond Dietary Oxalate, Ascorbic Acid (Vitamin C) Appears to Be the Only Other Major Dietary Precursor to Urinary Oxalate
Although the amount of both dietary oxalate and dietary calcium influence the urinary oxalate pool, the endogenous production of oxalate is a major contributor as well. Approximately one half of urinary oxalate is derived from endogenous synthesis, and ascorbic acid is thought to be the major precursor. 19 The contribution of ascorbic acid intake to endogenous oxalate production was established in the 1960s, indicating that it accounted for ∼40% of urinary oxalate excretion. 20,21 In 2008, Taylor and Curhan reported on factors influencing urinary oxalate excretion in 3348 female nurses and male health professionals. 22 Compared with individuals consuming <90 mg/day of ascorbic acid, individuals with an intake >1000 mg/day excreted 6.8 mg/day more urinary oxalate. The significant association of ascorbic acid intake with kidney stone formation was first reported in a large cohort study of 45,619 male health professionals 23 and recapitulated in a large cohort of Swedish men. 24 Studies evaluating the role of other potential dietary precursors of endogenous oxalate synthesis, such as hydroxyproline and glycine, 25,26 suggest lesser contributions than that of ascorbic acid.
Dietary Oxalate Potentially Negatively Impacts Kidney Function
Kidney stone formation is associated with chronic kidney disease (CKD). 27 It was also recently reported that urinary oxalate excretion is positively correlated with progression to end-stage kidney disease in those with underlying CKD. 28 This infers that dietary oxalate could play a role in these events. Furthermore, there have been reports of individuals who practice “juicing,” consumption of blended fruits and vegetables high in oxalate content, developing oxalate nephropathy. 29,30 Our research group has made headway in defining some of the mechanisms associated with kidney dysfunction and oxalate consumption. Individuals consuming a food-derived oxalate load (equivalent to a spinach salad) had an increase in the excretion of nanocrystals, which could incite kidney damage. 31 We have also found that such loads can result in increasing inflammatory responses and a decline in monocyte mitochondrial bioenergetic function, both of which could play a role in CKD as well as kidney stone formation. 32
The Low-Oxalate Diet Is Guideline Supported
The American Urological Association Guideline on Medical Management of Kidney Stones 33 endorses five diet therapies for patients with calcium oxalate stones. These include (1) a fluid intake that will achieve a urine volume of at least 2.5 L daily, (2) limiting sodium intake and consuming 1000 to 1200 mg of dietary calcium daily for patients with relatively high urinary calcium, (3) increasing intake of fruits and vegetables and limiting intake of nondairy animal protein for patients with relatively low urinary citrate, (4) limiting intake of nondairy animal protein for patients with relatively high urinary uric acid, and (5) limiting intake of oxalate-rich foods and maintaining normal calcium consumption for patients with relatively high urinary oxalate. It is specified that patients with calcium oxalate stones and hyperoxaluria should consume calcium from foods and beverages at meals to enhance binding of oxalate, and that patients with malabsorptive conditions may benefit from a more restrictive oxalate diet and higher calcium intake. In addition, the contribution of ascorbic acid to urinary oxalate is acknowledged. Guideline endorsement of the low-oxalate diet for calcium oxalate stone formers with relatively high urinary oxalate reinforces its standing as one of only a few nonpharmacologic interventions available to patients.
The Low-Oxalate Diet Is Here to Stay, and New Applications May Be on the Horizon
The available evidence indicates that dietary intake of oxalate, calcium, and ascorbic acid have strong associations with urinary oxalate and kidney stone risk. Thus, we stand on firm ground in endorsing low oxalate intake, normal calcium intake (1000–1200 mg/day), and no more than the recommended daily allowance of ascorbic acid (90 mg/day) for calcium oxalate stone formers. With new research elucidating the contribution of oxalate to kidney dysfunction, these dietary measures may be of even greater benefit to calcium oxalate stone formers with CKD.
Footnotes
Author Disclosure Statement
KDW is a consultant for Steris and Alnylam.
Funding Information
Urology Care Foundation Research Scholar Endourological Society/Raju Thomas, MD Award (JJC); National Institutes of Health 5K08DK115833-04 (KDW) and 5P20DK119788-04 (DGA).