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ood Oxalate: Factors Affecting Measurement,iological Variation, and Bioavailability

INDA K. MASSEY, PhD, RD

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BSTRACTood and nutrition professionals provide medical nutri-ion therapy for patients with kidney stones. If the stonesontain oxalate or the patient has been diagnosed withyperoxaluria, reduction of dietary oxalate may be appro-riate. Differences in oxalate values for a single food maye due to analytical methods, and/or biological variationrom several sources, including cultivar, time of harvest,nd growing conditions. Bioavailability of food oxalatend, thus, urine oxalate, will also be affected by saltorms of oxalate, food processing and cooking methods,eal composition, and the presence of Oxalabacter formi-

enes in the patient’s gut. Dietary advice for reducingrinary oxalate should include both reduction of dietaryxalate and simultaneous consumption of calcium-richood or supplement to reduce oxalate absorption.

Am Diet Assoc. 2007;107:1191-1194.

ntil recently, there was little interest in food oxalatevalues because the dominant paradigm was thatdietary oxalate contributed only 10% of daily oxalate

xcretion. This changed in 2001 when Holmes and col-eagues (1) showed that 24% to 53% of urinary oxalateriginated from dietary oxalate at typical intakes of 10 to50 mg per day. Their results clearly indicated that di-tary oxalate makes a much greater contribution to uri-ary oxalate than previously recognized. Holmes and As-imos (2) recently reviewed the evidence that thebsorption and excretion of dietary oxalate can be anmportant factor in calcium oxalate kidney stone forma-

. K. Massey is a professor, Department of Food Sciencend Human Nutrition, Washington State University,pokane.Address correspondence to: Linda K. Massey, PhD,D, Professor, Food Science and Human Nutrition,ashington State University, PO Box 1495, Spokane,A 99210-1495. E-mail: massey@wsu.eduCopyright © 2007 by the American Dietetic

ssociation.0002-8223/07/10707-0004$32.00/0

rdoi: 10.1016/j.jada.2007.04.007

2007 by the American Dietetic Association

ion. Although urinary oxalate concentration is only oneenth that of calcium (3), in most human urine, calciumxalate is near its saturation limit; even a small increasen oxalate concentration may increase risk of crystal pre-ipitation. Although dietary therapy has historically fo-used on reducing urinary calcium, Pak and colleagues4) found that calcium and oxalate contributed equally tohe urinary saturation of calcium oxalate.

Advice to reduce dietary oxalate intake requires knowl-dge of food oxalate values. However, food and nutritionrofessionals find that there are differences in publishedalues for some foods. Differences in oxalate values for aingle food may be due to biological variation from severalources, including cultivar (genetic variant less than apecies), time of harvest, and growing conditions, as wells analytical differences. Bioavailability of food oxalatend, thus, urine oxalate, will also be affected by saltorms of oxalate, food processing and cooking methods,eal composition, and the presence of Oxalabacter formi-

enes in the patient’s gut. These factors will be discussedn this review.

ETHODS OF OXALATE ANALYSISarly analysis of food oxalate was based on gravimetricethods (5). Oxalate was extracted with acid, precipi-

ated as the calcium salt, then analyzed colorimetricallyr with gas chromatography. An alternate method mea-ured the precipitated calcium by atomic absorption. Un-nown losses occurred during this analysis, which is also

abor and time intensive. Controversy continues about aecond probable source of variability in analysis of foodxalate, the extraction method. Honow and Hesse (6)howed that hot acid generated oxalate in cherry juice,rimarily from ascorbate. Their analysis of extractionechniques showed that oxalate extraction from cherryuice with room temperature 2N hydrochloric acid wasomplete and without generation of new oxalate. Methodsf analysis of the extracted oxalate that are reliable areon electrophoresis (7), capillary electrophoresis (7), higherformance liquid chromatography (8), gas chromatog-aphy (9), and enzymatic assays using oxalate oxidase10).

When foods are extracted with water only, the oxalate

eleased is called soluble oxalate. It is likely to be pre-

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ominantly potassium oxalate. Insoluble oxalate is calcu-ated as the difference between total oxalate and solublexalate. Insoluble oxalate is presumed to be mainly cal-ium oxalate, which is the primary form of calcium ox-late crystals in plants (11). Magnesium oxalate is alsooorly soluble in water; its extraction during these tworocedures currently used is unknown, as is its occur-ence in plants. The assumption that magnesium oxalatehould be considered insoluble is supported by the obser-ation that magnesium added to an oxalate load de-reases oxalate absorption nearly as well as calcium (12).ome evidence supports that oxalate absorption/excretion

s proportional to the amount of soluble oxalate not totalxalate (2,13).

OOKING METHODecause soluble oxalate is extracted from plants usingater, it is not surprising that cooking foods with waterffects oxalate content. Chei and Liebman (14) found thatoiling vegetables decreased total oxalate content 30% to7%, primarily by loss of soluble oxalate. In spinach andarrots the decrease in total oxalate corresponded to themount of oxalate found in the cooking water. Jaworska15), Savage and colleagues (16), and Judprasong andolleagues (17) found similar results when New Zealandnd Thai vegetables were boiled. Boiling vegetables maye an option to reduce soluble oxalate, if the cookingater is not consumed. In comparison, baking potatoes

14) or roasting peanuts (17) or sesame seeds (18) doesot affect oxalate content.

IOLOGICAL VARIATIONhere are at least three different biological causes ofariation between different samples of a food: the plantart (eg, stem vs leaf), genetic differences between culti-ars, and cultivation conditions.First, within the same plant, different parts may have

ifferent oxalate levels per weight of tissue. For example,amboo sprouts have three times the concentration ofxalate in younger vs older parts of the food (19). In wholerains, oxalate is concentrated in the bran fraction, so inrocessing wheat to refined flour, about one third of thexalate is lost (20). Albihn and Savage (21) reported thatifferences in location of oxalate in oca, a New Zealandam, were more significant than differences in cultivarsr cooking method, with the greatest concentration in thekin. In contrast, both the flesh and peel of potatoesontain oxalate in relatively similar concentrations (22).

Second, there are genetic differences in oxalate contentetween cultivars. Wilson and colleagues (23) found that5 cultivars of carambola (star fruit) had oxalate levelshat varied 10-fold. Libert and Creed (24) tested 78 rhu-arb cultivars and found oxalate ranged from 3.35% to.48% of dry weight; a threefold difference. In their study,ll the plants were grown in the same field the same yearnd harvested the same day, so growing practices wouldave had minimal influence on cultivar differences. Lib-rt calculated that 72% of the variability in oxalate orig-nated in genotype (25). Genetic variability due to differ-nces in cultivars has also been noted in soy and oca (New

ealand yam); Horner and colleagues (26) found that t

192 July 2007 Volume 107 Number 7

xalate ranged from 82 to 214 mg/100 g in 116 soy culti-ars they analyzed, whereas Sangketkit and colleagues27) found more than twofold differences in 14 oca culti-ars.The effect of cultivation differences has been reported,

n that the same soy cultivar harvested in different yearsad somewhat different values (26). Morita and col-

eagues (28) reported that increasing ammonium in theydroponic growing media decreased oxalate content ofea plants, while oxalate accumulation in rice was af-ected by the nitrate/ammonium ratio (29). Similar effectsf nitrogen form were reported by Zhang and colleagues30) in spinach. Jaworska (31) found that the amount ofxalate in oca varied with year and time of harvest. Inontrast, Streeter and colleagues (32) reported that in-reasing the nitrogen or calcium supply to developingoybeans made no difference in the amount of calcium orxalate in the mature seeds. However, the differences inxalate content of the final food due to modification ofultivation conditions are usually quite modest comparedo the oxalate differences in cultivars. Therefore, breed-ng of commercially viable low oxalate cultivars seems a

ore promising approach to reducing oxalate in foods.

BSORPTION AND BIOAVAILABILITYxalate is absorbed in the stomach and small and large

ntestines (33). Both paracellular and active and passiveranscellular uptake has been shown (33). With a suffi-ient oral load, plasma oxalate can be shown to increaseithin 1 hour, and peaks at 4 to 6 hours (34). Becausexalate is not significantly metabolized in human beings,rinary excretion also begins almost immediately, witheaks between 3 and 6 hours (34,35). Eighty percent to0% of an oral oxalate load is excreted within 8 to 11ours, with 95% to 100% excretion at the completion of 24ours (36,37). Therefore, increases in urinary excretion ofxalate after a load can be assumed to be equal to thebsorption of oxalate from that load.The amount of oxalate absorbed from a food is the

ritical aspect of dietary choice. This is influenced byhree major factors: the amount and form of oxalate in theood as consumed, the amount of calcium and magnesiumn the oxalate-containing food and/or meal, and the pres-nce or absence of oxalate-degrading bacteria in the gut.Some evidence supports that oxalate absorption ap-

ears to be proportional to the amount of soluble oxalate13). However, about 2% of calcium oxalate is absorbedntact by rats (38), so a small fraction of insoluble oxalate

ay be absorbed in human beings as well. When theoluble sodium oxalate salt is ingested by nonstoneform-ng human beings, absorption ranges from about 2% to1% (39). Chai and colleagues (37) found that hyperox-luric stoneformers absorbed more oxalate ion than nor-ooxaluric stoneformers over 24 hours, 10.9% vs 8.2%, as

id Krishnamurthy and colleagues (40), 3.9% vs 2.8%ver 6 hours. Voss and colleagues (41) also reported thatean intestinal oxalate absorption was higher in stone-

ormers. The range of oxalate absorption greatly overlapsetween stoneformers and non-stoneformers (37,39-41).esse and colleagues (42) propose using a cutoff of 15%

xcretion over 48 hours to define oxalate hyperabsorp-

ion. When this is done, more stoneformers have oxalate

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yperabsorption than nonstoneformers in the studiesited here.

The simultaneous consumption of calcium and magne-ium with oxalate reduces its absorption because insolu-le salts are formed. Liebman and Costa (12) reportedhat consumption of 300 mg of either calcium or magne-ium with a 198 mg oxalate load reduced absorption bybout one half. Recently Zimmerman and colleagues (43)eported that 240 mg magnesium consumed with 2.4 mgxalate as the sodium salt reduced oxalate absorptionrom 8.6% to 5.2% in healthy volunteers. When soybeansre processed into tofu, most of the oxalate appears to beound to calcium and magnesium, which are the insolu-le forms. Therefore, it is not surprising that oxalatebsorption from soybeans and tofu is relatively low, from% to 5% (44). Further research is needed on relativebsorption of soluble vs insoluble forms of food oxalate toefine dietary recommendations.

A number of intestinal microorganisms have been re-orted to degrade oxalate. The most studied is Ox-lobacter formigenes. The absence or low levels of O for-igines has been reported to be associated with higher

evels of urinary oxalate excretion (33). There appears toe some adaptation to continued high oxalate diets, as

Table. Range of published oxalate values (mg/100 g) for foods tobe restricted by patients with hyperoxaluriaa

Food (100 g) DescriptionRange of publishedvalues (mg)

Spinach Raw 400-900Rhubarb Raw or cooked 260-1,235Star fruit (carambola) Raw 80-730Beet Roots 76-675Beet Leaves 121-916Tea (100 mL) Black, brewed 48-92Tea (100 mL) Green, brewed 6-26Tea (100 mL) Herbal, brewed 0-8Chocolate Cocoa powder

(baking) 170-623Chocolate Milk chocolate

candy 42-123Tree nuts Almonds 431-490

Cashews 231-262Hazelnuts 167-222Walnuts 74Pecans 64Pistachios 49-57Macadamia 42

Bran Wheat 457Legumes Beans, cooked 8-91

Peanuts 96-705Soybeans, dried 82-214Tofu 3-280Textured vegetable

protein 58-150Meat substitutes,

links, patties 87-154

aIf only a single value is given, there has been only one analysis published.

immerman and colleagues (45) reported that after 6

eeks of consuming 600 mg oxalate per day, two of fourubjects had a lower percent absorption of oxalate thanfter habitual consumption of 63 mg per day. However,otal oxalate excretion was still higher after the 6-weekigh-oxalate diet.

ONCLUSIONShe American Dietetic Association’s Nutrition Care Man-al (46) recommendation for patients with kidney stones

s to restrict dietary oxalate to less than 40 to 50 mg peray. Because patients do not like to consult a long list ofoods or do not care to take the time needed to calculatectual intake in milligrams, the author advises the firsttep in dietary oxalate restriction is to avoid the foodsighest in oxalate (47): spinach, rhubarb, beets (roots and

eaves), black teas (not green or herbal), chocolate, someree nuts, bran concentrates and cereals, and legumesbeans, peanuts, soybeans and some soyfoods). Ranges ofublished values for these foods are given in the Table.ll plant foods contain some oxalate, but these foods haveeen shown to increase urinary oxalate after eating andave high amounts of oxalate. When these foods arevoided, oxalate content of the other low and moderatexalate foods typically eaten will often only add up to the0 to 50 mg daily dietary target. Oxalate values for otheroods of interest for a particular patient can be found ateveral Web sites as well as publications in print (48).The next recommendation is to add calcium to eacheal to bind oxalate (47). The total calcium intake for the

ay should be divided between as many eating occasionss possible. Calcium will bind oxalate in the gut, prevent-ng it from being absorbed. Patients should include about50 mg calcium in each meal. This is the amount found in⁄2 c milk, ice cream, yogurt, pudding, or a 3⁄4-oz slice ofheese. Studies done with added calcium carbonate (8)upport the use of calcium supplements with meals forhose who cannot or will not eat dairy products.

Differences in oxalate values for a single food may beue to analytical methods, and/or biological variationrom several sources including cultivar, time of harvest,nd growing conditions. Bioavailability of food oxalatend, thus, urine oxalate, will also be affected by saltorms of oxalate, food processing and cooking methods,eal composition, and the presence of O formigenes in the

atient’s gut.

reparation of this manuscript was funded by a contractrom the Oxalosis and Hyperoxaluria Foundation androject 0370, Agricultural Research Center, Washingtontate University.

eferences1. Holmes RP, Goodman HO, Assimos DG. Contribution of dietary ox-

alate to urinary oxalate excretion. Kidney Int. 2001;59:270-276.2. Holmes RP, Assimos DG. The impact of dietary oxalate on kidney

stone formation. Urol Res. 2004;32:311-316.3. Young DS. Implementation of SI units for clinical laboratory data.

Ann Intern Med. 1987;106:114-129.4. Pak CYC, Adams-Huet B, Poindexter JR, Pearle MS, Peterson RD,

Moe OW. Relative effect of urinary calcium and oxalate on saturationof calcium oxalate. Kidney Int. 2004;66:2032-2037.

5. Oxalic acid. In: Horwitz W, ed. AOAC Methods. 13th ed. Washington,

DC: American of Analytical Chemists; 1980:541-542.

6. Honow R, Hesse A. Comparison of extraction methods for the determi-

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nation of soluble and total oxalate in foods by HPLC-enzyme-reactor.Food Chem. 2002;78:511-521.

7. Holmes RP, Kennedy M. Estimation of the oxalate content of food anddaily oxalate intake. Kidney Int. 2000;57:1662-1667.

8. Honow R, Bonartz D, Hesse A. An improved HPLC-enzyme-reactormethod for the determination of oxalic acid in complex matrices. ClinChim Acta. 1997;261:131-139.

9. Ohkawa H. Gas chromatographic determination of oxalic acid infoods. J Assoc Off Anal Chem. 1985;68:18-111.

0. Kasidas GP, Rose GA. Oxalate content of some common foods: Deter-mination by an enzymatic method. J Human Nutr. 1980;34:255-266.

1. Libert B, Franceschi V. Oxalate in crop plants. J Agric Food Chem.1987;35:926-938.

2. Liebman M, Costa G. Effects of calcium and magnesium on urinaryoxalate excretion after oxalate loads. J Urol. 2000;163:1565-9.

3. Chai W, Liebman M. Assessment of oxalate absorption from almondsand black beans with and without the use of an extrinsic label. J Urol.2004;172:953-95712.

4. Chai W, Liebman M. Effect of different cooking methods on vegetableoxalate content. J Agric Food Chem. 2005;53:3027-3030.

5. Jaworska G. Content of nitrates, nitrites, and oxalates in New Zea-land spinach. Food Chem. 2005;89:235-242.

6. Savage GP, Vanhanen L, Mason SM, Ross AB. Effect of cooking on thesoluble and insoluble oxalate content of some New Zealand foods. JFood Comp Anal. 2000;13:201-206.

7. Judprasong K, Charoenkaitkul S, Sungpang P, Vasanachitt K, Nak-jamanong Y. Total and soluble oxalate contents in Thai vegetables,cereal grains and legume seeds and their changes after cooking. JFood Comp Anal. 2006;19:340-347.

8. Toma RB, Tabekhia MM, Williams JD. Phytate and oxalate contentsin sesame seed (Sesamum indicum l.) Nutr Reports Int. 1979;20:25-31.

9. Kozukue E, Kozukue N, Kurosaki T. Organic acid, sugar, and aminoacid composition of bamboo shoots. J Food Sci. 1983;48:935-938.

0. Chai W, Liebman M. Oxalate content of legumes, nuts, and grain-based flours. J Food Comp Anal. 2005; 18:723-729.

1. Albihn PBE, Savage GP. The effect of cooking on the location andconcentration of oxalate in three cultivars of New Zealand-grown oca(Oxalis tuberosa Mol). J Sci Food Agric. 2001;81:1027-1033.

2. Bushway RJ, Bureau JL, McGann DF. Determinations of organicacids in potatoes by high performance liquid chromatography. J FoodSci. 1984;49:75-81.

3. Wilson CW, Shaw PE, Knight RJ. Analysis of oxalic acid in carambola(Averrhoa carambola L.) and spinach by high-performance liquidchromatography. J Agric Food Chem. 1982;30:1106-1108.

4. Libert B, Creed C. Oxalate content of seventy-eight rhubarb cultivarsand its relation to some other characters. J Hort Sci. 1985;60:257-261.

5. Libert B. Genotypic and non-genetic variation of oxalate and malatecontent in rhubarb (Rheum spp. L.). J Hort Sci. 1987;62:513-521.

6. Horner, HT. Cervantes-Martinez T, Healy R, Reddy MB, DeardorffBL, Bailey TB, Al-Wahsh I, Massey LK, Palmer RG. Oxalate andphytate concentrations in seeds of soybean cultivars (Glycine max L.).J Agric Food Chem. 2005;53:7870-7877.

7. Sangketkit C, Savage GP, Martin RJ, Mason SL. Oxalate content ofraw and cooked oca (Oxalis tuberose). J Food Comp Anal. 2001;14:

389-397.

8. Morita A, Suzuki R, Yokota H. Effect of ammonium application on the4

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oxalate content of tea plants (Camellia sinensis L.) Soil Sci.2004;50:763-69.

9. Ji X-M, Peng X-X. Oxalate accumulation as regulated by nitrogenforms and its relationship to photosynthesis in rice (Oryza sativa L.).J Integrative Plant Biol. 2005;47:831-838.

0. Zhang Y, Lin X, Zhang Y, Zheng SJ, Du S. Effects of nitrogen levelsand nitrate/ammonium ratios on oxalate concentrations of differentforms in edible parts of spinach. J Plant Nutr. 2005;28:2011-2025.

1. Jaworska G. Nitrates, nitrites, and oxalates in products of spinachand New Zealand spinach. Food Chem. 2005;89:395-401.

2. Streeter JG. Effects of nitrogen and calcium supply on the accumu-lation of oxalate in soybean seeds. Crop Sci. 2005;45:1464-1468.

3. Hatch M, Freel RW. Intestinal transport of an obdurate anion: Ox-alate. Urol Res. 2005;33:1-18.

4. Holmes RP, Ambrosius WT, Assimos DG. Dietary oxalate loads andrenal oxalate handling. J Urol. 2005;174:943-947.

5. Hautmann RE. The stomach: A new and powerful oxalate absorptionsite in man. J Urol. 1993;1401-1404.

6. Prenen JAC, Boer P, Mees EJD. Absorption kinetics of oxalate fromoxalate-rich food in man. Am J Clin Nutr. 1984;40:1007-1010.

7. Chai, W, Liebman M, Kynast-Gales S, Massey L. Oxalate absorptionand endogenous oxalate synthesis from ascorbate in calcium oxalatestone formers and non-stone formers. Am J Kidney Dis. 2004;44:1060-1069.

8. Hanes DA, Weaver CM, Heaney RP, Wastney M. Absorption of cal-cium oxalate does not require dissociation in rats. J Nutr. 1999;129:170-173.

9. Hesse A, Schneeberger W, Engfeld S, von Unruh GE, Sauerbruch T.Intestinal hyperabsorption of oxalate in calcium oxalate stone form-ers: Application of a new test with [13C2]oxalate. J Am Soc Nephrol.1999;10(suppl):S329-S333.

0. Krishnamurthy MS, Hruska KA, Changhoke PS. The urinary re-sponse to an oral oxalate load in recurrent calcium stone formers.J Urol. 2003;169:2030-2033.

1. Voss S, Hesse A, Zimmerman DJ, Sauerbruch T, von Unruh G. Intes-tinal oxalate absorption is higher in idiopathic calcium oxalatestone formers than in healthy controls: Measurements with the[13C2]oxalate test. J Urol. 2006;175:1711-1715.

2. Von Unruh GE, Voss S, Sauerbruch T, Hesse A. Reference range forgastrointestinal oxalate absorption measured with a standardized[13C2]oxalate absorption test. J Urol. 2003;169:687-690.

3. Zimmerman DJ, Voss S, von Unruh GE, Hesse A. Importance ofmagnesium in absorption and excretion of oxalate. Urol Int. 2005:74:262-267.

4. Massey LK, Grentz LM, Horner HT, Palmer RG. Soybean and soyfoodconsumption increase oxalate excretion. Top Clin Nutr. 2002;17:49-59.

5. Zimmerman DJ, Hesse A, von Unruh GE. Influence of a high-oxalatediet on intestinal oxalate absorption. World J Urol. 2005;23:324-329.

6. Urolithiasis/urinary stones. In: ADA Nutrition Care Manual. Chicago,IL: American Dietetic Association; 2005.

7. Massey LK, Sutton RAL. Modification of dietary oxalate and calciumreduces urinary oxalate in hyperoxaluric patients with kidney stones.J Am Diet Assoc. 1993:93:1305-1307.

8. Marcason W. Where can I find information on the oxalate content offoods? J Am Diet Assoc. 2006;106:627-628.