Progress 10/01/06 to 09/30/09
Outputs
Funding was secured from the Oxalosis and Hyperoxaluria Foundation. 1) an update of the OHF patient-oriented database for food selection according to relative oxalate content. 2) Dr. Massey and her colleague Dr. Kynast-Gales posted an online database with over 1200 published food oxalate values. 3) Dr. Massey published a review for dietitians and other health professionals on sources of variability in published food oxalate values. Until recently, there was little interest in food oxalate values, as the dominant paradigm was that dietary oxalate contributed only 10% of daily oxalate excretion. This changed in 2001 when Holmes, Goodman and Assimos (Kidney Int. 2001;59:270-276.) showed that 24 to 53% of urinary oxalate originated from dietary oxalate at typical intakes of 10-250 mg/d. Their results clearly indicated that dietary oxalate makes a much greater contribution to urinary oxalate than previously recognized. Holmes and Assimos (Urol Res .2004;32:311-316) have
reviewed the evidence that the absorption and excretion of dietary oxalate can be an important factor in calcium oxalate kidney stone formation. Although urinary oxalate concentration is only one-tenth that of calcium, in most human urine calcium oxalate is near its saturation limit; therefore, even a small increase in oxalate concentration may increase risk of crystal precipitation. If the patient's stones contain oxalate or the patient has been diagnosed with hyperoxaluria, reduction of dietary oxalate may be appropriate. Advice to reduce dietary oxalate intake requires knowledge of food oxalate values. However, there are differences in published values for some foods. Massey at Washington State University Spokane has recently reviewed the sources of variation (J Amer Diet Assoc 107:1191-4, 2007). Massey concluded that differences in oxalate values for a single food may be due to biological variation from several sources including cultivar [genetic variant less than a species], time
of harvest and growing conditions as well as analytical differences. Although recent reports use reliable methods for analyzing oxalate extracted from foods, controversy continues about the extraction method. Honow and Hesse (Food Chem. 2002;78:511-521.) showed that hot acid generated oxalate in cherry juice, primarily from ascorbate. Their analysis of extraction techniques showed that oxalate extraction from cherry juice with room temperature 2N HCl was complete and without generation of new oxalate. Even if the food oxalate value is known, the bioavailability of the food oxalate, and thus urine oxalate, will also be affected by several factors. The major one is the salt form of oxalate, with calcium oxalate being very poorly soluble. Soluble oxalate is potassium or sodium oxalate, which is more absorbed. Methods of processing and cooking which include water immersion will reduce oxalate. The presence of calcium or magnesium in a will reduce oxalate absorption. Finally if the
patient's gut contains oxalate degrading bacteria such as Oxalabacter formigenes there will be less oxalate to be absorbed, then excreted in the urine.
Impacts
Previously, twelve different compiled lists had to be consulted to find all values for oxalate content of a food. Reasons for differences in published values were not discussed, and references to original methodology not given. The review article comprehensively reviews all factors that affect food oxalate amount and bioavailability. The supporting database gives all published values in a spreadsheet format, with references. This is a valuable resource not only for researchers but also practicing dietitians advising patients with calcium oxalate kidney stones or hyperoxaluria.
Publications
- Massey, LK. 2007. Magnesium and the Kidney: Overview. In: Recent Advances in Magnesium Research. Pages 289-292. Springer, London.
- Massey LK. 2007. Food Oxalate: Factors affecting measurement, biological variation and bioavailability. J Amer Diet Assoc 107:1191-4.
- Kynast-Gales SA, Massey LK. 2007. Food Oxalate: An international data base. J Amer Diet Assoc 107:1099.
- Bindler RCM, Massey LK, Shultz JA, Mills PE, Short R. 2007. Metabolic syndrome in a multi-ethnic sample of school children: Implications for the Pediatric Nurse.. J Pediatr Nurs 22(1):43-58.
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Progress 01/01/06 to 12/31/06
Outputs
Dietitians provide medical nutrition therapy for patients with kidney stones. If the stones contain oxalate or the patient has been diagnosed with hyperoxaluria, reduction of dietary oxalate may be appropriate. Differences in oxalate values for a single food may be due to analytical methods, and/or biological variation from several sources including cultivar, time of harvest and growing conditions. Bioavailability of food oxalate, and thus urine oxalate, will also be affected by salt forms of oxalate, food processing and cooking methods, meal composition and the presence of Oxalabacter formigenes in the patient's gut. A review was accepted for publication in 2007 which summarizes this information from published references. As a companion to the review, a database of all food oxalate values was published on the web. Values were collected from original research articles published in English since 1980, values from Ross Holmes for Ixion Biotech, values determined for a
list of foods for the Vulvar Pain Foundation by Michael Liebman, values determined by the Clinical Research Center at the University of California at San Diego, and values generated in the authors' laboratory for several metabolic feeding studies. Foods from as many countries as possible are included to increase its usefulness to international health professionals and scientists. Each value is accompanied by the reference for the article in which the value is given. This database makes no attempt at averaging or comparing values from different sources. Rather it is a compilation of all single values. However, even if the specific brand or variety is the same as the food you are looking for, it is likely there is some variation in different samples of that food. Differences in values from different sources may be due to genetic variations in cultivars, cultivation conditions, parts and ages of the plant, and/or cooking procedures. Because of the many sources of variation, researchers
who need the exact oxalate content of a food should directly determine it in the foods used in their study. Also food oxalate values from different sources may vary due to the different methodologies used to determine oxalate. Specifically when oxalate is extracted using hot acid, the values may be too high as oxalate may be generated from ascorbate; when oxalate is precipitated, values may be too low due to losses. The methodology used for oxalate extraction and analysis is given in brackets after each reference. Dietitians wanting food oxalate values grouped into patient-friendly categories should use the database of the Oxalosis and Hyperoxaluria Foundation at www.ohf.org/docs/Oxalate2004.htm, which was recently updated with additional values compiled from this database. The new WSU database was used by Dr. Susan Gales to categorize foods as low, moderate or high in oxalate for the Oxalosis and Hyperoxaluria Foundation tables.
Impacts
Previously, twelve different compiled lists had to be consulted to find all values for oxalate content of a food. Reasons for differences in published values were not discussed, and references to original methodology not given. The review article comprehensively reviews all factors that affect food oxalate amount and bioavailability. The supporting database gives all published values in a spreadsheet format, with references. This is a valuable resource not only for researchers but also practicing dietitians advising patients with calcium oxalate kidney stones or hyperoxaluria.
Publications
- No publications reported this period
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Progress 01/01/05 to 12/31/05
Outputs
Oxalate and phytate concentrations in seeds of soybean cultivars (Glycine max L.) This study analyzed soybean seeds from 116 cultivars (cvs) for total, insoluble, and soluble oxalate (Ox), phytate (InsP6), calcium (Ca), and magnesium (Mg) because of their potential beneficial or harmful effects to human nutrition. These cvs were divided into four groups (A-D) based on the year and geographic location where they were grown. Oxalate concentration ranged from about 82mg to 285mg per 100g dry seed. The InsP6 concentration ranged from 0.22-2.22g/100g dry seed. There was no correlation within or among the four groups of cvs. There was a significant correlation between total Ox and Ca, but not Mg, in Group D cvs (R=0.3705; p<0.0005), and no significant relationship was found in the Groups A-C cvs. Eleven Group D cvs had InsP6 less than 500mg/100g but all had Ox of 130mg/100g or greater. Five cvs from Groups A-C had relatively low Ox (<140mg/100g) and low InsP6 (Group B;
<=1.01g/100g). Two Group B cvs with Ox below 105mg/100g had InsP6 higher than 1.66g/100g. These seven cvs could be useful for producing soy foods beneficial to populations at risk for kidney stones, and for improved mineral bioavailability. Pedigrees of the 116 cvs indicate that choosing specific parents could generate seeds in succeeding generations with desirable Ox and InsP6 concentrations. Oxalate and Phytate of Soy Foods Consumption of foods made from soybeans is increasing because of their desirable nutritional value. However, some soy foods contain high concentrations of oxalate and/or phytate. Oxalate is a component of calcium oxalate kidney stones, whereas phytate is an inhibitor of calcium kidney stone formation. Thirty tested commercial soy foods exhibited ranges of 0.02 to 2.06 mg oxalate/g and 0.80 to 18.79 mg phytate/g. Commercial soy foods contained 2 to 58 mg of total oxalate per serving and 76 to 528 mg phytate per serving. Eighteen of 19 tofu brands and two soymilk
brands contained less than 10 mg oxalate per serving, defined as a low oxalate food. Soy flour, textured vegetable soy protein, vegetable soybeans, soy nuts, tempeh, and soynut butter exhibited greater than 10 mg per serving. The correlation between oxalate and phytate in the soy foods was significant (r = 0.71, P < 0.001) indicating that oxalate-rich soy foods also contain higher concentrations of phytate. There also was a significant correlation, based on molar basis, between the divalent ion binding potential of oxalate plus phytate and calcium plus magnesium (r = 0.90, P < 0.001) in soy foods. Soy foods containing small concentrations of oxalate and moderate concentrations of phytate may be advantageous for kidney stone patients or persons with high risk of kidney stones.
Impacts
Seven cvs could be useful for producing soy foods beneficial to populations at risk for kidney stones, and for improved mineral bioavailability. Pedigrees of the 116 cvs indicate that choosing specific parents could generate seeds in succeeding generations with desirable Ox and InsP6 concentrations. Soy foods containing small concentrations of oxalate and moderate concentrations of phytate may be advantageous for kidney stone patients or persons with high risk of kidney stones.
Publications
- Horner HT, Cervantes-Martinez T, Healy R, Reddby MB, Deardorff BL, Bailey TB, Al-Wahsh IA, Massey LK, Palmer RG. 2005. Oxalate and phytate concentrations in seeds of soybean cultivars. J Agricultural Food Chem 53:7870-7.
- Al-Wahsh IA, Horner HT, Palmer RG, Reddy MB, Massey LK. 2005 Oxalate and Phytate of Soy Foods. J Agric Food Chem 53:5670-4.
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Progress 01/01/04 to 12/31/04
Outputs
Background: Ascorbic acid (AA) supplementation is widely practiced in the US, with 12.4% of the US adult population (1) and 12-14% of stone formers reported taking 500 mg or more per day (2). A small percentage (1.5%) of ingested AA is converted in vivo to oxalate (3), which is excreted without further metabolism quantitatively in the urine over 24 hours. Ascorbate has also been demonstrated to increase absorption of dietary oxalate in stone formers (4). If AA supplements are taken, the increased urinary oxalate may increase the risk of calcium oxalate kidney stones. Increased rates of either oxalate absorption or endogenous oxalate synthesis can contribute to hyperoxaluria, a primary risk factor for the formation of calcium oxalate-containing kidney stones. This study involved a comparative assessment of oxalate absorption and endogenous oxalate synthesis in subpopulations of stone formers (SF) and non-stone formers (NSF) and an assessment of the effect of ascorbate
supplementation on oxalate absorption and endogenous oxalate synthesis. Methods: A randomized crossover controlled diet was tested in a University metabolic unit. Twenty-nine individuals with a history of calcium oxalate kidney stones (19 males, 10 females) and 19 age-matched NSF (8 males, 11 females) participated in two 6-day controlled feeding experimental periods: ascorbate supplement (2000 mg/day) and no supplement treatments. An oxalate load consisting of 118 mg unlabeled oxalate and 18 mg 13C2-oxalic acid was administered the morning of the sixth day of each experimental period. Results: Mean 13C2-oxalic acid absorption averaged across the ascorbate and no supplement treatments was significantly higher in SF (9.9 %) than in NSF (8.0 %). SF also had significantly higher 24-h post-oxalate load urinary total oxalate and endogenous oxalate on both treatments. Twenty-four hour urinary total oxalate was strongly correlated with both 13C2-oxalic acid absorption (r = 0.76, P < 0.01, SF;
r = 0.62, P < 0.01, NSF) and endogenous oxalate synthesis (r = 0.95, P < 0.01, SF; r = 0.92, P < 0.01, NSF). Tiselius Risk Index (TRI) for urinary calcium oxalate saturation was greater for SF vs. NS on both A (1.10 + 0.60 vs. 0.65 + 0.41), and N (0.94 + 0.45 vs. 0.61 + 0.45). Nineteen (12 SF, 7 NS) of the 48 participants were identified as responders, defined by increased 24 h total oxalate excretion > 10% on A versus N. Responders had increased 24 h TRI A vs. N (1.10 + 0.66 vs. 0.76 + 0.42) because of a 31% increase in percent oxalate absorption on A vs. N (10.5% vs. 8.0%) and a 39% increase in endogenous oxalate synthesis on A vs. N (544 vs. 391 famol/d). 1 gm AA twice a day resulted in an increase in TRI in 40% of study participants, including both SF and NS. Conclusions: SF are characterized by higher rates of both oxalate absorption and endogenous oxalate synthesis and both of these factors contribute to the hyperoxaluric state. The finding that ascorbate supplementation
increased urinary total and endogenous oxalate suggested that this practice could be a risk factor for individuals predisposed to kidney stones.
Impacts
Vitamin C supplements may increase risk of kidney stones for both stoneformers and non-stoneformers. This finding will impact the next version of the Dietary Allowances, which currently state that 2 g/d is the upper limit for safety.
Publications
- No publications reported this period
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Progress 01/01/03 to 12/31/03
Outputs
Background: A small percent of dietary ascorbate (vitamin C) is converted in humans to oxalate. Since oxalate cannot be further metabolized in humans, it is quantitatively excreted in the urine. Self-selected ascorbate supplementation of 1 g/d or more is quite common. Two of four studies on healthy non-stoneformers found supplemental ascorbate significantly increased urinary oxalate. In the single report to date of ascorbate loading in normooxaluric calcium oxalate stoneformers, doses of 500, 1000 or 2000 mg/d increased urinary oxalate. The increases of 6 to 13 mg/d were equivalent to metabolic conversion of 1.2 to 1.8% of the supplemental ascorbate to oxalate. Although small, this amount would increase the risk of stone recurrence, especially if the stone patient already had elevated urinary oxalate. Two grams of vitamin C (ascorbate) are being used in our study as this level saturates blood cells and plasma and larger amounts would not be expected to provide any
further health benefits. The current upper limit for vitamin C is 2 g in the current Dietary Recommended Intakes. Progress: Twenty-nine subjects with a history of at least one calcium oxalate kidney stone were recruited from volunteers previously screened for other dietary studies. Twenty age and gender-matched non-stoneformers were also recruited. Only volunteers who have a normal fasting calcium/creatinine ratio and normal calcium absorption as determined by four hour urinary calcium excretion after a 1000 mg oral calcium load were included in the study. The total study was divided into two experimental periods, each consisting of six consecutive days - one day in a metabolic unit, preceded by five days of pre-study dietary preparation/adaptation at which time the subject are free-living. Each day of one of the six-day experimental periods, each subject consumed a 1 g (1000 mg) vitamin C supplement with breakfast and dinner. On the first two days while free-living, subjects avoided
the ten foods known to be highest in oxalate. On day 3-5, they ate only the low oxalate foods provided by the investigators. Participants collected all urine voided each 24 hours for the five days preceding the one-day stay in the metabolic unit. While in the metabolic unit, participants ate a strictly controlled, nutritionally adequate, low-oxalate diet prepared from common foods. On day 6 (first day in the metabolic unit), subjects consumed a capsule with 131 mg oxalate, 13 mg of which was synthesized with a nonradioactive, stable isotope, carbon 13. Urine was collected at 2 hour intervals for the next 8 hours, then two 3 hour intervals, and finally overnight. The collection of timed urine samples post oxalate ingestion allowed the degree and time course of oxalate absorption and endogenous oxalate synthesis to be assessed as well as the effect of supplemental ascorbate compared to placebo treatment. All 49 volunteers have completed both the placebo and ascorbate weeks as of June
29th. Laboratory analysis should be completed by the end of February 2004.
Impacts
Results of this study will be used for making recommendations about the Upper Limit of vitamin C intake for safety by the Dietary Recommended Intakes committee at the national/international level.
Publications
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Progress 01/01/02 to 12/31/02
Outputs
Increases in dietary salt, i.e. sodium chloride (NaCl), increase urinary calcium over the range of intakes commonly consumed. Both salt loading studies and reports of within-population correlations find that increased urinary calcium losses are approximately 1 mmol (40 mg) for each 100 mmol (2300 mg) increase in dietary NaCl. Individuals with hypercalciuria and/or a history of calcium kidney stones appear to have 2 times greater proportional increases in urinary calcium per 100 mmol increase in salt intake. Reduction of dietary NaCl from typical intakes of 200 mmol/day to an intake of 50 mmol/day may decrease the risk of recurrence of calcium-containing kidney stones and slow rates of bone loss, thus reducing risk of osteoporosis as well. Twenty-seven subjects with a history of at least one calcium oxalate kidney stone were recruited; subjects were selected from qualifying volunteers so that one-half had normal urinary calcium levels (normocalciuria) on their usual
diet, while the other half had elevated levels (hypercalciuria). The dietary study consisted of two, seven-day periods. The first five days of each treatment (adaptation), the participants were free-living but consumed only a low-salt diet (50 mmol, one-half of the maximum recommended) provided by the investigators. One of the two weeks, 150 mmol supplemental salt was added as tablets taken with each meal; the total of 200 mmol (twice the amount recommended) is the average consumption measured in previous studies of stone formers. While free-living, each participant collected all urine voided each 24 hours for five days preceding th two-day stay in the FSHN metabolic unit. While in the metabolic unit each participant ate only the foods provided by the investigators, a nutritionally adequate diet prepared from common foods. All urine was collected, and a fasting blood sample was obtained on the morning of the eighth day, just prior to leaving the metabolic unit. The outcome measures
are urinary oxalate, calcium, magnesium, phosphate and citrate, and two measures of calcium salt saturation as indicators of risk of calcium salt precipitation. The two measures of calcium salt precipitability will be the Tiselius risk index, a measure of calcium oxalate precipitability from soluation which includes the effects of volume, magnesium and citrate concentrations as well as calcium and oxalate, and Ap (CaP), a measure of calcium phosphate precipitability from solution, which includes the effects of volume, citrate and pH as well as calcium and phosphate. Because increased urinary calcium loss from adding salt occurs, bone breakdown may be increased in compensation, so 4 markers of bone turnover will be measured. We will also compare the responsiveness of hypercalciuric vs normocalciuric participants for all the outcome variables, because the literature suggests that hypercalciuric stoneformers may be more sensitive to dietary salt effects on urinary calcium. The results of
this will be used to make dietary recommendations about the amount of dietary salt for calcium kidney stone formers. Analysis of urines is in progress.
Impacts
Results are expected to impact dietary counseling of kidney stone patients to prevent stone recurrence.
Publications
- No publications reported this period
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Progress 01/01/01 to 12/31/01
Outputs
High levels of oxalate in soybean seeds and soyfoods may increase human calcium oxalate kidney stone risk. Raw soybeans and common soyfoods, such as tofu, soy beverage, soynuts and textured vegetable protein (TVP), contain over 10 mg oxalate per serving. Oxalate in soybean seeds is primarily in the form of calcium oxalate crystals. Eleven soybean cultivars showed relatively high levels of total seed oxalate, from 0.67 g to 3.5 g/100 g dry weight. Oxalate is retained during processing as shown by the 182 to 7250 16 to 638 mg oxalate per serving in 13 tested commercial soyfoods. Calcium oxalate is considered insoluble, so it was previously assumed that the oxalate could not be absorbed. However, Hayes et al. (1999) described absorption of calcium oxalate in rats. The present study examined human oxalate absorption from soybean seeds and soyfoods after consumption by measuring changes in urinary oxalate excretion. Eight healthy individuals with no history of kidney
stones consumed eight oxalate feedings comprised of seeds from two soybean lines, five soyfoods (2 tofus, soy beverage, textured vegetable protein and soynuts) and 8.3 mmol sodium oxalate in solution. After correction for pre-load baseline excretion, increases in urinary oxalate ranged from 1.7 + 2.1 to 10.9 + 13.8 mg for the seeds of two soybean lines and five soyfoods during the eight hours after ingestion of each oxalate load. Absorption ranged from 2.1 + 2.1% from one high-oxalate soybean line to 5.4 + 4.2% from soynuts. Since normal urinary oxalate excretion is defined as 10 to 39 mg per day, frequent consumption of soybeans and soyfoods in the diet may increase urinary oxalate excretion to 40 mg or more per day, a concentration defined as hyperoxaluria, which is a risk factor for calcium-oxalate kidney stone formation in susceptible individuals.
Impacts
The observation that soybeans and soyfoods are high in oxalate is new. Some of this oxalate is absorbed. The consumption of soy products for health benefits may not be appropriate for those at risk of calcium oxalate kidney stones, also a new observation with obvious health impact.
Publications
- Grentz LM, Massey LK. 2001. Contribution of dietary oxalate to urinary oxalate excretion in health and disease. Topics Clinical Nutrition 17:60-70.
- Massey LK, Grentz LM, Horner HT, Palmer RG. 2001. Soybean and soyfood consumption increase urinary oxalate excretion. Topics Clinical Nutrition 17:49-59.
- Massey LK, Palmer R, Horner HT. 2001. Oxalate content of soybean seed (Glycine max:Leguminosa), soyfoods and other edible legumes. J Agric Food Chem 49:4262-6.
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Progress 01/01/00 to 12/31/00
Outputs
Soybeans and other legumes are relatively high in oxalate. Oxalate may be absorbed from the diet, but cannot be metabolized, so is excreted in the urine. Higher levels of oxalate in the urine increase risk of crystallization of calcium oxalate, which forms kidney stones. More commonly eaten soy foods such as tofu and textured vegetable protein also have oxalate. Bioavailability of oxalate from soy foods is relatively unstudied, but is expected to be from 2-6% of the total amount. Two high oxalate strains of soy beans and five soy foods, (2 tofus, soy "milk", textured vegetable protein and soynuts), were fed to 8 healthy non-stoneformers. After correction for endogenous oxalate synthesis, absorption ranged from 0.5% from the high oxalate soybeans to 6% from magnesium-precipitated tofu. Increases in 8 hour post-load urinary oxalate ranged from 11.8 to 20.8 mg oxalate. Since normal urinary excretion is 20-30 mg/d, increases of this level could increase urinary excretion
to over 40 mg/d, a level considered to increase risk of calcium-containing kidney stones.
Impacts
Frequent consumption of common soy foods may be a risk factor for calcium oxalate kidney stones.
Publications
- No publications reported this period
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