Perspective in practiceEffect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones☆
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OXALATE CHEMISTRY
Oxalate is the simplest dicarboxylic acid (Figure 1). Once synthesized by the body or absorbed from the gut, oxalate cannot be further metabolized by human beings and must be excreted in the urine. Calcium oxalate is poorly soluble in water—only 55 μmol/L at pH 7 at 37° C (6). Normal oxalate excretion in urine is 110 to 440 μmol in a 1- to 2-L volume (3), so human urine is often supersaturated with calcium oxalate. The urinary concentrations of both calcium and oxalate are important for the
OXALATE SOURCES
Oxalate is found in most plant tissues. The amount found in a plant depends on growth conditions, the part of the plant, and the plant's maturity. Oxalate may be present in plant tissues as sodium or potassium salts (soluble oxalate), as calcium oxalate, or as other bound forms (insoluble oxalate). Little consideration has been given to the salt form of oxalate in foods, that is, the difference in solubility of the salts in the gut lumen and thus their potential availability for absorption. For
OXALATE ANALYSES
Earlier analyses of the oxalate content of foods were done after extraction, then precipitation, of the oxalate. Oxalate can be generated from several compounds during these vigorous analytic procedures. Ascorbate decomposes to oxalate under alkaline conditions. Oxalate losses can occur during precipitation steps. Because of these technical difficulties, many classic analyses of the oxalate content of foods have been found to be erroneous when the same foods are analyzed using gentler
OXALATE METABOLISM
Oxalate is degraded by anaerobic microflora of the human intestine. A new genus and species, Oxalobacter formigenes, has been created for these oxalate-degrading microbes (17). Rates of oxalate degradation in healthy human beings are highly individual and range from 0.1 to 4.8 μmol per gram per hour (18). According to oxalate balance studies and rates of fecal degradation, microbial metabolism may account for the breakdown of 1,000 μmol oxalate per day (6). Kelsay and Prather (19) found that in
EFFECT OF DIETARY OXALATE ON URINARY OXALATE EXCRETION
Dietary oxalate appears to contribute only about 10% of the urinary oxalate in healthy non-stone-forming individuals who eat Western-type diets (5). However, the increase in urinary oxalate can be quite substantial when the dietary oxalate load is high and bioavailability or absorption is greater than normal. Brinkley et al 11., 30. and Finch et al (31) investigated the effect of various food sources of oxalate in healthy non-stone-forming subjects. The increment in urinary oxalate after
EFFECT OF DIETARY CALCIUM ON URINARY OXALATE EXCRETION
At the pH in the gut lumen, oxalate is present in the salt form rather than as free oxalic acid. The amount of oxalate present as the insoluble calcium oxalate form depends on the relative calcium to oxalate molar ratio, as well as on the presence of competing cations and other calcium-binding agents such as fiber or phytate.
Zarembski and Hodgkinson's (37) finding that a low-calcium diet (150 mg/day) increased urinary oxalate excretion showed the importance of dietary calcium in determining the
RECOMMENDATIONS FOR FURTHER RESEARCH
The effect of oxalate-containing foods on urinary oxalate excretion should be studied individually and in meals containing various forms and amounts of calcium. These studies need to be performed in stone-forming individuals who have normal and increased calcium absorption rates and in healthy control subjects. Oxalate bioavailability may be more important in patients with high rates of oxalate absorption, such as those with ileal disease or with high calcium absorption. High-oxalate foods,
APPLICATIONS
Initial dietary restriction for stone-forming patients can be limited to foods definitely known to increase urinary oxalate. To date, 8 foods have been shown to increase urinary oxalate excretion: spinach, nuts, tea, chocolate, beets, rhubarb, strawberries and wheat bran. The greatest risk of increasing urinary oxalate excretion by excessive consumption of dietary oxalate is for individuals with high rates of oxalate absorption, both with and without overt intestinal disease. This is frequently
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Preparation of this manuscript was supported by a Fogarty Senior International Research Fellowship, NIH F06 Tw01591-01, to L. K. Massey.