Oxalic acid excretion

The reason for the differences in zinc balances between these two studies was not clear. In an effort to determine if the oxalic acid in spinach in the first study could be responsible for at least part of the decrease in bioavailability of zinc in the first study, we determined oxalic acid content of feces. Mean oxalic acid excretion in feces when the subjects were on the highest fiber diet in study 2 was about 1/2 that on the higher fiber diet in study 1 (210 and 423 mg/day, respectively). Another factor which might help explain the results was the length of the dietary periods the dietary periods in study 1 were 5 days longer than in study 2. 

Oxalic acid is poorly absorbed with a bioavailability of 2-5%. It is excreted unchanged in the urine. Normal urinary oxalic acid excretion ranges from 8 to 40 mg day... 

If an accurate knowledge of the individual steps of the metabolic pathways leading to oxalic acid formation is necessary to understand oxaluria, an evaluation of the relative importance of each of these pathways in metabolism is of no less interest. In that respect, it is significant that under normal conditions the addition of 25-100 g of glycine to the diet does not affect of oxalic acid excretion. In contrast, the inclusion of 40 g of gelatin (corresponding to 10 g of glycine) doubles the amount of oxalic acid excreted. 

The main source of carbon dioxide is the C-1 atom of the ascorbic acid molecule, whereas the C atoms 1 and 2 represent the basic structure for oxalic acid. The formation of oxalic acid with excessive supplies of ascorbic acid has been used as one argument against pharmacological doses, especially for persons who are sensitive to the development of a nephrolithiasis. The human daily excretion amounts to 30-40 mg oxalic acid and originates 35-50% from the metabolism of ascorbic acid and 50-65% from glycine and glyoxalic acid. The additional supply of 1-9 g ascorbic acid per day led to an increase of the normal excretion of oxalic acid by 0.0-68.0 mg/day (Moser et al., 1982). Normal persons without any metabolic disease are therefore not seriously affected in their oxalic acid excretion by single excessive doses of ascorbic acid. 

In some patients with non-ketotic glycinaemia (including one patient shown to lack serine hydroxymethyltransferase) hypo-oxaluria has been found [98] though oxalic acid excretion is normal in others and, in some cases, hypo-oxaluria is intermittent. 

The results of experiments conducted by MacKenzie and McCollum (15) indicate that the effect of dietary oxalic acid on the rat depends on the composition of the diet. There was no effect on rate of growth or calcium excretion of 50 g rats fed for 10 weeks a diet containing 0.6% calcium, 0.7% phosphorus, and optimum vitamin D, when levels of potassium oxalate up to 2.5% were fed. The percent bone ash on the 2.5% oxalate diet was somewhat lower than on the control diet. On a 0.35% calcium, 0.35% phosphorus, and vitamin D-free diet, 1.7% potassium oxalate resulted in restricted growth and bone formation of weanling rats. 

McLaughlin (25) reported that although calcium balances for seven women were somewhat lower during 6 days in which spinach replaced milk in the diet, all balances were positive. The women were fed diets containing about 500 mg of calcium/day in which 79% came from milk for 6 days and 73% came from spinach (about 276 g/day) for 6 days. The spinach diet contained 2.0 g oxalic acid/day. The calcium excretion in urine was 2-3 times greater during the milk period. 

Bricker et al. (30) reported that there were no statistically significant differences between the calcium balances of eight women on cocoa and non-cocoa diets. The women were studied for three to seven 4-day periods. Calcium intake was 670 mg/day with the addition of milk and 679 and 755 mg/day with the addition of milk and cocoa. Five levels of cocoa, supplying from 5.6-52.6 g/day, were tested. These amounts would likely contain from 25-280 mg of oxalic acid, which was not nearly as much as was added when spinach was fed. With the inclusion of cocoa in the diet, the urinary calcium fell and fecal calcium rose. There were also increases in the fecal excretion of dry matter and nitrogen. 

In studies on test meals, Walker et al. (32) discovered that the calcium of Swiss chard, which has a high oxalic acid content, was poorly absorbed. Children excreted more calcium during the 6 hours after a test meal of milk, Pumpkin leaves, cassava leaves, or pigweed leaves than after Swiss chard. All supplements contained 200 mg calcium. 

In the studies on humans there appeared to be decreased calcium balances when 200 g or more of spinach per day was included in the diet. In two of the studies in which women were fed spinach, calcium intakes were below the Recommended Dietary Allowance of 800 mg/day (37). Some studies were conducted for short period of a week or less, which may not be sufficient time to adjust to a change in diet. From measurement of calcium excretion in urine after a test meal, it was shown that the calcium in oxalate-containing vegetables was less well-absorbed than that of milk or of vegetables not containing oxalic acid. However, this would not necessarily affect calcium balance, since the total amount of calcium in the diet would have to be considered. The effect of a combination of oxalic acid and fiber on calcium bioavailability should be further investigated. 

Calcium oxalate calculi Management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day (males) or 750 mg/day (females). Carefully assess therapy initially and periodically to determine that treatment is beneficial and that the benefits outweigh the risks. 

The presence of Ca in kidney stones and the abnormally high Ca levels in idiopathic (absorptive) hypercalciuric individuals that are inherently more prone to kidney stones, initially led to the belief that dietary Ca may be a cause of renal stone formation (Coe et al., 1992). Recent evidence suggests that, as a therapeutic approach to reducing the risk for kidney stones, Ca-restricted diets may pose a greater risk to normocalciuric individuals prone to kidney stone formation such an approach may increase urinary oxalate and the likelihood of recurrent stones, as well as promote bone loss (Borghi et ah, 2002 Coe et al., 1997 Curhan et ah, 1997). The amoimt of oxalate excreted in urine has been foimd to be positively associated with Ca oxalate supersaturation and stone formation (Holmes et ah, 2001). While free oxalic acid is readily absorbed from the gut lumen (Morozumi et ah, 2006), an increased dietary Ca to oxalate... 

In summary, >200 mg elemental Ca administered either as CaCOs or CCM reduced oxalate absorption and excretion in the event of an oxalic acid challenge. 

Ethylene glycol, an industrial solvent and an antifreeze compound, is involved in accidental and intentional poisonings. This compound is initially oxidized by alcohol dehydrogenase and then further biotransformed to oxalic acid and other products. Oxalate crystals are found in various tissues of the body and are excreted by the kidney. Deposition of oxalate crystals in the kidney causes renal toxicity. Ethylene glycol is also a CNS depressant. In cases of ethylene glycol poisoning, ethanol is administered to reduce the first step in the biotransformation of ethylene glycol and, thereby, prevent the formation of oxalate and other products. 

An alternative to thiazides is allopurinol. Some studies indicate that hyperuricosuria is associated with idiopathic hypercalcemia and that a small nidus of urate crystals could lead to the calcium oxalate stone formation characteristic of idiopathic hypercalcemia. Allopurinol, 300 mg daily, may reduce stone formation by reducing uric acid excretion. 

However, there are known instances of differences in the preferred route of metabolism, which are important in toxicity, as well as simple differences in the route of a particular oxidation. For example, the oxidative metabolism of ethylene glycol gives rise to either carbon dioxide or oxalic acid (Fig. 5.7). The relative importance of these two pathways is reflected in the toxicity. Thus, the production of oxalic acid is in the order cat>rat> rabbit, and this is also the order of increasing toxicity (Fig. 5.8). The aromatic hydroxylation of aniline (Fig. 5.9) shows marked species differences in the position of substitution, as shown in Table 5.9. Thus carnivores such as the ferret, cat, and dog excrete mainly o-aminophenol, whereas herbivores such as the rabbit and guinea pig excrete mainly p-aminophenol. The rat, an omnivore, is intermediate. 

The treatment for methanol or ethylene glycol poisoning is the same. The patient is given intravenous infusions of diluted ethanol. The ADH enzyme is swamped by all the ethanol, allowing time for the kidneys to excrete most of the methanol (or ethylene glycol) before it can be oxidized to formic acid (or oxalic acid). This is an example of competitive inhibition of an enzyme. The enzyme catalyzes oxidation of both ethanol and methanol, but a large quantity of ethanol ties up the enzyme, allowing time for excretion of most of the methanol before it is oxidized. 

Studies on the effect of oxalic acid in spinach on calcium balance in humans have shown a small decrease or no effect on calcium balance (12). However, when subjects were given test meals of either Swiss chard (13) or amaranth (, 1, which are rich in oxalic acid, urinary excretion of calcium indicated that the absorption of calcium from these sources was less than that of an equal amount of calcium from milk. Absorption of calcium from milk was also reduced when given along with amaranth (14). 

Disposition in the Body. Ethylene glycol is metabolised initially to glycoaldehyde and subsequently to lactic acid and oxalic acid. Calcium oxalate crystals are deposited in the kidneys and some oxalate may be excreted in the urine together with unchanged ethylene glycol. 

Disposition in the Body. Less than 5% of ingested oxalic acid is absorbed in healthy adults. About 8 to 40 mg of oxalic acid is normally excreted in the urine daily this is derived mainly from the metabolism of dietary ascorbic acid and glycine with small amounts from dietary oxalic acid and other minor metabolic sources. Calcium oxalate is a major constituent of kidney stones and is frequently found as crystals in freshly-voided urine. In normal subjects concentrations of oxalic acid in blood range from about 1 to 3 pg/ml. Small amounts of oxalate are produced as a metabolite of ethylene glycol. 

After intravenous administration of oxalic acid to normal subjects, more than 90% of the dose was excreted in the urine in 36 hours (T. D. Elder and J. B. Wyngaarden,din. Invest., 1960, 39, 1337-1344). 

Faber et al. (FI) studied the effects of induced pyridoxine and pantothenic acid deficiency, obtained by use of a semisynthetic formula and deoxypyridoxine and co-methyl pantothenic acid supplements for six weeks, by determining in 5 men nitrogen retention and the urinary excretions of xanthurenic and oxalic acids during deficiency and recovery. They postulated that tissue catabolism releases suflBcient pyri-doxine to partially metabolize a tryptophan load, after which the amounts of urinary oxalic acid were sharply increased for 1-2 days. 

Evidence for renal oxalate toxicity was found from studies describing urinary enzyme excretion suggesting renal (tubular) damage in patients with stones [25]. Rat models of stone disease have been used to study such damage in greater detail and revealed brush border loss, release of cellular enzymes, and epithelial erosion [19, 26, 27]. However, all these arguments are indirect and cannot distinguish oxalate (or oxalic acid) mediated effects from calcium oxalate crystal induced effects. 

Oxalic acid and its soluble salts are poisonous to humans and animals, whereas insoluble salts of calcium and magnesium oxalate are not. Oxalates ingested by humans may be precipitated by calcium as an insoluble complex, which then is excreted in feces [21, 22, 23]. In both cases reported by Chien et al [21], patients ingested sour carambola juice on an empty stomach so that the protective effect of calcium and magnesium in food was not present. The dehydration state may have contributed to the development of carambola- associated acute nephropathy. The authors do not report any concomitant neurological signs or symptoms [21]. 

Ascorbic acid is readily absorbed by an active process. Large doses can saturate this system, limiting the amounts absorbed. Once absorbed, it is distributed to all tissue. The vitamin is metabolized to oxalic acid before excretion. Ascorbic acid-2-sulfatc is also a metabolite found in the urine. Large doses result in the excretion of substantial amounts of unchanged ascorbic acid. The resultant acidification of the urine is the basis for most of the vitamin s adverse effects. 

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