Short bowel syndrome (SBS) occurs in patients who have had extensive resection. The primary physiologic consequence is malabsorption, resulting in fluid and electrolyte abnormalities and malnutrition. Nutrient digestion, absorption, and assimilation may also be diminished by disturbances in the production of bile acids and digestive enzymes. Small bowel dilation, dysmotility, loss of ileocecal valve, and anatomical changes combined with acid suppression and antimotility drugs increase the risk of small intestinal bacterial overgrowth, further contributing to malabsorption. Metabolic changes that occur in SBS due to loss of colonic regulation of gastric and small bowel function can also lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and the eventual development of bone disease. Persistent inflammation, steroid use, parenteral nutrition, chronic metabolic acidosis, and renal insufficiency may exacerbate the problem and contribute to the development of osteoporosis. Multiple factors increase the risk of nephrolithiasis in SBS. In the setting of fat malabsorption, increased free fatty acids are available to bind to calcium, resulting in an increased concentration of unbound oxalate, which is readily absorbed across the colonic mucosa where it travels to the kidney. In addition, there is an increase in colonic permeability to oxalate stemming from the effects of unabsorbed bile salts. The risk of nephrolithiasis is compounded by volume depletion, metabolic acidosis, and hypomagnesemia, resulting in a decrease in renal perfusion, urine output, pH, and citrate excretion. This review examines the causes and treatments of small intestinal bacterial overgrowth, bone demineralization, and nephrolithiasis in SBS.

This paper describes composition of dried plums and their products (prune juice and dried plum powder) with special attention to possibly bioactive compounds. Dried plums contain significant amounts of sorbitol, quinic acid, chlorogenic acids, vitamin K1, boron, copper, and potassium. Synergistic action of these and other compounds, which are also present in dried plums in less conspicuous amounts, may have beneficial health effects when dried plums are regularly consumed. Snacking on dried plums may increase satiety and reduce the subsequent intake of food, helping to control obesity, diabetes, and related cardiovascular diseases. Despite their sweet taste, dried plums do not cause large postprandial rise in blood glucose and insulin. Direct effects in the gastrointestinal tract include prevention of constipation and possibly colon cancer. The characteristic phenolic compounds and their metabolites may also act as antibacterial agents in both gastrointestinal and urinary tracts. The indirect salutary effects on bone turnover are supported by numerous laboratory studies with animals and cell cultures. Further investigation of phenolic compounds in dried plums, particularly of high molecular weight polymers, their metabolism and biological actions, alone and in synergy with other dried plum constituents, is necessary to elucidate the observed health effects and to indicate other benefits.

Oxalic acid and its salts occur as end products of metabolism in a number of plant tissues. When these plants are eaten they may have an adverse effect because oxalates bind calcium and other minerals. While oxalic acid is a normal end product of mammalian metabolism, the consumption of additional oxalic acid may cause stone formation in the urinary tract when the acid is excreted in the urine. Soaking and cooking of foodstuffs high in oxalate will reduce the oxalate content by leaching. The mean daily intake of oxalate in English diets has been calculated to be 70-150 mg, with tea appearing to contribute the greatest proportion of oxalate in these diets; rhubarb, spinach and beet are other common high oxalate-content foods. Vegetarians who consume greater amounts of vegetables will have a higher intake of oxalates, which may reduce calcium availability. This may be an increased risk factor for women, who require greater amounts of calcium in the diet. In humans, diets low in calcium and high in oxalates are not recommended but the occasional consumption of high oxalate foods as part of a nuritious diet does not pose any particular problem.

Over the past 10 years, major progress has been made in the pathogenesis of uric acid and calcium stones. These advances have led to our further understanding of a pathogenetic link between uric acid nephrolithiasis and the metabolic syndrome, the role of Oxalobacter formigenes in calcium oxalate stone formation, oxalate transport in Slc26a6-null mice, the potential pathogenetic role of Randall's plaque as a precursor for calcium oxalate nephrolithiasis, and the role of renal tubular crystal retention. With these advances, we may target the development of novel drugs including (1) insulin sensitizers; (2) probiotic therapy with O. formigenes, recombinant enzymes, or engineered bacteria; (3) treatments that involve the upregulation of intestinal luminal oxalate secretion by increasing anion transporter activity (Slc26a6), luminally active nonabsorbed agents, or oxalate binders; and (4) drugs that prevent the formation of Randall's plaque and/or renal tubular crystal adhesions.

To evaluate the influence of oxalic acid (OA) on nonhaem iron absorption in humans.

Two randomized crossover stable iron isotope absorption studies.

Zurich, Switzerland.

Sixteen apparently healthy women (18-45 years, <60 kg body weight), recruited by poster advertizing from the staff and student populations of the ETH, University and University Hospital of Zurich, Switzerland. Thirteen subjects completed both studies.

Iron absorption was measured based on erythrocyte incorporation of (57)Fe or (58)Fe 14 days after the administration of labelled meals. In study I, test meals consisted of two wheat bread rolls (100 g) and either 150 g spinach with a native OA content of 1.27 g (reference meal) or 150 g kale with a native OA content of 0.01 g. In study II, 150 g kale given with a potassium oxalate drink to obtain a total OA content of 1.27 g was compared to the spinach meal.

After normalization for the spinach reference meal absorption, geometric mean iron absorption from wheat bread rolls with kale (10.7%) did not differ significantly from wheat rolls with kale plus 1.26 g OA added as potassium oxalate (11.5%, P=0.86). Spinach was significantly higher in calcium and polyphenols than kale and absorption from the spinach meal was 24% lower compared to the kale meal without added OA, but the difference did not reach statistical significance (P>0.16).

Potassium oxalate did not influence iron absorption in humans from a kale meal and our findings strongly suggest that OA in fruits and vegetables is of minor relevance in iron nutrition.

Thirty-one women with vulval vestibulitis were evaluated for evidence of abnormal dietary oxalate intake and a wide range of dietary intakes was recorded. No woman was found to have abnormal urinary excretion. Sixteen women agreed to undertake a low oxalate diet and there was an apparent response in six (37%).

The aim of the present study was to evaluate Mg absorption from a test meal served with an oxalate-rich vegetable, spinach, as compared with a test meal served with a vegetable with a low oxalate content, kale. Mg absorption was measured by a stable-isotope technique based on extrinsic labelling of the test meals and faecal monitoring of the excreted isotope labels. Nine healthy adults participated in the study. The test meals were based on 100 g phytate-free white bread, served with 300 g spinach (6.6 mmol oxalate; 0.7 mmol (25)Mg label added, 5.0 mmol total Mg) or 300 g kale (0.1 mmol oxalate; 1.2 mmol (26)Mg label added, 4.8 mmol total Mg). The test meals were served on days 1 and 3, at breakfast and lunch, using a cross-over design. The results from the present study demonstrated that apparent Mg absorption was significantly lower from the meal served with spinach (26.7 (sd 10.4) %) than the meal served with kale (36.5 (sd 11.8) %) (P=0.01). However, the lower fractional apparent Mg absorption from the test meal served with spinach can be assumed to be, at least partly, counterbalanced by the higher native Mg content of spinach as compared with kale. Although based on indirect evidence, i.e. not based on an evaluation of added (or removed) oxalic acid, the difference in Mg absorption observed in the present study is attributed to the difference in oxalic acid content between the two vegetables.

The factors affecting the urinary excretion of oxalate are critical to the risk of forming calcium oxalate stones. This article reviews the role of dietary and intestinal oxalate in determining the level of oxalate excreted in urine. The amount of oxalate available for absorption throughout the intestine is highly dependent on the state of oxalate (a) in the food ingested, and (b) in the intestinal contents at each section of the intestinal tract since only the soluble form of oxalate can be absorbed. In this respect, the solubility of calcium oxalate (CaOx) under the prevailing conditions is paramount in determining the amount of oxalate available for absorption at any particular site. In turn, the main factors that control how much oxalate is in the soluble form are pH and the concentrations of calcium, magnesium and (indirectly) phosphate. Based on these parameters, a model of the intestine has been constructed which brings together the available evidence on the prevailing concentrations of these various factors at different sites in the intestine after allowing for dietary intake and the concentration of the above ions in intestinal secretions. The model then calculates the likely concentration of oxalate that is in the soluble form at each site and therefore available for passive absorption at that site. The model shows that oxalate is likely to be absorbed in the stomach, although it can be also absorbed in the small intestine, particularly at the distal end (after the absorption of calcium), and in the colon, since, on a normal intake of calcium and phosphate, most of the calcium in the large bowel would be anticipated to be precipitated as calcium phosphate under the prevailing alkaline conditions and high concentration of phosphate. The amount of free oxalate in the colon is also controlled by the presence or absence of Oxalobacter formigenes, an anaerobe that has an obligate requirement for oxalate as a source of energy and cellular carbon.

Thirty-two commercially available teas consisting of green, oolong and black teas were bought from supermarkets in Christchurch, New Zealand in June 2001. Fifteen herbal teas were also purchased at the same time. The soluble oxalate content of the infusate made from each of the teas was determined using high pressure liquid chromatography. The mean soluble oxalate contents of black tea in tea bags and loose tea leaves were 4.68 and 5.11 mg/g tea, respectively, while green teas and oolong tea had lower oxalate contents, ranging from 0.23 to 1.15 mg/g tea. The soluble oxalate content of the herbal teas ranged from not detected to 3.00 mg/g tea. A regular tea drinker consuming six cups of tea/day would have an intake of between 26.46 and 98.58 mg soluble oxalate/day from loose black tea, 17.88 and 93.66 mg soluble oxalate/day from black tea in tea bags and a maximum of 18.0 mg/day from herbal teas. The oxalate intake from the regular daily consumption of black teas is modest when compared to the amounts of soluble oxalate that can be found in common foods. However, oxalate in black teas has the potential to bind to a significant proportion of calcium in the milk, which is commonly consumed with the black teas.

To measure the availability of oxalate normally extracted when making tea from two commercially available black teas bought from a supermarket in Christchurch, New Zealand in July 2001.

A randomized double crossover study. Six students and four staff consumed six cups of each brand of tea both with and without added milk over a 24 h period. A total urine collection was taken for the initial 6 h followed by a further 18 h. The oxalate content of the urine voided was measured using an enzyme kit method and the availability of the soluble oxalate consumed was measured for the 6 h and the total 24 h sample.

University campus.

The mean soluble oxalate content of black tea in the two different commercial tea bags was respectively 6.1 and 6.3 mg soluble oxalate/g tea. The mean availability of the oxalate extracted from tea measured over a 6 h period ranged from 1.9 to 4.7% when tea was consumed without milk. The availability of the soluble oxalate from tea ranged from -3.0 to 2.3% for each of the two brands of tea investigated over a 24 h period.

These studies show that consuming black tea on a daily basis will lead to a moderate intake of soluble oxalate each day, however the consumption of tea with milk on a regular basis will result in the absorption of very little oxalate from tea.

Hyperoxaluria leads to increased calcium oxalate supersaturation and calcium oxalate stone formation. Excess oxalate can arise from endogenous overproduction as in primary hyperoxaluria or from dietary sources. In the last 15 years great strides have been made in the diagnosis and treatment of primary hyperoxaluria. However options still seem limited in treating the mild hyperoxaluria found in many stone formers. Inadequate knowledge of food oxalate content, the effect of dietary oxalate precursors on oxalate excretion, and the factors affecting handling of oxalate by the intestine prevent development of rational therapies for treatment of hyperoxaluria. Recent studies of oxalate degrading bacteria and renewed interest in the role of diet calcium in oxalate absorption may lead to better therapeutic strategies for hyperoxaluric calcium nephrolithiasis.

The amount of oxalate ingested may be an important risk factor in the development of idiopathic calcium oxalate nephrolithiasis. Reliable food tables listing the oxalate content of foods are currently not available. The aim of this research was to develop an accurate and reliable method to measure the food content of oxalate.

Capillary electrophoresis (CE) and ion chromatography (IC) were compared as direct techniques for the estimation of the oxalate content of foods. Foods were thoroughly homogenized in acid, heat extracted, and clarified by centrifugation and filtration before dilution in water for analysis. Five individuals consuming self-selected diets maintained food records for three days to determine their mean daily oxalate intakes.

Both techniques were capable of adequately measuring the oxalate in foods with a significant oxalate content. With foods of very low oxalate content (<1.8 mg/100 g), IC was more reliable than CE. The mean daily intake of oxalate by the five individuals tested was 152 +/- 83 mg, ranging from 44 to 352 mg/day.

CE appears to be the method of choice over IC for estimating the oxalate content of foods with a medium (>10 mg/100 g) to high oxalate content due to a faster analysis time and lower running costs, whereas IC may be better suited for the analysis of foods with a low oxalate content. Accurate estimates of the oxalate content of foods should permit the role of dietary oxalate in urinary oxalate excretion and stone formation to be clarified. Other factors, apart from the amount of oxalate ingested, appear to exert a major influence over the amount of oxalate excreted in the urine.

This review summarizes the recent discovery of the cupin superfamily (from the Latin term "cupa," a small barrel) of functionally diverse proteins that initially were limited to several higher plant proteins such as seed storage proteins, germin (an oxalate oxidase), germin-like proteins, and auxin-binding protein. Knowledge of the three-dimensional structure of two vicilins, seed proteins with a characteristic beta-barrel core, led to the identification of a small number of conserved residues and thence to the discovery of several microbial proteins which share these key amino acids. In particular, there is a highly conserved pattern of two histidine-containing motifs with a varied intermotif spacing. This cupin signature is found as a central component of many microbial proteins including certain types of phosphomannose isomerase, polyketide synthase, epimerase, and dioxygenase. In addition, the signature has been identified within the N-terminal effector domain in a subgroup of bacterial AraC transcription factors. As well as these single-domain cupins, this survey has identified other classes of two-domain bicupins including bacterial gentisate 1, 2-dioxygenases and 1-hydroxy-2-naphthoate dioxygenases, fungal oxalate decarboxylases, and legume sucrose-binding proteins. Cupin evolution is discussed from the perspective of the structure-function relationships, using data from the genomes of several prokaryotes, especially Bacillus subtilis. Many of these functions involve aspects of sugar metabolism and cell wall synthesis and are concerned with responses to abiotic stress such as heat, desiccation, or starvation. Particular emphasis is also given to the oxalate-degrading enzymes from microbes, their biological significance, and their value in a range of medical and other applications.

Oca (Oxalis tuberosa Mol.) or New Zealand yam, in common with other members of this genus, contains oxalate, an antinutritive factor. Twelve South American and two New Zealand cultivars of oca were analyzed for total and soluble oxalate contents of the tubers. The range of total oxalate levels was 92-221 mg/100 g of fresh weight. Levels of soluble and total oxalate extracted from the tubers were not significantly different, suggesting that no calcium oxalate is formed in the tubers. The oxalate concentrations obtained in this study for oca suggest that previously reported values are too low and that oca is a moderately high oxalate-containing food. This is the first report of a tuber crop containing moderate to high levels of soluble oxalates in the tubers and no insoluble oxalates.

Under the putative influence of dietary selection pressure, the subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT) has changed on many occasions during the evolution of mammals. Depending on the particular species, AGT can be found either in peroxisomes or mitochondria, or in both peroxisomes and mitochondria. This variable localization depends on the differential expression of N-terminal mitochondrial and C-terminal peroxisomal targeting sequences by the use of alternative transcription and translation initiation sites. AGT is peroxisomal in most humans, but it is mistargeted to the mitochondria in a subset of patients suffering from the rare hereditary disease primary hyperoxaluria type 1. Mistargeting is due to the unlikely combination of a normally occurring polymorphism that generates a functionally weak mitochondrial targeting sequence and a disease-specific mutation which, in combination with the polymorphism, inhibits AGT dimerization. The mechanisms by which AGT can be targeted differentially to peroxisomes and/or mitochondria highlight the different molecular requirements for protein import into these two organelles.

A shortened small intestine may end at a stoma or be anastomosed to the colon. Patients with a jejunostomy, but not those with a colon, lose large amounts of sodium. The intake and absorption of sodium can be increased by sipping a sodium-glucose solution; stomal loss can be reduced by restricting water or low-sodium drinks. If a stoma is situated less than 100 cm along the jejunum, a constant negative sodium balance may necessitate parenteral saline supplements. Gastric anti-secretory drugs or a somatostatin analogue reduce jejunostomy losses in such patients but do not restore a positive sodium balance. Loperamide or codeine phosphate benefit some patients. Magnesium deficiency can usually be corrected by oral magnesium oxide supplements. An elemental or hydrolysed diet is not beneficial. Patients with a jejunostomy can maintain a normal diet without fat reduction. When the colon is present, unabsorbed carbohydrate is fermented to absorbable short chain fatty acids. Unabsorbed long chain fatty acids and bile salts cause watery diarrhoea and increased colonic oxalate absorption with hyperoxaluria. Such patients benefit from a high carbohydrate, low-fat and low-oxalate diet. Parenteral nutrition is needed only by the few patients unable to maintain health or avoid socially disabling diarrhoea despite these measures.

The oxalate, hydrocyanic acid, phytic acid and phosphorus contents of twelve leafy vegetables were determined. The values ranged from 47.7-194.3 mg/100 g DM, 4.32-23.8 mg/100 g DM, 90-260 mg/100 g DM and 215-1110 mg/100 g DM, respectively. The ratio of phytic acid to phosphorus ranged from 13.9-90.7. The leaves contained low levels of hydrocyanic acid, while the oxalate, phytic acid and phosphorus contents were high. The results are discussed in terms of their clinical implications and nutritive values.

Dietary restriction of oxalate intake has been used as therapy to reduce the risk of recurrence of calcium oxalate kidney stones. Although urinary oxalate is derived predominantly from endogenous synthesis, it may also be affected by dietary intake of oxalate and calcium. The risk of increasing urinary oxalate excretion by excessive consumption of dietary oxalate is greatest in individuals with a high rate of oxalate absorption, both with and without overt intestinal disease. Although oxalate-rich foods enhanced excretion of urinary oxalate in normal volunteers, the increase was not proportional to the oxalate content of the food. Only eight foods--spinach, rhubarb, beets, nuts, chocolate, tea, wheat bran, and strawberries--caused a significant increase in urinary oxalate excretion. Restriction of dietary calcium enhances oxalate absorption and excretion, whereas an increase in calcium intake may reduce urinary oxalate excretion by binding more oxalate in the gut. This review of the literature indicates that initial dietary therapy for stone-forming individuals can be limited to the restriction of foods definitely shown to increase urinary oxalate. The effects of oxalate-restricted diets on urinary oxalate should be evaluated by means of laboratory analyses of urine composition. Subsequent long-term therapy can be recommended if beneficial results are obtained from oxalate restriction at an appropriate calcium intake.

Under the influence of dietary selection pressure, the intracellular compartmentalization of alanine:glyoxylate aminotransferase (AGT) has changed on many occasions during the evolution of mammals. In some mammals, AGT is peroxisomal in others it is mainly mitochondrial while in yet others it is more-or-less equally divided between both organelles. Although in normal human liver AGT is usually found exclusively within the peroxisomes, in some individuals a small proportion (approximately 5%) is found also in the mitochondria. This apparently trivial intracellular redistribution of AGT is caused by the presence of a Pro11Leu polymorphism which allows the N-terminus of AGT to fold into a conformation (ie a positively-charged amphiphilic alpha-helix) which functions as a mitochondrial targeting sequence. In one third of patients with the autosomal recessive disease primary hyperoxaluria type 1, there is a further redistribution of AGT so that the great majority (approximately 90%) is located in the mitochondria and only a small minority (10%) in the peroxisomes. AGT cannot fulfil its proper metabolic role in human liver (ie glyoxylate detoxification) when located in the mitochondria. The erroneous compartmentalization is due to the presence of a Gly170Arg mutation superimposed upon the Pro11Leu polymorphism. The Gly170Arg mutation appears to have no direct effect on mitochondrial targeting and is predicted to enhance mitochondrial import of AGT by interfering with its peroxisomal targeting and/or import. The mitochondrial targeting sequence generated by the Pro11Leu polymorphism is not homologous to that found in the AGT of other mammals which localise AGT within the mitochondria normally. The identity of the peroxisomal targeting sequence in AGT is unknown, but the Gly170Arg mutation is found in a highly conserved region of the protein which might be involved in some aspects of the peroxisomal import pathway for AGT.

A number of environmental factors are under discussion as possibly implicated in the etiology of RCU. On the basis of data in the literature and our own results, we attempted a critical weighting up of the possible contributions of climate, pollution, stress, nutrition in general and especially oxalate and minerals in the nutrition. It was concluded that there is a need for more in-depth research into the response of the body to challenges from the environment, in particular nutrition.

Oxalate bioavailability from sugar beet fibre (40 g), spinach (25 g) and a solution of sodium oxalate (182 mg) was tested in nine women using a triplicated 3 x 3 Latin square arrangement. Each test substance provided 120 mg oxalic acid. Throughout the study the volunteers consumed a control diet and the test substances were administered at breakfast on specified days. After an initial 2-day control period, oxalate was administered in three test periods that consisted of one test day followed by one control day. Urine collected during 24-hr periods was analysed daily for oxalate. Oxalate excretion did not differ among the five control days and was not increased significantly following the ingestion of sugar beet fibre by the volunteers. Oxalate excretion was greater (P less than 0.0001) for the mean of the spinach and sodium oxalate solution diets than for the mean of the sugar beet fibre and control diets. Oxalate bioavailability from sugar beet fibre was 0.7% compared with bioavailabilities of 4.5 and 6.2% for spinach and oxalate solutions, respectively. The low bioavailability of oxalate from sugar beet fibre may be attributable to its high ratio of minerals (calcium and magnesium) to oxalate, its complex fibre matrix or the loss of the soluble oxalate during processing of sugar beets.

The average daily dietary intake of 88 idiopathic renal stone cases and 88 age and sex matched controls was assessed by history using a standardised questionnaire. Statistical analysis was undertaken on the whole group and on male and female subgroups, to establish if there were any significant differences between cases and controls. There were statistically significant differences in dietary intake between the whole group, the female cases and the control group. Male cases showed only a significantly lower intake of thiamine compared to controls. There was little difference between cases and controls intake of iron or multivitamin supplements but vitamin C supplements (greater than 1 g/day) were taken more than twice as frequently by cases than controls. These results suggest that control dietary studies of renal stone patients without regard to their sex may conceal many differences in dietary intake between cases and controls.

A group of 30 meat eating normal subjects were compared with a second group of vegetarians matched for age and sex. Their diets and urinary excretion patterns were compared by statistical analysis. A link between protein intake, particularly animal protein, and urinary calcium excretion was demonstrated and also that dietary calcium was inversely related to urinary oxalate excretion. Urinary oxalate increases with the vegetable protein content of the diet, but within the limits of these diets, animal protein does not affect oxalate excretion though it does affect excretion of urinary urate.

Fifty-one first admission renal stone patients and an equal number of controls were interviewed and a dietary history of the average weekly intake was collected from each participant. A comparison of the dietary intake per kilogram body weight in each group was made using standard statistical procedures. None of the nutrient intakes showed a significant difference, but dietary fibre intake and the percentage of energy provided by carbohydrate were consistently higher in the control group, whereas the percentage of energy provided by fat was consistently higher in the renal stone group.

A specific enzymatic method was used to determine the oxalate content of some common foods. No preliminary isolation of oxalate was required and recoveries ranging from 95-110 per cent were obtained. Spinach, rhubarb, peanuts, chocolates, parsley and tea were found to contain high levels of oxalate as previously described by others. On the other hand the oxalate content of beetroot was found to be five times as high as previously reported, but coca-cola and beer were almost free from oxalate. Cereals and meat were either low or deficient in oxalate.