Recent advances in nutritional research on urolithiasis
Inappropriate dietary habits, overweight and lifestyle are suggested to contribute considerably to the increasing incidence and prevalence of urolithiasis. Numerous dietary factors can alter urinary composition and supersaturation, which can affect the process of stone formation. Dietary oxalate, calcium, protein, purines, sodium and ascorbic acid are known to be promoters of stone formation, whereas potassium and magnesium have been shown to be effective inhibitors. Although a high fluid supply has been demonstrated to decrease the incidence of urolithiasis, data from clinical and epidemiological studies on the effect of various beverages on the risk of urinary stone formation are conflicting. Continued research is warranted to clarify controversies concerning the impact of dietary calcium, oxalate, n-3 fatty acids, and phytate in calcium stone formation. Further randomized controlled studies should explore the long-term effects of dietary interventions in stone formers.
KeywordsDietary habitsUrinary stone diseaseUrolithiasisDietary risk factorsCalciumOxalate
Inadequate dietary habits, lifestyle and overweight are suggested to promote worldwide increasing incidence and prevalence of urolithiasis. Calcium oxalate is by far the most common stone component, occurring in 70–80% of stone formers. Up to 15% of urinary stones consist of uric acid. Specific dietary factors can alter urinary composition and supersaturation, which can affect the process of crystallization and stone formation. Putative dietary promoters are dietary oxalate, calcium, protein, purines, sodium and ascorbic acid, whereas fluid intake, dietary fibre, potassium, magnesium, n-3 fatty acids and phytate may inhibit calcium stone formation by their effects on urinary composition and supersaturation.
One of the most important dietary measures for the prevention of stone recurrence is a sufficient urine dilution accomplished by adequate fluid intake. A prospective, randomized study in idiopathic calcium oxalate stone formers revealed a significantly lower recurrence rate in patients in the intervention group with significantly higher urine volumes than in the control group with no changes in fluid intake . The study confirms that an increase in fluid intake to assure a consistent urine volume of at least 2 litres per day is the initial therapy for the prevention of stone recurrences.
There are conflicting data from clinical and epidemiological studies on the effect of various beverages on the risk of urinary stone formation. Assessing the data from an epidemiological study, Curhan et al. (1996) observed no association between the intake of sugared cola and the risk for stone formation , while a clinical trial in healthy subjects conducted by Rodgers (1999) suggested an increased risk due to a significant increase in urinary oxalate excretion by 60 μmol/24 h after consumption of 2.0 l of regular (non-diet) cola beverage .
In two prospective observational studies conducted by Curhan et al. (1996, 1998), a positive association between apple juice intake and the risk for stone formation has been shown in men but not in women [2, 4]. Substituting apple juice for water in healthy female volunteers, Hönow et al. (2003) failed to find a significant difference in the calculated supersaturation with calcium oxalate . Moreover, conflicting evidence exists regarding the effect of grapefruit juice on the risk of stone formation. Whereas epidemiological studies by Curhan et al. (1996, 1998) revealed a positive association between grapefruit juice and risk of stone formation in men and women [2, 4], no changes in lithogenicity were observed by Goldfarb and Asplin (2001) in healthy men and women . On the contrary, Hönow et al. (2003) were able to demonstrate a significant reduction in the calculated supersaturation with calcium oxalate .
The literature regarding the effect of cranberry juice on urinary stone risk factors has likewise yielded conflicting results. Urinary oxalate has been reported to be increased , decreased  or unchanged  in healthy subjects and to be increased in calcium oxalate stone formers . Urinary calcium excretion has been shown to be unchanged [7, 9] or decreased  in healthy subjects but to be increased in stone formers . Overall the risk of calcium oxalate stone formation was reduced  or unaffected [7, 9] by cranberry juice consumption in healthy subjects but increased in stone patients .
In two prospectively conducted studies, Curhan et al. (1996, 1998) showed that each 240 ml serving of caffeinated coffee was associated with a 10% decrease in risk of stone formation in men and women [2, 4]. A recent epidemiological study by Goldfarb et al. (2005) supported the protective effect of coffee for stone disease . However, no explanation is provided for this finding. In a recent interventional trial, Massey and Sutton (2004) examined the acute effect of caffeine consumption on urine composition and risk of stone formation in 39 normocalcaemic patients with calcium stones and 48 control subjects . The subjects received 6 mg caffeine/kg lean body mass in 180 ml of warm deionised water. The doses ranged from 250 to 400 mg caffeine, the equivalent of 11–17 oz (330–510 ml) of brewed coffee. Caffeine loading resulted in an increased urinary calcium/creatinine ratio and an elevated Tiselius risk index. Since caffeine induces hypercalciuria, affects hydration and may aggravate hypertension, patients should be recommended to consume caffeinated beverages in moderation and to drink water before or along with the coffee.
Although mineral water has been suggested to be a suitable beverage for urine dilution, the water composition has to be taken into account. The application of 1.4 litres of a mineral water rich in bicarbonate (3,388 mg/l), magnesium (337 mg/l) and calcium (232 mg/l) resulted in a significant increase in urinary pH, citrate, calcium and magnesium excretion, whereas no significant long-term reduction in urinary oxalate excretion was observed .
From these findings it can be concluded, that the type of beverage should be selected cautiously. Neutral beverages, i.e. fluids which dilute urine without affecting its composition, include tap water, mineral water with a low mineral content, fruit and herbal teas. Alkalizing beverages, i.e. fluids which additionally increase urinary pH and citrate excretion, are bicarbonate-rich mineral water, orange and lemon juice. Neutral and alkalizing beverages are suitable for metaphylactic treatment of the majority of urinary stones, i.e. calcium oxalate, uric acid and cystine.
Dietary calcium, oxalate, and ascorbate
Dietary calcium is suggested to be the most important factor to influence oxalate absorption. Von Unruh et al. (2004) assessed the association between calcium intake and gastrointestinal oxalate absorption of healthy subjects with a recently developed standardized [13C2]oxalate absorption test . Within the range of 200–1200 mg calcium per day, oxalate absorption was clearly a linear function of the calcium intake. Additional calcium intake beyond 1,200 mg/d had only a minor effect on intestinal oxalate absorption. However, the increase in calcium intake resulted in a significant increase in urinary calcium excretion.
A case-control study in 186 calcium oxalate stone patients with and without hyperoxaluria yielded an inverse association between urinary oxalate excretion and dietary calcium intake, and a positive relationship with dietary ascorbate and fluid intake .
Fruits and vegetables are the major sources of dietary oxalate. Meschi et al. (2004) studied the effect of supplementation with low-oxalate fruits and vegetables in 26 calcium stone formers characterized by hypocitraturia and a fruit-vegetable-free diet . After 1 month of supplementation with fruits and vegetables, urinary volume, pH, citrate and magnesium excretion increased significantly. No changes were observed in urinary calcium and oxalate excretion. The unchanged calcium excretion is explained with the relatively high sodium chloride intake on both diets, whereas no conclusive explanation is provided for the unchanged oxalate excretion.
Dietary phytic acid, predominantly present in cereals, nuts, legumes and oil seeds, is able to complex calcium and therefore to increase the absorption of dietary oxalate. However, urinary phytate has been demonstrated to exhibit a strong inhibitory effect on the crystallization of calcium salts. Grases et al. (2000) found a significantly lower urinary phytate excretion in calcium oxalate stone formers compared with healthy men (2.01 vs 3.27 mg/24 h) . Data from two large observational studies revealed an inverse association of phytate intake with risk of stone formation in women, but not in men [20, 21].
A study in healthy subjects revealed the strongest decrease in urinary risk factors for uric acid stone formation on the intake of a balanced vegetarian diet compared to two omnivorous diets . An epidemiological trial conducted by Choi et al. (2004) yielded an increased risk of gout among men with higher levels of meat and seafood consumption and a declined risk with a higher level of intake of dairy products. The risk of gout remained unaffected by moderate intake of purine-rich vegetables . Findings from a recent study suggest that increasing meat or seafood intake is associated with increasing serum levels of uric acid, whereas dairy consumption is inversely associated with the serum uric acid level .
Dietary fatty acids
Dietary fatty acids are suggested to influence calcium oxalate stone formation. An increased phospholipid arachidonic acid level, a n-6 fatty acid, may therefore induce hyperoxaluria, by activating the anion carrier and consequently the intestinal and renal transport of oxalate. Analyses of dietary records and 24-h urine samples of 58 idiopathic calcium oxalate stone formers revealed a positive correlation between the dietary content of arachidonic acid and urinary oxalate excretion . Fish oil supplementation has been demonstrated to induce a reduction in the plasma arachidonic acid level in patients , and to lower urinary calcium and oxalate excretion in idiopathic calcium oxalate stone formers [26–28]. A recent prospective trial based on data from a semiquantitative food-frequency questionnaire revealed no consistent association between fatty acid intake and the risk for stone formation . Higher intake of arachidonic and linoleic acid did not increase the risk, and greater intake of n-3 fatty acids did not reduce the risk for incident kidney stones.
Overweight and diet-related diseases
Overweight and associated dietary pattern are suggested to be significant risk factors for stone formation. Analysis of 527 idiopathic calcium oxalate stone formers with respect to their body mass index (BMI) yielded overweight or obesity in 44% of the women and in 59% of the men . Multiple linear regression analysis of urinary parameters with reference to weight parameters revealed a significant positive relationship between BMI and urinary uric acid, sodium, ammonium, and phosphate excretion and a negative correlation between BMI and urinary pH. The risk of stone formation computed as relative supersaturation for calcium oxalate was higher in overweight and obese compared to normal weight patients.
A recent prospective trial demonstrated that BMI, waist circumference and weight gain are positively associated with an increased risk of nephrolithiasis in both men and women . An examination of more than 4,500 patients with a history of kidney stones confirmed an inverse association between body weight and urinary pH . A study conducted by Gillen et al. (2005) revealed a lower estimated glomerular filtration rate among overweight patients with a history of stone disease, suggesting a decreased renal function . Further investigations are warranted to examine the responsible mechanisms.
A recent intervention study examined the effect of dietary treatment on urinary risk factors for stone formation in recurrent calcium oxalate stone patients . A total of 107 patients collected 24-h urine on their habitual, self-selected diets and on a balanced standardized diet according to the recommendations for calcium oxalate stone formers. The frequency of a urine volume below 2.0 l/24 h decreased from 58% on the usual diet to 10% on the balanced diet, hypercalciuria from 25 to 11%, hyperuricosuria from 41 to 19%, and hypocitraturia from 57 to 32%, whereas no change was observed in the frequency of hyperoxaluria (14 vs 13%). A low fluid intake and an increased intake of protein and alcohol were identified as essential dietary risk factors. The intake of the balanced diet according to the recommendations for calcium oxalate stone formers resulted in a significant reduction in the risk of stone formation.
Effective dietary measures in urolithiasis are a balanced diet and a sufficient fluid intake accomplished by suitable beverages to achieve a urine volume of at least 2.0 litres daily. Overweight and associated dietary pattern are suggested to be significant risk factors for stone formation. Furthermore, overweight and obesity were found to be associated with an increased frequency of diet-related diseases. Overweight should be reduced but without extreme fasting or high-protein weight-loss diets (e.g. Atkins diet). Continued research is warranted to clarify controversies concerning the impact of dietary calcium, oxalate, n-3 fatty acids, and phytate in calcium stone formation. Further randomized controlled trials should explore the long-term effects of dietary interventions in stone formers.