Do teas rich in antioxidants reduce the physicochemical and peroxidative risk factors for calcium oxalate nephrolithiasis in humans? Pilot studies with Rooibos herbal tea and Japanese green tea.

Several experimental and animal studies have demonstrated that substances rich in antioxidants can reduce the physicochemical and peroxidative risk factors for calcium oxalate (CaOx) renal stone formation in urine and blood. However, there are very few such investigations in humans. In the present pilot study, two varieties of tea, a green one from Japan (JGT) and a herbal one from South Africa (Rooibos) (RT), both rich in antioxidants, were administered to a group of CaOx stone formers (SF) (n = 8) for 30 days. Both teas were analysed for polyphenols by high-performance liquid chromatography and for minerals by plasma atomic and optical emission spectroscopy. 24 h urines (baseline and day 30) were analysed for lithogenic factors. CaOx metastable limits and crystal nucleation and growth kinetics were also determined in each urine sample. Deposited crystals were inspected by scanning electron microscopy. Blood samples were collected (baseline and day 30). Biomarkers of oxidative stress including plasma and urinary thiobarbituric acid reactive substances (TBARS) and urinary N-acetyl-ß-D-glucosaminidase (NAG) were also determined. Urinary physicochemical risk factors were also investigated after ingestion of RT for 30 days in two control groups (CG1 and CG2), the latter one of which consisted of habitual JGT drinkers. Statistical analyses were performed using Wilcoxon signed rank tests and Mann-Whitney tests for paired and independent measurements, respectively. Several flavonoids and catechins were quantified in RT and JGT, respectively, confirming that both teas are rich sources of antioxidants. Mineral content was found to be far below dietary reference intakes. There were no significant changes in any of the urinary physicochemical or peroxidative risk factors in the control groups or in SF, except for the supersaturation (SS) of brushite (Bru) which decreased in the latter group after ingestion of JGT. Crystal morphology showed a tendency to change from mixed CaOx mono- and di-hydrate to monohydrate after ingestion of each tea. Since the latter form has a stronger binding affinity for epithelial cells, this effect is not protective. Analysis of the physicochemical and peroxidative risk factors in CG1 and CG2 did not reveal any evidence of a synergistic effect between the two teas. Paradoxically, baseline risk factors in the habitual JGT control group were significantly raised relative to those in CG1. Our preliminary results suggest that ingestion of RT and JGT does not reduce the risk factors for CaOx stone formation in humans, but these findings need to be tested in further studies involving much larger sample sizes.

Chitosan for overweight or obesity.

BACKGROUND: Chitosan, a deacetylated chitin, is a dietary supplement reported to decrease body weight. It is widely available over the counter worldwide and although evaluated in a number of trials its efficacy remains in dispute. OBJECTIVES: To assess the effects of chitosan as a treatment for overweight and obesity. SEARCH STRATEGY: We searched electronic databases (MEDLINE, EMBASE, BIOSIS, CINAHL, The Cochrane Library), specialised web sites (Controlled Trials, IBIDS, SIGLE, Reuter's Health Service, Natural Alternatives International, Pharmanutrients), bibliographies of relevant journal articles, and contacted relevant authors and manufacturers. Last searches were completed in March 2004. SELECTION CRITERIA: Trials were included in the review if they were randomised controlled trials of chitosan a minimum of four weeks duration in adults who were overweight or obese. Authors of included studies were contacted for additional information where appropriate. DATA COLLECTION AND ANALYSIS: Details from eligible trials were extracted independently by two reviewers using a standardised data extraction form. Differences in data extraction were resolved by consensus. Continuous data were expressed as weighted mean differences and standard deviations. The pooled effect size was computed by using the inverse variance weighted method. MAIN RESULTS: Fourteen trials including a total of 1131 participants met the inclusion criteria. No trial to date has measured the effect of chitosan on mortality or morbidity. Analyses including all trials indicated that chitosan preparations result in a significantly greater weight loss (weighted mean difference -1.7 kg; 95% confidence interval (CI) -2.1 to -1.3 kg; P < 0.00001), decrease in total cholesterol (-0.2 mmol/L; 95% CI -0.3 to -0.1; P < 0.00001), decrease in systolic (-5.9 mmHg; 95% CI -7.3 to -4.6; P < 0.0001) and diastolic (-3.4 mmHg; 95% CI -4.4 to -2.4; P < 0.00001) blood pressure compared with placebo. There were no clear differences between intervention and control groups in terms of frequency of adverse events or in faecal fat excretion. However, the quality of many studies was sub-optimal and analyses restricted to studies that met allocation concealment criteria, were larger, or of longer duration showed that such trials produced substantially smaller decreases in weight and total cholesterol. AUTHORS' CONCLUSIONS: There is some evidence that chitosan is more effective than placebo in the short-term treatment of overweight and obesity. However, many trials to date have been of poor quality and results have been variable. Results obtained from high quality trials indicate that the effect of chitosan on body weight is minimal and unlikely to be of clinical significance.

Effect of chitosan on weight loss in overweight and obese individuals: a systematic review of randomized controlled trials.

This article aims to determine whether chitosan, a popular, over-the-counter, weight loss supplement, is an effective treatment for overweight and obesity. It is designed as a systematic review of randomized controlled trials. The data sources include the electronic databases Medline, EMBASE, Biosis, CINAHL and Cochrane Central Register of Controlled Trials (CCTR); the specialized websites Controlled Trials, International Bibliographic Information on Dietary Supplements (IBIDS), System for Information on Grey Literature in Europe (SIGLE), Reuter's Health Service, Natural Alternatives International and Pharmanutrients; and bibliographies of relevant journal articles. Included were randomized controlled trials of chitosan with a minimum duration of 4 weeks in adults who were overweight or obese and/or had hypercholesterolaemia at baseline. Fourteen trials involving a total of 1071 participants were included in the review. Analyses involving all trials indicated that chitosan preparations result in a small but statistically significant greater reduction in body weight (weighted mean difference -1.7 kg; 95% confidence interval -2.1, -1.3 kg, P < 0.00001) compared with placebo. Analyses restricted to high-quality studies showed that reductions in weight [-0.6 (-1.2, 0.1) kg, P = 0.11] were less than in lower quality studies [-2.3 (-2.7, -1.8) kg, P < 0.00001]. Results obtained from high-quality trials indicate that the effect of chitosan on body weight is minimal and unlikely to be of clinical significance.

The effect of the dietary supplement, Chitosan, on body weight: a randomised controlled trial in 250 overweight and obese adults.

CONTEXT: Chitosan, a deacetylated chitin, is a widely available dietary supplement purported to decrease body weight and serum lipids through gastrointestinal fat binding. Although evaluated in a number of trials, its efficacy remains in dispute. OBJECTIVE: To evaluate the efficacy of chitosan for weight loss in overweight and obese adults. DESIGN AND SETTING: A 24-week randomised, double-blind, placebo-controlled trial, conducted at the University of Auckland between November 2001 and December 2002. PARTICIPANTS: A total of 250 participants (82% women; mean (s.d.) body mass index, 35.5 (5.1) kg/m(2); mean age, 48 (12) y) INTERVENTIONS: Participants were randomly assigned to receive 3 g chitosan/day (n=125) or placebo (n=125). All participants received standardised dietary and lifestyle advice for weight loss. Adherence was monitored by capsule counts. MAIN OUTCOME MEASURES: The primary outcome measure was change in body weight. Secondary outcomes included changes in body mass index, waist circumference, body fat percentage, blood pressure, serum lipids, plasma glucose, fat-soluble vitamins, faecal fat, and health-related quality of life. RESULTS: In an intention-to-treat analysis with the last observation carried forward, the chitosan group lost more body weight than the placebo group (mean (s.e.), -0.4 (0.2) kg (0.4% loss) vs +0.2 (0.2) kg (0.2% gain), P=0.03) during the 24-week intervention, but effects were small. Similar small changes occurred in circulating total and LDL cholesterol, and glucose (P<0.01). There were no significant differences between groups for any of the other measured outcomes. CONCLUSION: In this 24-week trial, chitosan treatment did not result in a clinically significant loss of body weight compared with placebo.

Influence of cranberry juice on the urinary risk factors for calcium oxalate kidney stone formation.

OBJECTIVE: To investigate the potential influence of cranberry juice on urinary biochemical and physicochemical risk factors associated with the formation of calcium oxalate kidney stones, as this product might affect the chemical composition of urine. SUBJECTS AND METHODS: Urinary variables were assessed in a randomized cross-over trial in 20 South African men (students) with no previous history of kidney stones. The first group of 10 subjects drank 500 mL of cranberry juice diluted with 1500 mL tap water for 2 weeks, while the second group drank 2000 mL of tap water for the same period. This was followed by a 2-week 'washout' period before the two groups crossed over. During the experimental phase subjects kept a 3-day food diary to assess their dietary and fluid intakes; 24-h urine samples were collected at baseline and on day 14 of the trial periods, and analysed using modern laboratory techniques. Urine analysis data were used to calculate the relative urinary supersaturations of calcium oxalate, uric acid and calcium phosphate. Data were assessed statistically by analysis of variance. RESULTS: The ingestion of cranberry juice significantly and uniquely altered three key urinary risk factors. Oxalate and phosphate excretion decreased while citrate excretion increased. In addition, there was a decrease in the relative supersaturation of calcium oxalate, which tended to be significantly lower than that induced by water alone. CONCLUSION: Cranberry juice has antilithogenic properties and, as such, deserves consideration as a conservative therapeutic protocol in managing calcium oxalate urolithiasis.

Aspects of calcium oxalate crystallization: theory, in vitro studies, and in vivo implementation.

There are three main approaches to urolithiasis research: theory, basic science, and clinical implementation. Although each approach has yielded meaningful results, there does not appear to be complete synergy between them. This article examines these approaches as they pertain to urinary calcium oxalate crystallization processes. Theoretical calculations were performed to examine the role of oxalate concentration on calcium oxalate supersaturation. The effects of magnesium, citrate, and combinations thereof on calcium oxalate crystallization kinetics were examined in a mixed suspension, mixed product removal crystallizer. Finally, male volunteers were given supplements of calcium alone and binary combinations of calcium, magnesium, and citrate to investigate their effects on the urinary supersaturation of calcium oxalate. Calculations showed that oxalate is 23 times more potent than calcium in its effect on the supersaturation of calcium oxalate. In the in vitro experiments, magnesium and citrate reduced the growth and nucleation kinetics as well as the supersaturation. In combination, these two components were more effective than the individual components in reducing the growth rate and the supersaturation. All of the supplements favorably altered the kinetic and thermodynamic risk factors. Calcium was the most effective in reducing the urinary excretion of oxalate. Articulation of these three approaches is essential for the meaningful investigation and understanding of urolithiasis.

Trace metal excretion in patients with homozygous hypercholesterolaemia.

In patients with familial hypercholesterolaemia regular therapeutic apheresis is acknowledged to have long-term benefit. A previously unrecognised complication of such intervention is the development of anaemia that reflects a sub-optimal dietary iron intake coupled with accelerated loss of this trace metal in the fluid discarded after each procedure. Additional contributions result from enhanced urinary excretion as a result of chelation to citrate used as an anticoagulant and frequent blood sampling. The underlying pathophysiologic process appears to be reduced deformability. We now document similar and significant losses of zinc, copper and chromium in these circumstances. In the case of the latter three elements, no associated clinical syndromes have thus far been identified, probably because deficiency states are less well-recognised than that due to iron loss and, additionally, because critical reductions are avoided by their replenishment during a normal food intake. These studies are, nevertheless, relevant since they are the basis for recommending prophylactic supplementation during this form of management.

Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C.

BACKGROUND: Long-term or high-dosage consumption of vitamin C may play a role in calcium oxalate kidney stone formation. The present study was undertaken to determine the biochemical and physicochemical risk factors in a male subject who developed haematuria and calcium oxalate crystalluria after ingestion of large doses of ascorbic acid for 8 consecutive days. METHODS: Twenty-four-hour urine samples were collected before and during the ascorbic acid ingestion period as well as after the detection of haematuria. A special procedure was implemented for urine collections to allow for oxalate, ascorbate and other urinalysis. Oxalate was determined in the presence of EDTA to prevent in vitro conversion to ascorbic acid, whereas ascorbate itself was determined by manual titration in a redox method using the dye dichlorophenolindophenol. Urinalysis data were used to compute calcium oxalate relative supersaturations and Tiselius risk indices, whereas scanning electron microscopy was used to examine urinary deposits. RESULTS: Oxalate excretion increased by about 350% during ascorbate ingestion before haematuria. Ascorbate concentrations also increased dramatically but appeared to reach a plateau maximum. Increasing calcium excretion was accompanied by decreasing potassium and phosphate values. The calcium oxalate relative supersaturation and Tiselius risk index increased during vitamin C ingestion and large aggregates of calcium oxalate dihydrate crystals were observed by scanning electron microscopy immediately after the detection of haematuria. CONCLUSION: High percentage metabolic conversion of ascorbate to oxalate in this subject caused relative hyperoxaluria and crystalluria, the latter manifesting itself as haematuria. Clinicians need to be alerted to the potential dangers of large dose ingestion of vitamin C in some individuals.

The effect of ascorbic acid ingestion on the biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation.

The present study was undertaken to determine the effect of ingestion of large doses of vitamin C on urinary oxalate excretion and on a number of other biochemical and physicochemical risk factors associated with calcium oxalate urolithiasis. A further objective was to determine urinary ascorbate excretion and to relate it qualitatively to ingested levels of the vitamin and oxalate excretion. Ten healthy males participated in a protocol in which 4 g ascorbic acid was ingested for 5 days. Urines (24 h) were collected prior to, during and after the protocol. The urine collection procedure was designed to allow for the analysis of oxalate in the presence and absence of an EDTA preservative and for the analysis of ascorbic acid by manual titration using 2,6 dichlorophenolindophenol. Physicochemical risk factors such as the calcium oxalate relative supersaturation and Tiselius risk index were calculated from urine composition. The results showed that erroneously high analytical oxalate levels occur in the asence of preservative. In the preserved samples there was no significant increase in oxalate excretion at any stage of the protocol. Ascorbate excretion increased when vitamin C ingestion commenced but levelled out after 24 hours suggesting that saturation of the metabolic pool is reached within 24 hours after which ingested ascorbic acid is excreted unmetabolized in the urine. While transient statistically significant changes occurred in some of the biochemical risk factors, they were not regarded as being clinically significant. There were no changes in either the calcium oxalate relative supersaturation or Tiselius risk index. It is concluded that ingestion of large doses of ascorbic acid does not affect the principal risk factors associated with calcium oxalate kidney stone formation.

The influence of South African mineral water on reduction of risk of calcium oxalate kidney stone formation.

OBJECTIVES: This study was undertaken to identify a South African mineral water containing relatively high concentrations of calcium and magnesium and to investigate its effect on urinary biochemical and physicochemical risk factors associated with calcium oxalate kidney stone formation. DESIGN: The study followed a change-over design in which each subject followed a randomised sequence of three water-drinking protocols involving their normal diet, a calcium and magnesium-rich mineral water and a mineral water deficient in these elements. SETTING: University of Cape Town. SUBJECTS: 54 volunteers without any previous history of stone disease (27 men, 27 women) in the age group 21-35 years and 31 with a history of calcium oxalate kidney stones (24 men, 7 women) in the age group 25-45 years participated in the study. OUTCOME MEASURES: Both mineral waters favourably altered several risk factors. However, the effect of the calcium- and magnesium-rich water was shown to be significantly greater as it altered a larger number of these factors and induced several unique changes that were not achieved by the other water. CONCLUSIONS: The risk of calcium oxalate stone formation can be significantly reduced by consumption of mineral water which is rich in calcium and magnesium.

Phase I studies of fluorouracil, doxorubicin and vinorelbine without (FAN) and with (SUPERFAN) folinic acid in patients with advanced breast cancer.

PURPOSE: The Breast Cancer Site Group of the National Cancer Institute of Canada - Clinical Trials Group (NCIC-CTG) undertook two parallel phase I studies to determine the maximum tolerated dose (MTD) and recommended phase II dose of vinorelbine in combination with doxorubicin and fluorouracil (with or without folinic acid) in metastatic breast cancer. METHODS: Cohorts of five patients were to receive: (a) fluorouracil 500 mg/m2 and doxorubicin 50 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on days 1, 8 and 15 every 3 weeks (FAN regimen), or (b) fluorouracil 340 mg/m2 and folinic acid 200 mg/m2 on days 1, 2, 3, 4 and 5, doxorubicin 40 mg/m2 on day 1 only and escalating doses of vinorelbine (15, 20, 25, 30 mg/m2) on day 1 and again on day 5 every 4 weeks (SUPERFAN regimen). Eligibility included measurable or evaluable metastatic breast cancer and having received neither previous chemotherapy for metastatic disease nor anthracycline-containing adjuvant therapy. RESULTS: Of 26 and 12 patients enrolled in the FAN and SUPERFAN regimens, 26 and 12 were evaluable for toxicity and 21 and 9 for response, respectively. Median ages were 60.3 years (41-71 years) and 64.2 years (51-73 years). Both regimens required amendment after the first cohort with an original day- 15 vinorelbine dose omitted from the FAN regimen and more prolonged nadir granulocyte counts allowed. Myelosuppression was dose limiting. MTDs in the FAN and SUPERFAN regimens were vinorelbine 25 mg/m2 and 20 mg/m2. Other toxicities included mucositis, septicemia and febrile neutropenia. Peripheral neuropathy and constipation were mild. Of the 21 FAN patients evaluable for response, 3 (14%) had complete responses and 7 (33%) had partial responses, for an overall response rate of 48%; 9 (43%) had stable disease and 2 (9%) had progressive disease as their best response. Of the nine SUPERFAN patients evaluable for response, none had a complete response. There were two (22%) with partial responses, and six (67%) had stable disease and one (11%) had progressive disease as their best response. CONCLUSIONS: The SUPERFAN regimen was too toxic to pursue even at the lowest dose. The recommended phase II starting dose for the FAN regimen was vinorelbine 20 mg/m2. Although these were phase I studies response rates in evaluable patients were less than expected and toxicity did not allow the use of as much vinorelbine in the combinations as had been anticipated. The limited response data from our study would imply that combining vinorelbine with more toxic agents may not enhance response rates and may defeat the advantage of tolerability, especially in elderly patients.

Effect of mineral water containing calcium and magnesium on calcium oxalate urolithiasis risk factors.

Calcium oxalate kidney stone formers are invariably advised to increase their fluid intake. In addition, magnesium therapy is often administered. Recently, a prospective study showed that a high dietary intake of calcium reduces the risk of symptomatic kidney stones. The present study was performed to test whether simultaneous delivery of these factors--high fluid intake, magnesium ingestion and increased dietary calcium--could reduce the risk of calcium oxalate kidney stone formation. A French mineral water, containing calcium and magnesium (202 and 36 ppm, respectively) was selected as the dietary vehicle. Twenty calcium oxalate stone-forming patients of each sex as well as 20 healthy volunteers of each sex participated in the study. Each subject provided a 24-hour urine collection after ingestion of mineral water over a period of 3 days; after a suitable rest period the protocol was repeated using local tap water (Ca: 13 ppm, Mg: 1 ppm). In addition, 24-hour urines were collected by each subject on their free diets. The entire cycle was repeated at least twice by each subject. Several risk factors (excretion of oxalate; relative supersaturations of calcium oxalate, brushite and uric acid; calcium oxalate metastable limit; oxalate:magnesium ratio and oxalate:metastable limit ratio) were favourably altered by the mineral water and tap water regimens but the former was more effective. In addition, the mineral water protocol produced favourable but unique changes in the excretion of citrate and magnesium as well as in the relative supersaturation of brushite which were not achieved by the tap water regimen. To the contrary, tap water produced an unfavourable change in the magnesium excretion. The group which benefitted most were male stone formers in whom 9 risk factors were favourably altered by the mineral water protocol. It is concluded that mineral water containing calcium and magnesium, such as that used in this study, deserves to be considered as a possible therapeutic or prophylactic agent in calcium oxalate kidney stone disease.

Re-evaluation of the "week-end effect" data: possible role of urinary copper and phosphorus in the pathogenesis of renal calculi.

Early morning urinary concentrations of 10 elements which had demonstrated a "week-end effect" in a previous study, were subjected to a normalization procedure thereby allowing a re-assessment of their potential role in urolithiasis. After transformation of each concentration to a weighted proportion of the total concentration on each day, only Cu and P values were significantly different for kidney stone formers and healthy controls on all three days indicating that these elements may play a role in the pathogenesis of renal calculi. The results obtained in this study demonstrate that a more meaningful picture of the possible differences in the urinary concentrations of stone formers and normal controls might emerge if "proportional" rather than "raw" concentrations are compared.

Fluoride metabolism and fluoride content of stones from children with endemic vesical stones.

Twenty children with endemic vesical stones showed normal plasma and urinary excretion of fluoride on a mean fluoride intake of 2.5 +/- 0.8 mg/24 h. The mean fluoride content of the stones obtained from these children was 315.6 +/- 264.9 micrograms/g in the nucleus and 229.9 +/- 212.8 micrograms/g in the periphery (this was not statistically significant). Calcium-containing stones had a higher fluoride content than stones containing uric acid and ammonium urate. It was concluded that children with endemic vesical stones have normal fluoride metabolism. Trace quantities of fluoride present equally in the nucleus and peripheral parts of the stones suggest that fluoride does not cause initiation or growth of the nucleus of vesical stones and is adventitiously deposited with calcium salts in these stones.

Quantitative X-ray diffraction analysis of urinary calculi by use of the internal-standard method and reference intensity ratios.

The internal-standard method and the powder diffractometer have been applied here to the quantitative determination of urinary stone constituents by x-ray diffraction (XRD). Reference intensity ratios determined for six stone substances were used in the reduction of intensity data. Constituent concentrations calculated for 21 stones were compared with values obtained from an element-sensitive technique. We conclude that XRD analysis alone cannot be regarded as a routine technique for the quantitative characterization of uroliths, but that semiquantitative XRD analysis supplemented by accurate quantitative elemental data is more suitable for the precise determination of true stone composition.