Plasma concentrations of individual tea catechins after a single oral dose in humans.

1. Ten healthy volunteers ingested 1.5 mmole epicatechin gallate (ECg), epigallocatechin (EGC) or epigallocatechin gallate (EGCg) in a randomized crossover design. After deconjugation, catechins in plasma and 24-h urine samples were determined by high-performance liquid chromatography (HPLC). Antioxidant activity was measured in plasma by determining ferric reducing activity (FRAP). 2. The catechin levels in plasma after ingestion were significantly different: EGC rose quickly with a short elimination half-life (t1/2 elim = 1.7 h), ECg was intermediate in rise but slowest in decline (t1/2 elim = 6.9h), EGCg was slowest in rise but intermediate in decline (t1/2 elim = 3.9h). At 24h, EGC and EGCg had returned to base levels, but ECg was still elevated. Peak maximum varied between 1.3 (EGCg) and 5.0 micromol l(-1) (EGC). 3. Very limited interconversion (ECg-->epicatechin, EGCg-->EGC) occurred indicating that degallation is not required for uptake. 4. Up to 13.6% of the ingested EGC (partly methylated) was excreted in the urine, but ECg or EGCg were not detected. 5. EGC and ECg produced an increase in antioxidant activity in plasma, but with EGCg, no statistically significant effect was found. 6. The pattern of uric acid in plasma showed a clear resemblance with that of FRAP and linear regression analysis indicated a very significant relationship (R2 = 0.88, p < 0.0001). 7. It is concluded that tea catechins differ significantly in their pharmacokinetic behaviour.

Dietary non-tocopherol antioxidants present in extra virgin olive oil increase the resistance of low density lipoproteins to oxidation in rabbits.

Consumption of a range of dietary antioxidants may be beneficial in protecting low density lipoprotein (LDL) against oxidative modification, as studies have demonstrated that antioxidants other than vitamin E may also function against oxidation of LDL in vitro. In the present study, the effect of polyphenol antioxidants on the susceptibility of LDL to copper-mediated oxidation was investigated after feeding semi-purified diets to 3 groups of New Zealand white (NZW) rabbits. All diets comprised 40% energy as fat with 17% energy as oleic acid. Dietary fatty acid compositions were identical. Oils with different polyphenol contents were used to provide the dietary source of oleic acid-refined olive oil, extra virgin olive oil and Trisun high oleic sunflower seed oil. Polyphenolic compounds (hydroxytyrosol and p-tyrosol) could only be detected in the extra virgin olive oil. Vitamin E was equalised in all diets. LDL oxidizability in vitro was determined by continuously monitoring the copper-induced formation of conjugated dienes after 6 weeks of experimental diet feeding. The lag phase before demonstrable oxidation occurred was significantly increased in the high polyphenol, extra virgin olive oil group (P < 0.05) when compared with combined results from the low polyphenol group (refined olive oil and Trisun), even though the LDL vitamin E concentration in the high polyphenol group was significantly lower. The rate of conjugated diene formation was not influenced by the presence of dietary polyphenols. Results demonstrate that antioxidants, possibly phenolic compounds which are present only in extra virgin olive oil, may contribute to the endogenous antioxidant capacity of LDL, resulting in an increased resistance to oxidation as determined in vitro.

Increasing phosphorus intake reduces urinary concentrations of magnesium and calcium in adult ovariectomized cats fed purified diets.

We assessed the phosphorus requirement of adult cats and the relationship between phosphorus intake and the fecal and urinary excretion of calcium, magnesium and phosphorus. Female cats (ovariectomized at the onset of sexual maturity) were fed purified diets containing 4.6, 9.2, 18.4 or 27.7 mmol phosphorus/MJ in a 4 x 4-wk crossover study. During the experiment, balance studies were performed and blood samples were taken. A dietary level of 4.6 mmol phosphorus/MJ was found to be sufficient to maintain phosphorus balance and normal plasma concentrations of phosphorus in the adult ovariectomized cats. Increasing levels of dietary phosphorus in the form of NaH2PO4.2H2O caused lower urinary pH values, lower urinary concentrations of calcium and magnesium, and higher urinary concentrations of phosphorus. When dietary levels of phosphorus were raised, the percentage of apparent absorption of magnesium was lower, whereas that of phosphorus was higher. Although it could be predicted that dietary phosphorus levels higher than the National Research Council recommendation of 9.2 mmol/MJ markedly reduced urinary struvite saturation, these higher levels are discouraged because they are associated with lower plasma phosphorus concentrations and creatinine clearance.

Increasing calcium intakes lower urinary concentrations of phosphorus and magnesium in adult ovariectomized cats.

The effect of dietary calcium level on the fecal and urinary excretion of calcium, phosphorus and magnesium was studied in adult cats. Ovariectomized cats were fed purified diets containing 3.2, 4.8, 9.5 or 19.3 mmol calcium/MJ in a 4 x 4 wk crossover study. During the experiment, balance studies were performed and blood samples were taken. The adult ovariectomized cats maintained calcium balance at all four levels of calcium tested. Extra dietary calcium, in the form of CaCO3, caused a slight increase in urinary pH. Urinary concentrations of phosphorus and magnesium dropped, but that of calcium remained unchanged, when the cats were fed diets with increasing calcium levels. The percentages of apparent absorption of phosphorus and magnesium fell when calcium intake was raised. The dietary calcium level did not affect plasma concentrations of calcium, magnesium and phosphorus or plasma activity of alkaline phosphatase.

Long-term phosphorus restriction prevents corticomedullary nephrocalcinosis and sustains reproductive performance but delays bone mineralization in rats.

In a long-term experiment with three successive generations of rats, the influence of dietary phosphorus restriction (2 instead of 4 g phosphorus/kg diet) on nephrocalcinosis, reproduction and bone mineralization was studied. Nephrocalcinosis in female rats, as based on kidney calcium concentration and histological examination, was prevented by phosphorus restriction. The low phosphorus diet caused reduced femur concentrations of magnesium, calcium and phosphorus in rats of the first and second generation aged 4 to 12 wk. The low phosphorus diet resulted in lower plasma phosphorus concentrations. In the kidneys of female rats, immediately after lactation, a higher degree of tubular hyperplasia was seen after the low phosphorus diet was fed. Reproductive performance was not affected by phosphorus restriction. We conclude that 0.2% phosphorus in the diet prevents nephrocalcinosis in female rats while it sustains reproduction but delays bone mineralization.

Inbred strains of rats have differential sensitivity to dietary phosphorus-induced nephrocalcinosis.

The degree of nephrocalcinosis after increasing the dietary phosphorus concentration from 0.2 to 0.5 g/100 g was measured in weanling female rats of 10 inbred strains. Based on kidney calcium concentrations and histological kidney calcification scores, there were considerable strain differences in nephrocalcinogenesis; 86% of the strain variability in nephrocalcinosis was attributable to genetic factors. Two strains with the most extreme nephrocalcinogenic responses were retested and the strain difference was found to be reproducible. Mean plasma phosphorus concentrations after phosphorus feeding were lower in the sensitive strain than in the insensitive strain. The high phosphorus diet produced greater urinary phosphorus concentrations, with the increase being greater in the sensitive strain. The strain difference in the response of urinary phosphorus concentrations after raising dietary phosphorus level may determine the strain difference in phosphorus-induced nephrocalcinosis. After consuming the high phosphorus diet, RP rats housed in groups in solid-floored cages had significantly higher degrees of nephrocalcinosis than their counterparts housed individually in metabolism cages with wire-mesh bases.

Vitamin D, within its range of fluctuation in commercial rat diets, does not influence nephrocalcinogenesis in female rats.

Massive, toxic doses of vitamin D have been shown to cause nephrocalcinosis in rats, but the effect of this vitamin within its range of fluctuation in commercial rat diets was unknown. Therefore, in two experiments with young female rats, the effect on nephrocalcinosis of a moderately increased level of vitamin D in the diet was studied, that is 5000 IU/kg versus the recommended concentration of 1000 IU/kg. This was done using purified diets with 0.5% (w/w) calcium and 0.04% magnesium containing either 0.2 or 0.6% phosphorus (P). Rats fed the diets containing 0.6% P showed severe kidney calcification compared to those fed the 0.2%-P diets. The level of vitamin D in the 0.2 and 0.6%-P diets did not affect kidney calcification. Bone density was increased after feeding diets containing 5000 instead of 1000 IU of vitamin D/kg. This study suggests that, within 28 days, a moderate increase of the amount of vitamin D in the diet has no influence on the development of kidney calcification. This in turn suggests that the variation in nephrocalcinosis severity and incidence seen in practice in rats fed different commercial diets is unlikely to be related to the different vitamin D concentrations in these diets. However, in rats fed such diets bone metabolism may be influenced differently.

Dietary fluoride prevents phosphorus-induced nephrocalcinosis in female rats.

The effect of dietary fluoride (F) on nephrocalcinosis was studied in young, female rats. Nephrocalcinosis was induced by a diet rich in phosphorus (P). F in the diet effectively counteracted P-induced nephrocalcinosis in a dose-dependent fashion. The feeding of increasing amounts of F caused decreasing calcium (Ca) and F concentrations in kidney. This suggests that the amount of Ca in kidney determines F accumulation in this organ, rather than F intake. Increasing amounts of F in the diet caused increasing rates of urinary and fecal excretion and whole-body retention of F. Dietary F did not influence urinary and fecal excretion and plasma concentrations of Ca, magnesium (Mg), and P. The metabolic basis for the protective effect of F against the development of nephrocalcinosis remains to be established.

Commercial rodent diets and nephrocalcinosis in weanling female rats.

This study addresses the questions to what extent commercial rodent diets would induce nephrocalcinosis, and which dietary components would be responsible for inducing this condition. For this purpose, 10 commercial diets were analysed for selected components and fed to weanling female rats. On the basis of histological inspection of kidney sections, two diets were found to produce significant nephrocalcinosis. The condition could be considered relatively mild because concentrations of Ca in kidney tissue were not increased. There was considerable variation between the commercial diets in the (analysed) concentrations of Ca, P, Mg and protein as well as in the diet-induced urinary pH, urinary volume and caecal weight. Of these parameters, only the dietary Ca:P ratio and group mean urinary pH correlated significantly with the observed variation in group mean calcification scores, the relationships being negative. It is suggested that the Ca:P ratio of commercial rodent diets is an important determinant of nephrocalcinosis.