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Biomedical subjects

S Samman

Publications and source records attributed to S Samman.

50 records · Page 3Linked to original sources

Dietary protein and cholesterol metabolism--interaction of minerals.

Increased dietary zinc has been shown to reduce plasma total cholesterol in rabbits fed casein. However, the mechanism is not clear. The minerals associated with casein and soya protein are different and present in amounts which can alter the overall mineral composition of the diet. In particular, casein has a much higher ratio of zinc/copper than soy protein. Utilising a range of copper concentrations (2-80 micrograms/g diet) in 14 experiments with casein diets showed a linear relationship between the cholesterolaemic response and copper concentration (when both log transformed) in groups (n = 6) of rabbits fed for 12 weeks (r = -0.70, p less than 0.05). The lower the copper, the greater the response. In no case was the copper content deficient, indicating some interaction must be reducing its availability. Similar analysis utilising the range of zinc (10-125 micrograms/g) in the diets also showed an enhanced response at low intakes (r = -0.85, p less than 0.05). To elucidate the mechanism, 2 groups of rabbits were fed casein diets containing 21 and 68 mg zinc/kg diet for 12 weeks. Low density apolipoprotein B (LDL-apoB) turnover was carried out using 125I labelled LDL-apoB and data was fitted to the 2 pool model. The production of LDL-apoB was reduced in animals fed the higher dietary zinc. Zinc appears to act by enhancing the production of LDL-apoB in casein fed animals, perhaps by reducing the availability of copper.

Animals↗

Effects of dietary protein on composition and metabolism of plasma lipoproteins in rabbits.

Changes in the concentration and composition of serum VLDL, LDL, and HDL were studied in rabbits transferred from Chow diets to cholesterol-free, semipurified diets containing casein or isolated soy protein. During the first week on the casein diet, there was a marked increase in LDL-cholesterol and these higher levels were maintained during the subsequent 3 weeks of the study. Similar but less marked changes were obtained with the soy protein diet. When the percent composition of the particles was determined, both VLDL and LDL had a higher proportion of cholesterol. Turnover studies indicated that the FCRs for radiolabelled VLDL and LDL were reduced in casein-fed animals compared to those fed soy protein. The elevated LDL levels in casein-fed rabbits were primarily due to a reduction in receptor-mediated catabolism of LDL-apo B. Receptor-independent removal in the two groups was similar. These studies show that the hypercholesterolemia in casein-fed rabbits, compared to those fed soy protein, is associated with cholesterol enrichment of LDL and impaired receptor-dependent removal of LDL-apo B.

Animals↗

Turnover of 125I-VLDL and 131I-LDL apolipoprotein B in rabbits fed diets containing casein or soy protein.

Rabbits fed low-fat, cholesterol-free, semi-purified diets containing casein developed a marked hypercholesterolemia compared to rabbits fed a similar diet containing soy protein (plasma cholesterol 281 +/- 31 vs. 86 +/- 9 mg/dl; P less than 0.05). Turnover studies (three per dietary group) were carried out in which homologous 125I-labeled VLDL and 131I-labeled LDL were injected simultaneously into casein- (n = 8) or soy protein- (n = 9) fed rabbits. ApoB-specific activities were determined in VLDL, IDL and LDL isolated from the pooled plasma of two or three rabbits per dietary group. The production rate of VLDL apoB (1.20 +/- 0.3 vs. 1.09 +/- 0.1 mg/h per kg) was similar for the two dietary groups. The fractional catabolic rate of VLDL apoB was lower for the casein group (0.15 +/- 0.03 vs. 0.23 +/- 0.01.h-1; 0.05 less than P less than 0.10). Although the pool size of VLDL apoB was higher in the casein group (8 +/- 2 vs. 5 +/- 0.3 mg/kg), this value did not reach statistical significance. For LDL apoB, the increased pool size in casein-fed rabbits (30 +/- 5 vs. 5 +/- 1 mg/kg; P less than 0.01) was associated with a decreased fractional catabolic rate (0.03 +/- 0.005 vs. 0.08 +/- 0.008.h-1; P less than 0.01) and a 2-fold increase in the production rate of LDL apoB (1 +/- 0.3 vs. 0.4 +/- 0.06 mg/kg per h; 0.05 less than P less than 0.10) compared to rabbits fed soy protein. Analysis of precursor-product relationships between the various lipoprotein fractions showed that casein-fed rabbits synthesized a higher proportion of LDL apoB (95% +/- 2 vs. 67% +/- 2; P less than 0.001) independent of VLDL catabolism. These results support the concept that the hypercholesterolemia in casein-fed rabbits is associated with impaired LDL removal consistent with a down-regulation of LDL receptors. These changes do not occur when the casein is replaced by soy protein.

Animals↗

Effects of dietary casein and soy protein on metabolism of radiolabelled low density apolipoprotein B in rabbits.

Rabbits fed semipurified diets containing casein have elevated plasma cholesterol levels compared to those fed soy protein. As part of continuing studies on the mechanism of casein-induced hypercholesterolemia, two groups of six rabbits were fed these diets for 14 to 16 weeks. Animals fed the casein diet were found to have significantly higher plasma concentrations of protein, cholesterol, triacylglycerol, phospholipid and apolipoprotein B (apo B) associated with low density lipoprotein (LDL) than those fed the soy protein diet. Kinetic studies showed that the fractional catabolic rate of LDL-apo B was significantly lower in animals fed casein than in those fed soy protein regardless of whether the tracer LDL was obtained from donors fed casein or soy protein. The production rate of LDL-apo B was higher in casein-fed animals but this was not statistically significant. These results show that the efficiency of removal of LDL is significantly reduced in animals fed casein compared to those fed soy protein, and that the source of LDL did not affect the efficiency of its subsequent removal. The accumulation of LDL in casein-fed animals is consistent with down-regulation of the LDL receptor.

Animals↗

The effect of zinc supplements on lipoproteins and copper status.

As part of a study to determine the effect of 150 mg zinc/day on plasma lipoproteins, healthy young female (n = 26; mean age 27 years) and male (n = 21; mean age 28 years) volunteers took part in a double-blind cross-over trial lasting 12 weeks. During 6 weeks of supplementation, plasma Zn rose significantly in both groups, indicating compliance. Plasma total cholesterol remained unchanged in both males and females. However, mean LDL-cholesterol decreased from 2.38 to 2.17 mmol/l in females and there was a trend for total HDL-cholesterol to be redistributed in that HDL2 rose and HDL3 fell slightly. In parallel with these changes in females, Zn supplements reduced the ferroxidase activity of serum caeruloplasmin (from 13.0 to 11.3 U/ml) and the antioxidant activity of erythrocyte superoxide dismutase (E-SOD) (from 4557 to 3638 U/g Hb) and CuZn E-SOD (from 2184 to 1672 U/g Hb). Plasma Cu and haematocrit were unaffected. No such changes were seen in males in either lipoproteins or these indicators of Cu status. Since the females were lighter than the males but received the same dose, a dose-response effect rather than a sex difference cannot be ruled out. Overall, Zn supplements significantly decrease a major risk factor for CHD in females but reduced their Cu status.

Administration, Oral↗

The effect of zinc supplements on plasma zinc and copper levels and the reported symptoms in healthy volunteers.

Information from animal studies has demonstrated the harmful effects of zinc supplementation on copper transport. Although some studies have been carried out in humans, the effect on humans has not been as well documented as the effect on animals. Forty-seven healthy volunteers (26 women and 21 men) took part in a double-blind cross-over trial which lasted for 12 weeks. The subjects were asked to take 50 mg of elemental zinc (as 220 mg zinc sulphate) or placebo, three times a day for six weeks. Venous blood was collected for the analysis of plasma levels of copper and zinc. Symptoms, which included headaches, abdominal cramps, nausea, loss of appetite and vomiting, were registered from 84% of women and 18% of men. Six female volunteers discontinued the trial; five owing to gastric irritation and one owing to consistent headaches. Plasma zinc levels rose significantly in both men and women, the increase being 36% and 57%, respectively. Plasma copper levels did not change significantly. Our study suggests that the gastric discomfort that is associated with zinc supplementation may be related to body weight as symptoms were reported from the lower-weight volunteers. Our study also shows no detrimental effect of 150 mg of zinc a day on plasma copper levels in healthy volunteers over a period of six weeks.

Adult↗

The importance of the non-protein components of the diet in the plasma cholesterol response of rabbits to casein. Zinc and copper.

To characterize further the effect of protein-mineral interaction on plasma cholesterol, four groups of rabbits were placed on cholesterol-free, semi-purified diets for 12 weeks. The diets were similar in proximate composition with either casein or soya-bean protein isolate as the protein source (250 g/kg). The dietary zinc content of the casein diets was increased to 22 mg/kg to equal that of the soya-bean diets. The copper content was set at 2 and 6 mg/kg. There were no differences in weight gain; all animals grew at a similar rate. When the dietary Zn content was equalized, the plasma and liver cholesterol responses were similar regardless of the source of protein. Differences in liver Cu and Zn were observed. As dietary Cu increased, Cu decreased and Zn increased in the liver. Hepatic Zn was also higher in soya-bean-fed than in casein-fed animals. No effects on plasma Cu and Zn were seen. The addition of Zn to the casein diet resulted in a similar plasma cholesterol to that of animals fed on the soya-bean diet, suggesting that casein-induced hypercholesterolaemia is due to a marginal Zn intake.

Animals↗

The importance of the non-protein components of the diet in the plasma cholesterol response of rabbits to casein.

To characterize the hypercholesterolaemic effect of casein further, four groups of young male rabbits in two separate experiments were placed on cholesterol-free semi-purified diets for 12 weeks. The diets were similar in composition, with either casein or soya-bean-protein isolate providing the protein source (250 g/kg). In two of these diets the salt mix was reduced by 45% (normally 40 g/kg) and replaced by potassium bicarbonate. Growth was unaffected by these alterations in dietary salts except for one group given the soya-bean-reduced-salts diet. The mean concentrations of plasma cholesterol were significantly higher in all casein-fed groups as compared with their soya-bean-fed counterparts but the response was much greater in those given the casein-reduced-salts diet. Contrary to expectations, analysis of the diets showed the zinc and copper concentrations of the casein diets to be less than those of the soya-bean diets. This was due to the greater concentrations of Cu (threefold) and Zn (twofold) in the soya-bean-protein isolate compared with casein. The mean concentration of Zn in fur was significantly decreased in casein-fed rabbits and these animals also excreted less Zn but more Cu in their urine than those given the casein-reduced-salts diet. The rabbits given the casein diet with the least salt mix showed the greatest degree of hypercholesterolaemia, suggesting an interaction between trace elements and the casein effect.

Animals↗

The reproducibility of the plasma response to a physiological dose of zinc in healthy subjects. Implications for study design.

Zinc absorption may be estimated by measuring the area under the plasma zinc curve following the ingestion of a zinc supplement. The aim of this study is to determine the reproducibility of such a response when a small dose of zinc is administered to healthy volunteers. Five female subjects were asked to consume 4.5 mg elemental zinc, and blood samples were obtained at 30 min intervals for 5 h. The experiment was repeated in the same volunteers 12-16 d later. The area under the plasma zinc curve was 30% lower after the second zinc tolerance test compared with the first (11.0 vs 15.8 mumol/l h). This difference could not be explained by differences in the fasting plasma zinc levels (12.9 mumol/L Experiment one, 15.1 mumol/L Experiment 2) nor was it related to technical or clinical parameters. The area under the curve after 5 h was strongly correlated with the response after 4 h. Hence we conclude that a small dose of zinc can be used to determine zinc absorption and a shorter experimental period may be used. However, trials must be designed to take into account the sequence variability in the response.

Absorption↗

The role of boron in nutrition and metabolism.

A large number of responses to dietary boron occur when the boron content of the diet is manipulated. Numerous studies suggest that boron interacts with other nutrients and plays a regulatory role in the metabolism of minerals, such as calcium, and subsequently bone metabolism. Although the mechanism of action has not been defined, it may be mediated by increasing the concentration of steroid hormones such as testosterone and beta-oestradiol. Boron is obtained from a diet rich in fruits, vegetables, nuts and legumes. The daily intake has been estimated to range from 0.3-41 mg per day. The wide range is due to the variation of the analytical methods used and differences in the soil content of boron. Based on a limited number of studies, increasing dietary boron results in increases in the boron concentration of all tissues. Large amounts of boron are well tolerated while consistent signs of deficiency include depressed growth and a reduction in some blood indices, particularly steroid hormone concentrations. Via its effect on steroid hormones and interaction with mineral metabolism, boron may be involved in a number of clinical conditions such as arthritis. Further research is required before boron is accepted as an essential nutrient for humans.

Animals↗