Vitamin antioxidants, lipid peroxidation and the systemic inflammatory response in patients with prostate cancer.

The relationship between lipid soluble antioxidant vitamins, lipid peroxidation, disease stage and the systemic inflammatory response were examined in healthy subjects (n = 14), patients with benign prostate hyperplasia BPH (n = 20), localized (n = 40) and metastatic (n = 38) prostate cancer. Prostate cancer patients had higher concentrations of malondialdehyde (p < 0.05) and lower circulating concentrations of lutein (p < 0.05), lycopene (p < 0.001) and beta-carotene (p < 0.05). Patients with metastatic prostate cancer, when compared with patients having localized disease, had a higher Gleason score (p < 0.01) and had more hormonal treatment, but lower concentrations of PSA (p < 0.05), alpha-tocopherol (p < or = 0.05), retinol (p < 0.01), lutein (p < 0.05) and lycopene (p < 0.01). In the prostate cancer patients, PSA was correlated with the concentrations of the lipid peroxidation product, malondialdehyde (rs= 0.353, p = 0.002). C-reactive protein was not correlated with the vitamin antioxidants nor malondialdehyde. In contrast, there was a negative correlation between malondialdehyde concentrations and both lutein (rs= -0.263, p = 0.020) and lycopene (rs= -0.269, p = 0.017). These results indicate that lower concentrations of carotenoids, in particular, lycopene reflect disease progression rather than the systemic inflammatory response in patients with prostate cancer.

The relationship between the acute changes in the systemic inflammatory response, lipid soluble antioxidant vitamins and lipid peroxidation following elective knee arthroplasty.

BACKGROUND AND AIMS: The aim of the present study was to examine the time course of the change in the concentrations of plasma retinol, alpha-tocopherol, lutein, lycopene, alpha-carotene, beta-carotene (antioxidant vitamins) and malondialdehyde (lipid peroxidation) in patients following elective knee arthroplasty. METHODS: Patients (n=20) who underwent an elective knee arthroplasty, had venous blood samples withdrawn pre-operatively and at 12, 24, 48, 72 and 168 h after the start of surgery for the analysis of circulating concentrations of C-reactive protein, albumin, cholesterol, triglycerides and malondialdehyde and also the lipid soluble antioxidants vitamins. RESULTS: Over the study period of 0-168 h there was a significant increase in circulating C-reactive protein concentrations (peak 48 h, P<0.001) and a significant fall in albumin, cholesterol and triglyceride concentrations (trough 48 h, P<0.001). Malondialdehyde concentrations fell by approximately 35% (P<0.001) during the study period. However, they did not alter significantly over the study period when adjusted for triglyceride (P=0.309). The plasma concentrations of retinol, alpha-tocopherol, lutein, lycopene, alpha-carotene and beta-carotene all fell (P0.001). When adjusted for cholesterol, the reductions in plasma concentrations of alpha-tocopherol, lutein, lycopene, and beta-carotene in the post-operative period were no longer statistically significant. CONCLUSIONS: The results of the present study indicate that, in apparently healthy subjects undergoing an acute inflammatory insult, circulating lipid soluble vitamin antioxidants are transiently reduced. However, when corrected for lipids the concentrations were similar to those of baseline. In the absence of an increase in lipid peroxidation such falls in plasma concentrations of lipid soluble vitamins are unlikely to be a reliable measure of status.

Biological variation of vitamins in blood of healthy individuals.

BACKGROUND: Components of biological variation can be used to define objective quality specifications (imprecision, bias, and total error), to assess the usefulness of reference values [index of individuality (II)], and to evaluate significance of changes in serial results from an individual [reference change value (RCV)]. However, biological variation data on vitamins in blood are limited. The aims of the present study were to determine the intra- and interindividual biological variation of vitamins A, E, B(1), B(2), B(6), C, and K and carotenoids in plasma, whole blood, or erythrocytes from apparently healthy persons and to define quality specifications for vitamin measurements based on their biology. METHODS: Fasting plasma, whole blood, and erythrocytes were collected from 14 healthy volunteers at regular weekly intervals over 22 weeks. Vitamins were measured by HPLC. From the data generated, the intra- (CV(I)) and interindividual (CV(G)) biological CVs were estimated for each vitamin. Derived quality specifications, II, and RCV were calculated from CV(I) and CV(G). RESULTS: CV(I) was 4.8%-38% and CV(G) was 10%-65% for the vitamins measured. The CV(I)s for vitamins A, E, B(1), and B(2) were lower (4.8%-7.6%) than for the other vitamins in blood. For all vitamins, CV(G) was higher than CV(I), with II <1.0 (range, 0.36-0.95). The RCVs for vitamins were high (15.8%-108%). Apart from vitamins A, B(1), and erythrocyte B(2), the imprecision of our methods for measurement of vitamins in blood was within the desirable goal. CONCLUSIONS: For most vitamin measurements in plasma, whole blood, or erythrocytes, the desirable imprecision goals based on biological variation are obtainable by current methodologies. Population reference intervals for vitamins are of limited value in demonstrating deficiency or excess.

The relationship between plasma and red cell concentrations of vitamins thiamine diphosphate, flavin adenine dinucleotide and pyridoxal 5-phosphate following elective knee arthroplasty.

BACKGROUND & AIMS: Water soluble vitamins B1, B2 and B6 are essential precursors for a wide variety of coenzymes involved in intermediary metabolism and their status is usually assessed from blood samples. The aim of the study was to examine the relationship between plasma and intra-cellular B-vitamins following the systemic inflammatory response of surgery. METHODS: Patients (n = 10) who underwent an elective knee arthroplasty, had venous blood samples withdrawn pre-operatively and at 12, 24, 48, 72 and 168 h after the start of surgery for the analysis of circulating concentrations of C-reactive protein and albumin and also plasma and/ or red cell thiamine diphosphate (TDP), flavin adenine dinucleotide (FAD), pyridoxal 5-phosphate (PLP) as indicators of vitamins B1, B2, and B6 status respectively. RESULTS: Pre-operative, baseline vitamin assessments were all within population reference ranges. Over the study period of 0-168 h there was a significant increase in circulating C-reactive protein concentrations (peak 48 h, P < 0.001) and a significant fall in albumin concentrations (trough 48 h, P < 0.001). Plasma FAD and PLP concentrations fell transiently (P < 0.001) by approximately 40% reaching their nadir at approximately 48 h. CONCLUSIONS: The results of the present study indicate that plasma concentrations of FAD and PLP are transiently reduced following an inflammatory insult and therefore unlikely to be a reliable measure of status in the presence of a systemic inflammatory response. It may be that during such a response red cell concentrations provide a more reliable measure.

Optimisation and validation of a sensitive high-performance liquid chromatography assay for routine measurement of pyridoxal 5-phosphate in human plasma and red cells using pre-column semicarbazide derivatisation.

There are few studies in which direct measurement of vitamin B6 status in both plasma and red cells has been assessed. The aims of the present study were to evaluate the use of a simple, robust HPLC method of direct pyridoxal 5'-phosphate (PLP) measurement in plasma and red cells and to assess its use in establishing reference ranges in a healthy population. A reverse phase HPLC method with pre-column derivatisation using semicarbazide for the simultaneous measurement of PLP, its degradation product, 4-pyridoxic acid (PA) and pyridoxal (PL) in plasma and red cells was developed. Pre-column derivatisation, reverse phase chromatography and detection procedures were optimised. The recovery, precision, linearity and sensitivity of the assay for plasma and red cell PLP, PA and PL was established. The recovery of PLP was greater than 95% for both plasma and red cell samples. The Intra and Inter batch imprecision for PLP was less than 6% and 7%, respectively. The method for PLP was linear up to at least 1000 nmol/l and the detection limit was 2.1 nmol/l (limit of quantification; 5.8 nmol/l). Accuracy of PLP measurements in plasma were acceptable, showing a mean bias of 4.5% from the mean value of laboratories (N=34) participating in an external quality assurance scheme. Geometric mean (95% reference intervals) for plasma and red cell PLP in the healthy subjects (N=126) were 56 (21-138) nmol/l and 410 (250-680) pmol/g Hb, respectively. There was a strong positive correlation (r(2)=0.81) between plasma and red cell PLP levels in the reference population. The HPLC method described was found to be suitable for the routine measurement of PLP in both plasma and red cells.