Vitamin C and E supplementation blunts increases in total lean body mass in elderly men after strength training.

The aim of this study was to investigate the effects of vitamin C and E supplementation on changes in muscle mass (lean mass and muscle thickness) and strength during 12 weeks of strength training in elderly men. Thirty-four elderly males (60-81 years) were randomized to either an antioxidant group (500 mg of vitamin C and 117.5 mg vitamin E before and after training) or a placebo group following the same strength training program (three sessions per week). Body composition was assessed with dual-energy X-ray absorptiometry and muscle thickness by ultrasound imaging. Muscle strength was measured as one-repetition maximum (1RM). Total lean mass increased by 3.9% (95% confidence intervals: 3.0, 5.2) and 1.4% (0, 5.4) in the placebo and antioxidant groups, respectively, revealing larger gains in the placebo group (P = 0.04). Similarly, the thickness of m. rectus femoris increased more in the placebo group [16.2% (12.8, 24.1)] than in the antioxidant group [10.9% (9.8, 13.5); P = 0.01]. Increases of lean mass in trunk and arms, and muscle thickness of elbow flexors, did not differ significantly between groups. With no group differences, 1RM improved in the range of 15-21% (P < 0.001). In conclusion, high-dosage vitamin C and E supplementation blunted certain muscular adaptations to strength training in elderly men.

The aminothiol redox status in haemodialysis patients does not improve with folate therapy.

BACKGROUND: Patients on haemodialysis suffer from high cardiovascular morbidity and mortality, and oxidative stress may play a role in the pathophysiology of cardiovascular disease in these patients. Hyperhomocysteinemia is common in dialysis patients and may have pro-oxidant effects. Moreover, the redox status of the major plasma aminothiols (homocysteine [Hcy], cysteine and cysteinylglycine) may be regarded as a biomarker of oxidative stress. In the present study, we investigated the aminothiol redox status during a period of homocysteine-lowering therapy with folinic acid. MATERIAL AND METHODS: In the first part of the study, 32 stable patients receiving maintenance haemodialysis were compared with 32 reference subjects. In the second part, the patients were given folinic acid intravenously for 3 months. RESULTS: Before intervention with folinic acid, the patients had elevated concentrations of all redox species of Hcy. The aminothiol redox ratios were low. Folinic acid therapy lowered the concentrations of all Hcy redox species; however, the redox ratios did not improve. CONCLUSIONS: The low aminothiol redox ratios indicate the presence of oxidative stress in haemodialysis patients. Therapy with folinic acid lowered total Hcy concentrations, but did not improve the redox status. Thus, hyperhomocysteinemia appears to be of little importance in regard to the total level of oxidative stress in uraemia.

Holotranscobalamin and methylmalonic acid as prognostic markers following an acute myocardial infarction.

OBJECTIVE: To evaluate whether low levels of holotranscobalamin (holoTC) or elevated levels of methylmalonic acid (MMA), both indicators of vitamin B(12) deficiency, might predispose to new cardiovascular events following an acute myocardial infarction (MI). DESIGN: A prospective prognostic study. SETTING: One hospital center in Stavanger, Norway. SUBJECTS: A total of 300 patients admitted with an acute MI. METHODS: Registration of new TnT positive coronary events (defined as TnT>0.05 microg/l and a typical MI pattern) and/or cardiac death during a median follow-up time of 45 months. RESULTS: We compared the recurrence of events in the lowest quartile of holoTC (Q1<73.9 pmol/l) to the event rate above the 25% percentile (Q2-4). For methylmalonic acid (MMA) the same comparison was carried out for the upper quartile (Q4 > or =0.24 micromol/l) as compared with the event rate below the 75% percentile (Q1-3). After 18 and 45 months of follow-up, the odds ratio (OR) for Q1 vs Q2-4 for holoTC was 1.15 (95% confidence interval (CI) 0.91-1.46, P=0.25) and 1.05 (95% CI 0.86-1.29, P=0.64), respectively. For MMA the OR for Q4 vs Q1-3 was 0.95 (95% CI 0.76-1.19, P=0.67) after 18 months and 1.01 (95% CI 0.83-1.23, P=0.90) after 45 months. CONCLUSION: This study showed no increased risk of future cardiovascular events associated with low levels of holoTC or high levels of MMA following an acute MI.

Nutrient intakes; biochemical and risk indices associated with Type 2 diabetes and glycosylated haemoglobin, in the British National Diet and Nutrition Survey of people aged 65 years and over.

AIMS: To characterize nutritional differences between survey participants diagnosed with Type 2 diabetes; those without diabetes, and those with "undiagnosed diabetes" based on glycosylated haemoglobin (HbA(1c)). SUBJECTS AND METHODS: The 1994/5 British National Diet and Nutrition Survey, of people aged 65 years and over (mean age 78 years), included 73 respondents with diagnosed Type 2 diabetes [mean (sd) HbA(1c) = 7.06 (2.05)%], and 30 with "undiagnosed diabetes" (defined as HbA(1c) > 6.3%; mean (sd) HbA(1c) = 7.40 (1.66)%], among a representative sample of 1038 with anthropometry; 4-day weighed diet; blood and urine status measurements. RESULTS: The prevalence of Type 2 diabetes (diagnosed + undiagnosed) was 10%. In subjects without diagnosis of diabetes, those with HbA(1c) > 6.3% had on average a significantly higher body weight (73.6 vs. 67.9 kg), higher waist circumference (99.8 vs. 91.8 cm), higher body mass index (28.6 vs. 25.9 kg/m(2)) and higher white cell counts (7.64 vs. 7.09 x 10(9)/l), than those with mean HbA(1c) < or = 6.3%. Diagnosed diabetic subjects had significantly higher energy-adjusted intakes of protein, fibre, vitamins and minerals than those not in this category (P < 0.01). In contrast, those with undiagnosed diabetes (HbA(1c) > 6.3%) were nutritionally "at risk", having low plasma concentrations of lycopene (0.13 vs. 0.24 micromol/l) and high density lipoprotein cholesterol (0.99 vs. 1.27 micromol/l) and a trend towards low vitamin C (24 vs. 36 micromol/l) which was significant (P < 0.01) for men. HbA(1c) was positively correlated with white cell count, plasma fasting triglycerides, plasma alkaline phosphatase and homocysteine (all P < 0.01 overall), being particularly striking amongst men. CONCLUSIONS: Among older British citizens, those with diagnosed diabetes had healthier nutritional profiles than those undiagnosed with high HbA(1c). Important health-promoting benefits are therefore predicted following early diagnosis and nutritional advice for people with Type 2 diabetes.

Endothelial cell adhesion molecules in healthy adults during acute hyperhomocysteinemia and mild hypertriglyceridemia.

OBJECTIVE: Hyperhomocysteinemia and hypertriglyceridemia are independently associated with atherosclerotic disease. The process of atherogenesis involves inflammation and endothelial dysfunction. We tested whether concurrent acute hyperhomocysteinemia and mild hypertriglyceridemia increase the concentrations of circulatory cellular adhesion molecules in healthy subjects. STUDY DESIGN AND METHODS: Twelve healthy volunteers aged 37.5 years (range, 25-51) participated in the present study. The concentrations of plasma total homocysteine (p-tHcy), serum triglycerides, circulatory cellular adhesion molecules (CAMs), and concentrations of nitrate were measured at 0 (fasting), 2, 4, and 6 h after loading with (1) methionine, (2) fat, (3) methionine + fat, and (4) water (control). Wash out period between each loading was >or=1 week. RESULTS: Percent relative changes from baseline in the concentrations of p-tHcy, 2, 4, and 6 h after methionine and methionine + fat were significantly different from after water and fat loading. Changes in the concentrations of serum triglycerides 2 h after fat loading were significantly different from water loading, whereas methionine + fat loading caused a significant difference after 2, 4, and 6 h. We detected a synergistic increase in the triglyceride area response to methionine + fat loading. We detected also a significant difference in percent relative changes in the concentrations of P-selectin (PSEL) (P = 0.02), E-selectin (ESEL) (P = 0.003), and vascular cell adhesion molecule-1 (VCAM-1) (P = 0.005) 6 h after methionine + fat loading as compared to water loading. There was an additive increase in the PSEL area response to methionine + fat loading. Furthermore, area response to VCAM was greater to methionine loading than water loading (P = 0.01). A decrease in the concentration of NO(3) was more pronounced after methionine + fat loading and a significantly decreased area response of nitrate to methionine + fat loading was detected than to area response to water loading (P = 0.002). CONCLUSION: Inflammatory activation of the endothelium takes place during concurrent transient hyperhomocysteinemia and mild hypertriglyceridemia.

Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infarction.

OBJECTIVE: To assess the oxidative burden of a highly concentrated compound of n-3 PUFAs as compared to corn oil by measuring thiobarbituric acid-malondialdehyde complex (TBA-MDA) by HPLC. We also studied the influence on TBA-MDA of statins combined with n-3 PUFAs or corn oil. DESIGN: A prospective, randomised, double-blind, controlled study. SETTING: One hospital centre in Stavanger, Norway. SUBJECTS: A total of 300 subjects with an acute myocardial infarction (MI). INTERVENTIONS: Gelatine capsules, containing 850-882 mg EPA and DHA as concentrated ethylesters, or 1 g of corn oil, were ingested in a dose of two capsules twice a day for at least 1 y. Alpha-tocopherol (4 mg) was added to all capsules to protect the PUFAs against oxidation. RESULTS: After 1 y TBA-MDA increased modestly in the n-3 PUFA group (n=125), as compared to the corn oil group (n=130), P=0.027. Multiple linear regression analyses of fatty acids in serum total phospholipids (n=56) on TBA-MDA measured after 12 months intervention, showed no dependency. Performing best subsets regression, serum phospholipid concentration of arachidonic acid (20:4 n-6 PUFA) was identified as a predictor of TBA-MDA at 12 months follow-up, P=0.004. We found no impact of statins on TBA-MDA. CONCLUSION: TBA-MDA increased modestly after long-term intervention with n-3 PUFAs compared to corn oil post-MI, suggesting biological changes induced by n-3 PUFAs, rather than simply reflecting their concentration differences. The peroxidative potential of n-3 PUFAs was not modified by statin treatment. SPONSORSHIP: : Pharmacia A/S and Pronova A/S, Norway.

Relationship between methylmalonic acid, homocysteine, vitamin B12 intake and status and socio-economic indices, in a subset of participants in the British National Diet and Nutrition Survey of people aged 65 y and over.

OBJECTIVE: Assessment of functional vitamin B(12) status in a subset of the respondents in the British National Diet and Nutrition Survey of people aged 65 y and over. SETTING: National Diet and Nutrition Survey: a British nationwide cross-sectional sample of people aged 65 y and over, living either in the community or in institutions such as nursing homes, during one calendar year spanning 1994-1995. METHODS: Methylmalonic acid (MMA) concentrations were measured in plasma samples from 313 subjects (ca 14% of those originally enrolled in the survey). The results were compared with those for serum vitamin B(12), vitamin B(12) intakes and other status and intake estimates and with socio-demographic indices. RESULTS: Of the NDNS participants overall, 20% had serum vitamin B(12) concentrations<150 pmol/l. In the subset studied here, 24% of free-living and 46% of institution-living participants had MMA>0.5 micromol/l. Geometric mean MMA increased with age, from 0.25 micro mol/l in people aged 65-74 y to 0.38 micro mol/l in people aged 85+y. There was little evidence for any gender difference in MMA. It was inversely correlated with serum vitamin B(12) and with red blood cell folate; it was positively correlated directly with total homocysteine, but not significantly with serum folate or with vitamin B(12) intake. Among respondents with high MMA, a subgroup had normal serum vitamin B(12) but higher-than-average plasma urea and creatinine. Socio-demographic co-variates of MMA included receipt of State income benefits, social class of head of household, and educational attainment. These indices were not correlated with serum vitamin B(12). CONCLUSIONS: The progressive increase in MMA with age is metabolic evidence for increasing risk of functional vitamin B(12) deficiency with increasing age in older people. There is evidence that renal function is linked to high MMA in some older people. Age and renal function are thus both important when establishing upper reference limits for MMA. The socio-demographic observations suggest a link between poverty and poor functional vitamin B(12) status in older British people.

Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutrition Survey of young people aged 4-18 years, and a comparison with the survey of people aged 65 years and over.

Plasma total homocysteine (tHcy), cysteine and cysteinyl-glycine were measured in a representative sample of 922 young people aged 4-18 years, participating in the National Diet and Nutrition Survey in mainland Britain in 1997. Both tHcy and cysteine increased markedly with age; cysteinyl-glycine less so. Neither tHcy nor cysteine differed between genders; cysteinyl-glycine was higher in males. tHcy concentrations were lowest in the winter; cysteine and cysteinyl-glycine varied only slightly with season. In respondents aged >15 years, tHcy was higher in smokers, but in respondents aged 7-11 years, tHcy was higher in those whose mothers smoked. tHcy was inversely correlated with serum folate, serum vitamin B12 and vitamin B6 status, but neither cysteine nor cysteinyl-glycine shared these relationships. The relationships between tHcy and B-vitamin status indices ran parallel with those of the 65 years and over survey, but at much lower tHcy concentrations for any given B-vitamin concentration. Age-adjusted tHcy was not correlated with anthropometric indices, blood pressure, haematology, plasma creatinine, urea or cholesterol, but was directly correlated with fasting triacylglycerol. We conclude that disease-risk indices, like tHcy and perhaps cysteine, if established during early life, may be modulated by diet and lifestyle, thereby providing an opportunity for public health intervention.

Homocysteine, malondialdehyde and endothelial markers in dialysis patients during low-dose folinic acid therapy.

OBJECTIVES: Haemodialysis patients have elevated levels of the atherogenic amino acid homocysteine. We wanted to assess the effects of small doses of intravenous folinic acid (the active form of folic acid) on some biochemical risk factors of cardiovascular disease. DESIGN: Longitudinal and open intervention study. SETTING: Two dialysis units in the County of Rogaland. SUBJECTS: All patients on maintenance haemodialysis were invited, and 32 of 35 patients gave their informed consent. INTERVENTIONS: After each dialysis session, the patients were given 1.0 mg of folinic acid intravenously thrice a week for a period of 3 months. Prior to and during the study, all patients were on maintenance supplementation with small doses of vitamins B1, B2, B3, B5, B6 and B12. MAIN OUTCOME MEASURES: Changes in the levels of (i) plasma total homocysteine (p-tHcy) and folate, (ii) circulating endothelium related proteins--markers of endothelial activation and (iii) serum malondialdehyde (S-MDA)--a marker of oxidative stress and lipid peroxidation. RESULTS: The p-tHcy levels were reduced by 37% (P < 0.0001), whilst the serum and erythrocyte folate levels increased by 95 and 104%, respectively (P < 0.0001 for both). The circulating levels of endothelium related cellular adhesion molecules and haemostatic factors remained high and unchanged, except the thrombomodulin (TM) levels increased (P = 0.0004). The high levels of S-MDA were reduced by 26% (P = 0.003). CONCLUSIONS: Low doses of folinic acid given intravenously to dialysis patients reduced their levels of p-tHcy and S-MDA and thus improved their cardiovascular risk profile. The concurrent increment in TM levels was unexpected and of unknown clinical significance.

Geographical variations in nutrition-related vascular risk factors in the UK: National Diet and Nutrition Survey of People Aged 65 Years and Over.

BACKGROUND: There is a strong north-south gradient of vascular disease in Britain, whose aetiology is not fully understood. OBJECTIVE: To test the hypothesis, in a cross-sectional survey of older people, that intakes and status indices for protective micronutrients, particularly those for which fruit and vegetables are rich sources, also vary on a north-south axis. DESIGN: The 1994-5 National Diet and Nutrition Survey of People Aged 65 Years and Over has provided a uniquely appropriate data-set for this purpose. The analysis, confined to free-living participants, compared nutrient intakes and status between people living in the north of Britain, from Scotland to Humberside, with those living south of the Wash, excluding the Midlands and Wales. RESULTS: Highly significant north-south differences, especially for vitamin C, but also to a significant extent for B-vitamins and carotenoids, indicated a more vitamin-rich diet, with more frequent use of vitamin supplements, in the south. Vitamin D status and fibre intakes were also higher in the south; sodium intake was greater in the north. Blood lipid indices did not, however, differ between north and south. North-south differences in the likelihood of receiving income support, of having manual socio-economic status and of smoking habit, appeared to be significant underlying socio-demographic factors. CONCLUSION: These findings are consistent with the hypothesis that for older British people, differences in nutrient intake and status indices between the north and south of Britain run parallel with, and may contribute to, the north-south axis of vascular disease risk.

Haemostasis in ischaemic stroke and vascular dementia.

Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.

Antiepileptic drugs as independent predictors of plasma total homocysteine levels.

Low folate levels have consistently been reported in patients with epilepsy on phenytoin (PHT), phenobarbital (PB) and primidone (PRD), while data on valproate (VPA) are conflicting. Furthermore, antiepileptic drugs (AEDs) may be associated with high levels of plasma total homocysteine (p-tHcy). Therefore, we have investigated the levels of p-tHcy, serum folate (S-FA) and erythrocyte folate (E-FA) in patients on PHT, PB and PRD (Group 1, n=21) and VPA (Group 2, n=24). Both groups had their own matched controls. Blood samples were drawn fasting and 6 h post methionine loading (6 h-PML). The Group 1 patients had fasting and 6 h-PML p-tHcy levels significantly higher than their controls (P=0.05 and <0.0001, respectively), and patients without dietary multivitamin supplementation (n=14), had lower fasting S-FA and E-FA levels than their controls (P=0.02 and 0.0003, respectively). The Group 2 patients had fasting and 6 h-PML levels of p-tHcy, S-FA and E-FA not different from their controls. In a multiple stepwise regression model comprising all subjects (n=90), the AEDs of Group 1 and the S-FA levels were independent predictors of p-tHcy levels. Thus, PHT, PB and PRD are associated with high p-tHcy and low folate levels, whereas VPA does not influence S-FA, E-FA and p-tHcy levels in adult patients.

Folate, homocysteine and methionine loading in patients on carbamazepine.

OBJECTIVES: Some antiepileptic drugs (AEDs) are associated with low levels of serum (S-FA) and erythrocyte folate (E-FA) and high levels of plasma total homocysteine (p-tHcy). We have explored the concentrations of S-FA, E-FA and p-tHcy in patients on carbamazepine (CBZ). The methionine loading test was applied for better assessment of mildly impaired homocysteine metabolism. MATERIAL AND METHODS: The study comprised 42 adult patients on CBZ and 42 matched healthy controls. Blood samples were drawn prior to and 6 h post methionine loading (6 h-PML) (0.1 g/kg body weight). RESULTS: The patients on CBZ had significantly lower concentrations of fasting S-FA and E-FA than the controls (P=0.0004, P=0.003, respectively). Fasting and 6 h-PML p-tHcy concentrations were significantly higher in the patients than in the controls (P=0.03 and P=0.0001, respectively). The methionine loading test identified additional patients with hyperhomocysteinemia undetected by fasting p-tHcy. CONCLUSION: CBZ therapy may be associated with low folate and high p-tHcy levels.

Endogenous glutathione and platelet function in platelet concentrates stored in plasma or platelet additive solution.

Platelet function was studied in platelet concentrates by assay of the thrombin-induced release of endogenous serotonin and presence of the swirling phenomenon in relation to endogenous glutathione (GSH) and cysteine. In platelets stored in plasma, addition of cysteamine resulted in only a moderate fall in GSH after 5 days of storage, from an average of 14.91 to 11.46 nmol per 109 platelets. Exogenously added GSH had no effect, and addition of buthionine sulfoximine (BSO) resulted in almost complete depletion of GSH, to an average of 0.65 nmol per 109 platelets. Addition of cysteamine or GSH resulted in increased endogenous cysteine whereas BSO had no effect. In platelets stored in a platelet additive solution (T-sol), complete depletion of GSH was found in the presence of cysteamine, GSH and BSO. Endogenous serotonin was unchanged during storage both in plasma and in additive solution (2.8 nmol per 109 platelets). Despite almost total depletion of endogenous GSH, the thrombin-induced release of serotonin after 5 days' storage was significantly affected only in the presence of BSO in platelets stored in additive solution (mean values 72.3% vs. 63.3% of endogeneous serotonin, P < 0.05). Similarly, addition of cysteamine or GSH had no significant effect on swirling but BSO reduced the swirling score after 5 days' storage in platelet additive solution compared with plasma. After 10 days' storage, there was a significant reduction in swirling in the concentrates where BSO was added (P < 0.05).

Homocysteine concentrations and methionine loading in patients on antiepileptic drugs.

OBJECTIVES: A few reports have shown elevated fasting total plasma homocysteine (tHcy) in patients taking antiepileptic drugs (AEDs). In this study we determined the influence of AEDs on plasma tHcy levels prior to and following methionine loading. MATERIAL AND METHODS: Thirty-four patients on different AEDs and 34 matched controls were recruited. Blood samples were drawn prior to and 6 h post-methionine loading (6h-PML). RESULTS: The patients on AEDs inducing the cytochrome P450 (carbamazepine, phenytoin, phenobarbital, primidone), had higher fasting and 6h-PML plasma tHcy concentrations than the controls (P = 0.01 and P<0.001). Patients on AED inhibiting the cytochrome P450 (valproate [VPA]), had lower 6h-PML p-tHcy concentrations than controls (P = 0.01). CONCLUSIONS: Our data indicate that not only fasting but also 6h-PML tHcy levels should be determined in order to identify hyperhomocysteinemia among patients on AEDs. Inducer AEDs seem to have an opposite effect than the inhibitor VPA on plasma tHcy, erythrocyte folate and serum folate levels.

Correlation between plasma total homocysteine and copper in patients with peripheral vascular disease.

BACKGROUND: Increased concentrations of both plasma total homocysteine and copper are separately associated with cardiovascular disease. Correlations between plasma total homocysteine, trace elements, and vitamins in patients with peripheral vascular disease have not been investigated. METHODS: The concentrations of trace elements in plasma were determined by the multielement analytical technique of total-reflection x-ray fluorescence spectrometry. Plasma total homocysteine was determined by HPLC. RESULTS: In the univariate and multivariate regression analyses, copper was positively correlated with plasma total homocysteine in all subjects (coefficient +/- SE, 0.347 +/- 0.113; P = 0.0026 and coefficient +/- SE, 0.422 +/- 0.108; P = 0.0002, respectively), and in patients with peripheral vascular disease (coefficient +/- SE, 0.370 +/- 0.150; P = 0.016; and coefficient +/- SE, 0.490 +/- 0.151; P = 0.0025, respectively). Correlation between copper and plasma total homocysteine was not detected in healthy control subjects. The concentration of calcium in plasma (67.5 vs 80. 8 microg/g) was significantly lower in the patients than in the control subjects (P = 0.02). When the patients were divided into groups, the patients with suprainguinal lesions had significantly higher copper concentrations (P = 0.04) and significantly lower selenium and calcium concentrations (P = 0.01 and 0.008, respectively) than the healthy subjects. Patients had higher concentrations of autoantibodies against oxidized LDL and concentrations of thiobarbituric acid-reactive substance than the healthy subjects (P <0.0001 and P = 0.001, respectively). The concentrations of plasma total homocysteine and alpha-tocopherol were significantly higher, and the concentrations of vitamin B(6) and beta-carotene were lower in the patients than the healthy subjects. CONCLUSION: Our findings suggest that the atherogenicity of homocysteine may be related to copper-dependent interactions.

Comparison of Abbott IMx total homocysteine assay with a high pressure liquid chromatography method for the measurement of total homocysteine in plasma and serum from a Norwegian population.

In this study 189 samples were analysed for the measurement of homocysteine by the Abbott IMx homocysteine assay and an HPLC method. A strong correlation was obtained between the homocysteine measurements performed by the Abbott IMx homocysteine assay and the HPLC method (coefficient of correlation, r2 = 0.947, p < 0.0001). The plot of the difference for the homocysteine measurements between the two methods against the average of the two measurements resulted a mean difference of 0.80 +/- 6.66 (mean +/- 2SD), and 0.008 +/- 0.126 (mean +/- 2SD) for log converted values of homocysteine. The concentrations of homocysteine measured in all the samples by the two methods were not significantly different. However, the Abbott IMx homocysteine assay measured the concentrations of total homocysteine in hyperhomocysteinemia as significantly higher than the HPLC method (25.00 micromol/l vs. 23.12 micromol/l, p < 0.0001). More studies may be required to explore factors that may influence measurements of homocysteine by the Abbott IMx homocysteine assay and the HPLC method.

Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over.

Concentrations of pyridoxal phosphate and pyridoxic acid were measured in fasting plasma samples from British men and women aged 65 years and over, participating in a National Diet and Nutrition Survey during 1994-5, selected to be representative of the population of mainland Britain. In this population, the concentration of pyridoxal phosphate declined, whereas pyridoxic acid rose, with increasing age and frailty; however, both status indicators were strongly and directly (with a positive coefficient) correlated with estimates of vitamin B6 intake. This was little affected by the inclusion of food energy and protein intakes in the model. Forty-eight percent of the participants living in the community and 75% of those living in institutions had plasma pyridoxal phosphate concentrations below a range considered normal from other studies. In a univariate regression model, plasma pyridoxal phosphate concentrations were inversely correlated with plasma homocysteine concentrations, consistent with the hypothesis that vitamin B6 status may influence plasma homocysteine levels, and hence vascular disease risk. However, this relationship was partly attenuated in a multiple regression model including age, sex, domicile and biochemical status indices, including those of folate and vitamin B12. There was evidence that plasma pyridoxal phosphate was sensitive to metabolic conditions associated with inflammation and the acute-phase reaction, and that plasma pyridoxic acid was sensitive to renal function. Thus, neither index is an ideal predictor of vitamin B6 status in older people, unless these confounding factors are allowed for. Since poor vitamin B6 status may have health implications, e.g. for immune function, cognition, and for essential intermediary metabolic pathways in older people, it needs to be investigated as a possible public health problem.

Plasma total homocysteine response to oral doses of folic acid and pyridoxine hydrochloride (vitamin B6) in healthy individuals. Oral doses of vitamin B6 reduce concentrations of serum folate.

Plasma total homocysteine response was compared in four groups of healthy individuals given orally divided doses of vitamin supplementations for a duration of 5 weeks. The vitamin supplements; A, 0.3 mg folic acid; B, 120 mg vitamin B6; C, combination of 0.3 mg folic acid and 120 mg vitamin B6 or D, 0.6 mg folic acid reduced the concentrations of plasma total homocysteine 20, 17, 32 and 24%, respectively. However, the intergroup comparisons did not show a significant difference in the effects of vitamin supplements. Multivariate analysis with correction for differences in pre-supplement values indicated a significant effect of vitamin B6 supplementation on plasma total homocysteine and serum folate. Our data show that plasma total homocysteine concentrations are reduced with low to medium divided doses of folic acid alone or in combination with vitamin B6.

Atherothrombogenic risk modulation by n-3 fatty acids was not associated with changes in homocysteine in subjects with combined hyperlipidaemia.

Favourable effects of n-3 fatty acids on the atherogenic risk profile were recently demonstrated in subjects with combined (type IIb) hyperlipidaemia, not responding to a therapeutic diet. Re-examination of a previous patient material was performed to assess the influence of n-3 fatty acids on homocysteine and several coagulation factors. Subjects were randomly allocated to receive either a concentrated compound of 85% eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) (n = 28), or corn oil (n = 29), in a daily dose of 4g for 12 weeks. The intervention was double-blind. Homocysteine remained unchanged in both groups after 12-week treatment. N-3 fatty acids supplementation did not affect the levels of fibrinogen, coagulation factor VII or tissue factor pathway inhibitor (TFPI), while plasminogen activator inhibitor (PAI) increased significantly (Student's t-test; p <0.05). Total blood platelets were significantly reduced in subjects receiving n-3 fatty acids (Student's t-test; p <0.05), whereas bleeding times increased non-significantly.