Effect of Pb-exposure and B vitamin deficiencies on δ-aminolevulinic acid dehydratase activity among workers from Pb recycling plants.

Previous studies reported that Pb exposure causes a negative association with delta-aminolevulinic acid dehydratase activity (δ-ALAD), but the impact of Pb exposure (dose and time), B vitamin deficiencies, and lifestyle factors needs to be explored. In this study, the impact of Pb exposure, B vitamin deficiencies, and lifestyle factors on δ-ALAD activity among workers exposed to Pb from the Pb-recycling process was evaluated. Blood lead levels (BLLs), B vitamins (B6, B9, and B12), hematological factors (Hb% and HCT), lifestyle factors, and δ-ALAD activity was assessed in 170 male Pb-exposed workers engaged in the Pb recycling process. BLLs are estimated using the ICP-OES method. B vitamins in serum samples from workers were determined using the ELISA method. The δ-ALAD activity in whole blood samples was determined using the spectrophotometer method. The lifestyle factors were collected using a standard questionnaire. The δ-ALAD activity was significantly decreased in workers with the habits of alcohol use, tobacco consumption, hematocrit < 41%, mild and moderate categories of anemia, vitamin B6 and B12 deficiency, and BLL categories of 10-30, 30-50, and > 50 µg/dL. Multiple regression analysis revealed that the independent variables of alcohol consumption (ß = - 0.170; P = 0.025), BLLs (ß = - 0.589; P = 0.001) and Hb% (ß = 0.183; P = 0.001) significantly influenced the δ-ALAD activity with 44.2% (R2 = 0.442). Among the workers exposed to Pb from the Pb recycling plant, δ-ALAD activity was considerably reduced by Pb exposure, B vitamin deficiency, hematological parameters, and lifestyle factors.

Genetically predicted circulating B vitamins in relation to digestive system cancers.

BACKGROUND: Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations. METHODS: Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants. RESULTS: Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer. CONCLUSIONS: These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.

[Research of the cadmium intoxication effect on the model of vitamin-mineral deficiency in rats].

The article presents the results of the study aimed at confirmation of the effectiveness of the rats' adaptive potential reduction under conditions of cadmium salt toxic effects. The 65-days experiment was conducted in male and female Wistar rats. Animals were divided into 6 groups of 3 control and 3 experimental, 30 males and females in each. In total 360 rats were used in the experiment (180 females and 180 males). Rats of the 1st control group received a diet with optimal (75% of the standard semisyntethic diet content) dosage of vitamins B1, B2, B3, B6 and mineral substances, Fe3+ and Mg2+, the rats of the 2nd and the 3rd control group - diets with marginal (30% for males and 28% for females) and submarginal (19% for males and 18% for females) doses of essential micronutrients. Animals of the 1-3th experimental groups received Cd2+ on the background of optimal, marginal and submarginal providing of essential micronutrients. The hematological, biochemical and morphological parameters and the antioxidant status of rats have been studied. The obtained results allowed to identify patterns of cadmium toxic effect strengthen on the background of essential nutrients reducing (in the row from optimal to submarginal). These changes showed erythrocyte and platelet blood profiles, and a set of indicators of the antioxidant defense system and lipid peroxidation of blood and liver. Thus, the activity of erythrocyte antioxidant enzymes - glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase in rats of the 1st experimental group were on average by 23% higher than in animals of the 1st control group, the rats of the 2nd and the 3rd experimental groups by 62 and 67% higher, respectively. The content of lipid peroxidation products in blood and liver of male and female rats showed a similar trend: an increase by 5% in the 1st experimental group by 9 and 25% in the 2nd and 3rd experimental groups respectively. Thus, the modification of the diets' vitamin-mineral composition may be used as a model of adaptive potential reduction in rats in the toxicological research of objects with unknown toxicity, in particular novel food products.

Metabolomic Evaluation of the Consequences of Plasma Cystathionine Elevation in Adults with Stable Angina Pectoris.

Background: An elevated circulating cystathionine concentration, which arises in part from insufficiencies of vitamin B-6, B-12, or folate, has been shown to be associated with cardiovascular disease (CVD) risk. Hydrogen sulfide (H2S) is a gasotransmitter involved in vasodilation, neuromodulation, and inflammation. Most endogenously produced H2S is formed by pyridoxal phosphate (PLP)-dependent enzymes by noncanonical reactions of the transsulfuration pathway that yield H2S concurrently form lanthionine and homolanthionine. Thus, plasma lanthionine and homolanthionine concentrations can provide relative information about H2S production in vivo.Objective: To determine the metabolic consequences of an elevated plasma cystathionine concentration in adults with stable angina pectoris (SAP), we conducted both targeted and untargeted metabolomic analyses.Methods: We conducted NMR and LC-mass spectrometry (MS) metabolomic analyses on a subset of 80 plasma samples from the Western Norway Coronary Angiography Cohort and selected, based on plasma cystathionine concentrations, a group with high cystathionine concentrations [1.32 ± 0.60 µmol/L (mean ± SD); n = 40] and a group with low cystathionine concentrations [0.137 ± 0.011 µmol/L (mean ± SD); n = 40]. Targeted and untargeted metabolomic analyses were performed and assessed with the use of Student's t tests corrected for multiple testing. Overall differences between the cystathionine groups were assessed by untargeted NMR and LC-MS metabolomic methods and evaluated by partial least squares discriminant analysis (PLS-DA) with significant discriminating metabolites identified with 99% confidence.Results: Subjects with high cystathionine concentrations had 75% higher plasma lanthionine concentrations (0.12 ± 0.044 µmol/L) than subjects with low cystathionine concentrations [0.032 ± 0.013 µmol/L (P < 0.001)]. Although plasma homolanthionine concentrations were notably higher than lanthionine concentrations, they were not different between the groups (P = 0.47). PLS-DA results showed that a high plasma cystathionine concentration in SAP was associated with higher glucose, branched-chain amino acids, and phenylalanine concentrations, lower kidney function, and lower glutathione and plasma PLP concentrations due to greater catabolism. The high-cystathionine group had a greater proportion of subjects in the postprandial state.Conclusion: These data suggest that metabolic perturbations consistent with higher CVD risk exist in SAP patients with elevated plasma cystathionine concentrations.

Investigating Factors Involved in Post Laparoscopic Sleeve Gastrectomy (LSG) Neuropathy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity as the leading bariatric procedure for the treatment of morbid obesity. Due to the rising numbers of bariatric surgeries, neurologic complications have become increasingly recognized. Our aim was to examine biochemical and hormonal factors that are associated with neuropathy post-LSG. METHODS: Thirty-two patients were included: 16 patients with neuropathy in the neuropathic group (NG) and 16 patients without neuropathy in the control group (CG). Diagnosis was made by a consultant neurologist, and blood samples were taken to examine vitamin deficiencies and hormones involved in neuropathy. RESULTS: There was no significant difference between the BMI (p = 0.1) in both groups as well as excess weight loss percentages post-LSG at 12 months (p = 0.6). B12 levels were within normal range, but higher in NG (p = 0.005). Vitamin B1 and B2 levels were significantly lower in NG; p values are 0.000 and 0.031, respectively. Vitamin B6 levels were significantly higher in NG (p = 0.02) and copper levels were lower in NG (p = 0.009). There was no significant difference in GLP-1 response in both groups. CONCLUSION: Our data showed post-LSG neuropathy is associated with lower levels of vitamin B1, B2, and copper, plus patients who are older in age. Vitamin B6 was significantly higher in the NG, which is, at toxic levels, associated with neuropathy. No difference in preoperative BMI, excess weight loss percent at 1 year, and GLP-1 levels was found. Larger data is required to validate our results.

Hyperhomocysteinemia: Impact on Neurodegenerative Diseases.

Neurodegenerative diseases are the diseases of the central nervous system with various aetiology and symptoms. Dementia, Alzheimer's disease (AD), Parkinson's disease (PD) and autism are some examples of neurodegenerative diseases. Hyperhomocysteinemia (Hhcy) is considered to be an independent risk factor for numerous pathological conditions under neurodegenerative diseases. Along with genetic factors that are the prime cause of homocysteine (Hcy) imbalance, the nutritional and hormonal factors are also contributing to high Hcy levels in the body. Numerous clinical and epidemiological data confirm the direct correlation of Hcy levels in the body and generation of different types of central nervous system disorders, cardiovascular diseases, cancer and others. Till now, it is difficult to say whether homocysteine is the cause of the disease or whether it is one of the impacts of the diseases. However, Hhcy is a surrogate marker of vitamin B deficiency and is a neurotoxic agent. This Mini Review will give an overview of how far research has gone into understanding the homocysteine imbalance with prognostic, causative and preventive measures in treating neurodegenerative diseases.

Use of proton pump inhibitors is associated with anemia in cardiovascular outpatients.

BACKGROUND: Proton pump inhibitors (PPI) are frequently prescribed in combination with aspirin for preventing peptic ulcer in patients with atherosclerotic diseases. In contrast, long-term use of PPI has been suggested to be associated with iron or vitamin B12 deficiency. The effect of PPI on hemoglobin (Hb) concentration, however, has not been clarified in cardiovascular outpatients. METHODS AND RESULTS: We retrospectively investigated the clinical characteristics of 278 continuous outpatients who received blood test including complete blood count and serum creatinine concentration (mean age, 69.9 ± 10.8 years; male, 68.7%). The frequency of anemia was 51% in patients receiving PPI and 19% in those not receiving PPI (chi-squared test, P<0.001). On multivariate analysis female sex (P<0.001), peripheral artery disease (P=0.003), PPI (P=0.003), low white blood cell count (P=0.004), old age (P=0.007), and low estimated glomerular filtration rate (P=0.010) were independently associated with low Hb. Among these patients, we investigated the change in Hb after the initiation of PPI in 36 patients for whom data on Hb level within 1 year before and within 1 year after the initiation of PPI were available. Mean decrease in Hb after the initiation of PPI was 0.38 ± 0.87 g/dl (95% confidence interval: -0.67 to -0.09 g/dl). CONCLUSIONS: Use of PPI was associated with anemia in Japanese cardiovascular outpatients.

Serum estradiol associates with blood hemoglobin in elderly men: the MrOS Sweden study.

CONTEXT: Blood hemoglobin (Hb) declines with age in healthy elderly men, in whom decreasing T has been regarded as part of normal aging. However, the association between Hb and serum estradiol is incompletely known. OBJECTIVE: To determine whether estradiol is associated with anemia/Hb and established determinants of Hb in elderly men without prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: The MrOS (Osteoporotic Fractures in Men) is a population-based study (n = 918; median age, 75.3 y; range, 70-81 y). MAIN OUTCOME MEASURES: We evaluated total estradiol in relation to Hb and adjusted for potential confounders (ie, age, body mass index [BMI], erythropoietin [EPO], total T, cystatin C, and iron and B-vitamin status). RESULTS: Estradiol correlated negatively with age (r = -0.14; P < .001). Hb correlated (age adjusted) positively with estradiol (r = 0.21; P < .001) and T (r = 0.10; P < .01). Independent predictors for Hb in multivariate analyses were estradiol, EPO, BMI, transferrin saturation, cystatin C, and free T4, but not T. After exclusion of subjects with Hb <130 g/L and/or T < 8 nmol/L (n = 99), the correlation between Hb and T was no longer significant, whereas the associations between Hb and estradiol remained. After adjusting for age, BMI, and EPO, men with lower estradiol levels were more likely to have Hb in the lowest quartile of values (odds ratio per SD decrease in estradiol = 1.61 [95% confidence interval, 1.34-1.93]). Anemic subjects (Hb < 130 g/L) had lower mean estradiol than nonanemic subjects (67.4 vs 79.4 pmol/L; P < .001). CONCLUSIONS: Estradiol correlated positively and independently with Hb. Decreased estradiol might partly explain the age-related Hb decline observed in healthy elderly men.

Laboratory testing for and diagnosis of nutritional deficiencies in pregnancy before and after bariatric surgery.

OBJECTIVE: Bariatric surgery can reduce the risk of obesity-related complications of pregnancy, but may cause essential nutrient deficiencies. To assess adherence to laboratory testing guidelines, we examined frequency of testing for and diagnosis of deficiency during preconception and pregnancy using claims data in women with a delivery and bariatric surgery. METHODS: Retrospective analysis of claims from seven Blue Cross/Blue Shield plans between 2002 and 2008. We included women with a delivery and bariatric surgery within the study period. We used common procedural terminology (CPT) and ICD-9 codes to define laboratory testing and deficiencies for iron, folate, vitamin B12, vitamin D, and thiamine. Using Student's t-test and chi-square testing, we compared frequency of laboratory tests and diagnoses during 12 months preconception and 280 days of pregnancy between women with pregnancy before versus after surgery. We used multivariate logistic regression to evaluate for predictors of laboratory testing. RESULTS: We identified 456 women with pregnancy after bariatric surgery and 338 before surgery. The frequency of testing for any deficiency was low (9%-51%), but higher in those with pregnancy after surgery (p<0.003). The most common deficiency was vitamin B12 (12%-13%) with pregnancy after surgery (p<0.006). Anemia and number of health provider visits were independent predictors of laboratory testing. CONCLUSION: Women with pregnancy after bariatric surgery were tested for and diagnosed with micronutrient deficiencies more frequently than those with pregnancy before surgery. However, most laboratory testing occurred in less than half the women and was triggered by anemia. Increased testing may help identify nutrient deficiencies and prevent consequences for maternal and child health.

Low and high homocysteine are associated with mortality independent of B group vitamins but interactive with cognitive status in a free-living elderly cohort.

Hyperhomocysteinemia and cognitive impairment both predict mortality and partly because of dietary associations. We have hypothesized that for, nutritional reasons, homocysteine and cognition may act jointly to determine elder survival. In a Nutrition and Health Survey in Taiwan (1999-2000), some 1412 representative elderly were followed up for mortality up to 10 years. Cognition was assessed by the Short Portable Mental Status Questionnaire. Food and B vitamin intakes with their biomarkers, and plasma homocysteine, were measured at baseline. The possible effects of cognition on homocysteine-associated mortality were ascertained with Cox proportional-hazards models. Homocysteine was higher in those who were older, male, and single, consumed less fish and tea, and with alcohol and smoking. In models adjusted for these variables, when homocysteine exceeded 14.5 µmol/L, mortality was 1.80-fold more than when <9.3 µmol/L (hazard ratio [HR], 1.80; 95% confidence interval [95% CI], 1.20-2.71). P for trend was 0.002 and interactive with sex (P < .002). However, these homocysteine-mortality associations were dependent on cognition (P = .03); adjustment for food intake or nutrient status made little difference. Homocysteine did not predict cognitive impairment (adjusted OR, 1.40; 95% CI = 0.50-3.93). Vitamins B(1), B(2), and B(6) accounted somewhat for cognitive impairment. Cognition predicted mortality, fully adjusted for available covariates and also for homocysteine (HR, 3.66; 95% CI, 1.64-8.20) but interactively with homocysteine. Thus, the B-group vitamin insufficiency and cognitive impairment associations with premature mortality are confirmed. Yet cognition is inter-related with homocysteine in its association with survival in ways not detectably altered by foods or food-derived vitamins.

Nutritional B vitamin deficiency disrupts lipid metabolism causing accumulation of proatherogenic lipoproteins in the aorta adventitia of ApoE null mice.

SCOPE: Cardiovascular disease is the major cause of death in the world. Low dietary folate, elevated homocysteine, and high circulating cholesterol are risk factors. METHODS AND RESULTS: We investigated whether folate and/or B vitamin deficiency would change lipoprotein and fatty acid metabolism and lipid accumulation in the aorta adventitia of ApoE null mice. Mice (n = 10 per group) were fed a control (C; 4%) or high saturated fat (HF; 21%), and high cholesterol (0.15%) diet for 16 weeks. Folate (F-) or folate, B6 and B12 deficiency (F-B-) were imposed on these diets. Feeding a HF diet increased plasma and liver total cholesterol and HDL cholesterol (two- to threefold; p < 0.05). Total cholesterol increased (twofold; p < 0.05) in aorta adventitial lipid in response to HF. Feeding a diet depleted of folate and B vitamins (F-B-) significantly increased cholesterol accumulation in both liver and aorta adventitial lipid (approximately 50-70%; p < 0.05). Moreover, the proportions of fatty acids in hepatic and adventitial lipid was significantly changed by B vitamin depletion, measured as an increase in saturated fatty acids (approximately 15%) and a decrease (approximately 11%) in monounsaturated fatty acids (p < 0.05). CONCLUSION: B vitamin deficiency perturbs lipid metabolism in ApoE null mice, causing accumulation of proatherogenic cholesterol and fatty acids in the aorta adventitia.

Combined inadequacies of multiple B vitamins amplify colonic Wnt signaling and promote intestinal tumorigenesis in BAT-LacZxApc1638N mice.

The Wnt pathway is a pivotal signaling cascade in colorectal carcinogenesis. The purpose of this work is to determine whether depletion of folate and other metabolically related B vitamins induces in vivo activation of intestinal Wnt signaling and whether this occurs in parallel with increased tumorigenesis. A hybrid mouse was created by crossing a Wnt-reporter animal (BAT-LacZ) with a model of colorectal cancer (Apc1638N). A mild depletion of folate and vitamins B2, B6, and B12 was induced over 16 wk, and the control animals in each instance were pair fed a diet containing the basal requirement of these nutrients. The multiplicity of macroscopic tumors and aberrant crypt foci both increased by ~50% in the hybrid mice fed the depletion diet (P<0.05). A 4-fold elevation in Wnt signaling was produced by the depletion diet (P<0.05) and was accompanied by significant changes in the expression of a number of Wnt-related genes in a pattern consistent with its activation. Proliferation and apoptosis of the colonic mucosa both changed in a protransformational direction (P<0.05). In summary, mild depletion of multiple B vitamins produces in vivo activation of colonic Wnt signaling, implicating it as a key pathway by which B-vitamin inadequacies enhance intestinal tumorigenesis.

Prevalence of nutrient deficiencies in bariatric patients.

OBJECTIVE: The aims of this study were to determine the prevalence of nutrient deficiencies in patients who present for bariatric surgery, assess nutritional status after surgery, and compare these with preoperative levels. METHODS: A retrospective study was conducted to identify preoperative and 1-year postoperative nutrition deficiencies in patients undergoing bariatric surgery. The screening included serum ferritin, vitamin D, vitamin B(12), homocysteine, folate, red blood cell folate, and hemoglobin. Results were available for 232 patients preoperatively and 149 patients postoperatively. Two-tailed chi(2) tests and paired-sample t tests were used. RESULTS: Preoperatively, vitamin D deficiency was noted at 57%. The prevalence of abnormalities 1 year after roux-en-Y gastric bypass was higher compared with preoperative levels (P < .05). After surgery, anemia was detected in 17%, elevated homocysteine levels (women only) in 29%, low ferritin in 15%, low vitamin B(12) in 11%, and low RBC folate in 12%. Mean hemoglobin, ferritin, and RBC folate levels deteriorated significantly but remained well within normal ranges. The prevalence of vitamin D deficiencies decreased, but not significantly. In sleeve gastrectomy patients, mean ferritin levels decreased (P < .05), without any patient developing a deficiency. CONCLUSION: Vitamin D deficiency is common among morbidly obese patients seeking bariatric surgery. Because the prevalence of micronutrient deficiencies persists or worsens postoperatively, routine nutrition screening, recommendation of appropriate supplements, and monitoring adherence are imperative in this population.

Vitamins B depletion, lower iron status and decreased antioxidative defense in patients with chronic hepatitis C treated by pegylated interferon alfa and ribavirin.

BACKGROUND & AIMS: The impact of pegylated interferon combined with ribavirin upon the status of B vitamins, iron and oxidative stress in patients with hepatitis C virus (HCV) infection was examined. METHODS: Blood levels of B vitamins, iron status, and oxidative stress associated biomarkers were determined for 152 healthy controls and 109 HCV patients treated by pegylated interferon and ribavirin at three stages: before therapy, week 24 of treatment, and 48 weeks after therapy. RESULTS: HCV infection significantly lowered vitamin B(6) and folate (p<0.05). Therapy caused further decrease in vitamin B(6) (p<0.05), and also significantly decreased vitamins B(1) and B(2) (p<0.05). This anti-HCV therapy caused more patients to exhibit insufficient iron status. HCV infection elevated plasma level of malondialdehyde and 8-isoprostane, and therapy further exacerbated lipid oxidation (p<0.05). HCV infection significantly lowered vitamin C and glutathione levels (p<0.05); therapy significantly reduced alpha-tocopherol and activity of glutathione peroxidase and superoxide dismutase (p<0.05). CONCLUSION: This anti-HCV therapy elevated oxidative stress and depleted B vitamins and iron. Thus, the supplement of antioxidant agents, B vitamins and/or iron should be considered for patients with this therapy in order to avoid other healthy risk.

Drug-induced pertubation of the aminothiol redox-status in patients with epilepsy: improvement by B-vitamins.

OBJECTIVES: Patients with epilepsy have excess morbidity and mortality due to ischemic cardiovascular disease. Many of these patients have elevated concentrations of plasma total homocysteine (Hcy), which is an acknowledged risk factor for cardiovascular disease, venous thromboembolic disease, foetal malformations and dementia. Hyperhomocysteinemia may have negative effects through mechanisms involving oxidative damage. In the present study, we have investigated the aminothiol redox-status in patients on antiepileptic drugs. Thereafter, in a subset of patients with elevated total Hcy, we evaluated the effect of B-vitamin therapy. METHODS: In the first part of the study, 101 patients on antiepileptic drugs were compared with 101 matched healthy controls. The redox-species of Hcy, cysteine and cysteinylglycine, the major aminothiols in plasma, were analyzed by high-performance liquid chromatography (HPLC). Hyperhomocysteinemia was defined as fasting total Hcy above 12 micromol/L and/or post-methionine load concentrations above 38 micromol/L. In the second part of the study, 33 patients identified with hyperhomocysteinemia were supplemented with three B-vitamins for 30 days; folic acid (B9), pyridoxine (B6) and riboflavin (B2). RESULTS: All redox-species of Hcy were significantly elevated in the patients, except the fasting concentrations of reduced Hcy (p=0.09). The reduced/total ratio of cysteine in fasting plasma was lower in the patients than in the controls: 5.20% vs. 6.19%, respectively (p=0.006). After 30 days of B-vitamin supplementation, the plasma concentrations of reduced, oxidized and protein-bound Hcy species were significantly lowered by 17%, 22% and 28%, respectively. The reduced/total ratio of cysteine rose from 4.9% to 7.9% (p=0.007). CONCLUSIONS: Patients on antiepileptic drugs have abnormal aminothiol redox-status associated with hyperhomocysteinemia. This is similar to findings in patients with cardiovascular disease. B-vitamin supplementation partially corrects the abnormal aminothiol redox-status. Possibly, B-vitamin supplementation may be useful in drug-induced hyperhomocysteinemia.

[Vitamin B complex and homocysteine in chronic renal failure]. / Vitaminas B y homocisteína en la insuficiencia renal crónica.

Metabolic, biochemical, and hormonal changes occur in chronic renal failure usually associated with hyponutrition states. In predialysis patients, knowing the nutritional state about water-soluble vitamins such as thiamine, riboflavin, pyridoxine, cianocobalamine, and folic acid is becoming more and more important since some of the manifestations of chronic renal failure may be due to the deficiency of some of these water-soluble vitamins. The metabolic pathways in which most of these vitamins participate are interrelated and it is difficult to understand how the individual deficits of each vitamin affect renal pathology. This work aims at reviewing not only this issue but also the status of these water-soluble vitamins that different authors have found in groups of predialysis patients. On the other hand, the issue on the high prevalence of hyperhomocysteinemia in chronic renal failure as the main mortality risk factor due to cardiovascular pathologies as well as the implication of these vitamins in the metabolism of homocysteine, and consequently in plasma levels of this metabolite in predialysis patients is reviewed.

B vitamin plasma levels and the risk of ischemic stroke and transient ischemic attack in a German cohort.

BACKGROUND AND PURPOSE: Data from prospective studies on the associations between B vitamin plasma levels and the risk of stroke are limited. We investigated the individual and combined effects of plasma folate, vitamin B12, and pyridoxal 5-phosphate (PLP) levels on the risk of ischemic stroke and transient ischemic attack (TIA) in a large, prospective German cohort. METHODS: Incident cases of ischemic stroke or TIA were identified among 25 770 participants (age 35 to 65 years) of the European Prospective Investigation into Cancer and Nutrition-Potsdam Study during 6.0+/-1.5 years of follow-up. The present analysis is based on a case-cohort study comprising 779 subjects free from cardiovascular disease and 188 incident cases of cerebral ischemia (ischemic stroke or TIA). Multivariable Cox proportional-hazard models were applied to evaluate the association between B vitamin levels and risk of cerebral ischemia. RESULTS: Participants in the lowest tertile of vitamin B12 values were at increased risk of cerebral ischemia compared with subjects in the highest tertile; this was not observed, however, for either folate or PLP. In subgroup analyses, the relative risks were similar in magnitude for stroke and TIA. When various combinations of B vitamin tertile levels were analyzed, only combined low folate and vitamin B12 levels (relative risk, 2.24; 95% CI, 1.10 to 4.54) were significantly related to an increased risk of cerebrovascular ischemia. CONCLUSIONS: Our data suggest that low vitamin B12 plasma levels, particularly in combination with low folate levels, increase the risk of cerebral ischemia. This effect may be mediated at least partly through elevations of homocysteine levels.

B vitamins deficiency and decreased anti-oxidative state in patients with liver cancer.

BACKGROUND: This study examined the status of oxidative stress and B vitamins in hepatocellular carcinoma (HCC) patients in different tumor-node-metastasis stages. Patients were divided into two groups as I + II (n = 21) and III + IV (n = 19). METHODS: Plasma levels of lipid oxidation, alpha-tocopherol, beta-carotene, vitamin C, glutathione and the activity of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, catalase, and xanthine oxidase) were determined for evaluating oxidative status. Blood B vitamins (B(1), B(2), B(6), B(12), and folate) and serum ghrelin were analyzed, and the relationship between serum ghrelin and vitamins B(2) (or B(6)) was evaluated. RESULTS: HCC patients at III + IV stage showed significantly lower ghrelin, higher cholesterol, triglyceride, and uric acid than patients at I + II stage and healthy subjects (P < 0.05). Plasma lipid oxidation level in HCC patients was significantly greater than healthy subjects (P < 0.05). The activity of glutathione peroxidase, superoxide dismutase or catalase was significantly decreased, but xanthine oxidase activity was significantly elevated in HCC patients (P < 0.05). Plasma level of glutathione and vitamin C, not alpha-tocopherol and beta-carotene, in HCC patients was significantly lower (P < 0.05). Vitamins B(2) and B(6) levels in red blood cells from these HCC patients were significantly lower (P < 0.05). CONCLUSION: This study provided novel clinical findings regarding the status of oxidative stress and B vitamins in HCC patients. Plasma glutathione level may be a proper biomarker for evaluating oxidative status for HCC patients. Our data indicate that HCC patients might need B vitamins supplementation. The increased serum level of triglyceride and cholesterol might be a consequence of an impaired hepatic fat metabolism, and might be improved by a lower fat administration to these patients.

Effect of vitamin B6 deficiency on S-adenosylhomocysteine hydrolase activity as a target point for methionine metabolic regulation.

The objective of this study was to clarify the relationship between the accumulation of S-adenosylhomocysteine (SAH) and the change in the SAH hydrolase activity in vitamin B6 (B6). Male Wistar rats were fed a control diet (control and pair-fed groups) or B6-free diet (B6-deficient group) for 5 wk. Although the SAH-synthetic activity of SAH hydrolase significantly increased in the B6-deficient group, SAH-hydrolytic activity of SAH hydrolase showed no significant difference in the liver among the three groups. On the other hand, SAH hydrolase mRNA in the liver did not show any significant change. Thus, the accumulation of SAH would be due to the increased SAH-synthetic activity of SAH hydrolase. The disturbed methionine metabolism by B6-deficiency, such as a significant increase of plasma homocysteine, might induce the activation of SAH hydrolase in the direction of SAH synthesis.