vitamin-b-12 and Inflammation

AHR has been identified as ligand-modulated transcription factor and environmental sensor. However, explanation of its multiple agonistic and antagonistic ligands is far from complete. Studies of AHR's role in host-microbiome interaction are currently a fruitful area of research. Microbial products and virulence factors have been identified as AHR agonists. In steady state they are involved in safeguarding intestinal barrier integrity. When virulence factors from pathogenic bacteria are identified by AHR of intestinal immune cells, anti-microbial defense mechanisms are activated by generating reactive oxygen species (ROS) in intestinal epithelial cells and recruited immune cells. ROS production has to be strictly controlled, and anti-inflammatory responses have to be initiated timely in the resolution phase of inflammation to avoid tissue damage and chronic inflammatory responses. Surprisingly, bacteria-generated vitamin B12/cobalamin and vitamin B9/folic acid have been identified as natural AHR antagonists, stimulating the interest of biochemists. Hints for AHR-cobalamin antagonism are pointing to cobalamin-dependent enzymes leading to alterations of TCA cycle intermediates, and TCDD-mediated loss of serum cobalamin. Although we are still at the beginning to understand mechanisms, it is likely that scientific efforts are on a rewarding path to understand novel AHR functions.

Topics: Folic Acid; Humans; Inflammation; Ligands; Reactive Oxygen Species; Receptors, Aryl Hydrocarbon; Vitamin B 12

The 5-10-methylenetetrahydrofolate reductase (MTHFR) enzyme is vital for cellular homeostasis due to its key functions in the one-carbon cycle, which include methionine and folate metabolism and protein, DNA, and RNA synthesis. The enzyme is responsible for maintaining methionine and homocysteine (Hcy) balance to prevent cellular dysfunction. Polymorphisms in the

Topics: Carbon Cycle; Cardiovascular Diseases; Diabetes Mellitus; Epigenesis, Genetic; Female; Folic Acid; Heart Disease Risk Factors; Homocysteine; Humans; Inflammation; Male; Methionine; Methylenetetrahydrofolate Reductase (NADPH2); Polymorphism, Genetic; Vascular Diseases; Vitamin B 12

Psoriasis is caused by a complex interplay among the immune system, genetic background, autoantigens, and environmental factors. Recent studies have demonstrated that patients with psoriasis have a significantly higher serum homocysteine (Hcy) level and a higher prevalence of hyperhomocysteinaemia (HHcy). Insufficiency of folic acid and vitamin B12 can be a cause of HHcy in psoriasis. Hcy may promote the immuno-inflammatory process in the pathogenesis of psoriasis by activating Th1 and Th17 cells and neutrophils, while suppressing regulatory T cells. Moreover, Hcy can drive the immuno-inflammatory process by enhancing the production of the pro-inflammatory cytokines in related to psoriasis. Hcy can induce nuclear factor kappa B activation, which is critical in the immunopathogenesis of psoriasis. There may be a link between the oxidative stress state in psoriasis and the effect of HHcy. Hydrogen sulfide (H2S) may play a protective role in the pathogenesis of psoriasis and the deficiency of H2S in psoriasis may be caused by HHcy. As the role of Hcy in the pathogenesis of psoriasis is most likely established, Hcy can be a potential therapeutic target for the treatment of psoriasis. Systemic folinate calcium, a folic acid derivative, and topical vitamin B12 have found to be effective in treating psoriasis.

Topics: Animals; Cytokines; Folic Acid; Homocysteine; Humans; Inflammation; Psoriasis; Vitamin B 12

Homocysteine (Hcy) is a sulfur-containing amino acid that is generated during methionine metabolism. Physiologic Hcy levels are determined primarily by dietary intake and vitamin status. Elevated plasma levels of Hcy can be caused by deficiency of either vitamin B12 or folate. Hyperhomocysteinemia (HHcy) can be responsible of different systemic and neurological disease. Actually, HHcy has been considered as a risk factor for systemic atherosclerosis and cardiovascular disease (CVD) and HHcy has been reported in many neurologic disorders including cognitive impairment and stroke, independent of long-recognized factors such as hyperlipidemia, hypertension, diabetes mellitus, and smoking. HHcy is typically defined as levels >15 micromol/L. Treatment of hyperhomocysteinemia with folic acid and B vitamins seems to be effective in the prevention of the development of atherosclerosis, CVD, and strokes. However, data from literature show controversial results regarding the significance of homocysteine as a risk factor for CVD and stroke and whether patients should be routinely screened for homocysteine. HHcy-induced oxidative stress, endothelial dysfunction, inflammation, smooth muscle cell proliferation, and endoplasmic reticulum (ER) stress have been considered to play an important role in the pathogenesis of several diseases including atherosclerosis and stroke. The aim of our research is to review the possible role of HHcy in neurodegenerative disease and stroke and to understand its pathogenesis.

Topics: Animals; Homocysteine; Humans; Inflammation; Neurology; Practice Patterns, Physicians'; Reactive Oxygen Species; Vitamin B 12

The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism than its use during pregnancy, perhaps because of well-known deficiencies in the metabolic breakdown of pharmaceuticals during early development. Thus, one explanation for the increased prevalence of autism is that increased exposure to acetaminophen, exacerbated by inflammation and oxidative stress, is neurotoxic in babies and small children. This view mandates extreme urgency in probing the long-term effects of acetaminophen use in babies and the possibility that many cases of infantile autism may actually be induced by acetaminophen exposure shortly after birth.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Aspartame; Autistic Disorder; Child; Child, Preschool; Female; Folic Acid; Humans; Hyperbilirubinemia; Infant; Inflammation; Male; Metals, Heavy; Organophosphates; Oxidative Stress; Pregnancy; Risk Factors; Thimerosal; Vitamin B 12

Topics: Acetylcysteine; Animals; Antipsychotic Agents; Aripiprazole; Autistic Disorder; Complementary Therapies; Disease Models, Animal; Evidence-Based Medicine; Free Radical Scavengers; Gastrointestinal Tract; Humans; Inflammation; Mice; Oxidative Stress; Randomized Controlled Trials as Topic; Risperidone; United States; United States Food and Drug Administration; Vitamin B 12

To analyse the anti-inflammatory and antioxidant properties of vitamin B12 and evaluate current evidence on vitamin B12 status in the critically ill with systemic inflammation.. Data on vitamin B12 status of intensive care unit patients are scarce. Cobalamins could potentially be useful agents for inhibiting nitric oxide synthase and nitric oxide production, controlling nuclear factor-kappa B activation, and restoring optimal bacteriostasis and phagocytosis in which transcobalamins play a proven role. The antioxidant properties of vitamin B12, with a glutathione-sparing effect, are secondary to stimulation of methionine synthase activity and reaction with free oxygen or nitrogen radicals. Large parenteral doses are routinely administered for cyanide poisoning, with only mild, reversible side-effects. Current evidence suggests that high-dose parenteral vitamin B12 may prove an innovative approach to treat critically ill systemic inflammatory response syndrome patients, especially those with severe sepsis/septic shock. In this setting, vitamin B12 and transcobalamins could modulate systemic inflammation contributing to the anti-inflammatory cascade and potentially improve outcome.. Despite evidence from animal studies, so far there are no clinical intervention trials that have studied vitamin B12 as a pharmaconutrient strategy for critical care. Well designed animal and clinical studies are required to clarify several outstanding questions on the optimal posology, safety, and efficacy of high-dose vitamin B12 in the critically ill.

Topics: Animals; Antioxidants; Critical Illness; Humans; Inflammation; Sepsis; Vitamin B 12

Migraine is recognized as a complex neurological disorder that has imposed a social burden. We assessed the signaling pathways and molecular mechanisms based on the in silico analysis and predicted drug candidates by the biomedicine approach. Moreover, we evaluated high-intensity interval training and vitamin B12 + magnesium on women's migraine attacks and inflammatory status.. This study computed differential gene expression in migraine syndrome and the dimension network parameters visualized by software. Moreover, we proposed the functional mechanism and binding energy of essential micronutrients on macromolecules based on drug discovery. In this clinical trial, 60 cases were randomized to four groups, including applied high-intensity interval training (HIIT), cases consumed supplementation vitamin B12 and magnesium (Supp), cases applied high-intensity interval training, and consumed supplementation (HIIT + Supp), and migraine cases for 2 months. Serum levels of calcitonin gene-related peptide (CGRP) were measured at baseline and at the end of the study. In addition, migraine disability assessment score (MIDAS), frequency, intensity, and duration were recorded before and during interventions.. In silico study revealed the association between inflammation signaling pathways and pathogenesis of migraine attacks as a remarkable pathomechanism in this disorder. Furthermore, serum concentrations of CGRP were significantly declined in the HIIT + Supp compared with other groups. In addition, MIDAS, frequency, intensity, and duration were reduced in the HIIT + Supp group compared with the other groups.. We found that the synergistic effects of cobalamin and magnesium followed by regular exercise could silence the inflammation signaling pathway, and a combination of HIIT + Supp could ameliorate migraine pain.. This study was registered in the Iranian Registry of Clinical Trials; IRCT code: IRCT20170510033909N12. Approval Data: 2021/06/02.

Topics: Artificial Intelligence; Calcitonin Gene-Related Peptide; Exercise; Female; Humans; Inflammation; Iran; Magnesium; Migraine Disorders; Vitamin B 12

Vegans are at an increased risk for certain micronutrient deficiencies, foremost of vitamin B

Topics: Adult; Biomarkers; Cardiovascular Diseases; Cholesterol; Diet, Vegan; Fatty Acids; Female; Healthy Volunteers; Homocysteine; Humans; Inflammation; Male; Methylmalonic Acid; Micronutrients; Nutritional Status; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency

The aim of this study was to determine whether reducing plasma homocysteine concentrations with long-term, combined treatment with folic acid, vitamin B. These findings indicate that long-term, combined treatment with folic acid, vitamin B. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000541.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Double-Blind Method; Drug Combinations; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Inflammation; Inflammation Mediators; Middle Aged; Time Factors; Treatment Outcome; Vitamin B 12; Vitamin B 6; Vitamins

B-vitamin trials failed to demonstrate beneficial effects on cardiovascular outcomes, but hyperhomocysteinemia still stands out as an independent cardiovascular risk factor, particularly in elderly individuals. B-vitamins may influence early vascular dysfunction, such as endothelial dysfunction, or may have adverse effects, for example on inflammation. We investigated the effect of B-vitamins on endothelial function and inflammation within an interventional study. This study was conducted within the framework of the B-PROOF trial, which included 2919 hyperhomocysteinemic elderly individuals, who received daily vitamin B12 (500 μg) and folic acid (400 μg) or placebo for 2 years. Using an electrochemiluminescence platform, we measured intercellular adhesion molecule 1 (ICAM-1), vascular adhesion molecule 1 (VCAM-1), serum amyloid A (SAA), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) at baseline and follow-up in a subsample of 522 participants (271 intervention group; 251 placebo). Treatment effects were analyzed with ANCOVA. The participants had a mean age of 72 years, and 55% of them were male. At the 2-year follow-up, B-vitamins did not change the ICAM-1 (+36% change in the intervention group versus +32% change in the placebo group; p = 0.72), VCAM-1 (+27% vs +25%; p = 0.39), VEGF (-1% vs +4%; p = 0.40), SAA (+34% vs +38%; p = 0.85) or CRP levels (+26% vs +36%; p = 0.70) as compared to placebo. In conclusion, in elderly patients with hyperhomocysteinemia, vitamin B12 and folic acid are unlikely to influence either endothelial function or low-grade systemic inflammation. ClinicalTrials.gov Identifier: NCT00696514.

Topics: Age Factors; Aged; Aged, 80 and over; Analysis of Variance; Biomarkers; Dietary Supplements; Double-Blind Method; Drug Combinations; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Inflammation Mediators; Male; Netherlands; Time Factors; Treatment Outcome; Vitamin B 12

Background/Aims. Low serum folate levels can alter inflammatory reactions. Both phenomena have been linked to Alzheimer's disease (AD), but the effect of folic acid on AD itself is unclear. We quantified folate supplementation's effect on inflammation and cognitive function in patients with AD over the course of 6 months. Methods. Patients newly diagnosed with AD (age > 60 years; n = 121; mild to severe; international criteria) and being treated with donepezil were randomly assigned into two groups with (intervention group) or without (control group) supplemental treatment with folic acid (1.25 mg/d) for 6 months. The Mini-Mental State Examination (MMSE) was administered to all patients at baseline and follow-up, and blood samples were taken before and after treatment. We quantified serum folate, amyloid beta (Aβ), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), plasma homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and the mRNA levels of presenilin (PS), IL-6, and TNFα in leukocytes. Data were analyzed using a repeated-measures mixed model. Results. The mean MMSE was slightly increased in the intervention group compared to that in the control group (P < 0.05). Posttreatment, plasma SAM and SAM/SAH levels were significantly higher (P < 0.05), while Aβ 40, PS1-mRNA, and TNFα-mRNA levels were lower in the intervention group than in the control group (P < 0.05). The Aβ 42/Aβ 40 ratio was also higher in the intervention group (P < 0.05). Conclusions. Folic acid is beneficial in patients with AD. Inflammation may play an important role in the interaction between folic acid and AD. This trial is registered with clinical trial registration number ChiCTR-TRC-13003246.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Female; Folic Acid; Humans; Inflammation; Male; Middle Aged; Single-Blind Method; Vitamin B 12

To assess the impact of a personalized diet, with or without addition of VSL#3 preparation, on biomarkers of inflammation, nutrition, oxidative stress and intestinal microbiota in 62 healthy persons aged 65-85 years.. Open label, randomized, multicenter study.. High-sensitivity C-reactive protein.. Community.. Eight week web-based dietary advice (RISTOMED platform) alone or with supplementation of VSL#3 (2 capsules per day). The RISTOMED diet was optimized to reduce inflammation and oxidative stress.. Blood and stool samples were collected on days 1 and 56.. Diet alone reduced ESR (p = 0.02), plasma levels of cholesterol (p < 0.01) and glucose (p = 0.03). Addition of VSL#3 reduced ESR (p = 0.05) and improved folate (p = 0.007), vitamin B12 (p = 0.001) and homocysteine (p < 0.001) plasma levels. Neither intervention demonstrated any further effects on inflammation. Subgroup analysis showed 40 participants without signs of low-grade inflammation (hsCRP<3 mg/l, subgroup 1) and 21 participants with low-grade inflammation at baseline (hsCRP≥3 mg/l, subgroup 2). In subgroup 2 addition of VSL#3 increased bifidobacteria (p = 0.005) in more participants and improved both folate (p = 0.015) and vitamin B12 (p = 0.035) levels compared with subgroup 1. The increases were positively correlated to the change in the bifidobacteria concentration for folate (p = 0.023) and vitamin B12 (p = 0.001). As expected change in homocysteine correlated negatively to change in folate (r = -0.629, p = 0.002) and vitamin B12 (r = -0.482, p = 0.026).. Addition of VSL#3 increased bifidobacteria and supported adequate folate and vitamin B12 concentrations in subjects with low-grade inflammation. Decrease in homocysteine with VSL#3 was clinically relevant. suggesting protective potentials for aging-associated conditions, e.g. cardiovascular or neurological diseases. ClinicalTrials.gov: NCT01069445-NCT01179789.

Topics: Aged; Aged, 80 and over; Biological Products; Biomarkers; Blood Glucose; C-Reactive Protein; Cholesterol; Diet; Dietary Supplements; Feeding Behavior; Female; Folic Acid; Gastrointestinal Microbiome; Homocysteine; Humans; Inflammation; Intestines; Lactobacillus; Lactobacillus delbrueckii; Lactobacillus plantarum; Male; Oxidative Stress; Probiotics; Streptococcus thermophilus; Vitamin B 12

The effect of homocysteine (Hcy)-lowering therapy may be different in hemodialysis (HD) patients with and without diabetes mellitus (DM).. Stable HD patients with uremia were administered folic acid and vitamin B for 3 months. The impact of treatment was compared in patients with and without DM.. A total of 61 patients (31 men and 30 women) aged 56 ± 13 y completed the study. Among these, 44 patients (72%) did not have DM and 17 (28%) had DM. At baseline, total Hcy and high-sensitivity C-reactive protein (hsCRP) levels were similar. After treatment, the levels of total Hcy and hsCRP were significantly decreased in the nondiabetic group (total Hcy level decreased from 33.63 ± 14.13 μmol/l to 18.94 ± 8.46 μmol/l, p<0.001; hsCRP level decreased from 0.58 mg/dl [range, 0.21-1.05 mg/dl] to 0.22 mg/dl [range, 0.11-0.53 mg/dl], p<0.001) but not in the diabetic group (total Hcy level decreased from 34.97 ± 17.12 μmol/l to 29.53 ± 11.36 μmol/l, p=0.057; hsCRP level decreased from 0.80 mg/dl [range, 0.24-1.47 mg/dl] to 0.49 mg/dl [range, 0.45-0.98 mg/dl], p=0.28). Serial monitoring of total Hcy level showed a more sustained effect of therapy on patients without DM.. Folic acid and vitamin B administration significantly lower total Hcy and hsCRP levels in HD patients without DM but not in those with DM.

Topics: Biomarkers; C-Reactive Protein; Diabetes Complications; Dietary Supplements; Folic Acid; Homocysteine; Humans; Inflammation; Male; Middle Aged; Regression Analysis; Renal Dialysis; Uremia; Vitamin B 12

Hemodialysis (HD) patients have a greatly increased risk of cardiovascular morbidity and mortality. For this reason, attempts are often made to normalize hyperhomocysteinemia. This randomized prospective study sought to determine which risk factors are predictors of mortality and whether high doses of folates or 5-methyltetrahydrofolate (5-MTHF) could improve hyperhomocysteinemia and survival in HD patients.. 341 patients were divided into two groups: group A was treated with 50 mg i.v. 5-MTHF, and group B was treated with 5 mg/day oral folic acid. Both groups received i.v. vitamin B(6) and B(12). By dividing patients into C-reactive protein (CRP) quartiles, group A had the highest survival for CRP <12 mg/l, whereas no survival difference was found for group B. CRP was the only predictive risk factor for death (RR 1.17, range 1.04-1.30, p = 0.02). Dialysis age, hyperhomocysteinemia, methylenetetrahydrofolate reductase polymorphism, albumin, lipoprotein (a) and folate did not influence mortality risk. Survival in group A was higher than that in group B, namely 36.2 +/- 20.9 vs. 26.1 +/- 22.2 months (p = 0.003).. Our results suggest that CRP, but not hyperhomocysteinemia, is the main risk factor for mortality in HD patients receiving vitamin supplements. Intravenous 5-MTHF seems to improve survival in HD patients independent from homocysteine lowering.

Topics: Aged; C-Reactive Protein; Female; Humans; Hyperhomocysteinemia; Inflammation; Kidney Failure, Chronic; Male; Middle Aged; Models, Biological; Risk; Risk Factors; Tetrahydrofolates; Vitamin B 12; Vitamin B 6

Epidemiological and laboratory studies suggest that increasing concentrations of plasma homocysteine (total homocysteine [tHcy]) accelerate cardiovascular disease by promoting vascular inflammation, endothelial dysfunction, and hypercoagulability.. We conducted a randomized controlled trial in 285 patients with recent transient ischemic attack or stroke to examine the effect of lowering tHcy with folic acid 2 mg, vitamin B12 0.5 mg, and vitamin B6 25 mg compared with placebo on laboratory markers of vascular inflammation, endothelial dysfunction, and hypercoagulability.. At 6 months after randomization, there was no significant difference in blood concentrations of markers of vascular inflammation (high-sensitivity C-reactive protein [P=0.32]; soluble CD40L [P=0.33]; IL-6 [P=0.77]), endothelial dysfunction (vascular cell adhesion molecule-1 [P=0.27]; intercellular adhesion molecule-1 [P=0.08]; von Willebrand factor [P=0.92]), and hypercoagulability (P-selectin [P=0.33]; prothrombin fragment 1 and 2 [P=0.81]; D-dimer [P=0.88]) among patients assigned vitamin therapy compared with placebo despite a 3.7-micromol/L (95% CI, 2.7 to 4.7) reduction in total homocysteine (tHcy).. Lowering tHcy by 3.7 micromol/L with folic acid-based multivitamin therapy does not significantly reduce blood concentrations of the biomarkers of inflammation, endothelial dysfunction, or hypercoagulability measured in our study. The possible explanations for our findings are: (1) these biomarkers are not sensitive to the effects of lowering tHcy (eg, multiple risk factor interventions may be required); (2) elevated tHcy causes cardiovascular disease by mechanisms other than the biomarkers measured; or (3) elevated tHcy is a noncausal marker of increased vascular risk.

Topics: Biomarkers; Blood Coagulation; Cardiovascular Diseases; Endothelium, Vascular; Folic Acid; Homocysteine; Humans; Inflammation; Ischemic Attack, Transient; Pyridoxine; Risk Factors; Stroke; Vitamin B 12; Vitamin B Complex

Elevated plasma levels of total homocysteine (tHcy) are associated with an increased risk of developing occlusive vascular diseases. To better illustrate the relationship between plasma tHcy concentration, oxidative stress, and inflammation in patients with coronary artery disease (CAD), we measured plasma 8-isoprostane-prostaglandin F 2 (Iso-P), plasma malondialdehyde (MDA), and several markers of inflammation. We also aimed to demonstrate the effects of vitamin supplementation on these markers.. A total of 93 patients with ischemic heart disease were investigated. Of these, 34 had plasma tHcy < or =8 micromol/L, while 59 had plasma tHcy > or = 15.0 micromol/L. The 59 patients were randomized to open therapy with folic acid, 5 mg, pyridoxine, 40 mg, and cyancobalamin, 1 mg once daily for 3 months (n = 29) or to no vitamin treatment (n = 30). Blood samples were obtained from both groups before randomization and 3 months later. A sample was also obtained from the remaining 34 patients.. Plasma Iso-P, serum amyloid A (S-AA), and plasma intercellular adhesion molecule-1 (ICAM-1) concentrations were higher in patients with high plasma tHcy levels than in patients with low to normal tHcy levels. Plasma levels of P-, L-, E-selectins, MDA, C-reactive protein (CRP), and orosomucoid did not differ between the groups. Vitamin therapy reduced plasma tHcy from 17.4 (15.3/20.1) to 9.2 (8.3/10.3) micromol/L (25th and 75th percentiles in parentheses) (p<0.0001). Plasma levels of Iso-P remained unchanged and, of all inflammatory markers, only the S-AA concentrations were slightly reduced by the vitamin treatment, from 5.3 (2.2/7.0) ng/L at baseline to 4.6 (2.1/6.9) ng/L (p<0.05) after 3 months of vitamin supplementation.. Patients with CAD and high plasma tHcy levels had elevated plasma levels of Iso-P. The increase remained unaffected by plasma tHcy-lowering therapy, suggesting that homocysteine per se does not cause increased lipid peroxidation. Levels of plasma ICAM-1 and S-AA were increased in patients with high plasma tHcy, suggesting an association between homocysteinemia and low-grade inflammation.

Topics: Aged; Biomarkers; Coronary Artery Disease; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Pyridoxine; Vitamin B 12; Vitamins

The aim of this study was to assess the relationship between total plasma homocysteine (tHC) and several markers of endothelial function, coagulation, and pro-inflammatory status in renal transplant recipients. Our own previous study demonstrated the efficacy of folic acid (FA) and vitamin B(12) (B(12)) treatment to reduce tHC. Using 70 stable recipients, 56 of whom showed hyperhomocisteinemia (HHC) (tHC > or = 14 micromol/L) and a control group (n = 14, tHC < 14 micromol/L), we treated 29 patients in the HHC group (10 mg FA and 500 mg B(12) daily) and determined their endothelial function, inflammatory activity, and coagulation status. We assessed plasma levels of von Willebrand Factor and fibrinogen as the prothrombotic profile and C-reactive protein and plasma albumin as inflammation markers. We performed Doppler sonography of the brachial artery to assess endothelial function. The mean value of plasma tHC of 19.05 +/- 3.70 micromol/L before treatment decreased to 13.45 +/- 3.25 micromol/L after 3 months of treatment (P < .001). The vWF was significantly correlated with tHC (P < .05) and was higher in the HHC patients (P < .05). The fibrinogen mean level was also significantly higher in HHC patients (P < .05). The C-reactive protein level was significantly higher and the albumin level was lower among patients with HHC. The endothelium-dependent dilation (EDD) correlated with baseline tHC (P < .05). In preliminary data we observed that homocysteine-lowering therapy may provide cardiovascular protection by enhancing endothelial function, limiting oxidative stress, and reducing procoagulation status.

Topics: Adult; Aged; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Brachial Artery; Creatinine; Endothelium, Vascular; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Prospective Studies; Vitamin B 12

The aim of this study was to evaluate the variation of homocysteine (Hcy) levels in patients with rheumatoid arthritis (RA) and to analyze the relationship to inflammatory parameters, cardiovascular risk, and methotrexate (MTX).. This cross-sectional study assessed disease activity and treatment in RA patients. The European League Against Rheumatism (EULAR) 2015 HeartSCORE was performed for cardiovascular (CV) risk estimation and levels of plasma Hcy, serum folate concentrations, vitamin B12, and erythrocyte sedimentation rate (ESR) were measured.. A total of 103 participants with mean age 53 ± 10 years and mean disease duration 10.55 ± 7.34 years were included. Patients were treated with MTX in 69.9% of cases and corticosteroid in 80.5% of cases. Of all patients, 13% had a cardiovascular inheritance, 25% were hypertensive, and 18% had diabetes. The EULAR 2015 HeartSCORE was high and very high (≥5%) in 35% of cases. Mean Hcy level was 12.54 ± 4.2 µmol/L [6.89-32.92] and hyperhomocysteinemia was noted in 20.4% of patients. Analytic study demonstrated that hyperhomocysteinemia was associated with male gender (p = 0.01), MTX use (p = 0.01), smoking (p = 0.008), renal failure (p = 0.04), and high disease activity (p = 0.05), but there was no association with the HeartSCORE (p = 0.23). Hcy level was negatively correlated with folate (p = 0.009) and vitamin B12 level (p = 0.02) and positively with age (p = 0.01), C‑reactive protein (CRP; p = 0.05), and Simplified Disease Activity Index (SDAI; p = 0.03). In multivariate logistic regression analysis, current MTX use, levels of vitamin B12 and creatine, and Clinical Disease Activity Index (CDAI) appeared to be independent factors associated with hyperhomocysteinemia.. MTX use, CDAI, and the levels of vitamin B12 and creatine are independent factors associated with hyperhomocysteinemia.. HINTERGRUND: Ziel der vorliegenden Studie war es, Unterschiede in den Werten für Homocystein (Hcy) bei Patienten mit rheumatoider Arthritis (RA) und den Zusammenhang mit Entzündungsparametern, Herz-Kreislauf-Risiko und Methotrexat (MTX) zu untersuchen.. In dieser Querschnittstudie wurden Krankheitsaktivität und Therapie von RA-Patienten analysiert. Zur Abschätzung des kardiovaskulären Risikos wurde The European League Against Rheumatism (EULAR) 2015 HeartSCORE eingesetzt und die Werte für Plasma-Hcy, Folsäurekonzentration im Serum, Vitamin B12 und Blutsenkungsgeschwindigkeit (BSG) bestimmt.. Es wurden 103 Teilnehmer mit einem mittleren Alter von 53 ± 10 Jahren und einer mittleren Krankheitsdauer von 10,55 ± 7,34 Jahren in die Studie einbezogen. In 69,9% der Fälle wurden die Patienten mit MTX und in 80,5% mit Kortikosteroiden behandelt. Bei 13% der Patienten bestanden familiär kardiovaskuläre Erkrankungen, bei 25% Hypertonie und bei 18% Diabetes mellitus. In 35% der Fälle war der EULAR 2015 HeartSCORE hoch oder sehr hoch (>5%). Im Mittel betrug der Hcy-Wert 12,54 ± 4,2 µmol/l [6,89–32,92], und eine Hyperhomocysteinämie lag bei 20,4% der Patienten vor. Die Auswertung ergab, dass eine Hyperhomocysteinämie mit männlichem Geschlecht (p = 0,01), MTX-Therapie (p = 0,01), Rauchen (p = 0,008), Niereninsuffizienz (p = 0,04) und hoher Krankheitsaktivität (p = 0,05) assoziiert war, aber es gab keinen Zusammenhang mit dem HeartSCORE (p = 0,23). Der Hcy-Wert war negativ mit den Werten für Folsäure (p = 0,009) und Vitamin B12 (p = 0,02) korreliert und positiv mit dem Alter (p = 0,01), C‑reaktivem Protein (CRP; p = 0,05) und dem Simplified Disease Activity Index (SDAI; p = 0,03). In der multivariaten logistischen Regressionsanalyse schienen eine derzeitige MTX-Therapie, Werte für Vitamin B12 und Kreatin sowie der Clinical Disease Activity Index (CDAI) unabhängige Faktoren zu sein, die mit Hyperhomocysteinämie assoziiert waren.. MTX-Therapie, CDAI und die Werte für Vitamin B12 und Kreatin sind unabhängige, mit Hyperhomocysteinämie assoziierte Faktoren.

Topics: Adult; Arthritis, Rheumatoid; Cardiovascular Diseases; Creatine; Cross-Sectional Studies; Folic Acid; Heart Disease Risk Factors; Homocysteine; Humans; Inflammation; Male; Methotrexate; Middle Aged; Risk Factors; Vitamin B 12

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Topics: Anemia, Iron-Deficiency; Biomarkers; Child; Cross-Sectional Studies; Female; Folic Acid; Humans; Inflammation; Iron; Malaria; Male; Micronutrients; Nutritional Status; Uganda; Vitamin A; Vitamin B 12

In low-income countries, undernutrition and infections play a major role in childhood anemia. Stunted children may be at particular risk of anemia. In a cross-sectional study nested in a nutrition trial among 12-59-month-old stunted children in eastern Uganda, we measured hemoglobin (Hb) and markers of iron, cobalamin, folate and vitamin A status. We assessed low micronutrient status, socio-demography, stunting severity, inflammation and malaria as correlates of Hb and anemia using linear and logistic regression analyses, respectively. Of 750 stunted children, the mean ± SD age was 32.0 ± 11.7 months and 55% (n = 412) were male. The mean Hb was 104 ± 15 g/L and 65% had anemia, Hb < 110 g/L. In a multivariable model with age, sex and inflammation, the following were associated with lower Hb: serum ferritin < 12 µg/L (-5.6 g/L, 95% CI: -8.6; -2.6), transferrin receptors > 8.3 mg/L (-6.2 g/L, 95% CI: -8.4; -4.0), plasma folate <20 nmol/L (-4.6 g/L, 95% CI: -8.1;-1.1), cobalamin < 222 pmol/L (-3.0 g/L, 95% CI: -5.4; -0.7) and serum retinol-binding protein < 0.7 µmol/L (-2.0 g/L, 95% CI: -4.1; 0.2). In addition, severe stunting, inflammation and malaria were negative correlates. Anemia is common among stunted children in eastern Uganda; micronutrient deficiencies, inflammation and malaria are associated with low Hb.

Topics: Child, Preschool; Cross-Sectional Studies; Female; Folic Acid; Growth Disorders; Hemoglobins; Humans; Infant; Inflammation; Male; Malnutrition; Micronutrients; Trace Elements; Uganda; Vitamin B 12

Ovarian ischemia is a gynecological emergency case that occurs as a result of ovarian torsion. Oxidative stress and inflammation play central roles in the development of ischemia/reperfusion injuries. We investigated the effects of Vitamin B12, thought to possess antioxidant characteristics on oxidative stress and the toll-like receptor 4 (TLR-4)/nuclear factorkappa B (NF-κB) signaling pathway in the ovaries during ischemia-reperfusion. Forty-eight rats were randomly assigned into six groups and the groups are designed as follows: Control (C), Ischemia (I), Ischemia + Vitamin B12 (I + B12), Ischemia-Reperfusion (I/R), I/R + Vitamin B12 (I/R + B12) and Sham + Vitamin B12. Vitamin B12 was administered at a dose of 400 mcg/kg via the i.p. route once daily for three days before I/R procedure. Tissue interleukin-1β (IL-1β) and interleukin-6 (IL-6) and malondialdehyde (MDA) levels in ovarian tissue increased following I/R, while glutathione (GSH) levels decreased. Moreover, extensive congestion, edema, hemorrhage and defective follicle were observed. Both NF-κB and TLR-4 expression levels also increased in the group exposed to I/R. While GSH levels increased, IL-1β, IL-6, MDA, NF-κB and TLR-4 levels decreased with Vitamin B12 treatment. In addition, ovarian tissue without edema, mild congestion, and normal-appearing follicles were observed following Vitamin B12 administration. The findings showed that I/R in ovarian tissue resulted in significant tissue damage by increasing oxidative stress and inflammation. However, Vitamin B12 application was effective and alternative agent in reducing injury deriving from inflammation and oxidative stress developing in association with I/R in ovarian tissue.

Topics: Animals; Female; Glutathione; Inflammation; Interleukin-6; Ischemia; NF-kappa B; Ovary; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4; Vitamin B 12

Hyperhomocysteinemia (hypHcy) due to impaired folate metabolism is shown to be a risk factor for preterm birth (PTB) and low birth weight (LBW) in mothers. However, the relationship of fetal hypHcy with adverse pregnancy outcomes is under-represented. The present study aims to investigate the association of fetal hypHcy with oxidative stress and placental inflammation that can contribute to an early breakdown of maternal-fetal tolerance in pre-term birth (PTB).. Cord blood and placenta tissue were collected from PTB and term infant group. Levels of homocysteine, folic acid, vitamin B12 and oxidative stress markers (MDA, T-AOC, 8-OHdG) were measured in cord blood serum using ELISA and respective standard assay kits. Relative expression of candidate genes (TNF-α, IL-6, IL1-β, VEGF-A, MMP2 and MMP9) was also checked using RT-PCR and immunoblotting/immunohistochemistry.. PTB infants showed significantly higher levels of homocysteine (P = .02) and lower levels of vitamin B12 (P = .005) as compared to term infants. We also found that PTB infants with hypHcy had lower T-AOC (P = .003) and higher MDA (P = .04) levels as compared to term infants with normal homocysteine levels. The mRNA and protein levels of TNF-α, VEGF-A, MMP2 and MMP9 were significantly higher in hypHcy PTB infants.. Our results show that fetal hypHcy is associated with oxidative stress and an increase in inflammatory markers in the placenta. Thus, in conclusion, our study demonstrates that fetal hypHcy during pregnancy is a potential risk factor that may initiate an early breakdown of uterine quiescence due to activation of inflammatory processes leading to PTB.

Topics: Biomarkers; Female; Fetal Blood; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Infant; Infant, Newborn; Inflammation; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Placenta; Pregnancy; Premature Birth; Term Birth; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Vitamin B 12

Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B. We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B. The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B

Topics: Animals; Fatty Acids; Fibrosis; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Methionine; Mice; Non-alcoholic Fatty Liver Disease; Qa-SNARE Proteins; Vitamin B 12; Vitamins

We will conduct a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P). The search strategies and information sources for the literature will be PubMed, Google Scholar, Web of Science and Science direct. The literature search will include studies published from inception until 30 June 2022. All included studies will be evaluated for quality and risk of bias according to the Cochrane guidelines. To investigate the stability of the results, we will conduct a sensitivity analysis of the outcomes. All data analysis will be performed using Review Manager V.5. 4.. This systematic review and meta-analysis will not require ethical approval from an institution committee as it does not have direct participants. We will obtain all our data from previous studies. The findings will be disseminated through publications in peer-reviewed journals and presented at local and international seminars and conferences.

Topics: Diabetes Mellitus; Diabetic Neuropathies; Humans; Inflammation; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Thioctic Acid; Vitamin B 12; Vitamins

This study was carried out to investigate the potential effects of vitamin B12 and sitagliptin, and their possible synergistic effect with doxorubicin (DOX) on the Ehrlich solid tumor model. B12, sitagliptin, and their combination with DOX were administered to tumor-bearing mice for 21 days. Treatment with B12, sitagliptin, as well as their combinations with DOX caused a significant inhibition of tumor growth and increased the survival time. Malondialdehyde levels and the relative expression of tumor necrosis factor-α and nuclear factor kappa B were significantly decreased, whereas the total antioxidant capacity was significantly increased in all treated groups, except the DOX-treated one, when compared with the positive control group. Moreover, increased apoptosis was also observed by increased cleaved caspase-3 immunostaining and histopathological examination. In conclusion, the antitumor activity of B12 and sitagliptin could be attributed to their ability to induce apoptosis and suppress oxidative stress and inflammation.

Topics: Animals; Carcinoma, Ehrlich Tumor; Female; Inflammation; Mice; NF-kappa B; Oxidative Stress; Sitagliptin Phosphate; Tumor Necrosis Factor-alpha; Vitamin B 12

Osteoporosis is an age-related bone disease, affecting mainly postmenopausal women, characterized by decreased bone mineral density (BMD) and consequent risk of fractures. Homocysteine (Hcy), a sulfur-aminoacid whose serum level is regulated by methylenetrahydrofolate reductase (MTHFR) activity and vitamin B12 and folate as cofactors, is a risk factor for inflammatory diseases. Literature data concerning the link between Hcy and osteoporosis are still debated. The aim of our study was to assess the relationship among Hcy and BMD, inflammation, vitamin status and bone turnover in postmenopausal osteoporosis. In 252 postmenopausal women, BMD was measured by dual-energy X-ray absorptiometry (DXA). In addition to serum Hcy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and bone turnover markers (bone alkaline phosphatase-BAP, osteocalcin-OC, C-terminal telopeptide of type I collagen (CTX), vitamin deficiencies and MTHFR-C677T polymorphism were evaluated. Hcy, inflammation, bone resorption markers and prevalence of C677T polymorphism were higher, whereas vitamin D, B12, folate, and bone formation markers were lower in women with decreased BMD compared to those with normal BMD. Our results suggest a significant association between Hcy, BMD and inflammation in postmenopausal osteoporosis. The regulation of Hcy overproduction and the modulation of the inflammatory substrate could represent additional therapeutic approaches for osteoporosis prevention.

Topics: Bone Density; Female; Folic Acid; Folic Acid Deficiency; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Osteitis; Osteoporosis, Postmenopausal; Oxidoreductases; Polymorphism, Genetic; Postmenopause; Vitamin B 12; Vitamin B 12 Deficiency

Low-grade chronic inflammation is a condition underlying many serious diseases but there is no good single biomarker which can estimate and monitor the severity of the inflammation. C-reactive protein (CRP) is the best validated and most extensively used marker. The aims of the study were to investigate the extent to which CRP levels associate with levels of micronutrients.. We retrieved the levels of S-hsCRP and nutritional variables fB-β-carotenes, fS-Q10 (Ubiquinon), fS-Fe, E-Cu, fS-A vitamin, B-Se, B-Zn, and fB-B12 vitamin from the database of clinical laboratory Mila Oy from the years 1988-2018, a total of nearly 18 800 samples from outpatient clinics, Helsinki and Oulu, Finland. Sample sizes for nutritional variables measured concurrently with S-hsCRP varied between 4356 and 8621. S-hsCRP levels were categorized into five ordered categories. The levels of each micronutrient in those categories were compared using analysis of variance (ANOVA). Males and females were analyzed separately.. It was observed that an increase of S-hsCRP associated with the decrease of fS-Fe (p < 0.001 for both genders); fS-A vitamin (p < 0.001 for both genders), and fS-β-carotenes (p < 0.001 for both genders); these are considered negative acute phase reactants. For both genders there was no significant association between the levels of fS-B12 vitamin (p = 0.14 for males; p = 0.03 for females), fS-Q10 (p < 0.001 for males; p = 0.06 for females) and fB-Se (p < 0.001 for males; p = 0.01 for females) and the categorized S-hsCRP. In contrast, fB-Zn (p < 0.001 for both genders) behaved like a positive acute phase reactant whereas copper measured from washed blood cells (E-Cu) did not display any significant associations with S-hsCRP (p = 0.001 for males; p = 0.05 for females).. A linear association was observed for some micronutrients - the higher the degree of low-grade inflammation (S-hsCRP), the more disturbed were the levels of some micronutrients. For clinicians, this finding means that inflammation needs to be acknowledged when assessing micronutrient deficiency. Substitution therapy should be implemented only after the inflammation has been rectified.

Topics: Biomarkers; C-Reactive Protein; Cross-Sectional Studies; Female; Finland; Humans; Inflammation; Male; Micronutrients; Sex Factors; Vitamin B 12; Vitamins

Previous studies approved the important roles of CD68, as scavenger receptors, in Alzheimer's disease (AD). The aim of this study was to evaluate the effect of treatment with anti-psychotic drugs and vitamin B12 on the expression levels of CD68 in monocytes of psychotic AD patients.. Expression of CD68 on the monocytes was evaluated in the following groups: 1. age and sex matched healthy controls (Group 1), 2. non-psychotic AD patients (Group 2), 3. psychotic AD patients (Group 3), 4. psychotic AD patients treated with Risperidone (Group 4), 5. psychotic AD patients treated with Risperidone plus vitamin B12 (Group 5), 6. psychotic AD patients treated with Quetiapine (Group 6), psychotic AD patients treated with Quetiapine plus vitamin B12 (Group 7). The expression of CD68 has been performed using flow cytometry technique.. The results showed that CD68 levels were significantly increased in AD patients in comparison to healthy controls and in psychotic AD patients in comparison to non-psychotic AD patients. Treatment with anti-psychotic drugs decreased the expression of CD68. Expression of CD68 has a positive correlation with pain, dementia and mental disorders symptoms in psychotic AD patients.. CD68 may play key roles in the pathogenesis of AD and its complications may be via induction of inflammation. Therefore, it may be concluded that CD68 may be considered as a risk factor for development of AD and also psychotic symptoms in the patients.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antipsychotic Agents; Case-Control Studies; Drug Therapy, Combination; Female; Flow Cytometry; Humans; Inflammation; Male; Monocytes; Psychotic Disorders; Quetiapine Fumarate; Risk Factors; Risperidone; Vitamin B 12

Diabetes is considered an oxidative stress and a chronic inflammatory disease. The purpose of this study was to investigate the correlations between vitamin B-12 status and oxidative stress and inflammation in diabetic vegetarians and omnivores. We enrolled 154 patients with type 2 diabetes (54 vegetarians and 100 omnivores). Levels of fasting glucose, glycohemoglobin (HbA1c), lipid profiles, oxidative stress, antioxidant enzymes activity, and inflammatory makers were measured. Diabetic vegetarians with higher levels of vitamin B-12 (>250 pmol/L) had significantly lower levels of fasting glucose, HbA1c and higher antioxidant enzyme activity (catalase) than those with lower levels of vitamin B-12 (≤ 250 pmol/L). A significant association was found between vitamin B-12 status and fasting glucose (r = -0.17, p = 0.03), HbA1c (r = -0.33, p = 0.02), oxidative stress (oxidized low density lipoprotein-cholesterol, r = -0.19, p = 0.03), and antioxidant enzyme activity (catalase, r = 0.28, p = 0.01) in the diabetic vegetarians; vitamin B-12 status was significantly correlated with inflammatory markers (interleukin-6, r = -0.33, p < 0.01) in diabetic omnivores. As a result, we suggest that it is necessary to monitor the levels of vitamin B-12 in patients with diabetes, particularly those adhering to a vegetarian diet.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet, Vegetarian; Feeding Behavior; Female; Glycated Hemoglobin; Humans; Inflammation; Inflammation Mediators; Lipids; Male; Meat; Middle Aged; Nutritional Status; Oxidative Stress; Vegetarians; Vitamin B 12; Vitamin B 12 Deficiency; Young Adult

This study aimed to examine the relationship between changes in systemic vitamin B12 concentrations with pro-inflammatory cytokines, anthropometric factors and biochemical markers of cardiometabolic risk in a Saudi population.. A total of 364 subjects (224 children, age: 12.99 ± 2.73 (mean ± SD) years; BMI: 20.07 ± 4.92 kg/m² and 140 adults, age: 41.87 ± 8.82 years; BMI: 31.65 ± 5.77 kg/m²) were studied. Fasting blood, anthropometric and biochemical data were collected. Serum cytokines were quantified using multiplex assay kits and B12 concentrations were measured using immunoassay analyzer.. Vitamin B12 was negatively associated with TNF-α (r = -0.14, p < 0.05), insulin (r = -0.230, p < 0.01) and HOMA-IR (r = -0.252, p < 0.01) in all subjects. In children, vitamin B12 was negatively associated with serum resistin (r = -0.160, p < 0.01), insulin (r = -0.248, p < 0.01), HOMA-IR (r = -0.261, p < 0.01). In adults, vitamin B12 was negatively associated with TNF-α (r = -0.242, p < 0.01) while positively associated with resistin (r = 0.248, p < 0.01). Serum resistin was the most significant predictor for circulating vitamin B12 in all subjects (r² = -0.17, p < 0.05) and in children (r² = -0.167, p < 0.01) while HDL-cholesterol was the predictor of B12 in adults (r² = -0.78, p < 0.05).. Serum vitamin B12 concentrations were associated with pro-inflammatory cytokines and biochemical markers of cardiometabolic risks in adults. Maintaining adequate vitamin B12 concentrations may lower inflammation-induced cardiometabolic risk in the Saudi adult population.

Topics: Adiponectin; Adolescent; Adult; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Child; Cross-Sectional Studies; Female; Humans; Inflammation; Insulin; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Resistin; Risk Factors; Saudi Arabia; Tumor Necrosis Factor-alpha; Vitamin B 12; Waist Circumference

To investigate the vitamin B status, with particular focus on vitamin B6, in adults with and without incipient nephropathy secondary to type 2 diabetes mellitus.. Plasma and/or urine concentrations of vitamins B₆, B₁, B₁₂, related vitamers and biomarkers (including total homocysteine, methylmalonic acid) were measured in 120 adults with type 2 diabetes (including 46 patients with microalbuminuria) and 52 non-diabetic control subjects.. Plasma concentrations of pyridoxal 5'-phosphate (PLP) were significantly lower in patients with type 2 diabetes than in control subjects (median: 22.7 nmol/L, diabetes with microalbuminuria; 26.8 nmol/L, diabetes without microalbuminuria; 39.5 nmol/L, non-diabetic control; p<0.0001). The prevalence of low PLP (<30 nmol/L) was 63%, 58%, and 25% in the diabetes groups with and without microalbuminuria and the control group, respectively. Plasma levels of pyridoxine and pyridoxal were also lower (p<0.0001), but levels of pyridoxamine, pyridoxamine 5'-phosphate, and pyridoxic acid were higher in both groups with diabetes compared to the control group (p<0.001). Thiamine deficiency was highly prevalent in all groups, whereas low vitamin B₁₂ and elevated methylmalonic acid were rare. Increased levels of C-reactive protein and soluble vascular cell adhesion molecule-1 were observed in the groups with diabetes (p<0.05, versus healthy control).. Deficiency of vitamin B₆ (PLP, pyridoxine, pyridoxal) and vitamin B₁ (thiamine) was prevalent in type 2 diabetes. Incipient nephropathy was associated with more pronounced alterations in vitamin B₆ metabolism and stronger indications of endothelial dysfunction and inflammation.

Topics: Adult; Aged; Aged, 80 and over; Albuminuria; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Humans; Inflammation; Male; Middle Aged; Pyridoxic Acid; Thiamine; Vitamin B 12; Vitamin B 12 Deficiency; Vitamin B 6; Vitamin B 6 Deficiency; Young Adult

To evaluate serum concentrations of biochemical markers and survival time in dogs with protein-losing enteropathy (PLE).. Prospective study.. 29 dogs with PLE and 18 dogs with food-responsive diarrhea (FRD).. Data regarding serum concentrations of various biochemical markers at the initial evaluation were available for 18 of the 29 dogs with PLE and compared with findings for dogs with FRD. Correlations between biochemical marker concentrations and survival time (interval between time of initial evaluation and death or euthanasia) for dogs with PLE were evaluated.. Serum C-reactive protein concentration was high in 13 of 18 dogs with PLE and in 2 of 18 dogs with FRD. Serum concentration of canine pancreatic lipase immunoreactivity was high in 3 dogs with PLE but within the reference interval in all dogs with FRD. Serum α1-proteinase inhibitor concentration was less than the lower reference limit in 9 dogs with PLE and 1 dog with FRD. Compared with findings in dogs with FRD, values of those 3 variables in dogs with PLE were significantly different. Serum calprotectin (measured by radioimmunoassay and ELISA) and S100A12 concentrations were high but did not differ significantly between groups. Seventeen of the 29 dogs with PLE were euthanized owing to this disease; median survival time was 67 days (range, 2 to 2,551 days).. Serum C-reactive protein, canine pancreatic lipase immunoreactivity, and α1-proteinase inhibitor concentrations differed significantly between dogs with PLE and FRD. Most initial biomarker concentrations were not predictive of survival time in dogs with PLE.

Topics: Animals; Biomarkers; Blood Proteins; Calcium; Dog Diseases; Dogs; Female; Folic Acid; Food Hypersensitivity; Inflammation; Longevity; Male; Protein-Losing Enteropathies; Serum Albumin; Trypsin; Vitamin B 12

To evaluate the relationship between folate, cobalamin (Cbl), and homocysteine (Hcy), and markers of inflammation and oxidative stress within the periphery and central nervous system (CNS) of a healthy human cohort.. Thirty-five matched cerebrospinal fluid (CSF) and plasma samples were collected from consenting participants who required a spinal tap for the administration of anaesthetic. Plasma concentrations of Hcy and both plasma and CSF levels of folate, Cbl, nicotinamide adenine dinucleotide (NAD(H)) and markers of inflammation (interleukin-6, IL-6), and oxidative stress (F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and total antioxidant capacity (TAC)) were quantified.. In the peripheral circulation, positive associations were observed between plasma folate and Cbl, and plasma TAC (P ≤ 0.01; P ≤ 0.01) and plasma NAD(H) (P ≤ 0.05; P ≤ 0.05) levels, respectively. Plasma folate was inversely associated with plasma Hcy concentrations (P ≤ 0.05); however, no statistically significant relationships were observed between plasma Hcy and plasma markers of inflammation, oxidative stress, or [NAD(H)]. Within the CNS plasma Hcy correlated positively with CSF IL-6 (P ≤ 0.01) and negatively with CSF NAD(H) (P ≤ 0.05) concentrations. An inverse association was observed between CSF folate and CSF levels of IL-6 (P ≤ 0.05). Unexpectedly, a positive association between CSF Cbl and CSF 8-OHdG levels was also found (P ≤ 0.01).. These results indicate that folate and Cbl concentrations may influence the levels of oxidative damage, inflammation, and NAD(H), both systemically and within the CNS.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Antioxidants; Biomarkers; Central Nervous System; Deoxyguanosine; F2-Isoprostanes; Female; Folic Acid; Homocysteine; Humans; Inflammation; Interleukin-6; Linear Models; Male; Middle Aged; NAD; Oxidative Stress; Vitamin B 12

A high frequency of hypogonadism has been reported in male patients with advanced cancer. The current study was performed to evaluate the association between low testosterone levels, symptom burden, and survival in male patients with cancer.. Of 131 consecutive male patients with cancer, 119 (91%) had an endocrine evaluation of total (TT), free (FT), and bioavailable testosterone (BT); high-sensitivity C-reactive protein (CRP); vitamin B12; thyroid-stimulating hormone; 25-hydroxy vitamin D; and cortisol levels when presenting with symptoms of fatigue and/or anorexia-cachexia. Symptoms were evaluated by the Edmonton Symptom Assessment Scale. The authors examined the correlation using the Spearman test and survival with the log-rank test and Cox regression analysis.. The median age of the patients was 64 years; the majority of patients were white (85 patients; 71%). The median TT level was 209 ng/dL (normal: ≥ 200 ng/dL), the median FT was 4.4 ng/dL (normal: ≥ 9 ng/dL), and the median BT was 22.0 ng/dL (normal: ≥ 61 ng/dL). Low TT, FT, and BT values were all associated with worse fatigue (P ≤ .04), poor Eastern Cooperative Oncology Group performance status (P ≤ .05), weight loss (P ≤ .01), and opioid use (P ≤ .005). Low TT and FT were associated with increased anxiety (P ≤ .04), a decreased feeling of well-being (P ≤ .04), and increased dyspnea (P ≤ .05), whereas low BT was only found to be associated with anorexia (P = .05). Decreased TT, FT, and BT values were all found to be significantly associated with elevated CRP and low albumin and hemoglobin. On multivariate analysis, decreased survival was associated with low TT (hazards ratio [HR], 1.66; P = .034), declining Eastern Cooperative Oncology Group performance status (HR, 1.55; P = .004), high CRP (HR, 3.28; P < .001), and decreased albumin (HR, 2.52; P < .001).. In male patients with cancer, low testosterone levels were associated with systemic inflammation, weight loss, increased symptom burden, and decreased survival. A high frequency of hypogonadism has been reported in male patients with advanced cancer. In the current study, an increased symptom burden, systemic inflammation, weight loss, opioid use, and poor survival were found to be associated with decreased testosterone levels in male patients with cancer. Cancer 2014;120:1586-1593. © 2014 American Cancer Society.

Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Androgens; Anorexia; Biomarkers; C-Reactive Protein; Cachexia; Cost of Illness; Hemoglobins; Humans; Hydrocortisone; Hypogonadism; Inflammation; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms; Quality of Life; Retrospective Studies; Serum Albumin; Testosterone; Texas; Thyrotropin; Vitamin B 12; Vitamin D; Weight Loss

Folate-mediated one-carbon metabolism is essential for DNA synthesis, repair, and methylation. Perturbations in one-carbon metabolism have been implicated in increased risk of some cancers and may also affect inflammatory processes. We investigated these interrelated pathways to understand their relation. The objective was to explore associations between inflammation and biomarkers of nutritional status and one-carbon metabolism. In a cross-sectional study in 1976 women selected from the Women's Health Initiative Observational Study, plasma vitamin B-6 [pyridoxal-5'-phosphate (PLP)], plasma vitamin B-12, plasma folate, and RBC folate were measured as nutritional biomarkers; serum C-reactive protein (CRP) and serum amyloid A (SAA) were measured as biomarkers of inflammation; and homocysteine and cysteine were measured as integrated biomarkers of one-carbon metabolism. Student's t, chi-square, and Spearman rank correlations, along with multiple linear regressions, were used to explore relations between biomarkers; additionally, we tested stratification by folic acid fortification period and multivitamin use. With the use of univariate analysis, plasma PLP was the only nutritional biomarker that was modestly significantly correlated with serum CRP and SAA (ρ = -0.22 and -0.12, respectively; P < 0.0001). Homocysteine (μmol/L) showed significant inverse correlations with all nutritional biomarkers (ranging from ρ = -0.30 to ρ = -0.46; all P < 0.0001). With the use of multiple linear regression, plasma PLP, RBC folate, homocysteine, and cysteine were identified as independent predictors of CRP; and PLP, vitamin B-12, RBC folate, and homocysteine were identified as predictors of SAA. When stratified by folic acid fortification period, nutrition-homocysteine correlations were generally weaker in the postfortification period, whereas associations between plasma PLP and serum CRP increased. Biomarkers of inflammation are associated with PLP, RBC folate, and homocysteine in women. The connection between the pathways needs to be further investigated and causality established. The trial is registered at clinicaltrials.gov as NCT00000611.

Topics: Aged; Biomarkers; C-Reactive Protein; Carbon; Chronic Disease; Cross-Sectional Studies; Cysteine; Erythrocytes; Female; Folic Acid; Homocysteine; Humans; Inflammation; Linear Models; Middle Aged; Nutritional Status; Risk Factors; Serum Amyloid A Protein; Vitamin B 12; Vitamin B 6

To investigate diet and nutrition-related factors associated with bone loss in a group of postmenopausal (PM) women. Nutritional intake, inflammatory markers and body composition (weight, body mass index, fat/lean mass) were analysed for associations with bone mineral density (BMD).. A cross sectional study examining correlations between BMD (Duel-energy X ray absorptiometry; (DXA) and dietary intake (3-day diaries), body composition and plasma bone and inflammatory markers: C-terminal telopeptide of type I collagen (CTX) and procollagen type I N propeptide (P1NP), C- reactive protein (CRP), interleukin 6 and 10 (IL-6, IL-10), tumour necrosis factor (TNF) and osteoprotegerin (OPG).. Community dwelling women from the Auckland, Hawke's Bay and Manawatu regions in New Zealand.. 142 healthy, PM women aged 50-70 years.. OPG (per kilogram fat mass) was increased in women with osteoporosis (p<0.001) compared to groups classified with normal BMD and osteopenia. Protein, vitamin B12, zinc, potassium and dairy intake were all positively correlated with higher BMD while dairy and potassium intakes also inversely correlated with CTX. Body composition (weight, BMI and fat/lean mass) had strong positive associations with BMD. Multiple regression analysis showed body weight, potassium and dairy intake were predictors of increased BMD in PM women and explained 39% (r2=0.39, p< 0.003) of variance.. BMD was negatively correlated with OPG and positively with weight, dairy and potassium intake. This study highlights the importance of maintaining adequate body weight and emphasising dairy and potassium predominantly sourced from fruit/vegetables to reduce bone loss at midlife.

Topics: Absorptiometry, Photon; Aged; Body Composition; Body Mass Index; Body Weight; Bone Density; Bone Diseases, Metabolic; C-Reactive Protein; Collagen Type I; Cross-Sectional Studies; Cytokines; Dairy Products; Diet; Dietary Proteins; Female; Health; Humans; Inflammation; Interleukin-10; Interleukin-6; Middle Aged; New Zealand; Osteoporosis, Postmenopausal; Osteoprotegerin; Peptide Fragments; Peptides; Postmenopause; Potassium; Procollagen; Tumor Necrosis Factor-alpha; Vitamin B 12; Zinc

Pregnant adolescents (aged ≤ 18 y, n = 253) were followed from ≥ 12 wk of gestation to delivery to assess longitudinal changes in anemia and iron status and to explore associations between iron status indicators, hepcidin, and inflammatory markers. Hemoglobin, soluble transferrin receptor (sTfR), ferritin, serum iron, erythropoietin (EPO), hepcidin, C-reactive protein, interleukin-6 (IL-6), folate, and vitamin B-12 were measured, and total body iron (TBI) (milligrams per kilogram) was calculated using sTfR and ferritin values. Anemia prevalence increased from trimesters 1 and 2 (3-5%, <28 wk) to trimester 3 (25%, 33.2 ± 3.7 wk, P < 0.0001). The prevalence of iron deficiency (sTfR > 8.5 mg/L) doubled from pregnancy to delivery (7% to 14%, P = 0.04). Ferritin and hepcidin concentrations at delivery may have been elevated as a consequence of inflammation because IL-6 concentrations at delivery were 1.6-fold higher than those obtained at 26.1 ± 3.3 wk of gestation (P < 0.0001), and a positive association was found between IL-6 and both hepcidin and ferritin at delivery (P < 0.01). EPO was consistently correlated with hemoglobin (r = -0.36 and -0.43, P < 0.001), ferritin (r = -0.37 and -0.32, P < 0.0001), sTfR (r = 0.35 and 0.25, P < 0.001), TBI (r = -0.44 and -0.37, P < 0.0001), and serum iron (r = -0.22 and -0.16, P < 0.05) at mid-gestation and at delivery, respectively. EPO alone explained the largest proportion of variance in hemoglobin at 26.0 ± 3.3 wk of gestation (R(2) = 0.13, P = 0.0001, n = 113) and at delivery (R(2) = 0.19, P < 0.0001, n = 192). Pregnant adolescents are at high risk of anemia. EPO is a sensitive indicator of iron status across gestation, is not affected by systemic inflammation, and may better predict risk of anemia at term. The trial was registered at clinicaltrials.gov as NCT01019902.

Topics: Adolescent; Anemia, Iron-Deficiency; C-Reactive Protein; Cross-Sectional Studies; Delivery, Obstetric; Dietary Supplements; Erythropoietin; Female; Ferritins; Folic Acid; Hemoglobins; Hepcidins; Humans; Inflammation; Interleukin-6; Iron, Dietary; Longitudinal Studies; Multivariate Analysis; Nutrition Assessment; Nutritional Status; Pregnancy; Prevalence; Receptors, Transferrin; Regression Analysis; Surveys and Questionnaires; Vitamin B 12

Vascular dementia (VaD) is the second leading cause of dementia behind Alzheimer's disease (AD) and is a frequent comorbidity with AD, estimated to occur in as many as 40% of AD patients. The causes of VaD are varied and include chronic cerebral hypoperfusion, microhemorrhages, hemorrhagic infarcts, or ischemic infarcts. We have developed a model of VaD by inducing hyperhomocysteinemia (HHcy) in wild-type mice. By placing wild-type mice on a diet deficient in folate, B6, and B12 and supplemented with excess methionine, we induced a moderate HHcy (plasma level homocysteine 82.93 ± 3.561 μmol). After 11 weeks on the diet, the hyperhomocysteinemic mice showed a spatial memory deficit as assessed by the 2-day radial-arm water maze. Also, magnetic resonance imaging and subsequent histology revealed significant microhemorrhage occurrence. We found neuroinflammation induced in the hyperhomocysteinemic mice as determined by elevated interleukin (IL)-1β, tumor necrosis factor (TNF)α, and IL-6 in brain tissue. Finally, we found increased expression and increased activity of the matrix metalloproteinase 2 (MMP2) and MMP9 systems that are heavily implicated in the pathogenesis of cerebral hemorrhage. Overall, we have developed a dietary model of VaD that will be valuable for studying the pathophysiology of VaD and also for studying the comorbidity of VaD with other dementias and other neurodegenerative disorders.

Topics: Animals; Brain; Cerebral Hemorrhage; Dementia, Vascular; Diet; Disease Models, Animal; Folic Acid; Humans; Hyperhomocysteinemia; Inflammation; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Memory Disorders; Methionine; Mice; Mice, Inbred C57BL; Vitamin B 12; Vitamin B 6

In this study, the anti-nociceptive and anti-inflammatory effects of cyanocobalamin (Vit B12) against acute and chronic pain and inflammation were evaluated in mice. Vit B12 (0.87, 1 and 1.77 mg/kg) were injected intraperitoneally. The anti-nociceptive effects against acute pain were examined using hot-plate and writhing tests. The chronic pain was examined 14 days after sciatic nerve ligation using the hot-plate test. Morphine (10 mg/kg) was used as a positive control. Anti-inflammatory effects of Vit B12 against acute and chronic inflammation were assessed using xylene-induced edema in ears and granuloma caused by compressed cotton implantation, respectively. In these tests, sodium diclofenac (15 mg/kg) was used as a positive control. Vit B12 showed a dose related effect in acute anti-nociceptive test and increased the anti-nociceptive effect of morphine in chronic treatment. Vit B12 demonstrated an anti-nociceptive effect in chronic studies as single or continues daily treatment and increased significantly the anti-nociceptive effect of morphine. All doses of Vit B12 significantly decreased xylene-induced ear edema. Maximum anti-inflammatory effect (37.5%) was obtained at dose of 1 mg/kg. In chronic inflammation, Vit B12 significantly decreased granuloma formation in mice. In conclusion our work presents some experimental evidence supporting the administration of cyanocobalamin in controlling acute and chronic neuropathic pain. Cyanocobalamin may have anti-inflammatory effect. It may reduce tolerance to anti-nociceptive effect of morphine as well.

Topics: Acute Pain; Analgesics; Animals; Anti-Inflammatory Agents; Chronic Pain; Inflammation; Male; Mice; Mice, Inbred BALB C; Morphine; Vitamin B 12

To investigate the association of plasma total homocysteine (tHcy) with arterial stiffness, measured as brachial-ankle pulse wave velocity (baPWV), LDL atherogenicity, and inflammation profile in healthy men.. In this cross-sectional study, 612 healthy men aged 31-79 years were classified into quartiles according to plasma tHcy concentration. In the total study population, tHcy concentration showed positive correlation with age (r=0.083, P=0.040), interleukin (IL)-1β (r=0.249, P<0.001), TNF-α (r=0.150, P<0.001), IL-6 (r=0.154, P<0.001), oxidized LDL (oxLDL) (r=0.161, P=<0.001), and baPWV (r=0.087, P=0.032); and negative correlation with folate (r=-0.353, P<0.001) and vitamin B(12) (r=-0.269, P<0.001). In subgroup analysis based on plasma tHcy level, tHcy was associated with baPWV in men with high levels of tHcy (≥ 13.1μmol/L, n=153; r=0.258, P=0.001), but not in those with low-tHcy (<13.1 μmol/L, n=459; r=-0.033, P=0.478). The association between tHcy and baPWV in the high-tHcy group remained significant after adjustment for age, BMI, smoking, drinking, folate, and vitamin B₁₂. In the high-tHcy group, tHcy level was also positively correlated with IL-1β, TNF-α, oxLDL, and blood pressure; and negatively correlated with LDL particle size. In addition, baPWV showed negative correlation with LDL particle size and positive correlation with oxLDL in the high-tHcy group.. This study shows an association between high levels of plasma tHcy and more advanced arterial stiffness, smaller LDL particle size, and higher levels of oxLDL and cytokines in men with hyperhomocysteinemia. Enhanced arterial stiffness in hyperhomocysteinemia might be attributed, in part, to Hcy-related LDL atherogenicity.

Topics: Adult; Aged; Ankle; Ankle Brachial Index; Asian People; Atherosclerosis; Blood Flow Velocity; Blood Glucose; Blood Pressure; Brachial Artery; C-Reactive Protein; Cross-Sectional Studies; Folic Acid; Homocysteine; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Lipoproteins, LDL; Male; Middle Aged; Tumor Necrosis Factor-alpha; Vascular Resistance; Vitamin B 12

The aim of this study was to prospectively determine the etiology of anemia in a cohort of community-dwelling older outpatients with a comprehensive hematologic evaluation. Participants were men and women age 65 and older with anemia as defined by World Health Organization criteria recruited from outpatient hematology clinics at Stanford Hospital and Clinics (SHC) and Veterans Affairs Palo Alto Health Care System (VAPAHCS). Each participant underwent a history and physical examination, followed by a comprehensive hematologic evaluation, which in all participants included complete blood count, red cell indices, review of the blood smear, and assessment of vitamin B12, folate, iron status and renal function. Additional evaluation was obtained by clinical providers as per their discretion. 190 participants enrolled and completed the evaluation. Twelve percent of participants had iron deficiency anemia. Of those with iron deficiency in whom there was follow-up information, half normalized their hemoglobin in response to iron repletion, and half did not. Thirty-five percent of participants had unexplained anemia. Those with unexplained anemia had mildly increased inflammatory markers compared to non-anemic controls, and, at the lower hemoglobin ranges had relatively low erythropoietin levels. Sixteen percent of participants were categorized as being "suspicious for myelodysplastic syndrome." Thus, even with comprehensive hematologic evaluation, unexplained anemia is common in older anemic outpatients. Iron deficiency anemia is also common and can be difficult to diagnose, and frequently the anemia is not fully corrected with iron repletion.

Topics: Aged; Anemia, Iron-Deficiency; Blood Cell Count; Erythrocyte Indices; Female; Folic Acid; Hemoglobins; Humans; Inflammation; Iron, Dietary; Kidney Function Tests; Male; Myelodysplastic Syndromes; Outpatients; Prospective Studies; Vitamin B 12

Thirty-three inpatients (22 females, 11 males, aged 79.4 ± 9.5 years) were investigated in this prospective cohort study to study the prevalence of polyneuropathy (PNP) and dementia in geriatric inpatients. Clinical and electrodiagnostic investigations, routine laboratory, including thyroid parameters, folic acid, vitamin B(12), homocysteine, neopterin, fibrinogen and glycosylated hemoglobin were measured in serum, the mini-mental state examination and computed tomographic scanning were performed in each patient. PNP was found clinically and electrodiagnostically in 96% of patients. Age was the most precipitating factor for PNP, and was significantly correlated to electrodiagnostic changes in the nerves investigated in both, upper and lower extremities, while clinical symptoms were confined only to the feet. Correlation was seen between homocysteine and the amplitude of the sural nerve (surAmpl) (rs = -0.406, p = 0.029) as well as the sural nerve conduction velocity (surNCV) (rs = -0.389, p = 0.037), and between neopterin and the grade of denervation (rs = 0.445, p = 0.014) in our patients. Neopterin and fibrinogen did not correlate significantly, but there was a trend to higher fibrinogen concentrations in patients with higher neopterin levels (rs = 0.344, p = 0.062). A trend of a correlation was seen between higher homocysteine concentrations and the number of changes in electrodiagnostic measurements (rs = 0.354, p = 0.055). Twenty-one of the 33 patients (64%) were demented, 9 (27%) presented clinically as mild cognitive impairment, 3 (9%) were not demented. Vascular risk factors were found in 83%: hypertension in 58%, hypercholesterinemia in 39%, cardiac disease in 36%, diabetes mellitus (DM) in 21%, peripheral arterial disease (PAD) in 9%. A significant correlation was found between homocysteine and folic acid concentrations (rs = -0.401, p = 0.028). Falls were reported in 48% of cases, indicating PNP as a risk factor in this group of patients. In conclusion, PNP was found very common with a high coincidence with dementia and a female preponderance, suggesting an influence on daily life (falls) in our subjects studied. PNP correlated significantly with markers for vascular disease as well as immune activation (homocysteine and neopterin) similar to earlier findings in patients with neurodegenerative disorders, suggesting common therapeutic options in patients with PNP and dementia.

Topics: Aged; Aged, 80 and over; Aging; Cognition Disorders; Cohort Studies; Dementia; Female; Folic Acid; Geriatrics; Homocysteine; Humans; Inflammation; Male; Mental Status Schedule; Neopterin; Neural Conduction; Polyneuropathies; Sural Nerve; Vascular Diseases; Vitamin B 12

To evaluate the determinants of total plasma homocysteine levels and their relations with nutritional parameters, inflammatory status, and traditional risk factors for cardiovascular disease in renal failure patients on dialysis treatment.. The study was conducted on 70 clinically stable patients, 50 of them on hemodialysis (70% men; 55.3 ± 14.5 years) and 20 on peritoneal dialysis (50% men; 62 ± 13.7 years). Patients were analyzed in terms of biochemical parameters (serum lipids, creatinine, homocysteine [Hcy], creatine-kinase [Ck], folic acid, and vitamin B(12)), anthropometric data, markers of inflammatory status (tumor necrosis factor-alpha, C-reactive protein, interleukin-6), and adapted subjective global assessment.. The total prevalence of hyperhomocysteinemia (>15 μmol/L) was 85.7%. Plasma folic acid and plasma vitamin B(12) were within the normal range. Multiple regression analysis (r(2) = 0.20) revealed that the determinants of total Hcy were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Hcy was positively correlated with albumin and creatinine and negatively correlated with total cholesterol, high density lipoprotein cholesterol, folic acid, and vitamin B(12).. The determinants of total Hcy in the study sample were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Evidently, the small sample size might have had an effect on the statistical analyses and further studies are needed. However, Hcy in patients on dialysis treatment may not have the same effect as observed in the general population. In this respect, the association between malnutrition and inflammation may be a confounding factor in the determination of the true relationship between Hcy, nutritional status, and cardiovascular risk factors in this group.

Topics: Adult; Aged; Biomarkers; Brazil; C-Reactive Protein; Creatine Kinase; Creatinine; Female; Folic Acid; Follow-Up Studies; Homocysteine; Humans; Hyperhomocysteinemia; Inflammation; Interleukin-6; Kidney Failure, Chronic; Linear Models; Lipids; Male; Malnutrition; Middle Aged; Peritoneal Dialysis; Prevalence; Renal Dialysis; Risk Factors; Tumor Necrosis Factor-alpha; Vitamin B 12

Inflammation is involved in development and progression of atherosclerosis. Interleukin-2 (IL-2) and interleukin-6 (IL-6) have been correlated with various cardiovascular diseases. Hyperhomocysteinemia is an important risk factor for atherosclerosis and thrombotic disease. Recent studies have demonstrated that homocysteine (Hcy) enhances productions of several pro-inflammatory cytokines. In the light of these findings, we decided to determine if any relationship exists between IL-2 and IL-6, the pro-inflammatory cytokines, and total homocysteine (tHcy) in acute coronary syndrome (ACS). A total of 102 patients with ACS and 90 healthy subjects were included in the study. The levels of tHcy, IL-2 and IL-6 were higher and folic acid was lower in patients as compared with those of controls. Furthermore, data of the area under ROC plot for IL-2 demonstrated that IL-2 had higher sensitivity. These data suggest that enhanced inflammation may be associated with tHcy-related cardiovascular disease.

Topics: Cardiovascular Diseases; Case-Control Studies; Demography; Folic Acid; Homocysteine; Humans; Inflammation; Interleukin-2; Interleukin-6; Middle Aged; ROC Curve; Vitamin B 12

Anemia in older persons is commonly overlooked despite mounting evidence that low hemoglobin levels are a significant marker of physiologic decline. Using the World Health Organization definition of anemia (hemoglobin level less than 13 g per dL [130 g per L] in men and less than 12 g per dL [120 g per L] in women), more than 10 percent of persons older than 65 years are anemic. The prevalence increases with age, approaching 50 percent in chronically ill patients living in nursing homes. There is increasing evidence that even mild anemia is associated with increased morbidity and mortality. Anemia warrants evaluation in all older persons, except those at the end of life or who decline interventions. About one third of persons have anemia secondary to a nutritional deficiency, one third have anemia caused by chronic inflammation or chronic kidney disease, and one third have unexplained anemia. Nutritional anemia is effectively treated with vitamin or iron replacement. Iron deficiency anemia often is caused by gastrointestinal bleeding and requires further investigation in most patients. Anemia of chronic inflammation or chronic kidney disease may respond to treatment of the underlying disease and selective use of erythropoiesis-stimulating agents. The treatment of unexplained anemia is difficult, and there is little evidence that treatment decreases morbidity and mortality, or improves quality of life. Occasionally, anemia may be caused by less common but potentially treatable conditions, such as autoimmune hemolytic anemia, malignancy, or myelodysplastic syndrome.

Topics: Aged; Algorithms; Anemia; Deficiency Diseases; Erythrocyte Indices; Female; Ferritins; Folic Acid; Hematinics; Homocysteine; Humans; Inflammation; Iron Compounds; Male; Medical History Taking; Methylmalonic Acid; Physical Examination; Renal Insufficiency; Reticulocyte Count; Vitamin B 12

It is unknown whether biochemical vitamin deficiencies in critical illness are associated with severity of illness, organ dysfunction, inflammation or mortality. This nested cohort study recruited 98 patients admitted as emergencies to the intensive care unit, who had a stay of greater than 48 hours. Patient data were prospectively collected. Within the first 48 hours of admission, concentrations of C-reactive protein, vitamins A, E, B1, B12 and folate were measured on arterial blood. These measures were then repeated at least once during the later (> 48 hours) period of their stay. Seventy patients (71%) had completed vitamin studies eligible for inclusion in the analysis. Ten patients died (14.3%) during their hospital stay and mortality was associated with age, admission source and severity of illness scores. Vitamin B12 concentration was weakly associated with C-reactive protein concentrations on admission to the intensive care unit (r on days one and two = 0.4 [P = 0.002], 0.36 [P = 0.04], respectively) and with the Sequential Organ Failure Assessment score between days two and four (Spearman's r = 0.361 [P = 0.04], 0.42 [P = 0.02] and 0.48 [P = 0.02], respectively). Vitamin A concentration was weakly associated with the C-reactive protein concentrations on days one and five (Spearman's r = -0.5 [P = 0.001], -0.4 [P = 0.03], respectively). Change in deficiency status of any of the vitamins over time in the first week of intensive care admission did not appear to influence mortality. We conclude that while weak correlations were identified between vitamins A and B12 and C-reactive protein and Sequential Organ Failure Assessment scores, the importance of these associations and their relationship to hospital mortality remain to be determined.

Topics: Adult; Aged; APACHE; Avitaminosis; Biomarkers; C-Reactive Protein; Cohort Studies; Critical Illness; Female; Folic Acid; Humans; Inflammation; Male; Middle Aged; Multiple Organ Failure; Severity of Illness Index; Statistics, Nonparametric; Thiamine; Treatment Outcome; Vitamin A; Vitamin B 12; Vitamin E

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by selective degeneration of motor neurons. Mutations in copper/zinc superoxide dismutase (SOD1) account for 20% cases of familial ALS (fALS), but the underlying pathogenetic mechanisms are largely unknown. Using SOD1(G93A) mice model of ALS, we demonstrated that mutation in SOD1 caused a significant increase in the level of plasma homocysteine (Hcy). To investigate whether Hcy-lowering therapy is beneficial to this disease, we applied folic acid (FA) and vitamin B12 which are important factors involved in the Hcy metabolism to assess the neuroprotective effect of FA and B12 in the SOD1(G93A) mice. Our results showed FA or FA+B12 treatment significantly delayed the disease onset and prolonged the lifespan, accompanied by the significant reduction of motor neuron loss. Furthermore, we found that FA or FA+B12 treatment significantly attenuated the plasma Hcy level, suppressed the activation of microglia and astrocytes, and inhibited the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in spinal cord. Moreover, FA or FA+B12 treatment decreased the levels of cleaved caspase-3 and poly(ADP-ribose)polymerase (PARP) but up-regulated the level of anti-apoptotic protein Bcl-2. However, B12 treatment alone did not show any significant benefit to this disease. These results provide evidence to demonstrate that elevated Hcy is involved in the pathogenesis of fALS and FA therapy may have therapeutic potential for the treatment of the disease.

Topics: Amyotrophic Lateral Sclerosis; Animals; Apoptosis; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Folic Acid; Gas Chromatography-Mass Spectrometry; Homocysteine; Inflammation; Mice; Mice, Transgenic; Motor Neurons; Nitric Oxide Synthase Type II; Proto-Oncogene Proteins c-bcl-2; Random Allocation; Rotarod Performance Test; Spinal Cord; Superoxide Dismutase; Vitamin B 12; Vitamin B Complex

Hyperhomocysteinemia has been associated with vascular disease in many epidemiological studies. However, the pathophysiology is unclear. It is postulated that increased levels of homocysteine induce an inflammatory response in endothelial cells, mediated by pro-inflammatory cytokines and chemokines. The aim of this study was to investigate whether plasma concentrations of interleukin-6, interleukin-8, C-reactive protein, and monocyte chemoattractant protein-1 are increased with higher plasma homocysteine concentrations and whether decreasing homocysteine by vitamin supplementation decreases the concentration of these markers.. Plasma homocysteine, interleukin-6, interleukin-8, C-reactive protein, and monocyte chemoattractant protein-1 concentrations were measured in 230 volunteers before and after 8 weeks of multivitamin supplementation (folic acid, B(6), and B(12)).. At baseline, plasma homocysteine concentration was weakly associated with interleukin-8, but not with interleukin-6, C-reactive protein or monocyte chemoattractant protein-1. Vitamin supplementation resulted in a significant decrease in homocysteine concentration, but no effect on interleukin-6, interleukin-8, C-reactive protein or monocyte chemoattractant protein-1 was observed.. At baseline homocysteine was only weakly correlated with interleukin-8, but not with interleukin-6, C-reactive protein or monocyte chemoattractant protein-1. Vitamin supplementation affected homocysteine concentration, but not cytokine levels. The hypothesis that hyperhomocysteinemia increases arteriosclerotic or thrombotic risk through vascular inflammation was not supported by this study.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Chemokine CCL2; Dietary Supplements; Female; Folic Acid; Homocysteine; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Vitamin B 12; Vitamin B 6

Cobalamin carrier proteins,the Transcobalamins (TCS), are elevated during trauma, infections and chronic inflammatory conditions. This remains un-explained. It is proposed that such TC elevations signal a need for cobalamin central to the resolution of inflammation. Thus Cobalamin may regulate the transcription factor, NFkappaB, activation or suppression of which determines the inflammatory response and its resolution. Such regulation may involve at least 5 separate mechanisms: (i) hormone-like regulation of TNFalpha, through reduction of excess NO by cobalamin, as well as through the selective inhibition, in tandem with glutathione, of inducible nitric oxide synthase; (ii) quenching of nitric oxide radicals and reactive oxygen species, enhanced by cobalamin's glutathione sparing effect; (iii) the promotion of acetylcholine synthesis, central to the neuro-immune cholinergic anti-inflammatory pathway; (iv) the promotion of oxidative phosphorylation; (v) and a bacteriostatic role of the TCS released by neutrophil secondary granules during phagocytosis, which also appears to modulate the inflammatory response. TC elevations are dependent on NFkappaB activation, through crosstalk between NFkappaB and Sp1, another member of the helix-loop-helix protein family, which directly mediates transcription of the TCII gene. Sp1 also has binding sites on the TNFalpha and EGF gene promoters. NFkappaB may thus ensure sufficient cobalamin to determine its own eventual suppression. Cobalamin's established regulation of EGF may additionally preserve normal function of macrophages and the coagulation cascade in wound healing. By regulating NFkappaB, Cobalamin may also be the as yet unidentified mediator needed to potentiate the anti-inflammatory action of eicosanoids derived from omega-3 essential fatty acids. Moreover, animal and human clinical data suggests that high dose cobalamin may prove a promising approach to SIRS/sepsis/septic and traumatic shock.

Topics: Acetylcholine; Glutathione; Humans; Inflammation; Models, Biological; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Sepsis; Shock, Septic; Shock, Traumatic; Systemic Inflammatory Response Syndrome; Vitamin B 12

Little is known about the effects of commonly used vitamins on serum inflammatory markers and the hormonal balance in obese postmenopausal women. We studied the effects of an 8-week open-label supplementation with vitamins C (500 mg), B6 (25 mg), B12 (1 mg), and folate (5 mg) on C-reactive protein, interleukin-6, and estradiol levels in 20 obese (body mass index > or = 30) postmenopausal women. Outcomes were assessed in a blinded fashion. Folate and vitamin B12 levels rose significantly, suggesting that the supplement was well absorbed and that participants adhered to the protocol. Weight, blood pressure, and serum lipids remained stable. C-reactive protein, interleukin-6, and leptin levels remained unchanged. Estradiol levels rose from a median of 22.0 pg/mL (IQR = 15.9-25.8) at baseline to a median of 27.8 pg/mL (IQR = 23.1-33.9) at follow-up (p = 0.003). Increments in serum estradiol caused by vitamin supplementation in postmenopausal women have not been previously described and probably merit further investigation.

Topics: Ascorbic Acid; C-Reactive Protein; Dietary Supplements; Estradiol; Folic Acid; Inflammation; Interleukin-6; Leptin; Obesity; Postmenopause; Vitamin B 12; Vitamin B 6; Vitamin B Complex

Subclinical inflammation has been implicated in the initiation and/or progression of atherosclerosis. Diabetes mellitus and obesity are risk factors for atherosclerosis, and asymptomatic low grade inflammation occurs prior to overt vascular lesions in these patients. In contrast to adults, little information exists concerning low grade inflammation in young type 1 diabetes and juvenile obesity.. To investigate low grade inflammation and immune activation in juvenile diabetes mellitus and obesity.. hs-CRP, soluble interleukin-2 receptor (sIL-2R), C-peptide, insulin, cortisol, vitamin B12, folic acid, leptin, and homocysteine were determined in 148 patients with juvenile type 1 diabetes, 86 obese children and 142 normal weighted age-matched healthy controls. Intima-media thickness (IMT) and lumen diameter of both common carotid arteries (CCA) was measured by ultrasonography in 52 healthy pediatric controls, 10 diabetics, and 34 obese juveniles.. Serum hs-CRP was significantly elevated in patients with type 1 diabetes (p < 0.0001), and obese children (p < 0.0001) as compared to the control group. The obese juveniles (p < 0.0001) and the diabetics (p < 0.0001) showed significantly increased values for IMT of CAAs. Levels of homocysteine, sIL-2R, insulin, cortisol, vitamin B12, and folic acid did not differ from the controls. The elevation of hs-CRP was more pronounced in obesity as compared to type 1 diabetes (p < 0.0001), and the hs-CRP values correlated significantly with body mass index standard deviation score (BMI-SDS) values. Furthermore, the IMT and the luminal diameter of CCAs showed significant correlations with BMI-SDS values.. A low grade inflammation as determined by serum hs-CRP is significantly increased in children with type 1 diabetes, and even more pronounced in apparently healthy juveniles with obesity. The increased IMT of CCAs strongly argues for an association between this low grade inflammation and early atherosclerotic vessel injury.

Topics: Adolescent; Arteriosclerosis; Body Mass Index; C-Peptide; C-Reactive Protein; Carotid Artery, Common; Child; Diabetes Mellitus, Type 1; Female; Folic Acid; Homocysteine; Humans; Inflammation; Leptin; Male; Obesity; Receptors, Interleukin-2; Tunica Intima; Vitamin B 12

Topics: Adult; Arteriosclerosis; Aspirin; C-Reactive Protein; Case-Control Studies; Contraceptives, Oral; Female; Fibrinogen; Folic Acid; Humans; Hyperhomocysteinemia; Inflammation; Male; Meta-Analysis as Topic; Migraine Disorders; Risk Factors; Smoking; Stroke; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator; Vitamin B 12; Vitamin B 6

Lower vitamin B(6) concentrations are reported to confer an increased and independent risk for cardiovascular disease (CVD). The mechanism underlying this relationship, however, remains to be defined. Other diseases, such as rheumatoid arthritis, are associated with reduced vitamin B(6) levels. Despite a clear distinction in pathophysiology, inflammatory reaction may be the major link between these diseases. We hypothesized a relationship between pyridoxal 5'-phosphate (PLP), the active form of vitamin B(6), and the marker of inflammation C-reactive protein (CRP). We also evaluated whether total plasma homocysteine (tHcy), a well-defined risk factor for CVD and a major determinant of plasma PLP levels, had a possible role as a mediator of this hypothesized relationship.. Data from 891 participants from the population-based Framingham Heart Study cohort were analyzed. Subjects were divided into 2 groups according to normal or elevated CRP values: group 1, CRP <6 mg/L; group 2, CRP >/=6 mg/L. Plasma PLP levels were substantially lower in group 2 than in group 1 (mean values in group 2, 36.5 nmol/L versus 55.8 nmol/L in group 1, P<0.001). In a multiple logistic regression model adjusted for tHcy, the association of PLP with CRP remained highly significant (P=0.003).. Low plasma PLP is associated with higher CRP levels independently of tHcy. This observation may reflect a vitamin B(6) utilization in the presence of an underlying inflammatory process and represent a possible mechanism to explain the decreased vitamin B(6) levels in CVD.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Cohort Studies; Creatinine; Diet; Female; Folic Acid; Homocysteine; Humans; Inflammation; Logistic Models; Male; Massachusetts; Pyridoxal Phosphate; Pyridoxine; Risk Factors; Serum Albumin; Vitamin B 12

Measurements of tissue content of myeloperoxidase, a constituent of neutrophil azurophil granules and of unsaturated vitamin B12-binding protein from neutrophil-specific granules, have been used to assess intestinal inflammation. This paper reports results of a prospective evaluation of such measurements in serial colonoscopy biopsy specimens from patients with inflammatory bowel disease. Histologic grading of acute inflammation was based on perceived numbers of neutrophil polymorphs in sections from an immediately adjacent biopsy specimen. The mean + 2 SD range for unsaturated vitamin B12-binding protein activity in homogenates of histologically normal specimens was 62 pg mg protein-1. Values increased progressively up to 900 pg mg-1 protein in the most severely inflamed specimens. Unsaturated vitamin B12-binding protein measurements generally distinguished among histologic grades of inflammation, whereas myeloperoxidase activities failed to do this, probably because substantial myeloperoxidase activity was found in uninflamed colonic mucosa, suggesting a non-neutrophil source for this enzyme.

Topics: Acute Disease; Biopsy; Colonoscopy; Humans; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Peroxidase; Prospective Studies; Vitamin B 12

Topics: Administration, Oral; Anti-Inflammatory Agents; Dexamethasone; Humans; Inflammation; Injections, Intramuscular; Lipopolysaccharides; Pyrazoles; Rheumatic Diseases; Skin Tests; Vitamin B 12

Topics: Aminopyrine; Analgesics; Anti-Inflammatory Agents; Dexamethasone; Edema; Humans; Inflammation; Phenylbutazone; Prednisolone; Rheumatic Diseases; Vitamin B 12; Vitamins

Topics: Anemia; Blood Proteins; Humans; Inflammation; Leukemia, Myeloid; Liver Diseases; Neoplasms; Protein Binding; Vitamin B 12

Topics: Animals; Ascorbic Acid; Chloramphenicol; Drug Synergism; Female; Folic Acid; Inflammation; Male; Niacinamide; Penicillins; Phagocytosis; Pyridoxine; Rats; Riboflavin; Thiamine; Vitamin B 12; Vitamin K; Vitamins