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Association of High Intakes of Vitamins B6 and B12 From Food and Supplements With Risk of Hip Fracture Among Postmenopausal Women in the Nurses' Health Study.
Meyer, HE, Willett, WC, Fung, TT, Holvik, K, Feskanich, D
JAMA network open. 2019;(5):e193591
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Abstract
IMPORTANCE Vitamin supplementation far exceeding recommended doses is popular in segments of the population. However, adverse effects can occur. In a previous secondary analysis of combined data from 2 double-blind randomized clinical trials (RCTs), an unexpected increased risk of hip fracture was found among those treated with high doses of vitamin B6 in combination with vitamin B12. OBJECTIVES To study if high intakes of vitamins B6 and B12 from food and supplements were associated with a risk of hip fracture in the Nurses' Health Study and to investigate whether combined high intakes of both vitamins conferred a particularly increased fracture risk. DESIGN, SETTING, AND PARTICIPANTS In this prospective cohort study, 75 864 postmenopausal women in the United States were followed up from June 1984 through May 2014. The dates of analysis were July 2016 to June 2018. Information on hip fracture and a wide range of potential confounders was collected at baseline and with biennial follow-up questionnaires. Extensive dietary information was collected approximately every 4 years with a semiquantitative food frequency questionnaire. Relative risks (RRs) were calculated by Cox proportional hazards regression, with cumulative average intakes of vitamins B6 and B12 as main exposures, adjusting for potential confounders. MAIN OUTCOME AND MEASURE Hip fracture. RESULTS During follow-up, 2304 of 75 864 women had a hip fracture. Among the women with hip fractures, the median (range) age at hip fracture was 75.8 (46.7-93.0) years and the mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 24.3 (4.6). Median (interquartile range) cumulative average intakes of total vitamins B6 and B12 were 3.6 (4.8) mg/d and 12.1 (11.7) μg/d, respectively. Both vitamin B6 (RR, 1.29; 95% CI, 1.04-1.59 for an intake of ≥35 vs <2 mg/d; P = .06 for linear trend) and vitamin B12 (RR, 1.25; 95% CI, 0.98-1.58 for an intake of ≥30 vs <5 μg/d; P = .02 for linear trend) were associated with increased fracture risk. Risk was highest in women with a combined high intake of both vitamins (B6 ≥35 mg/d and B12 ≥20 μg/d), exhibiting an almost 50% increased risk of hip fracture (RR, 1.47; 95% CI, 1.15-1.89) compared with women with a low intake of both vitamins (B6 <2 mg/d and B12 <10 μg/d). CONCLUSIONS AND RELEVANCE In this cohort study, a combined high intake of vitamins B6 and B12 was associated with an increased risk of hip fracture. The intakes were far higher than the recommended dietary allowances. These findings add to previous studies suggesting that vitamin supplements should be used cautiously because adverse effects can occur.
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Flower Pollen Extract in Association with Vitamins (Deprox 500®) Versus Serenoa repens in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Comparative Analysis of Two Different Treatments.
Macchione, N, Bernardini, P, Piacentini, I, Mangiarotti, B, Del Nero, A
Anti-inflammatory & anti-allergy agents in medicinal chemistry. 2019;(2):151-161
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Abstract
OBJECTIVE Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is reported in the literature ranging from 1 to 14.2%. The aim of the present study was to assess the impact on patient's quality of life and symptoms of Flower pollen extract in association with vitamins (Deprox 500®) in comparison with Serenoa repens 320 mg (Permixon 320 mg® by Pierre Fabre) in patients with CP/CPPS. METHODOLOGY All consecutive patients, with a diagnosis of CP/CPPS, referred to our center from January to August 2016, were screened to be enrolled in this single-center, randomized, controlled trial. The main outcome measure was the evaluation of IPSS/NIHCPSI (International Prostatic Symptom Score/NIH-Chronic Prostatitis Symptom Index) score variation and the assessment of the quality of life and symptoms at the end of the therapy. The second outcome measure was the evaluation of the comorbidity role in the CP/CPPS therapy. 63 patients were analyzed; patients were randomized into two groups: 29 patients were treated with Deprox 500® 2 tablets/day for 6 weeks and 34 patients with Serenoa repens 320 mg, 1 tablet/day for 6 weeks. RESULTS The mean score variation for IPSS was -12.7 ± 4.3 in the Deprox 500® group and -7.8 ± 4.7 in the Serenoa repens group (p=0.0005) while for NIH-CPSI was -17.3±3.1 in the Deprox 500® group and -13.6±4.8 in the Serenoa repens group (p=0.0016). By accounting only the symptoms part of NIH-CPSI questionnaire, the mean score variation reported was -11.5±2.5 in the Deprox 500® group and -9.02±4.0 in the Serenoa repens group (p=0.009321). Furthermore, analyzing the comorbidity subgroups, in patients with hypertension, the mean IPSS score variation was -14.3±3.2 in the Deprox 500® group and - 9.02±4.0 in the Serenoa repens group. CONCLUSION In conclusion, in patients with CP/CPPS, Deprox 500® improves IPSS and NIH-CPSI scores up to 74.5% and 84.5% respectively. Furthermore, in patients with hypertension, the antioxidant effect of Deprox 500® reduces the mean IPSS score of 82.7%.
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The impact of homocysteine, B12, and D vitamins levels on functional neurocognitive performance in HIV-positive subjects.
Falasca, K, Di Nicola, M, Di Martino, G, Ucciferri, C, Vignale, F, Occhionero, A, Vecchiet, J
BMC infectious diseases. 2019;(1):105
Abstract
BACKGROUND The correlation among high levels of total homocysteine, low levels of B12vitamin, and neurocognitive impairment in HIV negative patients has been the main research topic in some of the latest reviews. The aim of this study was to examine if the alteration of homocysteine, B12 vitamin, and D vitamins plasma levels was present in HIV-positive, and their relationship with cognitive function. METHODS 57 HIV infected were enrolled and underwent the serum measurement of homocysteine, B12, and D vitamins. The neurocognitive evaluation investigated 5 cognitive domains, through a neuropsychological battery test RESULTS Homocysteine was found to be elevated in 70.2% of cases, B12 vitamin mean levels were low in 8 participants (14.0%), and 8 patients had D hypovitaminosis (14.0%). Abnormal homocysteine levels were associated with worse performance of verbal fluency (p = 0.003) and worse executive function (Stroop E test p = 0.040). The 25-OH D hypovitaminosis was associated with worse performances in executive functions in three different tests: Stroop E (p = 0.049), Trail B (p = 0.035), and Wais Digit Span (p = 0.042). Pathological levels of B12 Vitamin were also associated to worse performances in executive functions (Trail B Test and Wais Digit Span respectively p = 0.002 and 0.029) and with a lower speed in psychomotor processing (Peg Board Test on dominant hand, p = 0.014). CONCLUSIONS In this study serum homocysteine, B12, and D vitamin levels are associated with neurocognitive performances; in fact low performance neurocognitive was correlated with hyperhomocysteine and low B12vitamin, and D vitamin levels. Evidence of the alteration of these parameters could facilitate the early identification of a neurocognitive impairment.
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Effects of Folic Acid and Vitamin B12, Alone and in Combination on Cognitive Function and Inflammatory Factors in the Elderly with Mild Cognitive Impairment: A Single-blind Experimental Design.
Ma, F, Zhou, X, Li, Q, Zhao, J, Song, A, An, P, Du, Y, Xu, W, Huang, G
Current Alzheimer research. 2019;(7):622-632
Abstract
BACKGROUND Folate and vitamin B12 are well-known as essential nutrients that play key roles in the normal functions of the brain. Inflammatory processes play at least some role in the pathology of AD. Effective nutritional intervention approaches for improving cognitive deficits that reduce the peripheral inflammatory cytokine levels have garnered special attention. OBJECTIVE The present study aimed to determine whether supplementation with folic acid and vitamin B12, alone and in combination improves cognitive performance via reducing levels of peripheral inflammatory cytokines. METHODS 240 participants with MCI were randomly assigned in equal proportion to four treatment groups: folic acid alone, vitamin B12 alone, folic acid plus vitamin B12 or control without treatment daily for 6 months. Cognition was measured with WAIS-RC. The levels of inflammatory cytokines were measured using ELISA. Changes in cognitive function or blood biomarkers were analyzed by repeatedmeasure analysis of variance or mixed-effects models. This trial has been registered with trial number ChiCTR-ROC-16008305. RESULTS Compared with control group, the folic acid plus vitamin B12 group had significantly greater improvements in serum folate, homocysteine, vitamin B12 and IL-6, TNF-α, MCP-1. The folic acid plus vitamin B12 supplementation significantly changed the Full Scale IQ (effect size d = 0.169; P = 0.024), verbal IQ (effect size d = 0.146; P = 0.033), Information (d = 0.172; P = 0.019) and Digit Span (d = 0.187; P = 0.009) scores. Post hoc Turkey tests found that folic acid and vitamin B12 supplementation was significantly more effective than folic acid alone for all endpoints. CONCLUSIONS The combination of oral folic acid plus vitamin B12 in MCI elderly for six months can significantly improve cognitive performance and reduce the levels of inflammatory cytokines in human peripheral blood. The combination of folic acid and vitamin B12 was significantly superior to either folic acid or vitamin B12 alone.
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Brain Hemodynamic Intermediate Phenotype Links Vitamin B12 to Cognitive Profile of Healthy and Mild Cognitive Impaired Subjects.
Cecchetti, L, Lettieri, G, Handjaras, G, Leo, A, Ricciardi, E, Pietrini, P, Pellegrini, S, ,
Neural plasticity. 2019;:6874805
Abstract
Vitamin B12, folate, and homocysteine are implicated in pivotal neurodegenerative mechanisms and partake in elders' mental decline. Findings on the association between vitamin-related biochemistry and cognitive abilities suggest that the structural and functional properties of the brain may represent an intermediate biomarker linking vitamin concentrations to cognition. Despite this, no previous study directly investigated whether vitamin B12, folate, and homocysteine levels are sufficient to explain individual neuropsychological profiles or, alternatively, whether the activity of brain regions modulated by these compounds better predicts cognition in elders. Here, we measured the relationship between vitamin blood concentrations, scores at seventeen neuropsychological tests, and brain activity of sixty-five elders spanning from normal to Mild Cognitive Impairment. We then evaluated whether task-related brain responses represent an intermediate phenotype, providing a better prediction of subjects' neuropsychological scores, as compared to the one obtained considering blood biochemistry only. We found that the hemodynamic activity of the right dorsal anterior cingulate cortex was positively associated (p value < 0.05 cluster corrected) with vitamin B12 concentrations, suggesting that elders with higher B12 levels had a more pronounced recruitment of this salience network region. Crucially, the activity of this area significantly predicted subjects' visual search and attention abilities (p value = 0.0023), whereas B12 levels per se failed to do so. Our results demonstrate that the relationship between blood biochemistry and elders' cognitive abilities is revealed when brain activity is included into the equation, thus highlighting the role of brain imaging as intermediate phenotype.
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Incidence, Risk Factors, and Outcome of Immune-Mediated Neuropathies (IMNs) following Haploidentical Hematopoietic Stem Cell Transplantation.
Ren, XY, Liu, X, Huang, QS, Wang, QM, He, Y, Zhu, XL, Han, W, Chen, H, Chen, YH, Wang, FR, et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019;(8):1629-1636
Abstract
Immune-mediated neuropathies (IMNs) following hematopoietic stem cell transplantation have been described recently, which, excluding Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, may present with atypical patterns. This retrospective, nested, case-control study reviewed data from 3858 patients who received haploidentical hematopoietic stem cell transplantation (haplo-HSCT) during the past 10 years at a single center, and 40 patients (1.04%) with IMN following haplo-HSCT were identified. Chronic graft-versus-host disease (cGVHD) (P = .043) and cytomegalovirus (CMV) viremia (P = .035) were recognized as independent risk factors for the development of IMN after haplo-HSCT. There were no significant differences in overall survival (P = .619), disease-free survival (P = .609), nonrelapse mortality (P = .87), or the incidence of relapse (P = .583) between patients with and without IMN after haplo-HSCT. However, patients with post-transplant IMN were at higher risk of developing cGVHD (P = .012) than patients who did not develop IMN. Twenty-four of the 40 patients with IMN (60%) attained neurologic improvement after treatments including vitamins B1 and B12 and/or immunomodulatory agents. However, 19 (47.5%) patients still had persistent motor/sensory deficits despite receiving timely treatment. More studies are needed to help develop standardized diagnostic and therapeutic strategies for patients with post-transplant IMN.
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Association of vitamin D and vitamin B12 with cognitive impairment in elderly aged 80 years or older: a cross-sectional study.
da Rosa, MI, Beck, WO, Colonetti, T, Budni, J, Falchetti, ACB, Colonetti, L, Coral, AS, Meller, FO
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2019;(4):518-524
Abstract
BACKGROUND The present study aimed to assess the association of vitamin D and vitamin B12 with cognitive impairment in elderly people. METHODS The data were obtained from a cross-sectional study that included individuals aged 80 years or older living in the urban and rural areas of the cities of Siderópolis and Treviso in the state of Santa Catarina, Brazil. In total, 165 elderly people were included in the analysis. The outcome of cognitive decline was assessed by the Mini-Mental State Examination. Vitamin D and vitamin B12 levels were measured from blood samples. The socio-demographic, anthropometric and health variables used in the analysis were collected from a questionnaire. Crude and adjusted analyses of the relationship between vitamins D and B12 and cognitive decline were performed using a Poisson regression model. RESULTS The prevalence of cognitive decline was 35.2%. In the adjusted model, individuals who had vitamin D levels >19 ng mL-1 showed a lower prevalence of cognitive decline (prevalence ratio = 0.59; 95% confidence interval = 0.39-0.87). Those participants who had vitamin B12 levels of ≥496 pg mL-1 had a higher prevalence of cognitive decline (prevalence ratio = 1.90; 95% confidence interval = 1.08-3.36). CONCLUSIONS The present study showed that individuals aged ≥80 years who had vitamin D levels of ≤18 ng mL-1 had a higher prevalence of cognitive decline even after adjustment for potential confounders. In addition, the study demonstrated that vitamin B12 levels of ≥496 pg mL-1 in this population were also a risk factor for cognitive decline. A cross-sectional analysis does not enable the inference of a cause-effect relationship and additional studies are needed to understand these relationships.
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High-Dose Vitamin B12 in Vasodilatory Shock: A Narrative Review.
Patel, JJ, Venegas-Borsellino, C, Willoughby, R, Freed, JK
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2019;(4):514-520
Abstract
Vasodilatory shock, as observed in postoperative states and sepsis, is hallmarked by low systemic vascular resistance and low blood pressure compensated by increased cardiac output. Gasotransmitters, such as nitric oxide and hydrogen sulfide, are implicated in the development and perpetuation of vasodilatory shock. Established therapies do not target these physiologic drivers of vasodilation. Due to their nontoxic and pleotropic effects, micronutrients are being used as rescue therapy in postoperative vasoplegia and septic shock. Here, we outline the pathophysiology of vasodilatory shock, describe the rationale for vitamin B12 (hydroxocobalamin) in vasodilatory shock, and identify literature evaluating its use in vasoplegic states.
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Defining the plasma folate concentration associated with the red blood cell folate concentration threshold for optimal neural tube defects prevention: a population-based, randomized trial of folic acid supplementation.
Chen, MY, Rose, CE, Qi, YP, Williams, JL, Yeung, LF, Berry, RJ, Hao, L, Cannon, MJ, Crider, KS
The American journal of clinical nutrition. 2019;(5):1452-1461
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BACKGROUND For women of reproductive age, a population-level red blood cell (RBC) folate concentration below the threshold 906 nmol/L or 400 ng/mL indicates folate insufficiency and suboptimal neural tube defect (NTD) prevention. A corresponding population plasma/serum folate concentration threshold for optimal NTD prevention has not been established. OBJECTIVE The aim of this study was to examine the association between plasma and RBC folate concentrations and estimated a population plasma folate insufficiency threshold (pf-IT) corresponding to the RBC folate insufficiency threshold (RBCf-IT) of 906 nmol/L. METHODS We analyzed data on women of reproductive age (n = 1673) who participated in a population-based, randomized folic acid supplementation trial in northern China. Of these women, 565 women with anemia and/or vitamin B-12 deficiency were ineligible for folic acid intervention (nonintervention group); the other 1108 received folic acid supplementation for 6 mo (intervention group). We developed a Bayesian linear model to estimate the pf-IT corresponding to RBCf-IT by time from supplementation initiation, folic acid dosage, methyltetrahydrofolate reductase (MTHFR) genotype, body mass index (BMI), vitamin B-12 status, or anemia status. RESULTS Using plasma and RBC folate concentrations of the intervention group, the estimated median pf-IT was 25.5 nmol/L (95% credible interval: 24.6, 26.4). The median pf-ITs were similar between the baseline and postsupplementation samples (25.7 compared with 25.2 nmol/L) but differed moderately (±3-4 nmol/L) by MTHFR genotype and BMI. Using the full population-based baseline sample (intervention and nonintervention), the median pf-IT was higher for women with vitamin B-12 deficiency (34.6 nmol/L) and marginal deficiency (29.8 nmol/L) compared with the sufficient group (25.6 nmol/L). CONCLUSIONS The relation between RBC and plasma folate concentrations was modified by BMI and genotype and substantially by low plasma vitamin B-12. This suggests that the threshold of 25.5 nmol/L for optimal NTD prevention may be appropriate in populations with similar characteristics, but it should not be used in vitamin B-12 insufficient populations. This trial was registered at clinicaltrials.gov as NCT00207558.
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Vitamin B12 for the treatment of vasoplegia in cardiac surgery and liver transplantation: a narrative review of cases and potential biochemical mechanisms.
Charles, FG, Murray, LJ, Giordano, C, Spiess, BD
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2019;(12):1501-1513
Abstract
PURPOSE Hydroxocobalamin, or vitamin B12 (V-B12), is frequently used to treat smoke inhalation and cyanide poisoning. Recent reports have also described its use to treat vasoplegia in cardiac surgery and liver transplantation. This narrative review discusses this "off-label" indication for V-B12, focusing on the potential biochemical mechanisms of its actions. SOURCE PubMed, Cochrane, and Web of Science databases were searched for clinical reports on the use of V-B12 for vasoplegia in cardiac surgery and liver transplantation, with the biochemical mechanisms discussed being based on a survey of the related biochemistry literature. PRINCIPAL FINDINGS Forty-four patients have been treated with V-B12 for vasoplegia in various isolated case reports and one series. Although 75% of patients have increased blood pressure in response to V-B12, there were some "non-responders". The true efficacy remains unknown because clinical trials have not been performed, and significant reporting bias likely exists. Plausible biochemical explanations exist for the potential beneficial effects of V-B12 in treating vasoplegia, including binding nitric oxide and other gasotransmitters. Additional research is required to clarify if and how these mechanisms are causally involved in effective clinical responders and non-responders. CONCLUSIONS Although anecdotal reports utilizing V-B12 for vasoplegia are available, no higher-level evidence exists. Future work is necessary to further understand the dosing, timing, adverse events, and biochemical mechanisms of V-B12 compared with other therapies such as methylene blue.