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Vitamin B12, B6, or Folate and Cognitive Function in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis.
Zhang, C, Luo, J, Yuan, C, Ding, D
Journal of Alzheimer's disease : JAD. 2020;(2):781-794
Abstract
BACKGROUND Previous studies have indicated that B vitamin deficiencies are an essential cause of neurological pathology. There is a need to provide evidence of the benefit of B vitamins for the prevention of cognitive decline in community-dwelling older adults. OBJECTIVE To examine the association between intake and plasma levels of vitamins B12, B6, and folate and cognitive function in older populations through a systematic review and meta-analysis. METHODS Medline (PubMed), EMBASE, and Cochrane databases were used to search the literature though August 8, 2019. We included observational population-based studies evaluating the association between concentrations or intake levels of vitamins B6, B12, or folate and cognition in older adults aged ≥45 years. The quality of all studies was assessed by the modified Newcastle-Ottawa Scale. Odds ratios (ORs) and hazard ratios (HRs) were analyzed by the random-effects model. Sensitivity analyses were conducted by excluding the studies with significant heterogeneity. RESULTS Twenty-one observational studies with sample sizes ranging from 155-7030 were included in the meta-analysis. Higher levels of vitamin B12 (OR = 0.77, 95% CI = 0.61-0.97) and folate concentration (OR = 0.68, 95% CI = 0.51-0.90) were associated with better cognition in cross-sectional studies, but not in sensitivity analyses or prospective studies. High vitamin B6 concentrations showed no significant benefit on cognition and dementia risk. Prospective studies did not provide substantial evidence for the relationship. CONCLUSION The results from our meta-analysis suggest that vitamins B12, B6, and folate may not be modifiable risk factors for slowing cognitive decline among community-dwelling older individuals.
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Revised D-A-CH Reference Values for the Intake of Vitamin B6.
Jungert, A, Linseisen, J, Wagner, KH, Richter, M, ,
Annals of nutrition & metabolism. 2020;(4):213-222
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Abstract
BACKGROUND The Nutrition Societies of Germany, Austria, and Switzerland as the joint editors of the "D-A-CH reference values for nutrient intake" have revised the reference values for vitamin B6 in summer 2019. SUMMARY For women, the average requirement (AR) for vitamin B6 intake was derived on the basis of balance studies using a pyridoxal-5'-phosphate (PLP) plasma concentration of ≥30 nmol/L as a biomarker of an adequate vitamin B6 status. The recommended intake (RI) was derived considering a coefficient of variation of 10%. The RIs of vitamin B6 for men, children, and adolescents were extrapolated from the vitamin B6 requirement for women considering differences in body weight, an allometric exponent, growth factors as appropriate, and a coefficient of variation. For infants aged 0 to under 4 months, an estimated value was set based on the vitamin B6 intake via breast feeding. The reference value for infants aged 4 to under 12 months was extrapolated from the estimated value for infants under 4 months of age and the average vitamin B6 requirement for adults. The reference values for pregnant and lactating women consider the requirements for the foetus and the loss via breast milk. Key Messages: According to the combined analysis of 5 balance studies, the AR for vitamin B6 to ensure a plasma PLP concentration of ≥30 nmol/L is 1.2 mg/day for adult females and the extrapolated AR for adult males is 1.3 mg/day. The corresponding RIs of vitamin B6 are 1.4 mg/day for adult females and 1.6 mg/day for adult males, independent of age. For infants, the estimated value is 0.1 mg/day and 0.3 mg/day, depending on age. The AR of vitamin B6 for children and adolescents ranges between 0.5 and 1.5 mg/day, and the RI is between 0.6 mg/day and 1.6 mg/day. During pregnancy, the AR is 1.3 mg/day in the first trimester and 1.5 mg/day in the second and third trimesters; the RI is 1.5 mg/day in the first trimester and 1.8 mg/day in the second and third trimesters. For lactating women, the AR is 1.3 mg/day and the RI is 1.6 mg/day.
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The effectiveness of correcting abnormal metabolic profiles.
Clayton, PT
Journal of inherited metabolic disease. 2020;(1):2-13
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Abstract
Inborn errors of metabolism cause disease because of accumulation of a metabolite before the blocked step or deficiency of an essential metabolite downstream of the block. Treatments can be directed at reducing the levels of a toxic metabolite or correcting a metabolite deficiency. Many disorders have been treated successfully first in a single patient because we can measure the metabolites and adjust treatment to get them as close as possible to the normal range. Examples are drawn from Komrower's description of treatment of homocystinuria and the author's trials of treatment in bile acid synthesis disorders (3β-hydroxy-Δ5 -C27 -steroid dehydrogenase deficiency and Δ4 -3-oxosteroid 5β-reductase deficiency), neurotransmitter amine disorders (aromatic L-amino acid decarboxylase [AADC] and tyrosine hydroxylase deficiencies), and vitamin B6 disorders (pyridox(am)ine phosphate oxidase deficiency and pyridoxine-dependent epilepsy [ALDH7A1 deficiency]). Sometimes follow-up shows there are milder and more severe forms of the disease and even variable clinical manifestations but by measuring the metabolites we can adjust the treatment to get the metabolites into the normal range. Biochemical measurements are not subject to placebo effects and will also show if the disorder is improving spontaneously. The hypothesis that can then be tested for clinical outcome is whether getting metabolite(s) into a target range leads to an improvement in an outcome parameter such as abnormal liver function tests, hypokinesia, epilepsy control etc. The metabolite-guided approach to treatment is an example of personalized medicine and is a better way of determining efficacy for disorders of variable severity than a randomized controlled clinical trial.
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Impact of Glutathione and Vitamin B-6 in Cirrhosis Patients: A Randomized Controlled Trial and Follow-Up Study.
Lai, CY, Cheng, SB, Lee, TY, Hsiao, YF, Liu, HT, Huang, YC
Nutrients. 2020;(7)
Abstract
Vitamin B-6 and glutathione (GSH) are antioxidant nutrients, and inadequate vitamin B-6 may indirectly limit glutathione synthesis and further affect the antioxidant capacities. Since liver cirrhosis is often associated with increased oxidative stress and decreased antioxidant capacities, we conducted a double-blind randomized controlled trial to assess the antioxidative effect of vitamin B-6, GSH, or vitamin B-6/GSH combined supplementation in cirrhotic patients. We followed patients after the end of supplementation to evaluate the association of vitamin B-6 and GSH with disease severity. In total, 61 liver cirrhosis patients were randomly assigned to placebo, vitamin B-6 (50 mg pyridoxine/d), GSH (500 mg/d), or B-6 + GSH groups for 12 weeks. After the end of supplementation, the condition of patient's disease severity was followed until the end of the study. Neither vitamin B-6 nor GSH supplementation had significant effects on indicators of oxidative stress and antioxidant capacities. The median follow-up time was 984 d, and 21 patients were lost to follow-up. High levels of GSH, a high GSH/oxidized GSH ratio, and high GSH-St activity at baseline (Week 0) had a significant effect on low Child-Turcotte-Pugh scores at Week 0, the end of supplementation (Week 12), and the end of follow-up in all patients after adjusting for potential confounders. Although the decreased GSH and its related enzyme activity were associated with the severity of liver cirrhosis, vitamin B-6 and GSH supplementation had no significant effect on reducing oxidative stress and increasing antioxidant capacities.
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Acne related to dietary supplements.
Zamil, DH, Perez-Sanchez, A, Katta, R
Dermatology online journal. 2020;(8)
Abstract
Multiple prescription medications may cause or aggravate acne. A number of dietary supplements have also been linked to acne, including those containing vitamins B6/B12, iodine, and whey, as well as "muscle building supplements" that may be contaminated with anabolic-androgenic steroids (AAS). Acne linked to dietary supplements generally resolves following supplement discontinuation. Lesions associated with high-dose vitamin B6 and B12 supplements have been described as monomorphic and although pathogenesis is unknown, a number of hypotheses have been proposed. Iodine-related acne may be related to the use of kelp supplements and has been reported as monomorphic, inflammatory pustules on the face and upper trunk. Whey protein supplements, derived from milk and used for bodybuilding, are associated with papulonodular acne involving the trunk and sometimes the face. Finally, AAS-induced acne has been described as acne fulminans, acne conglobata, and acne papulopustulosa. With studies indicating that about half of US adults report using dietary supplements, it is important that dermatologists directly ask acne patients about their supplement use and educate them on the potential risks of even seemingly innocuous dietary supplements.
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Association Between One-carbon Metabolism-related Vitamins and Risk of Breast Cancer: A Systematic Review and Meta-analysis of Prospective Studies.
Zeng, J, Gu, Y, Fu, H, Liu, C, Zou, Y, Chang, H
Clinical breast cancer. 2020;(4):e469-e480
Abstract
Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B6, vitamin B2, vitamin B12) and breast cancer risk have reported inconsistent findings. We conducted a systematic search of the reported data and performed a meta-analysis of prospective case-control and cohort studies to derive a more precise evaluation. The PubMed and EMBASE databases were searched to identify eligible studies. A total of 27 studies involving 49,707 cases and 1,274,060 individuals were included in the meta-analysis. The results indicated that a high intake of folate, vitamin B6, and vitamin B2 might decrease the risk of breast cancer. The corresponding pooled relative risks (RRs) for the highest intake compared with the lowest were 0.93 (95% confidence interval [CI], 0.88-0.99; P = .018), 0.94 (95% CI, 0.89-1.00; P = .037) and 0.90 (95% CI, 0.82-0.99; P = .026). No significant association between vitamin B12 and breast cancer risk was found (RR, 0.99; 95% CI, 0.94-1.04; P = .604). Further study showed that folate and vitamin B6 might decrease the risk of estrogen receptor-negative (ER-)/progesterone receptor-negative (PR-) breast cancer but not ER+/PR+ breast cancer. The dose-response meta-analysis indicated a significant linearity relationship between folate intake and a reduced risk of ER-/PR- breast cancer. An increment of folate intake (100 μg/d) corresponded to a 7% deceased risk of ER-/PR- breast cancer (RR, 0.93; 95% CI, 0.89-0.98; P = .007). In conclusion, a high intake of 1-carbon metabolism-related vitamins might contribute to the prevention of breast cancer, especially ER-/PR- breast cancer.
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Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.
Cappuccilli, M, Bergamini, C, Giacomelli, FA, Cianciolo, G, Donati, G, Conte, D, Natali, T, La Manna, G, Capelli, I
Nutrients. 2020;(5)
Abstract
Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.
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Use of nutritional supplements based on melatonin, tryptophan and vitamin B6 (Melamil Tripto®) in children with primary chronic headache, with or without sleep disorders: a pilot study.
Bravaccio, C, Terrone, G, Rizzo, R, Gulisano, M, Tosi, M, Curatolo, P, Emberti Gialloreti, L
Minerva pediatrica. 2020;(1):30-36
Abstract
BACKGROUND Headache is one of the main complaints in pediatric neurology. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and sleep quality in children. Tryptophan as well plays a key role in sleep regulation. So far, no studies tried to analyze the effects of a combination of both melatonin and tryptophan in treating chronic headache in children affected also by night-time awakenings. METHODS Thirty-four children with a diagnosis of chronic headache (with or without sleep disorders) have been enrolled. The study was articulated in two steps: 1) each child was observed for one month without any intervention; 2) children have been then randomized into two groups: the "ME-group", which received the nutritional supplement melatonin for two months and the "MET-group", which received the nutritional supplements melatonin, tryptophan, and vitamin B6 for two months. RESULTS In terms of changes in number of headache events, responders in the ME-group were 91.7% and those in the MET-group were 66.7% (P=0.113). In terms of changes in number of night awakenings, in the ME group, mean number at baseline, after 30 days, and after 60 days were 3.6±3.2, 3.2±3.5, and 2.7±3.4 (P=0.495). In the MET group, mean number of night awakenings was 7.4±8.1, 4.0±4.4, and 3.3±2.9 (P=0.041). CONCLUSIONS Using either nutritional supplement for two months can help in decreasing the monthly number of headache episodes and night awakenings. The addition of tryptophan and vitamin B6 appears to have stronger influence on night awakenings reduction than melatonin only.
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[The effect of administration of dietary supplement with calcium and vitamins D3 and B6 on calcium homeostasis and falls incidence in patients with high fracture risk undergoing medical rehabilitation].
Marchenkova, LA, Fesyun, AD, Gerasimenko, MY, Makarova, EV
Voprosy pitaniia. 2020;(5):89-100
Abstract
Elimination of vitamin D and calcium deficiencies is of particular importance in older patients undergoing medical rehabilitation after a serious illness, surgery or injury and having a high risk of fractures. Preventing falls and fractures, including during the course of rehabilitation, is an important challenge that can be addressed in these patients, in particular through improved nutrition and vitamin D and calcium supplementation. The aim of the study was to evaluate the effect of long-term intake of a complex dietary supplement with calcium and vitamins D3 and B6 on calcium homeostasis and the frequency of falls in patients with high fracture risk undergoing medical rehabilitation. Material and methods. The study enrolled 109 women and 10 men (mean age 65.5±7.9 years) with high fracture risk who were undergoing medical rehabilitation. After baseline examination, 41 patients have been receiving antiresorptive therapy already comprised group 1, and patients who didn't receive osteoporotic therapy were randomized into groups 2 (n=39) and 3 (control, n=39). Patients in groups 1 and 2 for 12 months were prescribed a dietary supplement containing calcium in a daily dose of 200 mg (in the form of citrate 1000 mg), 600 IU of vitamin D3 and 2 mg of vitamin B6. All patients underwent assessment of bone mineral density (BMD), calculation of absolute 10-year fracture risk according to FRAX, assessment of food calcium intake, etermination of biochemical parameters of calcium-phosphorus metabolism and bone remodeling (total calcium, inorganic phosphorus, alkaline phosphatase activity - by colorimetric method in blood serum; immunoreactive parathyroid hormone (PTH) and osteocalcin - by electrochemiluminescence immunoassay in blood serum; β-isomer of C-terminal telopeptide of type I collagen (CTx) and 25(OH)D in blood plasma - by immunochemiluminescence analysis), cases of falls and fractures were fixed. Results. Average daily intake of calcium in the studied sample (n=119) was 782.9±243.4 mg, and 67.2% of patients consumed less than 800 mg of calcium daily. Vitamin D deficit was detected in 38.4% of the examined, its insufficiency - in 32.8%. An increase in 25(OH)D concentration was noted in groups 1 and 2 after 6 and 12 months (p<0.01), while in group 3 there was no dynamics of 25(OH)D (p>0.05). Patients in group 1 showed an increase in the level of osteocalcin and total calcium after 6 and 12 months, as well as alkaline phosphatase activity after 6 months (p<0.05). In group 3, there was an increase of PTH levels after 6 (p<0.05) and 12 months (p<0.01), CTx and alkaline phosphatase activity after 12 months (p<0.05). In group 1, there was an increase in BMD in the spine (+4.2%, p=0.024), femoral neck (+3.0%, p=0.041), and total femur (+2.7%, p=0.045), in patients of group 2 - an increase in BMD in the spine (+1.8%, p=0.048). In group 1, there was also a decrease in proportion of patients who fell after 6 months (χ2=4.97, p=0.026) and a decrease in the total number of falls after 12 months (χ2=4.89, p=0.027). Group 2 showed a decrease in the number of patients who fell after 6 and 12 months (χ2=48.58, p=0.0034 at both stages of the study) and the number of falls in general after 6 months (χ2=6.02, p=0.0142). Conclusion. The obtained data allow us to recommend prescription of dietary supplements containing calcium and vitamin D3 as a part of complex rehabilitation of patients with high fracture risk.
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Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort: The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study.
Minović, I, Kieneker, LM, Gansevoort, RT, Eggersdorfer, M, Touw, DJ, Voerman, AJ, Connelly, MA, Boer, RA, Hak, E, Bos, J, et al
Nutrients. 2020;(9)
Abstract
BACKGROUND a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation. METHODS we measured plasma pyridoxal 5'-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1-57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8-8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47-0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51-1.01) and 0.74 (95% confidence interval, 0.53-1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted Pinteraction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27-0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65-1.51). CONCLUSIONS in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women.