Satellite Cells Exhibit Decreased Numbers and Impaired Functions on Single Myofibers Isolated from Vitamin B6-Deficient Mice.

Emerging research in human studies suggests an association among vitamin B6, sarcopenia, and muscle strength. However, very little is known regarding its potential role at the cellular level, especially in muscle satellite cells. Therefore, to determine whether vitamin B6 affects the satellite cells, we isolated single myofibers from muscles of vitamin B6-deficient and vitamin B6-supplemented mice. Subsequently, we subjected them to single myofiber culture and observed the number and function of the satellite cells, which remained in their niche on the myofibers. Prior to culture, the vitamin B6-deficient myofibers exhibited a significantly lower number of quiescent satellite cells, as compared to that in the vitamin B6-supplemented myofibers, thereby suggesting that vitamin B6 deficiency induces a decline in the quiescent satellite cell pool in mouse muscles. After 48 and 72 h of culture, the number of proliferating satellite cells per cluster was similar between the vitamin B6-deficient and -supplemented myofibers, but their numbers decreased significantly after culturing the myofibers in vitamin B6-free medium. After 72 h of culture, the number of self-renewing satellite cells per cluster was significantly lower in the vitamin B6-deficient myofibers, and the vitamin B6-free medium further decreased this number. In conclusion, vitamin B6 deficiency appears to reduce the number of quiescent satellite cells and suppress the proliferation and self-renewal of satellite cells during myogenesis.

Depression and Vegetarians: Association between Dietary Vitamin B6, B12 and Folate Intake and Global and Subcortical Brain Volumes.

Deficiency of vitamin B6 and vitamin B12, mostly in vegetarians, is found to be associated with depression and adverse neurological function. We investigated whether vitamin B6, B12, and folate have an effect on brain structure, especially among depressed people who follow a specific diet. The study sample comprised 9426 participants from the UK Biobank cohort with a mean age of 62.4 years. A generalized linear model controlling for age, sex, body mass index, ethnicity, town send deprivation index, educational qualification, smoking, and alcohol intake was used to test the association between study groups and structural brain volumes. Depression was more prevalent, and intake of vitamin B6 and B12 was lower among vegetarians, while non-vegetarians had a lower intake of folate. Overall, no significant association was observed between vitamin B6, B12, and folate intakes and both global and subcortical brain volumes among participants with depression. However, vitamin B12 intake was positively associated with right pallidum among non-depressed participants, and a significant interaction between vitamin B12 intake and depression status on the right pallidum was observed. Also, a significant interaction between folate intake and depression status on grey matter (GM) volume and left thalamus was observed. Upon diet stratification, folate intake is associated with total brain volume and GM volume among vegetarians with depression. Furthermore, no significant associations were observed for subcortical regions. Our findings suggest that dietary intake of vitamin B6 and B12 might have an effect on brain structure. Vegetarians, particularly those who suffer from depression may benefit from supplementing their diets with vitamins B6, B12, and folate to ensure brain health. Further studies, especially with a larger sample size and longitudinal design, are needed to confirm these findings.

Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement.

BACKGROUND & AIM: Several studies explored the association of vitamin B6 intake with the risk of cancers. However, it is unclear whether different doses of vitamin B6 have distinct effects on the prognosis of nasopharyngeal carcinoma (NPC) patients. This study investigated the relationship between different doses of B6 intake and the prognosis of NPC patients. METHODS: This retrospective cohort analysis included 792 newly diagnosed NPC patients with a median follow-up of 62.05 months. Restricted cubic spline and maximally selected rank statistics were performed to determine the cut-off value of vitamin B6 during treatment (VB6DT). Kaplan-Meier method and log-rank tests were performed to analyze survival outcomes. A multivariable Cox proportional hazard model was performed to determine the independent prognostic factors. RESULTS: NPC patients were divided into three groups according to the cut-off value of VB6DT: non-users (0 mg/d), VB6DT > 8.6 mg/d, and VB6DT ≤ 8.6 mg/d. Patients with VB6DT > 8.6 mg/d had significantly lower 5-year overall survival (OS) (83.5% vs. 90.8%, p = 0.006), distant metastasis-free survival (DMFS) (83.5% vs. 91.0%, p = 0.004), and progression-free survival (PFS) (73.7% vs. 81.7%, p = 0.011) and slightly but not significantly lower 5-year local recurrence-free survival (LRFS) (87.7% vs. 90.7%, p = 0.214) than the non-users. Patients with VB6DT ≤ 8.6 mg/d had slightly but not significantly better 5-year OS (93.3% vs. 90.8%, p = 0.283) than the non-users, while all other primary endpoints were similar (p > 0.50). Multivariable analyses confirmed that VB6DT > 8.6 mg/d was an independent negative prognostic factor of OS (p = 0.010), DMFS (p = 0.017), and PFS (p = 0.030) but not of LRFS (p = 0.428). CONCLUSIONS: Excessive VB6DT higher than the cut-off value is an independent negative prognostic factor for NPC patients. Additionally, low dose intake improved OS only slightly but not significantly.

Gender Differences in the Associations of Plasma Pyridoxal 5'-Phosphate with Plasma Polyunsaturated Fatty Acids among US Young and Middle-Aged Adults: NHANES 2003-2004.

Vitamin B6-restricted diets and low plasma pyridoxal 5'-phosphate (PLP) status altered plasma polyunsaturated fatty acids (PUFA) compositions. Evidence suggests the role of gender in the metabolism of vitamin B6 and PUFA. However, no epidemiologic study examined the impact of gender on the relationship between vitamin B6 and PUFA status in adults. Thus, we investigated whether there were gender differences in the association of vitamin B6 intake and plasma PLP concentration with plasma PUFA concentrations and ratios (eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), EPA + DHA, EPA/AA, (EPA + DHA)/AA) in US young/middle-aged adults. In total, 864 participants (20-59 years; 484 men, 380 women) from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 were used for this cross-sectional study. Nutrient intakes were estimated from two 24 h recalls and supplement questionnaires; plasma PLP and PUFA were measured. Multivariate linear regression was utilized to obtain unstandardized (b) and standardized (ß) coefficients. Covariates included demographic, socioeconomic, dietary variables, physical activity level, cigarette smoking status, alcohol consumption, prescription medication use, and BMI. There were significant interactions between gender and PLP on EPA (P-interaction = 0.004), DHA (P-interaction = 0.020), EPA + DHA (P-interaction = 0.010), EPA/AA (P-interaction = 0.002), (EPA + DHA)/AA (P-interaction = 0.004), whereas no interaction between gender and B6 intake existed. In gender-stratified analyses, in men, PLP was positively associated with EPA (ß = 0.138, b = 0.104, p = 0.0004), DHA (ß = 0.101, b = 0.058, p = 0.036), EPA + DHA (ß = 0.125, b = 0.073, p = 0.005), EPA/AA (ß = 0.144, b = 0.099, p = 0.0002), (EPA + DHA)/AA (ß = 0.123, b = 0.068, p = 0.005). However, no associations between PLP and PUFA existed in women. In conclusion, gender differences were found in the relationships between plasma PLP and plasma EPA, DHA, EPA + DHA, EPA/AA, and (EPA + DHA)/AA, with significant direct associations in men only among US young/middle-aged adults.

Vitamin B-6 intake is related to physical performance in European older adults: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) study.

BACKGROUND: Maintenance of high physical performance during aging might be supported by an adequate dietary intake of niacin, vitamins B-6 and B-12, and folate because these B vitamins are involved in multiple processes related to muscle functioning. However, not much is known about the association between dietary intake of these B vitamins and physical performance. OBJECTIVES: The objectives of this study were to investigate the association between dietary intake of niacin, vitamins B-6 and B-12, and folate and physical performance in older adults and to explore mediation by niacin status and homocysteine concentrations. METHODS: We used baseline data from the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) trial, which included n = 1249 healthy older adults (aged 65-79 y) with complete data on dietary intake measured with 7-d food records and questionnaires on vitamin supplement use and physical performance measured with the short physical performance battery and handgrip dynamometry. Associations were assessed by adjusted linear mixed models. RESULTS: Intake of vitamin B-6 was related to lower chair rise test time [ß: -0.033 ± 0.016 s (log); P = 0.043]. Vitamin B-6 intake was also significantly associated with handgrip strength, but for this association, a significant interaction effect between vitamin B-6 intake and physical activity level was found. In participants with the lowest level of physical activity, higher intake of vitamin B-6 tended to be associated with greater handgrip strength (ß: 1.5 ± 0.8 kg; P = 0.051), whereas in participants in the highest quartile of physical activity, higher intake was associated with lower handgrip strength (ß: -1.4 ± 0.7 kg; P = 0.041). No evidence was found for an association between intake of niacin, vitamin B-12, or folate and physical performance or for mediation by niacin status or homocysteine concentrations. CONCLUSIONS: Vitamin B-6 intake was associated with better chair rise test time in a population of European healthy older adults and also with greater handgrip strength in participants with low physical activity only. Homocysteine concentrations did not mediate these associations. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

Ocoxin as a complement to first line treatments in cancer.

Chemotherapy and radiotherapy are the most frequent treatment for patients suffering from malignant progression of cancer. Even though new treatments are now being implemented, administration of these chemotherapeutic agents remains as the first line option in many tumor types. However, the secondary effects of these compounds represent one of the main reasons cancer patients lose life quality during disease progression. Recent data suggests that Ocoxin, a plant extract and natural compound based nutritional complement rich in antioxidants and anti-inflammatory mediators exerts a positive effect in patients receiving chemotherapy and radiotherapy. This mixture attenuates the chemotherapy and radiotherapy-related side effects such as radiation-induced skin burns and mucositis, chemotherapy-related diarrhea, hepatic toxicity and blood-infection. Moreover, it has been proven to be effective as anticancer agent in different tumor models both in vitro and in vivo, potentiating the cytotoxic effect of several chemotherapy compounds such as Lapatinib, Gemcitabine, Paclitaxel, Sorafenib and Irinotecan. The aim of this review is to put some light on the potential of this nutritional mixture as an anticancer agent and complement for the standard chemotherapy routine.

[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].

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; ß-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.

Depressive Symptoms in Middle-Aged and Elderly Women Are Associated with a Low Intake of Vitamin B6: A Cross-Sectional Study.

This study investigated the nutritional factors that are associated with anxiety and depressive symptoms in Japanese middle-aged and elderly women. We conducted a cross-sectional study with 289 study participants aged ≥40 years (mean age = 52.0 ± 6.9 years). Their dietary habits, menopausal status and symptoms, and varied background factors, such as body composition, lifestyle factors, and cardiovascular parameters, were assessed. Their anxiety and depressive symptoms were evaluated using the Hospital Anxiety and Depression Scale (HADS), where scores of 0-7 points, 8-10 points, and 11-21 points on either the anxiety or depression subscales were categorized as mild, moderate, and severe, respectively. The dietary consumption of nutrients was assessed using a brief self-administered diet history questionnaire. The relationships between the moderate-to-severe anxiety/depressive symptoms and the dietary intake of 43 major nutrients were investigated using multivariate logistic regression analyses. After adjusting for age, menopausal status, and the background factors that were significantly related to depressive symptoms, moderate and severe depression was significantly inversely associated with only vitamin B6 (adjusted odds ratio per 10 µg/MJ in vitamin B6 intake = 0.89, 95% confidence interval = 0.80-0.99). A higher intake of vitamin B6 could help relieve depressive symptoms for this population.

Impact of magnesium supplementation, in combination with vitamin B6, on stress and magnesium status: secondary data from a randomized controlled trial.

Primary findings from a recent study reported that magnesium supplementation significantly reduced stress in severely stressed subjects with low magnesemia, and additional vitamin B6 enhanced this effect. The mechanism by which combining magnesium and vitamin B6 leads to reduced stress in these subjects remains to be elucidated. This secondary analysis investigated the impact of magnesium and vitamin B6 supplementation and perceived stress on erythrocyte magnesium levels, as a marker of body magnesium status. This was a secondary analysis from an 8-week randomized controlled trial comparing oral magnesium (300 mg) and magnesium-vitamin B6 (300 mg + 30 mg) supplementation. Stress level and erythrocyte magnesium level at baseline, and change in erythrocyte magnesium and serum vitamin B6 levels at weeks 4 and 8, were analyzed. Overall, 264 subjects were randomized to treatment and had evaluable Depression Anxiety Stress Scale scores (132 in each treatment arm). At baseline, stress scores, and mean serum magnesium, erythrocyte magnesium, and serum vitamin B6 concentrations were similar between arms. Although not significant between groups, a significant increase over time in erythrocyte magnesium levels was observed in the subgroup of subjects with low baseline erythrocyte magnesium levels (<1.6 mmol/L) following treatment with magnesium and magnesium-vitamin B6 (week 4:0.21 mmol/L [95% confidence interval (CI), 0.10 to 0.31], p = 0.0003; and 0.13 mmol/L [95% CI, 0.02 to 0.23], p = 0.0233, respectively). Change from baseline in circulating vitamin B6 levels at weeks 4 and 8 in the magnesium-vitamin B6 supplemented group (314.96 nmol/L [95%CI, 294.61 to 335.31]) was significantly different (p < 0.0001) compared with the magnesium supplemented group (-0.39 nmol/L [95% CI, -20.73 to 19.94]). Magnesium alone and magnesium-vitamin B6 provided statistically significant increases in erythrocyte magnesium in subjects with low magnesium status (<1.6mmol/L). Vitamin B6 supplementation did not further increase magnesium levels.

Effect of sodium cantharidinate/vitamin B6 injection on survival, liver function, immune function, and quality of life in patients with hepatocellular carcinoma: Protocol for a meta-analysis.

BACKGROUND: Sodium cantharidinate/vitamin B6 (SC/VB6) injection, a famous insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy of SC/VB6 injection on survival, liver function, immune function, and quality of life (QoL) in patients with HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of SC/VB6 for patients with HCC were searched from ten electronic databases including PubMed, Google Scholar, Cochrane Library, Excerpt Medica Database (Embase), Medline, Web of Science (WOS), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ), and Wanfang Database. Papers in Chinese or English published from January 2000 to July 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall survival (OS), QoL, liver function, immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the clinical trials was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of SC/VB6 on survival, liver function, immune function, and QoL in patients with HCC. INPLASY REGISTRATION NUMBER: INPLASY202070121.

Riboflavin Is an Important Determinant of Vitamin B-6 Status in Healthy Adults.

BACKGROUND: Riboflavin is required to generate the active form of vitamin B-6 (pyridoxal 5'-phosphate; PLP) in tissues, but the relevance of this metabolic interaction for nutritional status of vitamin B-6 is unclear because riboflavin biomarkers are rarely measured in human studies. OBJECTIVES: The purpose of this study was to identify the determinants of biomarkers of vitamin B-6 and riboflavin status and to examine the relationship between these nutrients in healthy adults. METHODS: Multiple linear regression was performed on observational data in 407 healthy adults aged 18-92 y who did not use B-vitamin supplements. Vitamin B-6 status was assessed by plasma PLP concentrations and erythrocyte glutathione reductase activation coefficient (EGRac) was used as a functional indicator of riboflavin status. RESULTS: Dietary intakes of vitamin B-6 and riboflavin were below the average requirements in 10% and 29% of participants, respectively. Suboptimal status of vitamin B-6 (PLP ≤30.0 nmol/L) was more prevalent in adults aged ≥60 y than in younger participants (i.e., 14% compared with 5%), whereas a high proportion (i.e., overall 37%) of both age groups had deficient riboflavin status (EGRac ≥1.40). In multiple regression analysis, EGRac (P = 0.019) was a significant determinant of plasma PLP, along with dietary vitamin B-6 intake (P = 0.003), age (P < 0.001), BMI (kg/m2) (P = 0.031), and methylenetetrahydrofolate reductase gene (MTHFR) genotype (P < 0.001). Significant determinants of EGRac were dietary riboflavin intake (P < 0.001), age (P < 0.001) and MTHFR genotype (P = 0.020). Plasma PLP showed a stepwise decrease across riboflavin status categories from optimal (EGRac ≤1.26) to low (EGRac 1.27-1.39) to deficient status (P = 0.001), independent of dietary vitamin B-6 intake. CONCLUSIONS: The findings are consistent with the known metabolic dependency of vitamin B-6 on riboflavin status and indicate that riboflavin may be the limiting nutrient, particularly in older people, for maintaining adequate vitamin B-6 status.

Oral Nutritional Supplementation Affects the Dietary Intake and Body Weight of Head and Neck Cancer Patients during (Chemo) Radiotherapy.

Considering the symptoms of (chemo) radiotherapy and the reduction in food intake in head and neck cancer (HNC) patients, this study aimed to investigate the association between treatment time points and oral nutritional supplementation (ONS) on dietary intake to estimate the frequency of energy and nutrient inadequacy, and also to evaluate body weight changes (BWC). Dietary intake data of 65 patients were obtained from 24-h dietary recalls and prevalence of inadequacy was calculated before or at the beginning (T0), in the middle (T1), and at the end of treatment (T2). BWC were calculated as the weight difference considering the previous weight reported and/or measured. Energy and macronutrient intake decreased in T1 and then improved in T2 (p < 0.001 for both). Micronutrient intake increased during treatment due to ONS use, but still presented a high probability of inadequate intake. In particular, calcium, magnesium, and vitamin B6 showed almost 100% of probability of inadequacy for those who did not use ONS. Finally, overweight patients suffered a higher weight accumulated deficit with a delta of -15 kg compared to other BMI (body mass index) categories. Therefore, we strongly recommend initiating nutritional counseling in conjunction with prophylactic ONS prescription from diagnosis to adjust nutrient intake and minimize weight loss.

Intakes of Folate, Vitamin B6, and Vitamin B12 in Relation to Diabetes Incidence Among American Young Adults: A 30-Year Follow-up Study.

OBJECTIVE: To prospectively examine intakes of folate, vitamin B6, and vitamin B12 in relation to diabetes incidence in a large U.S. cohort. RESEARCH DESIGN AND METHODS: A total of 4,704 American adults aged 18-30 years and without diabetes were enrolled in 1985-1986 and monitored until 2015-2016 in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Dietary assessment was conducted by a validated dietary history questionnaire at baseline, in 1992-1993, and in 2005-2006. The cumulative average intakes of folate, vitamin B6, and vitamin B12 were used in the analyses. Incident diabetes was ascertained by plasma glucose levels, oral glucose tolerance tests, hemoglobin A1c concentrations, and/or antidiabetic medications. RESULTS: During 30 years (mean 20.5 ± 8.9) of follow-up, 655 incident cases of diabetes occurred. Intake of folate, but not vitamin B6 or vitamin B12, was inversely associated with diabetes incidence after adjustment for potential confounders. Compared with the lowest quintile of total folate intake, the multivariable-adjusted hazard ratios (95% CI) in quintiles 2-5 were 0.85 (0.67-1.08), 0.78 (0.60-1.02), 0.82 (0.62-1.09), and 0.70 (0.51-0.97; P trend = 0.02). Higher folate intake was also associated with lower plasma homocysteine (P trend < 0.01) and insulin (P trend < 0.01). Among supplement users, folate intake was inversely associated with serum C-reactive protein levels (P trend < 0.01). CONCLUSIONS: Intake of folate in young adulthood was inversely associated with diabetes incidence in midlife among Americans. The observed association may be partially explained by mechanisms related to homocysteine level, insulin sensitivity, and systemic inflammation.

High-dose vitamin B supplementation for persistent visual deficit in multiple sclerosis: a pilot study.

The aim of this study is to investigate the potential neuroprotective effect of high-doses vitamins B1, B6 and B12 in patients with relapsing-remitting multiple sclerosis (RRMS) and persistent visual loss after acute optic neuritis (AON). Sixteen patients (20 eyes) diagnosed with RRMS and visual permanent disability following AON were enrolled for the present open, pilot study. Each patient was treated with oral high-doses 300 mg of vitamin B1, 450 mg of vitamin B6 and 1,500 mcg of vitamin B12, as add-on treatment to concomitant disease-modifying therapies (DMTs) for consecutive 90 days. Outcome measures were to determine changes from baseline to month three in visual acuity (VA) and visual field (VF) testing, with correlations with clinical parameters. Logistical regression was performed to evaluate predictors of final VA. A statistically significant improvement was registered in visual acuity (p = 0.002) and foveal sensitivity threshold (FT) (p = 0.006) at follow-up compared to baseline. A similar trend was demonstrated for mean deviation (MD) (p < 0.0001), and pattern standard deviation (PSD) (p < 0.0001). Age at the time of inclusion was positively correlated with latency time (rho = 0.47, p = 0.03), while showing a negative correlation with visual acuity (rho = - 0.45, p = 0.04) and foveal sensitivity threshold (rho = - 0.6, p = 0.005) at follow up. A statistically significant correlation was demonstrated between foveal sensitivity threshold and visual acuity at baseline (rho = 0.79, p < 0.0001). In a linear regression model, the main predictor of visual acuity at follow up was the foveal sensitivity threshold (B = 1.39; p < 0.0001). Supplemental high-dose vitamins B1, B6 and B12 resulted as effective therapy to improve visual function parameters in MS-related visual persistent disability.

Impact of Glutathione and Vitamin B-6 in Cirrhosis Patients: A Randomized Controlled Trial and Follow-Up Study.

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.

Mineral Intake and Clinical Symptoms in Adult Patients with Hypophosphatasia.

BACKGROUND: Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by deficient activity of the tissue-nonspecific alkaline phosphatase entailing impaired turnover of phosphorus metabolites. Dietary mineral intake is suspected to influence clinical symptoms of HPP, but scientific evidence is missing. METHODS: Cross-sectional matched-pairs study collecting comprehensive data on nutrient intake in 20 HPP patients and 20 unaffected, age- and gender-matched controls. Dietary information and clinical symptoms were documented in detail over 7 consecutive days using structured diaries. RESULTS: Baseline data and type of energy-supplying nutrients were balanced between both groups. Median nutritional intake of phosphorus and calcium were significantly lower in HPP patients versus controls, which is partially attributable to lower energy consumption in HPP patients. Differences regarding phosphorus and calcium (Ca/P) ratio and uptake of magnesium, zinc, and vitamin B6 were not statistically significant. Both high (≥ 1375 mg/d) and low intakes (< 1100 mg/d) of phosphorus were significantly associated with an increased frequency of neuropsychiatric symptoms (P = 0.02). Similarly, very high and very low intake of calcium was significantly associated with musculoskeletal (P < 0.01), gastrointestinal (P = 0.02), and neuropsychiatric (P < 0.001) symptoms. An increased Ca/P ratio was associated with increased tiredness/fatigue (P < 0.01), whereas a decreased Ca/P was associated with gastrointestinal issues (P = 0.01). CONCLUSION: Phosphorus and calcium intake seem reduced in HPP patients along with reduced total energy consumption. Particularly high as well as very low absolute or unbalanced phosphorus and calcium intake are associated with an increased frequency of clinical symptoms.

Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery.

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.

Older adults with obesity have higher risks of some micronutrient inadequacies and lower overall dietary quality compared to peers with a healthy weight, National Health and Nutrition Examination Surveys (NHANES), 2011-2014.

OBJECTIVE: To evaluate total usual intakes and biomarkers of micronutrients, overall dietary quality and related health characteristics of US older adults who were overweight or obese compared with a healthy weight. DESIGN: Cross-sectional study. SETTING: Two 24-h dietary recalls, nutritional biomarkers and objective and subjective health characteristic data were analysed from the National Health and Nutrition Examination Survey 2011-2014. We used the National Cancer Institute method to estimate distributions of total usual intakes from foods and dietary supplements for eleven micronutrients of potential concern and the Healthy Eating Index (HEI)-2015 score. PARTICIPANTS: Older adults aged ≥60 years (n 2969) were categorised by sex and body weight status, using standard BMI categories. Underweight individuals (n 47) were excluded due to small sample size. RESULTS: A greater percentage of obese older adults compared with their healthy-weight counterparts was at risk of inadequate Mg (both sexes), Ca, vitamin B6 and vitamin D (women only) intakes. The proportion of those with serum 25-hydroxyvitamin D < 40 nmol/l was higher in obese (12 %) than in healthy-weight older women (6 %). Mean overall HEI-2015 scores were 8·6 (men) and 7·1 (women) points lower in obese than in healthy-weight older adults. In addition, compared with healthy-weight counterparts, obese older adults were more likely to self-report fair/poor health, use ≥ 5 medications and have limitations in activities of daily living and cardio-metabolic risk factors; and obese older women were more likely to be food-insecure and have depression. CONCLUSIONS: Our findings suggest that obesity may coexist with micronutrient inadequacy in older adults, especially among women.

One-carbon metabolism-related micronutrients intake and risk for hepatocellular carcinoma: A prospective cohort study.

Deficient intake of micronutrients involved in one-carbon metabolism (eg, choline, methionine, vitamin B12 and folic acid) leads to hepatocellular carcinoma (HCC) development in rodents, but is under-investigated in humans. We investigated the association between one-carbon metabolism-related micronutrient intake and HCC risk in a prospective cohort of 494 860 participants with 16 years of follow-up in the NIH-AARP study. Dietary intakes and supplement use were ascertained at baseline using a food-frequency questionnaire. Total intake (diet plus supplements) of the following one-carbon metabolism-related micronutrients were calculated: folate, methionine and vitamins B2 (riboflavin), B3 (niacin), B6 and B12 . These micronutrients were examined both individually and simultaneously, with adjustment for covariates. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over the 16-year follow-up period, 647 incident HCC cases were diagnosed. When examined individually, higher total vitamin B3 intake was associated with a lower HCC risk (HRQ5 vs Q1 = 0.60; 95% CI = 0.42-0.85; Ptrend = .008), and the association remained significant when all six micronutrients were examined simultaneously (HRQ5 vs Q1 = 0.32; 95% CI = 0.18-0.55; Ptrend < .0001). Among participants with >3 years of follow-up, higher total vitamin B3 intake was again associated with lower risk (HRQ5 vs Q1 = 0.37; 95% CI = 0.20-0.68; Ptrend = .001), whereas higher total vitamin B6 intake was associated with higher risk (HRQ5 vs Q1 = 2.04; 95% CI = 1.02-4.07; Ptrend = .04). Restricted cubic spline analyses showed a dose-response inverse association between total vitamin B3 intake and HCC risk, and dose-response positive association between total vitamin B6 intake and HCC risk. The study suggests that higher vitamin B3 intake is associated with lower HCC risk, whereas higher vitamin B6 intake is associated with increased risk.

Responsiveness of sphingosine phosphate lyase insufficiency syndrome to vitamin B6 cofactor supplementation.

Sphingosine-1-phosphate (S1P) lyase is a vitamin B6-dependent enzyme that degrades sphingosine-1-phosphate in the final step of sphingolipid metabolism. In 2017, a new inherited disorder was described caused by mutations in SGPL1, which encodes sphingosine phosphate lyase (SPL). This condition is referred to as SPL insufficiency syndrome (SPLIS) or alternatively as nephrotic syndrome type 14 (NPHS14). Patients with SPLIS exhibit lymphopenia, nephrosis, adrenal insufficiency, and/or neurological defects. No targeted therapy for SPLIS has been reported. Vitamin B6 supplementation has therapeutic activity in some genetic diseases involving B6-dependent enzymes, a finding ascribed largely to the vitamin's chaperone function. We investigated whether B6 supplementation might have activity in SPLIS patients. We retrospectively monitored responses of disease biomarkers in patients supplemented with B6 and measured SPL activity and sphingolipids in B6-treated patient-derived fibroblasts. In two patients, disease biomarkers responded to B6 supplementation. S1P abundance and activity levels increased and sphingolipids decreased in response to B6. One responsive patient is homozygous for an SPL R222Q variant present in almost 30% of SPLIS patients. Molecular modeling suggests the variant distorts the dimer interface which could be overcome by cofactor supplementation. We demonstrate the first potential targeted therapy for SPLIS and suggest that 30% of SPLIS patients might respond to cofactor supplementation.