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The B-vitamins comprise a group of eight water soluble vitamins that perform essential, closely inter-related roles in cellular functioning, acting as co-enzymes in a vast array of catabolic and anabolic enzymatic reactions. Their collective effects are particularly prevalent to numerous aspects of brain function, including energy production, DNA/RNA synthesis/repair, genomic and non-genomic methylation, and the synthesis of numerous neurochemicals and signaling molecules. However, human epidemiological and controlled trial investigations, and the resultant scientific commentary, have focused almost exclusively on the small sub-set of vitamins (B9/B12/B6) that are the most prominent (but not the exclusive) B-vitamins involved in homocysteine metabolism. Scant regard has been paid to the other B vitamins. This review describes the closely inter-related functions of the eight B-vitamins and marshals evidence suggesting that adequate levels of all members of this group of micronutrients are essential for optimal physiological and neurological functioning. Furthermore, evidence from human research clearly shows both that a significant proportion of the populations of developed countries suffer from deficiencies or insufficiencies in one or more of this group of vitamins, and that, in the absence of an optimal diet, administration of the entire B-vitamin group, rather than a small sub-set, at doses greatly in excess of the current governmental recommendations, would be a rational approach for preserving brain health.

Background Vitamin B deficiency and elevated total plasma homocysteine have been associated with cognitive impairment and dementia in later life, although it is unknown if treatment with these vitamins improves cognitive outcomes. Objectives The objectives of this study were to examine the efficacy of treatment with vitamin B 12 , vitamin B 6 , or folic acid in slowing cognitive decline amongst older adults with and without cognitive impairment. Methods We summarized findings from previous systematic reviews of clinical trials and performed a new systematic review and meta-analysis of 31 English-language, randomized placebo-controlled trials of B-vitamin supplementation of individuals with and without existing cognitive impairment. Results Previous reviews have generally reported no effect of B vitamins on cognitive function in older adults with or without cognitive impairment at study entry, although these vitamins effectively lowered total plasma homocysteine levels in participants. Ten randomized placebo-controlled trials of 1925 participants with pre-existing cognitive impairment and 21 trials of 15,104 participants without cognitive impairment have been completed to date but these generally confirmed findings from previous reviews with the exception of two trials that showed a modest but clinically uncertain benefit for vitamins in people with elevated plasma homocysteine. B-vitamin supplementation did not show an improvement in Mini-Mental State Examination scores for individuals with (mean difference 0.16, 95% confidence interval − 0.18 to 0.51) and without (mean difference 0.04, 95% confidence interval − 0.10 to 0.18) cognitive impairment compared to placebo. Conclusions Raised total plasma homocysteine is associated with an increased risk of cognitive impairment and dementia, although available evidence from randomized controlled trials shows no obvious cognitive benefit of lowering homocysteine using B vitamins. Existing trials vary greatly in the type of supplementation, population sampled, study quality, and duration of treatment, thereby making it difficult to draw firm conclusions from existing data. Findings should therefore be viewed in the context of the limitations of the available data and the lack of evidence of effect should not necessarily be interpreted as evidence of no effect.

The triage theory posits that modest micronutrient deficiencies may induce reallocation of nutrients to processes necessary for immediate survival at the expense of long-term health. Neglected processes could in time contribute to the onset of age-related diseases, in which oxidative stress is believed to be a major factor. Vitamin B (B12) appears to possess antioxidant properties. This review aims to summarise the potential antioxidant mechanisms of B12 and investigate B12 status in relation to oxidative stress markers. A systematic query-based search of PubMed was performed to identify eligible publications. The potential antioxidant properties of B12 include: (1) direct scavenging of reactive oxygen species (ROS), particularly superoxide; (2) indirect stimulation of ROS scavenging by preservation of glutathione; (3) modulation of cytokine and growth factor production to offer protection from immune response-induced oxidative stress; (4) reduction of homocysteine-induced oxidative stress; and (5) reduction of oxidative stress caused by advanced glycation end products. Some evidence appears to suggest that lower B12 status is related to increased pro-oxidant and decreased antioxidant status, both overall and for subclinically deficient individuals compared to those with normal B12 status. However, there is a lack of randomised controlled trials and prospective studies focusing specifically on the relation between B12 and oxidative stress in humans, resulting in a low strength of evidence. Further work is warranted.

B group vitamins represent essential micronutrients for myriad metabolic and regulatory processes required for human health, serving as cofactors used by hundreds of enzymes that carry out essential functions such as energy metabolism, DNA and protein synthesis and other critical functions. B vitamins and their corresponding vitamers are universally essential for all cellular life forms, from bacteria to humans. Humans are unable to synthesize most B vitamins and are therefore dependent on their diet for these essential micronutrients. More recently, another source of B vitamins has been identified which is derived from portions of the 1013 bacterial cells inhabiting the gastrointestinal tract. Here we review the expanding literature examining the relationship between B vitamins and the immune system and diverse cancers. Evidence of B vitamin’s role in immune cell regulation has accumulated in recent years and may help to clarify the disparate findings of numerous studies attempting to link B vitamins to cancer development. Much work remains to be carried out to fully clarify these relationships as the complexity of B vitamins’ essential functions complicates an unequivocal assessment of their beneficial or detrimental effects in inflammation and cancers.

There is an unmet need to develop therapeutic interventions directed at the neurodegeneration that underlies progression in multiple sclerosis. High-dose, pharmaceutical-grade biotin (MD1003) might enhance neuronal and oligodendrocyte energetics, resulting in improved cell function, repair, or survival. The MS-SPI randomised, double-blind, placebo-controlled study found that MD1003 improved disability outcomes over 12 months in patients with progressive multiple sclerosis. The SPI2 study was designed to assess the safety and efficacy of MD1003 in progressive forms of multiple sclerosis in a larger, more representative patient cohort. SPI2 was a randomised, double-blind, parallel-group, placebo-controlled trial done at 90 academic and community multiple sclerosis clinics across 13 countries. Patients were aged 18–65 years, had a diagnosis of primary or secondary progressive multiple sclerosis fulfilling the revised International Panel criteria and Lublin criteria, a Kurtzke pyramidal functional subscore of at least 2 (defined as minimal disability), an expanded disability status scale (EDSS) score of 3·5–6·5, a timed 25-foot walk (TW25) of less than 40 s, evidence of clinical disability progression, and no relapses in the 2 years before enrolment. Concomitant disease-modifying therapies were allowed. Patients were randomly assigned (1:1) by an independent statistician using an interactive web response system, with stratification by study site and disease history, to receive MD1003 (oral biotin 100 mg three times daily) or placebo. Participants, investigators, and assessors were masked to treatment assignment. The primary endpoint was a composite of the proportion of participants with confirmed improvement in EDSS or TW25 at month 12, confirmed at month 15, versus baseline. The primary endpoint was assessed in the intention-to-treat analysis set, after all participants completed the month 15 visit. Safety analyses included all participants who received at least one dose of MD1003. This trial is registered with ClinicalTrials.gov (NCT02936037) and the EudraCT database (2016-000700-29). From Feb 22, 2017, to June 8, 2018, 642 participants were randomly assigned MD1003 (n=326) or placebo (n=316). The double-blind, placebo-controlled phase of the study ended when the primary endpoint for the last-entered participant was assessed on Nov 15, 2019. The mean time in the placebo-controlled phase was 20·1 months (SD 5·3; range 15–27). For the primary outcome, 39 (12%) of 326 patients in the MD1003 group compared with 29 (9%) of 316 in the placebo group improved at month 12, with confirmation at month 15 (odds ratio 1·35 [95% CI 0·81–2·26]). Treatment-emergent adverse events occurred in 277 (84%) of 331 participants in the MD1003 group and in 264 (85%) of 311 in the placebo group. 87 (26%) of 331 participants in the MD1003 group and 82 (26%) of 311 participants in the placebo group had at least one serious treatment-emergent adverse event. One (<1%) person died in the MD1003 group and there were no deaths in the placebo group. Despite use of mitigation strategies, MD1003 led to inaccurate laboratory results for tests using biotinylated antibodies. This study showed that MD1003 did not significantly improve disability or walking speed in patients with progressive multiple sclerosis and thus, in addition to the potential of MD1003 for deleterious health consequences from interference of laboratory tests, MD1003 cannot be recommended for treatment of progressive multiple sclerosis. MedDay Pharmaceuticals.

Water-soluble B vitamins, mainly obtained through dietary intake of fruits, vegetables, grains, and dairy products, act as co-factors in various biochemical processes, including DNA synthesis, repair, methylation, and energy metabolism. These vitamins include B1 (Thiamine), B2 (Riboflavin), B3 (Niacin), B5 (Pantothenic Acid), B6 (Pyridoxine), B7 (Biotin), B9 (Folate), and B12 (Cobalamin). Recent studies have shown that besides their fundamental physiological roles, B vitamins influence oncogenic metabolic pathways, including glycolysis (Warburg effect), mitochondrial function, and nucleotide biosynthesis. Although deficiencies in these vitamins are associated with several complications, emerging evidence suggests that excessive intake of specific B vitamins may also contribute to cancer progression and interfere with therapy due to impaired metabolic and genetic functions. This review discusses the tumor-suppressive and tumor-progressive roles of B vitamins in cancer. It also explores the recent evidence on a comprehensive understanding of the relationship between B vitamin metabolism and cancer progression and underscores the need for further research to determine the optimal balance of B vitamin intake for cancer prevention and therapy.

B vitamin therapy lowers plasma total homocysteine concentrations, and might be a beneficial intervention for stroke prevention; however, cyanocobalamin (a form of vitamin B12) can accelerate decline in renal function and increase the risk of cardiovascular events in patients with impaired renal function. Although early trials did not show benefit in reduction of stroke, these results might have been due to harm in participants with impaired renal function. In patients with diabetic nephropathy, cyanocobalamin is harmful, whereas B vitamins appear to reduce cardiovascular events in study participants with normal renal function. Our meta-analysis of individual patient data from two large trials of B vitamin therapy (VISP and VITATOPS) indicates that patients with impaired renal function who are exposed to high-dose cyanocobalamin do not benefit from therapy with B vitamins for the prevention of stroke (risk ratio 1·04, 95% CI 0·84–1·27), however, patients with normal renal function who are not exposed to high-dose cyanocobalamin benefit significantly from this treatment (0.78, 0·67–0·90; interaction p=0·03). The potential benefits of B vitamin therapy with folic acid and methylcobalamin or hydroxycobalamin, instead of cyanocobalamin, to lower homocysteine concentrations in people at high risk of stroke warrant further investigation.

Is it possible to prevent atrophy of key brain regions related to cognitive decline and Alzheimer’s disease (AD)? One approach is to modify nongenetic risk factors, for instance by lowering elevated plasma homocysteine using B vitamins. In an initial, randomized controlled study on elderly subjects with increased dementia risk (mild cognitive impairment according to 2004 Petersen criteria), we showed that high-dose B-vitamin treatment (folic acid 0.8 mg, vitamin B6 20 mg, vitamin B12 0.5 mg) slowed shrinkage of the whole brain volume over 2 y. Here, we go further by demonstrating that B-vitamin treatment reduces, by as much as seven fold, the cerebral atrophy in those gray matter (GM) regions specifically vulnerable to the AD process, including the medial temporal lobe. In the placebo group, higher homocysteine levels at baseline are associated with faster GM atrophy, but this deleterious effect is largely prevented by B-vitamin treatment. We additionally show that the beneficial effect of B vitamins is confined to participants with high homocysteine (above the median, 11 µmol/L) and that, in these participants, a causal Bayesian network analysis indicates the following chain of events: B vitamins lower homocysteine, which directly leads to a decrease in GM atrophy, thereby slowing cognitive decline. Our results show that B-vitamin supplementation can slow the atrophy of specific brain regions that are a key component of the AD process and that are associated with cognitive decline. Further B-vitamin supplementation trials focusing on elderly subjets with high homocysteine levels are warranted to see if progression to dementia can be prevented.

ObjectivesGut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome’s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation.DesignWe performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice.ResultsSevere obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration.ConclusionStrategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity.Trial registration number NCT02059538.

This study aimed to evaluate the effects of systemic cholecalciferol (vitamin D3) and vitamin B complex (B1, B6, B12) on crush-injured mental nerve in rats using histopathological and immunohistochemical analyses to assess nerve degeneration and regeneration. Thirty-two Wistar Albino rats were subjected to standardized mental nerve crush injury using a Yasargil aneurysm clip and divided into four groups: Control /Sham (Group 1), B vitamin (intraperitoneal) (Group2), D vitamin (oral) (Group 3), and combined (B + D) (Group 4). After 4 weeks, nerve samples were excised for histopathological evaluation (ghost cell and hyperchromatic nuclei counts) and immunohistochemical analysis (S100β and BIII tubulin scores). Data were analyzed using Generalized Linear Models with Bonferroni post-hoc tests. Treatment groups showed significantly lower ghost cell counts (e.g., Group 3: 15.33 ± 3.50 vs. Control: 53.67 ± 9.63, p  < 0.001) and hyperchromatic nuclei counts (e.g., Group 4: 28.00 ± 5.40 vs. Control: 34.33 ± 4.37, p  = 0.004) compared to controls. Immunohistochemically, Group 4 exhibited significantly higher ßIII tubulin scores (3.17 ± 0.39 vs. Control: 1.75 ± 0.46, p  < 0.001), indicating enhanced axonal regeneration, while S100β scores were similar between Group 3 and 4 (1.83 ± 0.39, p  = 1.000). After a 4-week healing period, cholecalciferol and vitamin B complex, particularly in combination, significantly reduced axonal degeneration and promoted early nerve regeneration in a rat mental nerve injury model. These findings suggest potential as adjunctive therapies for nerve recovery in oral and maxillofacial surgery, pending clinical validation.