B Vitamins as Adjunctive Treatment for Chronic Heart Failure.

INTRODUCTION: Vitamin B deficiency causes cardiac hypertrophy, reduced cardiac contractility, and arrhythmias.The purpose of this study is to perform a network meta-analysis of randomized controlled trials of vitamin B supplements in a group of 150 patients who meet the eligibility criteria.The study also aims to describe the effect of synthetic multivitamins (pyridoxine, folic acid, and cyanocobalamin) on the laboratory findings reflecting the severity of chronic heart failure (cholesterol, glucose, and fibrinogen). METHODS: The experiment involved a group of people (150 individuals) diagnosed with chronic heart failure with reduced left ventricular ejection fraction. The study compared serum levels of B vitamins measured after the therapy and at baseline. The second part of the study focused on the assessment of the laboratory findings reflecting the severity of cardiovascular pathology and indicating an increased risk of vascular catastrophes. RESULTS: Clinical trials among patients diagnosed with chronic heart failure showed that the intake of synthetic forms of pyridoxine, folic acid, and cyanocobalamin slightly increases systolic, diastolic and central venous pressure while decreasing the heart rate and increasing LVEF. Thiamine acts as a vasodilator. It reduces the cardiac afterload and improves heart function. CONCLUSION: The results obtained can be useful in terms of improving the comprehensive treatment strategy for chronic heart failure and further investigation of the effects produced by the intake of B vitamins.

Dietary pattern, food, and nutritional supplement effects on cognitive outcomes in mild cognitive impairment: a systematic review of previous reviews.

CONTEXT: Nutritional interventions may benefit cognition in people with mild cognitive impairment (MCI). However, evidence is yet to be synthesized in a way that can inform recommendations for clinical and public health settings. OBJECTIVE: To systematically review evidence on the effect of dietary patterns, foods, and nutritional supplements on cognitive decline in individuals with MCI. DATA SOURCES: Guided by the Preferred Reporting items for Systematic Review and Meta-Analysis Protocols 2015 statement, the Medline, EMBASE, and CINAHL databases, the JBI Database of Systematic Reviews and Implementation Reports, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched (publication years 2005 to 2020). Included studies were English-language systematic reviews and meta-analyses of randomized controlled trials and cohort studies reporting on the effectiveness of nutritional interventions on cognition of individuals with MCI. DATA EXTRACTION: Two reviewers independently selected studies and extracted data on cognitive outcomes and adverse events. Review quality was assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews-2). Primary study overlap was managed following Cochrane Handbook guidelines. DATA ANALYSIS: Of the 6677 records retrieved, 20 reviews were included, which, in turn, reported on 43 randomized controlled trials and 1 cohort study that, together, addressed 18 nutritional interventions. Most reviews were limited by quality and the small number of primary studies with small sample sizes. Reviews were mostly positive for B vitamins, omega-3 fatty acids, and probiotics (including 12, 11 and 4 primary studies, respectively). Souvenaid and the Mediterranean diet reduced cognitive decline or Alzheimer's disease progression in single trials with <500 participants. Findings from studies with a small number of participants suggest vitamin D, a low-carbohydrate diet, medium-chain triglycerides, blueberries, grape juice, cocoa flavanols, and Brazil nuts may improve individual cognitive subdomains, but more studies are needed. CONCLUSIONS: Few nutritional interventions were found to convincingly improve cognition of individuals with MCI. More high-quality research in MCI populations is required to determine if nutritional treatments improve cognition and/or reduce progression to dementia. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework protocol identifier DOI:10.17605/OSF.IO/BEP2S.

B-vitamin supplementation on mitigating post-stroke cognition and neuropsychiatric sequelae: A randomized controlled trial.

BACKGROUND AND PURPOSE: A third of stroke patients suffer from post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. B-vitamin supplementation provides a possible safe and affordable treatment to mitigate post-stroke neuropsychiatric sequelae via reducing homocysteine levels. Our study aims to examine the effect of B-vitamin supplementation in the prevention of post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. Our secondary aims were to investigate associations between baseline factors and the three outcomes. METHODS: Patients were recruited as part of a Singaporean substudy of a randomized controlled trial that examined the effect of B-vitamin supplementation on recurrent cardiovascular events. Cognitive decline, depressive symptoms, and anxiety symptoms were assessed with neuropsychological assessments and Hospital Anxiety and Depression Scale 6 monthly. Cox regression analyses were performed to determine treatment efficacy. Logistic regression used to examine factors associated with cognitive decline, depressive symptoms, and anxiety symptoms. RESULTS: A total of 707 were included in the analyses. Survival and hazards ratio analysis showed no treatment effect of B-vitamins on cognitive decline, depressive symptoms, and anxiety symptoms. Cognitive decline was only associated with age. Depressive symptoms were associated with large anterior cerebral infarcts and hyperlipidemia. CONCLUSIONS: Our study showed no benefit of supplementation with B-vitamins for post-stroke cognitive decline, depressive symptoms, or anxiety symptoms. Depressive symptoms were associated with larger anterior cerebral infarcts, which may be reflective of the disability associated with larger infarcts.

The effects of multi-nutrient formulas containing a combination of n-3 PUFA and B vitamins on cognition in the older adult: a systematic review and meta-analysis.

There is now evidence to suggest that there may be an interaction between B vitamins and n-3 PUFA, with suggestions that increasing intake of both nutrients simultaneously may benefit cognition in older adults. The aim of this systematic review was to investigate whether supplementation with a combination of n-3 PUFA and B vitamins can prevent cognitive decline in older adults. Randomised controlled trials conducted in older adults that measured cognitive function were retrieved. The included trials provided a combination of n-3 PUFA and B vitamins alone, or in combination with other nutrients. Trials that provided n-3 PUFA alone and also measured B vitamin status or provided B vitamin supplementation alone and measured n-3 PUFA status were also included. The databases searched were The Cochrane Library, EMBASE, CINAHL, Scopus and MEDLINE. A total of 14 papers were included in the analysis (n 4913; age: 60-70 years; follow-up 24 weeks to 4 years). The meta-analysis results found a significant benefit of nutrient formulas, which included both n-3 PUFA and B vitamins alongside other nutrients, v. placebo on global cognition assessed using composite scores from a neuropsychological test battery (G = 0·23, P = 0·002), global cognition using single measures of cognition (G = 0·28, P = 0·004) and episodic memory (G = 0·32, P = 0·001). The results indicate that providing a combination of n-3 PUFA and B vitamins as part of a multi-nutrient formula benefits cognition in older adults v. a placebo, and the potential for an interaction between these key nutrients should be considered in future experimental work.

B Vitamins, Glucoronolactone and the Immune System: Bioavailability, Doses and Efficiency.

The present review deals with two main ingredients of energy/power drinks: B vitamins and glucuronolactone and their possible effect on the immune system. There is a strong relationship between the recommended daily dose of selected B vitamins and a functional immune system. Regarding specific B vitamins: (1) Riboflavin is necessary for the optimization of reactive oxygen species (ROS) in the fight against bacterial infections caused by Staphylococcus aureus and Listeria monocytogenes. (2) Niacin administered within normal doses to obese rats can change the phenotype of skeletal fibers, and thereby affect muscle metabolism. This metabolic phenotype induced by niacin treatment is also confirmed by stimulation of the expression of genes involved in the metabolism of free fatty acids (FFAs) and oxidative phosphorylation at this level. (3) Vitamin B5 effects depend primarily on the dose, thus large doses can cause diarrhea or functional disorders of the digestive tract whereas normal levels are effective in wound healing, liver detoxification, and joint health support. (4) High vitamin B6 concentrations (>2000 mg per day) have been shown to exert a significant negative impact on the dorsal root ganglia. Whereas, at doses of approximately 70 ng/mL, sensory symptoms were reported in 80% of cases. (5) Chronic increases in vitamin B12 have been associated with the increased incidence of solid cancers. Additionally, glucuronolactone, whose effects are not well known, represents a controversial compound. (6) Supplementing with D-glucarates, such as glucuronolactone, may help the body's natural defense system function better to inhibit different tumor promoters and carcinogens and their consequences. Cumulatively, the present review aims to evaluate the relationship between the selected B vitamins group, glucuronolactone, and the immune system and their associations to bioavailability, doses, and efficiency.

An unusual case of subacute combined degeneration due to nitrous oxide abuse, which relapsed after bariatric surgery: A case report.

RATIONALE: Several studies have reported subacute combined degeneration (SCD) induced by nitrous oxide (N2O) abuse. However, few studies have reported that N2O-induced SCD recurred because of sleeve gastrectomy after neurological symptoms improved. PATIENT CONCERNS: We report the case of an 18-year-old woman who developed paresthesia, weakness in 4 limbs, and an unstable gait after frequent, excessive N2O inhalation. DIAGNOSIS: The patient was diagnosed as having SCD. INTERVENTIONS AND OUTCOMES: Nineteen days after intravenous mecobalamin and supplementation with other kinds of vitamin B, her weakness and paresthesia resolved. However, 7 months after discharge, the patient experienced recurrence following sleeve gastrectomy. Blood biochemistry revealed low vitamin B12 levels. After a 22-day treatment, similar to the first hospitalization, her residual numbness and unsteady gait improved. LESSONS: This case highlights that patients, especially those at high risk of vitamin B12 deficiency, undergoing sleeve gastrectomy require careful nutritional follow-up and routine monitoring of micronutrients such as vitamin B12 and homocysteine. Continuous vigilance is essential for patients with common and rare neurological complications.

Effects of Wolbachia elimination and B-vitamin supplementation on bed bug development and reproduction.

Obligate blood feeders, such as Cimex lectularius (common bed bug), have symbiotic associations with nutritional endosymbionts that produce B-vitamins. To quantify the symbiont's contribution to host fitness in these obligate mutualisms, the symbiont must be eliminated and its absence rigorously confirmed. We developed and validated procedures for complete elimination of Wolbachia (Wb) in bed bugs and quantified development and reproduction in bed bugs with and without Wb and with and without B-vitamins supplementation. Aposymbiotic bed bugs had slower nymphal development, reduced adult survivorship, smaller adult size, fewer eggs per female, and lower hatch rate than bed bugs that harbored Wb. In aposymbiotic bed bugs that were fed B-vitamins-supplemented blood, nymph development time, adult survivorship and hatch rate recovered to control levels, but adult size and egg number only partially recovered. These results underscore the nutritional dependence of bed bugs on their Wb symbiont and suggest that Wb may provide additional nutritional benefits beyond the B-vitamin mix that we investigated.

Do B Vitamins Enhance the Effect of Omega-3 Polyunsaturated Fatty Acids on Cardiovascular Diseases? A Systematic Review of Clinical Trials.

Studies have suggested that B vitamins or omega-3 polyunsaturated fatty acids (PUFAs) may deter the development of cardiovascular disease (CVD). This systematic review aims to examine whether the combined supplementation of both B vitamins and omega-3 PUFAs could provide additional beneficial effects to prevent CVD beyond the effect of each supplement based on clinical trials published up to December 2021. The overall findings are inconsistent and inconclusive, yet the combined supplementation of these two nutrients may be more effective at reducing plasma homocysteine, triglyceride, and low-density lipoprotein-cholesterol than the individual components. The underlying mechanisms mainly include alleviating endothelial dysfunction, inhibiting atherosclerosis and lesion initiation, reducing oxidative stress, suppressing activation of pro-inflammatory cytokines, regulating endothelial nitric oxide synthase, and interfering with methylation of genes that promote atherogenesis. Although biologically plausible, the existing literature is insufficient to draw any firm conclusion regarding whether B vitamins can further enhance the potential beneficial effects of omega-3 PUFA intake on either primary or secondary prevention of CVD. The inconsistent findings may be largely explained by the methodological challenges. Therefore, well-designed high-quality trials that will use the combined supplementation of B vitamins and omega-3 PUFAs or dietary patterns rich in these two types of nutrients are warranted.

Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.

OBJECTIVES: Gut 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. DESIGN: We 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. RESULTS: Severe 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. CONCLUSION: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity. TRIAL REGISTRATION NUMBER: NCT02059538.

Adequate Intake and Supplementation of B Vitamins, in Particular Folic Acid, can Play a Protective Role in Bone Health.

In vitro and animal model studies have shown that vitamin B (VB) deficiency has negative consequences on bone as a result of direct or mediated activity of hyperhomocysteinemia. However, there are still no precise indications regarding a possible VB role in order to maintain bone health. So, the aim of this narrative review was to consider state of the art correlation between VB dietary intake, blood levels and supplementation and bone health (bone mineral density (BMD), bone turnover markers and fractures risk) in humans. This review includes 29 eligible studies. Considering VB blood levels, the 14 studies considered have shown that low serum folate can be a risk factor for reduced BMD and fractures in the elderly, particularly women; no independent association was found for other VB. Studies that evaluate the relationship between VB dietary intake and BMD are only 2; one, conducted on 1869 women, demonstrated a positive effect of folate intake on BMD. Another demonstrated a dose-dependent inverse relationship between vitamin B6 dietary intake and risk of hip fracture, but only for 35298 female participants. Regarding the relationship between BV supplementation and bone health (9 studies with only VB and 4 with other nutrients), all studies that considered patients with hyperhomocysteinemia or with low folate blood levels, are in agreement in demonstrating that folate supplementation (500mcg- 5mg) is useful in improving BMD. In conclusion, a request for folate and homocysteine blood levels in elderly patients with osteopenia/osteoporosis is mandatory. For patients with hyperhomocysteinemia or with low folate blood levels, folate supplementation (500mcg-5mg) is crucial.

The role of B vitamins in stroke prevention.

Elevated plasma levels of homocysteine (Hcy) are a recognized risk factor for stroke. This relationship represents one aspect of the debated `Hcy hypothesis'. Elevated Hcy may be an independent and treatable cause of atherosclerosis and thrombotic vascular diseases. Further observations indicate that proper dietary supplementation with B-vitamins decreases total plasma Hcy concentrations and may be an effective intervention for stroke prevention. Metabolic vitamin B12 deficiency is a nutritional determinant of total Hcy and stroke risk. Genetic factors may link B vitamins with stroke severity due to the impact on Hcy metabolism of polymorphism in the genes coding for methylenetetrahydrofolate reductase, methionine-synthase, methionine synthase reductase, and cystathionine ß-synthase. Several meta-analyses of large randomized controlled trials exist. However, they are not completely in agreement about B vitamins' role, particularly folic acid levels, vitamin B12, and B6, in lowering the homocysteine concentrations in people at high stroke risk. A very complex relationship exists between Hcy and B vitamins, and several factors appear to modify the preventive effects of B vitamins in stroke. This review highlights the regulating factors of the active role of B vitamins active in stroke prevention. Also, inputs for further large, well-designed studies, for specific, particularly sensitive subgroups are given.

Excess folic acid supplementation before and during pregnancy and lactation activates ß-catenin in the brain of male mouse offspring.

Folic acid (FA) supplementation in early pregnancy is recommended to protect against birth defects. But excess FA has exhibited neurodevelopmental toxicity. We previously reported that the mice treated with 2.5-fold the dietary requirement of FA one week before mating and throughout pregnancy and lactation displayed abnormal behaviors in the offspring. Here we found the levels of non-phosphorylated ß-catenin (active) were increased in the brains of weaning and adult FA-exposed offspring. Meanwhile, demethylation of protein phosphatase 2 A catalytic subunit (PP2Ac), which suppresses its enzyme activity in regulatory subunit dependent manner, was significantly inhibited. Among the upstream regulators of ß-catenin, PI3K/Akt/GSK-3ß but not Wnt signaling was stimulated in FA-exposed brains only at weaning. In mouse neuroblastoma N2a cells, knockdown of PP2Ac or leucine carboxyl methyltransferase-1 (LCMT-1), or overexpression of PP2Ac methylation-deficient mutant decreased ß-catenin dephosphorylation. These results suggest that excess FA may activate ß-catenin via suppressing PP2Ac demethylation, providing a novel mechanism for the influence of FA on neurodevelopment.

Effectiveness of B Vitamins and Their Interactions with Aspirin in Improving Cognitive Functioning in Older People with Mild Cognitive Impairment: Pooled Post-Hoc Analyses of Two Randomized Trials.

BACKGROUND AND OBJECTIVES: A randomized placebo-controlled trial found a significant negative interaction between aspirin and B vitamins in cognitive functioning in older people with mild cognitive impairment (MCI). To validate this finding, we pooled data of this trial with that of a similar B-vitamin trial (VITACOG) to examine the effectiveness of B vitamins and their interactions with aspirin in improving global cognitive functioning and slowing brain atrophy in older people with MCI. DESIGN: Pooled post-hoc analyses of two randomized placebo-controlled trials. PARTICIPANTS: In total, 545 older people with MCI were included in the study. INTERVENTION: Placebo or B-vitamin supplements (vitamin B12, folic acid with or without vitamin B6) for 24 months. MEASUREMENTS: The primary outcome was the Clinical Dementia Rating scale-global score (CDR-global). The secondary outcomes were CDR-sum of box score (CDR-SOB), memory Z-score, executive function Z-score, and whole brain atrophy rate. RESULTS: 71 (26.2%) and 83 (30.3%) subjects in the active and placebo group respectively were aspirin users. Overall, B vitamins reduced whole brain atrophy rate significantly (P = 0.003), but did not have significant effect on CDR-global, CDR-SOB, memory and executive function. Aspirin use had significant negative interaction effects on B vitamins in CDR-global and CDR-SOB (Beta = 0.993, P = 0.038, and Beta = 0.583, P = 0.009, respectively), but not in memory or executive function Z-scores. Among aspirin non-users, B-vitamin group subjects had more favourable changes in CDR-global and CDR-SOB (P = 0.019 and 0.057, respectively). B vitamins significantly slowed brain atrophy in aspirin non-users (P = 0.001), but not in aspirin users, though the interaction term was not significant (Beta = 0.192, P = 0.276). CONCLUSION: In older people with MCI, B vitamins had significantly favourable effects on global cognitive functioning and whole brain atrophy rate in those who were not taking aspirin, but not in aspirin users.

Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells.

Nicotinamide, the amide form of Vitamin B3, is a common nutrient supplement that plays important role in human fetal development. Nicotinamide has been widely used in clinical treatments, including the treatment of diseases during pregnancy. However, its impacts during embryogenesis have not been fully understood. In this study, we show that nicotinamide plays multiplex roles in mesoderm differentiation of human embryonic stem cells (hESCs). Nicotinamide promotes cardiomyocyte fate from mesoderm progenitor cells, and suppresses the emergence of other cell types. Independent of its functions in PARP and Sirtuin pathways, nicotinamide modulates differentiation through kinase inhibition. A KINOMEscan assay identifies 14 novel nicotinamide targets among 468 kinase candidates. We demonstrate that nicotinamide promotes cardiomyocyte differentiation through p38 MAP kinase inhibition. Furthermore, we show that nicotinamide enhances cardiomyocyte survival as a Rho-associated protein kinase (ROCK) inhibitor. This study reveals nicotinamide as a pleiotropic molecule that promotes the derivation and survival of cardiomyocytes, and it could become a useful tool for cardiomyocyte production for regenerative medicine. It also provides a theoretical foundation for physicians when nicotinamide is considered for treatments for pregnant women.

B Vitamins Supplementation Can Improve Cognitive Functions and May Relate to the Enhancement of Transketolase Activity in A Rat Model of Cognitive Impairment Associated with High-fat Diets.

OBJECTIVE: To determine whether B vitamin treatment was sufficient to reduce cognitive impairment associated with high-fat diets in rats and to modulate transketolase (TK) expression and activity. METHODS: To test this, we separated 50 rats into five groups that were either fed a standard chow diet (controls) or a high-fat diet (experimental groups H0, H1, H2, and H3). H0 group animals received no additional dietary supplementation, while H1 group animals were administered 100 mg/kg body weight (BW) thiamine, 100 mg/kg BW riboflavin, and 250 mg/kg BW niacin each day, and group H2 animals received daily doses of 100 mg/kg BW pyridoxine, 100 mg/kg BW cobalamin, and 5 mg/kg BW folate. Animals in the H3 group received the B vitamin regimens administered to both H1 and H2 each day. RESULTS: Over time, group H0 exhibited greater increases in BW and fat mass relative to other groups. When spatial and memory capabilities in these animals were evaluated via conditioned taste aversion (CTA) and Morris Water Maze (MWM), we found B vitamin treatment was associated with significant improvements relative to untreated H0 controls. Similarly, B vitamin supplementation was associated with elevated TK expression in erythrocytes and hypothalamus of treated animals relative to those in H0 (P<0.05). CONCLUSION: Together, these findings suggest B vitamin can modulate hypothalamic TK activity to reduce the severity of cognitive deficits in a rat model of obesity. As such, B vitamin supplementation may be a beneficial method for reducing cognitive dysfunction in clinical settings associated with high-fat diets.

Dexpanthenol Promotes Cell Growth by Preventing Cell Senescence and Apoptosis in Cultured Human Hair Follicle Cells.

Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP; ß-catenin; versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-ß1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation; was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles.

Potential mental and physical benefits of supplementation with a high-dose, B-complex multivitamin/mineral supplement: What is the evidence?

INTRODUCTION: Objective: to perform a systematic literature review to examine the effects of high-dose, B-complex multivitamin/mineral supplementation on physical, mental, and energy outcomes in healthy and 'at-risk' (suboptimal nutritional status/subclinical symptoms at baseline) adult populations. Methods: PubMed was searched for relevant randomized controlled trials until January 2020. Results: overall, 136 publications were identified. In the seven randomised, double-blind, placebo-controlled studies considered eligible for inclusion, supplementation in healthy populations predominantly showed improvements in perceived stress, physical stamina, concentration, and general mental health, and significant reductions in anxiety and improvements in self-reported vigour. However, not all of these outcomes were significant, and statistical correction for multiple outcomes was not commonly employed. Studies investigating brain mapping following supplementation indicated increased functional activity in brain regions related to processing of attention, executive control, and working memory during cognitive tasks. Conclusions: while there is certainly a need for further studies on the neurocognitive and physical benefits of micronutrient supplementation, this review provides generally supportive evidence for the benefits of a high-dose, B-complex multivitamin/mineral supplement in healthy and at-risk populations in terms of physical, mental, and energy outcomes.

INTRODUCCIÓN: Objetivo: realizar una revisión sistemática de la literatura para valorar los efectos de la administración de suplementos multivitamínicos/minerales del complejo B en dosis altas sobre los resultados físicos, mentales y energéticos en poblaciones adultas sanas y en situaciones especiales de riesgo (estado nutricional subóptimo/síntomas subclínicos al inicio del estudio). Métodos: se realizaron búsquedas en PubMed de ensayos controlados aleatorios relevantes hasta enero 2020. Resultados: en total se identificaron 136 publicaciones. En los siete estudios aleatorizados, doble ciego y controlados con placebo considerados elegibles para la inclusión, la suplementación en poblaciones sanas mostró predominantemente mejoras en la percepción del estrés, la resistencia física, la concentración y la salud mental general, así como una reducción significativa de la ansiedad y mejoras en la vitalidad según la autoevaluación de los participantes. Sin embargo, no todos estos resultados fueron significativos y la corrección estadística para múltiples resultados no se empleó habitualmente. Los estudios sobre el mapeo cerebral después de la suplementación, indicaron un aumento de la actividad funcional en las regiones del cerebro relacionadas con el procesamiento de la atención, el control ejecutivo y la memoria de trabajo durante tareas cognitivas. Conclusiones: si bien ciertamente existe la necesidad de realizar más estudios sobre los beneficios neurocognitivos y físicos de la suplementación con micronutrientes, esta revisión proporciona evidencia en general sobre los beneficios de un suplemento multivitamínico/mineral del complejo B en dosis altas, en poblaciones sanas y en situaciones de riesgo, en términos de resultados físicos, mentales y energéticos.

Differential Gene Expression and Biological Analyses of Primary Hepatocytes Following D-Chiro-Inositol Supplement.

Dietary supplements have improved the prevention of insulin resistance and metabolic diseases, which became a research hotspot in food science and nutrition. Obesity and insulin resistance, caused by a high-fat diet, eventually result in severe metabolic diseases, can be prevented with the dietary supplement D-chiro-inositol (DCI). In this work, we isolated mice primary hepatocytes with palmitic acid stimulation and DCI was applied to compare and contrast its effects of in primary hepatocyte biology. Before and after intervention with DCI, we used RNA-Seq technology to establish a primary hepatocyte transcriptome gene profile. We found that both PA and DCI cause a wide variation in gene expression. Particularly, we found that DCI plays critical role in this model by acting on glycolysis and gluconeogenesis. Overall, we generated extensive transcripts from primary hepatocytes and uncovered new functions and gene targets for DCI.

Identification of vitamin B6 as a PD-L1 suppressor and an adjuvant for cancer immunotherapy.

Interaction of programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) inhibits T cell activation. Tumor tissues can evade immune surveillance by expressing higher levels of PD-L1. Identification of potential regulators of PD-L1 through natural metabolites may contribute to discovering new drugs for immunotherapy. By using a metabolite library screen, we showed that pyridoxal (PL) significantly suppresses PD-L1 expression. Mechanistically, PL accelerates PD-L1 degradation in a proteasome-dependent manner, and STUB1 serves as an E3 ligase during the process. Functionally, PL enhances T cell killing activity by blocking the PD-1/PD-L1 signaling pathway. Thus, we have identified PL as an inhibitor of PD-L1, which provides a feasible option for combination immunotherapy.

Changes in Biothiol Levels Are Closely Associated with Alzheimer's Disease.

BACKGROUND: Serum homocysteine (Hcy) level is considered to be an important biomarker for Alzheimer's disease (AD); however, the status of Hcy in brain tissue, and the association between brain and serum levels of Hcy in AD patients remain unclear. OBJECTIVE: We aimed to examine whether the changes of three thiols are consistent in serum of AD patients and the brain of APP/PS1 mice, and to verify the effectiveness of Hcy as a biomarker for early AD detection. METHODS: The levels of Hcy, cysteine (Cys), and glutathione (GSH) in Aß1-42-treated PC12 cells, the brain and hippocampus of APP/PS1 mouse, and the serum of AD patients were evaluated using ethyl (E)-3-(9-chloro-11-oxo-2,3,6,7-tetrahydro-1H,5H,11H-pyrano[2,3-f] pyrido [3,2,1 -ij] quinolin-10-yl)-2-cyanoacrylate (Probe 1) and ELISA assay or LC-MS. RESULTS: Measurement by Probe 1 revealed a significant increase in Hcy level, and a decrease in Cys and GSH levels in Aß1-42-treated PC12 cells and the serum of AD patients. The hippocampus and whole brain of APP/PS1 mice also showed a significant increase in Hcy level alongside the accumulation of age-related AD symptoms. The upregulation of Hcy and the downregulation of Cys and GSH were reversed in the Aß1-42-treated PC12 cells and the brain of APP/PS1 mice when supplemented with VB6. CONCLUSION: Changes in Hcy, Cys, and GSH levels in the brain of APP/PS1 mice and Aß1-42-treated PC12 cells were observed in situ with a new fluorescent probe, which were consistent with the abnormal changes in Hcy, Cys, and GSH levels in the serum of AD patients. VB6 supplementation was successful in ameliorating abnormal increases in Hcy levels.