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It has been hypothesized that ultraviolet (UV) radiation can lead to depletion of plasma folate and B 12 vitamin, but few studies have investigated effects of other parameters of solar and geomagnetic activity (SGA). We investigated the association between four SGA parameters-interplanetary magnetic field (IMF), sunspot number (SSN), K p index, and ground shortwave solar radiation (SWR)-and three plasma B-complex vitamins-folate, B 6 , and B 12 -in 910 participants from the Normative Aging Study (NAS) between 1998 and 2017. Mixed-effects regression models were used for 1- to 28-moving day averages of SGA exposure, adjusted for covariates. We compared the impact of SGA in individuals under higher and lower B-complex supplementation (> or < 50th quartile). Our findings show that increases in solar activity variables IMF and SSN were found to be significantly associated with decreases in B 12 vitamin. IMF and SSN were associated with decrease in folate levels, especially in individuals under higher levels of B-complex supplementation. No associations were found for SWR and K p index. To our knowledge, this is the first study that demonstrated the detrimental impact of solar activity on plasma B 12 and folate in a large cohort. These findings have clinical implications during periods of high solar activity., (© 2024. The Author(s).)

Previous studies show that B vitamins and homocysteine (Hcy) may be associated with mental disorders, but the accurate causal relationship remains unclear. This study aimed to elucidate the potential causal relationship of serum B vitamins and Hcy levels with five common mental disorders through a two-sample Mendelian randomization (MR) study. In this MR analysis, 50 single-nucleotide polymorphisms (SNPs)-13 related to folate, 17 to vitamin B6, 8 to vitamin B12 and 12 to Hcy-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). The MR analyses were conducted using the inverse variance weighted (IVW), weighted median (WM), MR-Egger methods and sensitivity analyses were further performed to test the robustness. This MR study found a suggestive causal relationships between serum vitamin B12 levels and the risk of anxiety disorders (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.01-1.78, p = 0.046) and bipolar affective disorders (OR: 1.85, 95% CI: 1.16-2.96, p = 0.010). However, folate, vitamin B6 and Hcy levels may not be causally associated with the risk of mental disorders. In conclusion, this study reveals that elevated serum vitamin B12 levels might suggestively increase the risk of anxiety and bipolar affective disorders, even though horizontal pleiotropy cannot be completely eliminated. The potential implications of our results warrant validation in larger GWAS based on diverse populations.

Background and Aims: Type 2 diabetes (T2D) is a global and complex public health challenge, and dietary management is acknowledged as critical in its prevention. Recent studies have highlighted the involvement of micronutrients in T2D pathophysiology; our study aims to assess the association between B vitamin intake and T2D risks and the mediating role of inflammation., Methods: In a prospective cohort design, data on B vitamins intake, including thiamine (B1), riboflavin (B2), niacin (B3), pyridoxine (B6), folate (B9), and cobalamin (B12), was obtained using a validated food frequency questionnaire (FFQ), and blood inflammatory biomarkers were analyzed according to standard protocol in the local hospitals at baseline from 44,960 adults in the Shanghai Suburban Adult Cohort and Biobank (SSACB). Incident T2D cases were identified according to a physician's diagnosis or medication records from the electronic medical information system. We employed logistic and weighted quantile sum regression models to explore the associations of single and combined levels of B vitamins with T2D and mediation analyses to investigate the effects of inflammation., Results: Negative correlations between B vitamins and T2D were observed in the single-exposure models, except for B3. The analyses of joint exposure (B1, B2, B6, B9, and B12) also showed an inverse association (OR 0.80, 95% CI 0.71 to 0.88), with vitamin B6 accounting for 45.58% of the effects. Further mediation analysis indicated a mediating inflammatory impact, accounting for 6.72% of the relationship., Conclusions: Dietary intake of B vitamins (B1, B2, B6, B9, B12) was associated with a reduced T2D risk partially mediated by inflammation in Shanghai residents.

Elevated plasma concentrations of several one-carbon metabolites are associated with increased CVD risk. Both diet-induced regulation and dietary content of one-carbon metabolites can influence circulating concentrations of these markers. We cross-sectionally analysed 1928 patients with suspected stable angina pectoris (geometric mean age 61), representing elevated CVD risk, to assess associations between dietary macronutrient composition (FFQ) and plasma one-carbon metabolites and related B-vitamin status markers (GC-MS/MS, LC-MS/MS or microbiological assay). Diet-metabolite associations were modelled on the continuous scale, adjusted for age, sex, BMI, smoking, alcohol and total energy intake. Average (geometric mean (95 % prediction interval)) intake was forty-nine (38, 63) energy percent (E%) from carbohydrate, thirty-one (22, 45) E% from fat and seventeen (12, 22) E% from protein. The strongest associations were seen for higher protein intake, i.e. with higher plasma pyridoxal 5'-phosphate (PLP) (% change (95 % CI) 3·1 (2·1, 4·1)), cobalamin (2·9 (2·1, 3·7)), riboflavin (2·4 (1·1, 3·7)) and folate (2·1 (1·2, 3·1)) and lower total homocysteine (tHcy) (-1·4 (-1·9, -0·9)) and methylmalonic acid (MMA) (-1·4 (-2·0, -0·8)). Substitution analyses replacing MUFA or PUFA with SFA demonstrated higher plasma concentrations of riboflavin (5·0 (0·9, 9·3) and 3·3 (1·1, 5·6)), tHcy (2·3 (0·7, 3·8) and 1·3 (0·5, 2·2)) and MMA (2·0 (0·2, 3·9) and 1·7 (0·7, 2·7)) and lower PLP (-2·5 (-5·3, 0·3) and -2·7 (-4·2, -1·2)). In conclusion, a higher protein intake and replacing saturated with MUFA and PUFA were associated with a more favourable metabolic phenotype regarding metabolites associated with CVD risk.

Objective: Previous observational studies have identified a correlation between elevated plasma homocysteine (Hcy) levels and polycystic ovary syndrome (PCOS). This study aimed to determine whether a causal relationship exists between Hcy and PCOS at the genetic level., Methods: A two-sample Mendelian Randomization (TSMR) study was implemented to assess the genetic impact of plasma levels of Hcy, folate, vitamin B12, and vitamin B6 on PCOS in individuals of European ancestry. Independent single nucleotide polymorphisms (SNPs) associated with Hcy (n=12), folate (n=2), vitamin B12 (n=10), and vitamin B6 (n=1) at genome-wide significance levels ( P <5×10 -8 ) were selected as instrumental variables (IVs). Data concerning PCOS were obtained from the Apollo database. The primary method of causal estimation was inverse variance weighting (IVW), complemented by sensitivity analyses to validate the results., Results: The study found no genetic evidence to suggest a causal association between plasma levels of Hcy, folate, vitamin B12, vitamin B6, and PCOS. The effect sizes, determined through random-effect IVW, were as follows: Hcy per standard deviation increase, OR = 1.117, 95%CI: (0.842, 1.483), P = 0.442; folate per standard deviation increase, OR = 1.008, CI: (0.546, 1.860), P = 0.981; vitamin B12 per standard deviation increase, OR = 0.978, CI: (0.808, 1.185), P = 0.823; and vitamin B6 per standard deviation increase, OR = 0.967, CI: (0.925, 1.012), P = 0.145. The fixed-effect IVW results for each nutrient exposure and PCOS were consistent with the random-effect IVW findings, with additional sensitivity analyses reinforcing these outcomes., Conclusion: Our findings indicate no causal link between Hcy, folate, vitamin B12, vitamin B6 levels, and PCOS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Li, Xia, Huang and Chen.)

Previous studies reported that Pb exposure causes a negative association with delta-aminolevulinic acid dehydratase activity (δ-ALAD), but the impact of Pb exposure (dose and time), B vitamin deficiencies, and lifestyle factors needs to be explored. In this study, the impact of Pb exposure, B vitamin deficiencies, and lifestyle factors on δ-ALAD activity among workers exposed to Pb from the Pb-recycling process was evaluated. Blood lead levels (BLLs), B vitamins (B6, B9, and B12), hematological factors (Hb% and HCT), lifestyle factors, and δ-ALAD activity was assessed in 170 male Pb-exposed workers engaged in the Pb recycling process. BLLs are estimated using the ICP-OES method. B vitamins in serum samples from workers were determined using the ELISA method. The δ-ALAD activity in whole blood samples was determined using the spectrophotometer method. The lifestyle factors were collected using a standard questionnaire. The δ-ALAD activity was significantly decreased in workers with the habits of alcohol use, tobacco consumption, hematocrit < 41%, mild and moderate categories of anemia, vitamin B6 and B12 deficiency, and BLL categories of 10-30, 30-50, and > 50 µg/dL. Multiple regression analysis revealed that the independent variables of alcohol consumption (β = - 0.170; P = 0.025), BLLs (β = - 0.589; P = 0.001) and Hb% (β = 0.183; P = 0.001) significantly influenced the δ-ALAD activity with 44.2% (R 2  = 0.442). Among the workers exposed to Pb from the Pb recycling plant, δ-ALAD activity was considerably reduced by Pb exposure, B vitamin deficiency, hematological parameters, and lifestyle factors., (© 2024. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

The Western-style diet, which is common in developed countries and spreading into developing countries, is unbalanced in many respects. For instance, micronutrients (vitamins A, B complex, C, D, E, and K plus iron, zinc, selenium, and iodine) are generally depleted in Western food (causing what is known as 'hidden hunger'), whereas some others (such as phosphorus) are added beyond the daily allowance. This imbalance in micronutrients can induce cellular damage that can increase the risk of cancer. Interestingly, there is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific. The present review summarized the literature regarding vitamins and cancer risk to assess whether these could be used as diagnostic or prognostic markers, thus confirming their potential as biomarkers. Despite many studies that highlight the importance of monitoring vitamin blood or tissue concentrations in cancer patients and demonstrate the link between vitamin intake and cancer risk, there is still an urgent need for more data to assess the effectiveness of vitamins as biomarkers in the context of cancer. Therefore, this review aims to provide a solid basis to support further studies on this promising topic.

Background: Atrophic gastritis (AG) and use of proton pump inhibitors (PPIs) result in gastric acid suppression that can impair the absorption of vitamin B-12 from foods. The crystalline vitamin B-12 form, found in fortified foods, does not require gastric acid for its absorption and could thus be beneficial for older adults with hypochlorhydria, but evidence is lacking., Objectives: To investigate associations of AG and PPI use with vitamin B-12 status, and the potential protective role of fortified foods, in older adults., Methods: Eligible participants (n = 3299) not using vitamin B-12 supplements were drawn from the Trinity-Ulster and Department of Agriculture cohort, a study of noninstitutionalized adults aged ≥60 y and recruited in 2008-2012. Vitamin B-12 status was measured using 4 biomarkers, and vitamin B-12 deficiency was defined as a combined indicator value < -0.5. A pepsinogen I:II ratio <3 was considered indicative of AG., Results: AG was identified in 15% of participants and associated with significantly lower serum total vitamin B-12 (P < 0.001) and plasma holotranscobalamin (holoTC; P < 0.001), and higher prevalence of vitamin B-12 deficiency (38%), compared with PPI users (21%) and controls (without AG and nonusers of PPIs; 15%; P < 0.001). PPI drugs were used (≥6 mo) by 37% of participants and were associated with lower holoTC concentrations, but only in participants taking higher doses (≥30 mg/d). Regular, compared with nonregular, consumption of fortified foods (i.e., ≥5 and 0-4 portions/wk, respectively) was associated with higher vitamin B-12 biomarkers in all participants, but inadequate to restore normal vitamin B-12 status in those with AG., Conclusions: Older adults who have AG and/or use higher doses of PPIs are more likely to have indicators of vitamin B-12 deficiency. Fortified foods, if consumed regularly, were associated with enhanced vitamin B-12 status, but higher levels of added vitamin B-12 than currently provided could be warranted to optimize status in people with AG., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Although populations from low- and middle-income countries are at higher risk for thiamine (vitamin B-1) deficiency, accurate data on the global prevalence of thiamine deficiency are still lacking due to the difficult blood collection in remote regions. Volumetric absorptive microsampling (VAMS) from finger prick blood, generating dried blood microsamples, could simplify blood collection and allow the setup of epidemiological studies to improve the diagnosis, treatment, and prevention of thiamine deficiency., Objectives: To explore the potential of VAMS to serve as an alternative, patient-centric sampling strategy to evaluate the thiamine status., Methods: Venous liquid, venous VAMS, and capillary VAMS samples were collected from 50 healthy volunteers to compare thiamine diphosphate results, as a marker of thiamine (vitamin B-1) status, in the different sample types. In addition, capillary VAMS samples were sent through regular mail to evaluate the influence of noncontrolled transport on the final results. All samples were analyzed using previously described fully validated LC-MS/MS methods., Results: A good agreement (94-100% of the results lying within 20% of their mean) was obtained for all comparisons: venous VAMS compared with venous liquid blood samples, capillary VAMS compared with venous VAMS samples, and capillary VAMS compared with venous liquid blood samples, with no significant bias (maximum mean bias of -1.0%; 95% CI: -4.1%, 2.0%) observed between the different methods. Finally, we demonstrated that VAMS samples can be safely transported through regular mail without affecting the final results., Conclusions: VAMS sampling can be used as a reliable alternative tool to evaluate the thiamine status, starting from only one drop of finger prick blood, in both developed and developing countries., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

There is little evidence regarding the association between serum vitamin B6 concentration and subsequent mortality. We aimed to evaluate the association of serum vitamin B6 concentration with all-cause, cardiovascular disease (CVD), and cancer mortality in the general population using data from the National Health and Nutrition Examination Survey (NHANES). Our study examined 12,190 adults participating in NHANES from 2005 to 2010 in the United States. The mortality status was linked to National Death Index (NDI) records up to 31 December 2015. Pyridoxal 5'-phosphate (PLP) is the biologically active form of vitamin B6. Vitamin B6 status was defined as deficient (PLP < 20 nmol/L), insufficient (PLP ≥ 20.0 and <30.0 nmol/L), and sufficient (PLP ≥ 30.0 nmol/L). We established Cox proportional-hazards models to estimate the associations of categorized vitamin B6 concentration and log-transformed PLP concentration with all-cause and cause-specific mortality by calculating hazard ratios (HRs) and 95% confidence intervals (95%CIs). In our study, serum vitamin B6 was sufficient in 70.6% of participants, while 12.8% of the subjects were deficient in vitamin B6. During follow-up, a total of 1244 deaths were recorded, including 294 cancer deaths and 235 CVD deaths. After multivariate adjustment in Cox regression, participants with higher serum vitamin B6 had a 15% (HR = 0.85, 95%CI = 0.77, 0.93) reduced risk of all-cause mortality and a 19% (HR = 0.81, 95%CI = 0.68, 0.98) reduced risk for CVD mortality for each unit increment in natural log-transformed PLP. A higher log-transformed PLP was not significantly associated with a lower risk for cancer mortality. Compared with sufficient vitamin B6, deficient (HR = 1.37, 95%CI = 1.17, 1.60) and insufficient (HR = 1.19, 95%CI = 1.02, 1.38) vitamin B6 level were significantly associated with a higher risk for all-cause mortality. There was no significant association for cause-specific mortality. Participants with higher levels of vitamin B6 had a lower risk for all-cause mortality. These findings suggest that maintaining a sufficient level of serum vitamin B6 may lower the all-cause mortality risk in the general population.

Background: Elevated plasma homocysteine has been found to be associated with an increased risk of osteoporosis, especially hip and vertebral fractures. The plasma concentration of homocysteine is dependent on the activities of several B vitamin-dependent enzymes, such as methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), methionine synthase reductase (MTRR), and cystathionine β-synthase (CBS)., Objectives: We investigated whether genetic variants in some of the genes involved in 1 carbon metabolism modify the association of B vitamin-related measures with bone mineral density (BMD) and strength., Methods: We measured several B vitamins and biomarkers in participants of the Framingham Offspring Study, and performed analyses of methylmalonic acid (MMA) continuously and <210 nmol/L; pyridoxal-5'-phosphate; vitamin B-12 continuously and ≥258 pmol/L; and folate. The outcomes of interest included areal and volumetric BMD, measured by DXA and quantitative computed tomography (QCT), respectively. We evaluated associations between the bone measures and interactions of single nucleotide polymorphism with a B vitamin or biomarker in Framingham participants (n = 4310 for DXA and n = 3127 for QCT). For analysis of DXA, we validated the association results in the B-PROOF cohort (n = 1072). Bonferroni-corrected locus-wide significant thresholds were defined to account for multiple testing., Results: The interactions between rs2274976 and vitamin B-12 and rs34671784 and MMA <210 nmol/L were associated with lumbar spine BMD, and the interaction between rs6586281 and vitamin B-12 ≥258 pmol/L was associated with femoral neck BMD. For QCT-derived traits, 62 interactions between genetic variants and B vitamins and biomarkers were identified., Conclusions: Some genetic variants in the 1-carbon methylation pathway modify the association of B vitamin and biomarker concentrations with bone density and strength.  These interactions require further replication and functional validation for a mechanistic understanding of the role of the 1-carbon metabolism pathway on BMD and risks of fracture., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The role of haem in the activity of cystathionine β-synthase (CBS) is reviewed and a hypothesis postulating multiple effects of haem on enzyme activity under conditions of haem excess or deficiency is proposed, with implications for some therapies of acute hepatic porphyrias. CBS utilises both haem and pyridoxal 5'-phosphate (PLP) as cofactors. Although haem does not participate directly in the catalytic process, it is vital for PLP binding to the enzyme and potentially also for CBS stability. Haem deficiency can therefore undermine CBS activity by impairing PLP binding and facilitating CBS degradation. Excess haem can also impair CBS activity by inhibiting it via CO resulting from haem induction of haem oxygenase 1 (HO 1), and by induction of a functional vitamin B6 deficiency following activation of hepatic tryptophan 2,3-dioxygenase (TDO) and subsequent utilisation of PLP by enhanced kynurenine aminotransferase (KAT) and kynureninase (Kynase) activities. CBS inhibition results in accumulation of the cardiovascular risk factor homocysteine (Hcy) and evidence is emerging for plasma Hcy elevation in patients with acute hepatic porphyrias. Decreased CBS activity may also induce a proinflammatory state, inhibit expression of haem oxygenase and activate the extrahepatic kynurenine pathway (KP) thereby further contributing to the Hcy elevation. The hypothesis predicts likely changes in CBS activity and plasma Hcy levels in untreated hepatic porphyria patients and in those receiving hemin or certain gene-based therapies. In the present review, these aspects are discussed, means of testing the hypothesis in preclinical experimental settings and porphyric patients are suggested and potential nutritional and other therapies are proposed., (© 2021 The Author(s).)

Background: Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations., Methods: Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants., Results: Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (OR SD , 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (OR SD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined OR SD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer., Conclusions: These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.

Background: B vitamins have been associated with the risk and progression of colorectal cancer (CRC), given their central roles in nucleotide synthesis and methylation, yet their association with quality of life in established CRC is unclear., Objectives: To investigate whether quality of life 6 months postdiagnosis is associated with: 1) circulating concentrations of B vitamins and related biomarkers 6 months postdiagnosis; 2) changes in these concentrations between diagnosis and 6 months postdiagnosis; 3) B-vitamin supplement use 6 months postdiagnosis; and 4) changes in B-vitamin supplement use between diagnosis and 6 months postdiagnosis., Methods: We included 1676 newly diagnosed stage I-III CRC patients from 3 prospective European cohorts. Circulating concentrations of 9 biomarkers related to the B vitamins folate, riboflavin, vitamin B6, and cobalamin were measured at diagnosis and 6 months postdiagnosis. Information on dietary supplement use was collected at both time points. Health-related quality of life (global quality of life, functioning scales, and fatigue) was assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 6 months postdiagnosis. Confounder-adjusted linear regression analyses were performed, adjusted for multiple testing., Results: Higher pyridoxal 5'-phosphate (PLP) was cross-sectionally associated with better physical, role, and social functioning, as well as reduced fatigue, 6 months postdiagnosis. Associations were observed for a doubling in the hydroxykynurenine ratio [3-hydroxykynurenine: (kynurenic acid + xanthurenic acid + 3-hydroxyanthranilic acid + anthranilic acid); an inverse marker of vitamin B6] and both reduced global quality of life (β = -3.62; 95% CI: -5.88, -1.36) and worse physical functioning (β = -5.01; 95% CI: -7.09, -2.94). Dose-response relations were observed for PLP and quality of life. No associations were observed for changes in biomarker concentrations between diagnosis and 6 months. Participants who stopped using B-vitamin supplements after diagnosis reported higher fatigue than nonusers., Conclusions: Higher vitamin B6 status was associated with better quality of life, yet limited associations were observed for the use of B-vitamin supplements. Vitamin B6 needs further study to clarify its role in relation to quality of life., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Diet is a modifiable factor that ensures optimal growth, biochemical performance, improved mood and mental functioning. Lack of nutrients, notably vitamin B, has an impact on human health and wellbeing. The United Arab Emirates is facing a serious problem of micronutrient deficiencies because of the growing trend for bariatric surgery, including Roux-en-Y gastric bypass and sleeve gastrectomy. People undergoing bariatric surgery are at high risk of developing neurological, cognitive, and mental disabilities and cardiovascular disease due to deficiency in vitamin B. Vitamin B is involved in neurotransmitter synthesis, including γ-aminobutyric acid, serotonin, dopamine, and noradrenaline. Deficiency of vitamin B increases the risk of depression, anxiety, dementia and Alzheimer's disease. In addition, vitamin B deficiency can disrupt the methylation of homocysteine, leading to hyperhomocysteinemia. Elevated homocysteine levels are detrimental to human health. Vitamin B deficiency also suppresses immune function, increases the production of pro-inflammatory cytokines and upregulates NF-κB. Considering the important functions of vitamin B and the severe consequences associated with its deficiency following bariatric surgery, proper dietary intervention and administration of adequate supplements should be considered to prevent negative clinical outcomes.

Folate, a cofactor for the supply of one-carbon groups, is required by epigenetic processes to regulate cell lineage determination during development. The intake of folic acid (FA), the synthetic form of folate, has increased significantly over the past decade, but the effects of high periconceptional FA intake on cell lineage determination in the early embryo remains unknown. Here, we investigated the effect of maternal high FA (HFA) intake on blastocyst development and expression of key regulatory genes. C57BL/6 adult female mice were fed either Control diet (1 mg FA) for 4 weeks before conception and during the preimplantation period (Con-Con); Control diet for 4 weeks preconception, followed by HFA (5 mg FA) diet during preimplantation (Con-HFA); or HFA diet for 4 weeks preconception and during preimplantation (HFA-HFA). At E3.5, blastocyst cell number, protein, and mRNA expression were measured. In HFA-HFA blastocysts, trophectoderm cell numbers and expression of CDX2, Oct-4, and Nanog were reduced compared with Con-Con blastocysts; Con-HFA blastocysts showed lower CDX2 and Oct-4 expression than Con-Con blastocysts. These findings suggest periconceptional HFA intake induces changes in key regulators of embryo morphogenesis with potential implications for subsequent development., (© 2021 Wiley Periodicals LLC.)

Beriberi is a nutritional complication of gastric surgery, caused by deficiency of vitamin B1, or thiamine. Thiamine deficiency leads to impaired glucose metabolism, decreased delivery of oxygen by red blood cells, cardiac dysfunction, failure of neurotransmission, and neuronal death. This review describes the history and pathophysiology of beriberi as well as the relationship between beriberi and nutritional deficiencies after gastric surgery. A literature review of the history and pathophysiology of beriberi and the risk factors for thiamine deficiency, particularly after gastric resection or bariatric surgery, was performed. Recommendations for nutritional follow-up post gastric surgery are based on current national guidelines. Patients may have subclinical thiamine deficiency after upper gastrointestinal surgery, and thus beriberi may be precipitated by acute illness such as sepsis or poor dietary intake. This may occur very soon or many years after gastrectomy or bariatric surgery, even in apparently well-nourished patients. Prompt recognition and administration of supplemental thiamine can decrease morbidity and mortality in patients with beriberi. Dietary education post surgery and long-term follow-up to determine nutritional status, including vitamin and mineral assessment, is recommended for patients who undergo gastric surgery., (© The Author(s) 2020. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Multivitamin and mineral (MVM) supplements are frequently used amongst older populations to improve adequacy of micronutrients, including B-vitamins, but evidence for improved health outcomes are limited and deficiencies remain prevalent. Although this may indicate poor efficacy of supplements, this could also suggest the possibility for altered B-vitamin bioavailability and metabolism in older people. This open-label, single-arm acute parallel study, conducted at the Liggins Institute Clinical Research Unit in Auckland, compared circulatory and urinary B-vitamer responses to MVM supplementation in older (70.1 ± 2.7 y, n = 10 male, n = 10 female) compared to younger (24.2 ± 2.8 y, n = 10 male, n = 10 female) participants for 4 h after the ingestion of a single dose of a commercial MVM supplement and standardized breakfast. Older adults had a lower area under the curve (AUC) of postprandial plasma pyridoxine ( p = 0.02) and pyridoxal-5'phosphate ( p = 0.03) forms of vitamin B 6 but greater 4-pyridoxic acid AUC ( p = 0.009). Urinary pyridoxine and pyridoxal excretion were higher in younger females than in older females (time × age × sex interaction, p < 0.05). Older adults had a greater AUC increase in plasma thiamine ( p = 0.01), riboflavin ( p = 0.009), and pantothenic acid ( p = 0.027). In older adults, there was decreased plasma responsiveness of the ingested (pyridoxine) and active (pyridoxal-5'phosphate) forms of vitamin B 6 , which indicated a previously undescribed alteration in either absorption or subsequent metabolic interconversion. While these findings cannot determine whether acute B 6 responsiveness is adequate, this difference may have potential implications for B 6 function in older adults. Although this may imply higher B vitamin substrate requirements for older people, further work is required to understand the implications of postprandial differences in availability.

The central position of methionine (Met) in protein metabolism indicates the importance of this essential amino acid for growth and maintenance of lean body mass. Therefore, Met might be a tempting candidate for supplementation. However, because Met is also the precursor of homocysteine (Hcy), a deficient intake of B vitamins or excessive intake of Met may result in hyperhomocysteinemia (HHcy), which is a risk factor for cardiovascular disease. This review discusses the evidence generated in preclinical and clinical studies on the importance and potentially harmful effects of Met supplementation and elaborates on potential clinical applications of supplemental Met with reference to clinical studies performed over the past 20 y. Recently acquired knowledge about the NOAEL (no observed adverse effect level) of 46.3 mg · kg-1 · d-1 and the LOAEL (lowest observed adverse effect level) of 91 mg · kg-1 · d-1 of supplemented Met will guide the design of future studies to further establish the role of Met as a potential (safe) candidate for nutritional supplementation in clinical applications., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

One-carbon metabolism (OCM) plays a pivotal role in both the stability and integrity of DNA and is mainly regulated by B-vitamins. This study aims to investigate the clinical relevance of B-vitamins and single nucleotide polymorphisms (SNPs) on OCM-related genes in diffuse large B-cell lymphoma (DLBCL). A total of 322 newly diagnosed DLBCL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone-based immunochemotherapy were recruited into this study. The serum levels of B-vitamins (folate, vitamin B2 [riboflavin], vitamin B6 [pyridoxal 5'-phosphate], and vitamin B12 [cobalamin]), as well as SNPs on methylenetetrahydrofolate reductase, methionine synthase (MTR), MTR reductase (MTRR) and cystathionine gamma-lyase (CTH) genes, were assessed at diagnosis. The prognostic values were estimated using the Kaplan-Meier method and Cox proportional hazards regression methods. Overall, the low serum concentration of folate and vitamin B2, as well as the presence of CTH1364 TT genotype, were significantly associated with poor treatment response in DLBCL. Multivariate analysis indicated that compared with patients in the medium and high serum folate tertiles, low serum folate tertile patients had both significantly inferior progression-free survival (P = .033, Tertile 2 vs Tertile 1, and P = .031, Tertile 3 vs Tertile 1) and overall survival time (P < .001, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1). Compared with patients in the medium and high serum vitamin B2 tertiles, low serum vitamin B2 tertile patients had both significantly inferior progression-free survival (P = .006, Tertile 2 vs Tertile 1, and P = .001, Tertile 3 vs Tertile 1) and overall survival time (P = .030, Tertile 2 vs Tertile 1, and P = .255, Tertile 3 vs Tertile 1). In conclusion, alterations in B-vitamin metabolism significantly affected disease progression and had a prognostic impact on DLBCL., (© 2020 John Wiley & Sons Ltd.)

Objective: To evaluate the effect of folate and vitamin B 12 levels on pregnancy progression and outcomes., Methods: The present study is a prospective follow up study of 100 pregnant women. Biochemical investigations (plasma homocysteine, folate, and vitamin B 12 levels) were performed on all pregnant women in first, second, and third trimesters. Nonparametric tests were used to compare the differences in median levels and odds ratio analysis for the assessment of the risk between the selected biomarkers and adverse pregnancy progression and outcomes., Results: The pregnant women at their first antenatal care visit were found to be predominantly folate replete (97%) and vitamin B 12 deficient (60%). Hyperhomocysteinemia in first and second trimesters was found to pose more than 3-fold increased risk for adverse pregnancy outcomes (P = .006 and .0002, respectively). Low birth weight (LBW) was found to be the most common adverse pregnancy outcome (52%), and was significantly associated with vitamin B 12 deficiency in the first and second trimesters (82%, P < .0001; 71.4%, P = .04, respectively)., Conclusion: The vitamin B 12 deficiency is more common among Indian pregnant women as compared to folate deficiency. Hyperhomocysteinemia is an independent risk factor for pregnancy complications. Vitamin B 12 deficiency in first and second trimesters is associated with LBW babies., (© 2020 Wiley Periodicals, Inc.)

We and others have reported associations between B vitamins principally involved in one-carbon metabolism and increased lung cancer risk; however, results for women have been inconsistent. Here we report on the association of supplemental vitamins B 6 , folic acid and B 12 intake and lung cancer risk using data from the Women's Health Initiative (WHI) study of postmenopausal women. Between 1993 and 1998, 161,808 women were recruited to participate in the WHI at 40 clinical centers in the US. After exclusions, 159,232 women were available for analysis and followed prospectively for an average of 18.3 years. Among them, 3,836 incident lung cancer cases were diagnosed. At baseline, supplemental B vitamins from multivitamins, vitamin mixtures and individual supplements were assessed. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between supplemental B vitamin intake and lung cancer risk. Relative to no intake, women who took ≥50 mg/day of vitamin B 6 had 16% (HR 0.84, 95% CI: 0.71-0.99) reduced lung cancer risk. Associations did not differ significantly by smoking status or lung cancer histology. Intakes of folic acid and vitamin B 12 were not associated with risk. There is a need for replication of our findings from other large, prospective studies with similar high-quality measurement of supplement intakes before any recommendations can be made at present on B 6 supplementation for lung cancer prevention in women., (© 2020 UICC.)

B vitamins involved in one-carbon metabolism have been implicated in the development of inflammation- and angiogenesis-related chronic diseases, such as colorectal cancer (CRC). Yet, the role of one-carbon metabolism in inflammation and angiogenesis among CRC patients remains unclear. The objective of this study was to investigate associations of components of one-carbon metabolism with inflammation and angiogenesis biomarkers among newly diagnosed CRC patients (n 238) in the prospective ColoCare Study, Heidelberg. We cross-sectionally analysed associations between twelve B vitamins and one-carbon metabolites and ten inflammation and angiogenesis biomarkers from pre-surgery serum samples using multivariable linear regression models. We further explored associations among novel biomarkers in these pathways with Spearman partial correlation analyses. We hypothesised that pyridoxal-5'-phosphate (PLP) is inversely associated with inflammatory biomarkers. We observed that PLP was inversely associated with C-reactive protein (CRP) (r -0·33, Plinear < 0·0001), serum amyloid A (SAA) (r -0·23, Plinear = 0·003), IL-6 (r -0·39, Plinear < 0·0001), IL-8 (r -0·20, Plinear = 0·02) and TNFα (r -0·12, Plinear = 0·045). Similar findings were observed for 5-methyl-tetrahydrofolate and CRP (r -0·14), SAA (r -0·14) and TNFα (r -0·15) among CRC patients. Folate catabolite acetyl-para-aminobenzoylglutamic acid (pABG) was positively correlated with IL-6 (r 0·27, Plinear < 0·0001), and pABG was positively correlated with IL-8 (r 0·21, Plinear < 0·0001), indicating higher folate utilisation during inflammation. Our data support the hypothesis of inverse associations between PLP and inflammatory biomarkers among CRC patients. A better understanding of the role and inter-relation of PLP and other one-carbon metabolites with inflammatory processes among colorectal carcinogenesis and prognosis could identify targets for future dietary guidance for CRC patients.

Purpose: Higher folate and vitamin-B12 have been linked to lower risk of overweight. However, whether this is a causal effect of these B-vitamins on obesity risk remains unclear and evidence in older individuals is scarce. This study aimed to assess the role of B-vitamin supplementation and levels on body composition in older individuals., Methods: A double-blind, randomized controlled trial in 2919 participants aged ≥ 65 years with elevated homocysteine levels. The intervention comprised a 2-year supplementation with a combination of folic acid (400 µg) and vitamin B12 (500 µg), or with placebo. Serum folate, vitamin-B12, active vitamin-B12 (HoloTC), methylmalonic acid (MMA), and anthropometrics were measured at baseline and after 2 years of follow-up. Dietary intake of folate and vitamin-B12 was measured at baseline in a subsample (n = 603) using a validated food-frequency questionnaire. Fat mass index (FMI) and fat-free mass index (FFMI) were assessed with Dual Energy X-ray absorptiometry (DXA)., Results: Cross-sectional analyses showed that a 1 nmol/L higher serum folate was associated with a 0.021 kg/m 2 lower BMI (95% CI - 0.039; - 0.004). Higher HoloTC (per pmol/L log-transformed) was associated with a 0.955 kg/m 2 higher FMI (95% CI 0.262; 1.647), and higher MMA (per μgmol/L) was associated with a 1.108 kg/m 2 lower FMI (95% CI - 1.899; - 0.316). However, random allocation of B-vitamins did not have a significant effect on changes in BMI, FMI or FFMI during 2 years of intervention., Conclusions: Although observational data suggested that folate and vitamin B12 status are associated with body composition, random allocation of a supplement with both B-vitamins combined versus placebo did not confirm an effect on BMI or body composition.

Although physiologic and neurologic consequences of micronutrient deficiencies have been addressed extensively, less is known about their impact on developing gut microbiota. Vitamin B12 deficiency is a common micronutrient deficiency in infants. We aimed to analyze the gut microbial composition of exclusively breastfed infants aged between 4 and 6 months with and without vitamin B12 deficiency by 16S rRNA gene sequencing. In a subgroup of infants with vitamin B12 deficiency, stool samples are recollected and reanalyzed after vitamin B12 supplementation. A total of 88 infants' stool samples (median age 4 months [IQR 4-5], 50% males) were analyzed, of which 28 (31.8%) were vitamin B12 sufficient and 60 (68.2%) were vitamin B12 insufficient. Comparisons between vitamin B12-sufficient and vitamin B12-insufficient infants revealed no evidence of differences in the microbiota. Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the most abundant phyla in all groups. There was no difference between the pre- and post-treatment composition of gut microbiota.Conclusion: Vitamin B12-deficient infants have similar gut microbial composition as vitamin B12-sufficient infants. Since the samples were collected at an early period of life and the exposure to deficiency was relatively short, it may be possible that the effects were not fully established.What is Known: • Vitamin B12 is an essential vitamin for humans and also a crucial compound for human gut microbiota. • Vitamin B12 deficiency is common in exclusively breastfed infants. • In contrast to the adult gut microbiota, infant gut microbiota has been shown to have decreased capacity for de novo synthesis of vitamin B12 and depend on dietary source of vitamin B12.What is New: • There is no difference in the gut microbial composition of vitamin B12-deficient and vitamin B12-sufficient infants.

Background: Because of the subjective nature of current pain assessments, limited efficacy of treatment options and risks associated with opioid abuse and diversion, the need for objective data to assist with chronic pain management has never been greater. Successful identification of mechanistic biomarkers would not only improve our understanding and ability to accurately diagnose pain disorders but would also facilitate the development of disease-modifying pain drugs., Objectives: The objective of this study was to determine and evaluate the prevalence of abnormal biomarker findings in a population of patients with chronic pain., Study Design: Retrospective, observational study., Setting: Data analysis of biomarker test results was performed at a single industry site (Ethos Research & Development, Newport, KY) from clinical samples collected and analyzed from July to December 2018., Methods: A novel, pain-specific biomarker test panel that evaluates biomarkers of systemic inflammation, oxidative stress, neurotransmitter turnover, and micronutrient status was employed to determine the prevalence of abnormal findings in 17,834 unique patient samples analyzed at a national reference laboratory (Ethos Laboratories, Newport, KY). Patient biomarker results were considered abnormal if they were outside of the 95% confidence interval reference ranges established using a healthy population of donors who had no history of chronic pain or opioid use., Results: A total of 77% of patients with chronic pain exhibited at least one abnormal biomarker result (n = 13,765). The most common abnormal biomarker finding was elevated quinolinic acid, which was observed in 29% of patients (n = 5,107). Elevated pyroglutamate, indicative of glutathione depletion, was observed in 19% of patients (n = 3,314). Elevated xanthurenic acid, indicative of vitamin B6 insufficiency, was observed in 17% of patients (3,025). Elevated levels of the acrolein metabolite 3-hydroxypropyl mercapturic acid were observed in 21% of patients (n = 3,667). Elevated methylmalonic acid, indicative of a vitamin B12 deficiency, was observed in 10% of patients (n = 1,827), whereas abnormally low levels of neurotransmitter metabolites were observed in 8% of patients (n = 1,456)., Limitations: Medications and/or conditions other than those associated with chronic pain were not evaluated as potential causes of abnormal biomarker findings., Conclusions: A novel biomarker assay that measures objective correlates to the neurobiological processes underlying chronic pain reveals a high prevalence of atypical biochemistry in a population of patients with pain. Abnormal biomarker findings presented here provide objective support for the role of cytokine-mediated inflammation, oxidative stress, abnormally low production of neurotransmitters, and micronutrient deficiencies in the development or worsening of chronic pain. This unique panel of functional pain biomarkers provides practitioners with novel, objective insight into the underlying causes of pain, which will pave the way for truly personalized pain medicine. Correcting abnormal biomarker findings with targeted, nonopioid therapies to improve patient function and alleviate pain potentially could lessen the opioid burden and drastically reduce health care costs., Key Words: Biomarker, pain, inflamation, oxidative stress, neurotransmitter, micronutrient deficiency, Kynurenine Pathway.

Introduction: Peroxisome proliferator-activated receptors (PPARs) have been suggested to be involved in the regulation of one-carbon metabolism. Previously we have reported effects on plasma concentrations of metabolites along these pathways as well as markers of B-vitamin status in rats following treatment with a pan-PPAR agonist. Here we aimed to investigate the effect on these metabolites after specific activation of the PPARα and PPARγ subtypes., Methods: For a period of 12 days, Male Wistar rats (n = 20) were randomly allocated to receive treatment with the PPARα agonist WY-14.643 (n = 6), the PPARγ agonist rosiglitazone (n = 6) or placebo (n = 8). The animals were sacrificed under fasting conditions, and plasma concentration of metabolites were determined. Group differences were assessed by one-way ANOVA, and planned comparisons were performed for both active treatment groups towards the control group., Results: Treatment with a PPARα agonist was associated with increased plasma concentrations of most biomarkers, with the most pronounced differences observed for betaine, dimethylglycine, glycine, nicotinamide, methylnicotinamide, pyridoxal and methylmalonic acid. Lower levels were observed for flavin mononucleotide. Fewer associations were observed after treatment with a PPARγ agonist, and the most notable was increased plasma serine., Conclusion: Treatment with a PPARα agonist influenced plasma concentration of one-carbon metabolites and markers of B-vitamin status. This confirms previous findings, suggesting specific involvement of PPARα in the regulation of these metabolic pathways as well as the status of closely related B-vitamins., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: ØM and PMU are employed by BEVITAL A/S (www.bevital.no), who performed the biochemical analyses for this study. This commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors have declared no competing interests.

Purpose: The aim of this study was to investigate circulating folic acid (FA) and predict circulating FA concentrations in the population related to dietary intake, vitamin concentrations, and interaction with the genetic variants involved in folate metabolism., Methods: Data were from the 'Health Survey of São Paulo' a cross-sectional population-based survey, conducted in São Paulo City, Brazil. The participants (n = 750) provided fasting blood samples and food intake data. Folate, homocysteine, and B6 and B12 vitamins were assayed. DNA was isolated, and the genotypes for polymorphisms involved in folate metabolism were determined. A generalized linear model was performed to predict circulating FA concentration., Results: The circulating FA was detected in 80.0% of the population, with a median concentration of 1.6 nmol/L (IQR 0.5-2.9). The increase of circulating FA concentrations was directly associated with total folate concentration (β coeff. 1.03; 95% CI 1.02-1.04), age (β coeff. 1.01; 95% CI 1.01-1.02), current smoker (β coeff. 1.51; 95% CI 1.16-1.97), self-reported skin color (β coeff. 1.83; 95% CI 1.51-2.20), as well as interaction between folate concentration and 19-bp deletion polymorphism in DHFR (β coeff. 1.02; 95% CI 1.01-1.03), and inversely associated with vitamin B6 (β coeff. 0.99; 95% CI 0.98-0.99)., Conclusions: In the current study, the presence of detectable circulating folic acid is high, and its concentration is elevated compared with other populations. Age, smoking, lower concentration of vitamin B6 and genetic variant are associated with increased levels of circulating FA. Further researches are needed to acknowledge and guarantee the safety of exposure to folic acid, especially in countries which have mandatory fortification.

B-vitamin deficiency is common in ageing populations either due to altered dietary habits or altered digestive and metabolic functions. There is limited data on the acute circulating concentrations of B-vitamins and their various forms (vitamers), following ingestion of realistic meals. This study compared the acute circulating B-vitamin and vitamer responses to either an energy-dense (ED) or a nutrient-dense (ND) breakfast meal, consumed in a randomized cross-over sequence, in older and younger adults ( n = 15 and 15, aged 67.3 ± 1.5 and 22.7 ± 0.5 years (mean ± SEM), respectively). Eleven differing B-vitamins and vitamers were determined in plasma samples by ultra-high-performance liquid chromatography-tandem mass spectrometry, in the fasting and postprandial state (hourly for 5 h). While postprandial thiamine concentration increased following both meals, riboflavin increased only following a ND meal in both age groups. Many vitamins including nicotinic acid, pantothenic acid, pyridoxal, pyridoxamine, pyridoxal-5'phosphate, and 4-pyridoxic acid remained unaltered, and flavin mononucleotide (FMN), nicotinamide and nicotinuric acid concentrations reduced following both meals. Biological age and food composition had minimal impact on postprandial B-vitamin concentrations, yet the differences between the ED and ND meals for riboflavin highlight the importance of riboflavin intake to achieve adequacy.

Herein, we propose a facile chemical reduction method to synthesize the molybdenum carbide (Mo 2 C) nanoparticles and its application for the electrochemical detection of folic acid (FA) through imprinting technique. Raman scattering, photoelectron spectroscopy and electron microscopy techniques were employed to study the properties of Mo 2 C nanoparticles. FA imprinting was carried out in the presence of pyrrole monomer over Mo 2 C modified glassy carbon electrode (GCE). The proposed sensor showed the detection behavior for wide range of FA concentrations from 0.01 μM to 120 μM with an excellent LOD value of 4 nM and good selectivity toward FA as compared to other co-existing species in real samples. The fabricated MIP-Mo 2 C/GCE sensors were able to be replicated with ∼1.9% RSD, and their reproduced sensor offered good repeatability (RSD; 1.6%) and stability., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B 12 concentrations, which could have hematological or neurological implications. This meta-analyses reviewed all available studies on associations between metformin use and vitamin B 12 levels, anemia, and neuropathy in diabetic patients., Methods: PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes., Results: Thirty-one studies were included in the meta-analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B 12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I 2  = 64%) and significantly lower serum vitamin B 12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I 2  = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B 12 concentrations from baseline in diabetic patients (MD -14.68%; 95% CI -17.98%, -11.39%; P < 0.00001; I 2  = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy., Conclusions: Metformin use led to significantly lowered vitamin B 12 concentrations and significantly higher risk of vitamin B 12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B 12 assessment in diabetic patients taking metformin is recommended., (© 2019 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Vitamin B12 plays an essential role in one-carbon metabolism in the human body. A deficiency in this vitamin can lead to severe haematopoietic and neuropsychiatric disorders and is currently treated by oral or parenteral administration of exogenous vitamin. Unfortunately, the absorption of orally taken vitamin B12 is low and highly variable, while injections can cause pain and anxiety. Thus, an efficient alternative drug delivery system for overcoming these shortcomings is highly desirable. Novel polymeric microneedle (MN) arrays have the potential for minimally invasive transdermal treatment of vitamin B12 deficiency. Bilayer dissolving MN arrays (19 × 19 needles, 600 µm height) containing 135 µg vitamin B12 were cast using two different aqueous polymer blends. MN arrays showed sufficient mechanical strength for skin insertion, dissolved rapidly and delivered 72.92% of their drug load in vitro over 5 h. Ultimately, the potential of delivering a therapeutically relevant dose of vitamin B12 transdermally was demonstrated in vivo in Sprague-Dawley rats by comparison to subcutaneous injections. Maximum plasma levels of 0.37 µg/mL occurred 30 min post-MN application, highlighting the ability of fabricated MN arrays to rapidly deliver vitamin B12 transdermally., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: We examined the association of plasma B-vitamins and metabolites, and related genetic variants, with risk of breast cancer among predominantly premenopausal women., Methods: We conducted a nested case-control study within the Nurses' Health Study II. From blood samples collected in 1996-1999 and follow-up through 2007, plasma measures were available for 610 cases and 1207 controls. Unconditional multivariable logistic regression was used to estimate relative risks (RR) of breast cancer and 95% confidence intervals (CIs). We examined whether associations varied by methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase polymorphisms, breast cancer risk factors, or tumor characteristics., Results: Plasma vitamin B 12 was associated with a 64% higher risk of breast cancer comparing the highest versus lowest quintile (95% CI 1.17-2.29, p-trend = 0.02). Plasma folate (comparable RR = 1.18, 95% CI 0.84-1.66), pyridoxal 5'-phosphate (RR = 1.18, 95% CI 0.85-1.64), homocysteine (RR = 0.93, 95% CI 0.67-1.28), cysteine (RR = 1.14, 95% CI 0.81-1.62), and cysteinylglycine (RR = 0.93, 95% CI 0.66-1.31) were not associated with overall breast cancer risk. Folate was significantly positively associated with invasive and estrogen receptor-positive/progesterone receptor-positive breast cancer, and this association was suggestively stronger for bloods collected post-fortification. Several nutrient/breast cancer associations varied across subgroups defined by age, smoking, alcohol, multivitamin use, and MTHFR status (p-interaction < 0.05)., Conclusions: Overall, plasma B-vitamins and metabolites were not associated with lower breast cancer risk. Plasma vitamin B-12 was positively associated with higher risk of overall breast cancer, and plasma folate was positively associated with risk of invasive breast cancer. Additionally, there may be associations in subgroups defined by related genetic variants, breast cancer risk factors, and tumor factors. Further studies in younger women and in the post-fortification era are needed to confirm these findings.

There are several methods to treat vitamin B12 deficiency (VB12d): intramuscular (IM), oral, sublingual (SL), and intranasal vitamin B12 (VB12) preparations. Large studies comparing the efficacy of SL vs. IM supplements are lacking. The aim of the present study was to compare the efficacy of SL versus the standard IM administration of VB12 in restoring B12 levels. This was a retrospective analysis of data from the computerized pharmacy records of Maccabi Health Service (MHS). Data were recorded for all patients older than 18 years of age who were prescribed VB12 during January 2014-December 2017. The main outcome was the change in levels of serum vitamin B12 (sVB12) after treatment. Overall, there were 4281 patients treated with VB12 supplements. Of them, 830 (19.3%) patients were treated with VB12 IM injections and 3451 (80.7%) with SL tablets. The mean ± SD difference between sVB12 levels before and after administration of VB12 supplements was significantly higher in the SL group vs. IM injection group (252 ± 223 vs. 218 ± 184 ng/L, p < 0.001). SL VB12 significantly increased the odds ratio (OR) for an increase of sVB12 levels, compared to the IM group, OR 1.85, CI 95% 1.5-2.3, p < 0.001. This is the largest study that documents therapy with SL preparations of VB12 sufficient and even superior to the IM route. The SL overcomes the challenges of IM injections and should be the first line option for patients with VB12d.

Background: Diet may influence vascular function through elevated homocysteine (Hcy) concentrations. However the relationship between dietary patterns (DP), characterised by Hcy and its associated nutrients is unknown., Objective: To identify a DP characterised by plasma Hcy, dietary folate and dietary vitamin B12, and examine its associations with two markers of vascular function: carotid intima-media thickness (cIMT) and pulse wave velocity (PWV)., Methods: 1562 participants of the MRC National Survey of Health and Development (NSHD), a British birth cohort, with dietary data measured at least once between 36 and 60-64 years, and cIMT or PWV measured at 60-64 years were included. DPs were derived using reduced rank regression with three intermediate variables: 1) plasma Hcy (μmol/L) 2) folate intake (μg/1000 kcal) 3) vitamin B12 intake (μg/1000 kcal). Multiple regression models assessed associations between the derived DP z-scores and vascular function adjusting for dietary misreporting, socioeconomic position, BMI, smoking, physical activity and diabetes., Results: A DP explaining the highest amount of shared variation (4.5%) in plasma Hcy, dietary folate and dietary vitamin B12 highly correlated with folate (r = 0.96), moderately correlated with vitamin B12 (r = 0.27), and weakly correlated with Hcy (r = 0.10). This "high B-vitamin" DP (including folate) was characterised by high intakes of vegetables, fruit and low fibre breakfast cereal, and low intakes of processed meat, white bread, sugar and preserves. No associations were observed between DP z-scores and vascular function at any time point following adjustment for covariates., Conclusion: This study explored a specific hypothesised pathway linking diet to vascular function. Although we found no consistent evidence for an association between a high B-vitamin DP and vascular function, we did observe an association with CRP and triglycerides in secondary analyses. Further analyses using strongly correlated and biologically relevant intermediate variables are required to refine investigations into diet and CVD in longitudinal cohort data., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Mental health disorders are major contributors to disease burden in older people. Deficient status of folate and the metabolically related B vitamins may be implicated in these conditions. This study aimed to investigate folate, vitamin B 12 , vitamin B 6 , and riboflavin in relation to depression and anxiety in aging and also considered the role of fortified foods as a means of optimizing B-vitamin status and potentially reducing the risk of these mental health disorders., Design: The Trinity Ulster Department of Agriculture (TUDA) aging study was a cross-sectional cohort study., Setting and Participants: Community-dwelling adults (n = 5186; ≥60 years) recruited from 2 jurisdictions within the island of Ireland from 2008 to 2012., Measures: Depression and anxiety were assessed using the Centre for Epidemiological Studies Depression (CES-D) and the Hospital Anxiety and Depression (HAD) scales, respectively. The following B-vitamin biomarkers were measured: red blood cell folate, serum total vitamin B 12 , plasma pyridoxal-5-phosphate (PLP; vitamin B 6 ), and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin)., Results: Biomarker values in the lowest 20% of status for folate (odds ratio [OR] 1.79; 95% CI 1.23-2.61), vitamin B 6 (OR 1.45, 95% CI 1.01-2.06), or riboflavin (OR 1.56, 95% CI 1.10-2.00), but not vitamin B 12 , were each associated with an increased risk of depression (CES-D score ≥16). Correspondingly, B vitamin-fortified foods if consumed daily were associated with a reduced risk of depression (OR 0.54, 95% CI 0.41-0.70). A deficient status of vitamin B 6 (OR 1.73, 95% CI 1.07-2.81), but not other vitamins, was associated with increased anxiety., Conclusions/implications: Better B-vitamin status may have a role in impacting positively on mental health in older adults. Regular intake of fortified foods can provide a means of optimizing B-vitamin status and thus could contribute to reducing depression. If confirmed by a randomized trial, these results may have implications for nutrition and mental health policy, and thus quality of life, in older people., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

B-group vitamins, as components of the one carbon metabolism pathway, are involved in DNA synthesis, repair and methylation. Our aim was to investigate associations between circulating plasma levels of B vitamins and urothelial cell carcinoma (UCC). We conducted a nested case-control study of UCC within the Melbourne Collaborative Cohort Study. B vitamins were measured in pre-diagnostic plasma samples. Conditional logistic regression was used to estimate odds ratios (OR) for UCC risk associated with circulating B vitamins in 363 matched cases and controls. In a case-only analysis (N = 390), hazard ratios (HR) for overall survival associated with plasma B vitamins were estimated using Cox regression. There were no strong associations between UCC risk and pre-diagnostic levels of plasma B vitamins. No heterogeneity in UCC risk was observed by subtype (invasive or superficial), sex, smoking status or alcohol intake. There was no heterogeneity by country of birth for most B vitamins, except for folate (p-homogeneity = 0.03). In UCC cases, there were no strong associations between plasma B vitamins and overall survival. We found no associations between pre-diagnostic plasma concentrations of B-group vitamins and UCC risk or survival., (© 2018 UICC.)

The potential for B-vitamins to reduce plasma homocysteine (Hcy) and reduce the risk of Alzheimer's disease (AD) has been described previously. However, the role of Apolipoprotein E є4 (APOE4) in this relationship has not been adequately addressed. This case-control study explored APOE4 genotype in an Australian sample of 63 healthy individuals (female = 38; age = 76.9 ± 4.7 y) and 63 individuals with AD (female = 35, age = 77.1 ± 5.3 y). Findings revealed 55 of 126 participants expressed the APOE4 genotype with 37 of 126 having both AD and the APOE4 genotype. Analysis revealed an increased likelihood of AD when Hcy levels are >11.0 µmol/L (p = 0.012), cysteine levels were <255 µmol/L (p = 0.033) and serum folate was <22.0 nmol/L (p = 0.003; in males only). In females, dietary intake of total folate <336 µg/day (p=0.001), natural folate <270 µg/day (p = 0.011), and vitamin B2 < 1.12 mg/day (p = 0.028) was associated with an increased AD risk. These results support Hcy, Cys, and SF as useful biomarkers for AD, irrespective of APOE4 genotype and as such should be considered as part of screening and managing risk of AD.

Here, an ultrasensitive and low-cost electrochemical aptasensing assay is developed based on the applicability of a fabricated nanocomposite from nitrogen-doped graphene quantum dots (N-GQDs) and gold nanoparticles (AuNPs). A modified glassy carbon electrode (GCE) with the AuNPs@N-GQDs nanocomposite (AuNPs@N-GQDs/GCE) as an efficient platform has some unique properties such as high surface area and electrical conductivity. Furthermore, the prepared platform is capable of more loading of aptamer (Apt) molecules as a biological recognition element of Ibuprofen (IBP) on the modified electrode surface. It is noteworthy that in this study, riboflavin (RF) as a universal green probe is used for the first time for electrochemical detection of IBP. According to the proposed strategy and under the optimum condition, the unprecedented detection limit (LOD) of this assay (33.33 aM) is lower than previously reported analytical methods. The results demonstrate the ability of the nanocomposite for designing of the aptasensor, integrated within the electrode format, to cheaper and simpler detection of the IBP with a specificity and sensitivity sufficient for analysis in real samples. It seems that the proposed strategy based on the AuNPs@N-GQDs nanocomposite can be expanded to other nanomaterials. So, this is expected to have promising implications in the design of electrochemical sensors or biosensors for the detection of various targets., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Imbalance of homocysteine (Hcy) metabolism links with several pathologies; nevertheless, it is poorly characterized in pediatric populations. This study investigated the impact of age on plasma concentrations of Hcy and relevant biomarkers along with correspondent genotype interactions., Methods: A healthy pediatric cohort aged 9 ( n = 195) and 17 ( n = 128) years old (yo) was studied. Immunoassays and GC-MS-SIM-mode quantified plasma levels of Hcy and biomarkers. PCR-RFLP or quantitative-PCR assays assessed common variations in related genes., Results: Age impacted on levels of Hcy and metabolic markers: older children presented with the lowest folates and total-cobalamin (tCbl), while with the highest Hcy concentrations, whereas methylmalonic acid (MMA) and holotranscobalamin (Holo-TC) levels remained similar in 9-yo and 17-yo children. The relationships between B-vitamins and metabolic markers were also dependent on age. Only in the older children, MMA correlated with tCbl and Holo-TC, and MMA levels were markedly higher in the 17-yo subjects presenting with the lowest quartiles of Holo-TC concentrations. Lastly, age also impacted on the correlations between genotype and biomarkers. In the 17-yo group, however not in the 9-yo children, tHcy differed between MTHFR 677 genotypes, with subjects who had the MTHFR 677TT genotype displaying the highest tHcy concentrations., Conclusions: Age impacts on the Hcy metabolism dynamics in a pediatric population.

A central aim of research in the psychological and brain sciences is to establish therapeutic interventions to promote healthy brain aging. Accumulating evidence indicates that diet and the many bioactive substances present in food are reasonable interventions to examine for dementia prevention. However, interdisciplinary research that applies methods from nutritional epidemiology and network neuroscience to investigate the role of nutrition in shaping functional brain network efficiency remains to be conducted. The present study therefore sought to combine methods across disciplines, applying nutrient biomarker pattern (NBP) analysis to capture the effects of plasma nutrients in combination and to examine their collective influence on measures of functional brain network efficiency (small-world propensity). We examined the contribution of NBPs to multiple indices of cognition and brain health in non-demented elders (n = 116), investigating performance on measures of general intelligence, executive function, and memory, and resting-state fMRI measures of brain network efficiency within seven intrinsic connectivity networks. Statistical moderation investigated whether NBPs influenced network efficiency and cognitive outcomes. The results revealed five NBPs that were associated with enhanced cognitive performance, including biomarker patterns high in plasma: (1) ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), (2) lycopene, (3) ω-3 PUFAs, (4) carotenoids, and (5) vitamins B (riboflavin, folate, B12) and D. Furthermore, three NBPs were associated with enhanced functional brain network efficiency, including biomarker patterns high in plasma: (1) ω-6 PUFAs, (2) ω-3 PUFAs, and (3) carotene. Finally, ω-3 PUFAs moderated the fronto-parietal network and general intelligence, while ω-6 PUFAs and lycopene moderated the dorsal attention network and executive function. In sum, NBPs account for a significant proportion of variance in measures of cognitive performance and functional brain network efficiency. The results motivate a multidisciplinary approach that applies methods from nutritional epidemiology (NBP analysis) and cognitive neuroscience (functional brain network efficiency) to characterize the impact of nutrition on human health, aging, and disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background:: Folate and vitamin B 12 are essential micronutrients, the deficiency of which can be associated with public health problems worldwide., Aim:: The aims of this study were to assess the folate and vitamin B 12 status of healthy adults and the effect of gender differences on their deficiency using serum folate, vitamin B 12 and red blood cell (RBC) folate as biomarkers and their relation to hematological indices., Methods:: This study was a part of the Azar cohort study, which is designed as a noncommunicable disease survey in the population of Shabestar, East Azerbaijan, Iran. A total of 95 healthy adults (35 men, 60 women) were chosen according to exclusion criteria and assessed using demographic characteristics and blood sampling., Results:: Low concentrations of serum folate, vitamin B 12 and RBC folate were detected in 16.8%, 61.1% and 40% of all subjects, respectively. Prevalence of low serum folate and vitamin B 12 was higher in men than women (25.7% versus 11.7% for serum folate, 77.1% versus 51.7% for serum vitamin B 12 ).A significant positive correlation was found between hemoglobin and serum folate, vitamin B 12 and RBC folate concentrations ( r = 0.279, 0.335, 0.228, respectively). No statistically significant correlation between mean corpuscular volume and serum folate, vitamin B 12 and RBC folate was seen ( r = -0.049, -0.030, -0.016, respectively)., Conclusions:: There was a high prevalence of low folate and vitamin B 12 concentrations in our community. Regarding the impact of these two vitamins deficiency on overall health, we suggest further investigations with more participants. In addition, monitoring hematological indices could be useful in people with folate and vitamin B 12 deficiency.

Purpose: We compare the effect of 8-week oral supplementation with cyano-B12 (currently used in vitamin pills) and hydroxo-B12 (predominant form in the diet) in a population with nutritional vitamin B12 deficiency., Methods: Fifty-one healthy Indian adults with baseline serum cobalamin < 200 pmol/L were supplied for 8 weeks with daily oral supplements of 3-µg cyano-B12 (n = 15), 3-µg hydroxo-B12 (n = 16), or a placebo (n = 20). Blood at baseline, and each following week, was examined for total cobalamin, holotranscobalamin, methylmalonic acid, and homocysteine., Results: The study groups did not differ at baseline and were characterized by [median (range)] serum cobalamin [128 (68-191) pmol/L], holotranscobalamin [16 (6-41) pmol/L], methylmalonic acid [0.8 (0.3-1.7) µmol/L], homocysteine [17.9 (8.5-100.9) µmol/L], and a combined indicator of B12 status 4cB12 of - 1.65 (- 0.64 to - 4.07). The group supplemented with cyano-B12 showed a higher increase in total serum cobalamin than the group treated with hydroxo-B12, while other biomarkers changed comparably in the two groups. After 8 weeks of treatment, the biomarker values of the supplemented groups (pooled) differed significantly from the placebo group. Yet, the vitamin B12 status was still poor [cobalamin: 168 (87-302) pmol/L; holotranscobalamin: 19 (8-45) pmol/L; methylmalonic acid: 0.7 (0.2-1.7) µmol/L; homocysteine: 17.2 (2.6-96.8) µmol/L; 4cB12 = - 1.34 (- 0.33 to - 3.3)]., Conclusion: 8-week supplementation with 3-µg cyano-B12 elevated serum cobalamin more than 3 µg hydroxo-B12, but all other biomarkers changed similarly in both groups. Supplementation with 3 µg vitamin B12 did not reverse the low status in individuals with nutritional vitamin B12 deficiency., Clinical Trial Registry of India: REF/2017/02/013343.

Objective: To describe the reference intervals of folate, vitamin B12, vitamin B6, and vitamin B1 by sex and age., Methods: The study was performed by gathering data on 55,811 subjects from 57 medical centers. Groups were categorized based on age and grouped according to statistical significance values. The reference values for the different groups were determined using the Bhattacharya and Hoffmann methods., Results: Vitamin B1 and B6 values and folate (vitamin B9) levels between the sexes were statistically significantly increased in the group aged 0 to 10 years. Likewise, we witnessed a similar increase in vitamin B12 levels in the group aged 0 to 5 years. However, low vitamin B6 levels (P <.001) were detected in nongeriatric patients (aged 0-60 years), and the reference intervals (3.4-41.9 µg/L) also were significantly different from those in the geriatric group (aged 61-100 years; 2.0-29.4 µg/L)., Conclusion: A lower vitamin B6 reference limit allows detection of subclinical vitamin deficiency more precisely in the geriatric group; respective reference intervals should be revised accordingly.

Objectives: Biotin is a component of the vitamin B complex used in standard immunoassays to detect serum levels of various hormones and non-hormones, including thyrotropin (TSH) and thyroxine. These assays involve a strong bond between streptavidin and biotin, which serves as an anchor for measured analytes. Large doses of exogenous biotin for the treatment of certain medical conditions have resulted in assay interference, causing TSH to be spuriously lowered. Smaller doses of biotin found in dietary supplements also have caused assay interference., Methods: We describe four cases in which over-the-counter (OTC) biotin caused erroneous thyroid diagnosis and clinical confusion in patients with preexisting thyroid disease. Serum TSH and thyroxine were measured by the Vitros 5600 assay., Conclusions: Although the biotin-streptavidin interaction is sensitive for detecting serum levels of TSH, it is subject to interference by exogenous biotin at levels found in OTC products. The widespread use of OTC biotin for cosmetic purposes can adversely affect the diagnosis of the entire spectrum of functional thyroid disorders. Physicians must carefully and routinely question for the use of biotin before thyroid function testing., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The objective of this study was to determine the relationship between glucose dosage in parenteral nutrition and reductions in levels of body thiamine in rats. Vitamin-free infusions with differing amounts of glucose were administered to normal or thiamine-deficient rats for 5 days, after which urinary thiamine excretion and the amounts of thiamine in the blood, liver, brain, and skeletal muscles were measured. The total energy dosage was set at three levels (98, 140, and 196 kcal/kg), and the dose of amino acids was constant among all groups. Urinary thiamine excretions on Day 5 decreased with increasing glucose dosage in the infusions. In normal rats, the amount of thiamine in the blood and all organs decreased compared with the diet group; however, no significant differences were found among the infusion groups. In thiamine-deficient rats, on the other hand, the amount of thiamine in the liver and skeletal muscles did not differ significantly among infusion groups; however, the amount of thiamine in the brain and blood decreased with increasing glucose dosage. An organ-specific correlation was found between glucose dosage in infusions and reductions in levels of thiamine. To prevent thiamine deficiencies from affecting the central nervous system, greater caution must be exercised during high-caloric parenteral nutrition. However, a constant supply of thiamine seemed to be essential, irrespective of the amount of energy supplied via parenteral nutrition, to maintain a sufficient level of thiamine in the body., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Vitamin B deficiency in patients with inflammatory bowel disease (IBD) is well-documented; however, few studies have explored genomic damage in patients with IBD using the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. This study investigated the frequency of micronuclei (MNi) using the CBMN-Cyt assay and the level of vitamin B in patients with IBD. This prospective study was conducted in 15 patients with ulcerative colitis, 15 patients with Crohn's disease, and 30 healthy controls from one tertiary hospital. Serum vitamin B and homocysteine levels were measured, and the MNi status was analyzed using the CBMN-Cyt assay. The patients with IBD showed significantly lower serum pyridoxine levels and significantly higher homocysteine levels than controls. The frequencies of binucleated cells (BNCs) with MNi, nucleoplasmic bridges (NPBs), and nuclear buds (Nbuds) were 8.5 [5.8-13.5], 1.0 [0.0-1.9], and 5.4 [4.3-7.4] for the IBD group, and 5.9 [4.8-7.7], 0.2 [0.0-1.0], and 3.5 [2.9-5.4] for the control group (P =  0.011, P =  0.010, and P =  0.002), respectively. This study suggests that patients with IBD have increased frequencies of MNi and decreased levels of pyridoxine than healthy controls., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This report on vitamin B-12 (B12) is part of the Biomarkers of Nutrition for Development (BOND) Project, which provides state-of-the art information and advice on the selection, use, and interpretation of biomarkers of nutrient exposure, status, and function. As with the other 5 reports in this series, which focused on iodine, folate, zinc, iron, and vitamin A, this B12 report was developed with the assistance of an expert panel (BOND B12 EP) and other experts who provided information during a consultation. The experts reviewed the existing literature in depth in order to consolidate existing relevant information on the biology of B12, including known and possible effects of insufficiency, and available and potential biomarkers of status. Unlike the situation for the other 5 nutrients reviewed during the BOND project, there has been relatively little previous attention paid to B12 status and its biomarkers, so this report is a landmark in terms of the consolidation and interpretation of the available information on B12 nutrition. Historically, most focus has been on diagnosis and treatment of clinical symptoms of B12 deficiency, which result primarily from pernicious anemia or strict vegetarianism. More recently, we have become aware of the high prevalence of B12 insufficiency in populations consuming low amounts of animal-source foods, which can be detected with ≥1 serum biomarker but presents the new challenge of identifying functional consequences that may require public health interventions.

The possible roles of selected B vitamins in the development and progression of sarcopenia are reviewed. Age-related declines in muscle mass and function are associated with huge and increasing costs to healthcare providers. Falls and loss of mobility and independence due to declining muscle mass/function are associated with poor clinical outcomes and their prevention and management are attractive research targets. Nutritional status appears a key modifiable and affordable intervention. There is emerging evidence of sarcopenia being the result not only of diminished anabolic activity but also of declining neurological integrity in older age, which is emerging as an important aspect of the development of age-related decline in muscle mass/function. In this connection, several B vitamins can be viewed as not only cofactors in muscle synthetic processes, but also as neurotrophic agents with involvements in both bioenergetic and trophic pathways. The B vitamins thus selected are examined with respect to their relevance to multiple aspects of neuromuscular function and evidence is considered that requirements, intakes or absorption may be altered in the elderly. In addition, the evidence base for recommended intakes (UK recommended daily allowance) is examined with particular reference to original datasets and their relevance to older individuals. It is possible that inconsistencies in the literature with respect to the nutritional management of sarcopenia may, in part at least, be the result of compromised micronutrient status in some study participants. It is suggested that in order, for example, for intervention with amino acids to be successful, underlying micronutrient deficiencies must first be addressed/eliminated.