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Genes Oct 2021The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon... (Review)
Review
The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B, vitamin B, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (>17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538-1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (<7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.
Topics: Brain; Carbon; Embryonic Development; Female; Fetal Development; Fetus; Folic Acid; Humans; Pregnancy; Vitamin B 12
PubMed: 34681028
DOI: 10.3390/genes12101634 -
Advances in Nutrition (Bethesda, Md.) Mar 2022Vitamin B-12 deficiency is a major public health problem affecting individuals across the lifespan, with known hematological, neurological, and obstetric consequences.... (Review)
Review
Vitamin B-12 deficiency is a major public health problem affecting individuals across the lifespan, with known hematological, neurological, and obstetric consequences. Emerging evidence suggests that vitamin B-12 may have an important role in other aspects of human health, including the composition and function of the gastrointestinal (gut) microbiome. Vitamin B-12 is synthesized and utilized by bacteria in the human gut microbiome and is required for over a dozen enzymes in bacteria, compared to only 2 in humans. However, the impact of vitamin B-12 on the gut microbiome has not been established. This systematic review was conducted to examine the evidence that links vitamin B-12 and the gut microbiome. A structured search strategy was used to identify in vitro, animal, and human studies that assessed vitamin B-12 status, dietary intake, or supplementation, and the gut microbiome using culture-independent techniques. A total of 22 studies (3 in vitro, 8 animal, 11 human observational studies) were included. Nineteen studies reported that vitamin B-12 intake, status, or supplementation was associated with gut microbiome outcomes, including beta-diversity, alpha-diversity, relative abundance of bacteria, functional capacity, or short-chain fatty acids (SCFA) production. Evidence suggests that vitamin B-12 may be associated with changes in bacterial abundance. While results from in vitro studies suggest that vitamin B-12 may increase alpha-diversity and shift gut microbiome composition (beta-diversity), findings from animal studies and observational human studies were heterogeneous. Based on evidence from in vitro and animal studies, microbiome outcomes may differ by cobalamin form and co-intervention. To date, few prospective observational studies and no randomized trials have been conducted to examine the effects of vitamin B-12 on the human gut microbiome. The impact of vitamin B-12 on the gut microbiome needs to be elucidated to inform screening and public health interventions.
Topics: Animals; Humans; Gastrointestinal Microbiome; Vitamin B 12; Microbiota; Eating; Bacteria; Vitamins; Observational Studies as Topic
PubMed: 34612492
DOI: 10.1093/advances/nmab123 -
American Family Physician Sep 2021
Meta-Analysis
Topics: Helicobacter Infections; Helicobacter pylori; Humans; Network Meta-Analysis; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome
PubMed: 34523899
DOI: No ID Found -
Arquivos de Gastroenterologia 2021The vitamin B12 absorption can be affected in patients with nonalcoholic fatty liver disease (NAFLD), and low serum vitamin B12 levels has been related to the high... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The vitamin B12 absorption can be affected in patients with nonalcoholic fatty liver disease (NAFLD), and low serum vitamin B12 levels has been related to the high homocysteine (HCY) levels and to the degree of NAFLD.
OBJECTIVE
To carry out a systematic review and metanalysis of serum vitamin B12 and HCY levels in patients with NAFLD.
METHODS
Original studies including serum vitamin B12 and HCY levels in humans with NAFLD were included. The searches were performed in four databases.
RESULTS
159 studies were identified, and after excluding the duplicates and non-eligible titles, eight original articles were included. Six out of eight showed higher B12 levels in NAFLD patients (404.9±136.2 pg/mL in relation to controls 353.91±117.3 pg/mL). Seven of the eight studies also showed higher HCY levels in NAFLD patients (14.2±3.44 umol/L in relation to controls 11.05±3.6 umol/L). The results for serum vitamin B12 and HCY levels were submitted to metanalysis, showing no difference in the vitamin B12 levels between patients with NAFLD and controls. However, the levels of Hcy were higher in NAFLD patients than in controls.
CONCLUSION
There was no relashionship between the vitamin B12 levels and NAFLD. The levels of HCY were significantly higher in patients with NAFLD, suggesting this could be a potential marker for liver damage.
Topics: Biomarkers; Folic Acid; Homocysteine; Humans; Non-alcoholic Fatty Liver Disease; Vitamin B 12
PubMed: 34287533
DOI: 10.1590/S0004-2803.202100000-42 -
Medicine Jun 2021Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atorvastatin treatment has been suggested as a therapeutic method for women with polycystic ovary syndrome (PCOS) in many clinical studies. Nonetheless, the effects of atorvastatin on insulin resistance in PCOS patients still remain controversial.
OBJECTIVE
The aim of this report was to evaluate the effects of atorvastatin therapy on the insulin resistance in the treatment of PCOS compared to that of placebo, in order to confer a reference for clinical practice.
METHODS
Randomized controlled trials (RCTs) of atorvastatin for PCOS published up to August, 2020 were searched. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated, and heterogeneity was measured by the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: fasting glucose concentration, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) or body mass index (BMI) value.
RESULTS
Nine RCTs with 406 participants were included. The difference of fasting glucose concentration in PCOS patients between atorvastatin group and placebo group was not statistically significant (8 trials; SMD -0.06, 95% CI -0.31 to 0.20, P = .66). PCOS patients in atorvastatin group had lower fasting insulin level than those in placebo group (7 trials; SMD -1.84, 95% CI -3.06 to -0.62, P < .003). The homeostasis model assessment of insulin resistance (HOMA-IR) value showed significant decrease in the atorvastatin therapy compared to placebo (6 trials; SMD -4.12, 95% CI -6.00 to -2.23, P < .0001). In contrast to placebo, atorvastatin therapy did not decrease the BMI value significantly in PCOS patients (7 trials; SMD 0.12, 95% CI -0.07 to 0.31, P = .22).
CONCLUSIONS
Atorvastatin therapy can reduce insulin resistance in the treatment of patients with PCOS. In addition, further large-sample, multi-center RCTs are needed to identify these findings.
Topics: Adolescent; Adult; Atorvastatin; Blood Glucose; Body Mass Index; Fasting; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Treatment Outcome; Young Adult
PubMed: 34128863
DOI: 10.1097/MD.0000000000026289 -
Advances in Nutrition (Bethesda, Md.) Dec 2021Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise...
Although levodopa remains the most effective drug for symptomatic management of Parkinson's Disease (PD), treatment during advanced disease stages may raise unpredictable motor fluctuations and other complications. Counteracting these complications with other pharmacological therapies may prompt a vicious circle of side effects, and here, nutritional therapy may have great potential. Knowledge about the role of diet in PD is emerging and multiple studies have investigated nutritional support specifically with respect to levodopa therapy. With this systematic review, we aim to give a comprehensive overview of dietary approaches to optimize levodopa treatment in PD. A systematic search was performed using the databases of PubMed and Scopus between January 1985 and September 2020. Nutritional interventions with the rationale to optimize levodopa therapy in human PD patients were eligible for this study and their quality was assessed with the Cochrane risk-of-bias tool. In total, we included 22 papers that addressed the effects of dietary proteins (n = 10), vitamins (n = 7), fiber (n = 2), soybeans (n = 1), caffeine (n = 1), and ketogenic diets (n = 1) on levodopa therapy. Interventions with protein redistribution diets (PRDs), dietary fiber, vitamin C, and caffeine improved levodopa absorption, thereby enhancing clinical response and reducing motor fluctuations. Furthermore, supplementation of vitamin B-12, vitamin B-6, and folic acid successfully reduced high homocysteine concentrations that emerged from levodopa metabolism and promoted many metabolic and clinical complications, such as neuropathology and osteoporosis. In conclusion, dietary interventions have the potential to optimize levodopa efficacy and control side effects. Nutrition that improves levodopa absorption, including PRDs, fiber, vitamin C, and caffeine, is specifically recommended when fluctuating clinical responses appear. Supplements of vitamin B-12, vitamin B-6, and folic acid are advised along with levodopa initiation to attenuate hyperhomocysteinemia, and importantly, their potential to treat consequent metabolic and clinical complications warrants future research.
Topics: Antiparkinson Agents; Diet; Humans; Levodopa; Parkinson Disease; Vitamin B 12
PubMed: 34113965
DOI: 10.1093/advances/nmab060 -
IUBMB Life Jan 2022Hyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B , B , and folate. Previous findings...
Hyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B , B , and folate. Previous findings suggest that adequate intake of these vitamins may reduce homocysteine levels. This review aimed to assess the effects of treatment with vitamins B B , and/or folic acid in the homocysteine levels in patients with mild cognitive impairment (MCI). A systematic literature review was conducted in EMBASE, MEDLINE®, PsycINFO, and Cochrane Central Register of Controlled Trials. The research question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: in patients with MCI (P); what is the efficacy of vitamins B , B , and/or folic acid intake (I); compared with baseline values, and/or compared with controls (C); in reducing homocysteine levels from baseline (O). A total of eight primary studies with a total of 1,140 participants were included in the review. Four were randomized controlled trials, one was a quasi-controlled trial, and three were observational studies. All studies included folic acid in their intervention, seven vitamin B , and four vitamin B . Mean (SD) length of the intervention period was 18.8 (19.3) months, ranging from 1 to 60 months. All studies showed a statistically significant decrease in homocysteine levels in groups treated with vitamins B B , and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms whereas it increased by 0.7% in the control arm. This review identified evidence of a reduction of plasma homocysteine levels in MCI patients taking vitamins B B , and/or folic acid supplements, with statistically significant declines being observed after 1 month of supplementation. Findings support that supplementation with these vitamins might be an option to reduce homocysteine levels in people with MCI and elevated plasma homocysteine.
Topics: Cognitive Dysfunction; Dietary Supplements; Folic Acid; Homocysteine; Humans; Randomized Controlled Trials as Topic; Vitamin B 12; Vitamin B 6; Vitamins
PubMed: 34058062
DOI: 10.1002/iub.2507 -
Clinical Otolaryngology : Official... Sep 2021Novel cancer immunotherapy seeks to harness the body's own immune system and tip the balance in favour of antitumour activity. The intracellular enzyme indoleamine...
BACKGROUND
Novel cancer immunotherapy seeks to harness the body's own immune system and tip the balance in favour of antitumour activity. The intracellular enzyme indoleamine 2,3-dioxygenase (IDO) is a critical regulator of the tumour microenvironment (TME) via tryptophan metabolism. The potential immunotherapeutic role of IDO in head and neck squamous cell carcinoma (HNSCC) requires further exploration. We aim to assess the evidence on IDO in HNSCC.
METHODS
A systematic review of literature and clinical trials databases.
RESULTS
We included 40 studies: seven involved cell lines: eight assessed tumour immunohistochemistry: ten measured IDO gene transcription: 15 reported on clinical trials. Increased cell line IDO expression was postulated to adversely affect tumour metabolism and apoptosis. Immunohistochemical IDO expression correlated with worse survival. Gene transcription studies associated IDO with positive PD-L1 and human papillomavirus (HPV) status. Phase I/II clinical trials showed (a) overall response (34%-55%) and disease control rates (62%-70%) for IDO1 inhibitor in combination with a PD-1 inhibitor, (b) similar safety profiles when both are used in combination therapy compared to each as monotherapies and (c) IDO gene expression as a predictive biomarker for response to PD-L1 therapy.
CONCLUSIONS
IDO expression is increased in the TME of HNSCC, which correlates with poor prognosis. However, the exact mechanism of IDO-driven immune modulation in the TME is an enigma. Future translational studies should map IDO activity during HNSCC treatment and elucidate its precise role in the TME, such research will underpin the development of clinical trials establishing the efficacy of IDO inhibitors in HNSCC.
Topics: Biomarkers, Tumor; Cell Line, Tumor; Humans; Immunotherapy; Indoleamine-Pyrrole 2,3,-Dioxygenase; Squamous Cell Carcinoma of Head and Neck; Tumor Microenvironment
PubMed: 34053179
DOI: 10.1111/coa.13794 -
Frontiers in Endocrinology 2021Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current...
Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India.
BACKGROUND
Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy.
METHODS
A systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
RESULTS
Of the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT's -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT's) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring.
CONCLUSION
In the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia.
SYSTEMATIC REVIEW REGISTRATION
[website], identifier [registration number].
Topics: Female; Folic Acid; Humans; India; Pregnancy; Pregnancy Outcome; Vitamin B 12
PubMed: 33912132
DOI: 10.3389/fendo.2021.619176 -
Nutrients Mar 2021Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12... (Meta-Analysis)
Meta-Analysis
Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.
Topics: Cognition; Depression; Dietary Supplements; Fatigue; Humans; Vitamin B 12; Vitamins
PubMed: 33809274
DOI: 10.3390/nu13030923