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Concept: B vitamins

232

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

Concepts: Metabolism, Nutrition, Niacin, Vitamin, Folic acid, B vitamins, Thiamine, Pyridoxine

189

Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were “irritability, regressive behavior, apathy, crying and truancy” which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg’s sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg’s sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features especially with accompanying extrapyramidal symptoms lacking a clear etiology may be rare manifestation of vitamin B12 and/or folate deficiency in children and adolescents and be potentially amenable to treatment.

Concepts: Vitamin, Ataxia, Helicobacter pylori, Folic acid, Megaloblastic anemia, Vitamin B12, B vitamins, Vitamin B12 deficiency

166

Over the past few decades, food fortification and infant formula supplementation with high levels of vitamins have led to a sharp increase in vitamin intake among infants, children and adults. This is followed by a sharp increase in the prevalence of obesity and related diseases, with significant disparities among countries and different groups within a country. It has long been known that B vitamins at doses below their toxicity threshold strongly promote body fat gain. Studies have demonstrated that formulas, which have very high levels of vitamins, significantly promote infant weight gain, especially fat mass gain, a known risk factor for children developing obesity. Furthermore, ecological studies have shown that increased B vitamin consumption is strongly correlated with the prevalence of obesity and diabetes. We therefore hypothesize that excess vitamins may play a causal role in the increased prevalence of obesity. This review will discuss: (1) the causes of increased vitamin intake; (2) the non-monotonic effect of excess vitamin intake on weight and fat gain; and (3) the role of vitamin fortification in obesity disparities among countries and different groups within a country.

Concepts: Nutrition, Fat, Vitamin, Dietary supplement, Vitamins, Folic acid, B vitamins, Thiamine

149

Cobalamin/Vitamin B12 (Cbl) is an essential vitamin, supplied mainly as hydroxocobalamin (OHCbl) by animal products, including cows' milk. Cyanocobalamin (CNCbl) is the usual form in vitamin pills. The aim was to explore absorption and tissue accumulation of two Cbl forms, administered alone or bound to milk protein.

Concepts: Nutrition, Milk, Vitamin B12, Vitamin A, B vitamins, Cyanocobalamin, Hydroxocobalamin, Vitamer

139

To investigate the absorption of synthetic cyanocobalamin and natural occurring hydroxocobalamin in populations with low and normal cobalamin (vitamin B12) status.

Concepts: Vitamin B12, B vitamins, Methylcobalamin, Cyanocobalamin, Hydroxocobalamin

98

Ambient fine particle (PM2.5) pollution triggers acute cardiovascular events. Individual-level preventions are proposed to complement regulation in reducing the global burden of PM2.5-induced cardiovascular diseases. We determine whether B vitamin supplementation mitigates PM2.5 effects on cardiac autonomic dysfunction and inflammation in a single-blind placebo-controlled crossover pilot trial. Ten healthy adults received two-hour controlled-exposure-experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. At pre-, post-, 24 h-post-exposure, we measured resting heart rate (HR) and heart rate variability (HRV) with electrocardiogram, and white blood cell (WBC) counts with hematology analyzer. Compared to sham, PM2.5 exposure increased HR (3.8 bpm, 95% CI: 0.3, 7.4; P = 0.04), total WBC count (11.5%, 95% CI: 0.3%, 24.0%; P = 0.04), lymphocyte count (12.9%, 95% CI: 4.4%, 22.1%; P = 0.005), and reduced low-frequency power (57.5%, 95% CI: 2.5%, 81.5%; P = 0.04). B-vitamin supplementation attenuated PM2.5 effect on HR by 150% (P = 0.003), low-frequency power by 90% (P = 0.01), total WBC count by 139% (P = 0.006), and lymphocyte count by 106% (P = 0.02). In healthy adults, two-hour PM2.5 exposure substantially increases HR, reduces HRV, and increases WBC. These effects are reduced by B vitamin supplementation.

Concepts: Immune system, White blood cell, Blood, Blood vessel, Vitamin, Folic acid, Vitamin B12, B vitamins

56

Purpose Inconsistent findings have been reported of a link between the use of one-carbon metabolism-related B vitamins and lung cancer risk. Because of the high prevalence of supplemental vitamin B use, any possible increased association warrants further investigation. We examined the association between long-term use of supplemental B vitamins on the one-carbon metabolism pathway and lung cancer risk in the Vitamins and Lifestyle (VITAL) cohort, which was designed specifically to look at supplement use relative to cancer risk. Methods A total of 77,118 participants of the VITAL cohort, 50 to 76 years of age, were recruited between October 2000 and December 2002 and included in this analysis. Incident, primary, invasive lung cancers (n = 808) were ascertained by prospectively linking the participants to a population-based cancer registry. The 10-year average daily dose from individual and multivitamin supplements were the exposures of primary interest. Results Use of supplemental vitamins B6, folate, and B12 was not associated with lung cancer risk among women. In contrast, use of vitamin B6 and B12 from individual supplement sources, but not from multivitamins, was associated with a 30% to 40% increase in lung cancer risk among men. When the 10-year average supplement dose was evaluated, there was an almost two-fold increase in lung cancer risk among men in the highest categories of vitamin B6 (> 20 mg/d; hazard ratio, 1.82; 95% CI, 1.25 to 2.65) and B12 (> 55µg/d; hazard ratio, 1.98; 95% CI, 1.32 to 2.97) compared with nonusers. For vitamin B6 and B12, the risk was even higher among men who were smoking at baseline. In addition, the B6 and B12 associations were apparent in all histologic types except adenocarcinoma, which is the type less related to smoking. Conclusion This sex- and source-specific association provides further evidence that vitamin B supplements are not chemopreventive for lung cancer and may be harmful.

Concepts: Epidemiology, Cancer, Lung cancer, Vitamin, Dietary supplement, Folic acid, Vitamin B12, B vitamins

43

Subclinical micronutrient deficiency in older adults is associated with chronic age-related diseases and adverse functional outcomes. In Germany, the older population is at risk of insufficient micronutrient intake, but representative studies on micronutrient status in old and very old adults are scarce. This study’s objectives were to estimate the prevalence of subclinical vitamin D, folate, vitamin B12 and iron deficiencies among older adults, aged 65 to 93, from the KORA-Age study in Augsburg, Germany (n = 1079), and to examine associated predictors, using multiple logistic regression. Serum concentrations of 25-hydroxyvitamin D (25OHD), folate, vitamin B12, and iron were analyzed. The prevalence of subclinical vitamin D and vitamin B12 deficiencies were high, with 52.0% and 27.3% of individuals having low 25OHD (<50 nmol/L) and low vitamin B12 concentrations (<221 pmol/L), respectively. Furthermore, 11.0% had low iron (men <11.6 µmol/L, women <9.0 µmol/L) and 8.7% had low folate levels (<13.6 nmol/L). Common predictors associated with subclinical micronutrient deficiency included very old age, physical inactivity, frailty and no/irregular use of supplements. Subclinical micronutrient deficiency is a public health concern among KORA-Age participants, especially for vitamins D and B12. The predictors identified provide further rationale for screening high-risk subgroups and developing targeted public health interventions to tackle prevailing micronutrient inadequacies among older adults.

Concepts: Vitamin D, Vitamin, Gerontology, Vitamins, Ageing, Folic acid, Vitamin B12, B vitamins

40

Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections, in vital combination with oral folic acid. However, there is no established algorithm for individualized optimal dosages, and rate of improvement may differ considerably between responders.

Concepts: Vitamin, Folic acid, Vitamin B12, Fibromyalgia, Fatigue, Chronic fatigue syndrome, B vitamins, Vitamin B12 deficiency

37

Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world.

Concepts: Bacteria, Amino acid, Metabolism, Staphylococcus aureus, Antibiotic resistance, Vitamin, Cofactor, B vitamins