Ácido fólico em excesso: efeitos sobre o metabolismo das vitaminas B2 e B6, o catabolismo do triptofano e a resposta imune / Folic acid excess: effects on vitamin B2 and B6 metabolism, tryptophan catabolism and immune response

Introdução: A suplementação com ácido fólico (AF) é recomendada em algumas condições para evitar a deficiência de folato, como para mulheres no período periconcepcional e durante a gestação. Atualmente, existe uma preocupação quanto ao consumo excessivo de AF pela população pelo uso de suplementos com altas doses dessa vitamina. As vitaminas B6 e B2 agem como cofatores no metabolismo de um carbono, e o uso de altas doses de AF pode influenciar o metabolismo de ambas vitaminas e, consequentemente, interferir em metabolismos importantes das quais elas participam, como a via das quinureninas, e no sistema imune. Objetivo: Avaliar os efeitos da intervenção diária com uma alta dose de AF (5 mg) por 90 dias sobre marcadores do estado das vitaminas do complexo B, e as consequências sobre os metabólitos da via das quinureninas e o sistema imune em adultos saudáveis. Material e Métodos: 64 indivíduos saudáveis foram submetidos à intervenção diária com 5 mg de AF por 90 dias. Coletas de sangue foram realizadas antes (baseline) e após 45 e 90 dias de intervenção. As concentrações séricas de folato e vitamina B12 foram avaliadas por métodos microbiológicos. As concentrações séricas das vitaminas B6 (piridoxal 5'-fosfato (PLP), piridoxal (PL) e ácido 4-piridóxico (PA)), B2 (riboflavina e flavina mononucleotídeo (FMN)), B1 (tiamina e tiamina monofosfato (TMP)) e B3 (ácido nicotínico, nicotinamida e N1-metilnicotinamida), bem como de triptofano, quinurenina e metabólitos, foram avaliadas por LC-MS/MS. A proteína C-reativa ultrassensível (PCRus) foi determinada por imunoturbidimetria, e as concentrações séricas de interleucina (IL)-6, IL-8, IL-10, interferon gama (IFN-γ) e fator de necrose tumoral alfa (TNF-α) foram avaliadas por ensaio multiplex. A expressão de RNAm de DHFR (dihidrofolato redutase), MTHFR (metilenotetrahidrofolato redutase), IL8, TNFA e IFNG em leucócitos mononucleares (PBMC) foram avaliadas por PCR em tempo real. O número de células T regulatórias (Treg) (CD3+, CD4+, CD25high, FoxP3+, CD127-) foi avaliado após incubação dos PBMC com PMA e ionomicina ou veículo por 18h, por imunofenotipagem. Resultados: Houve um grande aumento das concentrações de folato sérico após 45 e 90 dias de intervenção com AF. Não houve diferença nas concentrações de vitamina B12 antes e após a intervenção. As concentrações séricas de PLP foram semelhantes antes e após a intervenção, entretanto, um aumento de PL sérico foi observado após 45 e 90 dias, e de PA após 45 dias, quando comparado ao baseline. Riboflavina e FMN foram maiores após 45 e 90 dias em relação ao baseline. A tiamina sérica foi menor após 45 dias, e as concentrações de TMP foram maiores após 90 dias quando comparados aos períodos anteriores. Não houve diferença nas concentrações de vitamina B3 antes e após a intervenção. Dentre os metabólitos da via das quinureninas, apenas o ácido antranílico apresentou aumento após 45 e 90 dias, enquanto o ácido picolínico diminuiu após 90 dias. PCRus, IL-6, IL-8, IL-10, IFN-γ e TNF-α séricos foram semelhantes no baseline e após a intervenção. Um aumento da expressão de RNAm de DHFR e TNFA foi observado após, respectivamente, 90 dias e 45 e 90 dias de intervenção. Após 90 dias de intervenção com AF, foi observada diminuição do número de células Treg após estímulo com PMA e ionomicina. Conclusão: O uso diário de 5 mg de AF foi associado a alterações nas concentrações séricas de marcadores do estado de vitaminas do complexo B e da via das quinureninas, bem como a diminuição do número de células Treg

Introduction: Folic acid (FA) supplementation is recommended in some conditions to avoid folate deficiency, as women during periconceptional period and pregnancy. Currently, there is a concern about the excessive consumption of FA by population by using supplements with high doses of this vitamin. Vitamins B6 and B2 are cofactors of enzymes of one carbon metabolism and, consequently, may disturb key metabolism in which they participate, as kynurenine pathway, and the immune system. Aim: To assess the effects of a daily intervention with high dose of FA (5 mg) for 90 days on biomarkers of complex B vitamins status and its outcomes in kynurenine pathway metabolites and immune system in healthy adults. Material and Methods: 64 healthy individuals were submitted to a daily intervention with 5 mg of FA for 90 days. Blood samples were collected before (baseline) and after 45 and 90 days of intervention. Serum folate and vitamin B12 were assessed by microbiological assays. Serum vitamin B6 (pyridoxal 5'-phosphate (PLP), pyridoxal (PL) and 4-pyridoxic acid (PA)), vitamin B2 (riboflavin and flavin mononucleotide (FMN)), vitamin B1 (thiamin and thiamin monophosphate)) and vitamin B3 (nicotinic acid, nicotinamide and N1-methylnicotinamide), as well as tryptophan, kynurenine and metabolites, were assessed by LC-MS/MS. C-reactive protein (hs-CPR) was assessed by immunoturbidimetry, and serum interleukin (IL)-6, IL-8, IL-10, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were assessed by multiplex assay. Mononuclear leukocytes mRNA expression of DHFR (dihydrofolate reductase), MTHFR (methylenetetrahydrofolate reductase), IL8, TNFA and IFNG were assessed by real time PCR. Regulatory T Cell (Treg) number (CD3+, CD4+, CD25high, FoxP3+, CD127-) was determined after mononuclear leukocytes incubation with PMA and ionomycin or vehicle for 18h, by immunophenotyping. Results: A great increase on serum folate was observed after 45 and 90 days of FA intervention. No differences in serum vitamin B12 were observed before and after intervention. Serum PLP was similar before and after intervention, however, an increase in serum PL was observed after 45 and 90 days, and in PA after 45 days, when compared to baseline. Riboflavin and FMN were increased after 45 and 90 days than in baseline. Serum thiamine was decreased after 45 days than in baseline. Serum TMP was increased after 90 days when compared with previous timepoints. No differences in vitamin B3 were observed after and before FA intervention. Among kynurenine pathway metabolites, anthranilic acid was increased after 45 and 90 days, while picolinic acid was decreased after 90 days. hs-CPR, serum IL-6, IL-8, IL-10, IFN-γ and TNF-α were similar at baseline and after intervention. An increase on mRNA expression of DHFR and TNFA was observed after, respectively, 90 days and 45 and 90 days of intervention. After 90 days of FA intervention, it was observed a decrease on Treg cell number after PMA and ionomycin stimulation. Conclusion: Daily use of 5 mg of FA was associated with changes in serum markers of B-complex vitamins status and kynurenine pathway, as well as decreased number of Treg cells

Use of Indian Date and Vitamin B-3 to Reduce Blood Pressure and to Raise HDL-Cholesterol

Background: Coronary artery disease is a complex syndrome to get initiation from formation of atherosclerotic plaques in systemic circulation to cardiac arrhythmia causing morbidity/mortality. This study was conducted to compare hypolipidemic effects of Niacin and Indian date (Jujuba) in hyperlipidemic patients. Methods: Study was conducted from July 2015 to December 2015 at National Hospital Lahore-Pakistan. Sixty participants were enrolled of both gender male and female patients age range from 25 to 60 years. Consent was taken from all patients. They were divided in two groups. Group-I was advised to take 2 grams Niacin in divided doses for the period of two months. Group-II was advised to take 500 grams of fruit Jujube daily for the period of two months. All patients’ systolic and diastolic blood pressure was noted. Their baseline LDL and HDL cholesterol was determined by conventional method of measuring Lipid Profile. Results: After two months therapy, their post treatment blood pressure and lipid profile was measured and mean values with ± SEM were analyzed biostatistically. Group-I which was on Niacin their blood pressure was reduced but it was non-significant change, LDL cholesterol decreased significantly and HDL cholesterol was increased significantly. In group-II patients LDL cholesterol was decreased significantly but HDL increase was not significant with p-value of >0.05. Conclusions: It was concluded from the research work that Niacin is potent in lowering LDL and increasing HDL cholesterol, while Jujube has significant effect as LDL cholesterol lowering potential, but it does not increase HDL cholesterol significantly. Jujubes and vitamin B-3 did not reduced blood pressure, when analyzed statistically.

Interactive effccts of salinity stress and nicoinamide on physiological and biiochemical parameters of faba bean plntt / Efectos combinados del estrés por salinidad y la nicotinamida sobre parámetros bioquímicos y fisiológicos en plantas de haba

A possible survival strategy for plants under saline conditions is to use some compounds that could alleviate the salt stress effect. One of these compounds is nicotinamide (vitamin B3/niacin). The effect of exogenous application of nicotinamide with different concentrations (0, 200 or 400 mg l-1) on faba bean (Vicia faba L.) plant grown at different NaCl levels (0, 50 or 100 mM) was investigated in the wire house of the National Research Centre, Cairo, Egypt. Salinity stress significantly reduced the photosynthetic pigments, polysaccharides, total carbohydrates, total-N contents of shoot, plant height, leaves number, fresh and dry weights of shoot, seed yield, total carbohydrates and total crude protein of the yielded seeds compared with those of the control plants. In contrast, salinity induced marked increases in sucrose, total soluble sugars, total free amino acids, proline, lipid peroxidation product (MDA) and some oxidative enzymes (polyphenol-oxidase and peroxidase). Also, salinity stress increased Na+ contents with the decreases of other macro and micro elements contents (P, K+, Mg2+, Ca2+, Fe2+, Mn2+, Zn2+ and Cu2+) of shoots and the yielded seeds of faba bean. Foliar spraying of nicotinamide alleviated the adverse effects of salinity stress through increased the photosynthetic pigments, polysaccharides, total carbohydrates, total N concentration of shoot, plant height, leaves number, fresh and dry weights of shoot, and seed yield as well as, sucrose, total soluble sugars, total free amino acids and proline, compared with those of the corresponding salinity levels, while decreased lipid peroxidation product as malondialdehyde (MDA) and the oxidative enzymes (polyphenol oxidase and peroxidase enzymes). Nicotinamide inhibited the uptake of Na+ and accelerated the accumulation of P, K+, Mg2+, Ca2+, Fe2+, Mn2+, Zn2+ and Cu2+ concentrations in the shoots of salt stressed plants and enhanced total carbohydrate and total crude protein percentage and solutes concentrations in seeds of salinity treated plants. Nicotinamide, not only neutralized the effect of salinity stress but resulted in a significant improvement in physiological and biochemical parameters as well as the concentrations of soluble sugars, proline, amino acids, and total N and other mineral contents.

Una posible estrategia de supervivencia para plantas que se desarrollan bajo condiciones de salinidad es emplear algunos compuestos que les permitan disminuir el estrés salino. Uno de estos compuestos es la nicotinamida (vitamina B3/ niacina). Se investigó el efecto de la aplicación exógena de nicotinamida en diferentes concentraciones (0, 200 o 400 mg l-1) sobre plantas de haba (Vicia faba L.) creciendo a diferentes niveles de NaCl (0, 50 o 100 mM) en los terrenos del National Research Centre, Cairo, Egipto. El estrés por salinidad reduce significativamente los contenidos de pigmentos fotosintéticos, polisacáridos, carbohidratos totales, nitrógeno total, peso de las plantas, número de hojas, pesos fresco y seco de tallos, rendimiento de semillas, y contenido de carbohidratos y proteina cruda total en semillas comparado con plantas control. En contraste, la salinidad induce incrementos marcados en sacarosa, azúcares solubles totales, aminoácidos libres totales, prolina, productos de peroxidación de lípidos como el malondialdehido (MDA) y algunas enzimas oxidativas (polifenol oxidasa y peroxidasa). También, el estrés por salinidad incrementa el contenido de Na+ y genera disminución de otros macronutrientes y micronutrientes (P, K+, Mg2+, Ca2+, Fe2+, Mn2+, Zn2+ y Cu2+) de los tallos y el rendimiento de semillas en plantas de haba. La aspersión foliar de nicotinamida disminuye los efectos adversos del estrés salino incrementando los pigmentos fotosintéticos, polisacáridos, carbohidratos totales, concentración total de nitrógeno en tallos, peso de las plantas, número de hojas, pesos frescos y secos de tallos, y rendimiento de semillas; así como los niveles de sacarosa, azúcares solubles totales, aminoácidos libres totales y prolina, comparado con aquellos correspondientes al estrés por salinidad, mientras disminuyeron los productos de peroxidación de lípidos (MDA) y las enzimas oxidativas (polifenol oxidasas y peroxidasas). La nicotinamida inhibe la toma de Na+ y acelera la acumulación de P, K+, Mg2+, Ca2+, Fe2+, Mn2+, Zn2+ y Cu2+ en los tallos de plantas bajo estrés salino, y aumenta el porcentaje total de carbohidratos y proteína cruda y la concentración de solutos en semillas obtenidas de plantas tratadas contra el estrés salino. La nicotinamida no solo neutraliza el efecto del estrés salino, sino que mejora significativamente parámetros fisiológicos y bioquímicos tales como la concentración de azúcares solubles, prolina, aminoácidos y contenido total de nitrógeno y otros minerales.

Two Cases of Pellagra in Alcoholics / 대한피부과학회지

Pellagra is a chronic wasting disorder characterized by 3 clinical distinct symptoms; dermatitis; dementia; and diarrhea. It results from a marked cellular deficiency of water-soluble vitamin B3, also called niacin. Dermatitis begins as an erythema and shows bilateral symmetrical eruption at cutaneous sites of solar exposure. Herein we report 2 cases of pellagra in chronic alcoholics.