Warfarin drug interaction with vitamin K and other foodstuffs / Interacción de la droga warfarina con la vitamina K y otros productos alimenticios

Vitamin K is found in higher concentrations in dark green plant and in vegetable oils. The adequate intake of vitamin K is 90 and 120ug/day for adult elderly men and women, respectively. The main function of vitamin K is to act as an enzymatic cofactor for hepatic prothrombin synthesis, blood coagulation factors, and anticoagulant proteins. Prominent among the many available anticoagulants is warfarin, an antagonist of vitamin K, which exerts its anticoagulant effects by inhibiting the synthesis of vitamin K1 and vitamin KH2. From the beginning of the therapy it is necessary that the patients carry out the monitoring through the prothrombin time and the international normalized ratio. However, it is known that very low intake and/or fluctuations in vitamin K intake are as harmful as high consumption. In addition, other foods can interact with warfarin, despite their content of vitamin K. The aim of this study was to gather information on the drug interaction of warfarin with vitamin K and with dietary supplements and other foods.

La vitamina K se encuentra en concentraciones más altas en plantas de color verde oscuro y en aceites vegetales. La ingesta adecuada de vitamina K es de 90 y 120 ug/día para hombres y mujeres adultos mayores, respectivamente. La función principal de la vitamina K es actuar como un cofactor enzimático para la síntesis de protrombina hepática, factores de coagulación de la sangre y proteínas anticoagulantes. Entre los muchos anticoagulantes disponibles destaca la warfarina, un antagonista de la vitamina K, que ejerce sus efectos anticoagulantes al inhibir la síntesis de la vitamina K1 y la vitamina KH2. Desde el inicio de la terapia, es necesario que los pacientes realicen el monitoreo a través del tiempo de protrombina y la proporción normalizada internacional. Sin embargo, se sabe que una ingesta muy baja y/o fluctuaciones en la ingesta de vitamina K son tan dañinas como un consumo alto. Además, otros alimentos pueden interactuar con la warfarina, a pesar de su contenido de vitamina K. El objetivo de este estudio fue recopilar información sobre la interacción de los medicamentos de la warfarina con la vitamina K y con los suplementos dietéticos y otros alimentos.

The role of daily physical activity and nutritional status on bone turnover in cystic fibrosis: a cross-sectional study

ABSTRACT Background Nutritional status and daily physical activity (PA) may be an excellent tool for the maintenance of bone health in patients with cystic fibrosis (CF). Objective To evaluate the relationship between nutritional status, daily physical activity and bone turnover in cystic fibrosis patients. Method A cross-sectional study of adolescent and adult patients diagnosed with clinically stable cystic fibrosis was conducted. Total body, femoral neck, and lumbar spine bone mineral density (BMD) were determined by dual energy X-ray absorptiometry and bone metabolism markers ALP, P1NP, PICP, and ß-CrossLaps. PA monitoring was assessed for 5 consecutive days using a portable device. Exercise capacity was also determined. Serum 25-hydroxyvitamin D and vitamin K were also determined in all participants. Results Fifty patients (median age: 24.4 years; range: 16-46) were included. BMI had positive correlation with all BMD parameters, with Spearman’s coefficients ranging from 0.31 to 0.47. Total hip bone mineral density and femoral neck BMD had positive correlation with the daily time spent on moderate PA (>4.8 metabolic equivalent-minutes/day; r=0.74, p<0.001 and r=0.72 p<0.001 respectively), daily time spent on vigorous PA (>7.2 metabolic equivalent-minutes/day; r=0.45 p<0.001), body mass index (r=0.44, p=0.001), and muscle mass in limbs (r=0.41, p=0.004). Levels of carboxy-terminal propeptide of type 1 collagen were positively associated with the daily time spent on moderate (r=0.33 p=0.023) and vigorous PA (r=0.53, p<0.001). Conclusions BMI and the daily time spent on moderate PA were found to be correlated with femoral neck BMD in CF patients. The association between daily PA and biochemical markers of bone formation suggests that the level of daily PA may be linked to bone health in this patient group. Further research is needed to confirm these findings.

Vitamina K: metabolismo, fontes e interação com o anticoagulante varfarina / Vitamin K: metabolism, sources and interaction with the anticoagulant warfarin

A vitamina K é lipossolúvel, principalmente, na coagulação sanguínea. Se apresenta sob as formas de filoquinona (K1-predominante), dihidrofiloquinona (dK), menaquinona (K2) e menadiona (K3). Os fatores que interferem em sua absorção são: má absorção gastrintestinal, secreção biliar, ingestão insuficiente e uso de anticoagulantes, entre outros. As principais fontes de vitamina K são os vegetais e óleos, sendo esses os responsáveis pelo aumento da absorção da filoquinona. Os alimentos folhosos verde escuro, os preparados à base de óleo, oleaginosas e frutas como o kiwi, abacate, uva, ameixa e figo contêm teores significantes de vitamina K, enquanto que os cereais, grãos, pães e laticínios possuem teores discretos. A ingestão diária de aproximadamente 1 micro grama por quilo de peso é considerada a mais segura, inclusive para a utilização de anticoagulantes orais, em que a concentração estável da vitamina proporciona a eficácia no tratamento. A droga anticoagulante oral geralmente utilizada é a varfarina, administrada como profilática e para tratamento de fenômenos tromboembólicos. Essa intervenção medicamentosa é monitorada pelo tempo de protrombina expresso pela razão normalizada internacional, tendo como objetivo estabelecer a faixa terapêutica entre 2 e 3, minimizando o risco de hemorragias. O efeito anticoagulante pode ser reduzido por fatores como ganho de peso, diarréia, vômito, idade menor que 40 anos e consumo excessivo de vitamina K na dieta alimentar.

Vitamin K is a fat-soluble substance, mainly involved in the blood coagulation. It is presented as Phylloquinone (K1-predominant), Dihydrophyloquinone (dK), Menaquinone (K2), and Menadione (K3). The factors that interfere with its absorption are: gastrointestinal malabsorption, biliary secretion, inadequate ingestion and anticoagulant use, among others. The main vitamin K sources are vegetables and organic lipids, that are involved in the increased absorption of phylloquinone. Dark green leafy vegetables, usually mixed with oils, nuts and some fruits, including kiwi, avocado, grapes, plums, and figs are rich sources of vitamin K, whereas cereals, grains, breads, and dairy products present low amounts. The daily ingestion of approximately 1 micro gram per kg body-weight is considered safe, even with concomitant oral anticoagulant use, since stable vitamin concentration contributes to anticoagulant efficacy. The most commonly used oral anticoagulant formation is warfarin, that is indicated to both prophylactic and therapeutic tromboembolic phenomena. It is currently monitored by assessing prothrombin time, after adjusting for the international normalized ratio (INR). Usually, the oral dose is adjusted to set the INR in the range of 2 - 3, in order to achieve the treatment objective. The anticoagulating efficacy is influenced by a variety of clinical factors, such as weight gain, diarrhoea, vomiting, age under 40, and excessive vitamin K daily consumption.