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Abstract(s)
A vitamina K é uma família de vitaminas lipossolúveis composta por duas formas
principais, a K1 (filoquinona) e a K2 (menaquinona), ambas com estruturas contendo um
anel conhecido como menadiona, ou vitamina K3, e cadeias laterais isoprenoides
variáveis. Enquanto a vitamina K1 é sintetizada por organismos vegetais e amplamente
presente em dietas ocidentais, a vitamina K2 é produzida por bactérias intestinais e possui
diferentes formas com diferentes tamanhos de cadeias laterais, designados por "MK-n".
A absorção de ambas as formas de vitamina K ocorre através do sistema linfático
e é influenciada pela presença de sais biliares. A vitamina K1 é transportada no sangue
por quilomicras, enquanto a vitamina K2 é associada a lipoproteínas de baixa densidade
(LDL) ou muito baixa densidade (VLDL), com a MK-7 demonstrando maior
biodisponibilidade em relação à vitamina K1. Vários fatores podem afetar a absorção da
vitamina K, incluindo o estado nutricional, doenças concomitantes ou a utilização de
determinados fármacos. No fígado, a vitamina K1 é metabolizada e armazenada,
enquanto a vitamina K2 também é distribuída para tecidos extra-hepáticos, sendo que
ambas são catabolizadas, gerando metabolitos de cadeias laterais mais curtas, que são
subsequentemente excretados.
Na dieta é encontrada em diversos alimentos sendo a vitamina K1 mais abundante
em vegetais e a K2 presente em alimentos fermentados, laticínios e carnes provenientes
de animais alimentados com menadiona. Suplementos de vitamina K, principalmente na
forma de K1 e K2 (MK-4 e MK-7), são comumente utilizados de modo a promover a
saúde e prevenir a doença.
A vitamina K desempenha, então, um papel fundamental na ativação de proteínas
dependentes da vitamina K (VKDPs), que estão envolvidas em diversas funções
fisiológicas, tais como a coagulação sanguínea, saúde óssea, resposta imunológica entre
outras.
Quanto à ingestão adequada, as diretrizes são adaptadas para diferentes faixas
etárias, sendo expressa em microgramas (μg) e destinada a indivíduos saudáveis. Em
casos específicos, como doentes sob nutrição parenteral total ou em terapia anticoagulante
com varfarina, a ingestão de vitamina K requer atenção e ajustes cuidadosos para evitar
interferências no efeito anticoagulante do medicamento.A deficiência em vitamina K pode resultar num aumento da propensão a hemorragias, devido à redução dos fatores de coagulação dependentes dessa vitamina.
Em adultos saudáveis, a deficiência é rara, no entanto, em bebés já se torna mais comum
e preocupante, podendo levar à DHRN. Por outro lado, não existem registos significativos
de toxicidade sistémica relacionada com a ingestão de vitamina K.
Atualmente, o doseamento preciso dos níveis de vitamina K representa um
desafio, sendo frequentemente utilizados questionários alimentares ou parâmetros
indiretos para estimar sua ingestão. A ausência de um biomarcador único para a
determinação da ingestão de vitamina K a longo prazo é uma limitação na pesquisa
científica nesta área.
Vitamin K is a family of fat-soluble vitamins composed of two primary forms, K1 (phylloquinone) and K2 (menaquinone), both with structures containing a ring known as menadione, or vitamin K3, and variable isoprenoid side chains. While plant organisms synthesize vitamin K1 and is widely present in Western diets, vitamin K2 is produced by intestinal bacteria and has different forms with varying side chain lengths, designated as "MK-n." Both vitamin K forms are absorbed through the lymphatic system and influenced by the presence of bile salts. Vitamin K1 is transported in the blood by chylomicrons, whereas vitamin K2 is associated with low-density lipoproteins (LDL) or very low- density lipoproteins (VLDL), with MK-7 demonstrating higher bioavailability compared to vitamin K1. Several factors can affect vitamin K absorption, including nutritional status, concurrent diseases, or the use of certain drugs. Vitamin K1 is metabolized in the liver, while vitamin K2 is also distributed to extrahepatic tissues. Both are catabolized, producing metabolites with shorter side chains, which are subsequently excreted. As for its sources, vitamin K is found in various foods, with K1 being more abundant in vegetables and vitamin K2 in fermented foods, dairy, and meats from animals fed menadione. Vitamin K supplements, mainly in K1 and K2 (MK-4 and MK-7), are commonly used to promote health and prevent disease. Vitamin K plays a crucial role in activating vitamin K-dependent proteins (VKDPs), which are involved in several physiological functions, such as blood coagulation, bone health, and immune response. Regarding adequate intake, guidelines are adjusted to different age groups, expressed in micrograms (μg), and targeting healthy individuals. In specific cases, such as patients receiving total parenteral nutrition or on anticoagulant therapy with warfarin, vitamin K intake requires careful attention and adjustments to avoid interference with the medicine’s anticoagulant effect. Vitamin K deficiency may lead to an increased propensity for bleeding due to a reduction in vitamin-dependent coagulation factors. In healthy adults, deficiency is rare. However, it becomes more common and concerning in infants, potentially leading to Hemorrhagic Disease of Newborn (HDN). On the other hand, there are no significant records of systemic toxicity related to vitamin K intake. The accurate measurement of vitamin K levels is a challenge, with dietary questionnaires or indirect parameters often used to estimate intake. The absence of a unique biomarker for determining long-term vitamin K intake remains a limitation in scientific research in this area.
Vitamin K is a family of fat-soluble vitamins composed of two primary forms, K1 (phylloquinone) and K2 (menaquinone), both with structures containing a ring known as menadione, or vitamin K3, and variable isoprenoid side chains. While plant organisms synthesize vitamin K1 and is widely present in Western diets, vitamin K2 is produced by intestinal bacteria and has different forms with varying side chain lengths, designated as "MK-n." Both vitamin K forms are absorbed through the lymphatic system and influenced by the presence of bile salts. Vitamin K1 is transported in the blood by chylomicrons, whereas vitamin K2 is associated with low-density lipoproteins (LDL) or very low- density lipoproteins (VLDL), with MK-7 demonstrating higher bioavailability compared to vitamin K1. Several factors can affect vitamin K absorption, including nutritional status, concurrent diseases, or the use of certain drugs. Vitamin K1 is metabolized in the liver, while vitamin K2 is also distributed to extrahepatic tissues. Both are catabolized, producing metabolites with shorter side chains, which are subsequently excreted. As for its sources, vitamin K is found in various foods, with K1 being more abundant in vegetables and vitamin K2 in fermented foods, dairy, and meats from animals fed menadione. Vitamin K supplements, mainly in K1 and K2 (MK-4 and MK-7), are commonly used to promote health and prevent disease. Vitamin K plays a crucial role in activating vitamin K-dependent proteins (VKDPs), which are involved in several physiological functions, such as blood coagulation, bone health, and immune response. Regarding adequate intake, guidelines are adjusted to different age groups, expressed in micrograms (μg), and targeting healthy individuals. In specific cases, such as patients receiving total parenteral nutrition or on anticoagulant therapy with warfarin, vitamin K intake requires careful attention and adjustments to avoid interference with the medicine’s anticoagulant effect. Vitamin K deficiency may lead to an increased propensity for bleeding due to a reduction in vitamin-dependent coagulation factors. In healthy adults, deficiency is rare. However, it becomes more common and concerning in infants, potentially leading to Hemorrhagic Disease of Newborn (HDN). On the other hand, there are no significant records of systemic toxicity related to vitamin K intake. The accurate measurement of vitamin K levels is a challenge, with dietary questionnaires or indirect parameters often used to estimate intake. The absence of a unique biomarker for determining long-term vitamin K intake remains a limitation in scientific research in this area.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Keywords
Vitamina K Varfarina Coagulação VKDP DHRN Mestrado Integrado - 2023