Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients.

Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of "functional vitamin D deficiency", i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

Development of a liquid chromatography mass spectrometry method for the determination of vitamin K1, menaquinone-4, menaquinone-7 and vitamin K1-2,3 epoxide in serum of individuals without vitamin K supplements.

OBJECTIVES: Vitamin K and metabolites have a beneficial role in blood coagulation, bone metabolism and growth. However, the determination of vitamin K concentrations in the blood in patients consuming a diet with naturally occurring vitamin K is currently challenging. We aim to develop a cost-effective and rapid method to measure vitamin K metabolites with potential application for clinics and research. METHODS: We developed a simple liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination of vitamin K1, menaquinone-4 (MK-4), menaquinone-7 (MK-7) and vitamin K1-2,3 epoxide in human serum and validated the method in a study cohort of 162 patients tested for carbohydrate malabsorption and in 20 patients with oral phenprocoumon intake. RESULTS: The overall precision (CVs) ranged between 4.8 and 17.7% in the specified working range (0.06-9.0 nmol/L for all analytes except for MK-7 with 0.04-6.16 nmol/L). In the malabsorption cohort samples, measured values were obtained for all different vitamin K metabolites except for vitamin K1-2,3 epoxide. This metabolite could be detected only in patients with phenprocoumon intake. The good performance of the method is especially achieved by the interaction of three factors: the use of lipase in the sample preparation, the use of an atypical fluorinated reversed phase column, and a logarithmic methanol gradient. CONCLUSIONS: The described method is able to determine the concentration of four vitamin K metabolites in a time-efficient, simple and cost-effective manner. It can be suitable for both routine clinics and research.

Histamine Intolerance Originates in the Gut.

Histamine intolerance (HIT) is assumed to be due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO) and, therefore, the food component histamine not being degraded and/or absorbed properly within the GI tract. Involvement of the GI mucosa in various disorders and diseases, several with unknown origin, and the effects of some medications seem to reduce gastrointestinal DAO activity. HIT causes variable, functional, nonspecific, non-allergic GI and extra-intestinal complaints. Usually, evaluation for HIT is not included in differential diagnoses of patients with unexplained, functional GI complaints or in the here-listed disorders and diseases. The clinical diagnosis of HIT is challenging, and the thorough anamnesis of all HIT-linked complaints, using a standardized questionnaire, is the mainstay of HIT diagnosis. So far, DAO values in serum have not been established to correlate with DAO activity in the gut, but the diagnosis of HIT may be supported with determination of a low serum DAO value. A targeted dietary intervention, consisting of a histamine-reduced diet and/or supplementation with oral DAO capsules, is helpful to reduce HIT-related symptoms. This manuscript will present why histamine should also be taken into account in the differential diagnoses of patients with various diseases and disorders of unknown origin, but with association to functional gastrointestinal complaints. In this review, we discuss currently increasing evidence that HIT is primarily a gastrointestinal disorder and that it originates in the gut.