Figure - available from: Current Nutrition Reports
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Canonical vitamin K cycle. The carboxylation cycle of glutamate (Glu) residues into gamma-carboxyglutamate (Gla) through reduction and conversion of vitamin K to vitamin K epoxide (KO), and the recycle of vitamin K by the vitamin K epoxide reductase (VKOR). Image made with https://biorender.com/
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Purpose of Review
This narrative review aimed to summarize the current evidence on the connection between dysbiosis and vitamin K deficiency in patients with chronic kidney disease (CKD). The presence of dysbiosis (perturbations in the composition of the microbiota) has been described in several non-communicable diseases, including chronic kidney d...
Citations
... (13) Gut dysbiosis is another mechanistic speculative reason for altered vitamin K status in dialysis patients. (17) Consequences of vitamin K deficiency Low vitamin K intake leads to increased risk of severe aortic calcification and increased mortality in elderly patients. (18) Chronic kidney disease patients with optimal vitamin K status (low plasma dp-ucMGP and high plasma phylloquinone) have better survival than patients with vitamin K deficiency. ...
Vitamin K supplementation has been considered recently as a potential treatment for addressing vascular calcification in chronic kidney disease patients. We conducted a systematic review and meta-analysis to summarize the impact of vitamin K supplementation in dialysis patients.
Electronic databases were searched for clinical randomized trials among patients treated with vitamin K. Random effects models were performed and risk of bias was evaluated with Cochrane tools and search was conducted until 15 of September 2023.
Eleven trials comprising 830 patients (both adult and pediatric, mainly hemodialysis) compared vitamin K with different controls: lower doses of vitamin K, standard care or placebo. Vitamin K supplementation had no effect on mortality. Vitamin K administration improved vitamin K levels and led to lower levels of dp-uc-MGP and moderately increased Calcium levels (0,18 [0,04–0,32]). Vitamin K1 proved more potency in reducing dp-uc-MGP (SMD −1,64 [−2,05, −1,23] vs. −0,56 [−0,82, −0,31]) and also raised serum vitamin K levels in comparison with vitamin K2 (5,69 [3,43, 7,94]) vs. 2,25 [−2.36, 6,87]). While it did not have a proved benefit in changing calcification scores (−0,14 [−0,37–+0,09]), vitamin K proved to be a safe product. There was some concern with bias.
Vitamin K supplementation has no impact on mortality and did not show significant benefit in reversing calcification scores. Vitamin K1 improved vitamin K deposits and lowered dp-uc-MGP which is a calcification biomarker more than vitamin K2. As it proved to be a safe product, additional randomized well-powered studies with improved treatment regimens are needed to establish the true impact of vitamin K in dialysis patients.
... Menaquinone has multiple subtypes characterised as MK-4 through MK-13 based on the length of their isoprenoid side chain. The vast majority of facultative or obligate anaerobes in the gut, such as Escherichia coli, Bacteroides fragilis, Eggerthella lenta, and Lactococcus lactis, produce all different subtypes of menaquinones, whereas their imbalance seen in intestinal microflora dysbiosis can negatively impact the production [2,3]. ...
Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.
Long-term usage of bisphosphonates, especially zoledronic acid (ZA), induces osteogenesis disorders and medication-related osteonecrosis of the jaw (MRONJ) in patients, thereby contributing to the destruction of bone remodeling and the continuous progression of osteonecrosis. Menaquinone-4 (MK-4), a specific vitamin K2 isoform converted by the mevalonate (MVA) pathway in vivo, exerts the promotion of bone formation, whereas ZA administration suppresses this pathway and results in endogenous MK-4 deficiency. However, no study has evaluated whether exogenous MK-4 supplementation can prevent ZA-induced MRONJ. Here we showed that MK-4 pretreatment partially ameliorated mucosal nonunion and bone sequestration among ZA-treated MRONJ mouse models. Moreover, MK-4 promoted new bone regeneration and inhibited osteoblast apoptosis in vivo. Consistently, MK-4 downregulated ZA-induced osteoblast apoptosis in MC3T3-E1 cells and suppressed the levels of cellular metabolic stresses, including oxidative stress, endoplasmic reticulum stress, mitochondrial dysfunction, and DNA damage, which were accompanied by elevated sirtuin 1 (SIRT1) expression. Notably, EX527, an inhibitor of the SIRT1 signaling pathway, abolished the promotional effects of MK-4 on ZA-induced cell metabolic stresses and osteoblast damage. Combined with experimental evidence from MRONJ mouse models and MC3T3-E1 cells, our findings suggested that MK-4 prevents ZA-induced MRONJ by inhibiting osteoblast apoptosis through suppression of cellular metabolic stresses in a SIRT1-dependent manner. The results provide a novel translational direction for the clinical application of MK-4 for preventing MRONJ.
