Vitamin K and Calcium Chelation in Vascular Health.

The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health.

Effects of an Intervention with Selenium and Coenzyme Q10 on Five Selected Age-Related Biomarkers in Elderly Swedes Low in Selenium: Results That Point to an Anti-Ageing Effect-A Sub-Analysis of a Previous Prospective Double-Blind Placebo-Controlled Randomised Clinical Trial.

Background: Ageing is associated with cardiovascular disease (CVD). As no single biomarker reflects the full ageing process, we aimed to investigate five CVD- and age-related markers and the effects of selenium and coenzyme Q10 intervention to elucidate the mechanisms that may influence the course of ageing. Methods: This is a sub-study of a previous prospective double-blind placebo-controlled randomized clinical trial that included 441 subjects low in selenium (mean age 77, 49% women). The active treatment group (n = 220) received 200 µg/day of selenium and 200 mg/day of coenzyme Q10, combined. Blood samples were collected at inclusion and after 48 months for measurements of the intercellular adhesion molecule (ICAM-1), adiponectin, leptin, stem cell factor (SCF) and osteoprotegerin (OPG), using ELISAs. Repeated measures of variance and ANCOVA evaluations were used to compare the two groups. In order to better understand and reduce the complexity of the relationship between the biomarkers and age, factor analyses and structural equation modelling (SEM) were performed, and a structural model is presented. Results: Correlation analyses of biomarker values at inclusion in relation to age, and relevant markers related to inflammation, endothelial dysfunction and fibrosis, demonstrated the biomarkers' association with these pathological processes; however, only ICAM1 and adiponectin were directly correlated with age. SEM analyses showed, however, that the biomarkers ICAM-1, adiponectin, SCF and OPG, but not leptin, all had significant associations with age and formed two independent structural factors, both significantly related to age. While no difference was observed at inclusion, the biomarkers were differently changed in the active treatment and placebo groups (decreasing and increasing levels, respectively) at 48 months (p ≤ 0.02 in all, adjusted), and in the SEM model, they showed an anti-ageing impact. Conclusions: Supplementation with selenium/Q10 influenced the analysed biomarkers in ways indicating an anti-ageing effect, and by applying SEM methodology, the interrelationships between two independent structural factors and age were validated.

Selenium and coenzyme Q10 improve the systemic redox status while reducing cardiovascular mortality in elderly population-based individuals.

BACKGROUND: Serum sulfhydryl groups (R-SH, free thiols) reflect the systemic redox status in health and disease, and may be amenable to therapeutic modulation. Since R-SH are readily oxidized by reactive species, oxidative stress is characterized by reduced serum R-SH levels. Selenium and coenzyme Q10 supplementation may improve the systemic redox status. This study aimed to evaluate the effect of supplementation with selenium and coenzyme Q10 on serum free thiols and to study associations with the risk of cardiovascular mortality in elderly community-dwelling individuals. METHODS: In this randomized, double-blind, placebo-controlled trial, serum R-SH were measured colorimetrically and adjusted for albumin in 434 individuals at baseline and after 48 months of intervention. Selenium yeast (200 µg/day) and coenzyme Q10 (200 mg/day) or placebo were provided as dietary supplements. RESULTS: After 48 months of intervention, participants receiving combined selenium and coenzyme Q10 supplementation demonstrated increased levels of serum R-SH compared to placebo (P = 0.002). In prospective association analysis, the highest rate of cardiovascular mortality after a median follow-up of 10 years (IQR: 6.8-10.5) was observed in the lowest quartile (Q1) of R-SH levels. Baseline albumin-adjusted serum R-SH were significantly associated with the risk of cardiovascular mortality, even after adjustment for potential confounding factors (hazard ratio [HR] 1.98 per SD, 95% CI: 1.34-2.91, P < 0.001). CONCLUSION: Supplementation with selenium and coenzyme Q10 to an elderly community-dwelling population low on the two substances, significantly improved serum R-SH levels, supporting a reduction in systemic oxidative stress. Low serum R-SH levels were significantly associated with an increased risk of cardiovascular mortality in elderly individuals.

Postoperative Osteoporosis in Subjects with Morbid Obesity Undergoing Bariatric Surgery with Gastric Bypass or Sleeve Gastrectomy.

Obesity has become a worldwide epidemic accompanied by adverse health effects. The limited efficiency of traditional weight reduction regimens has led to a substantial increase in the use of bariatric surgery. Today, sleeve gastrectomy (SG) and Roux-en-Y-gastric bypass (RYGB) are the most used procedures. The present narrative review focuses on the risk of developing postoperative osteoporosis and summarizes some of the most relevant micronutrient deficiencies associated with RYGB and SG. Preoperatively, the dietary habits of obese individuals might lead to precipitated deficiencies in vitamin D and other nutrients affecting bone mineral metabolism. Bariatric surgery with SG or RYGB can aggravate these deficiencies. The various surgical procedures appear to affect nutrient absorption differently. Being purely restrictive, SG may particularly affect the absorption of vitamin B12 and also vitamin D. In contrast, RYGB has a more profound impact on the absorption of fat-soluble vitamins and other nutrients, although both surgical methods induce only a mild protein deficiency. Despite adequate supplementation of calcium and vitamin D, osteoporosis may still occur after the surgery. This might be due to deficiencies in other micronutrients, e.g., vitamin K and zinc. Regular follow-ups with individual assessments and nutritional advice are indispensable to prevent osteoporosis and other adverse postoperative issues.

Chelation Combination-A Strategy to Mitigate the Neurotoxicity of Manganese, Iron, and Copper?

The chelating thiol dimercaptosuccinate (DMSA) and the traditional agent D-penicillamine (PSH) are effective in enhancing the urinary excretion of copper (Cu) and lead (Pb) in poisoned individuals. However, DMSA, PSH, EDTA (ethylenediamine tetraacetate), and deferoxamine (DFOA) are water-soluble agents with limited access to the central nervous system (CNS). Strategies for mobilization of metals such as manganese (Mn), iron (Fe), and Cu from brain deposits may require the combined use of two agents: one water-soluble agent to remove circulating metal into urine, in addition to an adjuvant shuttler to facilitate the brain-to-blood mobilization. The present review discusses the chemical basis of metal chelation and the ligand exchange of metal ions. To obtain increased excretion of Mn, Cu, and Fe, early experiences showed promising results for CaEDTA, PSH, and DFOA, respectively. Recent experiments have indicated that p-amino salicylate (PAS) plus CaEDTA may be a useful combination to remove Mn from binding sites in CNS, while the deferasirox-DFOA and the tetrathiomolybdate-DMSA combinations may be preferable to promote mobilization of Fe and Cu, respectively, from the CNS. Further research is requested to explore benefits of chelator combinations.

Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality-Sub-Study of a Randomized Clinical Trial.

Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q10 is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q10 supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70−80 years, were included. Intervention time was 4 years, with 10 years' follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. −0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p < 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q10 supplementation associated with reduced cardiovascular mortality.