Study: Randomised Trial: 16 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Effect of Glycocalyx-targeted Therapy on Vascular Function in Older Adults: A Randomized Controlled Trial
In this small double-blind, placebo-controlled pilot trial, 23 older adults took a glycocalyx-targeted supplement (Endocalyx Pro, 3,712 mg/day) or placebo for 12 weeks. The supplement did not significantly change overall sublingual glycocalyx thickness (perfused boundary region), brachial artery flow-mediated dilation, blood pressure, or aortic stiffness. Two secondary/exploratory signals were seen: greater capillary glycocalyx thickness among participants not on antihypertensive medication, and improved FMD normalized to shear rate.
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Published paper
The effect of 6-month treatment with coenzyme Q10 on endothelial, vascular and myocardial function in patients with nonalcoholic fatty liver disease
In this randomized placebo-controlled trial, 52 patients with non-alcoholic fatty liver disease received either 240 mg/day coenzyme Q10 or placebo for six months. The CoQ10 group showed improvements in sublingual microvascular glycocalyx thickness (perfused boundary region), arterial stiffness, brachial artery flow-mediated dilation, left ventricular global longitudinal strain, and liver steatosis on FibroScan, while the placebo group showed no significant change. The findings are reported as a conference abstract, so detailed methods and between-group statistics are not available.
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Published paper
Impact of dietary supplementation of glycocalyx precursors on vascular function in type 2 diabetes
This combined preclinical and clinical study tested whether a dietary mixture of glycocalyx precursors (glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) could restore the endothelial glycocalyx and improve vascular function in type 2 diabetes. In diabetic db/db mice, four weeks of supplementation restored glycocalyx length and improved flow-mediated dilation and arterial stiffness, and the same mixture promoted glycocalyx growth in cultured endothelial cells. However, in a pilot double-blind randomized placebo-controlled trial of 22 Veterans with type 2 diabetes, eight weeks of supplementation did not improve glycocalyx integrity or vascular function compared with placebo.
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Published paper
Six-month supplementation with high dose coenzyme Q10 improves liver steatosis, endothelial, vascular and myocardial function in patients with metabolic-dysfunction associated steatotic liver disease: A Randomized Double-blind, Placebo Controlled Trial
In this single-center, double-blind randomized trial, 60 non-diabetic patients with MASLD received either a supplement containing 240 mg/day coenzyme Q10 (plus choline, milk thistle, cynara, selenium, vitamin C and B vitamins) or placebo for 6 months, alongside Mediterranean diet and exercise advice. The CoQ10 group showed reductions in liver fat (CAP), sublingual perfused boundary region (a marker of thicker endothelial glycocalyx), arterial stiffness and blood pressure, plus improved brachial flow-mediated dilation, coronary flow reserve and left ventricular global longitudinal strain, while the placebo group showed no significant change. Reductions in liver steatosis correlated with the vascular and myocardial improvements.
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Published paper
Role of dietary interventions on microvascular health in South-Asian Surinamese people with type 2 diabetes in the Netherlands; a randomized controlled trial
This three-arm randomized, placebo-controlled trial tested a monthly 5-day fasting-mimicking diet (Prolon) versus a glycocalyx-mimetic supplement (Endocalyx, containing fucoidan, glucosamine sulfate and hyaluronic acid) versus placebo for 3 months in 56 South-Asian Surinamese patients with type 2 diabetes, with follow-up at 6 months. Sublingual microvascular measures were made with SDF imaging and GlycoCheck software. The fasting-mimicking diet lowered BMI and HbA1c temporarily but was associated with worsening of the dynamic perfused boundary region, while the supplement group showed improved dynamic PBR and microvascular health score and lower urinary MCP-1 relative to placebo.
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Published paper
Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study
This small double-blind randomized trial gave 23 ICU patients with sepsis or septic shock either high-dose intravenous ascorbic acid (50 mg/kg every 6 hours for 96 hours) or placebo, and measured sublingual microcirculation with handheld video microscopy plus glycocalyx thickness with GlycoCheck-based perfused boundary region (PBR). The ascorbic acid group showed a higher proportion of perfused small vessels at 6 hours and a lower PBR in the smallest capillaries right after the first infusion, but there were no differences in most other microcirculatory, hemodynamic, inflammatory, or mortality outcomes.
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Published paper
Apremilast improves endothelial glycocalyx and microvascular perfusion: a possible protective mechanism against COVID-19
In this randomized comparison, 90 patients with psoriasis received apremilast, etanercept, or cyclosporine for 4 months, with sublingual glycocalyx (perfused boundary region, GlycoCheck/SDF imaging), arterial stiffness, and echocardiographic measures assessed before and after treatment. Only apremilast was associated with a reduction in PBR (indicating thicker glycocalyx) and it produced greater improvements in microvascular perfusion, pulse wave velocity, central systolic blood pressure, and left ventricular strain than the comparators. The authors speculate that glycocalyx protection could relate to reported benefits of apremilast in COVID-19, but no COVID-19 outcomes were studied.
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Published paper
Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study
In this randomized trial, 270 post-STEMI patients received either one cycle or two cycles of bilateral arm-cuff remote ischemic conditioning (RIC), or no conditioning. A single RIC cycle produced greater improvement in sublingual microvascular glycocalyx integrity (perfusion boundary region) and arterial stiffness, along with increases in cardioprotective microRNA-144 and nitrate-nitrite and reduced oxidative stress. At one year, single-cycle RIC was associated with greater reduction in left ventricular end-systolic volume, suggesting more favorable cardiac remodeling.
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Published paper
Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19
Eighty patients with rheumatoid arthritis were randomized to 3 months of the IL-6 receptor blocker tocilizumab or to intensified conventional DMARDs plus glucocorticoids, with 40 age- and sex-matched healthy subjects as a comparison group. Endothelial glycocalyx thickness (sublingual perfused boundary region, PBR), arterial stiffness, echocardiographic myocardial work/strain, and inflammatory and oxidative stress markers were measured before and after treatment. Tocilizumab was associated with reduced PBR (indicating thicker glycocalyx), lower arterial stiffness, greater falls in CRP and oxidative stress markers, and greater improvement in myocardial deformation and work than conventional treatment.
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Published paper
Effects of Glucagon Like Peptide 1 Receptor Agonists, Sodium Glucose Cotransporter 2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12 Month Treatme
In this 12-month randomized trial, 160 patients with type 2 diabetes were assigned to add-on insulin, liraglutide (GLP-1RA), empagliflozin (SGLT-2i), or the GLP-1RA/SGLT-2i combination. Despite similar HbA1c reductions across groups, the newer agents and especially the combination produced greater improvements in sublingual glycocalyx thickness (perfused boundary region), arterial stiffness, central blood pressure, and echocardiographic myocardial strain and work indices than insulin.
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Published paper
Microvascular Alterations During Cardiac Surgery Using a Heparin or Phosphorylcholine-Coated Circuit
In this single-center randomized, blinded trial, 26 adults having on-pump CABG surgery received either a heparin-coated or a phosphorylcholine-coated cardiopulmonary bypass circuit. Sublingual sidestream dark-field imaging (GlycoCheck) and plasma shedding markers showed glycocalyx thinning and shedding in the phosphorylcholine group but not the heparin-coated group, while the fall in perfused vessel density during bypass was similar in both groups.
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Published paper
Impact of Intravenous Fluid Challenge Infusion Time on Macrocirculation and Endothelial Glycocalyx in Surgical and Critically Ill Patients.
This open randomized single-center trial compared fast (5-10 min) versus slow (20-30 min) infusion of a 5 ml/kg balanced crystalloid fluid challenge in 50 spinal surgery patients and 16 septic patients, measuring sublingual perfused boundary region (PBR, a marker inversely related to glycocalyx integrity) with GlycoCheck side-stream dark-field imaging plus standard hemodynamics. Fluid administration raised PBR regardless of infusion speed, with recovery by 60 minutes in surgical patients but persistent elevation in septic fluid responders. Infusion time did not change the rate of fluid responsiveness, though fast boluses produced a larger but transient blood pressure rise.
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Published paper
Effects of varenicline and nicotine replacement therapy on arterial elasticity, endothelial glycocalyx and oxidative stress during a 3-month smoking cessation program
In this randomized trial, 188 smokers received either varenicline or nicotine replacement therapy for three months, with vascular and oxidative stress measures taken at baseline, 3 months, and 12 months. Both treatments reduced exhaled carbon monoxide, oxidative stress markers, and arterial stiffness (augmentation index), and improved endothelial glycocalyx integrity measured as sublingual perfusion boundary region. Improvements were somewhat greater with varenicline and were sustained at one year only in those who remained abstinent.
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Published paper
Effect of an acute and chronic slat load on microvascular permeability in healthy subjects.
In a randomized crossover study, 12 healthy men followed 8 days of a low-sodium diet and 8 days of a high-sodium diet, and also received an acute intravenous hypertonic saline load. Microvascular permeability (transcapillary escape rate of radiolabeled albumin) rose after the acute salt infusion but not after chronic dietary salt loading, while sublingual glycocalyx measures (perfused boundary region) and microvascular perfusion were unchanged in all conditions.
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Published paper
Plasma free hemoglobin and microcirculatory response to fresh or old blood transfusions in sepsis
This secondary analysis of a randomized pilot trial compared transfusion of fresh (<10 days) versus old (>15 days) non-leukodepleted red blood cells in 20 septic ICU patients, measuring plasma free hemoglobin, sublingual microcirculation by sidestream dark-field imaging (including perfused boundary region as a glycocalyx index), and near-infrared spectroscopy variables. Plasma free hemoglobin rose after old blood transfusion despite similar free hemoglobin in the blood units themselves, while sublingual microcirculatory parameters, including PBR, did not change significantly in either group. Larger increases in plasma free hemoglobin correlated with decreases in microvascular density and less increase in tissue hemoglobin index.
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Published paper
Microcirculatory effects of the transfusion of leukodepleted or non-leukodepleted red blood cells in patients with sepsis: a pilot study
This small randomized pilot trial compared sublingual microcirculatory and tissue oxygenation responses one hour after transfusion of leukodepleted versus non-leukodepleted red blood cells in 20 septic ICU patients. Most between-group differences were not significant, though microvascular flow index and blood flow velocity changed more favorably with leukodepleted units. Glycocalyx was assessed by sidestream dark-field perfused boundary region (GlycoCheck software) and by serum syndecan-1, hyaluronan, and heparan sulfate.
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