133 published papers on the glycocalyx
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
Relationship of the main indicators of systemic COVID-associated endotheliopathy with the morphofunctional state and hemodynamics of the retina and chorioid in the acute period of the disease
Russian researchers compared retinal and choroidal imaging (OCT) with sublingual microvascular glycocalyx measurements (GlycoCheck PBR) in 44 people convalescing from moderate or severe COVID-19 and 18 healthy volunteers. Patients showed thicker choroids and wider peripapillary retinal vessels in proportion to disease severity, and these ocular changes correlated with inflammatory/coagulation blood markers and with glycocalyx indices. The authors interpret this as indirect evidence linking post-COVID retinal microangiopathy to systemic endotheliopathy.
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Published paper
Variability of microcirculatory measurements in healthy volunteers
Two experienced operators each performed three consecutive sublingual GlycoCheck (sidestream dark-field) microcirculation measurements in 49 healthy volunteers to test reproducibility. Single measurements of perfused boundary region (PBR), red blood cell filling percentage, and microvascular vessel density had poor intraobserver reliability, but averaging three measurements raised reliability to acceptable levels. Agreement between the two observers was only fair for PBR and RBC filling and poor for vessel density, though no systematic bias was found.
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Published paper
A Dietary Supplement Containing Fucoidan Preserves Endothelial Glycocalyx through ERK/MAPK Signaling and Protects against Damage Induced by CKD Serum
Researchers tested whether a commercial dietary supplement containing fucoidan, glucosamine sulfate, hyaluronan and antioxidants could protect the endothelial glycocalyx in laboratory models. Using atomic force microscopy on living endothelial cells, the supplement and fucoidan alone increased glycocalyx thickness, prevented heparinase-induced degradation, and reversed thinning caused by pooled serum from hemodialysis patients; effects depended on ERK/MAPK (and to a lesser extent PI3K) signaling and Golgi-dependent vesicular transport. In mice fed the supplement for two weeks, sidestream dark-field imaging of cremaster microvessels showed a reduced perfused boundary region, consistent with a thicker glycocalyx.
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Published paper
Differences in coronary flow reserve and flow-mediated dilation between plaque psoriasis and psoriatic arthritis
This cross-sectional study compared vascular and cardiac function in 311 patients with psoriatic disease (185 plaque psoriasis, 126 psoriatic arthritis) and 150 risk-factor-matched controls. Patients with psoriatic disease had thicker perfused boundary region (indicating a thinner, more damaged endothelial glycocalyx), lower coronary flow reserve, lower brachial flow-mediated dilation, and reduced left ventricular longitudinal strain. Glycocalyx impairment was similar in both psoriatic subgroups, whereas coronary microvascular and brachial endothelial function were worse in psoriatic arthritis.
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Published paper
Endothelial glycocalyx improvement after six months and one-year of antiretroviral therapy in treatment naive patients with human immunodeficiency virus
This conference abstract reports on 54-58 newly diagnosed, treatment-naive HIV patients whose sublingual microvascular glycocalyx was measured with sidestream dark-field imaging (GlycoCheck) before and after starting antiretroviral therapy. Perfusion boundary region (PBR), an inverse marker of glycocalyx thickness, fell at 6 months and further at 12 months, indicating improved glycocalyx integrity, even though body weight and blood pressure rose over the same period.
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Published paper
Perfused boundary region as biomarker for endothelial integrity in former preterms in adolescence
In the Belgian PREMATCH cohort, researchers measured sublingual perfused boundary region (PBR, an inverse index of glycocalyx thickness) by sidestream dark-field imaging in 93 adolescents born at extremely low birth weight (ELBW) and 87 healthy controls, alongside blood pressure, cystatin-C-based eGFR, and retinal vessel imaging. PBR did not differ between the groups even though ELBW survivors had higher blood pressure, lower eGFR, and altered retinal vessel width and tortuosity. The authors provide reference PBR values for adolescents but conclude that PBR correlates too weakly with other microvascular markers to serve as a stand-alone marker of endothelial integrity in this group.
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Published paper
Persistent capillary rarefication in long COVID syndrome
This prospective observational study used sublingual sidestream dark-field videomicroscopy with GlycoCheck software to compare microvascular structure and function in 27 long COVID patients, 15 healthy controls, and 16 historical critically ill COVID-19 patients. Long COVID patients showed a marked loss of the smallest capillaries and impaired capillary recruitment a median of ~18 months after infection, while glycocalyx thickness (PBR) was similar to healthy controls. The authors conclude that COVID-19 may leave persistent capillary rarefication, though the design cannot establish causality with symptoms.
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Published paper
Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study
This multi-center observational study compared sublingual microcirculation, glycocalyx dimensions (PBR by GlycoCheck) and 184 plasma proteins in 22 COVID-19 patients, 43 bacterial sepsis patients and 10 healthy controls. Microvascular and proteomic abnormalities were largely similar in the two diseases and tracked with illness severity rather than diagnosis. Two mutually opposed coregulated protein clusters were identified, and their ratio ("Microcode") predicted 28-day mortality/intubation in an independent COVID-19 cohort.
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Published paper
The microvascular endothelial glycocalyx: An additional piece of the puzzle in veterinary medicine
This narrative review summarizes the structure, functions, and disease relevance of the endothelial glycocalyx (eGlx), with a focus on the near-absence of research in cats and dogs. It compares direct visualization methods (perfusion/immersion fixation electron microscopy, lectin staining) with clinically applicable indirect methods (ELISAs for shed hyaluronan, syndecan-1, heparan sulfate; sidestream dark-field imaging of the perfused boundary region). It also reviews evidence for glycocalyx damage in sepsis, kidney disease, hypervolemia and hypertension, and outlines candidate protective or restorative strategies.
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Published paper
Endothelial glycocalyx integrity in oncological patients
This study compared sublingual microvascular glycocalyx thickness (measured as perfused boundary region, PBR) in 64 cancer patients versus 32 controls with similar cardiovascular risk profiles. Cancer patients had significantly higher PBR values, indicating a thinner/damaged glycocalyx, even though arterial stiffness and standard echocardiographic measures were largely comparable. The impairment tracked with cancer stage rather than with traditional risk factors or anticancer treatment.
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Published paper
Ways and Means of Cellular Reconditioning for Kidney Regeneration
This narrative review proposes 'cellular reconditioning' — repairing individual damaged cell components to trigger broader recovery — as an addition to regenerative nephrology. It catalogs mitochondrial, lysosomal/autophagy, and peroxisomal dysfunction alongside loss of endothelial glycocalyx integrity as interconnected contributors to acute and chronic kidney disease, and reviews the enzymes (metalloproteinases, heparanase-1, hyaluronidases) that shed the glycocalyx. It also summarizes clinical glycocalyx biomarkers and imaging methods, plus reported preventive and restorative interventions.
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Published paper
Mutations in the heparan sulfate backbone elongating enzymes EXT1 and EXT2 have no major effect on endothelial glycocalyx and the glomerular filtration barrier
Researchers tested whether people carrying a single defective copy of the heparan sulfate chain-elongating genes EXT1 or EXT2 (causing multiple osteochondromas) have a damaged endothelial glycocalyx or leaky glomerular filtration barrier. Using sublingual GlycoCheck measurements and urine albumin testing in 19 patients versus 19 matched controls, plus review of archived kidney biopsies from 24 osteochondroma cases, they found no meaningful differences. Only one archival case showed the rare fibrillar glomerular deposits previously described as 'glomerulopathy of hereditary multiple exostoses'.
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Published paper
Vascular Endothelial Glycocalyx Damage in COVID-19
This narrative review, which includes a small structured literature search, argues that damage to the vascular endothelial glycocalyx is a common mechanism linking COVID-19 risk factors (hypertension, diabetes, obesity, smoking, cardiovascular disease) to severe outcomes such as ARDS, DIC, and microvascular thrombosis. The author proposes a new concept, 'systemic inflammation-reactive microvascular endotheliopathy' (SIRME), defined by inflammation, thrombogenic endothelial damage with increased permeability, and organ injury, with shed glycocalyx fragments or bilateral ground-glass lung shadows marking progression. Of six eligible clinical reports identified, all showed elevated circulating glycocalyx components in severe COVID-19.
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Published paper
Endothelial glycocalyx and microvascular perfusion are associated with carotid intima-media thickness and impaired myocardial deformation in psoriatic disease
This study compared sublingual endothelial glycocalyx and microvascular perfusion measures in 297 patients with psoriatic disease against 150 risk-factor-matched controls. Psoriatic patients showed a thinner glycocalyx (higher perfused boundary region) and poorer microvascular perfusion, and these changes tracked with disease severity, carotid intima-media thickness, coronary flow reserve, and left ventricular deformation.
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Published paper
Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C)
This single-center case report describes two critically ill children with MIS-C in whom endothelial glycocalyx damage was documented using plasma syndecan-1 and sublingual video microscopy (GlycoCheck) alongside a marked systemic inflammatory response. Both children had abnormal perfused boundary region (PBR) values and reduced capillary density compared with a postoperative control child, and PBR normalized (1.68 and 1.54 microns) before transfer out of intensive care after immunoglobulin and methylprednisolone treatment plus supportive care. The authors argue that microcirculatory and glycocalyx involvement may partly explain shock, capillary leak, and prothrombotic features in MIS-C.
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Published paper
Association of Gestational Diabetes With Subclinical Cardiovascular Disease on Echocardiogram and Endothelial Function Testing (Abstract 12986)
This conference abstract reports a cross-sectional analysis of 217 women assessed roughly nine years after pregnancy, 53 of whom had a history of gestational diabetes. Women with prior gestational diabetes showed greater left ventricular wall thickness, worse diastolic function, and worse endothelial and glycocalyx measures (EndoPAT reactive hyperemia index and GlycoCheck parameters). Some hypertrophy differences were explained by BMI, hypertension, and diabetes, but the diastolic and vascular findings persisted after adjustment.
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Published paper
Impaired Endothelial Glycocalyx Predicts Adverse Outcome in Subjects Without Overt Cardiovascular Disease: a 6-Year Follow-up Study
In 600 subjects free of overt cardiovascular disease, researchers measured the perfused boundary region (PBR) in sublingual microvessels using sidestream dark-field imaging as an index of endothelial glycocalyx integrity, then followed them for 6 years. Higher PBR (indicating a thinner glycocalyx) independently predicted major adverse cardiovascular events beyond conventional risk factors and the European Heart SCORE.
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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
Endothelial glycocalyx integrity and microvascular perfusion are associated with novel echocardiographic markers and carotid intima-media thickness in patients with psoriasis
Researchers used sublingual sidestream dark-field imaging (GlycoCheck) to compare endothelial glycocalyx barrier properties and microvascular perfusion in 297 psoriasis patients versus 150 risk-factor-adjusted controls. Psoriasis patients showed a thicker perfused boundary region (indicating a thinner glycocalyx) and poorer microvascular perfusion, which correlated with reduced coronary flow reserve, impaired left ventricular deformation, and greater carotid intima-media thickness.
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Published paper
Links between Endothelial Glycocalyx Changes and Microcirculatory Parameters in Septic Patients
In this single-center prospective observational study, sublingual microcirculation (Cytocam incident dark field imaging) and glycocalyx perfused boundary region (PBR, GlycoCheck) were compared between adults with sepsis or septic shock and healthy age-matched volunteers. Septic patients had significantly increased PBR (indicating thinner glycocalyx) across all vessel diameter classes, and PBR in the smallest capillaries correlated inversely with capillary density measures. The authors conclude there may be a functional link between glycocalyx damage in the smallest capillaries and sepsis-related microcirculatory alterations.
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Published paper
Microvascular Differences in Individuals With Obesity At Risk of Developing Cardiovascular Disease
In a cross-sectional analysis of 813 middle-aged adults with overweight/obesity, sublingual microcirculation was imaged using sidestream dark-field video microscopy with new GlycoCheck software that adds red blood cell velocity analysis. Participants at high 10-year cardiovascular risk (Framingham) had fewer perfused small capillaries and faster red cell velocity than low-risk participants, whereas velocity-corrected perfused boundary region (a glycocalyx index) did not differ between risk groups.
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Published paper
May We Use Non-Invasive Indices of Aortic Stiffness and Endothelial Glycocalyx as Biomarkers for Idiopathic Pulmonary Artery Hypertension Follow-Up?
This single-patient case report tracks three annual evaluations (2018-2020) of a woman with idiopathic pulmonary arterial hypertension, comparing invasive hemodynamics and exercise capacity with two non-invasive systemic vascular measures: carotid-femoral pulse wave velocity (aortic stiffness) and sublingual perfused boundary region (endothelial glycocalyx, GlycoCheck). When her pulmonary vascular resistance worsened, glycocalyx measures worsened (higher PBR, lower red blood cell filling), and both improved after treatment was changed. The authors suggest these indices deserve further study as non-invasive follow-up markers, but a single case cannot establish this.
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Published paper
Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study (link to Critical Care)
This single-center observational study used sublingual sidestream dark-field videomicroscopy with a new GlycoCheck software version to analyze microvessels in 1-micrometer diameter classes (4-25 um) in 34 septic ICU patients and 17 healthy controls. Sepsis was associated with loss of the very smallest capillaries, impaired capillary recruitment, and increased perfused boundary region (indicating a thinner/more permeable glycocalyx). The authors combined capillary blood volume and PBR into a composite 'Microvascular Health Score' that separated patients from controls and correlated with sepsis severity.
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Published paper
Non-invasive evaluation of macro- and microhemodynamic changes during induction of general anesthesia – A prospective observational single-blinded trial
In 150 women undergoing gynecologic surgery, non-invasive bioimpedance monitoring showed that induction of general anesthesia caused a larger fall in cardiac output (~40%) than in mean arterial pressure (~26%). Patients who later needed norepinephrine already had lower baseline cardiac output, stroke volume and contractility, and norepinephrine raised blood pressure without restoring cardiac performance. Sidestream dark-field imaging in a subset showed a 6.4% rise in perfused boundary region by the end of surgery, consistent with glycocalyx impairment.
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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
Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates
This prospective observational study used sidestream dark-field imaging with GlycoCheck software to measure the perfused boundary region (PBR, an inverse marker of endothelial glycocalyx thickness) in the skin microcirculation of 85 term and 39 preterm newborns. Preterm infants, especially those born before 30 weeks, had lower PBR (i.e., larger glycocalyx dimensions) than term infants, and PBR rose (glycocalyx thinned) with increasing postnatal age. Extremely preterm infants reached higher PBR values by 6-7 weeks of life than moderately preterm or term babies measured at the same corrected gestational age.
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Published paper
Does sublingual microscopy correlate with nailfold videocapillaroscopy in systemic sclerosis?
This single-center cross-sectional study compared automated sublingual videomicroscopy (GlycoCheck) with nailfold videocapillaroscopy (NVC), the standard test for scleroderma microvascular damage, in 39 systemic sclerosis patients on the same clinic day. Sublingual microvascular density correlated moderately with nailfold capillary number and inversely with the NVC microangiopathy evolution score. Functional measures (red blood cell fraction and glycocalyx perfused boundary region) did not correlate with NVC parameters in this mostly late-pattern cohort.
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Published paper
Assessment of the sublingual microcirculation with the GlycoCheck system: Reproducibility and examination conditions
This randomized, controlled methodological study tested how reproducible sublingual glycocalyx measurements with the GlycoCheck system (perfused boundary region, PBR, and red blood cell filling) are, and how they are affected by smoking, a high-calorie meal, and coffee. Reproducibility of single measurements was poor to moderate but improved substantially when 3-5 measurements were averaged, with no meaningful differences between investigators. All three acute exposures worsened PBR and RBC filling, with effects still detectable at 180 minutes.
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Published paper
Evaluation of jejunal microvasculature of healthy anesthetized dogs with sidestream dark field video microscopy
This veterinary study tested whether sidestream dark field (SDF) video microscopy could image and quantify the small blood vessels of the jejunum (small intestine) in 30 healthy anesthetized dogs during spay surgery. Imaging was feasible and produced reference values for microvascular density, red blood cell filling, vessel width, and the perfused boundary region (PBR), an indirect index of glycocalyx thickness. The authors conclude the technique warrants further study, including in dogs with intestinal disease.
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Published paper
Visual and Biochemical Evidence of Glycocalyx Disruption in Human Dengue Infection, and Association With Plasma Leakage Severity
This prospective observational study in Vietnam re-analyzed stored sublingual sidestream dark-field videos with GlycoCheck software and measured plasma syndecan-1 and endocan in 75 patients with confirmed dengue and 12 outpatients with other febrile illness. Patients with the most severe grade of plasma leakage showed a thinner, more degraded glycocalyx (higher perfused boundary region) and much higher plasma levels of shed glycocalyx proteoglycans during the critical illness phase. There were no significant glycocalyx differences between mild outpatient dengue and other febrile illnesses.
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Published paper
Microvascular dysfunction in COVID-19: the MYSTIC study
This prospective, multi-center cross-sectional study used sublingual sidestream dark-field video microscopy (GlycoCheck) plus blood biomarkers to characterize microvascular and endothelial glycocalyx changes in 23 hospitalized COVID-19 patients versus 15 healthy controls. Patients showed marked loss of small capillaries, slower red blood cell velocity, and evidence of glycocalyx damage, most pronounced in those on mechanical ventilation. Higher perfused boundary region (thinner glycocalyx) and lower ADAMTS13 were associated with 60-day in-hospital mortality.
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Published paper
Evaluation of endothelial glycocalyx in healthy volunteers – An observational study
This observational study measured the endothelial glycocalyx in 21 young healthy adults using sublingual sidestream dark-field imaging with GlycoCheck software (perfused boundary region, PBR) and plasma syndecan-1 by ELISA. It reports reference values for both measures in a healthy cohort, with a median PBR of 1.82 um and median syndecan-1 of 0.3 ng/ml. The authors note their values do not fully agree with previously published healthy-subject data.
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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
Sex-related associations of high-density lipoprotein cholesterol with aortic stiffness and endothelial glycocalyx integrity in treated hypertensive patients
This cross-sectional study of 193 treated hypertensive patients examined whether HDL cholesterol levels relate to aortic stiffness (carotid-femoral pulse wave velocity) and endothelial glycocalyx integrity (sublingual perfused boundary region measured by sidestream dark-field imaging/GlycoCheck). Higher HDL-C was weakly and inversely associated with aortic stiffness in the whole group, and with PBR5-9 (a marker where higher values indicate a thinner glycocalyx) specifically in men, regardless of smoking status. No such glycocalyx association was seen in women, despite their higher HDL-C levels.
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Published paper
Immediate effects of whole blood donation on the endothelial surface layer and glycocalyx shedding
Researchers measured the sublingual microcirculation and blood markers of glycocalyx shedding in healthy volunteers immediately before and after donating 500 mL of whole blood. Using sidestream dark-field imaging with GlycoCheck software, they found no significant immediate change in the perfused boundary region (PBR) or red blood cell filling percentage. Plasma heparan sulfate and hyaluronan fell slightly while syndecan-1 was unchanged, suggesting the endothelial surface layer remains structurally stable after a standard donation.
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Published paper
Variability of Microcirculatory Measurements in Critically Ill Patients
This study tested how reproducible sublingual GlycoCheck microcirculation measurements are in 60 critically ill patients, using repeated measurements by one or two experienced observers. Single measurements of glycocalyx thickness (perfused boundary region) showed poor reliability, while red blood cell filling percentage and vessel density were more consistent. Averaging three consecutive measurements substantially improved reproducibility for all parameters.
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Published paper
Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis
Researchers measured sublingual glycocalyx thickness (as the perfused boundary region, PBR) with sidestream dark-field imaging and GlycoCheck software within 24 hours of ICU admission in 21 septic patients, and compared results with plasma markers and survival. Patients who did not survive to hospital discharge had a thinner glycocalyx (higher PBR) than survivors, and admission PBR discriminated survivors from non-survivors moderately well. PBR correlated with angiopoietin-2 but not with syndecan-1 or severity scores.
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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
In Vivo Imaging of the Buccal Mucosa Shows Loss of the Endothelial Glycocalyx and Perivascular Hemorrhages in Pediatric Plasmodium falciparum Malaria
Researchers used incident dark-field video microscopy of the inner cheek (buccal mucosa) in Tanzanian children to measure the perfused boundary region (PBR), an inverse indicator of endothelial glycocalyx thickness, alongside plasma glycocalyx shedding markers. Children with severe malaria had a significantly increased PBR and higher circulating hyaluronic acid, heparan sulfate, sulfated glycosaminoglycans, syndecan-1 and glypican-1 than healthy controls, consistent with substantial glycocalyx loss. Imaging also revealed perivascular hemorrhages and sequestering late-stage parasites, and markers of vascular instability (low angiopoietin-1, high angiopoietin-2) tracked with these changes.
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