Nutrition & supplementation: 17 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
Early impairment of skeletal muscle endothelial glycocalyx barrier properties in diet-induced obesity in mice.
This mouse study examined whether the endothelial glycocalyx in skeletal muscle microvessels is damaged early in the course of diet-induced obesity. Using intravital measurement of glycocalyx barrier properties (accessibility of the glycocalyx to circulating tracers/red blood cells) in mice fed a high-fat diet, the authors found loss of glycocalyx barrier function before or alongside the development of overt metabolic disease. The findings suggest the glycocalyx is an early target of obesogenic diet rather than a late consequence of established obesity.
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Published paper
Rapid insulin-mediated increase in microvascular glycocalyx accessibility in skeletal muscle may contribute to insulin-mediated glucose disposal in rats.
In rats, systemic insulin infusion rapidly increased the accessible (perfused) volume of the endothelial glycocalyx in skeletal muscle microvessels, measured as increased distribution volume of a glycocalyx-permeable tracer. Enzymatic degradation of the glycocalyx with hyaluronidase blunted both this insulin-induced increase in glycocalyx accessibility and insulin-mediated glucose disposal. The authors conclude that insulin-driven changes in glycocalyx accessibility may contribute to how insulin promotes glucose uptake by muscle.
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Published paper
Rhamnan sulfate enhances the endothelial glycocalyx and decreases the LDL permeability of human coronary artery endothelial cells in vitro
Human coronary artery endothelial cell monolayers were treated for 24 hours with two isoforms of rhamnan sulfate (a sulfated polysaccharide) and then tested for how easily LDL cholesterol crossed the cell layer. Both isoforms cut LDL permeability about 5-fold and prevented the permeability rise caused by chemically induced apoptosis, while immunostaining showed greater heparan sulfate coverage, a key glycocalyx component. The authors propose that a thicker glycocalyx adds resistance to the 'leaky junction' route that LDL uses to cross the endothelium.
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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
Associations Between Adipose Tissue Glycocalyx Quality, Nox Activity, and Microvascular Blood Flow
This undergraduate honors thesis reports a small within-subject human physiology experiment in which sublingual microvascular measures (GlycoCheck perfused boundary region, capillary density, red blood cell velocity) were compared under fasting conditions and during a hyperinsulinemic-euglycemic clamp, alongside adipose tissue microdialysis measures of lipolysis (glycerol), reactive oxygen species and blood flow. Insulin infusion was associated with a small but statistically significant increase in perfused boundary region (suggesting thinner/less dense glycocalyx) and decreases in red blood cell velocity and some vessel-diameter-specific densities, while microdialysis measures did not change significantly. The work is descriptive and exploratory, with only 6-8 participants analyzed per outcome.
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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
Sex-related differences in arterial stiffness in type 2 diabetics: role of uric acid
This is a clinical trial protocol/registration document (NCT03648996) rather than a report of results. It describes a planned study testing whether a low-fructose diet (isocaloric or hypocaloric) or the xanthine oxidase inhibitor allopurinol changes arterial stiffness in people with type 2 diabetes, with attention to sex-related differences and the role of uric acid. No outcome data are presented in the provided text.
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Published paper
Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction
In mice, researchers reduced glycocalyx thickness by knocking down hyaluronan synthase 2 (Has2) and found this reproduced hallmarks of arterial aging: impaired endothelium-dependent dilation and increased aortic stiffness. Conversely, feeding old mice for 10 weeks with a glycocalyx-component supplement (Endocalyx, containing high-molecular-weight hyaluronan, glucosamine sulfate, fucoidan and superoxide dismutase) or with high-molecular-weight hyaluronan alone restored glycocalyx thickness and barrier function and improved endothelial function, aortic stiffness and blood pressure. Aortic wall composition (collagen, elastin) in supplemented old mice also resembled that of young mice.
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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
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
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
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
Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion
In a population-based sample of 915 middle-aged Dutch adults, researchers used sidestream dark-field imaging with automated GlycoCheck software to measure the perfused boundary region (PBR, a marker of how deeply red blood cells penetrate the endothelial glycocalyx) in sublingual microvessels. Deeper red-cell penetration (higher PBR) was strongly associated with poorer microvascular perfusion, measured as the percentage of time vessel segments contained red blood cells. The authors interpret a low PBR (thicker glycocalyx) as reflecting more efficient microvascular perfusion.
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