Dextran

Dextran: A Comprehensive Reference

1. Identity

Chemical and Systematic Names

Dextran is a complex branched glucan — a polysaccharide derived from the condensation of glucose. IUPAC defines dextrans as "Branched poly-α-d-glucosides of microbial origin having glycosidic bonds predominantly C-1 → C-6." It carries the basic chemical formula H(C₆H₁₀O₅)_nOH. Its CAS registry number is 9004-54-0. This characteristic branching distinguishes dextran from dextrin, which is a straight-chain glucose polymer tethered by α-1,4 or α-1,6 linkages.

Molecular Architecture and Variants

Dextran is a neutral polymer with α-(1→6) glucopyranosyl linkages, which constitute 50–97% of linkages; in addition, there also exists a small proportion of α-(1→2), α-(1→3), and α-(1→4) linkages, which produce a highly branched molecule. Dextran chains are of varying lengths, ranging from 3 to 2,000 kilodaltons. Native dextran has been found to have a molecular weight (MW) in the range of 9 million to 500 million; lower MW dextrans exhibit slightly less branching and have a more narrow range of MW distribution.

Industrial dextran production is mainly from a strain of Leuconostoc mesenteroides, which yields a polysaccharide with about 95% 1→6 linkages and 5% 1→3 linkages and has a molecular mass of about 4–5 × 10⁷. For the production of dextrans of medium molecular weight, the initial high molecular weight product must be hydrolyzed with acid or with enzymes and fractionated under carefully controlled conditions.

Natural Sources and Producing Organisms

Dextran is a complex branched polysaccharide derived primarily from the fermentation of sucrose by certain bacteria, most notably Leuconostoc mesenteroides. It is an α-type glucan produced from sucrose by the action of the bacterial extracellular enzyme dextransucrase. This enzyme is produced by the mesophilic and thermophilic bacterial genera Leuconostoc, Gluconobacter, Streptococcus, and Lactobacillus. Dextrans are highly branched polymers; although dextrans are obtained from a multitude of bacteria, most of the industrially produced products are obtained from Leuconostoc mesenteroides and Leuconostoc dextranicum.

Leuconostoc produces the enzyme dextransucrase and secretes it into the culture medium in the presence of sucrose. This enzyme, dextransucrase, synthesizes dextran from the sucrose substrate, catalyzing the transfer of glucosyl residues from sucrose to the dextran polymer and liberating fructose. The chemical and physical properties of native dextran powder change in function of the microbial strain from which it is produced and/or by the production method.

Common Forms and Preparations

Clinically and commercially, dextran is standardized by its average molecular weight. Dextrans are highly branched polysaccharide molecules, commonly described by their number-averaged molecular weight (MW_n): dextran 40 and dextran 70 have MW_ns of 40 and 70 kDa, respectively. Key pharmaceutical grades include:

• Dextran 1 (MW ~1,000 Da): used as a hapten inhibitor to pre-empt anaphylactoid reactions before infusion of higher-MW dextrans.
• Dextran 40 (MW ~40,000 Da): a low molecular weight polymer of glucose with a molecular weight range of approximately 10,000–90,000; linkages are principally of the 1,6-glucosidic type; it occurs as a white, amorphous powder and is soluble in water.
• Dextran 70 (MW ~70,000 Da): listed on the WHO Model List of Essential Medicines as one of the most important medications needed in a health system.
• Iron dextran: an injectable complex comprising ferric hydroxide and a low-molecular-weight fraction of dextran, tailored to treat iron deficiency anemia.
• Ophthalmic solutions: dextran is formulated with hypromellose and glycerin as artificial tears for dry eye relief.
• Sephadex® gels: cross-linked dextran beads used in biochemical size-exclusion chromatography.

Dextran is defined as a bacterial polysaccharide primarily formed from sucrose, consisting of branched chain polymers of glucose; it is soluble in water and can be converted into insoluble hydrophilic gels through cross-linking.

2. Historical and Traditional Use

Early Discovery (19th Century)

The discovery of dextran dates back to 1861, when it was identified by Louis Pasteur as a fermentation byproduct of wine. It was later named "dextran" by Scheibler in 1869 because of its similarities to dextrin. Dextran was thus originally derived from wine. At that time, dextran was not intentionally produced; it was recognized primarily as a problematic contaminant. Bacterial polyglucans were a significant issue in sugar processing for more than 100 years.

Industrial Nuisance to Medical Breakthrough (1940s–1950s)

During the 1940s, a team of Swedish scientists led by Anders Grönwall and Björn Ingelman discovered that bacterial dextran could serve as a blood plasma substitute — an unexpected finding made while investigating contaminations in sugar beet juice. Collaborating with the company Pharmacia, they developed the first clinical dextran solution, and in 1947 Pharmacia launched Macrodex, a dextran-based intravenous plasma expander.

Meanwhile, in the United States, chemist Allene R. Jeanes pioneered a method to mass-produce dextran via fermentation, which the U.S. Army deployed as a life-saving blood volume expander during the Korean War. Dextran solution could be sterilized, stored without refrigeration, and contained no blood products — advantages that made it an invaluable emergency substitute for blood plasma on the battlefield.

By chance, a soda company sent the Northern Regional Research Laboratory (NRRL) in Peoria, Illinois, a batch of root beer that had strangely become thick and viscous; Jeanes discovered that bacteria which produced dextran, a thickening agent, had infected the soda. By isolating these bacteria, she discovered a cheap way to produce large quantities of dextran. When the Korean War broke out in 1950, dextran was approved for medical use in the military, enabling wounded soldiers to survive until they could receive treatment.

Dextran was the first α-glucan to be industrially used as a blood plasma substitute in the 1940s.

Traditional Presence in Fermented Foods

Lactic acid bacteria (LAB) are generally regarded as safe (GRAS) for human beings in their daily diet and can be commonly isolated from fermented foods, including wine, yogurt, milk, and kimchi. Dextran produced by LAB has therefore been a constituent of traditionally fermented foods for millennia, though it was not recognized as a distinct substance until the 19th century. Mono-polysaccharides and oligosaccharides such as dextran and fructan are produced from whole grain flour in sourdough by LAB fermentation, so sourdough bread generally has a high amount of dextran-type exopolysaccharides.

3. Key Constituents and Active Compounds

Structural Identity as the Active Entity

Unlike botanically derived supplements, dextran's "active compound" is the polysaccharide itself. This microbially produced polymer of glucose possesses multi-faceted characteristics such as its solubility in different solvents and the formation of dextran solutions of needed viscosity; several preparations can be formulated for desired thermal and rheological properties. Due to such multifunctional characteristics, dextran with different structural specifications is a desired polysaccharide for clinical, pharmaceutical, and food industry commercial applications.

The structure of dextran is mainly dependent on the type of dextransucrase (DSR) present in the bacterial strains and on growth conditions such as sucrose amount, acidity, and temperature. Dextran structure and molecular weight are important features, as they determine its functionality in food applications.

Derivatives with Distinct Functions

• DEAE-dextran (diethylaminoethyl dextran): a polycationic derivative that can be used as a component/adjuvant in vaccines, for transfection and gene therapy, as a stabilizer of proteins, and in drug delivery.
• Hydrogenated dextran (Hydrodextran): differs from regular dextran as it is non-reducing; the hydrogenation process produces a carbohydrate that retains most of the physical properties of the original dextran but is chemically more stable and inert.
• Iron dextran: a complex of ferric hydroxide and low-MW dextran, FDA-approved for treating iron deficiency anemia.
• Fluorescein-labeled dextran (FITC-dextran): used as a research probe for measuring gut permeability and microvascular integrity.

4. Mechanisms of Action

Plasma Volume Expansion (Colloidal Oncotic Effect)

Dextran replaces blood proteins such as albumins to provide colloid osmotic pressure, so that fluid is pulled from the interstitial space into the plasma. The principal effect of dextran 40 following IV administration is plasma volume expansion, resulting from the drug's colloidal osmotic effect in drawing fluid from the interstitial to the intravascular spaces. Dextran 40 produces a plasma volume expansion slightly greater than the volume of dextran 40 solution infused.

Antithrombotic and Antiplatelet Mechanisms

The antithrombotic effect of dextran is mediated through its binding of erythrocytes, platelets, and vascular endothelium, increasing their electronegativity and thus reducing erythrocyte aggregation and platelet adhesiveness. Dextrans also reduce factor VIII-Ag Von Willebrand factor, thereby decreasing platelet function.

Clots formed after administration of dextrans are more easily lysed due to an altered thrombus structure (more evenly distributed platelets with coarser fibrin). By inhibiting α-2 antiplasmin, dextran serves as a plasminogen activator, so it also possesses thrombolytic features.

These effects reduce clot production and sustainability, and dextran's oncotic effects reduce plasma hematocrit and thus viscosity. This combination achieves an improvement in blood flow.

Hemorheological Effects

Dextran 40 can improve blood flow by reducing blood viscosity and inhibiting erythrocyte aggregation. Improvement of blood flow occurs because of a reduction in plasma viscosity and possibly by reducing the interaction between the vascular endothelium and the cellular components of blood.

Ophthalmic Lubrication

Hypromellose/glycerin/dextran combination ophthalmic solutions act as eye lubricants (artificial tears); they work similarly to natural tears, providing temporary relief from burning and discomfort due to eye dryness by maintaining proper eye lubrication and acting as a protectant against further irritation.

Prebiotic / Gut-Fermentation Activity

Dextrans can be directly added to fermented food products to enhance texture and provide functional properties, and are also utilized as prebiotic ingredients, promoting the growth of beneficial gut bacteria. Oligosaccharides derived during dextran-producing fermentation processes can act as prebiotics.

Food-Technological Functions

Exopolysaccharides (EPS) such as dextran formed during sourdough fermentation influence the dough's viscoelastic properties and improve the texture and shelf-life; in this context, EPS can replace hydrocolloids used as bread improvers and meet consumer demands for reduced use of food additives. High-molecular-weight dextran-enriched sourdough improved bread quality by increasing bread volume from 3.86 cm³/g to 5.04 cm³/g, and the bread staling rate decreased by 49.02% compared with the control.

5. Scientific Evidence by Area of Use

5.1 Plasma Volume Expansion (Hypovolemia and Hemorrhagic Shock)

Evidence strength: Well-established; supported by decades of clinical use and inclusion in the WHO Essential Medicines List.

Dextran is used in managing and treating various clinical conditions, including hemorrhage, shock, surgical procedures, and radiological imaging. In the operating room and intensive care unit settings, dextran is used osmotically as a colloid to treat hypovolemia and/or hemorrhage from trauma, burns, or surgeries when ABO compatibility tests are not possible in time.

Clinical grades of dextrans with molecular weights of 40,000, 60,000, and 70,000 g/mol (designated as dextran 40, 60, and 70, respectively) have been used to replace moderate blood loss and to improve blood flow by the reduction of blood viscosity as well as inhibition of erythrocyte aggregation. Intravenous solution with dextran 60 is commonly used as a blood volume expander and parenteral nutrition that provides osmotically neutral fluid after being digested into glucose and water.

Animal data support volume expansion in burn injuries: animal studies demonstrated that dextrans are effective volume expanders that limit resuscitation requirements and fluid shifts into unburned soft tissues and lung, minimizing edema formation compared with crystalloids; however, concerns about dextran-associated anaphylactic reactions, coagulopathy, and possible renal toxicity have limited use of this volume expander in clinical burn resuscitation.

5.2 Antithrombotic Prophylaxis (Deep Vein Thrombosis and Pulmonary Embolism)

Evidence strength: Established clinical use, but increasingly supplanted by newer anticoagulants due to safety concerns.

Antithrombotic effects of clinical dextrans provide prophylactic treatment for deep venous thrombosis and postoperative pulmonary embolism. Dextran 40 is hyperoncotic and initially acts as a plasma expander before its rapid elimination by the kidneys; its main use is for promoting peripheral blood flow (in prophylaxis for deep vein thrombosis and in maintaining graft patency in flap surgery).

These agents are used commonly by microsurgeons to decrease vascular thrombosis. A scoping review protocol published in PMC (2025) specifically notes that the current literature on the indications and efficacy of clinical dextrans as antiplatelet and anticoagulant agents spans both non-operative and operative settings, including trauma, reconstructive surgery, transplantation, and vascular surgery. The quality of evidence in the literature is acknowledged to be heterogeneous.

Regarding microsurgery outcomes, a ScienceDirect analysis of head and neck microvascular reconstruction reported that other serious side effects have also been associated with dextran use including anaphylaxis, anaphylactoid reactions, pseudotumor cerebri, benign intracranial hypertension, and renal failure; in conclusion, dextrans do not seem to offer any reduction in postoperative complication rates in head and neck microvascular reconstruction and could increase medical complication rates. This finding indicates that clinical benefit in microvascular surgery specifically is not firmly established and risk must be weighed carefully.

5.3 Iron Deficiency Anemia (Iron Dextran)

Evidence strength: High; FDA-approved indication with well-characterized pharmacology.

Iron dextran has been approved by the U.S. Food and Drug Administration (FDA) for treating iron deficiency anemia in patients who are unresponsive to oral iron therapy or cannot tolerate it. Iron dextran is an intravenous iron solution tailored to treat iron deficiency anemia; oral iron therapy is frequently used first, but certain patients either exhibit inadequate responses to oral iron or encounter difficulties in its administration.

5.4 Ophthalmic Use (Dry Eye / Xerophthalmia)

Evidence strength: Established for symptomatic relief; regulatory approval as an artificial tear.

Dextran has several ophthalmic applications as solutions for relieving ocular irritation or xerophthalmia. Formulations combining dextran 70 with hypromellose and glycerin are FDA-approved for dry eye disease. As a formulated component in eye drops, dextran will usually be administered 1 to 2 drops at a time. Eye lubricants containing dextran keep the eye moist, help to protect the eye from injury and infection, and decrease symptoms of dry eyes such as burning, itching, and the feeling of a foreign body in the eye.

5.5 Radiological Imaging (Diagnostic Use)

Evidence strength: Established clinical use, specialized application.

Labeled with technetium Tc-99m, clinicians use intravenous dextran during radiographic imaging such as nuclear medicine, MRI, or scintigraphy, and as a contrast agent to detect and diagnose conditions such as ventricular aneurysms and pericardial effusions.

5.6 Prebiotic and Gut Microbiome Effects

Evidence strength: Preliminary to moderate; largely from in vitro, animal, and food-science studies. Direct human clinical trials specifically isolating dextran as a prebiotic supplement are sparse.

Dextrans are utilized as prebiotic ingredients, promoting the growth of beneficial gut bacteria. Dextran-producing LAB (homopolysaccharides) have potential applications in the pharmaceutical industry as antioxidants, immunomodulators, anticancer agents, anticoagulants, antivirals, and anti-cholesterol agents — however, the preponderance of these claims rests on in vitro or animal data. Microbial-derived carbohydrates such as beta-glucan and dextran may have potential effects on IBS symptoms and require further investigation.

In sourdough research, one mouse feeding study found that white bread containing 40% sourdough (containing LAB-produced dextran and fructan) reduced the glycemic index compared with yeast-leavened white bread, suggesting a diabetes-lowering effect, probably due to the presence of dietary fiber and short-chain fatty acids. This was an animal study and cannot be directly extrapolated to human clinical outcomes.

5.7 Drug Delivery Systems

Evidence strength: Strongly supported in pharmaceutical science; most applications remain preclinical or in early-stage clinical development.

Dextran is a natural polysaccharide having 1,6-linked glucose molecules with two OH groups per glucose unit; as it is biocompatible as well as biodegradable, it is a suitable biomaterial for the delivery of numerous drug molecules. It has been extensively used as a major component in many types of drug-delivery systems (DDS), which can be submitted to in vivo testing stages and may be proposed for clinical trials or pharmaceutical use approval. An important aspect to maintain high DDS biocompatibility is the use of dextran obtained by fermentation processes with a minimum chemical modification degree.

6. Body Systems and Health Areas

• Cardiovascular and Circulatory System: Plasma volume restoration, reduction of blood viscosity, maintenance of microcirculation, antithrombotic prophylaxis in surgery.
• Hematological System: Inhibition of platelet adhesiveness, reduction of von Willebrand factor activity, enhancement of fibrinolysis, and (as iron dextran) treatment of iron deficiency anemia.
• Renal System: Smaller dextran fractions are eliminated by glomerular filtration; high doses or accumulation can impair renal function (see Safety section).
• Ophthalmic System: Lubrication and protection of the ocular surface in dry eye disease.
• Gastrointestinal and Microbiome: Dextran produced during LAB fermentation in sourdough, yogurt, and other fermented foods contributes to dietary fiber intake and potential prebiotic activity.
• Immune System: In the pharmaceutical industry, DEX is used as an antioxidant and free radical scavenging agent, and as an inducing agent for interferon biosynthesis.

7. Pharmacokinetics

Absorption After Oral Administration

After oral administration in rats, dextrans could not be detected in serum, and on the basis of urine data, only negligible amounts of the macromolecules were absorbed into the systemic circulation (less than 0.4% of the dose). This confirms that orally ingested dextran is not meaningfully absorbed as an intact macromolecule, instead passing into the large intestine where it may be fermented.

Distribution and Elimination After IV Administration

According to their average molecular weight, dextrans can be differentiated into dextran 1, dextran 40, dextran 60, and dextran 70. Metabolism of dextrans by dextranases and extrarenal excretion account for only 2 to 10% of the overall drug loss from the body. Persistence of dextrans in the systemic circulation and elimination by the renal route are dependent on the size of dextrans and their molecular weight distribution.

Dextran species with a molecular weight below 15,000 daltons are filtered unrestricted, and consequently the elimination half-life of dextran 1 is relatively short (2 hours) and that of dextran 40 (10 hours) or dextran 60 (42 hours) much longer. Dextrans are available in multiple molecular weights ranging from 3,000 Da to 2,000,000 Da. The larger dextrans (>60,000 Da) are excreted poorly from the kidney, so they remain in the blood for as long as weeks until they are metabolized. Consequently, they have prolonged antithrombotic and colloidal effects.

About 70% of a dose of dextran 40 is excreted unchanged in urine within 24 hours after administration. Dextran molecules of molecular weight 50,000 or greater are not excreted by the kidneys but are slowly degraded to glucose, which is then metabolized to carbon dioxide and water. A small amount of the infused dextran is also excreted into the GI tract and eliminated in feces.

In patients with renal insufficiency, elimination is impaired in parallel to the reduction in glomerular filtration rate, and smaller doses are advisable in these patients. Dosage reduction might also be indicated if multiple infusions of dextrans are used, since dextran 40 accumulates considerably during long-term use, particularly the fractions with higher molecular weights.

8. Dosage Forms and Dosages Reported in Studies

Intravenous Formulations

Each 500 mL of the commercially available colloidal solution containing 10% dextran 40 in 0.9% sodium chloride provides 77 mEq of sodium (pH 3.5–7). A colloidal solution of 10% dextran 40 in 5% dextrose has a pH of 3–7.

Doses above 1.5 g/kg produce a coagulopathy. Dosage reduction is indicated if multiple infusions of dextrans are used, since dextran 40 accumulates considerably during long-term use.

Dextran-40 (MW: 40,000 Da) has been the most popular member for anticoagulation therapy; close to 70% of dextran-40 is excreted in urine within the first 24 hours after intravenous infusion, while the remaining 30% are retained for several more days.

Ophthalmic Formulations

Dextran as a formulated component in eye drops is usually administered 1 to 2 drops at a time. A representative commercial formulation is dextran 70 (0.1%) combined with hypromellose (0.3%) in an ophthalmic solution.

Oral / Food Contexts

No standardized oral dosage has been established for dextran as a dietary supplement. Resistant dextrin — a related low-molecular-weight, water-soluble dietary fiber made from natural corn starch — is used as a functional dietary ingredient. In sourdough fermentation, dextran is generated endogenously and consumed as part of the food matrix rather than as a defined supplement dose.

9. Safety Considerations and Drug Interactions

General Safety Profile

Adverse effects of dextran are uncommon when administered appropriately. However, allergic reactions — ranging from localized injection site responses to systemic anaphylactic or anaphylactoid events — can occur. Signs such as rash, hives, wheezing, chest tightness, or shortness of breath should alert healthcare providers to the possibility of a serious reaction.

Although relatively few side effects are associated with dextran use, these side effects can be very serious. They include anaphylaxis, volume overload, pulmonary edema, cerebral edema, or platelet dysfunction.

Anaphylaxis and Anaphylactoid Reactions

Clinical dextrans such as Dextran 40 and Dextran 70 are associated with anaphylactoid reactions caused by dextran-reactive immunoglobulin G antibodies. When infused immediately before clinical dextrans, dextran 1 significantly reduces the incidence of severe anaphylactoid reactions. A review of FDA adverse event data found that the FDA received 366 clinical dextran adverse event reports from 1969 to 2004, of which 90 (24.6%) were anaphylaxis/anaphylactoid events.

Renal Toxicity

Dextran use has been linked to direct nephrotoxicity causing acute kidney injury (AKI). Dextran 40 can cause acute kidney injury; the dextran molecules are filtered by the glomeruli but are reabsorbed in the renal tubules, where they can cause a high viscosity of the tubular fluid. This can lead to tubular obstruction and a form of kidney damage known as osmotic nephrosis. The risk is significantly higher in patients with pre-existing renal disease, dehydration, or those receiving other nephrotoxic drugs.

Despite the greater effects of intravascular volume expansion, dextran solutions are associated with acute renal failure, likely due to their accumulation in the renal tubules.

Coagulopathy

At doses higher than recommended, dextran 40 can interfere with coagulation. It can cause a decrease in platelet adhesiveness and depress the activity of Factor VIII, leading to a prolonged bleeding time. Other associated negative side effects include more severe anaphylaxis when compared to gelatins or starch solutions and coagulopathy due to its effect on platelet adhesion, fibrinolysis, and Factor VIII.

Fluid Overload and Cardiopulmonary Complications

A significant increase in postoperative pulmonary complications (defined as pulmonary edema, pleural effusion, adult respiratory distress syndrome, or pneumonia) and cardiac complications (defined as congestive heart failure, arrhythmias, or ischemia confirmed on electrocardiogram or radiograph) have been reported. A dose-specific response was identified, with the number of complications greatest in the group that received dextran for 120 hours.

Current Clinical Status

Dextran 70 remains approved for volume expansion in hypovolemia due to trauma, burns, or surgery, but is rarely used due to risks such as anaphylaxis, renal impairment, coagulopathy, and issues with blood crossmatching.

Drug Interactions

Angiotensin-converting enzyme (ACE) inhibitors decrease the breakdown of kinins and may increase the risk of anaphylaxis when administered with iron dextran. Dimercaprol binds to iron, forming a nephrotoxic complex; co-administration of dimercaprol with iron dextran is not recommended.

Dextrans reduce platelet adhesiveness, enhance fibrinolysis, and may reduce factor VIII activity — making concurrent use with anticoagulants or antiplatelet agents a potential risk for additive bleeding effects. Blood crossmatching can be interfered with by dextran, necessitating that blood specimens for typing and crossmatching be drawn before dextran infusion when possible.

Toxicology

Some reports have shown adverse effects when used in therapeutic doses and some teratogenic effects have been demonstrated when used in large doses. The current LD50 reported in rats is 10,700 mg/kg.

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