Polysaccharides

Polysaccharides: A Comprehensive Reference

1. Identity, Chemical Classification, and Natural Sources

Polysaccharides are usually composed of more than ten monosaccharide units, which are connected by linear or branched glycosidic bonds. Each monosaccharide molecule is connected by glycosidic bonds and can be represented by the general formula (C₆H₁₀O₅)n. The structures of polysaccharides generally contain linear or branched side chains, and the molecular weight is distributed over the range of tens of thousands to millions.

Several polysaccharides, such as starch, cellulose, alginate, chitin, and chitosan, have been mainly studied in the recent decade due to some distinguished characteristic properties and are divided into two major types: digestible and indigestible. Digestible polysaccharides (starch and glycogen) are broken down to sugar by digestive enzymes in the stomach and absorbed, transported through the body. The FAO (Food and Agriculture Organization) defined dietary fibers as a variety of indigestible plant polysaccharides including pectins, cellulose, gums, hemicelluloses, oligosaccharides, and various lignified compounds.

The inherent complexity of polysaccharide structures, derived from the diversity of plant sources and potential chemical modifications, results in a wide range of different physicochemical properties, making them flexible for various applications in the food industry.

Among the most scientifically studied polysaccharides as dietary supplements are:

• β-Glucans: Cereal β-glucans have a specific combination of β-(1→4) and β-(1→3) linkages into linear long-chain polysaccharides of high molecular weight. Cell walls of the endosperm and aleurone layer of barley and oat grains contain the highest amounts of β-glucan compared to other cereals.
• Fungal polysaccharides (including Ganoderma β-glucans): Modern pharmacology studies have proven that Ganoderma β-d-glucan exhibits versatile biological activities, such as immunomodulatory, antitumor, antioxidant, and antiviral properties, as well as gut microbiota regulation.
• Astragalus polysaccharides (APS): Astragalus polysaccharide (APS) has been found to promote dendritic cell (DC) activation by increasing the expression of some immune-related suppressors such as CD86, CD80 and MHC-II on the DCs surface, resulting in enhanced interaction between DCs and T cells.
• Fucoidan: Marine brown seaweed species have been shown to have sulfated polysaccharides (such as alginate or fucoidan) in their extracts.
• Inulin and fructooligosaccharides (FOS): Gums, inulin, and pectin are capable of slowing down the passage of food in the digestive tract, reducing serum cholesterol concentrations, hindering the absorption of sugar from food to bloodstream and, therefore, avoiding sudden hyperglycemic conditions post food ingestion.

Polysaccharides are derived from multiple natural resources such as plants, animals, bacteria, fungi, algae, and arthropods. Plant polysaccharides contain photosynthetic by-products that are found in a wide range of plant parts, including leaves, pods, flowers, fruits, nuts, cereals, roots, tubers, corms, gums, and exudates.

Key Structural Determinants of Activity

Molecular weight, monosaccharide composition (including galactose, mannose, rhamnogalacturonan-I, arabinogalactan and uronic acid), functional groups (namely sulfate, selenium, and acetyl groups), types of glycoside bond connection (including β-1,3-D-glucosyl, α-1,4-D-glucosyl, β-1,4-D-glucosyl, α-1,6-D-glucosyl, β-1,4-D-mannosyl, and β-1,4-D-Xylopyranosyl), conformation and the branching degrees are systematically identified as contributors to the immunostimulatory activity of polysaccharides.

The addition of sulfate, selenium, and acetyl groups to the polysaccharides modifies their structures to easily enter the cells of the immune system and hence may trigger different immune stimulation responses. Polysaccharides have different conformations; both triple-helix and random coil have their own characteristics and can be recognized by the receptors of immune cells.

2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

Traditional Chinese Medicine (TCM) has been used to treat diseases in China for thousands of years. TCM compositions are complex, using as their various sources plants, animals, fungi, and minerals. Polysaccharides are one of the active and important ingredients of TCMs. For thousands of years, TCM has been the most important therapeutic method in China and even the whole of East Asia. The compositions of traditional Chinese medicines are complex, and their active ingredients are often polysaccharides, saponins, flavonoids, polyphenols, and polypeptides.

Fungal traditional Chinese medicine is a medicinal resource with a long history and widespread application in China. Accumulating evidence confirms that polysaccharide is the main pharmacodynamic material on which fungal TCM is based. Through literature review, it was found that polysaccharide is an important active ingredient of fungal traditional Chinese medicine, such as Ganoderma lucidum, Auricularia auricula-judae, and Portulaca oleracea.

Polygonatum sibiricum is one of the most widely used plants in the Liliaceae family, renowned for its dual medicinal and edible properties. Polygonatum sibiricum polysaccharides, as the main pharmacological active ingredient, have various excellent physiological activities, such as antioxidant, immune enhancement, and hypoglycemic activities. In the Pharmacopoeia of the People's Republic of China 2020, Polygonatum kingianum, Polygonatum sibiricum, and Polygonatum cyrtonema are the sources of Polygonatum sibiricum, which are traditional Chinese medicinal materials.

Ayurveda and Other Traditions

Plants such as Centella asiatica (L.) Urban, commonly known as Gotu Kola or Brahmi, have been traditionally used in various medicinal systems, including Traditional Chinese Medicine (TCM), Ayurveda, and African herbal practices. These traditions employed polysaccharide-rich plant preparations primarily as whole-herb decoctions, infusions, and powders, rather than as isolated polysaccharide fractions — a critical distinction from modern supplemental forms.

Oats and Cereal Grains

Oat products have been used for centuries for medicinal and cosmetic purposes; however, the specific role of β-glucan was not explored until the 20th century. β-glucans were first discovered in lichens, and shortly thereafter in barley.

3. Key Constituents, Active Compounds, and Mechanisms of Action

Immunomodulatory Mechanisms

Polysaccharides enhance immune function by activating macrophages, natural killer cells, and T cells, thereby promoting phagocytosis and cytokine production. The binding of β-glucan initiates the activation of MAPK and NF-κB signaling pathways, both of which play pivotal roles in cytokine production and immune regulation.

The mechanism by which low-molecular-weight heteropolysaccharides derived from the fruiting bodies of Ganoderma leucocontextum (GLP-1) activate macrophages is closely related to three major signaling pathways: mitogen-activated protein kinases (MAPKs), phosphoinositide-3 kinase/protein kinase B (PI3K/Akt), and nuclear factor κB (NF-κB).

The immunomodulatory activity of polysaccharides is closely related to the types and proportions of their constituent monosaccharides, the types of glycosidic bonds, and their molecular weight. In addition, the immunomodulatory effects of tonifying polysaccharides are not restricted to a solitary receptor or a discrete signaling cascade, but rather exhibit characteristics of multi-level, multi-pathway, and bi-directional target regulation, thereby modulating the body's immune capacity.

Prebiotic and Gut Microbiota Mechanisms

Polysaccharides are key regulators of colon physiology and the changing intestinal environment, and they are selectively used by gut microbiota to enhance the selection, colonization, and survival of probiotic bacteria acting as prebiotics. Short-chain fatty acids (SCFAs) are key molecules mediating the dialogue between the intestinal microbiota and the host.

Antitumor Mechanisms

Ample evidence indicates that polysaccharides can inhibit tumors through direct anticancer activity, such as inducing apoptosis of tumor cells and inhibiting migration. The mechanism of action involves apoptosis, inhibition of cellular proliferation, angiogenesis, and antimetastatic effects through multiple pathways.

Research elucidates three core epigenetic mechanisms of plant polysaccharides (e.g., Astragalus and Ganoderma lucidum): (1) TET2-mediated DNA demethylation; (2) inhibition of histone-modifying enzymes including JMJD2D; (3) regulation of tumor-suppressive miRNAs such as miR-139-5p.

Metabolic and Cholesterol-Lowering Mechanisms

Due to their particular structure, cereal β-glucans generate viscosity within the intestinal tract, which is thought to be the main mechanism of action responsible for their positive health effects. Barley β-glucan reduces blood cholesterol levels via interrupting bile acid metabolism.

Biodegradation and Metabolic Fate

Natural polysaccharides have been proven as biodegradable polymers, and under physiological conditions, their chains can be easily broken by various enzymes in the mucous surfaces, in the stomach, or produced by the normal intestinal flora. Studies have shown that the degradation of natural polysaccharides does not lead to the accumulation or retention of decaying substances in the body. The products of their metabolism are oligosaccharides, which either enter the metabolic pathways of glycosaminoglycans and glycoproteins, or they are directly excreted through the kidneys.

4. Scientific Evidence by Area of Use

4.1 Cardiovascular Health and Cholesterol Reduction

This is one of the best-supported areas of human evidence for polysaccharides, particularly oat and barley β-glucans.

β-glucan, a viscous soluble dietary fibre found naturally in oats and barley, has a number of potentially beneficial physiological effects which include reducing both postprandial glycaemic responses (PPGR) and serum cholesterol.

A meta-analysis was performed on epidemiological studies to assess the relation between β-glucan consumption from oats and from barley on blood cholesterol level, triglyceride/triacylglycerol (TGL/TAG) level, and blood glucose level in humans. In addition, the effect of β-glucan on total cholesterol (TC) and blood glucose level was translated into an empirical dose-response model. Thirty research articles that evaluated the effect of different exposure levels of β-glucan on blood cholesterol and blood glucose level were analyzed, yielding 126 clinical studies. There was a significant inverse relation in TC (−0.60 mmol/L, 95% CI −0.85 to −0.34), low-density lipoprotein (−0.66 mmol/L, 95% CI −0.96 to −0.36), and TGL/TAG (−0.04 mmol/L, 95% CI −0.15 to 0.07) after consumption of β-glucan.

The dose-response model showed that a 3 g/day dose of oat or barley β-glucan was sufficient to decrease total cholesterol. Consumption of 3 g/day of oat or barley β-glucan is sufficient to decrease blood cholesterol, whereas the effect on blood glucose level is still inconclusive, with high heterogeneity, and requires further clinical research studies with longer intervention periods.

Due to their property to lower serum total cholesterol and low-density lipoprotein cholesterol, and potentially reduce the risk of cardiovascular diseases, oat β-glucans have been assigned a qualified health claim by the European Food Safety Authority and the US Food and Drug Administration.

A comprehensive meta-analysis of 58 clinical trials and 3,974 subjects showed that oat beta-glucan significantly affects the serum concentrations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein-B (apo-B), concluding that the inclusion of oat-containing foods in the diet may be a valid strategy to prevent the onset of cardiovascular disease. These effects can theoretically play a major preventive role among the general population, since each 1% reduction in TC or LDL-C corresponds to an equivalent 1% decrease in the risk of developing a coronary heart disease event over time.

Evidence strength: Strong for LDL and total cholesterol reduction with oat and barley β-glucan in humans; supported by multiple randomized controlled trials and meta-analyses, and endorsed by major regulatory bodies (EFSA, FDA).

4.2 Blood Glucose Regulation

The ability of β-glucan to reduce postprandial glycaemic responses (PPGR) was established by a European Food Safety Authority (EFSA) Panel review that concluded that 4 g of either oat β-glucan or barley β-glucan per 30 g of available carbohydrates is required to obtain a consistent reduction in PPGR.

A systematic review and meta-analysis searched MEDLINE, EMBASE, and Cochrane databases through October 2020 for acute, crossover, controlled feeding trials investigating the effect of adding oat β-glucan to carbohydrate-containing test-meals in humans regardless of health status. A total of 103 trial comparisons (N = 538) were included. The analysis showed a significant change in blood glucose level (−2.58 mmol/L, 95% CI −3.22 to −1.84) with high heterogeneity between (I² = 97%) and across (τ² = 5.88) the studies. The high heterogeneity underscores the variable nature of glycaemic effects across preparations and populations.

Numerous studies have shown that especially the consumption of β-glucan from oat and barley may reduce the risk for the development of cardiovascular disease or type 2 diabetes mellitus.

Evidence strength: Moderate-to-strong for acute postprandial glucose reduction; weaker for long-term glycaemic outcomes in type 2 diabetes due to high heterogeneity across studies.

4.3 Immunomodulation

β-glucans are complex polysaccharides that are found in several plants and foods, including mushrooms. β-glucans display an array of potentially therapeutic properties. β-glucans have metabolic and gastrointestinal effects, modulating the gut microbiome, altering lipid and glucose metabolism, reducing cholesterol. β-glucans also have immune-modulating effects, leading to their investigation as adjuvant agents for cancers (solid and haematological malignancies), for immune-mediated conditions (e.g., allergic rhinitis, respiratory infections), and to enhance wound healing.

The therapeutic potential of β-glucans is evidenced by the fact that two glucan isolates were licensed as drugs in Japan as immune-adjuvant therapy for cancer in 1980.

Clinical studies have shown that Astragalus polysaccharide injection (PG2) significantly reduces the neutrophil-lymphocyte ratio (NLR) in advanced lung cancer patients receiving immune checkpoint inhibitor therapy.

Several polysaccharides have been used clinically to improve the body's immune function, such as Cheonggukjang polysaccharides, Ginseng polysaccharides, and Ganoderma atrum polysaccharides.

Significant challenges exist to further clinical testing and translation of β-glucans. The diverse range of conditions for which β-glucans are in clinical testing underlines the incomplete understanding of the diverse mechanisms of action of β-glucans, a key knowledge gap. Furthermore, important differences appear to exist in the effects of apparently similar β-glucan preparations, which may be due to differences in sources and extraction procedures, another poorly understood issue.

Evidence strength: Promising but heterogeneous. Preclinical and some clinical data support immunomodulatory activity; however, variability in preparations and study designs limits definitive clinical conclusions. Most robust human evidence exists for cancer immune-adjuvant use in Japan.

4.4 Gut Microbiota Modulation

In addition to stimulating the growth of certain intestinal bacteria, polysaccharides may also promote health benefits by modulating the gut microbiota. In the last years, studies about the triad gut microbiota–polysaccharides–health have increased exponentially.

Numerous clinical trials have already been conducted addressing a wide range of diseases (from obesity to chronic kidney disease) through dietary intervention with different polysaccharides.

Population studies have shown that barley β-glucan increases the abundance of Bacteroides and Bifidobacteria in older adults, highlighting its prebiotic potential.

Fructans, such as fructooligosaccharides (FOS) and inulin, are considered to be "gold standard" prebiotics, with human clinical trials supporting their beneficial effect in acute and chronic diseases such as obesity and type 2 diabetes (T2D), allergy, inflammatory bowel disease (IBD), Traveler's diarrhea and constipation.

Several clinical studies show that xylo-oligosaccharides (XOS) and arabino-xylo-oligosaccharides (AXOS) could exert protective effects on intestinal homeostasis and metabolic status.

The metabolic benefits of fermented polysaccharides via microbiota reshaping do not follow a linear dose-response relationship.

Evidence strength: Moderate-to-strong for inulin and FOS as prebiotics (human trials documented); moderate for other polysaccharides (barley β-glucan, XOS). Many studies are still at the in vitro or early clinical phase, with considerable inter-individual variability in microbiota responses.

4.5 Antitumor and Oncology-Adjuvant Activity

Accumulating evidence suggests that astragalus polysaccharide (APS) may enhance the efficacy of conventional cancer therapies through multiple mechanisms. However, the synergistic effects of APS have not been systematically quantified. A meta-analysis was conducted to quantify these potential synergistic antitumor effects and provide preclinical evidence to inform future clinical trials.

This meta-analysis provides preclinical evidence that APS may serve as an adjunctive agent to enhance the efficacy of conventional cancer therapies. However, given the low certainty of current evidence, further mechanistic studies and well-designed clinical trials are urgently warranted to establish its efficacy and therapeutic role in oncology.

Most of the antitumor polysaccharide studies explore algae polysaccharides (43.2%), followed by mushrooms (13.5%), plants (13.5%), fruits (10.8%), fungus (2.7%), bacteria (2.7%), and sea animals (2.7%). A total of 8.1% investigated only in vitro models, 62.1% evaluated only in vivo models, and 29.7% evaluated in vitro and in vivo models.

Fucoidan in colorectal cancer patients enhances chemotherapy sensitivity by upregulating Akkermansia abundance and suppressing TLR4/NF-κB signaling. A clinical trial (NCT04128072) demonstrated that inulin combined with immune checkpoint inhibitors improved melanoma patients' objective response rate (45% vs 28%).

Robust evidence exists, supplemented by preclinical studies and reports from select clinical trials, that polysaccharides influence the responsiveness of therapy and relieve treatment-related adverse reactions by regulating immune function, redox balance, and inflammatory signals. Compared with traditional small-molecule anticancer drugs, polysaccharides are mostly multi-target molecules with low systemic toxicity and good biocompatibility.

Evidence strength: Predominantly preclinical (in vitro and animal models). The clinical evidence for antitumor polysaccharides is preliminary, with a small number of human trials. The two mushroom-derived β-glucan drugs approved in Japan for cancer immune-adjuvant use remain the strongest validated clinical precedents. Large, well-controlled human trials for most polysaccharides in oncology are lacking.

4.6 Liver Protection

Polysaccharides are currently considered promising alternatives to traditional drugs because of their extensive activity and low toxicity. This area of research investigated hepatoprotective polysaccharides, detailing their hepatoprotective effects, potential mechanisms, and drug carrier applications. These findings suggest that polysaccharides have prominent preventive and therapeutic effects on various liver diseases such as drug-induced liver injury, alcoholic liver disease, hepatitis B, non-alcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma.

Polysaccharides are important active ingredients that are widely present in medicinal plants and fungi such as Ganoderma lucidum, Astragalus membranaceus, and Angelica sinensis.

Evidence strength: Preliminary to moderate. Most hepatoprotective evidence derives from preclinical models and animal studies; adequately powered human clinical trials remain limited as of current literature.

4.7 Autoimmune and Inflammatory Conditions

In rheumatoid arthritis, β-glucan activates Dectin-1 to promote regulatory T cell (Treg) differentiation and reduce pro-inflammatory cytokines (e.g., IL-17, TNF-α). Bioactive properties have been reported for polysaccharides with the effects of antioxidant, antitumor, immunomodulatory, immunostimulatory, anti-inflammatory, antinociception, anticoagulant, antiviral, antiprotozoal, antibacterial, and antihyperlipidemic activity.

Evidence strength: Primarily preclinical. Human-trial data in specific autoimmune conditions are very limited.

4.8 Vaccine Adjuvant Activity

Tonifying polysaccharides hold potential as vaccine adjuvants in antiviral immunization strategies. Polysaccharide from Ganoderma lucidum (PS-G), as a mucosal immunopotentiator, significantly enhanced EV-A71 vaccine-induced mucosal (IgA) and systemic (IgG) antibody responses, increased the secretion of IFN-γ and IL-17, and stimulated Th1/Th17-type cellular immunity, thereby providing protection against lethal viral infections.

Astragalus polysaccharide (ASP), as an adjuvant for inactivated SARS-CoV-2 vaccine and recombinant SARS-CoV-2 vaccine, possesses bi-directional immunomodulatory functions.

Evidence strength: Primarily preclinical and early-phase; no approved polysaccharide vaccine adjuvant for these specific purposes has yet been cleared in major Western regulatory markets as of current sources.

5. Body Systems and Health Areas of Association

• Cardiovascular system: LDL and total cholesterol reduction; risk factor modification for coronary heart disease (β-glucan from oats and barley; robust human evidence)
• Metabolic/endocrine system: Postprandial blood glucose attenuation; potential relevance in type 2 diabetes management (oat β-glucan; moderate-to-strong human evidence)
• Immune system: Macrophage activation, NK cell stimulation, cytokine modulation, dendritic cell activation; adjuvant activity (various β-glucans, Astragalus, Ganoderma polysaccharides; preclinical and some clinical evidence)
• Gastrointestinal system: Prebiotic support of gut microbiota, SCFA production, intestinal barrier integrity; management of IBS and IBD (inulin, FOS, resistant starch, herbal polysaccharides; moderate evidence)
• Hepatic system: Hepatoprotective effects against DILI, NAFLD, liver fibrosis (preclinical predominant)
• Oncology: Immune-adjuvant support during cancer therapy; direct apoptotic and antimetastatic actions in preclinical models (β-glucans, APS, fungal polysaccharides; mostly preclinical or early clinical)
• Antioxidant defense: Free radical scavenging across multiple systems (broad; mostly in vitro and animal studies)

Polysaccharides and triterpenoids demonstrate promising clinical application prospects in metabolic diseases, inflammatory conditions, neurodegenerative disorders, and cancer immunotherapy, attributed to their multi-target immunomodulatory activities and prebiotic properties.

6. Common Dosage Forms and Reported Dosages

Application of bioactive polysaccharides as pharmaceutical excipients in orally administered drug delivery systems has been explored to enhance the solubility and bioavailability of drugs, to increase the final product (drug) stability, and to attain release profile from final formulations.

Polysaccharides are commercially available and administered in the following forms:

• Oral powders and capsules: The most common supplemental form for isolated polysaccharides (β-glucan concentrates, Ganoderma extract, Astragalus extract)
• Functional foods and beverages: Cereal (1,3)(1,4)-β-d-glucans are cell wall polysaccharides observed in selected plants of grasses, and oats and barley are their good natural sources. Thanks to their physicochemical properties, β-d-glucans have therapeutic and nutritional potential and a specific place for their functional characteristics in diverse food formulations.
• Injectable preparations: Lentinan (a β-glucan from Lentinus edodes) and PSK (protein-bound polysaccharide from Trametes versicolor) are administered intravenously or intramuscularly in clinical settings in Japan for cancer immune-adjuvant use.
• Fast-dissolving oral films: Fast-dissolving films (FDFs) can be prepared from natural polysaccharides, such as pullulan, for oral dosage delivery.

Specific Dosages Reported in Clinical Studies

• Oat/barley β-glucan for cholesterol reduction: A 3 g/day dose of oat or barley β-glucan was sufficient to decrease total cholesterol in a dose-response model.
• β-glucan for postprandial glycaemic response: An EFSA Panel concluded that 4 g of either oat β-glucan or barley β-glucan per 30 g of available carbohydrates is required to obtain a consistent reduction in postprandial glycaemic response.
• Animal study reference (not human dose): In a rat model, a sulphated polysaccharide from Undaria pinnatifida (SPUP) at 300 mg/kg by oral route for 20 weeks significantly inhibited tumor growth. This is a preclinical dosage only and does not translate directly to human supplementation.

Nutraceuticals generally show limited aqueous solubility and bioavailability that can be enhanced using nanotechnology via nano-scale formulation and encapsulation of bioactive compounds that can help in release or delivery of nano-sized nutraceuticals to the desired place.

7. Safety Considerations and Interactions

General Safety Profile

Previous studies have already shown that polysaccharides found in plants are not likely to be toxic. The number of in vitro and in vivo studies proved their non- or low toxicity, immunoregulatory capability, and few side effects compared to synthetic drugs.

Polysaccharides are currently considered promising alternatives to traditional drugs because of their extensive activity and low toxicity. Studies have shown that the degradation of natural polysaccharides does not lead to the accumulation or retention of decaying substances in the body.

Standardization and Reproducibility Concerns

Studies on the structure-activity relationships of polysaccharides are limited due to their low purity and high heterogeneity. Incomplete reporting of product provenance and batch consistency, molecular weight and side-chain profiles, endotoxin and impurity limits further undermines reproducibility and external validity.

This heterogeneity has direct safety implications: a polysaccharide from one manufacturer or extraction process may differ substantially in composition and bioactivity from another ostensibly identical product.

Immunostimulatory Concerns

The diverse range of conditions for which β-glucans are in clinical testing underlines the incomplete understanding of the diverse mechanisms of action of β-glucans, a key knowledge gap. Because polysaccharides can significantly upregulate immune responses, there is a theoretical concern regarding their use in individuals with autoimmune conditions or those receiving immunosuppressive therapy, though direct human evidence on this specific interaction is limited in the reviewed sources.

Lipid-Lowering Study Limitations

The lipid-lowering studies of polysaccharides are mainly based on animal models and human diet experiments, and lack long-term efficacy and toxicity observation. It is necessary to carry out safety and toxicology studies.

Translation from Preclinical to Clinical Contexts

The antitumor, anti-obesity, and immunomodulatory effects demonstrated in in vitro studies are considered preliminary. All in vitro fermentation data must undergo sequential validation in animal models, pharmacokinetic studies, and stratified human trials before translating to clinical outcomes.

Dose-Response Complexity

The metabolic benefits of fermented polysaccharides via microbiota reshaping do not follow a linear dose-response relationship. This non-linearity complicates the determination of safe, effective supplemental doses for any given individual.

Need for Ongoing Research

Despite promising applications in treating metabolic, inflammatory, and neurodegenerative diseases, further research is needed to fully elucidate the molecular mechanisms and potential of polysaccharides in precision medicine. Future human intervention and clinical trials involving polysaccharides should be conducted with adequate sample size estimation and appropriately designed controls, while also balancing achievable human dosages and dietary feasibility.

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