Exploring the dual role of a natural compound in immune enhancement and metabolic regulation
In the relentless battle against COVID-19, scientists have uncovered an unexpected warrior—a natural compound that not only boosts immunity but also balances metabolism. While vaccines target the virus directly, β-glucan, a humble polysaccharide found in yeast, mushrooms, and oats, works behind the scenes to prepare our bodies for the complex challenges of SARS-CoV-2 infection.
Recent research reveals that its benefits extend far beyond immune enhancement, reaching into the realm of metabolic regulation that may be crucial in determining COVID-19 outcomes. This article explores the science behind β-glucan's dual protective effects and how this natural compound could become a valuable ally in pandemic defense.
β-glucans are found in many common foods including oats, barley, mushrooms, and yeast, making them easily accessible for dietary supplementation.
β-glucans are natural polysaccharides consisting of glucose molecules linked together by specific bonds (β-(1,3) and β-(1,6) glycosidic linkages). These compounds are abundant in the cell walls of yeasts, mushrooms, bacteria, and cereals like oats and barley [8].
What makes β-glucans medically interesting is their classification as biological response modifiers—substances that can enhance the body's defense mechanisms through non-specific immune stimulation.
Trained immunity (TRIM) represents a paradigm shift in immunology. Unlike traditional adaptive immunity that relies on antigen-specific memory, trained immunity involves enhanced innate immune responses after initial stimulation [6].
This phenomenon allows innate immune cells like monocytes and macrophages to respond more vigorously to subsequent challenges, even if they're unrelated to the initial trigger.
The COVID-19 pandemic has revealed striking connections between metabolic health and infection outcomes. Patients with diabetes, obesity, and dyslipidemia face significantly higher risks of severe COVID-19 and death [4].
High blood glucose levels create a proinflammatory state through constant recognition by C-type lectin receptors, which worsens disease severity in COVID-19.
Emerging evidence suggests that β-glucan may help address these metabolic risk factors. Clinical studies have shown that specific β-glucans can maintain fasting plasma glucose levels and bring high levels in diabetic patients back to normal ranges [4].
Additionally, certain β-glucans have demonstrated beneficial effects on lipid profiles, decreasing LDL levels while increasing lower HDL levels to reach normal ranges.
A 2025 randomized clinical trial published in Global Advances in Integrative Medicine Health provides compelling evidence for β-glucan's effects on COVID-19 [2]. The study involved 40 RT-PCR positive COVID-19 patients divided into two groups:
Researchers measured key inflammatory biomarkers—IL-6, CRP, ferritin, and D-dimer—at baseline, day 7, and day 15. These biomarkers were selected because they are established predictors of disease severity and respiratory failure in COVID-19 patients.
| Biomarker | Group | Baseline | Day 7 | Day 15 | Statistical Significance |
|---|---|---|---|---|---|
| IL-6 | Treatment | Not specified | Significant decrease | Not significant | P=0.03 at day 7 |
| Control | Not specified | No significant change | No significant change | - | |
| CRP (mg/L) | Treatment | Not specified | 5.53 ± 8.21 | 5.42 ± 10.41 | Not significant vs control |
| Control | Not specified | 4.91 ± 12.54 | 14.0 ± 37.16 | ||
| Ferritin (ng/mL) | Treatment | 560.58 ± 537.30 | Not specified | 127.51 ± 215.91 | Significant decrease |
| Control | Not specified | Not specified | Increased | P=0.98 | |
| D-dimer | Treatment | Not specified | Not specified | Decreased | Not significant vs control |
| Control | Not specified | Not specified | No significant change |
| Reagent/Resource | Function in Research | Example Applications |
|---|---|---|
| AFO-202 β-glucan | Specific variant derived from Aureobasidium pullulans | Clinical studies on metabolic parameters and immune function |
| N-163 β-glucan | Another strain of Aureobasidium pullulans-produced β-glucan | Used in combination with AFO-202 for enhanced effects |
| Dectin-1 antibodies | Block Dectin-1 receptor to study mechanism | Determining receptor specificity of β-glucan effects |
| Cytokine ELISA kits | Measure IL-6, TNF-α, IFN-γ levels | Quantifying inflammatory responses in COVID-19 |
| Flow cytometry antibodies | Identify immune cell populations and activation markers | Assessing CD86, CD40 expression on trained macrophages |
β-glucan exerts its immune effects through multiple receptor-mediated pathways. The primary receptor is Dectin-1, a C-type lectin receptor expressed on monocytes, macrophages, neutrophils, dendritic cells, and T lymphocytes [3].
This binding activates the inflammasome and various transcription factors, resulting in production of cytokines, chemokines, and reactive oxygen species. β-glucan also enhances NK cell cytotoxic activity by binding directly to the NKp30 activating receptor.
The metabolic benefits of β-glucan appear to be closely intertwined with its immune effects. Immuno-metabolic circuits are increasingly recognized as critical components of trained immunity [4].
β-glucan may help reverse metabolic dysfunction through insulin sensitization, potentially creating a more balanced immunological state that is beneficial in COVID-19. By normalizing blood glucose and lipid levels, β-glucan may help create an internal environment less conducive to the hyperinflammatory response.
Emerging evidence suggests that β-glucan may enhance vaccine responses. A 2025 study in mice demonstrated that β-glucan training administered a week before vaccination elicited higher antigen-specific antibody levels than in untrained mice [5].
The mechanism appears to involve enhanced antigen presentation by trained macrophages, increased co-stimulatory marker expression (CD86 and CD40), and improved CD4+ T cell proliferation. These findings position β-glucan as a potential vaccine adjuvant that could improve efficacy.
The potential applications of β-glucan in COVID-19 management are multifaceted. As a prophylactic agent, it could boost innate immune readiness against SARS-CoV-2 infection, potentially reducing infection severity.
As an adjunct to standard treatment, it may help modulate the excessive inflammatory response and address metabolic abnormalities that worsen outcomes. The oral bioavailability of β-glucan makes it particularly attractive as a widely accessible intervention [6].
While the evidence for β-glucan's benefits is promising, some research suggests potential complexities. A 2025 study found that systemic administration of β-glucan in mice reprogrammed alveolar macrophages in a way that exacerbated lung injury following bacterial or viral challenges [7].
This highlights the importance of route of administration, dosing, and timing in harnessing β-glucan's benefits while avoiding potential drawbacks.
| Research Area | Key Questions | Potential Impact |
|---|---|---|
| Optimal formulation | Which β-glucan sources and structures are most effective for immune/metabolic benefits? | Development of targeted formulations for specific conditions |
| Dosing and timing | When should β-glucan be administered relative to infection or vaccination? | Optimization of clinical protocols for preventive use |
| Population studies | Which patient populations benefit most from β-glucan supplementation? | Personalized medicine approaches to COVID-19 prevention |
| Long-term effects | What are the consequences of prolonged β-glucan use? | Safety data for chronic administration in metabolic disorders |
| Combination therapies | Can β-glucan enhance effects of other treatments or vaccines? | Development of synergistic therapeutic approaches |
The exploration of β-glucan as a protective agent against COVID-19 represents a fascinating convergence of immunology and metabolic medicine. Beyond its established role in trained immunity, β-glucan's ability to balance blood glucose and lipid levels addresses key risk factors for severe COVID-19 that have emerged throughout the pandemic.
While more research is needed to optimize its use and understand potential limitations, β-glucan represents a promising natural intervention that could be deployed widely against COVID-19 and potentially other viral infections. Its dual action on both immune and metabolic pathways makes it particularly well-suited to address the complex pathophysiology of SARS-CoV-2 infection.
As we continue to battle COVID-19 and prepare for future pandemics, harnessing the power of natural biological response modifiers like β-glucan—especially for vulnerable populations with metabolic conditions—may prove to be an important addition to our arsenal of preventive strategies.