Immunomodulation

1. What This Mechanism of Action Entails

Immunomodulation refers to the targeted influence on the immune system by exogenous or endogenous substances. This encompasses the regulation of immune cells (e.g., T cells, macrophages) and signalling molecules (cytokines, chemokines) that control inflammatory processes. The aim is often to dampen excessive reactions (e.g., in autoimmune diseases) or to strengthen defence mechanisms (e.g., in infections). The mechanism is complex, as the immune system consists of numerous interconnected components. Substances may bind directly to receptors, modulate signalling pathways, or act indirectly via the microbiome. These interactions are dynamic and context-dependent, varying with health status, age, or genetic predisposition.

Measurability in humans poses challenges, as immune responses vary individually and are influenced by many factors. Laboratory findings (e.g., cell cultures) often demonstrate clear effects but cannot be directly extrapolated to humans. Animal studies provide insights but are limited by species-specific differences. Controlled human trials are the gold standard but require large sample sizes and long observation periods to detect clinically relevant effects. Biomarkers such as cytokine levels or immune cell activity are useful but not always correlated with clinical outcomes. Additionally, placebo effects and confounders (e.g., diet, stress) are difficult to control.

2. Substances Associated with This Mechanism

All substances in the database for which this mechanism of action is described—ranked by the extent of human testing. The numbers represent studies per type of investigation.

3. How Robust This Evidence Is

Substances such as vitamin D, omega-3 fatty acids, probiotics, and zinc are well supported by a large number of controlled human studies. Chronic inflammation and the gut microbiome show the strongest evidence in this regard. Other substances, such as turmeric, beta-glucans, or adaptogens, also have controlled studies, though in smaller numbers. Humic acid complexes, berberine, or mineral binders, by contrast, are primarily characterised by laboratory findings and animal studies. Here, meaningful human data are still lacking to derive clinical relevance.

Many of the substances studied act through similar mechanisms, such as the modulation of cytokines or the influence on the microbiome. This suggests that findings from well-researched substances (e.g., omega-3 fatty acids) could potentially be extrapolated to less studied ones. However, such extrapolation is not automatic, as substances exhibit different target structures and potencies. For example, humic acid complexes show immunomodulatory effects in the laboratory, but whether these are similarly pronounced in the human organism remains unclear. The combination of substances (e.g., probiotics with vitamin D) may also have synergistic effects, but this is still insufficiently investigated.

4. Key Human Studies

• 1 Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Ra (2020) — Chronic inflammation
• 2 Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for the <i>COVID-Omega-F</i> Trial (2020) — Chronic inflammation
• 3 REmoval of cytokines during CArdiac surgery (RECCAS): a randomised controlled trial (2024) — Chronic inflammation
• 4 Supplementation with short-chain fatty acids and a prebiotic improves clinical outcome in Parkinson's disease: a randomized double-blind prospective s (2025) — Gut microbiome
• 5 Fecal microbiota transplantation plus immune checkpoint inhibitor rechallenges in patients with advanced non-small cell lung cancer: a single-arm expl (2025) — Gut microbiome
• 6 Multistrain Probiotics Plus Vitamin D Improve Gut Barrier Function and Gut Microbiota Composition in Irritable Bowel Syndrome Without Constipation: Re (2025) — Gut microbiome
• 7 Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBM (2020) — Vitamin D
• 8 Vitamin D Supplementation in COVID-19 Patients: A Clinical Case Series (2020) — Vitamin D
• 9 Ergocalciferol in New-onset Type 1 Diabetes: A Randomized Controlled Trial (2022) — Vitamin D
• 10 A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer (2019) — Probiotics
• 11 The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: a systematic review and meta-analysis of rando (2018) — Probiotics
• 12 Role of Probiotics in Non-alcoholic Fatty Liver Disease: Does Gut Microbiota Matter? (2019) — Probiotics
• 13 Effects of Curcuminoids on Systemic Inflammation and Quality of Life in Patients with Colorectal Cancer Undergoing Chemotherapy: A Randomised Controlled Trial (2021) — Turmeric and Curcumin
• 14 A Phase 2 Study to Assess the Immunomodulatory Capacity of a Lecithin-Based Delivery System of Curcumin in Endometrial Cancer (2018) — Turmeric and Curcumin
• 15 Comparison of Oral Nano-Curcumin with Oral Prednisolone in Oral Lichen Planus: A Randomised Double-Blind Clinical Trial (2020) — Turmeric and Curcumin
• 16 Mushrooms and Immunity (2021) — Beta-Glucans
• 17 Randomised Phase III Study of S-1 Alone Versus S-1 Plus Lentinan for Unresectable or Recurrent Gastric Cancer (JFMC36-0701) (2016) — Beta-Glucans
• 18 Beneficial Effects of Novel Aureobasidium pullulans Strains Producing Beta-1,3-1,6 Glucans on Interleukin-6 and D-Dimer Levels in COVID-19 Patients: A Retrospective Study (2022) — Beta-Glucans
• 19 Effect of Zinc Supplementation on Serum Zinc Concentration and T Cell Proliferation in Nursing Home Elderly: A Randomised, Double-Blind, Placebo-Controlled Trial (2016) — Zinc
• 20 Low Zinc Levels at Admission Associate with Poor Clinical Outcomes in SARS-CoV-2 Infection (2021) — Zinc
• 21 Zinc Lozenges as a Cure for the Common Cold—A Review and Hypothesis (2010) — Zinc
• 22 Safety and Clinical Effectiveness of Withania somnifera (Linn.) Dunal Root in Human Ailments (2020) — Adaptogens
• 23 Double-Blind Randomised Controlled Trial for Immunomodulatory Effects of Tulsi (Ocimum sanctum Linn.) Leaf Extract on Healthy Volunteers (2011) — Adaptogens
• 24 Adjunctive Use of a Standardised Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomised, Double-Blind, Placebo-Controlled Trial (2018) — Adaptogens

5. Open Questions

• Humic Acid Complexes: Which specific immune cells or signalling pathways are affected in humans?
• Combination Therapies: Are there synergistic effects when combining substances (e.g., probiotics + vitamin D)?
• Long-Term Effects: How do immunomodulatory substances act over months or years?
• Individual Variability: Which factors (genetics, microbiome) determine the response to immune modulation?
• Clinical Endpoints: Do biomarkers (e.g., cytokines) correlate with patient-relevant outcomes?
• Dosage: Are there optimal dose–response relationships for substances such as humic acid complexes?

See also the gap list across all substances. This page is recalculated with each update.