Humic Substances

1. What This Class of Substances Is

Humic acid complexes are high-molecular-weight, heterogeneous compounds formed through the decomposition of organic matter. They comprise humic acid complexes, fulvic acids, hymatomelanic acids, and humins. These materials vary in composition, molecular weight, and functional groups depending on their origin (lignin and wood residues, soils, peat and moorland, lignite and leonardite, compost, water bodies and sediments, shilajit). Humic acid complexes contain phenolic structures, carboxyl groups, and aromatic rings, which confer redox-active, chelating, and surface-active properties. Fulvic acids are of lower molecular weight and more water-soluble than humic acid complexes, influencing their bioavailability. Shilajit consists largely of humic acid complexes but also contains minerals and low-molecular-weight organic compounds such as dibenzo-α-pyrones.

Measuring the effects of humic acid complexes in humans is challenging because they do not represent a uniform chemical entity. Standardised extraction and analytical methods are often lacking, complicating the comparability of studies. Furthermore, their mechanisms of action are diverse and partly non-specific, for example, through receptor binding, modulation of signalling pathways, or interactions with microorganisms. Topical applications are easier to control, whereas systemic effects are more difficult to assess. The heterogeneity of these materials necessitates precise characterisation of the preparations used to achieve reproducible results.

2. Which Materials Are Included

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

3. How Robust the Evidence Is

Controlled human studies exist primarily for humic acid complexes, vitamin D, creatine, magnesium, probiotics, and adaptogens. Humic acid complexes demonstrate the most extensive evidence base, with 28 controlled studies, particularly concerning chronic inflammation, topical wound healing, and hormonal effects. Vitamin D and creatine are also well-supported, with clear applications in bone health, muscle metabolism, and cognitive function. In contrast, substances such as quercetin, sulforaphane, or astaxanthin are primarily characterised by laboratory and animal studies, with only isolated or absent controlled human trials. The evidence base for gut microbiome interventions is growing but remains heterogeneous.

Humic acid complexes, fulvic acids, and shilajit share structural and functional similarities, such as chelation capacity, antioxidant properties, and interactions with microorganisms. These similarities suggest that effects observed for one substance may potentially be transferable to others. For example, anti-inflammatory or immunomodulatory effects of humic acid complexes could also be relevant for fulvic acids. However, direct comparative studies systematically investigating such transfers are lacking. Furthermore, these materials vary in bioavailability and potency, precluding any blanket extrapolation.

4. Key Human Studies

• 1 Clinical evaluation of purified Shilajit on testosterone levels in healthy volunteers (2015) — humic acid complexes
• 2 Effects of Rhythmic Embrocation Therapy With Solum Oil in Chronic Pain Patients (2008) — humic acid complexes
• 3 Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment (2011) — humic acid complexes
• 4 The Effect of Nutritional Support Based on the Dietary Anti-Inflammatory Index on Cancer-Related Fatigue in Lung Cancer Patients Undergoing Chemotherapy (2023) — Chronic inflammation
• 5 Mango Consumption Is Associated with Increased Insulin Sensitivity in Participants with Overweight/Obesity and Chronic Low-Grade Inflammation (2025) — Chronic inflammation
• 6 Efficacy of carbon dioxide laser combined with photodynamic therapy in the treatment of chronically infected wounds (2025) — Chronic inflammation
• 7 Effects of creatine supplementation on oxidative stress and inflammatory markers after repeated-sprint exercise in humans (2013) — Creatine
• 8 Efficacy and safety of creatine supplementation in childhood-onset systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, crossover study (2014) — Creatine
• 9 Creatine fails to augment the benefits from resistance training in patients with HIV infection: a randomised, double-blind, placebo-controlled study (2009) — Creatine
• 10 Vitamin D supplementation improves cognitive function through reducing oxidative stress regulated by telomere length in older adults with mild cognitive impairment (2020) — Vitamin D
• 11 Chromatin and transcriptional dynamics underlying the immune-modulatory effects of vitamin D₃ in vivo (2025) — Vitamin D
• 12 Effect of single high-dose vitamin D administration in critically ill vitamin D-deficient paediatric patients: a randomised trial (2025) — Vitamin D
• 13 Effect of a multistrain probiotic on leaky gut in patients with diarrhoea-predominant irritable bowel syndrome: a pilot study (2023) — Gut microbiome
• 14 Impact of daily avocado consumption on gut microbiota in adults with abdominal obesity: an ancillary study of HAT, a randomised controlled trial (2025) — Gut microbiome
• 15 Gut microbiota modulation via repeated donor faecal transplantation improves motor and gastrointestinal symptoms in drug-naïve Parkinson’s disease: a randomised controlled trial (2026) — Gut microbiome
• 16 Systematic review and meta-analysis: sodium picosulfate/magnesium citrate vs. polyethylene glycol for colonoscopy preparation (2016) — Magnesium
• 17 Efficacy and acceptability of sodium picosulfate/magnesium citrate vs. low-volume polyethylene glycol plus ascorbic acid for colon cleansing: a randomised controlled trial (2013) — Magnesium
• 18 A randomised, double-blind, placebo-controlled, repeated-dose pilot study of the safety, tolerability, and preliminary effects of a cannabidiol (CBD)- and magnesium-based supplement (2023) — Magnesium
• 19 Efficacy of standardised extract of <i>Bacopa monnieri</i> (Bacognize®) on cognitive functions of medical students: a six-week, randomised placebo-controlled trial (2016) — Adaptogens
• 20 Effects of acute ashwagandha ingestion on cognitive function (2022) — Adaptogens
• 21 Acute and repeated ashwagandha supplementation improves markers of cognitive function and mood (2024) — Adaptogens
• 22 Randomised clinical trial examining the impact of <i>Lactobacillus rhamnosus</i> GG probiotic supplementation on cognitive functioning in middle-aged adults (2020) — Probiotics
• 23 The effect of probiotic supplementation on episiotomy wound healing among primiparous women: a triple-blind randomised clinical trial (2023) — Probiotics
• 24 Examining the cognitive benefits of probiotic supplementation in physically active older adults: a randomised clinical trial (2022) — Probiotics

5. Open Questions

• Standardisation: Which extraction and analysis methods enable reproducible results for humic acid complexes in human studies?
• Systemic effects: Can the topically observed effects of humic acid complexes (e.g., wound healing) also be demonstrated with oral or parenteral administration?
• Long-term effects: Are there robust data on the safety and efficacy of humic acid complexes with long-term use?
• Combination therapies: Can humic acid complexes act synergistically with other substances (e.g., probiotics, vitamin D), particularly in chronic inflammation?
• Target groups: Which patient groups (e.g., those with autoimmune diseases, metabolic syndrome) benefit most from humic acid complexes?
• Mechanistic clarification: Which signalling pathways are specifically modulated by humic acid complexes, and how do these differ from other antioxidants?
• Dose-response relationship: Is there an optimal dosage for humic acid complexes, and how does this vary depending on the mode of application?

See also the gap list for all substances. This page is recalculated with each harvest.