About Humic & Fulvic Substances


Humic is not Toxic:
Humic substances are ubiquitous in soils and waters. These complex superstructures are derived from the decomposition of dead plant and animal matter and are vital to soil health. Their heterogenous composition is specific to their site of origin and is comprised of weakly bound aggregates of small organic compounds that can sequester minerals and make them available to plants. As such, they may possess potential nutritional value for humans, and extractions of fulvic and humic acids can be produced that could be suitable for such purposes. For this reason, we evaluated the toxicological profile of a specific preparation (blk. 333) of fulvic and humic acids derived from a lignite deposit in Alberta, Canada and found it to lack genotoxic potential in a bacterial reverse mutation test, in vitro mammalian chromosomal aberration test, and in vivo mammalian micronucleus test. No general or organ toxicity was observed in Wistar rats following 90 days of continuous exposure, and a no observed adverse effect level (NOEAL) was determined at 2000 mg/kg bw/day, the highest tested dose. Our results suggest the feasibility of further evaluation for development of the preparation as a nutritional supplement infood.

The Effect of Humic Acid Substances (HAS) on the Thyroid Function and Structure in Lead Poisoning.
Results suggest that HAS may bind to heavy metals and play a role in the recovery of thyroid gland structure and function.

Effect of humic acids on thyroidal function.

In the presence of humic acids, erythrocytes carry a higher percentage of oxygen to tissues.

Humic Acid Enhances Wound Healing in the Rat Palate.

Overall, the results of this study showed that humic acid, which has previously been shown to
have antibacterial and anti-inflammatory properties, enhances wound healing in the oral cavity.
The humic acid treatment was even superior to chlorhexidine gluconate, which is widely used
for the treatment of oral wounds. To the best of our knowledge, this is the first study to show
that humic acid treatment can be used for the treatment of wounds in the oral cavity.

The Effect of Humic Acid Substances on the Thyroid Function and Structure in Lead Poisoning.
Lead (Pb) is a heavy metal, which adversely affects thyroid gland function and structure. Due to its high molecular weight and abundant functional groups, humic acid substances (HAS) can form chelates with heavy metals. The experiment was conducted to evaluate the prophylactic effect of HAS on thyroid hormone levels and histopathological lesions of laying hens exposed to lead (Pb) poisoning. After a week of adaptation, 192 Lohmann White laying hens (25 weeks of age) were fed one of four diets: a basal diet (BD) or the BD with HAS (0.15%), with Pb (0.3 g/kg), or with both. Experimental groups were replicated in 12 cages, with four hens each. Pb poisoning did not alter triiodothyronine (FT3; 3.22 ± 0.20 ng/dL) or thyroxine (FT4; 0.71 ± 0.08 ng/dL) concentrations, but caused a 167% increase in thyroid stimulating hormone (TSH) concentration. HAS supplementation returned the high TSH levels of hens exposed to Pb poisoning to normal values. Degenerative changes in the epithelial cells of the thyroid gland of the hens exposed to Pb poisoning were evidenced. Connective tissue cells in the interfollicular area and total amount of colloids with partially atrophic follicles were observed. These histopathological findings were less severe when HAS was added to the diet. In conclusion, HAS alleviates the effects of Pb poisoning on thyroid gland function and structure, possibly preventing its internalization by the tissue by forming chelates and exerting anti-inflammatory effects.

An in vitro investigation of the anti-inflammatory properties of potassium humate.
In this study the anti-inflammatory potential of potassium humate, derived from bituminous coal, has been investigated in vitro. Exposure of resting and phorbol-12-myristate-13-acetate (PMA) stimulated human neutrophils to potassium humate resulted in a decreased expression of CR3 by activated, but not resting cells, in a dose-related way. Humate also inhibited the adhesion of PMA-stimulated neutrophils to a baby hamster kidney cell line expressing ICAM1 (the CR3 ligand) (BHK331-7). Similar results were obtained using normal BHK cells indicating that this inhibition does not only target specific adhesion molecules on the neutrophil and eosinophil membrane by activated phagocytes, but also affects other mechanisms involved in cell adhesion. Opsonised Sephadex or FMLP/Cyto B-induced degranulation of neutrophils and eosinophils were also decreased by humate treatment. Inhibition of the adhesion of activated phagocytes, as well as inhibition of the release of granule polypeptides, both of which are responsible for tissue damage during inflammatory processes, are attractive targets for anti-inflammatory drugs. Because humate is well tolerated with an excellent safety profile it merits further evaluation in patients suffering from inflammatory conditions.

Impact of humic acids on the colonic microbiome in healthy volunteers.
Humic acids have a profound effect on healthy colonic microbiome and may be potentially interesting substances for the development of drugs that control the innate colonic microbiome.


Peat: A Natural Source for Dermatocosmetics and Dermatotherapeutics.
In recent years the interest for natural substances in dermatotherapy and cosmetics has increased. Peat is a complex natural source of humic substances that are of potential interest in both dermatology and cosmetology. Humic substancesin peat have been partially characterized and pharmacologic and biologic activities have been documented. Possible clinical applications are outlined.

Review of Humic Acid May 2016.

Download the podcast here.

Effects of Humic Acid on Animals and Humans: An Overview of Literature and a Review of Current Research.

Sodium humate accelerates cutaneous wound healing by activating TGF-β/Smads signaling pathway in rats.
Sodium humate (HA-Na) has been topically used as a wound healing and anti-inflammatory agent in folk medicine. In the present study, HA-Na was investigated for cutaneous wound healing in Sprague-Dawley rats. HA-Na solution (1.0%, w/v) was topically administered to rats undergoing excision wound models. Healing was assessed with a recombinant bovine basic fibroblast growth factor for external use as positive control. Wound healing rates were calculated on Day 3, 6, 9, 14 and 21 after injury, and tissues were also harvested after the same intervals for histological analysis. In addition, tissue hydroxyproline levels were measured. Furthermore, mRNA levels and protein expressions of transforming growth factor-β1, 2, 3 (TGF-β1, 2, 3) were determined by RT-PCR and western blot. Protein expression levels of Smad-2, -3, -4 and -7 were also detected by western blot. Our study demonstrates that HA-Na has the capacity to promote wound healing in rats via accelerated wound contraction and increased hydroxyproline content. More importantly, these wound healing effects of HA-Na might be mediated through the TGF-β/Smad signaling pathway. HA-Na may be an effective agent for enhanced wound healing.

Toxicology of Humic Substances:

Humic substances are ubiquitous in soils and waters. These complex superstructures are derived from the decomposition of dead plant and animal matter and are vital to soil health. Their heterogenous composition is specific to their site of origin and is comprised of weakly bound aggregates of small organic compounds that can sequester minerals and make them available to plants. As such, they may possess potential nutritional value for humans, and
extractions of fulvic and humic acids can be produced that could be suitable for such purposes. For this reason, we evaluated the toxicological profile of a specific preparation (blk. 333) of fulvic and humic acids derived from a lignite deposit in Alberta, Canada and found it to lack genotoxic potential in a bacterial reverse mutation test, in vitro mammalian chromosomal aberration test, and in vivo mammalian micronucleus test. No general or organ toxicity was observed in Wistar rats following 90 days of continuous exposure, and a no observed adverse effect level (NOEAL) was determined at 2000 mg/kg bw/day, the highest tested dose. Our results suggest the feasibility of further evaluation for development of the preparation as a nutritional supplement in food.


The Anti-inflammatory Properties of Humic Substances: A Mini Review.

Humic substances are effective in the suppression of delayed type hypersensitivity, rat paw oedema, a graft-versus-host reaction and contact hypersensitivity in rats. They reduce the C-reactive protein levels of patients suffering from osteoarthritis of the knee and the wheel and flare reaction of patients suffering from hay fever. They have also been described as cardioprotective and pro-angiogenic. Toxicity studies have indicated that potassium humate is safe in humans up to a daily dosage of 1 g/kg, whereas fulvic acid is safe in humans up to a daily dosage of 1.8 g per adult. The anti-inflammatory action of potassium humate can be contributed to the inhibition of the release of inflammatory-related cytokines, an adhesion molecule, oxidants and components of the complement system.

Humic Acids as Therapeutic Compounds in Lead Intoxication.

This review is therefore a description of the mechanism of lead toxicity as well as of possible interventions for the detoxification of the body. Part of the clinical intervention is the provision of chelates that form insoluble complexes with lead and eliminate the load in tissues. Most of these chelating agents have a number of side effects. It is therefore not surprising that active compounds with distinctive antioxidant and chelating properties are being sought after. Conclusion: The possibility of administering lower amounts, and the corresponding decrease in side effects, would be important for clinical practice. Both prospective studies and our initial studies on humic acids have highlighted positive effects based on their antioxidant and chelating properties.

Effects of Humic Acids in Chronic Lead Poisoning.

Chronic exposure to lead causes disruption to energy production mechanisms and tissue damage, in particular through its binding to thiol groups and competition for zinc binding sites. We investigated the possibility of preventing the consequences of chronic lead poisoning by administration of three different doses of humic acids (HAs) into feed with the aim of establishing an effective HA dose. During the 10-week experiment, a sub-lethal dose of lead acetate was given to rats during the first 5 weeks, with continuous administration of HA over 10 weeks. Measurements were taken to determine the content of the metals Pb, Mn, Cu, Fe and Zn; the metalloid Se; and selected antioxidant markers in the heart, liver, kidney and plasma after the first, fifth and tenth weeks of experiment. The administration of lead and HAs clearly affects the redistribution of the elements and the activity of the antioxidant enzymes. This fact was particularly highlighted in the lead-only group as, within the experiment, significantly higher Pb concentrations were found only in the plasma of this group. However, in the group with 1% HA administered with lead, we observed a rise in Zn concentrations in the organs and the deposition of Fe into the liver. Decreased glutathione reductase activity in the plasma and balanced reduced glutathione concentrations indicated sufficient efficiency of redox reactions. SOD activities were among those affected most strongly, with only the 1% HA group showing no effect on heavy metal redistribution as a result of HA administration.


Effect of humic acids on lead poisoning in bones and on a subcellular level in mitochondria.

Humic acids (HA) are natural substances which exhibit a remarkable spectrum of health benefits, such as their role in chelation. This study aims to supplement the current knowledge on the chelating effects of HA in chronic lead intoxication in rat femurs and in liver, heart and kidney mitochondria in an experiment lasting 10weeks. Lead acetate trihydrate was administered to rats for 5weeks at a daily dose of 155.5mg/kg body weight. At the same time, rats were given three concentrations of HA, with their effect measured over the following 5weeks. Increased Pb concentrations were detected in the femur after the first week, while HA-administered groups showed a tendency towards inhibiting the increase in Pb deposition. After 5weeks, Pb concentrations dropped significantly in the HA groups. At the same time, however, other elements were redistributed, with a decrease in Se and Zn being particularly noteworthy. While an increase in Pb concentrations was found after 5weeks of Pb administration, a concentration of 1% HA resulted in the least significant increase in Pb as well as an increase/decrease in Se/Cu, respectively. In mitochondria, an increase in Pb content was detected after the first and fifth weekswith concomitant redistribution of other elements. At the end of the experiment, again in the 1% HA group, Pb concentrations remained higher only in the liver with the other elements sufficiently normalized, indicating this concentration to be useful in the treatment of Pb intoxication.

Zinc and lead detoxifying abilities of humic substances.

The effect of humic substances (HS) and their different fractions (humic acids (HA) and hymatomelanic acids (HMA)) on the toxicity of zinc and lead to different strains of bacteria was studied. All tested bacteria demonstrated a lower resistance to zinc than lead showing minimum inhibitory concentrations of 0.1 -0.3 mM and 0.3-0.5 mM, respectively. The highest resistance to lead was characteristic of Pseudomonas chlororaphis PCL1391 and Rhodococcus RS67, while Pseudomonas chlororaphis PCL1391 showed the greatest resistance to zinc. The combined fractions of HS and HA alone reduced zinc toxicity at all added concentrations of the organic substances (50 –200 mg L-1) to all microorganisms, while hymatomelanic acids reduced zinc toxicity to Pseudomonas chlororaphis PCL1391 at 200 mg L-1 organic concentration only. The HS fractions imparted similar effects on lead toxicity also. This study demonstrated that heavy metal toxicity to bacteria could be reduced through complexation with HS and their fractions. This was particularly true when the metal-organic complexes held a high stability, and low solubility and bioavailability.Numerous studies have shown that humic substances (HS) are capable of altering both the chemicaland physical speciation of trace elements and affecting their bioavailability and toxicity (Tipping, 2004; Tang et al., 2014; Zhou et al., 2005; Kostić et al., 2013; Boguta and Sokołowska, 2016). The structural complexity of HS creates opportunities for abroad range of chemical interactions with heavy metals and other pollutants. The mechanisms of these interactions include ion exchange, complexation, redox transformations, hydrophobic bonding, coagulation, peptization, etc. (Boguta and Sokołowska, 2016).

Impact of humic acids on the colonic microbiome in healthy volunteers.

Study Conclusion: Humic acids exert profound effects on the colonic microbiota and may be an interesting group of substances for the development of specific drugs, which deliberately influence colonic fermentation in an inflamed colon, obesity, rheumatic and neurologic disorders

Effect of humic acid on oxidative stress and neuroprotection in hypoxic-ischemic (HIE) brain injury: Part 1

This is the first study which investigates the role of HA in HIE model. HA reduces apoptosis and neuronal injury in cerebral tissue of the rats. Thefindings suggest that HA may be a viable protective agent against HIE.


Humic acid enhances the cytotoxic effects of arsenic trioxide on human cervical cancer cells.

Cervical cancer is the second leading cancer affecting women, and recent studies have demonstrated arsenic trioxide (As2O3) has therapeutic effects on cervical cancer by promoting apoptosis and inhibiting metastasisin vitroandin vivo. Humic acid (HA) possesses various pharmacologic properties, including anti-inflammatory, anti-neoplastic, and anti-proliferative effects by inducing apoptosis. We examined the growth inhibition properties and the combined effects of HA and As2O3in human cervical adenocarcinoma celllines. Our results shown both As2O3and HA-induced inhibition of cell growth, most likely by ROS-mediated cell damage and activation of the apoptosis pathway, and HA enhanced the anti-proliferative action of As2O3in HeLa and SiHa cells, which reduced theLC50about 57.62 or 73.52% (300μg HA/mL) to 83.67 or 79.03% (500μg HA/mL), respectively. This study is relevant to the development of chemotherapeutic approaches using As2O3in treating human cervical cancer.

Antitumor effect of humus extract on murine transplantable L1210 leukemia.

Humic substances are formed during the decomposition of organic matter in humus that found in many natural environments in which organic materials and microorganisms have been present. In the present study, humus extract exhibited antitumor effect on L1210 tumor development in isogeneic DBA/2 mice with the delay of tumor formation and a significant smaller tumor mass that infer a significant increase of life span of mice. The antitumor effect was not due to direct killing of L1210 or induction of apoptosis in tumor cells by humus extract.

General Info on Humic Acid

Recently, an increase has been observed in the interest to the application of humic acids (HA) in medicine. These are the examples of HA effect on some vitally important properties of human organism [1]:

Antioxidant properties. A humic complex manifests an explicit ability to support chemical balance in organism. Depending on the situation, humic acid can behave itself either as donor or electron acceptor. This makes humic acid a powerful, natural antioxidant, the trap of free radicals that damage protein structures and DNA molecules of cells, break their genetic code, and, in particular, promote the development of oncological diseases.

Antiviral activity. Humic acids exhibit a high antiviral activity. A humic acid molecule covers a virus as a “coat” to block its escape into the bulk and prevents its reproduction. In this case, humic acid sends a signal to immune system about the appearance of an invader. This pushes the immune system to fight the virus which is in a vulnerable position (bound to a humic acid molecule). As a result, the number of viruses decreases, and the immune system successfully fights the disease.

Detoxicant and hepatoprotector. Humic acids are a powerful means of complexing. They bind and remove heavy metals (lead, copper, mercury, cadmium, cobalt, zinc, etc.) from the body. At a certain concentration, these cause severe poisoning and cell mutations. Heavy metals are not removedindependently without special therapeutic measures. Humic acids participate actively in liver metabolism and act as a filter for heavy metals. They capture and immobilize toxic substances, preventing them from taking part in chemical reactions. Thereafter, toxin is readily removed from the body.


Effect of fulvic and humic acids on performance, immune response and thyroid function in rats.
Humic acid and FA supplementation resulted in strong humoral immune stimulation. Our data also indicate that FA content is responsible for the mild hypothyroid effect of humic substances.


Carbohydrate-derived fulvic acid is a highly promising topical agent to enhance healing of wounds infected with drug-resistant pathogens.
CHD-FA showed strong activity against a variety of bacterial and fungal pathogens with minimum inhibitory concentration values equal or less than 0.5%. Compared with infected but untreated wounds, improved wound healing upon CHD-FA treatment was observed in both infection models, demonstrated by wound surface area measurement, histopathologic examination, and expression profiling of wound healing genes. Up-regulation of proinflammatory cytokine interleukin 6 (IL-6) at Day 3 after infection was significantlydampened at Days 6 and 10 in the CHD-FA-treated wounds in both infection models, displaying an improved and accelerated wound healing.

Topical application of oxifulvic acid suppresses the cutaneous immune response in mice.
The anti-inflammatory activity of topically applied coal-derived fulvic acids (called oxifulvicacid) at 4.5% and 9% was compared with that of diclofene sodium at 1% and betamethasone at 0.1% in a murine model of contact hypersensitivity. Mice were sensitized with dinitrofluorobenzene and challenged 6 days later by application to the dorsal surface of the right ear. The inflamed ears of the mice were then treated topically, and the thickness of the ears was measured daily. Oxifulvic acid at both concentrations compared favorably with both diclofene sodium and betamethasone in suppressing the cutaneous inflammatory response. Oxifulvic acid possesses anti-inflammatory properties and may be of clinical benefit in the treatment of inflammatory skin conditions in humans.

Nutraceutical Properties of Fulvic.
Fulvic acid (FA), a humic substance, has several nutraceutical properties, including anti-inflammation, antimicrobial, and immune regulation abilities. However, systematic safety assessment remains insufficient. In the present study, a battery of toxicological studies was conducted per internationally accepted standards to investigate the genotoxicity and repeated-dose oral toxicity of FA. Sprague-Dawley (SD) rats or ICR mice were used. Compared to the control group, there were no significant changes (allp> 0.05) in all FA treatment groups in the bacterial reverse mutation test,in vitromammalian chromosome aberration test,in vivosperm shape abnormality assay, andin vivomouse micronucleus assay. The acute toxicity test showed that no mortality or toxic effect was observed following oral administration of the maximum dose of 5,000 mg/kg BW/day to mice or rats. A 60-day sub-chronic study was conducted at 0 (control), 200, 1,000, and 5,000 mg/kg/day. Compared to the control group, there were no significant changes (allp> 0.05) in the body weights, feed consumption, clinical signs, hematology, clinical chemistry, organ weights, or histopathology examinations. In conclusion, the no-observed-adverse-effect-level (NOAEL) of FA supplementation from the 60-day study was determined to be 5,000 mg/kg body weight/day, the highest dose tested. Our findings suggest that the oral administration of FA may have higher safety.

Pilot study to evaluate the safety and therapeutic efficacy of topical oxifulvic acid in atopic volunteers.

The study objectives were to establish first the safety and second the therapeutic efficacy of topically applied oxifulvic acid compared to 1% hydrocortisone and placebo creams. Oxifulvic acid has established antiinflammatory properties in vitro. It also inhibits elicited ear inflammation in mice at concentrations of 4.5 and 9%. In this double-blind cross-over study, 23 healthy volunteers allergic to grass or house dust mite allergen were recruited and included after signing informed consent. During the initial run-in period all volunteers were randomized to apply either 4.5 or 9% oxifulvic acid for 2 weeks on the volare aspect of one forearm (100 mm diameter) and rechallenged 21 days later to establish sensitization. Thereafter, volunteers were randomized to either placebo. 1% hydrocortisone, 4.5 or 9% oxifulvic acid creams. Creams were applied under occlusions 1 h prior to intradermal allergen challenge and every 8 h thereafter for 3 days (21-day intervals). The surface areas of the immediate and late phase skin reactions were calculated. Liver and kidney function tests as well as full blood counts were done at screening and thereafter weekly for the first 2 weeks and then at each follow-up visit. Topically applied oxifulvic acid had no significant effect on any of the safety parameters and also did not induce sensitization when applied on the skin. Oxifulvic acid (4.5%) caused inhibition of the elicited inflammatory reaction at 15 min and differed significantly from the 9% cream at 24 h. These changes were similar to that caused by hydrocortisone. No other significant changes were detected. Drug Dev. Res. 57:40–43, 2002. © 2002 Wiley-Liss, Inc

Weight Loss & Fulvic:

The experiment was conducted to investigate the effects of dietary supplementation of fulvic acid on lipid metabolism of finishing pigs. One hundred eighty crossbred barrows (Landrace × Yorkshire, 60 ± 2.5 kg) were randomly allotted to 5 dietary treatments (36 pigs/treatment) and fed a basal diet supplemented with 0, 0.2%, 0.4%, 0.6%, and 0.8% fulvic acid for 42 d. Thirty pigs (6 pigs/treatment) were slaughtered at the end of the experiment. Blood samples and adipose tissue were collected for determination of blood parameters and lipid metabolic enzymes. The results showed that compared with the control group, dietary supplementation of 0.2%, 0.4%, and 0.6% fulvic acid significantly reduced mean backfat thickness of pigs (P < 0.05). The serum concentrations of low-density lipoprotein, leptin, growth hormone, insulin, and triiodothyronine were significantly increased by adding fulvic acid in diets (P < 0.05). With the raised concentration of dietary fulvic acid, hormone sensitive lipase (HSL) activity was significantly increased (P < 0.05), and lipoprotein lipase (LPL) activity was significantly decreased (P < 0.05) in adipose tissue. In conclusion, dietary supplementation of fulvic acid reduced the mean backfat thickness of pigs. This change related to the increased activity of HSL and the decreased activity of LPL in adipose tissue.

Investigating the biological properties of carbohydrate derived fulvic acid (CHD-FA) as a potential novel therapy for the management of oral biofilm infections.

Overall, CHD-FA was shown to possess broad-spectrum antibacterial activity, with a supplementary function of being able to down-regulate inflammation. These properties offer an attractive spectrum of function from a naturally derived compound, which could be used as an alternative topical treatment strategy for oral biofilm diseases. Further studiesin vitroandin vivoare required to determine the precise mechanism by which CHD-FA modulates the host immune response.

Carbohydrate-derived Fulvic acid (CHD-FA) inhibits Carrageenan-induced inflammation and enhances wound healing.

The objectives of this study were to evaluate the safety and anti-inflammatory and wound-healing characteristics of carbohydrate-derived fulvic acid (CHD-FA) in rats.

Randomized, parallel-group, double-blind, controlled study to evaluate the efficacy and safety of carbohydrate-derived fulvic acid in topical treatment of eczema.
The purpose ofthis study was to evaluate the efficacy and safety of carbohydrate derived fulvic acid (CHD-FA) inthe treatment of eczema in patients two years and older.CHD-FA was well tolerated, withno difference in reported side effects otherthan a short-lived burning sensation on application. CHD-FA significantly improved some aspects of eczema. Investigator assessment of global response to treatment withCHD-FA was significantly better than that with emollient therapy alone.The results ofthis small exploratory study suggestthat CHD-FA warrants further investigation in the treatment of eczema.

Fulvic Increased Collagen Levels:

In order to investigate the impact of fulvic acid (FA) on the hydroxylysyl glycosylation in collagen bio-synthesis, 40 NMRI mice were divided into two groups (n = 20 in each group, consisting 10 females and 10 males). The animal was maintained for two generations by different diets: control group with normal water and food and study group with water containing 30 mg/L FA and normal food. The second generation of the animal was slaughtered, and the biochemical parameters of collagen content and the degree of collagen hydroxylysyl glycosylation in skin, rib and tibia were detected by biochemical methods. The mean value of collagen in the study group was increased slightly, and no significant difference between study group and control group was found (P > 0.05), but the content of glucose-glactose-hydroxylysine (GGH) was significantly decreased in the study group in comparison with the control group (P<0.01). It was suggested that through the decrease of GGH 30 mg/L FA could inhibit the activity of galactosyl-hydroxylysylglucosyl-transferase and further disturb the post-translational modification of collagen intracellularly.

Fulvic is angiogenic - increases the growth of blood vessels:

Fulvic acid (FA) is a natural mineral medicine with a long medical history in folk. However, the active chemicals of FA remain unknown due to its diversity of sources and the complexity of compositions, which have become a bottleneck in quality control and medicinal development. Based on the traditional effect on angiogenesis, FAs from eight different coal sources were prepared and their active fractions were investigated by the CAM model, resulting that most of acetonitrile dissolved parts of these FAs (DFAs) produced angiogenesis effects. Through chemical analysis on DFAs by GC-FID/MS, six shared organic acids with low molecular weights were identifiedand quantified, which showed the promoting effects on capillary areas, VEGF, b-FGF, and Ang-1 at different degrees. The PCA analysis showed that the five shared organic acids with high recognition are the active chemicals in different sources of FAs whichmay be responsible for the angiogenesis effects

Characterization of Fulvic Acid Beverages by Mineral Profile and Antioxidant Capacity.
The main purpose of the study was to investigate the quality of fulvic acid-based food products. The concentrations of Ca, K, Mg, Na, Cu, Fe, Mn, and Zn, and antioxidant capacities of fulvic acid concentrates and ready-to drink beverages available on the global market were determined. The concentrations of minerals were determined using microwave plasma-atomic emission spectrometry. Antioxidant capacity was expressed as total polyphenol (TP) and flavonoid (TF) contents, the trolox equivalent antioxidant capacity (TEAC) and ferric reducing ability of plasma (FRAP) values. The daily portion of eight out of 14 products realized 45–135% of recommended daily allowance (RDA) for Fe. One of ready-to-drink beverages was also a good source of Mg (about 40% of RDA), and another one of Mn (about 70% of RDA). The concentrations of TP and TF in ready-to-drink beverages varied from 6.5 to 187 μg/mL, whereas in concentrates, from 5886 to 19,844 μg/mL. Dietary supplements or food products with fulvic acids may be a good source of antioxidant polyphenolic compounds and some minerals.

Therapeutic Potential of Fulvic Acid in Chronic Inflammatory Diseases and Diabetes.
Chronic inflammatory diseases like diabetes are on a rise in the Western world. Based on the tsunami of new cases every year, new therapeutic measures must be considered. A promising avenue might involve the attenuation of underlying inflammation through natural health products (NHPs). This is because most NHPs have a rich history in traditional medicine and might be considered safer under appropriate doses and conditions. However, the biggest impediment in NHP research isthat rarely do these products come with verified health benefits or dosing schedules established through modern scientific research. Fulvic acid (FvA), one such NHP, comes from humic substances produced by microorganisms in soil. Traditional medicine and modern research claim FvA can modulate the immune system, influence the oxidative state of cells, and improve gastrointestinal function; all of which are hallmarks of diabetes. This minireview outlines the available peer-reviewed research on FvA and examines its anecdotal health claims. We show that although available research has been minimal, there is substantial evidence to pursue FvA research in preventing chronic inflammatory diseases, including diabetes.

Candida Albicans: Carbohydrate derived fulvic acid: an in vitro investigation of a novel membrane active antiseptic agent against Candida albicans biofilms.

New strategic insights into managing fungal biofilms.

With a limited availability of antifungals within our arsenal, new therapeutic approaches able to address both host and pathogenic factors that promote fungal disease progression, i.e., chronic inflammation and biofilm formation, could represent an advantage in the clinical setting. In this paper we discuss the antifungal properties of myriocin, fulvic acid, and acetylcholine in light of their already known anti-inflammatory activity and as candidate dual action therapeutics to treat opportunistic fungal infections.

Humic and Fulvic Acids as Potentially Toxic Metal Reducing Agents in Water.

Industrial activity has contributed to potentially toxic metal pollution in various ecosystems throughout the world. During this study the ability of humic and fulvic acids (isolated from lignite with a simple, rapid and inexpensive method) to reduce toxic metals' concentration of contaminated water was examined. More specifically, the effect of these compounds was tested on water contaminated (at various concentrations) with Cd, Cr, Cu, Ni and Pb. The determination was performed by inductively coupledplasma-optical emission spectrometry. The maximum binding capacity was presented by fulvic acids in the following order Cr >; Pb >; Ni >; Cu >; Cd (97.8, 96.5, 95.4, 95.1 and 83.3%, respectively), while for humic acids it was Pb >; Ni >; Cr >; Cu >; Cd (81.3, 70.7, 68.6, 67.0 and 66.8%, respectively). The binding activity was also tested on water contaminated with two metals simultaneously.


Absorption of Vitamins/Minerals.

It can be claimed that the presence of the fulvic or humic acid do have significant effects on the absorption of the different drugs and vitamins which are generally lower than the controls but enhances the ionic mineral absorption significantly. Both these outcomes highlight the fact that both health professionals and patients should be made aware of the fact that concomitant administration of prescription drugs and any humic substances will probably lead to altered bioavailability which could affect the clinical outcome of the drugs.

Fulvic Acid Inhibits Aggregation and Promotes Disassembly of Tau Fibrils associated with Alzheimer’s Disease.

We show that the fulvic acid is an active compound against preformed fibrils affecting the whole structure by diminishing length of PHFs and probably acting at the hydrophobic level, as we observed by atomic force techniques. Thus, fulvic acid is likely to provide new insights in the development of potential treatments for Alzheimer's disease using natural products.

Antioxidant activity of fulvic acid: A living matter-derived bioactive compound.

The antioxidant properties of FA described in this work could explain some of the health beneficial effects of this compound since the excessive production of O2•–, HOCl, H2O2, OH•,ONOO– and 1O2 are involved in several pathologies. Moreover, they could be a good candidate for use in pharmaceutical or food industries as an accessible source of natural antioxidants and for the improvement of food quality by retarding lipid oxidation.


Fulvic acid promotes extracellular anti-cancer mediators from RAW264.7 cells, causing to cancer cell death in vitro.

Enhanced cell death in various human cancer cells such as Hep3B, LNCaP, and HL60. Fulvic Acid most likely stimulates immune-modulating molecules such as Nitric Oxide and induces cancer cell apoptosis.

Fulvic Acid Attenuates Resistin-Induced Adhesion of HCT-116 Colorectal Cancer Cells to Endothelial Cells.

A high level of serum resistin has recently been found in patients with a number of cancers, including colorectal cancer (CRC). Hence, resistin may play a role in CRC development. Fulvic acid (FA), a class of humic substances, possesses pharmacological properties. However, the effect of FA on cancer pathophysiology remains unclear. The aim of this study was to investigate the effect of resistin on the endothelial adhesion of CRC and to determine whether FA elicits an antagonistic mechanism to neutralize this resistin effect. Human HCT-116 (p53-negative) and SW-48 (p53-positive) CRC cells and human umbilical vein endothelial cells (HUVECs) were used in the experiments. Treatment of both HCT-116 and SW-48 cells with resistin increases the adhesion of both cells to HUVECs. This result indicated that p53 may not regulate this resistin effect. A mechanistic study in HCT-116 cells further showed that this resistin effect occurs via the activation of NF-κB and the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Co-treating cells with both FA and resistin revealed that FA significantly attenuated the resistin-increased NF-κB activation and ICAM-1/VCAM-1 expression and the consequent adhesion of HCT-116 cells to HUVECs. These results demonstrate the role of resistin in promoting HCT-116 cell adhesion to HUVECs and indicate thatFA might be a potential candidate for the inhibition of the endothelial adhesion of CRC in response to resistin.

Hypoglycemic Effect of Fulvic Acid and Sodium Fulvate on Diabetic Mice.

The hypoglycemic effect of fulvic acid and sodium fulvate is studied,and its hypoglycemic mechanism is also preliminarily discussed.The diabetic mice model is induced by the intraperitoneal injection of alloxan.The influences of fulvic acid and
sodium fulvate on blood glucose level of normal mice,blood glucose level,total cholesterol(TC),triglyceride(TG)and oral glucose tolerance of diabetic mice are then studied.It is shown through the results that the middle and high doses of fulvic acid and sodium fulvate can significantly reduce the blood glucose of normal mice(P0.01);the middle and high doses of fulvic acid and sodium fulvate can significantly reduce the blood glucose,TC and TG levels of diabetic mice(P0.05 or P0.01).The low doses of sodium fulvate,”Handilong” and “Shuanglong” sodium fulvate have the different effects.The middle and high doses of fulvic acid and sodium fulvate can significantly reduce the blood glucose of diabetic mice in the oral glucose tolerance test(P0.05).It is concluded that fulvic acid and sodium fulvate can significantly reduce the blood glucose,TC and TG levels of mice,and increase oral glucose tolerance of mice.This indicates that fulvic acid and sodium fulvate has hypoglycemic activity and can improve the lipid metabolism of diabetes.

Characterization of Fulvic Acid Beverages by Mineral Profile and Antioxidant Capacity.

Nowadays, there is a growing interest among consumers for products made from natural ingredients, not containing preservatives, and having beneficial effects on humans. Besides economic factors, the taste and the health awareness of consumers on the importance of nutrients supplied with food to the human body have a great impact on the food market, including beverages.
The results of the present study on beverages containing fulvic acids, available in the form of concentrates and ready-to-drink beverages, showed that they may contain substantial amounts of Fe (up to about 130% of RDA), Mg (up to about 40% of RDA), and Mn (up to about 70% of RDA). They can also be a good source of polyphenolic compounds (up to about 19.8 mg/mL) with high antioxidant activity. Therefore, they may become interesting and valuable food products or food ingredients with potential effects on human health.


Efficacy of Liquid Plant-derived Minerals on Soil Fertility.

Our study provides empirical evidence that addition of fulvic acid from MDLF and PDLF had more positive effects on soil properties and plant growth than fulvic acid from PDSF. This investigation suggests that application of fulvic acid in liquid form can improve nutrient availability and affect other important chemical, biological, and physical properties of soils.