“The FA-CM augmented MCA-102 fibrosarcoma cell apoptosis; however, an NO inhibitor N(G)-monomethyl-l-arginine (NMMA) slightly inhibited the FA-CM-mediated MCA-102 fibrosarcoma cell apoptosis, which was accompanied by low levels of NO. In the present study, we found that FA induces the generation of NO and iNOS in RAW 264.7 cells by inducing NF-κB activation; however, NO did not significantly stimulate MCA-102 fibrosarcoma cell apoptosis in the current study. In addition, FA-CM enhanced cell death in various human cancer cells such as Hep3B, LNCaP, and HL60. Taken together, FA most likely stimulates immune-modulating molecules such as NO and induces cancer cell apoptosis.”
Humic acid inhibits HBV-induced autophagosome formation and induces apoptosis in HBV-transfected Hep G2 cells.
This is very interesting in vivo research. From the abstract, the researchers wrote
“Hepatitis B Virus (HBV) utilizes several mechanisms to survive in the host cells and one of the main pathways being autophagosome formation. Humic acid (HA), one of the major components of Mineral pitch, is an Ayurvedic medicinal food, commonly used by the people of the Himalayan regions of Nepal and India for various body ailments. We hypothesized that HA could induce cell death and inhibit HBV-induced autophagy in hepatic cells……These data showed that HA induced apoptosis and inhibited HBV-induced autophagosome formation and proliferation in hepatoma cells.”
“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 antiinflammatory 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.”
Dr Richard Laub was researching humic acid for many years. When a pharmaceutical company (and now, more than one) began researching synthetic oxyhumates for drug discovery, he began his own research into the natural earth mineral compounds in humates and their effects on human health. The results are simply stunning.
In a study published in the journal Environmental Science Technology the activity of different kinds of humic acid forms are compared in terms of their ability to bind to lead (Pb). The group found that “Pb binding to humic substances (HS) increased with increasing pH and decreasing ionic strength.”
Another animal study strengthens the case for natural organic matter (NOM) containing humic acid as a way to remediate heavy metal excess in the environment and in living things.
Published in the journal Ecotoxicology Environmental Safety, JD Oullet et al concluded ” Collectively, these findings suggest that metal accumulation caused by chronic 45 percent PWE exposure cannot solely explain the reproductive toxicity in fish, and decrease in food availability (decrease in C. dilutus abundance in 45 percent PWE exposures) might have played a role. In addition, it appears that NaHCO3 or humic acid mitigated reproductive toxicity in fish exposed to 45 percent PWE by their direct beneficial effects on the physiological status of fish.”
Natural humic acids in veterinary medicine
The study of humates (primarily comprised of humic acid and fulvic acid) is a relatively new subject, particularly as it pertains to human health. A growing body of research suggests that these novel compounds may be very beneficial to living things, from plants and soil to animals and human beings.
To the naturalist these connections will not be surprising because for many “the micro is the macro.” We see the behavior of organisms on a cellular level is very similar in many ways. The unique properties which humic substances exert on plants may be very similar to those which it exerts on humans and other animals.
In 1991 German researchers wrote “The chemical structure of humic substances has been the subject of much speculation and research over the past 200 years. In spite of the availability of abundant experimental data in the literature, soil and environmental scientists as yet have not been able to propose a valid concept of the chemical structure of these materials.”
It is currently believed that humates or humic substances are natural complexes formed when organic matter is broken down by bacterial decomposition. They are found in both land and water, being a major component of sea water, peat, dystrophic lakes and soil.
Humic acids are believed to be heterogeneous, polydisperse mixtures of natural organic polyelectrolytes, containing a large number of different functional groups. 
Fulvic acid is a type of humic acid that is of lower molecular weight and higher oxygen content. It has also been researched for many of the same characteristics as other types of humic acid.
One of the most notable characteristics of humic substances is that they have the ability to form colloids with ions existing in the natural environment. This is considered to be mostly because of their content of carboxyl and phenolate groups.
They also seem to have a great affinity for conducting electricity, existing as a natural poly-electrolyte. Humic acid’s ability to act as both an electron donor, and an electron receptor, gives it the ability to bind to ions with either a negative charge or a positive charge.
A paper published in 1997 by Geoffrey Davies , et al,in the Journal of the Chemistry Society, Dalton Reactions, explored tight-binding of Copper, Iron and Manganese to Humic acid in soil. The authors found specific binding sites in carboxylic groups and in the Humic acid helix, noting rapidly transfer between specific HA binding sites affecting the rate of release of metals, and their transfer to minerals.
This propensity to chelate with minerals, and to act as a useful transport of different kinds of compounds, has made Humic acid popular as a natural plant fertilizer, as well as for soil and water remediation, and more recently, when highly purified, as a dietary supplement to the human diet.
Humic acid has a high binding affinity for heavy metals, affecting their transport in aquatic systems. Humic acid has been used to reduce pollution and levels of heavy metals in the environment.  The propensity of HA to complex metal ions and sequester organic molecules suggests that it may be used to remove contaminants from polluted water.
Humic acid has been shown to reduce heavy metal in tissues when co-administered with toxic doses of cadmium in chickens. This suggests that in addition to reducing heavy metals in the environment, humates can also reduce the levels of heavy metals in live animals.
In another study conducted on livestock animals, a mixture of humic acid and fulvic acids showed an increased growth rate in cows compared to a control group. This speaks to humic acid’s ability to aid the growth process by helping bring in nutrition on a cellular level.
We can infer here that humic substances’ unique ability to chelate with different kinds of metals is useful both in their ability to bind with heavy metals which may be potentially dangerous to an organism, and also to escort beneficial mineral compounds into the tissues. This may account for the increased growth rates seen in the above study, and in other examples of biomineralization which we will explore in subsequent chapters.
This type of bioregulation is a defining characteristic of humic substances. Humic acids have the ability to donate, as well as to accept, electrons. This gives them the ability to bind to negatively-charged, as well as positively-charged, ions.
This is definitely of interest to people interested in taking humates as a dietary supplement, because it may explain some of the different ways in which they behave in the human ecosystem. Indeed, we find that the way that humic substances behave in the geopshere may be quite similar to the functions that they serve when taken internally.
Reports have also emerged that humates may have benefit as an agent againt viral infection. In addition to supporting the transport of nutrients and waste products throughout the body, they may have direct action against viruses in the body.
Research has also shown that humic acid can be a potent anti-viral, blocking the viruses ability to replicate. Humates have been shown to exert anti-viral activity againt both Herpes simle 1 and 2 A synthetic analogue of humic acid has been shown to inhibit HIV-1 in vitro.
Fulvic acid has been described by researchers at the University of Massachusetts as an EVNC (envelope virus neutralizing compound) as . They reported that fulvic acid was able to render vaccinia virus, HIV and SARS virus non-infectious.
The title of this article, published in the journal Vaccine in 2008, was “Genetic diversity-independent neutralization of pandemic viruses (e.g. HIV), potentially pandemic (e.g. H5N1 strain of influenza) and carcinogenic (e.g. HBV and HCV) viruses and possible agents of bioterrorism (variola) by enveloped virus neutralizing compounds (EVNCs).” The research showed that both fulvic acid and pomegranate juice rendered viruses non-infectious.
The author also noted “Recently, both fulvic acid and pomegranate juice have been shown to inactivate genetically diverse strains of influenza including H5N1, further confirming the broad spectrum nature of these agents.”
Interestingly, pharmaceutical researchers have researched synthetic humic acid analogues, and have been able to create compounds which are also anti-viral against viruses such as HIV-1. In an editorial in a natural health website, Brian Sakae writes “Pharmaceutical companies have been rushing to patent synthetic versions of this natural substance, and dozens of patents have been approved. Yet Mother Nature has them all beat because they’ll never be able to duplicate her handiwork. This substance is far too complex!”
 Schulten, HR et al. A chemical structure for humic substances. Naturwissenschaften July 1991, Volume 78, Issue 7, pp 311-312
 Replace with textbook reference
 Andjelkovic, J, et al. BINDING OF LEAD TO HUMIC ACID RELATED TO ITS CARBOXYL AND PHENOL GROUPS CONTENTS. University of Ni, Serbia
 Davies, Geoffrey, et al. Tight metal binding by humic acids and its role in biomineralization Journal of the Chemical Society, Dalton Transactions
Issue 21, 1997
 Herzig I, et al. [The effect of sodium huminate on cadmium deposition in the organs of chickens]. [Article in Czech] Vet Med (Praha). 1994;39(4):175-85. PMID: 8085303
 Cusack PM. Effects of a dietary complex of humic and fulvic acids (FeedMAX 15) on the health and production of feedlot cattle destined for the Australian domestic market. Aust Vet J. 2008 Jan-Feb;86(1-2):46-9. doi: 10.1111/j.1751-0813.2007.00242.x. PMID: 18271826
 Coates, John D. Diversity and Ubiquity of Bacteria Capable of Utilizing Humic Substances as Electron Donors for Anaerobic Respiration. Appl. Environ. Microbiol. May 2002 vol. 68 no. 5 2445-2452 doi: 10.1128/AEM.68.5.2445-2452.2002
 Kotwal GJ.Genetic diversity-independent neutralization of pandemic viruses (e.g. HIV), potentially pandemic (e.g. H5N1 strain of influenza) and carcinogenic (e.g. HBV and HCV) viruses and possible agents of bioterrorism (variola) by enveloped virus neutralizing compounds (EVNCs). Vaccine. 2008 Jun 6;26(24):3055-8. doi: 10.1016/j.vaccine.2007.12.008. Epub 2007 Dec 26. PMID: 18241960
 Schneider J, et al. Inhibition of HIV-1 in cell culture by synthetic humate analogues derived from hydroquinone: mechanism of inhibition. Virology. 1996 Apr 15;218(2):389-95.
Very impressive study showing dibenzo-α-pyrones , and fulvic acids from Shilajit were effective against CFS in rats.
Shilajit reversed the CFS-induced increase in immobility period and decrease in climbing behavior as well as attenuated anxiety in the EPM test. Shilajit reversed CFS-induced decrease in plasma corticosterone level and loss of adrenal gland weight indicating modulation of HPA axis. Shilajit prevented CFS-induced mitochondrial dysfunction by stabilizing the complex enzyme activities and the loss of MMP. Shilajit reversed CFS-induced mitochondrial oxidative stress in terms of NO concentration and, LPO, SOD and catalase activities.
This is a pretty interesting 1994 paper from the Institute of Freshwater Ecology in the UK, proposing a new model for exploring ion-binding by Humic Acids. The author E. Tipping notes “WHAM combines Humic Ion-Binding Model V with a simple inorganic speciation code for aqueous solutions. Precipitation of aluminum and iron oxides, cation-exchange on an idealized clay mineral, and adsorption-desorption reactions of fulvic acid also are taken into account”