**3.9 Microbial activity and gut health**

*Humic Substances*

**3.8 Cancer research**

The ages-old FvA-rich compound, Shilajit is known to reduce hyperglycaemia in diabetic animal models and increase SOD activity in pancreatic beta cells. They have the ability to significantly increase superoxide dismutase (SOD) activity that helps preventing and combating free radical damage to pancreatic B islet cells. This property, as shown in several hospital studies, stops the advancement and progression of diabetes, plus assists in the treatment. With fulvic acid treatment, diabetes patients became more energetic and the tingling, painful feeling and numbness experienced

Fulvic acid (FvA) belong to the category of natural health products (NHP) known to cure diseases associated with chronic inflammation such as diabetes, cardiovascular diseases, and colitis. They also help in relieving inflammatory states of the cervix, especially cervical erosion (generally known as cervicitis), swelling from joint inflammation as in Rheumatoid Arthritis (RH). HSs have been shown to

The neuroprotective effect of HAs on cerebral ischemia rat model [70] and gerbil Hippocampus [71], therapeutic effects in renal ischemia reperfusion injury in rats [72], protective effects in iron-induced hepatotoxicity and cardiotoxicity in rats [73] have been associated with their antioxidant and free radical scavenging effects. Administration of fulvic acid to rats for 4 weeks [74] and fish for 60 days [75] showed significant decrease in lipid peroxidation and increase in the expression of

Conventional anti-cancer therapies like chemotherapy, radiotherapy, immunotherapy and surgical approaches for cancer treatment often result in recurrence of the symptoms. During the procedures of cancer chemotherapy and radiation therapy, large amounts of free radicals are generated which damage the normal cells around the tumor cell. Hence, there has always been search for development of

The naturally occurring humic substances, consisting of 60–80% fulvic acids, have known anticarcinogenic properties. Naturally-occurring humic substances have proven antioxidant, anti-inflammatory, antiviral, antimutagenic, heavy metal chelating, apoptotic and photo-protective properties. These properties make them useful agents for cancer therapy and prevention. Another plus point is that when taken orally, HSs have no reported side effects and can be administered as a nutritional and rejuvenating tonic in daily routine of the patient. Numerous hospital studies have shown that humic substances, especially fulvic acids, have the power to protect against cancer and related cancer-causing viruses. Humic extracts destroy cancer cells as well as decrease cell proliferation and angiogenesis and thus, curb growth of the cancer. Special humic substance therapies have shown promising

Molecular structure of humic substances gives them excellent free radical scavenging and antioxidant properties. This antioxidant activity increases with increasing concentration of the humic extracts present in the compounds used in cancer therapy. Naturally-occurring humic substances stimulate the production of cytokines, including interferon-gamma, interferon-alpha, interferon-beta, and

The effect of fulvic acid on three cancer cells lines - Hep3B, HT29 and PC3 at different concentrations of FvA using MTT assay [76]. The assay revealed that FvA inhibited the proliferation of cancer cellsas well as upregulated the mRNA levels of apoptotic genes in all the three cell lines. The cytotoxic effect ofHA with Arsenic trioxide on human cervical cancer cells [77], FvA on hepatic cell lines [78] and HA

bond to the collagen fibres to aid in repair of damaged tendons and bone.

antioxidant enzymes glutathione, superoxide dismutase and catalase.

cancer management approaches using non-toxic and natural products.

results in reversing deadly cancers and tumors.

tumor necrosis factor-alpha.

in the nerve endings disappears or gets reduced [54].

**10**

Sufficient evidences link imbalance in the gut microbiome with inflammation and bowel diseases. Humic substances are known to improve the gut flora, increase the expression and activity of gut enzymes that aid in nutrient absorption and settle certain gut disorders. In other words, humic substances promote microbial activity in gut and thus, enhance nutrient absorption.

When used as feed additives, humic substances may increase rumen microbial population or shift microbiota in the gut to suit animal requirements. Increased microbial activity, in turn, improves fermentation and digestibility of nutrients in the gut rumen. HSs act as natural antibiotics, resulting in increased growth performance in farm animals and early-weaned baby animals. HSs boost the animal gut by promoting good microbes and inhibiting bad microbes when fed at high concentrations in the diet. Several studies have shown that specific species of microbes such as *Turicibacter, Clostridium, Campylobacter, Dehalobacterium, Desulfuvibrio,* and *Paludibacter* are promoted while *Prevotella, Blautia, Faecalibacterium, Lactobacillus*, and *Coprococcus* are inhibited in the cecum and colon of the animals when fed on humate supplemented diet [81, 82]. Similarly, a high relative abundance of *Serratia*, *Acinetobacter*, *Aeromonas* and *Edwardsiella* and low abundance of *Lactobacillus* was obtained in the intestine of fish fed on FvA rich diet for 60 days. The activity of digestive enzymes like lysozyme, proteases, and acid/alkaline phosphatases was also increased [75].

Humic substances particularly FvA increases the absorption of metal ions and other nutrients. There are significant proofs to show their influence on absorption of drugs in the body. FvA has also been shown to mediate drug delivery in animal models. Studies have shown that FvA enhances the uptake of iron, making it more bioavailable to bone marrow stem cells for formation of blood as well as supplying hormone stimulating micronutrients. In Broiler chicken, supplementation of diet with HA improved the utilization of nutrients and growth performance by improving the overall gut health [83, 84].

#### **3.10 Immune support**

Use of humic substances exert a beneficial effect on the animal immune system, including humans. Humates possess ability to bind sugars and assemble them to form complex saccharides within the body like glycoproteins that function as modulators of intercellular interaction. Glycoproteins bind to T cells and Killer cells, keeping them in balance and thus, regulating the immune system. Excessive T cells may lead to development of auto-immune diseases while excess killer cells can attack bone and joints causing arthritis.

Administration of HSs, especially fulvic acids, both topically and orally can bolster the immune system. They act as powerful immunomodulators, may show potent antioxidant and anti-inflammatory properties that can be used to enhance immunity and overall growth of the organism. This has been observed in growing swine [85], juvenile Loach [75] and broiler chicken [86]. Medical studies have indicated that HSs prove more effective than several currently prescribed immune regulatory drugs. Studies on mice have reported strong humoral immune stimulation by HA and FvA supplemented diets [87].

In addition, HSs have proved effective in alleviating the adverse effects of lethal doses of irradiation and reducing the incidence of infections, increasing the life span of the animal. This was directly correlated with the increasing capability of immune system to recognize its own dead cells, following administration with HSs supplemented diet or topical application of HSs. The overall health of animals improves with food and water supplemented with HSs [88].

#### **3.11 Anti-viral properties**

Anti-viral properties of soil-derived humate materials have traditionally been known to humans and have been studied experimentally since decades. Exploration into the mechanism by which humic substances inhibit viral cytopathicity revealed that these substances attach to the viral envelope protein, thereby coating its receptor sites. This further disables the virus from being able to bind and infect host cells, thus combating viral replication. Their potential range of applications cove both naked and enveloped DNA viruses.

Viral pathogens for which HSs have been found effective include Coxsackie virus A9, herpes simplex virus type 1 and 2, human immunodeficiency virus (HIV), influenza type A and B, cytomegalovirus (CMV) and Vaccinia virus as well as other respiratory tract infections. Excellent multimodal anti-HIV properties of humic substances extracted from mud [89], Shilajit [90] and Lignin-rich solid waste resulting from the processing of vegetable feedstock [91] have been demonstrated. Researches are also underway to explore the potential of HSs against the novel coronavirus COVID-19 [92].

#### **3.12 Overall growth rate**

Humic substances, with their miraculous anti-inflammatory, anti-oxidative, immunomodulatory, detoxifying, gut-promoting and nutritional properties helps in improving the overall growth and development of animal body. In animal husbandry, use of humic substances as feed additives promotes the animal growth rate, improves feed efficiency, prevents intestinal diseases and boosts overall immunity, thereby improving the economics and ecology of animal production.

Administration of HA improved the final body weight, daily weight gain and feed conversion ratio in broilers [88], increased the milk output and its quality in goats, and also growth rate of their kids with no adverse effects [63]. Even their young ones show higher survival values and better ability to overcome the effect of weaning at early stages when given diet supplemented with HSs [82].

#### **3.13 Safety aspects**

Humic substances are soil-borne materials, so humans and animals are naturally exposed to them. Industry has safely used these products for industrial exposure to heavy metals in both humans and in animals. Various studies have been conducted on both animals and humans over several years to test the effectiveness and safety of fulvic acids on human diseases [54, 93]. Most of those studies suggested that they are safe for oral or topical use, though recommended further exploration to confirm their safety to be used as food additives. No significant changes in body weights, hematological variables, indices of thyroid function, and microscopic organ histology were obtained when adult rats were orally administrated with HA [94]. No mutagenic or genotoxic effects of acute toxic and subtoxic doses of FvA in female rats [95].

However, some studies also hint upon the harmful effects HSs may be associated with. HA can induce oxidative DNA damage and genotoxicity in human

**13**

**Author details**

\* and Madhu Dhingra<sup>2</sup>

provided the original work is properly cited.

So, explore and reveal the power of 'dirt'!

\*Address all correspondence to: pwpriya@gmail.com

1 Department of Zoology, Deen Dayal Upadhyaya College (University of Delhi),

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 Plant Physiologist, Punjab Agricultural University, Ludhiana, Punjab, India

Priya Goel1

Delhi, India

*Humic Substances: Prospects for Use in Agriculture and Medicine*

but no confirmatory studies have been made so far.

lymphocytes [96]. Some studies also hint upon goitrogenic aspects of HSs [97–99]

Humic substances are a group of organic macromolecules formed from dead tissues of plant and animals transformed over the years by physical, chemical and microbiological processes. They exist ubiquitously in soil, sediments and various terrestrial and aquatic environments. The entire group of HSs can be divided into three components based on their solubility: fulvic acids, humic acids, and humin fragments. Specific properties of humic substances and their products qualifies their uses in both agriculture and medicine. Exploration of compounds present in HAs and their potential in agricultural, pharmaceutical and biomedical industry is

In the era of depleting natural resources, increasing food demands and degrading environment, global warming and erratic weather conditions, we cannot afford more devastation of environment by utilization of chemical fertilizers, pesticides, insecticides etc. Humic substances pose to be potential candidates for improving soil structure and nutrient status along with beneficial effects on plant growth and

Primarily used to enhance growth and vigour of the organisms, HSs are increas-

ingly being used to treat several body ailments. Their potential as anti-ageing, anti-oxidative, anti-inflammatory, anti-cancer, immunostimulatory and growthpromoting agents is largely being explored. This will help bringing these organic molecules into the niche market where they can largely replace chemical substances.

yield; thus, giving a pavement towards sustainable agriculture.

*DOI: http://dx.doi.org/10.5772/intechopen.99651*

**4. Conclusion**

of utmost importance.

lymphocytes [96]. Some studies also hint upon goitrogenic aspects of HSs [97–99] but no confirmatory studies have been made so far.
