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Polyphenols (Fulvic Acid) and Immune Response

The complex role of phytochemicals in the body

A diet full of natural foods is our best defense against pathogens as they contain polyphenols or plant chemicals aka: phytochemicals. One class of phytochemicals are polyphenols. Polyphenols are a large group of micronutrient compounds found mostly in plants, including fruits, vegetables, nuts, seeds, and cereals, as well as natural nutraceuticals such as MLG-50 fulvic mineral powder, or beverages such as tea, coffee and wine[1].

Polyphenols have tremendous potential to health and prevention of disease [2,3,4,5]. Their sub-categories flavonoids and phenolic acids perform many biological activities throughout the body.

Scientific research suggested beneficial effects of polyphenols include anticarcinogenic [6,7], antiatherogenic [8,9], antiulcer [10], antithrombotic [11,12], anti-inflammatory [13,14], antiallergenic [15,16], anticoagulant [17], immune modulating [18], antimicrobial [19,20], vasodilatory [21], and analgesic activities [22].

(To access the list of references and science presented here, see the white paper at

To achieve these health benefits, polyphenols require processing by the gut microbiota to be transformed into a potentially more bioactive, low-molecular-weight metabolite [23].

“A huge proportion of your immune system is actually in your GI tract,” says Dan Peterson, assistant professor of pathology at the Johns Hopkins University School of Medicine"[1A]. 

There is a reciprocal relationship between polyphenols and our gut microbiota. A healthy microbial balance is crucial in protecting against gastrointestinal disorders and pathogens, processing nutrients, reducing serum cholesterol, strengthening intestinal epithelial tight cell junctions, producing antibodies, increasing mucus secretion and modulating intestinal immune response through cytokine stimulus [34,35].

Gut Health, Inflammation and Immunity

Gut Microbiota (GM) diversity is affected by diet. Our GM influences metabolic and immune functions of the host’s physiology. Consequently, an imbalance of GM, or dysbiosis, may be the cause or at least may lead to the progression of various pathologies such as infectious diseases, gastrointestinal cancers, inflammatory bowel disease, and even obesity and diabetes. Therefore, GM is an appropriate target for nutritional interventions to improve health.

For this reason, phytochemicals, such as polyphenols (e.g. fulvic acids) that can influence GM and have recently been studied as adjuvants for the treatment of obesity, inflammatory diseases and overall immune health.

Phytochemicals include prebiotics and probiotics, as well as several chemical compounds such as polyphenols and derivatives, carotenoids, and thiosulfates. The largest group of these comprises polyphenols, which can be subclassified into four main groups:

1. flavonoids (including eight subgroups)

2. phenolic acids (such as curcumin)

3. stilbenoids (such as resveratrol)

4. and lignans

Once nutrients and nutraceuticals (e.g. polyphenols) have been incorporated into the body, the gut environment is essential in maintaining homeostasis. The integrity of the intestinal mucous membrane plays a fundamental role in the preservation of homeostasis. Consequently, the correct functioning of its permeability is of great importance [36].

Humans possess two interacting genomes: their own complete set of DNA and that of the microbiome genome the majority of which resides in the gut.

The microbiome enables our body to manufacture vitamins and nutrients to feed our cells, thereby establishing a beneficial ecosystem for our physiology and preventing the proliferation of pathogens [38}. Thus, a symbiotic relationship is established between both genomes, through the expression of pattern recognition receptors (PRRs) that sense the presence of intestinal microbiota, through the microbe-associated molecular patterns (MAMPs).

Polyphenols and Cytokine Modulation

Cytokines are important mediator proteins, essential in networking communication for the immune system. Cytokines can be produced with pro-inflammatory and anti-inflammatory effects. The equilibrium between pro-inflammatory cytokines and anti-inflammatory cytokines are thought to be an important parameter in immune response homeostasis and inflammation underlining many disease states [43].

In vivo and in vitro studies demonstrate that polyphenols exhibit anti-inflammatory effects. Several flavonoids are found to inhibit the expression of various pro-inflammatory cytokines. Modulation of inflammatory cytokines is one of many common mechanisms by which polyphenols in general exert their immunomodulatory effects.

Polyphenols, Oxidative Stress, and Inflammation

Oxidative stress occurs in our body as a result of our metabolism and burning calories but also we are bombarded with chemicals in everyday products we use and air pollution. Free radicals damage healthy proteins and lipids within cells and speed up age-related diseases[59]. Subsequently these inflammatory molecules and inflammatory signals are triggered by protein oxidations [60]. Furthermore, overproduction of free radicals can prompt tissue injury that initiates the inflammatory process [61-65].

Therefore, the classical antioxidant actions of polyphenols undoubtedly contribute to their anti-inflammatory roles by interrupting the free radical (Reactive Oxygen Species ROS) inflammation cycle. Polyphenols are known for their antioxidant activities; they scavenge a wide-ranging selection of ROS. Polyphenols can scavenge radicals and chelate metal ions [66]. They also inhibit multiple enzymes responsible for free radical generation [67].

To the opposite, polyphenols are able to chelate metal ions, and free radicals which lead to a reduction of highly oxidizing free radicals in the body [68]. As a result, ROS production is diminished.

Polyphenols exert the anti-inflammatory action by different mechanisms: radical scavenging, metal chelating, NOX inhibition, tempering the mitochondrial respiratory chain, inhibition of certain enzymes involved in ROS production, like xanthine oxidase and upregulation of endogenous antioxidant enzymes.


It is generally believed that polyphenol activity is principally located in the gut where their immune-protective and anti-inflammatory activities are initiated and subsequently ensuring systemic anti-inflammatory effects. Since different polyphenols can have multiple intracellular targets, additional data is needed to determine the consequences of the interaction or the synergistic effects between multiple polyphenolic compounds or polyphenols and commonly used medications. Moreover, further in vivo and meta-analysis studies in humans are necessary to fully reveal the mechanisms of action of polyphenols in several physiological conditions in order to produce important insights into their prophylactic and therapeutic uses.

MLG-50™ Fulvic Mineral Powder is a concentration of ancient plant polyphenols with twenty-two flavonoid molecules along with organic and amino acids, and trace micronutrients. It is an outstanding source of natural phytonutrients for nutraceuticals, functional foods, and beverages.

This article is meant for educational purposes only. These statements have not been evaluated by the Food and Drug Administration. Topics in this article and product is not intended to diagnose, treat, cure, or prevent any disease.”


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