Plant Phenolic Compounds, Part I: Their Relevance, Diversity, and Biosynthesis

"It is important to draw wisdom from different places. If you take it from only one place, it becomes rigid and stale." -Iroh

Due to the relevance of phytochemicals (mainly phenolic compounds) to the future discussion on kombucha's health benefits, and with so much current research surrounding their antioxidant and antimicrobial properties, in particular, we wanted to devote an entire set of posts to said topic.

Phenolic compounds - via antioxidant, antimicrobial, and protein/enzyme neutralization/modulation mechanisms - have been shown to exert preventative action against infectious and degenerative diseases, inflammation and allergies (1).

Before diving into these topics let's take a look at what exactly phenolic compounds are and how they become important in our diets and, ultimately, in our kombucha.

Plant-Derived Phenolic Compounds

Introduction

Phenolic compounds - in relation to our discussion on beverages - are reactive plant metabolites present in most plant-derived foods (e.g. chaga, berries, citrus fruit, cocoa, grapes, onions, broccoli, tea, coffee, wine) (1). Generally speaking, phenolic compounds interact with proteins and work as terminators of free radicals and chelators of metal ions which are capable of catalyzing lipid oxidation (as usual oxidation is going to be very important in this post).

Occurrence

As is surely no secret by now, plants are rich sources of nutrients, which individually, or in combination, can be beneficial for human health. Specifically - pertinent to the current discussion - the consumption of plant derived phenolic compounds. This topic has received much attention as of late, with in vitro, clinical, and epidemiological studies (along with their meta-analyses) showing promising, yet in some cases still conflicting, results (1,2,3,4,5,6,7).

Upwards of 8000 different phenolic compounds have been identified throughout various plant species. Plant phenolic compounds are secondary metabolites of plants and are generally involved in defense against UV radiation or encroachment of pathogens and pests (2). In our diets, plant phenolics are mainly found in fruits, vegetables, cereals, and beverages. In such beverages, phenolics contribute to the bitterness, astringency, color, flavor, odor, and oxidative stability, or shelf-life (1,2).

Structure & Classes

Phenolic compounds are typically present in conjugated forms, with one or more sugar residues linked to hydroxyl groups or, perhaps less commonly, directly to an aromatic carbon. Phenolic compound association with other compounds is also common, such as: carboxylic and organic acids, amines, lipids, and other phenols.

Ultimately, plant derived phenolic compounds are typically classified into different groups based on the number of phenol rings they contain and the types of structural elements that bind these rings to one another (Fig 1a). In order to recognize - and avoid confusion surrounding - a somewhat varied and evolving classification system, for the purpose of this discussion we will classify plant phenolic compounds into four distinct groups: phenolic acids, flavonoids, lignins/tannins and stilbenes (1,2,3).

Figure 1a

Chemical Structures of the Different Classes of Polyphenols

Ferulic acid (a phenolic acid) is actually a fascinating beer related topics, and we hope to cover that in the future.

Figure 1b

Main Classes of Phenolic Compounds (“Polyphenols”)

Chemistry of Phenolic Compounds

The term "phenolic" can be defined chemically as a compound possessing an aromatic ring, bearing one or more hydroxyl substituents, including functional derivatives (i.e. esters, glycosides, etc.) (3). Their structure may vary from that of a simple monomeric phenol (e.g. hydroquinone) to that of a high-molecular weight complex polymer (e.g. quercetin), or "polyphenol" (Fig 2). Despite this diversity, phenolic compounds have become popularly referred to solely as "polyphenols".

Figure 2

Some Common Phenolic Compounds

Biochemistry of Plant Polyphenols

The plant shikimate pathway is the entry point to the biosynthesis of polyphenols. All plant polyphenols arise from common amino-acid endpoints, or intermediates, of the shikimate pathway - phenylalanine and tyrosine - or a close precursor, shikimic acid (2). These core structures derived from the shikimate pathway act as a nucleation point ("molecular starters") for the production of a diverse set of compounds, called phenylpropanoids; which in turn through the phenylpropanoid pathway (or phenylpropanoid metabolism) produce a wide array of metabolites (among which are polyphenols).

Intermediate metabolite 4-coumaroyl CoA represents the most important branch point within the central phenylpropanoid biosynthesis, in plants (8). It is the product of phenolic acids and is either the direct precursor (e.g. flavonoids, lignins) or the indirect precursor (e.g. stilbenes) for polyphenol biosynthesis (Fig 3).

Figure 3

Diversification of Phenylpropanoids Based on the General Phenylpropanoid & Shikimate Pathways (the metabolites of the shikimate pathway and the central metabolite, 4-coumaroyl CoA, are shaded in gray) (8)

In general, phenylpropanoid metabolism generates an enormous array of secondary metabolites based on the few intermediates and products of the shikimate pathway, mentioned above, as the core unit. The resulting compounds are amplified in several enzymatic cascades by a combination of reductases, oxygenases, and transferases; resulting in a specific pattern of metabolites, characteristic for each plant species. While these biosynthetic pathways are often regarded as secondary metabolism, they actually turn out to be as equally relevant to plant survival as photosynthesis or the citric acid cycle.

In other words, phenylpropanoids, as with the resulting and concurrent polyphenol production, contribute to all aspects of plant responses towards biotic and abiotic stimuli (Fig 4) (8,9,10). They are not only indicators of plant stress responses to variation of light or mineral treatment, but are also key mediators of a plant's: resistance towards pests, invasion of new habitats, response to environmental damage (e.g. wounding and drought), and successful reproduction (11,12,13).

Figure 4

Overview of Plant Compound Formation

Aside from the production of compounds crucial to a plants survival, phenylpropanoid metabolism leads to the production of most characteristic plant volatile compounds (characteristic aromas), while themselves exhibiting some important characteristic aromas (e.g. eugenol exhibiting the characteristic aroma of cloves).

When you see the suffix "-ase" you should be thinking enzymes! If you are a bit unclear on enzymes please watch this video for a brief tutorial.

The shikimate pathway is not found in humans. As humans require the products of this pathway - phenylalanine and tyrosine - they represent essential amino-acids that must be obtained from bacteria, fungi or plants (or animals which eat bacteria, fungi or plants) in the our diet. However, our gastro-intestinal tract is home to trillions of such creatures already, so surely they can help provide us with these essential amino-acids, right? Ideally, unfortunately they still require feeding from us, and our diets are full of nasty little surprises.

In fact, much concern is being be raised as to the use of pesticides and herbicides, such as glyphosate (trade name "Roundup"), which actually inhibit the shikimate pathway; as a mechanism of action for killing the unwanted plants. But how does this herbicide not then kill the desired plant (e.g. wheat, corn)? Because these have been genetically modified to resist glyphosate; they are "Roundup" ready.

As herbicides are commonly used in high amounts to treat gluten-rich crops - such as wheat - speculation as to the mechanism of occurrence of the relatively recent surge in inflammatory gastro-intestinal diseases - such as celiac's and Krohn's - is being questioned. In other-words, is the culprit here actually just the inflammatory response to the protein gluten, or is it the alteration of key biosynthetic pathways - such as the shikimate - which then leave us deficient of such essential amino acids; which in turn affects our immune response?

This can be seen as a beautiful example of how fluid our grasp of the natural sciences actually is, through continued research (perhaps in a few years time young minds will be learning of the shikimate pathway with the same implied importance of photosynthesis and the Kreb's cycle). While current scientific consensus is undoubtedly a useful tool, it is by no means an ultimate comprehensive truth, or endpoint, and should not limit our views and investigation; one should strive to broaden their scientific knowledge.

General Molecular Mechanisms of Dietary Polyphenols

Antioxidant Potential

Oxidation can be thought of as the addition of oxygen, or the removal of hydrogen. More precisely, oxidation occurs when an atom loses electron(s) to another atom. The atom taking the electron(s) is reduced. Understanding oxidation states - difference between number of valence electrons a neutral atom of that element has and the number associated with it when bound to other atoms – helps conceptualize how various compounds are affected.

For example, consider the formation of aldehydes from the oxidation of alcohols (important for you drinkers out there). As seen from the Lewis structures for the central carbon atoms, two electrons are lost (Fig 5). In other words, the carbon atom, which has 4 valence electrons in a neutral state - and hence why you often see its ionic form written as C4+ - has 5 electrons associated with it when bonding in the alcohol, but only 3 when in the aldehyde form. There are now 2 less electrons associated with that carbon atom when the alcohol becomes an aldehyde. The carbon atom has lost 2 electrons, and has thus been "oxidized". One may also notice that this occurred through the loss of hydrogen atoms, but the oxidation mechanism can also occur through the addition of an oxygen.

Oxidation does not occur directly from molecular oxygen, or dioxygen, but through activated oxygen intermediates, or free radicals14, with the aid of enzymes such as peroxide dismutase and catalase (Fig 6).

Free radicals can damage important bio-molecules (e.g. lipids, proteins, enzymes), cause cellular membrane peroxidation and attract various inflammatory mediators (e.g. cytokines) (15).

Antioxidants, such as polyphenols, can rapidly "trap" free radicals (e.g. superoxide) by reacting with them to form stabilized radicals that do not continue the "chain", or oxidation, of other, perhaps more important, molecules. In other words, antioxidants act as a sort or "sacrificial" molecule - free radical terminators, if you will.

Historically, the most notable property of dietary polyphenols has been this antioxidant capacity towards free radicals; which are normally produced by cellular metabolism or in response to external stresses. However, keep in mind that oxidant properties of polyphenols may be both anti-oxidant and/or pro-oxidant, based upon the structure of the particular polyphenol and the specific cellular redox environment (e.g. increased levels of oxidant scavenging proteins or decreased levels of oxidized proteins and lipids, enzyme activity, pH) (16).

The three main proposed mechanisms through which dietary plant polyphenols play a protective antioxidant role are: hydrogen atom transfer, single electron transfer and metals chelations (15).

Hydrogen Atom Transfer (HAT) Mechanism

The HAT mechanism is characterized by the polyphenol antioxidant - ArOH - reacting with the free radical - R· - by transferring to it a hydrogen atom, through homolytic rupture of the O–H bond:

ArOH + R· → ArO· + RH

The products of this reaction are the harmless RH species and the oxidized ArO· radical. Even though the reaction leads to the formation of another radical, said radical is less reactive with respect to the original radical - R· - because it is stabilized by several factors (e.g. the newly obtained odd electron on the antioxidant has the possibility to spread over an entire molecule which leads to radical stabilization) (15).

In this case, the bond dissociation enthalpy (BDE), or energy required to break a bond homolytically, of the phenolic O-H bond is crucial in determining the potential antioxidant capability; the lower the BDE, the easier the dissociation of the O-H bond and thus the more likely the reaction with the free radical.

The mechanism of action of polyphenol oxidation can be conceptualized by considering a common utilitarian example: the reversible oxidation of hydroquinone in mitochondria (i.e. hydroquinone has pro and anti-oxidative potential).

Oxidation of hydroquinone (1,4-benzenediol), a dehydrogenation reaction (loss of a hydrogen molecule), leads to para-benzoquinone and is initiated by mild oxidizing compounds (Fig 8).

Cells make use of this enzyme-catalyzed reversible reaction in the transport of electron pairs from one place to another. Important compounds of this type are called "ubiquinones", and with the addition of highly polar side chains, their solubility in the mitochondrial membrane facilitates their diffusion, and cascading involvement in the electron transport chain; eventually becoming crucial compounds such as vitamin K1 (involved in blood coagulation).

Single Electron Transfer (SET) Mechanism

The SET mechanism sees the polyphenol able to donate an electron to the free radical:

ArOH + R· → ArOH+· + R-

The anion R- is energetically stable, with an even number of electrons, and the cation ArOH+· is also less reactive than the original free radical; in fact, similarly to ArO· from the HAT mechanism, it is an aromatic structure in which the odd electron has the ability to spread over the entire molecule, thus stabilizing itself. Analogously to the BDE of the HAT mechanism, the SET antioxidant capacity is characterized by the ionization potential (IP) of the aromatic hydroxyl group; the lower the IP, the easier the reaction with the free radical (15.

Transition Metal Chelation (TMC) Mechanism

Certain metals, in particular transition metals, take part in reactions which generate free radicals. Notably, some metals in their low oxidation state (mainly Fe2+) are involved in an important set of reactions with hydrogen peroxide, called Fenton reactions; from which the very dangerous reactive oxygen species (ROS) OH· is formed:

H2O2 + Mn+ → HO-+ HO∙ + M(n+1)+

The HO∙ (hydroxyl) radical is generally regarded as one of the most reactive radicals; it has a very short half-life and a very high reactivity. Furthermore, in contrast to the hydroperoxides that are metabolized by superoxide dismutase (SOD), hydroxyl radicals cannot be eliminated by enzymatic reactions; meaning they can react with every kind of substrate they encounter (17).

Transition metals (e.g. copper, manganese, cobalt) in ionic form, not bound to proteins or chelators, are able to catalyse these Fenton reactions, under certain conditions. Fenton-like reactions may then take place and cause site specific accumulation of free radicals and initiate bio-molecular damage.

Beer brewers: unchecked Fenton reactions during the mash process will lead to downstream beer staling reactions.

The TMC antioxidant mechanism exploits the possibility that transition metal ions may be chelated by polyphenols, leading to stable complexed compounds. The polyphenol antioxidants can basically entrap metals, preventing them from taking part in the reactions generating free radicals (e.g. Fenton reactions). More specifically, metal-chelating compounds work to remove the metals and alter their redox potentials, rendering them inactive.

Moreover, the use of natural metal-chelators such as polyphenols (e.g. flavonoids) should be favoured against other synthetic chelators which may present some problems of toxicity (15). Many polyphenols (e.g. flavonoids) possess multiple hydroxyl groups and a carbonyl group, which offer several available sites for metal-chelation (Fig 8).

Figure 8

Polyphenol Antioxidant Mechanisms

Other Bioactive Actions of Polyphenols

Many studies often report the biological effects of food polyphenols without clearly defining the underlying molecular, cellular, and physiological mechanisms. The reason for this being that there are many obstacles to defining related mechanistic studies (e.g. non-specific effects due to polyphenols with pleiotropic activities, complex mechanisms of action). Despite said difficulties, recent studies have begun to elucidate more detailed molecular mechanisms underlying the bioactive actions of polyphenols, beyond solely their antioxidant mediation.

While many polyphenols potentially share beneﬁcial effects against common age-related diseases (e.g. cancer, inﬂammation, diabetes, cardiovascular disease), individual polyphenols have distinct specific molecular targets in various tissues with different efficiencies and bioavailabilities (19). These topics will be covered in future posts, but we will introduce some of these mechanisms incipiently, namely: the interaction with plasma membrane proteins and phospholipids, the regulation of signal transduction pathways, DNA methylation, the modulation of metabolic enzymes, and cellular autophagy (19,20,21,22).

Cell Surface Receptors

Polyphenols have now been shown to interact with receptors capable of initiating cell signaling. I wont get into the mechanisms in this post, but essentially certain polyphenols have been shown to bind directly to membrane proteins and lipids. This has many important health related implications. For example, binding to the the platelet-derived growth factor receptor (PDGFR-BB) inhibits PDGFR-BB stimulated signal transduction pathways in vascular smooth muscle cells, thereby inhibiting platelet-derived growth factor stimulated narrowing of the blood vessel (23).

Furthermore, polyphenols such as epigallocathechin 3-gallate (EGCG) have been shown to significantly regulate activities of cell-surface growth factor receptors, most notable several tyrosine kinases (RTK): epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), insulin-like growth factor receptor (IGFR), and the insulin receptor (InsR) (15,23). Most RTKs are involved in cell proliferation, survival and angiogenesis (e.g. InsR is important for regulation of cellular metabolism and survival). EGCG has been shown to act beneficially by inhibitting EGFR, VEGFR and IGFR; while enhancing InsR signalling (25).

Epigallocathechin 3-gallate (EGCG) is a major polyphenol constituent in green tea!

Overview of signal transduction:

An environmental signal, such as a hormone, is first received by interaction with a cellular component, most often a cell-surface receptor (receptor-ligand complexation). The information that the signal has arrived is then converted into other chemical forms, or "transduced", within the cell. The signal is often amplified before evoking a response (second messengers). The signalling process is continuously regulated by feedback control (24).

Intra-cellular Signaling Pathways

As mentioned, polyphenols such as EGCG have been shown to exhibit low level pro-oxidative effects, as well. The production of low reactive oxygen species, such as hydrogen peroxide, by EGCG, has been shown to act as secondary messengers for downstream signalling pathways (26). Moreover, EGCG has been shown to increase other second messengers, including: Ca2+, cAMP, and cGMP.

Second messengers:

Intracellular molecules that change in concentration in response to environmental signals (Fig 9). This change in concentration conveys information inside the cell (24).

Example of potential impact from polyphenol-mediated effects on signaling pathways:

Adenosince monophosphate kinase (AMPK) is an energy sensing molecule that is also activated by EGCG in hepatocytes, adipocytes, cancer cells, and endothelial cells. AMPK contributes to inhibition of gluconeogenesis, stimulation of lipolysis, apoptosis, and reduction of endothelin-1 expressions (27).

Such activities, alone or in combination, may contribute to improvement of insulin sensitivity, lipid metabolism and vasodilation (28).

Nuclear Function - Regulation of Transcription Factors & DNA Methylation

As noted above, cellular responses in intra-cellular signal transduction pathways generally occur acutely, or are isolated in their occurrence. In contrast, chronic cellular responses often involve nuclear functions that regulate gene expression and chromosomal modifications. For example, abnormal methylations at CG sites (cytosine followed by guanine; typically found at or near transcription starting points) can cause genetic silencing which leads to an altered cellular physiology and/or cell proliferation. Certain polyphenols have been shown to impose epigenetic functions in chromosomes by interfering with such sequences (30).

Polyphenols, such as EGCG, have been shown to modulate gene expression by inhibiting the action of various specific transcription factors (e.g. NF-kB, FOX01) (29). Notably, EGCG inhibits DNA methyltransferase (DNMT) which reverses methylation-induced gene silencing, by directly binding to DNMT. The specific genes affected by this mechanism, however, are not clear.

Mitochondrial Function

The mitochondria are the big energy producing organelles in our cells and their function is key to burning off that dreaded fat, and supplying energy to crucial biological functions (such as hair growth!). Polyphenols, such as EGCG, have been shown to enhance mitochondrial fat utilization and reduce adipogenesis (generation of adipose tissue, or fat cells) by reducing the expression of leptin and stearyl-CoA desaturase in white adipose cells, while increasing fat oxidation (31).

Autophagy

Autophagy is a lysosomal catabolic process that degrades accumulated and unnecessary intra-cellular materials. Autophagy is a process that destroys bio-energetic macro-molecular reserves - including proteins, lipids, and nucleic acids - to generate energy by replenishing ATP levels.

The decline in the energetic status of a cell triggers autophagy by increasing the the activity of the AMP-kinase pathway, while simultaneously suppressing the mTOR pathway. With its link to "anti-ageing", autophagy has garnered a lot of interest of late, especially where diet is concerned. Specifically, the timing of food intake on metabolism (32,33).

As a cellular energy sensor responding to low ATP levels, AMPK activation positively regulates signaling pathways that replenish cellular ATP supplies, including fatty acid oxidation as well as autophagy. AMPK negatively regulates ATP-consuming biosynthetic processes including gluconeogenesis, lipid, and protein synthesis. This is accomplished through direct phosphorylation of a number of enzymes directly involved in these processes as well as through transcriptional control of metabolism by phosphorylating transcription factors, co-activators, and co-repressors.

Autophagy requires a highly complex and organized interaction of molecules to help determine cell death or survival. Most polyphenols induce autophagy, and this is likely where their main interest in "anti-ageing" is paramount. The anti-ageing effects of polyphenols have been shown to mimic the effects of caloric restrictions; preventing chronic diseases characterized by inflammation and oxidative stress (34).

Due to its role as a central regulator of both lipid and glucose metabolism, AMPK is considered to be a potential therapeutic target for the treatment of type II diabetes, obesity, and cancer. AMPK has also been implicated in a number of studies as a critical modulator of ageing through its interactions with mTOR.

mTOR is a pathway which is activated by insulin growth factor-1 (IGF-1) and is associated with cellular growth. AMP kinase, conversely, is a pathway important in regulating cellular energy homeostasis by inhibiting the synthesis of fatty acids and triglycerides and activating fatty acid uptake and beta-oxidation in the liver.

Antimicrobial Potential

Several polyphenols of tea products have significant antimicrobial effects (e.g. EGCG); most notably green and white tea. The mechanisms of action for polyphenol antimicrobial properties are still not fully understood, but have been somewhat elucidated (35).

The susceptibility of bacterial strains to tea polyphenols has been shown to be related to the interaction with certain cell wall components; a result of the negatively charged polyphenol, such as EGCG, binding strongly to the positively charged lipid bi-layer of Gram-positive bacteria. Polyphenols partitioning in the lipid bi-layer membrane result in loss of cell structure, function, and finally in cell death.

Furthermore, polyphenols have been reported to exhibit antimicrobial activities by:

binding with protein-related polyamide polymers (36)
iron deprivation or hydrogen binding with vital proteins such as microbial enzymes (37)
toxicity following oxidized condensation of phenols

It has been postulated that the presence of the hydroxyl group members at 3', 4', and 5' on the B ring, and the gallic moeity, of the catechin and epicatechin molecules is a major factor contributing to the inhibitory activity of both green and white tea (Fig 10). The oxidation process involved in the production of black tea, however, means a reduction in antimicrobial properties resulting from a loss in the catechin polyphenols.

Relevance to Consumers

Before moving forward into the mechanisms behind the elucidated health benefits - especially from tea and kombucha polyphenols - in future posts, we would like to put things into context and take a look at what all of this means to the consumer.

Is the phenolic content uniform and are the unique content of phenolics important to consider?

Sure, rosemary and cacao might be vastly more dense in phenolic compounds than turnips, but there is much more to consider here before running to the store to buy a weeks supply of rosemary and chocolate to pack into your meals, and expecting great things. First of all, one can only consume so much of these phenolic-dense foods and secondly, these plants are not all created equal. Moreover, bioavailability and consumer genetics must be considered. At the risk of sounding like a broken record - we must be more granular in our assessment and keep our expectations realistic.

The potential health benefits of dietary polyphenols depend on their absorption and metabolism, which in turn are determined by their structure; including conjugation with other phenolics, degree of glycosilation/acylation, molecular size and solubility. As it has been demonstrated that some of the bioactive effects from polyphenol consumption can in fact be attributed, in part, to phenolic secondary metabolites, things become even more complicated. The extent to which these changes vary during passage through the wall of the small intestine, into the circulatory system and eventually into the liver and portal vein becomes paramount.

The metabolites of polyphenols are rapidly eliminated from plasma, thus, a significant daily consumption of plant products is essential in order to supply high enough metabolite concentrations in the blood. So what is a good baseline, or yardstick, for what constitutes a "significant" amount of polyphenols? Well, one could say a value that elicits a desirable toxicological response in your body; a topic which we have discussed in length, in previous posts (The Low-Down on Fermented Tea, Part II: Metabolism & Detoxification).

Unfortunately, there seems to be no consensus on such values, and there are many factors to consider (i.e. age, sex, genetics, diet, etc.). Not to mention, most often studies are carried out at levels which just are not achievable through a regular diet. Moreover, often the most abundant polyphenols in our diet aren't necessarily the most bioavailable.

Let’s illustrate this with some numbers. Take phenol dense berries - such as blueberries - which can contain between 100 and 150mg of polyphenols, per 50 grams fresh weight (approximate weight of one serving), and Japanese matcha green tea, which can have upwards of 900mg per serving (38). These sound great, right? Especially that matcha tea, why bother with the berries? Well, simply looking at the antioxidant level in a food and judging it as good is almost useless, and borderline irresponsible. This number says nothing of which polyphenols are present in the berries or matcha, and as you will see by the end of this set of posts, not all polyphenols behave the same way in the human body.

In most cases, foods contain a very complex mixture of polyphenols and there is no relation between the quantity of polyphenols in food and their bioavailability in the human body (2). In fact, the forms reaching the blood and tissues are different from those present in food and it is resultantly very difficult to identify all of the metabolites and their biological activity. Ultimately, it is the chemical structure of the polyphenols and not their concentration in our food which determines their impact on our health.

Bioavailability is the proportion of a nutrient that is digested, absorbed and metabolized through normal pathways (2).

Stay tuned for Part II on polyphenols to read more on this, and if that green tea is as desirable as it sounds with those high levels of polyphenols!

We chose words such as "irresponsible" and "desirable" as over-consumption of antioxidants, such a phenolic compounds, can inhibit several essential physiological processes which require oxidation to occur (i.e. tumor suppressor genes) (39,40). Moreover, each of these foods is loaded with other chemical components which must be considered when assessing their impact on our diets and health (e.g. sugars and caffeine). Unfortunately, we cannot simply cram as many antioxidants into our body as we wish and cure all ailments of ageing; biology is not so simple.

After considering the importance of the chemical structure, as well as the quantity, of polyphenols in our food, we would be amiss not to consider the state of the food itself. The quality, and quantity, of polyphenols found in plants will be drastically affected by: plant genetics, cultivar, soil and growing conditions, maturity state, post-harvest conditions and of course the state of the food when it is consumed (old wilting rosemary will have a reduced level of bioavailable phenolic compounds in comparison to fresh rosemary). The phenolic content of foods change during storage due to - you guessed it - oxidation (39,40,41,42,43). Such changes can be beneficial, as is the case with black tea (well, sort of) or harmful, as with browning of fruit (42, 44,45,46).

It has been shown that following six months of storage, wheat flour loses up to 70% of its phenol content.

Cooking also has a major effect on the concentration of phenolic compounds. Onions and tomatoes lose roughly 80% of their initial quercetin (a common phenolic compound) content after boiling for 15 minutes, and 30% after frying (43). Once again, however, we cannot limit our scope of analysis. In fact, proper sautéing (less than 5 minutes) of onions has been shown to increase the quercetin content. And if we look beyond phenolic content, cooking tomatoes actually helps to enhance the bioavailability of other nutrients within the fruit, namely lycopene (47,48). Not to mention the potent non-phenolic antioxidants created from the Maillard reactions (i.e. melanoidins) during cooking.

Lycopene is a compound that contributes to the red colour of fruits and vegetables and is a carotenoid antioxidant.

Lycopene is found in high amounts in tomatoes but is also present in watermelons, pink grapefruits, apricots, and pink guavas. Processing raw tomatoes using heat transforms lycopene to trans-lycopene, a form that has a higher bioavailability.

Additionally, the distribution of phenolics in plants at the tissue, cellular and sub-cellular levels is not uniform (2). Insoluble phenolics are found in the cell walls, while those which are soluble can be found in the cell vacuoles. That being said, the outer layers of plants contain higher levels of phenolics than those located at the inner parts (do you peel your fruits and vegetables?). Moreover, the degree of ripeness has a considerable effect on the concentrations and proportions of various phenolic compounds (41).

Conclusion

This post was intended to serve as an introduction to dietary plant phenolic compounds. Let’s summarize:

upwards of 8000 different polyphenols identified throughout plant species
plant polyphenols are secondary plant metabolites involved in defence & survival
biosynthesis occurs through phenylpropanoid & shikimate pathways
dietary polyphenols mainly found in fruits, vegetables, cereals, and beverages (e.g. berries, chaga, citrus fruit, cocoa, onions, broccoli, yerba mate, tea, coffee, wine)
contribute to bitterness, astringency, color, flavor, odor, and shelf-life
4 groups of plant polyphenols : phenolic acids, flavonoids, tannins & stilbenes
dietary plant polyphenols are of interest to human health
dietary plant polyphenols may play an antioxidative protective role through: hydrogen atom transfer, single electron transfer & metal chelations
cellular mechanisms modulated by polyphenols include: interaction with membrane proteins & phospholipids, regulation of signal transduction pathways, DNA methylation, modulation of metabolic enzymes, and cellular autophagy
antimicrobial effects of polyphenols likely due to cell membrane interactions
studies on biological effects of food polyphenols beginning to more clearly define underlying molecular, cellular, and physiological mechanisms
more in vitro and clinical studies needed to refine health benefits

In future posts we will investigate each class of dietary plant polyphenols individually. These investigations will include a more in depth look at: their biosynthesis, in what foods they are most common, their bioavailability and metabolism, and their potential impact on human health. This will ultimately lead into a discussion on tea, yerba mate, and chaga polyphenols; and finally segway into kombucha fermentation.

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