Expert answers to common questions
Questions and answers on Polyphenols
Polyphenols are claimed to have antioxidant properties and are as such suitable for partial replacement of vitamin E supplementation in animal diets. Despite showing antioxidant properties in vitro there is no scientific evidence in vivo. The discrepancy is mainly caused by the low bioavailability of polyphenols and the lack of accumulation in target tissues. The impact on meat quality traits measured through final oxidation products does not prove any equivalence with vitamin E. Moreover polyphenols do not play any role in immune stimulation or reproduction. Scientists agree that polyphenols can’t replace vitamin E.
Polyphenols are a large and heterogeneous class of compounds, with more than 8000 known in plants. They are usually classified as flavonoid or non-flavonoid, and the most common chemical form is glycoside.
They protect plants against harmful environmental conditions (e.g. UV radiation), attack by microorganisms and herbivores. In addition they contribute to the development of several other characteristics (e.g. color).
We are talking about several thousand types of compounds and it is virtually impossible to define common properties. Polyphenols show large differences in physical (e.g. stability in thermal feed processing), chemical and biochemical properties (e.g. behavior at the gut level and at different gut pH, absorption, etc.).
Polyphenols are not well absorbed. Typical oral bioavailability is 10% or less, with a range of 2–20% being quite common. The glycoside form (very polar large molecules) reduces the passage through membranes. Even the aglycone form, produced after the removal of the glucose molecule by enzymatic action in the gut, does not improve absorption as these compounds generally have poor solubility (Hu M., 2007).
Their low bioavailability is supported by the fact that polyphenols, in in vivo trials, were not detected in tissues. There has not been any research done to understand the mode of action of the polyphenols at the cellular level.
Polyphenols may bind to proteins, amino acids, carbohydrates, enzymes and trace-elements, forming complexes within the digestive tract. This binding property, coupled with the amount of polyphenol ingested may either exert beneficial effects or may negatively affect the host.
Polyphenols are poorly conserved in the body (less than 5%), with most of what is absorbed, as chemically modified metabolites, rapidly excreted. Overall it’s clear that the body sees polyphenols as foreign compounds or xenobiotic and is trying to get rid of them (Halliwell et al., 2007).
Most of the early research focused on the antioxidant function of polyphenols. However, this is no longer the case. Modern research is actually oriented in studying other aspects such as the direct effect of these compounds on intestinal cells.
Massive research carried out in the last 20 years indicates that in vitro polyphenols are good antioxidants (and can influence the measurement parameters like ORAC value) but antioxidant effects in vivo are negligible or absent and data are confusing and equivocal. Moreover the chemical structure of various polyphenols indicates that they cannot be considered as antioxidants, since under certain reaction conditions they can also display prooxidant activity.
Research has clearly established that the transfer of in vitro data (e.g. ORAC assay values) in vivo is definitely not straight forward or even meaningless. Such an approach does not consider that “in between” there is a living organism! In other words: in vitro, polyphenols are in contact with substrates used for measuring the antioxidant effect whilst in vivo they must be ingested, absorbed and then display their antioxidant function. Therefore low bioavailability may explain the large differences.
The answer lies in very simple evidence: the maximal plasma concentrations, even after high levels of polyphenol intake, are usually low and therefore insufficient to exert significant systemic antioxidant effects (Hu M., 2007).
Plasma total antioxidant capacity is > 103mmol/L. A statistically significant increase would therefore require a minimum of 20–50 mmol/L extra antioxidant to be present. Concentrations of polyphenols found in vivo, even with high dietary intakes, are far below this, usually<1 mmol/L (Halliwell et al., 2005). The conclusion is quite obvious: dietary polyphenols have little or no direct antioxidant food value following digestion.
Because what we measure is not caused directly by the polyphenols, but most likely results from increased ascorbate and urate levels derived from metabolism of flavonoids and increases in urate concentration are not necessarily beneficial (Halliwell et al., 2007).
Yes, but other than the dietary antioxidant vitamins, i.e. vitamin A, vitamin C and vitamin E, no food compounds have been proven to have antioxidant efficacy in vivo. Regulatory agencies around the world have published guidelines disallowing food product labels to claim or imply an antioxidant benefit based on in vitro data only (e.g. ORAC values). Such physiological evidence must also be proven in vivo.
If polyphenols are not antioxidants, why has there been such so much focus by researchers on these compounds?
Little is known in vivo about the functions of polyphenols at the tissue and cellular level. Polyphenols may exert direct effects within the gastrointestinal tract. For example they may bind pro-oxidant iron, scavenge reactive nitrogen, chlorine and oxygen species. Reports on polyphenol activities have been largely associated with enzyme inhibition and proliferative activity, which are dependent on their particular molecular structures. Therefore polyphenols can have an antioxidant function in the gut environment but this is not directly comparable to the antioxidant effect of vitamin E, vitamin C or Glutathione.
Commercial products (Nor-Grape, Grape PP Concentrate, Proviox and Trouw AO-mix) are basically grape extracts containing different polyphenols. Their composition, extraction methods, chemical structure or biological properties are not disclosed.
There is no reliable method for controlling these products. This implies that is not possible to ensure that the commercial products have a constant composition. As they are produced by extraction, variability is expected to be high. The Product Data Sheets of some commercial products at times give information on protein, ash, calcium and sodium values but say nothing about the polyphenol content. In some other cases a very generic level of polyphenols (e.g. >3.8%) are given. In both cases a user cannot be sure what he or she is using.
From a Regulatory perspective, it appears even stranger, as the analytical method is usually a must for complying with international quality control standards.
Commercially available products made of polyphenols are claimed to be an effective (partial) replacement of vitamin E: what’s the basis for such a claim?
It’s a very flawed and speculative suggestion since there is no data on polyphenol content in muscle cells. It has clearly been documented in scientific papers that polyphenols are not sufficiently absorbed. Even if found in muscle cells, the active concentration would be much lower than necessary to provide antioxidant protection. The absence in cells also implies that polyphenols cannot have any effect on immune stimulation and reproduction. It is not possible that polyphenols can replace vitamin E.
But some research in poultry and livestock suggests that polyphenols can replace vitamin E improving meat quality traits: how is it possible?
It is well known that lipid peroxidation in muscle depends on a range of factors (e.g. amount and composition of lipids, concentration and distribution of iron and copper possessing pro-oxidant properties, etc.). The few published data on polyphenols provide information about the final product of lipid peroxidation (MDA). Its reduction is most probably due to the fact that polyphenols can bind iron and copper in the gastrointestinal tract, reducing the formation of activated oxygen measured by a decreased MDA. In practice this effect has nothing to do with the well documented activity of vitamin E in protecting cell membranes.
Attempts to replace vitamin E in the animal (and human) diet with polyphenols and other plant extracts have no scientific basis to substantiate the claims. In the few available animal trials the replacement of vitamin E by polyphenols was normally done at high supplemental vitamin E levels. What is actually required, is to conduct the replacement study with the condition of a commercial standard supplemental level of vitamin E.
Vitamin E is well recognized and accepted as nature’ s most effective lipid-soluble, chain-breaking antioxidant, protecting cellular membranes from being attacked by lipid peroxyl radicals.
Although primarily known as an efficacious biological antioxidant, the physiological importance of vitamin E is much broader:
- it is required for normal growth and reproduction
- it helps to maintain the structural integrity of all tissues
- it supports the development of the nervous system and substantially contributes to optimum health and disease resistance of farm animals due to its modulating effects on the immune system
- it safeguards events in case of disease outbreaks or stress related happenings (high density, handling etc.)
- it plays an important role in enhancing the nutritional value and the organoleptic properties of meat and eggs
|Action||Vitamin E||Plant extracts (polyphenols)|
|Composition||Well defined, tocopherols||Variable, 1000 of various compounds|
|Absorption||Well defined, small intestine||Poorly absorbed|
|Tissue metabolism||a-tocopherol is active form after supplementation||Quickly transformed in various metabolites|
|Delivery to target tissues||Effectively delivered||Negligible concentration in target tissues|
|Effect on nutrient digestion||Improves digestion of many nutrients||Decrease digestion of many nutrients (fats, protein)|
|Antioxidant (AO) properties||Main chain-breaking biological AO; well proven||Depending on condition can be AO or pro-oxidant|
|Effects on immunity||Positive on immune competence||Not consistent effects on immune competence|
|Effects on egg/ova and female reproduction||Positive effect; well documented||No proven effects|
|Effects on sperm male reproduction||Positive effect; well documented||No proven effects|
|Effects on meat quality||Positive effects; well documented||Some positive effects but mode of action still inclear|