Vitamin E: irreplaceable nutrient for science

The multiple essential functions of vitamin E in animal nutrition were reviewed in the article Vitamin E: more than nature’s most powerful antioxidant. Vitamin E is the most effective lipid-soluble chain-breaking antioxidant, it maintains the tissue’s structural integrity, supports neural growth and reproduction as well as modulating immunity. It also enhances meat quality, the nutritional value and the organoleptic properties of meat and eggs.

This article will review the current scientific knowledge behind the hypothesis of replacing vitamin E with other compounds. Phytochemicals, emphasis polyphenols, have been extensively studied for their antioxidant properties in human nutrition and health but overall results failed to prove their antioxidant properties. The current research focus has shifted to other functionalities like signaling molecules or gut health influencers. In addition, the bioavailability of polyphenols is generally low, making their potential effect in the body questionable. In animal nutrition, a partial replacement of dietary vitamin E with polyphenol-based extracts has been proposed, claiming antioxidant properties and immune function. As human-oriented trials did not prove such an effect, by analogy, currently animal research tends to look in the same direction. Thus, vitamin E should be considered a key player of the antioxidant system in living organisms, and it cannot be recommended to replace this essential nutrient in the diet with polyphenols. It remains to be elucidated if dietary polyphenols can play a role  in gut ecology and health of monogastric animals.

As described in the article “Vitamin E: more than nature’s most powerful antioxidant”, vitamin E possesses multiple functionalities, most of them centered around its well documented and proven effect as free radical scavenger, hence a very peculiar antioxidant function. In addition, the multiple functionalities of vitamin E reflected with most symptoms of deficiency related to disorders of the cellular membrane, due to the oxidative degradation of polyunsaturated fatty acids, indicate that vitamin E is the most effective lipid-soluble, chain-breaking antioxidant in the living organism. In human nutrition, plant phytochemicals, a large group of compounds including polyphenols, have attracted the attention of the scientific community for many years. Being present in many food items and wine, their function has been associated with antioxidant properties: but is it true?

Polyphenols are a family of around 8,000 compounds usually clustered as flavonoids – the largest family - and non-flavonoids (Manach et al., 2004). Amongst different functionalities attributed to polyphenols, their antioxidant properties have attracted the interest of scientists (Fig.5). In addition, consumer interest on these compounds started because of the so-called “French paradox”, the apparently paradoxical epidemiological observation that French people have a relatively low incidence of coronary heart disease (CHD), while having a diet relatively rich in saturated fats. It has been suggested that France's high red wine consumption is a primary factor in the trend because of one of the components of red wine potentially related to this effect is resveratrol, a polyphenol. It has however been shown that the amount of resveratrol and other polyphenols absorbed by drinkers of red wine is minimal and that it is unlikely to explain the paradox (Ferrières, 2004). Despite several years of epidemiological and intervention studies, the evidence for in vivo antioxidant effect of polyphenols in red wine remains confusing and equivocal (Halliwell et al., 2005; Croft, 2016).

For some years, and sometimes still today, in vitro measurements of antioxidant efficacy of polyphenols and other substances has been extensively used. Values of antioxidant capacity measured for example with the ORAC (oxygen radical absorbance capacity) technique have been used by private companies to promote their products - and by consumers to guide their food and dietary supplement choices – and published by independent bodies. Later it has been recognized that in vitro measurements do not reflect the in vivo properties and rankings based on in vitro assessments have been withdrawn and not considered scientifically sounding (USDA, 2016).

The main reason for the discrepancies between in vitro and in vivo can, according to most scientists, be ascribed to the low bioavailability of polyphenols and hence the very limited plasma concentration, clearly insufficient for exerting significant antioxidant effects in the system (Halliwell et al., 2005). In fact, maximal concentration of flavonoids in plasma after absorption via the gastrointestinal tract would not exceed 1mmol/L (Halliwell et al., 2005). This concentration is far below the total plasma antioxidant capacity in humans, which measured by a range of assays is >103 mmol/L (Halliwell and Gutteridge 2007).

Some authors have drawn quite straightforward conclusions stating that dietary flavonoids cannot be significant antioxidants in humans (Frei, 2009). In July 2008, the FDA republished guidance for industry using antioxidant claims and stated that “as only dietary vitamins A, C and E are verified as physiological antioxidant nutrients, just these vitamins-not polyphenols-qualify for an antioxidant nutrient claim” (FDA, 2009). The same position has been taken in Europe by the European Food Safety Authority in different opinions (EFSA, 2010).

It has been postulated that the increased antioxidant capacity measured in vivo in blood after ingestion of polyphenols could be caused by the increased concentration of plasma antioxidants like urates, an effect which cannot not be considered only beneficial since elevated urate level may be a risk factor for some diseases (Halliwell, 2003).

There are clear gaps in human nutrition between observational studies and intervention trials using food extracts or pure polyphenol compounds (Croft, 2016). Most recent hypothesis are based either on considering polyphenols signaling molecules, playing a role in anti-inflammatory processes or on assessing the effect of these molecules on gut microbiota (Williamson and Clifford, 2017).

First of all, it must be noticed that in animal nutrition most of the research has been conducted with the use of mixtures of many polyphenolic compounds – like those found in grape or pomace extracts – more than single flavonoids, which is predominant in human intervention studies.

Moreover, most animal studies did not measure bioavailability in different animal species. Most studies have applied in vitro measurements like ORAC ex vivo techniques as assessment of the antioxidant capacity of the extracts used: hence in both cases bioavailability has not considered.

Finally, most of the intervention studies in poultry and swine have compared performance and some other parameters like meat quality such as oxidative stability of muscles of animals receiving medium-high levels of vitamin E against other fed with diets containing polyphenols and still a generous supplementation with vitamin E. In these studies, vitamin E was partially replaced with grape or pomace extracts but most of the time maintaining a dietary vitamin E level much above minimum requirements (Lipinsky et al., 2017).

The lack of statistical significance on animal performance, and in parallel same oxidative stability of meat measured with Thiobarbituric Acid Reactive Substances (TBARS) technique has been taken by some authors as demonstration that these citrus fruit extracts can effectively replace part of vitamin E. It is not surprising that a reduction of some 30% of generous vitamin E supplementation does not exert impact on performance in healthy animals, as vitamin E levels above physiological requirements are not expected to enhance growth. Moreover, the claimed protective effect on meat oxidative stability by grape or pomace extracts could have been indirectly caused by the presence of higher uric acid concentration or of other substances - a known consequence of dietary polyphenols - interfering with techniques like FRAP and TBARS. In general, those techniques are not considered reliable for investigating antioxidant activity in vivo, and therefore studies on polyphenols claiming antioxidant activity in vivo based on this technique should be taken with serious caution.   

In a recent and extensive review of intervention studies with polyphenols in poultry and swine (Lipinski et al., 2017) it has been concluded that “polyphenols exert an ambiguous effect on nutrient digestibility and animal performance”. Not considering possible interference of secondary metabolites on meat quality parameters the authors postulate an effect on this aspect but, having observed results when associated with vitamin E, it remains unclear what intervention is really driver of the beneficial effects. Final recommendation calls for additional research on polyphenols in animal nutrition.

Given their low absorption, it seems likely that the gut it the primary site for antioxidant action of polyphenols.  Gut health has become a subject of increasing interest in pig and poultry research. The gut is the main site of potential exposure to pathogens, and when gut function is impaired because of infectious diseases, nutrient digestion and absorption is affected, which compromises animal performance.

It was recommended already in 2005 that greater attention of the biological effects of the polyphenols and their metabolites in the gastrointestinal tract should be given (Halliwell et al, 2005). A recent review (Bradbury et al. 2018) still attributes antioxidant functionalities to polyphenols more for historical reason but focuses most on gut health modulating properties, including the composition of the commensal microflora towards higher proportion of beneficial bacteria; and anti-bacterial effects on pathogens. In their survey, Dueñas et al. (2015) summarized studies in animals with the effect of polyphenols on the modulation of the intestinal microflora. For instance, in pigs, the administration of tea polyphenols increased the levels of lactobacilli whilst diminishing the levels of total bacteria and Bacteroidaceae (Hara et al., 1995). Furthermore, some studies have obtained a positive effect of dietary polyphenol-rich plants on performance of pigs, and this effect has been ascribed to an alteration in the microbial composition and anti-inflammatory effects on the intestine. In the colon, polyphenols are broken down to metabolites, of which the microbial degradation results in high concentration of phenols rather than flavonoids (Halliwell et al, 2005). Theoretically, an antioxidant function of polyphenols may protect vitamin E and C from oxidation when present in the small intestine prior to their absorption, however, this requires more well-controlled studies to verify this.

To the best of our knowledge, no subsequent studies are available addressing the importance of polyphenols for monogastrics that could lead to different conclusion than stated in an interesting and extensive paper on this topic (Surai, 2013), and in agreement with findings in human nutrition: “antioxidant properties of polyphenols/flavonoids observed in in vitro systems are convincing but…. antioxidant activities of polyphenols/flavonoids in in vivo biological systems are not straightforward depending on multiple factors like the efficiency of absorption, the active concentrations in the target tissues, which are extremely low and metabolic transformation”.

It looks reasonable to conclude that the functionalities of vitamin E  are peculiar and its supplementation in feed is recommended at higher levels than minimum requirements in order to benefit of its multiple functionalities. Based on the existing knowledge we would like to remind that the network of antioxidants in the body does not call for replacement of one antioxidant with another but supply all the required elements for the antioxidant system to ensure an efficient protection of the body towards oxidative stress.