Vitamin E is an effective antioxidant that helps to protect against ageing and disease. It is, however, also expensive – especially when you consider that its bioavailability is limited. A good alternative to addressing the issue of oxidative stress is the use of natural polyphenols. When carefully blended, these can not only partially replace vitamin E in animal feed, they also make it possible to boost antioxidant defences beyond the capabilities of vitamin E alone.

Free radicals – the cause of oxidative stressThe production of free radicals, which cause oxidative stress, is a natural result of day-to-day metabolism. Most notably during energy (ATP) production, large amounts of superoxide, hydrogen peroxide and hydroxyl radicals are formed. An animal’s growth rate and health status influence free radical production. Periods of rapid growth go hand-in-hand with higher metabolic activity, which results in exponentially increasing oxidative stress.

When there are health issues, the immune system generates extra free radicals to kill invading bacteria or viruses. This, however, also increases oxidative stress, which negatively impacts animal health.

Oxidative stress results in tissue damagesFree radicals are reactive, and can attack and damage cell membranes, proteins and DNA. Cell membranes can lose their fluidity, which affects nutrient transport. Proteins can lose their structure and their ability to catalyse reactions. DNA can be altered or broken, which leads to translational errors. All of these forms of free-radical damage can have serious implications for an animal’s overall health, vitality and productivity.

Figure 1: Antioxidant defences in a cell (modified after Surai, 2007)

Oxidative stress is managed by enzymes, antioxidants, and damage repairThere are two key ways to combat free radicals and prevent oxidative stress (Figure 1). The first line of defence consists of enzymes that can convert free radicals into water and oxygen. Examples of such enzymes are catalase, superoxide dismutase and glutathione peroxidase (a selenium-containing enzyme). The second line of defence – which we are focusing on here – consists of antioxidants, such as vitamin E and C, lipoic acid and glutathione.

Polyphenols: a natural antioxidant alternative for vitamin E

Trial report

NUCLEUSLysosomes

Mitochondria

GSH-PX (Se)

GSH, Lipoic acid

Polyphenols

Cu, Zn-SOD

Mn-SOD

Catalase

Vitamin C

GSH-Px (Se)

Vitamin E,carotenoids,ubiquinols

Peroxisomes

DNA

Vitamin E

Membranes

Antioxidants

Enzymes

PH-GSH-Px

Antioxidants neutralise free radicalsAntioxidants are molecules that are capable of ‘donating’ a hydrogen atom, which neutralises free radicals. For example, vitamin E’s key feature (Figure 2) is a benzene ring with a hydroxyl group attached. Because the electrons in this benzene ring are mobile, the hydrogen in the hydroxyl group can be split off to neutralise a free radical. Beyond this, vitamin E has a long lipophilic tail because of which it behaves as a fat both in digestion and in the body.

potential (Figure 3). Not all of these polyphenols, however, are suitable as one-on-one replacements for the antioxidant function of vitamin E. Bioavailability, radical affinity, tissue distribution and metabolism need to be considered as well.

Figure 3: Molecular structure of Naringenin

Vitamin E – gene regulator first, antioxidant secondWhen considering vitamin E’s role in nutrition, its antioxidant function is usually seen as the most important. This, however, is not the case: its function as a gene regulator is even more crucial – nothing can replace vitamin E in this role. But in preventing and fighting free-radical damage, other antioxidants can easily act as a vitamin E substitute – and sometimes even more effectively – providing they can act in the same cellular location and with a similar affinity for free radicals.

Vitamin E – a handicapped ally Using other antioxidants in the battle against free radicals can actually deliver even better results, since the synthetic vitamin E of the type customarily used in animal nutrition is a rather handicapped ally. This synthetically produced blend contains eight stereo-isomers, but only one of these is natural vitamin E with its desirable benefit of good bioavailability (and this is only so if incorporated in a high-fat diet). The other seven stereo-isomers, however, are not well recognised by the liver, and are predominantly returned to the intestinal tract. In fact, the actual bioavailability of synthetic vitamin E is only 33% for swine and 12% for cattle. A second handicap of vitamin E is that its half-life decreases with increasing doses. In practice, this means it is nearly impossible to reach plasma levels higher than three times baseline level.

In order to ensure a high level of antioxidant defence for animals (particularly those that are rapidly growing or health challenged), it is paramount to focus on combining a variety of antioxidants that act in synergy and complement each other, and which do not induce their own degradation.

Polyphenols: potent alternatives to vitamin EIn nature, there is a specific range of plant compounds with antioxidant potential: the polyphenols. As the name implies, the basic structure of these compounds includes a phenol group just like vitamin E. The antioxidant potential of polyphenols has long been known; nearly a century ago, they even came close to being classified as vitamins because of the antioxidant protection they offered in some diseases. Even more interesting, within the polyphenols range there are compounds that have more hydroxy groups attached to benzene rings per unit of weight than vitamin E does – which means they have an even higher antioxidant

Bioavailability crucial to antioxidant effectivenessThe bioavailability of polyphenols is a crucial factor that has not yet received much attention until now. It is important to take this into consideration for two reasons. First, because it is not an antioxidant’s oxygen radical absorbance capacity (ORAC) that determines the level of free-radical protection delivered, but the dORAC – the amount of the ORAC that is actually absorbed. And second, because the monogastric and ruminant digestive systems are quite different.

In ruminants, Nutreco found that bioavailability is directly linked to the polyphenol’s susceptibility to fermentation in the rumen, the type of fermentation products produced, and the bioavailability of bypass polyphenols or polyphenol fermentation products. For instance, naringenin, which is found in citrus, can bypass fermentation in the rumen and has good bioavailability in the small intestines. In contrast, proanthocyanidins are too large to be digested in the small intestines and depend on fermentation to yield absorbable antioxidants. In short, both the substrate and fermentation conditions affect how much bio-efficacy will result – if any.

For the monogastric digestive system, the polyphenols need to be selected based on digestibility and intestinal absorption. For instance, studies indicate that rosmarinic acid and resveratrol have good bioavailability, while grape-based proanthocyanidins yield virtually no usable antioxidants (Figure 4).

Figure 4: Vitamin E50% and various polyphenol sources evaluated and compared by ORAC, bioavailability, and the resulting dORAC values in monogastrics

Figure 2: Molecular structure of vitamin E

ORAC9.000

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Vitamin E-50 Grape Curcumin Resveratrol Rosmarinic

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ioxi

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nt c

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ty

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C in

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ol/

kg)

Bio

ava

ilab

ility

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dORAC bioavailability

Species-specific approach for maximum bioavailabilityBecause of the major differences between monogastrics and ruminants in the bio-efficacy of polyphenols, Nutreco formulated species-specific alternatives to vitamin E. For ruminants, plant extracts were selected which either contain bypass polyphenols or which are fermented into potent and bioavailable polyphenols. For monogastrics, plant extracts were selected in which the polyphenols have a good digestibility. The resulting products are capable of substituting and/or complementing the antioxidant protection that most livestock currently get from vitamin E – with the fringe benefit that they bypass the diminishing returns of higher doses of vitamin E. Because of this, a higher degree of antioxidant protection is possible than with vitamin E alone. In vivo trials confirm efficacyAnimal trials have proven that this works in practice as well as in theory. A trial in which sheep were fed a diet high in unprotected linseed oil showed that our polyphenol blends both delayed and slowed down the rate of fat peroxidation. In trials with poultry and pigs (Figure 5), animals fed on our polyphenol blends that experienced heat stress did not suffer from a related increase in oxidative stress in line with what a high dose of vitamin E would achieve. Most importantly, field experience has proven that part of vitamin E can be safely and effectively replaced with Selko AOmix.

Bioavailable polyphenols – an effective alternative to vitamin EIn summary, polyphenols that are carefully selected taking into consideration the differences in digestive physiology, radical affinity, and tissue distribution can provide/meet the antioxidant needs of an animal currently met by vitamin E. This results in a multi-pronged approach that offers broader protection against free radicals.

Selko is a brand of Trouw Nutrition, a Nutreco company. This trial report is supported by Trouw Nutrition R&D. For more information www.selko.com

Footnotes:

ORAC = oxygen radical absorbance capacity, an in-vitro measure of

antioxidant capacity obtained using biologically-relevant

free radicals

dORAC = digestible oxygen radical absorbance capacity

(ORAC x bioavailability)

MDA = Malondialdehyde, one of the most frequently used indicators of

lipid peroxidation, and a marker for oxidative stress

MDA pre-stress

*

9.0

8.5

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Vit E, 80 ppmControl, 11ppm 11E + AO mix

MDA post-stress

MD

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naly

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as

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DA

))

Figure 4: Vitamin E50% and various polyphenol sources evaluated and compared by ORAC, bioavailability, and the resulting dORAC values in monogastrics