Feed additives

Nutritionals – Vitamins, Minerals (Oligominerals), Aminoacids

ProNutritionals – Antibiotics, Probiotics, Prebiotics, Enzymes, Emulsifiers, Antioxidants..
Technologicals (Non-Nutritionals) – Flavours, Sweeteners, Preservatives (Mould / bacterial
inhibitors), Binders/Pelletants, Pigments..
Medicinals (Prophilactics) – Anticoccidials, Botanicals (plant extracts..)
Feed additives are materials that are administered to animals to enhance the effectiveness of nutrients and
other many reasons: enhance production (quantity/quality), prevent health, environment, efficiency-money...
There are clear theoretical reasons why these additives should be effective
but it is often difficult to demonstrate the effects in practice.
Less than 1% in feed, usually... Conditions: Efficiency, Economy, Safety.

1 ANTIBIOTICS
Antibiotics are chemical compounds that, when given in small amounts, halt the growth of bacteria.
They are produced by some microorganisms (fungi), and similar substances are now also synthesised.
Normally, they are used at therapeutic levels, by injection or in food or water, to treat diseases caused by
bacteria. In addition, subtherapeutic levels of antibiotics are added to the food to enhance the rate of growth.
The various groups of antibiotics act in different ways to reduce the numbers of specific bacteria in the gut,
and thereby increase the efficiency of nutrient utilisation. This is brought about by:
- reduction or elimination of the activity of pathogenic bacteria that may cause subclinical infection, thus
allowing the host to achieve production levels closer to their potential;
- elimination of bacteria that produce toxins that reduce the growth of the host animal;
- stimulation of the growth of microorganisms that synthesise unidentified nutrients;
- decrease the thickness of the intestinal wall and increase absorptive capacity of the small intestine.
These effects may be coupled with a reduced turnover of mucosal cells and reduced mucous secretion. The
gut accounts for a large proportion of the energy and protein required to maintain an animal, and any
reduction in the mass of the gut and cell turnover will release nutrients for other purposes such as growth.
Ionophore antibiotics case: These interfere with the electrolyte balance (Na/K) of the bacterial cell by
transporting potassium into the cell, which then requires energy to pump it out. Eventually the ion pump fails
to operate efficiently and potassium accumulates inside the cell; water enters by osmosis and the cell
ruptures. Monensin sodium is an example of this type of antibiotic.
Antibiotic growth promoters have been used mainly in pig and poultry foods, typically at levels of 20–
40 mg/kg, which give improvements of 4–16 % in growth rate and 2–7 % in efficiency of food conversion.
The response is greatest in young animals and animals consuming diets containing vegetable protein rather
than animal protein. Mortality in young pigs is also reduced. The effect is less in healthy herds and flocks.
Pre-ruminant calves also respond to growth-promoting antibiotics in the same manner as non-ruminants.
Since ruminants depend primarily on bacteria in the rumen for their nutrient supply, the use of antibiotics in
ruminant diets might be considered to be disadvantageous. However, certain antibiotics of the ionophore
type (e.g. monensin sodium) have been found to be effective, particularly with low-roughage/high-
concentrate diets, in controlling the proportion of undesirable bacteria in the rumen without disturbing the
overall fermentation. There are small changes in the fermentation, however, such as reduced methane
production and increased propionic acid proportions, which improve productivity. Monensin sodium at 20–30
mg/kg of food improves the efficiency of food conversion by increasing the rate of gain with the same food
intake or by maintaining the rate of gain at a lower food intake. Amino acid degradation is decreased and the
additional propionic acid may, under certain circumstances, spare amino acids for gluconeogenesis.
The widespread use of antibiotics coupled with the ability of resistant bacterial strains to evolve over
a short period of time and transfer resistance to other strains has resulted in populations of bacteria that are
resistant to many antibiotics. This has limited the effectiveness of antibiotic treatment against disease and,
whereas at one time a bacterial infection could be treated with a range of antibiotics, now some bacteria are
sensitive to a single antibiotic only. There is concern that if such bacteria gain resist-ance to this antibiotic,
then the disease becomes untreatable. For this reason, the use of antibiotics as growth promoters has been
curtailed by legislation in last years, and in the EU the use of antibiotics as growth promoters is banned.
 Another material that enhances the growth of pigs, and is thought to act via the antibacterial effects
described above, is copper. When added to their food, as copper sulphate, at levels far in excess of the
requirement for normal functions (e.g. 200 mg Cu/kg compared with 5 mg Cu/kg), pigs grow faster.
Concern over the accumulation of copper in the environment, and the potential toxic effect of
applying manure of high copper content to pasture grazed by sheep, has resulted in legislation in the EU to
control the amount of copper that may be added to pig foods. The food of young pigs up to 12 weeks of age
may contain 170 mg Cu/kg, but this must be reduced to 25 mg/kg thereafter, as for other classes of pig.

2 PROBIOTICS
In contrast to the use of antibiotics as nutritional modifiers, which destroy bacteria, the inclusion of
probiotics in foods is designed to encourage certain strains of bac-teria in the gut at the expense of less
desirable ones.A probiotic is defined as a live microbial food supplement that beneficially affects the host
animal by improving the intestinal microbial balance.Although the digestive tract of all animals is sterile at
birth, contact with the mother and the environment leads to the establishment of a varied microflora. The
beneficial microorganisms produce enzymes that comple-ment the digestive ability of the host, and their
presence provides a barrier against invading pathogens. Digestive upsets are common at times of stress
(e.g. weaning), and feeding desirable bacteria such as Lactobacilli in these situations is preferable to using
antibiotics, which destroy the desirable bacteria as well as the harmful species.
It has been suggested that the desirable bacteria exert their effects in a number of ways:
A. Adhesion to the digestive tract wall to prevent colonisation by pathogenic micro-organisms:
Detrimental bacteria, such as E. coli, need to become attached to the gut wall to exert their harmful effects.
Attachment is achieved by means of hair-like structures, called fimbriae, on the bacterial surface. The
fimbriae are made up of proteins, called lectins, which recognise and selectively combine with specific
oligosaccharide receptor sites on the gut wall. Lactobacilli successfully compete for these attachment sites,
as shown in next Figure:
Pathogenic bacteria vs. Non-pathogenic bacteria

(a) Gut wall

(b) Gut wall and Pathogenic vs. Non-pathogenic bacteria

Fig. 1. (a) A mixed population of bacteria with substantial attachment of pathogenic bacteria.
(b) Competitive exclusion of pathogens due to preferential attachment of non-pathogens. It should be noted that
the recognition of receptor sites (carbohydrates) by the bacterial fimbriae (lectins) is very specific to different types of organism .
(Adapted from Ewing W N and Cole D J A 1994 The Living Gut)

B. Neutralisation of enterotoxins produced by pathogenic bacteria that cause fluid loss: There is
some evidence that live probiotic bacteria can neutralise these toxins, but the active substance has not been
identified.
C. Bactericidal activity: Lactobacilli ferment lactose to lactic acid, thereby reducing the pH to a level
that harmful bacteria cannot tolerate. Hydrogen peroxide is also produced, which inhibits the growth of
Gram-negative bacteria. It has also been reported that lactic acid producing bacteria of the Streptococcus
and Lactobacillus species produce antibiotics.
D. Prevention of amine synthesis: Coliform bacteria decarboxylate amino acids to produce amines,
which irritate the gut, are toxic and are concurrent with the incidence of diarrhoea. If desirable bacteria
prevent the coliforms proliferating, then amine production will also be prevented.
E. Enhanced immune competence: Oral inoculation of young pigs with Lactobacilli has elevated
serum protein and white blood cell counts.This may aid the develop-ment of the immune system by
stimulation of the production of antibodies and increased phagocytic activity.
Other postulated effects include beneficial interaction with bile salts, increased digestive enzyme
production, more efficient absorption of nutrients, and greater vitamin production.
 In a review of the response of pigs of various ages to the administration of probiotics, it was concluded
that probiotics were effective for young pigs, in which the digestive tract is still developing after weaning.
However, probiotics were less effective for growing and finishing pigs, which already have a balanced
population of microorganisms. To be effective, the desirable microorganism should not be harmful to the host
animal, should be resistant to bile and acid, should colonise the gut efficiently, should inhibit pathogenic
activity, and should be viable and stable under manufacturing and storage conditions.
In monogastric animals, strains of Lactobacilli, Bacillussubtilis and Streptococci have been used as
probiotics. In ruminant animals, the application of yeast (Saccharomyces cerevisiae) in the form of live
culture, or dead cells with culture extracts, has proved successful in beneficially modifying rumen
fermentation.
In ruminants, yeast cultures can stimulate forage intake by increasing the rate of digestion of fibre in the
rumen in the first 24 hours after its consumption. Overall digestibility is not affected. It is likely that this
improvement in early digestion and intake is brought about by alterations in the numbers and species of
microorganisms in the rumen. The precise means by which the effect is achieved have not yet been
confirmed, but there are a number of probable mechanisms (Figure 2).

Removal of starch /sugars Lower lactic acid production Buffering action

Improved rumen pH stability

Fig. 2 Suggested modes of action of yeast cultures in the rumen.

(Adapted from Offer N W 1991 Yeast culture: its role in maximising fibre digestion in the rumen. FeedCompounder Jan. 16–19.)

It is thought that metabolites of dead and live yeast cells (B vitamins, branched-chain fatty acids, amino
acids and peptides) stimulate the growth of the bacterial species Megasphaera elsdenii. This utilises the
lactic acid produced from the rapid fermentation of starch and sugars associated with high-concentrate diets.
Live yeasts ferment sugars derived from the degradation of starch, thus competing with the lactic-acid-
producing bacteria, and thereby stabilise rumen pH and reduce the risk of acidosis. Live yeast cultures also
scavenge oxygen in the rumen, helping to maintain anaerobic conditions and favouring the growth of
cellulolytic bacteria. The increase in forage intake can result in improved liveweight gain, milk yield and milk
fat content, although the effects are often small in dairy cows. The addition of yeast to intensive beef diets
has increased daily liveweight gain and food conversion efficiency. Improved fibre digestion has also been
reported in horses when yeast cultures have been given.
3. PREBIOTICS

3a ORGANIC ACIDS
Efficient digestion of food in young pigs depends on the secretion of sufficient acid in the stomach.Acid
additives have been used mainly in the diets of early-weaned pigs. Here their use relates to the digestive
physiology of the young pig and the replace-ment of sow’s milk with solid food at weaning. The suckled piglet
obtains nutrients on a little-and-often basis,sucking about once every hour. The milk clots in the stom-ach,
and the limited secretion of hydrochloric acid is augmented by lactic acid produced from the fermentation of
lactose by Lactobacilli. This ensures that the pH falls to a level that favours efficient protein hydrolysis and
suppresses harmful bacteria. Thereafter, there is a steady release of nutrients from the clot to the small
intestine. The solid food presented at weaning is less digestible than milk, is consumed in larger, less
frequent meals, and has a higher buffering capacity. The limited hydrochloric acid production is not sufficient
to ensure that the pH falls to a level that prevents the growth of pathogenic bacteria. In addition, the nutrients
may overload the immature digestive and absorptive capacity of the small intestine, and their fer-mentation in
the hind gut results in diarrhoea.
In order to overcome these problems, acids have been added to weaning diets to augment gastric HCl,
giving a rapid fall in pH with beneficial effects on protein di-gestion and the gut microflora. Although inorganic
acids have been used to supply hydrogen ions, and hence reduce pH, organic acids have additional
desirable proper-ties. In their salt form, they are odourless and easy to handle; they lower the pH and acid
binding capacity of the food; and the anion has an antimicrobial effect on moulds and bacteria in the food,
thereby improving food quality. The anion has been reported to act as a complexing agent for cations, such
++ ++
as Ca and Mg , thus improving their retention. It is also suggested that the presence of short-chain fatty
acids in the small intestine reduces the damage to the villi of the gut wall that is associated with weaning.
It has proved difficult to obtain experimental evidence for all of these purported effects of organic acids.
Only a few studies have demonstrated a reduction in gastric pH, but the methodology of sampling is difficult,
given diurnal variations, differing proportions of food and secretions, and timing of sampling. To confirm such
effects of organic acids, a study is required with permanent fixed pH electrodes within the stomach. There is
evidence of a positive effect on the ileal di-gestibility of amino acids and the retention of nutrients in growing
pigs. The magni-tude of the effect depends on the acid used and its concentration, the age of the pig and the
composition of the diet.With regard to minerals, the absorption of calcium and phosphorus has been
improved, but variable results have been obtained for the retention of these minerals. Addition of organic
acids has had beneficial effects on microbial counts and species in some studies, but there has been little
work on the effects on gut morphology to test the theory of an improvement of the structure of the villi.
Antimicrobial action of organic acids
Organic acids change from the undissociated to the dissociated form, depending on the pH of the
environment. In the undissociated form they can diffuse rapidly through the semi-permeable mem-brane into
the cytoplasm of the microorganism. Once inside, at a pH of around 7, the acid becomes dissociated and
acts by suppressing the cellular enzyme and transport systems. Acids with a high pKa (which are 50 per cent
dissociated), longer-chain-length acids and unsaturated acids are the most effective.
Although the exact modes of action of the acids are not clear, their addition to pig diets has proved
beneficial in terms of nutrient digestibility, growth and food conversion efficiency. This is so particularly for
newly weaned pigs, when coupled with good feeding management procedures.
Formic and propionic acids are more effective than fumaric or citric acids at the same rate of inclusion
because the former have a lower molecular weight. Suggested levels of inclusion of acid (kg/tonne diet) are
formic acid 6–8, propionic acid 8–10, fumaric acid 12–15 and citric acid 20–25, but recommendations vary.

3b OLIGOSACCHARIDES
Oligosaccharides (2–20 monosaccharide units..) have been claimed as beneficial nutritional modifiers for
monogastric farm animals. They fall into the group of materials also known as prebiotics, which are defined
as compounds other than dietary nutrients that modify the balance of the microfloral population by promoting
the growth of beneficial bacteria and thereby provide a healthier intestinal environment.
Oligosaccharides occur naturally in foods (but are also produced commercialy):
- soya bean meal, rapeseed meal and legumes contain galactooligosaccharides (GOS);
- cereals contain fructo-oligosaccharides (FOS); milk products have trans-galacto... (TOS);
- yeast cell walls contain mannanoligosaccharides (MOS).
 It has been suggested that these compounds achieve their beneficial effects in the gut in two ways.
First, although they are not easily digested by the host digestive enzymes, compounds such as FOS
can be fermented by the favourable bacteria (e.g. Bifidobacteria and Lactobacilli), giving them a competitive
advantage against the harmful species.
Second, the gut microbial population may be altered by the oligosaccharide inter-fering with the
attachment of harmful bacteria to the gut wall. As a means of cell recognition, all cell types have a unique
configuration of carbohydrate-containing compounds (glycoproteins and glycolipids) on their surface. As
described above in the section on probiotics, pathogenic bacterial cells have surface compounds called
lectins that recognise these carbohydrates and by which they attach to the gut cells. Once attached, the
bacteria are able to multiply and produce their harmful effects. Species such as Salmonella and E. coli have
a mannose-specific lectin that binds to mannose residues on the gut mucosal surface. By introducing
mannose-containing compounds (MOS) into the diet, the binding by pathogenic bacteria is disrupted and
instead they bind to the oligosaccharide and are carried out of the gut with the pas-sage of the digesta.
Yeasts have mannans in the cell wall structure and form the basis of some commercial products that are
claimed to act in this way.

The efficacy of products containing oligosaccharides is currently the subject of ac-tive experimentation.
There can be no guarantee that an oligosaccharide will favour the growth of beneficial species in a complex
microflora such as that found in the pig intestine. Experiments have shown that piglets given an oral challenge of
E. coli responded to GOS with a reduced pH of ileal digesta and reduced population of col-iforms. Supplements of
FOS and TOS have reduced the numbers of aerobic bacteria in the gut of weaned piglets, and there are reports of
a reduced incidence of diarrhoea. Under farm conditions, improvements in gain and food conversion efficiency of
the order of 4–6 per cent have been recorded. In other experiments, reduced digesta pH has been reported, but
without a detectable change in the composition of the microflora, microbial metabolites or production responses.
These conflicting results may have arisen because the diet already contained some oligosaccharides or because
experimental conditions tend to be less stressful than those on farms.

4 ENZYMES
Not all compounds in foods are broken down by these enzymes, and so some potential nutrients are un-
available. The chemical structure of plant cells (fibre), the limited time available for activity in certain parts of the
gut and the presence of antinutritive compounds in some foods hinder the release of nutrients. Early experiments
with supplemental enzymes to overcome these limitations yielded variable responses, mainly because they were
impure materials.As a result of advances in biotechnology, more effective enzyme preparations can now be
produced in large quantities and relatively inexpensively. Therefore, supplementation of the diet as a means of
improving nutritive value is becoming commonplace.
The enzymes used as food additives act in a number of ways.
First, they can improve the availability of plant storage polysaccharides (e.g. starch), oils and proteins, which
are protected from digestive enzymes by the impermeable cell wall structures. Thus, cellulases can be used to
break down cellulose, which is not degraded by en-dogenous mammalian enzymes. Even in ruminant animals, in
which the rumen microflora possess cellulase, fibrolytic enzymes have been used, but responses have been
variable owing to the complex nature of the rumen fermentation system and other factors such as lignin
encrustation of cellulose. Responses in pigs and poultry of the order of 5–10 per cent improvement in liveweight
gain and 10 per cent im-provement in food conversion efficiency have been recorded. Supplementation of a wheat
by-product diet with cellulase increased the ileal digestibility of non-starch polysaccharides from 0.192 to 0.359
and crude protein from 0.65 to 0.71.
Second, enzymes are employed to break down materials that interfere with the digestion, absorption and
utilisation of nutrients. The major application in this area has been to break down carbohydrate fractions in
cereal cell walls, the beta-glucans and arabinoxylans, which are resistant to attack by digestive enzymes.
These materials hinder the digestion and absorption of other nutrients by forming a viscous gum in the
digestive tract. In pigs, it has been suggested that the increased viscosity brought about by beta-glucans in
the stomach contents may affect the natural sieving of particles. Thus, large particles are suspended in the
viscous digesta and pass through to the duodenum It is also possible that the increase in viscosity disturbs
peristalsis and pancreatic secretion. In poultry, the viscous nature of the digesta results in poor performance
and sticky droppings, which present a problem in the management of litter waste. Supplements of beta-
glucanase to barley-based diets improved the rate of gain and food conversion efficiency of broilers to values
similar to those for wheat- or maize-based diets. The beta-glucanase also reduced litter problems and
improved the metabolisable energy of the diet.
 Supplementation of pig foods improves ileal and whole tract digestibility of nu-trients. In breaking down the
beta-glucans, the enzymes reduce the viscosity of the digesta, thus allowing better movement of
endogenous enzymes through the mass and more efficient digestion and absorption of nutrients. It is still not
clear whether viscosity per se is responsible for the effects or whether it is an indicator of conditions
pertaining in the gut lumen that cause the problems. The response differs between pigs and poultry because
of differences in digestive physiology between the two species (see Box 24.2).
Enzyme action in pigs and poultry
Enzymes have found major commercial application in pig and poultry diets and are used extensively for the
latter. Differences in efficiency have been reported between the species, the effect generally being greater in
poultry; this is possibly due to the differences in gut physiology between the two species. There is a greater
reduction in the viscosity of digesta in the small intestine by enzymes in poultry, probably because of the
lower water content than in pigs. The longer retention time in the stomach and acidic nature of stomach
contents in the pig (around pH 3) is more destructive to enzymes than the milder conditions in the crop (pH
4–5). New commercial enzymes have been selected for their pH stability. Finally, pigs have a longer small
intestine than poultry and the resultant increased retention time allows more time for the endogenous
enzymes to act. Thus,there is more opportunity for supplemental enzymes to have an effect in poultry owing
to their limited digestive tract.
Phytase in monogastrics
Phytase is in this category of enzyme. It releases the orthophosphate groups from phytic acid, which is
only partially broken down by non-ruminants and is the major form of phosphorus in cereal grains and
oilseeds.This results in a greater availability of phosphorus to the animal, and the amount of inorganic
phosphorus added to the diet can be reduced, with beneficial effects on the environment through reduced
phosphorus excretion.
In the third area of enzyme application, the aim is to supplement the enzyme complement of young
animals, in which the rate of endogenous enzyme production may be limiting. Early-weaned pigs have
limited amylase, protease and lipase activity, and enhancement of the extent of digestion of nutrients would
improve performance and reduce the incidence of the diarrhoea that results from undigested nutrients
reaching the hind gut and being fermented by bacteria.
Finally, enzymes can increase the efficiency of utilisation of nutrients in monogastric animals by releasing
them for uptake from the small intestine rather than allowing fermentation in the hind gut, which results in
products of lower value to the animal (e.g. volatile fatty acids).
In order to be effective when incorporated into the animal’s diet, enzymes must survive storage at ambient
temperature, the manufacturing process (heating and pel-leting) and wide fluctuations in pH in the gut, be
resistant to intestinal proteases, and have specific activity on feed components in the upper digestive tract.
The enzyme should be selected on the basis of its target substrate. Commercial enzymes are derived from a
wide range of sources, particularly fungi such as Trichoderma longi-brachiatum, Aspergillus niger and
Humicola insolens.

5 MODIFIERS OF RUMEN FERMENTATION

Rumen fermentation processes are usually kept within narrow bounds and, as they form an
integrated system, any changes made have more than one outcome. Thus, modification of the processes to
one desired target is difficult. Nevertheless, there are products that are used to modify the fermentation to
achieve specific results.
The use of ionophore antibiotics and probiotics was discussed above. Other rumen modifiers
include buffers, methane inhibitors and bloat-preventing substances.
Buffers are included in ruminant diets to regulate rumen pH to levels that favour the activity of
cellulolytic organisms (pH 6–7). Diets rich in readily fermentable carbohydrate create acidic conditions and
increase lactic acid formation, both of which are detrimental to the cellulolytic bacteria. This reduces food
intake and predisposes the animal to acidosis. Secondary problems include reduced milk fat production,
rumenitis, ketosis, laminitis and liver abscesses. Chemicals such as sodium bicarbonate, sodium carbonate,
calcium carbonate and magnesium oxide buffer the hydrogen ions and increase the dilution rate of the
liquids in the rumen. This increases the efficiency of microbial protein synthesis and, as a result of the
shorter retention time, allows starch and protein to escape to the intestines. The activity of cellulolytic bac-
teria and the proportion of acetate in the rumen volatile fatty acids are increased. In the USA it has become
common to add up to 200 g NaHCO3/day, and sometimes also MgO, to the rations of cows in early lactation.
It has been suggested that, since bicarbonate buffers are expended once the CO2 is released, it would be
advanta-geous to use certain clays and bentonites that contain insoluble and hence undegradable anions
and would allow the buffering action to be carried further down the digestive tract.
Antibiotics such as virginiamycin and monensin have been used to select against bacteria that
produce lactic acid. Certain probiotics encourage the uptake of lactic acid .
The production of methane in the rumen is a wasteful process (up to 10% of the gross energy) and
contributes to the earth’s greenhouse gases. The use of some additives to suppress/ reduces the methane
production.