Introduction

The legislation on additives and premixes, in most countries, defines them as substances that are added to the food of healthy animals, in order to increase their productivity and improve environmental respect. However knowledge of the difficulties of using additives as well as new advances in molecular biology, genetic goal and at the same time make necessary the introduction of new postulates that must be taken into account when updating the modern concept of Additives or premixes:

(1) An additive should only be used in healthy animals. This postulate excludes in itself the use of substances with pharmacological effect.

(2) An additive should only be used to improve animal productivity or environmental compliance

(3) The mechanism of action to increase productivity should be known and should not have a pharma dynamic effect (i.e. association with protein receptors or enzymatic proteins). The additive should not, therefore, be temporarily or permanently associated with a protein in the body.

(4) Confining animals on farms deprives them of accessing substances that they naturally used in their diet in the wild, to add these substances to the diet of farm animals can be considered as a nutritional supplement.

(5) The way animals are fed on the farm produces a nutritional deficiency that reduces the physiological activity of the organs, so adding these substances in the diet in order to maintain the normal state of the organs cannot be considered as a pharmacological effect.

In our opinion the inclusion of these 5 postulates in the definition of additive or premix would greatly clarify the limits in which nutrition specialists can move without entering the pharmacological space. In the following sections we will explore each one of them.

Postulate nº1: their use in healthy animals, molecules and daily dose

In this section the route of administration we will pay attention on the dose, the duration and the molecule.

It is obvious that if we consider an additive as a substance, other than a drug, the route of administration of the additives can only be through the feeding of healthy animals (dry food or drinking water). This excludes other routes of administration such as aerogena, transcutanea and parenteral. It does not depend on the molecule; it depends on the route of administration.

If we focus on the daily dose, it may cause a confusion to decide, whether it is a drug or an additive, depending on the situation of the target animal and not on the molecule or route of administration. For example, different legislation currently considers vitamins A, D3 and E as additives if they are administered at certain doses to meet the physiological needs of healthy animals and as drugs if they are administered at higher doses to compensate a lack of previous nutrition. Thus deficient administration over a period of time may make it necessary to increase the dose and apply the same molecule at higher doses to regain normality. Also difficulty of defining the daily dose required depending on the animal strains or their age. The same dose of vitamins A, D3 or E is not required throughout the gestation of a cow. It does not depend on the molecule; it depends on the relation between the daily dose and the daily physiological needs of the strains and the ages of the animals.

Finally, if we focus on the molecules with the above considerations, we can define whether or not a molecule is an additive.

This leads us to the formulation of the first postulate: "A molecule must be considered as an additive, or not, according to itself and not according to its dose. For this legislation even the cost becoming complex should adjudicate to each molecule, once defined as an additive, a range of daily doses, and duration, depending on the physiological needs of the strain and the age of the animals.

Postulate nº2: The mechanism of action and effect

If we consider an additive as a molecule without pharmacological effect we must exclude from the list of additives any molecule that possesses pharmacological action.

(1) It is therefore important to define exactly "pharmacological action". It is about modifying or changing a biochemical process giving rise to an observable effect. This action, the drugs are mostly made by binding to a specific protein either an enzyme receptor of the organism or a receptor of an external agent. Thus, we can define that any pharmacological action is linked to the binding of the drug with a receptor, mostly of protein structure. This union initiates a modification, or alteration of a biochemical process, either an ionic transportation system or the alteration of the permeability of a membrane.

The process from administration to receptor binding and its elimination is called (1.1) pharmacokinetics, whereas the effects of this binding are called (1.2) pharmacodynamics.

(2) Let’s take a look at some examples of molecules that are part of the nutrition of healthy animals.

(2.1) Ascorbic acid is necessary for the formation of collagen and lipid synthesis. It is also reversibly oxidized to dehydroascorbic acid.

(2.2) Calcium is necessary to maintain to form barriers, around or inside of injured areas and is involved in muscle contraction. However calcium does not bind to any receptor it only binds to plasma albumin, as a means of transportation to reach the bones that act as a calcium reserve reservoir.

(2.3) Phenylalanine is an essential amino acid, a component of plant and animal proteins. Its presence in the feeding is fundamental since the animal cells cannot produce it from other amino acids. The animal organism produces many substances from the phenylalanine: catecholamines, epinephrine, tyrosine or aspartame. The case of phenylalanine is especially didactic because it clearly marks the boundary between an essential nutrient (obliged its ingestion by the animal to be a molecule of exclusively vegetable synthesis) and its natural or synthetic derivatives that they can have physiological or pharmacological.

Apart from these arguments, we can establish Postulate 2, which must comply with the additive molecules, relative to their mechanism of action and effect: "A molecule must be considered as an additive if, with its presence in the organism no process is altered by its permanent or transitory union with a receptor. Therefore a molecule can be considered as an additive if its presence in the organism serves as a means for the organism to elaborate other substances necessary to maintain the physiological functioning of its tissues.

Postulate nº3: Return to the natural: Animal welfare, management and pronutrients

The strong implantation of industrial methods for breeding the birds from the decade of 1950 caused the separation of the birds from their natural surroundings and prevented that some ingredients disappeared of the formulation of the foods. Thus, birds, like the old navigators, began to present deficiencies by the exclusion of these natural ingredients in food and from the 1960s started the search for chemical solutions to the deficiencies of natural products in birds.Thus an intestinal mucosa aged by the deficient of natural and colonized regeneration by superficial bacteria, treated with antibiotics to which they denominated, erroneously promoters of growth.Time by time this chemical practice was extended to the control of the coccidia, hepato protectores and immune potenciadores. Not only in poultry, but the practice of using chemical additives was also extended in swine industry. However, from the 1980s sufficient data were available to affirm that the use of chemical substances in animal feed as additives had some advantages and some disadvantages. The presence of residues of these additives in food for human consumption, the possible appearance of bacterial resistance to antibiotics, the presence of anabolics and betagonists in food or the increase of certain minerals such as copper, cadmium in soils began a stage of restricting the use of such substances through national or transnational legislation.

According to the above mentioned, it is concluded that in addition to vitamins, minerals and other compounds of natural origin are necessary for physiological functioning although at the moment many of them are not yet taken into account when formulating food. The need to incorporate these pronutrients was already described by Gordon Rosen in the 1950s and his zootechnical classification updated in 2005 by us from observations made on industrial farms: 1. Intestinal mucosal conditioners, 2.Initial intestinal mucosal improvers, 3.Hepatore generators, 4. Immune modulators, 5. Mineral absorption promoters, 6. Food optimizers, 7. Free antiarrhythmics, 8. Epithelial conditioner, 9. (Royal Academy of Veterinary Sciences, Session of December 21, 2005, on "Benefits of the use of natural pronutrients in veterinary medicine").

The future of additives in animal production should be framed as philosophy of Return to the natural- Postulate # 3: Apply measures of animal welfare, improve available surface, increase accessibility to water and food, restrict the use of chemical additives and include additives of natural origin that originally formed part of the feeding of wild animals or domesticated animals exploited in a natural environment.