Dietary Nucleotides

There is an increasing interest in the application of yeast-derived nucleotides for livestock nutrition due mainly to the growing body of research that is showing the health- and growth-promoting properties of this group of dietary supplements. Originally the focus of human pediatric and geriatric nutrition, research on nucleotides in all livestock categories is now routinely presented at scientific meetings and published in leading scientific journals.

However, the amount of information specific to poultry in general and chickens specifically is still limited. What exactly are nucleotides, what is their mode of action and how they should be applied and incorporated into poultry nutrition so as to maximize performance and reduce antibiotic usage are the questions this article will address.

What are nucleotides?
Similar to how amino acids are the building blocks of protein, nucleotides serve as the building blocks of DNA and RNA, the genetic currency of all living cells. Just as there are many different individual amino acids, so too are there multiple nucleotides. Chemically, nucleotides are one part non-protein nitrogen, one part sugar and one part phosphorus, and are grouped into two categories: purines and pyrimidines. It is the specific base pairing between these two groups that gives DNA and RNA their characteristic double helix structure and the alignment, or “sequence,” of nucleotides within the DNA and RNA molecules that makes up individual genes and the overall genetic code.

Where are they found?
Nucleotides can be found in nearly all tissue types and because of their association with DNA and RNA are involved in almost all metabolic processes from protein synthesis and cell division to energy metabolism and immune functioning. Nucleotides participate in this wide array of processes not only by being required for DNA and RNA synthesis, but also by assisting in cell signalling and acting as enzyme co-factors for multiple pathways.   

Nucleotides are components of the non-protein nitrogen fraction of milk, yeast and other ingredients with high cellular density. Yeast and yeast byproducts such as live yeasts and yeast extracts are typically the best nucleotide sources. However, there exists considerable variation between commercial products (see Table 1). When procuring a dietary nucleotide supplement, it is a good idea to obtain a certificate of analysis showing the total level of all nucleotides present in the product.

Dietary inclusion, antibiotic replacement and economics
In mammals, where, as mentioned above, the bulk of dietary nucleotide research has been conducted, there appears to be an evolved requirement for dietary nucleotides, which serves as the rationale for dietary nucleotide supplementation. Although, like mammals, poultry can synthesize nucleotides de novo, it is currently thought that the capacity for nucleotide production, especially in young animals, may not be enough to meet demand. Because of this, nucleotides have been described as being conditionally essential, and will be most beneficial under periods of stress, such as during disease and health challenges, high stocking densities, periods of rapid growth and antibiotic replacement or removal. 

Because predicting when birds will become stressed is so difficult, a prudent feeding strategy is to ensure a constant supply of dietary nucleotides during production stages when the birds are at high risk of becoming stressed. That is, starter birds and flocks being raised under specific production conditions such as under “antibiotic-free” feeding programs should be fed a steady diet
of nucleotides.

There are few, if any, published studies that report a minimum level of dietary nucleotides required to elicit a feeding response. This is likely due to the inherent variability of the nucleotide levels within the supplements, the nucleotide source (ingredient), as well as the method of evaluation and inconsistencies in analytical methods used to measure individual and total nucleotide levels, making it challenging to formulate to a minimum dietary nucleotide level.

An alternative, and potentially more practical, strategy is to choose a specific supplement and inclusion level based on a certain economic position. Then employ a specific feeding program and/or location, and allow bird performance to dictate future dietary inclusion adjustments.

As an example, Table 2 shows how dietary nucleotide supplementation can be used to maintain chicken performance under relatively high stocking densities without the use of supplemental antibiotics. Therefore, because bird performance was statistically the same between treatments, dietary nucleotide supplementation effectively replaced antibiotics in this particular study.  

Of course, feeding costs ultimately drive inclusion decisions, so nucleotide inclusion must be at least “iso-economical” within the particular feeding program being evaluated. In the Table 2 example, the costs associated with nucleotide and antibiotic supplementation were nearly identical, so there was no feed cost disadvantage accompanying nucleotide supplementation. However, the conditions of that particular trial may not be applicable to a wide range of production programs.

Table 3 shows the average body weights of broiler chickens raised under commercial conditions and fed either a control diet, a diet supplemented with a source of nucleotides or a diet supplemented with antibiotics. Under these more typical conditions, although FCR was not affected by treatment, average daily gain of birds supplemented with dietary nucleotides was numerically greater than that of control birds and statistically the same as birds fed antibiotics. As in the previous study, cost of gain between the nucleotide- and antibiotic-supplemented diets were nearly identical at the time of this study.  

Based on the scenario presented in Table 3, it is noteworthy that, in addition to having the potential to mediate stressful production conditions, dietary nucleotide supplementation may also lead to performance gains under standard production conditions. However, inclusion costs must be kept in mind and, given that the product used in these two studies cost roughly $10/kg, nucleotide supplementation represented a cost increase of approximately 1.5 per cent above non-supplemented diets, using $325 as an average per-tonne feed cost. So, even though nucleotide supplementation did not statistically improve performance per se, there was an economic advantage to nucleotide supplementation, given the 5.6 per cent improvement in ADG and 2.9 per cent improvement in FCR. However, it goes without saying that such cost improvements may not be realized in every production system and that factors such as inclusion level, stage of production, genetics, species and environment will all contribute to overall flock performance.

SUMMARY
Although a consensus on the mode of action of dietary nucleotides has yet to be reached, the potential they have to improve the performance and stress associated with production within poultry species is promising. The study data presented in this article shows the ability of dietary nucleotides to reduce feeding costs while simultaneously serving as a potential replacement to growth-promoting antibiotics. Looking forward, as Canadian regulating bodies move towards greater management and perhaps restriction of antibiotic supplementation, finding alternative technologies that are both viable and economical will be a challenge the Canadian poultry industry will have to address. Incorporating and investing in new innovative technologies, such as dietary nucleotides, is one way the Canadian poultry industry can be competitive economically in a rapidly changing marketplace.