Nucleotide Nutrition: Present Status and Prospects in Aquaculture

  • Shyam Prasad. M
  • Muralidhar P. Ande
  • Syamala Karthireddy
  • Chadha N.K
  • Gireesh Babu.P
  • Paramita Banerjee Sawant

Due to the rise in the World population, animal nutrition plays a vital role in meeting the food demand as well as nutritional requirements for mitigating food security. On similar lines, we need to concentrate on fish health, immunity, metabolism, growth, and nutrition to alleviate the present and future challenges. As per the advances taking place in aquaculture nutrition, nucleotides are the relevant potential functional feeds for sustainable aquaculture production. Nucleotides are essential metabolites involved in cellular activities and play a key role in growth, physiological, biological, energy and other regulatory functions. Dietary nucleotides enhance the reproductive performance of brood fish, larval quality, and growth in the early stages of development and increase the gut microbiota of finfish and shellfish. Commercially available cost-effective nucleotides like IMP, GMP, AMP, CMP and UMP are used in aquaculture for the past four decades. There are numerous gaps in the correct understanding of administration, dose, digestion, absorption, metabolism and age/size relationships of nucleotides on various species. Furthermore, there is a need to develop cheaper production techniques for nucleotides by studying the cell signaling pathways, leaching loss, the ratio of various types of nucleotides, nutrient metabolism in response with nucleotide application along with available alternative protein and lipid-based ingredients in the near future.


Nucleotide nutrition, feed attractants, important metabolites, alternative protein & lipid-based diets


Aquaculture is the fast-growing food sector in animal nutrition, which can fulfill future food demand without compromising sustainable production. However, World aquaculture is at present facing challenges like climatic change, pathologies, the decline of marine catches, the prohibition of growth promoters, increasing the cost of raw materials etc. To lessen these challenges, we need to concentrate on aquaculture to develop significant lines for improvement of genetics, increased knowledge of biology and handling, improved rearing facilities, and advances in fish nutrition. It is possible to get the maximum yield from the aquaculture by lowering the Food conversion ratio (FCR) only; that is why we need to focus more on feed formulation, various feeding strategies, physiology, immunity, growth and metabolism of the fish. Hence, we should consider more emphasis on advances in fish nutrition to get sustainable production.

Nucleotides have various physiological and biological functions, mediate metabolism and cell signaling pathways as non-essential nutrients. When administered through exogenous diet, they act as essential nutrients to conquer stress condition, growth enhancement and gives more benefits to the fish health. In the past 40 years, efforts were made on the evaluation of dietary supplementation of nucleotides and administration on 28 fish species, including finfish and shellfish worldwide (Hossain et al., 2019).


Nucleotides (NT) are the crucial metabolites with low molecular weight and play a vital role in all the biochemical processes and are basic building blocks of DNA and RNA. Nucleotides consist of a nitrogenous base, sugars (deoxyribose and ribose), and phosphate groups (Gil, 2002). Dietary NT serves as a growth enhancer in the early stages, improves the reproductive performance, modulate the immune function, improves the intestinal morphology, and improves gut microflora.

Possible involvement:

Under natural conditions, Nucleotides (NT) aid in diet palatability, stimulation of feeding behavior, and the biosynthesis of nucleic amino acids. When supplemented through an exogenous diet, they enhance immunity, improve disease resistance against pathogens or stress, boost the growth, improves reproductive performance, and better growth in the early stages of the offspring (Li et al., 2004).


In adult animals through the salvage pathway or de novo synthesis, nucleotides are produced by reuse of nucleic acids from dead cells without loss of its functions (Fustin et al., 2012). In this situation, NT act as a non-nutritional supplement only. At this juncture, Nucleotides have become essential nutrients or potential functional feed supplements to manage the harmful effects of stress and the expense of performances for growth, health, reproduction and development.

Digestion and absorption:

NT digestion and absorption takes place in the small intestine or the stomach based on different feed products by various fish species. Generally, in the presence of enzymes proteases and phosphodiesterases, nucleoproteins are broken down into nucleotides. Nucleotides are further broken down by enzyme alkaline phosphatases and form nucleosides. These nucleosides are absorbed into enterocyte in the form of purine and pyrimidine by nucleosidase (Hess and Greenberg, 2012). The digestion process breaks down purines into uric acid and pyrimidines into beta-alanine and bet-amino isobutyric acid.

Mode of action:

Dietary nucleotides are important tools in fish nutrition for the optimization of various biological activities like cellular growth, physiological responses, immune responses, and reproductive performances.

Effect on Muscle:

Nucleotides affect muscle growth by enhancing digestion capacity. Growth performance in hybrid tilapia improved with yeast-originated NT mixture with 0.60% inclusion levels and also boosted the growth-related genes (Li et al., 2004). Dietary NT has effects on growth performance, notably in the early growth period in Atlantic salmon, grouper, rainbow trout, pacific white shrimp (Li et al., 2007). In the initial growth stages of fish, NT average production might be insufficient to support the rapid cell growth and hence dietary NT supplementation reduces the demand of NT production (Li et al., 2004).

Effect on gut:

RNA/Nucleotides supplemented diet improves the intestine structure through increased intestinal fold height, microvillus & enterocyte height in fishes (Peng et al., 2013). Increased enterocyte height facilitates for more digestion and absorption and simultaneously get sustainable growth with the involvement of increased enzyme secretions and increase beneficial microbiota.

Effect on Gonads:

When the brood fish supplemented with the NT, it develops or improves the reproductive performance, improves the quality of broodstock, and produces quality offsprings. In the Pacific white shrimp, NT supplementation showed a positive effect on the hepatopancreatic index, hemocyte count, and low fatty acid profile with a latency period (Arshadi et al., 2018).

Anti-stress effect of NT:

Dietary NT supplementation increases the stress tolerance capacity by reducing the oxidative stress and enhancing the osmoregulatory functions. Lenordi et al. (2003) reported that NT feed supplement reduces the levels of cortisol and improves the capacity of osmoregulatory function in salmonids. In Red seabream, down-regulation was observed in stress parameters like glucose, cortisol levels with NT mixture supplementation in the diet (Hossain et al., 2016) whereas cortisol levels were abnormal with a regular diet without NT mixture.

Feeding stimulatory properties of NT:

With NT supplementation, there are positive effects on growth performance by increasing feeding stimulation and increased feed intake (Hossain et al., 2016). NT are treated as alternative protein-based diets by reducing feed losses, water quality amelioration, reduce feed cost, reduces the negative effect of alternative proteins, and increase the efficiency of utilizing alternative proteins. Yaghobi et al. (2014) observed the lower FCR in Striped catfish, Pangasianodon hypophthalmus and Channel catfish, Ictalurus punctatus fed with NT supplemented diet recorded better growth performance compared to the normal diet.

Immuno-modulatory effects of NT on gill, liver, spleen & kidney:

Dietary nucleotides enhance the immune system in finfish and shellfish by increasing the disease resistance power against the pathogens. NT supplemented diet increases immune competence and health welfare by boosting immune gene expression, improving disease resistance, innate and adaptive immunity. Exogenous NT influence humoral and cellular immunity and support lymphoid tissues that have limited de novo synthesis capacity (Li et al., 2004). The crucial cells of the immune system like skin, gill, liver, and kidney will stimulate the production of leukocyte with a circulation pool of nucleosides through supplementation of nucleotides through diets (Sakai et al., 2001). NT provide immuno-modulatory effects on lymphocyte maturation, proliferation, immunoglobulin responses and phagocytosis.

Effect on defense:

NT nutrition protects from external parasites by increasing the first-line defense mechanism and also enhanced lymphocyte proliferation resulting in enhanced immune responses. Hossain et al. (2018) reported that from the skin, gill, and intestinal mucosa-associated lymphoid tissues involved in the expression of gene related to transferrin, lysozyme and cytokines, which play a crucial role in defense mechanism (Burells et al., 2001). In Red seabream, Amberjack and Nile Tilapia, NT dietary supplementation increased serum lysozyme activity, serum complement activity, bactericidal activity (Kedar et al., 2018).

Present status of NT in Aquaculture:

Several reports are available on dietary supplementation of nucleotides with different proportions with various beneficial effects like growth performance, disease resistance, tolerance to stress, and increase immune responses in various species.

Table:1. Research on potential functional feeds (dietary nucleotide supplementation) in fishes

(Source: Hossain et al., 2019)

NT administration dose:

Till now, studies on dose-inclusion and its effect on dietary nucleotides are very few; Hence, there is a need to emphasize the administration of NT in various diets according to the species to understand the mechanism of the nucleotides (Xiong et al., 2018). The table mentioned below consists of various exogenous NT doses and their influence on various activities in different fishes.

Table:2. Research on a different dosage of dietary NT supplementation in fishes


Dietary nucleotide supplementation in fish and shrimp majorly helpful in three pathways:

  1. Nutritional aspects: Gustatory responses to NT can help in the development of eco-friendly functional feed.
  2. Husbandry responses: NT nutrition has a significant effect on reproductive performance and early stages of larvae, growth enhancement, feed utilization, and control monitoring of biometric indices of fish and shrimp.
  3. Immunity and health: Dietary supplementation of NT can increase immunity and adaptive immunity, disease resistance, stress resistance, improve gastrointestinal health of fish and shrimp. It also reduces pathogenic infections and can be used as an alternative tool for antibiotics.

Nucleotides (NT) are relatively costlier and there is a need to identify the production technology to avoid adverse interaction between nucleotides and other nutrients. Dietary NT role is limited in some physiological responses of fish, such as exposure to stressors and molting.

Future Research in NT nutrition:

There is a need to select the appropriate sources of NT to develop procedural techniques for the production of cheaper nucleotides without impacting their functions. Need to study the leaching loss of nucleotides in water after feeding, the ratio of various types of nucleotides, dose, administration regime, the efficacy of NT, age/size-related responses of fish, the influence of different forms of NT in different species.

There is also a need to understand Cell signaling pathways to exogenous NT, nutrient metabolism in responses to NT, the effect on gut microflora, mediating energy metabolism, alternate protein & lipid-based diets, development of novel molecular tools in NT application. We should also concentrate on the influence of intestinal microbiota by dietary nucleotides in fish species in the future.


To escalate the aquaculture production and to meet the food stipulation, we have to concentrate on multifunctional feed supplements like nucleotides. When the body is in demand for various biological functions, this potential feed supplementation can help in the improvement of the growth, health benefits, immunity, and antioxidant status. As such, these functional nutrients will help to solve the aquaculture problems like diseases, antibiotic issues, environmental hazards, suppression of immune systems to promote aquaculture production. However, there is a need for a detailed study to fulfill the gaps in nucleotide nutrition for better understanding and to get sustainable production to meet the food demand.


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Fustin J.M., Masao D., Yamada H., Komatsu R., Shimba S., Okamura H. (2012) Rhythmic nucleotide synthesis in the liver: temporal segregation of metabolites. Cell Reports, 341-349.

Gil A. (2002) Modulation of the immune response mediated by dietary nucleotides. European journal of clinical nutrition, 56:1-4.

Guo J., Guo B., Zhang H., Xu W., Zhang W., Mai K. (2016) Effects of nucleotides on growth performance, immune response, disease resistance and intestinal morphology in shrimp Litopenaeus vannamei. Aquaculture International, 24: 1007–1023.

Hess, J. R., & Greenberg N. A. (2012) The role of nucleotides in the immune and gastrointestinal systems: potential clinical applications. Nutrition in Clinical Practice, 27(2): 281-294.

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Kader M.A., Bulbul M., Abol-Munafi A. B., Asaduzzaman M., Mian S., Noordin N. B. M. (2018) Modulation of growth performance, immunological responses and disease resistance of juvenile Nile tilapia (Oreochromis niloticus) (Linnaeus, 1758) by supplementing dietary inosine monophosphate. Aquaculture Reports, 10: 23–31.

Leonardi M., Sandino A.M., Klempau A. (2003) Effect of a nucleotide-enriched diet on the immune system, plasma cortisol levels and resistance to infectious pancreatic necrosis (IPN) in juvenile rainbow trout (Oncorhynchus mykiss). Bull Eur Assoc Fish Pathol, 23: 52-9.

Li P., Lawrence A.L, Castille F.L, Gatlin DM III (2007) Preliminary evaluation of a purified nucleotide mixture as a dietary supplement for Pacific white shrimp Litopenaeus vannamei. Aquaculture research, 38: 887-90.

Li P., Lewis D.H., Gatlin III D.M., (2004) Dietary oligonucleotide from yeast RNA influences immune responses and resistance of hybrid striped bass to Streptococcus iniae infection. Fish Shellfish Immunology, 16:561-569.

Peng M., Xu W., Ai Q., Mai K., Liufu Z., Zhang K. (2013) Effects of nucleotide supplementation on growth, immune responses, and intestinal morphology in juvenile turbot fed diets with graded levels of soybean meal (Scophthalmus maximus L.). Aquaculture, 392 395: 51–58.

Peterson, B.C., Booth, N.J., Manning, B.B. (2011) Replacement of fish meal in juvenile channel catfish, Ictalurus punctatus, diets using a yeast‐derived protein source: the effects on weight gain, food conversion ratio, body composition and survival of catfish challenged with Edwardsiella ictaluri. Aquaculture nutrition,

Sakai M., Taniguchi, K., Mamoto K., Ogawa H., Tabata, M. (2001) Immunostimulant effects of Nucleotide isolated from yeast RNA on carp, Cyprinus carpio L. Journal of Fish Diseases, 24: 433–438.

Song J.W., Lim S.J., Lee K.J. (2012) Effects of dietary supplementation of inosine monophosphate on growth performance, innate immunity, and disease resistance of olive flounder (Paralichthys olivaceus). Fish and Shellfish Immunology, 33: 1050–1054.

Xiong J., Jin M., Yuan Y., Luo J. X., Lu Y., Zhou Q. C. (2018) Dietary nucleotide-rich yeast supplementation improves growth, innate immunity and intestinal morphology of Pacific white shrimp (Litopenaeus vannamei). Aquaculture Nutrition, 24: 1425–1435.

Yaghobi M., Paykan H.F., Akhlaghi M., Dorafshan S., Mahmoudi N. (2014) Intestinal microbiota of striped catfish, Pangasianodon hypophthalmus (Sauvage, 1878) fed on the dietary Nucleotide. Iranian Journal of Ichthyology, 1: 274–280.