Dietary Nucleotides and their Role in Human Health, Sports Nutrition and Muscle Gain

Nucleotides are not a buzz word we hear on bodybuilding and fitness nutrition forums, nor do we see them plugged on supplement product labels. This strikes me as odd, because, although their positive effects are nothing mind-blowing, the are very likely to have possible benefits which is a lot more that you can say for the bulk of supplement ingredients touted to be the next best thing.

Whilst nucleotides are far from ‘the next best thing’, they do warrant some consideration and may well crop up in sports supplement formulas following the valid research for their use in infant formulas.

After all, isn’t infant feeding where the idea of whey protein supplementation in bodybuilders came from?

What are nucleotides?

DNA is the most basic genetic material found in the nucleus of a cell. It forms the blueprint of life and nucleotides form the backbone of the DNA double helix. Nucleotides consist of a nitrogen-containing base, a sugar (ribose or deoxyribose) and phosphates.

What are the functions of nucleotides?

They form the structure of DNA and RNA and are essential in the production of energy. They play an important part in the metabolism of fat, protein, carbohydrate and nucleic acids.

Cells which have a high turnover rate have a higher requirement for nucleotides; this includes immune cells and enterocytes of the wall of the small intestine. Nucleotides are also involved in boosting levels of good gut microflora and helping white blood cells. Therefore they help in the digestion and absorption of food and in the immune system – two vital areas for health and sports performance.

Sources of nucleotides

There are four ways in which we can obtain essential nucleotides:

  1. They can be synthesised in the body from some amino acids or from glucose
  2. They can be salvaged from DNA and RNA degredation
  3. They can be obtained through the diet
  4. They can be taken in the form of a nutritional supplement

It is considered more efficient to utilise dietary nucleotides and derivatives because making them in the body is metabolically costly. Indeed some tissues have such a high demand for nucleotides that dietary supply may be crucial to their function, eg enterocytes, bone marrow and lymphoid tissue.

Nucleotides are a normal component of the adult diet and are ingested in the form of nucleoproteins. There are digestive enzymes in the gut which breakdown nucleoproteins and nucleic acids.

Proteases and nucleases are the enzymes which degrade nucleoproteins and nucleic acids into nucleotides; phosphatases and nucleotidases then break off the phosphate to give nucleosides. Whether the resulting substrate nucleotides can be fully absorbed through the intestinal wall is an issue of debate, some texts report that they are incorporated into tissues (Sanchez-Pozo & Gil 2002) and others suggest intestinal cells do not let them through and they are degraded and eliminated in urine and faeces (Carver 1999).

However it does appear that up to 5% of dietary nucleotides are incorporated into intestinal tissue, the liver and skeletal muscle (Carver 1999; Lopez-Navarro, et al 1996), and seeing as nucleotides are abundant in our diet, this is a significant figure.

Are nucleotides essential?

In short yes, nucleotides are essential. However, it does seem likely that essentiality can easily be met by nucleotides salvaged and synthesised from within the body (Sanchez-Pozo & Gil 2002), especially in older children and adults.

But the evidence is different in babies where as much as a third of requirements could be met by human milk. In Japan infant formulas have been supplemented with nucleotides since 1965, yet they didn’t start appearing in infant feeds elsewhere in the World until the 1980s and 90s (Loads & Denby 2008).

Supplementation of infant feeds with nucleotides has been shown to improve bifidobacteria, a friendly gut bacteria (Singhal, et al 2008), reduce pathogenic bacteria (Gil 2002) and improve immune function (Yu 2002).

Dietary nucleotides are not considered essential in the traditional sense because they can be synthesised in the body (Sanchez-Pozo & Gil 2002), but they may well be conditionally essential in three scenarios:

  1. During periods of insufficient food intake (developing countries famine and clinical conditions with high metabolic demand and low food intake)
  2. In the presence of disease
  3. Where there is a high level of growth and repair (Yu 2002), as in infant growth, post trauma and bodybuilders

It has also been shown that the enterocytes of the small intestine have a very high metabolic demand for nucleotides, but are not very good synthesisers of them, so dietary intake of them could improve function (Yu 2002). Nucleotides have also been examined in relation to irritable bowel syndrome (IBS) and it was shown that they may be semi-essential in certain people (Dancey, et al 2006).

No specific deficiency disease or condition has been identified in respect of nucleotides. But this may simply be because both salvage from recycled products of metabolism and de novo synthesis may be upregulated to compensate.

This is certainly sufficient for most cells, but in some specific cells, like enterocytes and immune system cells there may be some conditionally essentiality. Indeed, as mentioned above, in Japan, nucleotides are considered essential for infants, and are beginning to be thought of this way too.

Dietary Sources of Nucleotides

There is very little data available on the nucleotide content of foods in the raw state, let alone after processing. Free nucleic acids and nucleotides are present in all foods of animal and vegetable origin and are thus abundant in our diet. The amounts present in foods are dependant on cell density.

For example, larger amounts are found in meat, fish and seeds, whereas milk, eggs and fruit have lower amounts (Gil 2002). Indeed, growing conditions, methods of storage and food preparation methods can affect content significantly.

Nucleotide Supplements

A number of studies examining the effects of supplemental nucleotides have been carried out. In relation to IBS there has been improvement (Dancey, et al 2006) possibly though improved gut function from increased mucosal protein, DNA and villus height.

In athletes’ immune systems a number of aspects exhibit transient dysfunction following heavy exercise, meaning we are more open to infection.

If you’re ill, you can’t train and improve as efficiently. Improved immune function in athletes has been observed following nucleotide supplementation (Kulkarni, et al 1994). The immunoglobulin IgA is found in saliva where it is the first line of defence against upper respiratory tract infections. Salivary IgA has been shown to be reduced in endurance exercise (Nieman 2007). McNaughton, et al in two trials (2006, 2007) showed nucleotide supplementation increased salivary IgA post exercise in athletes. This certainly warrants further investigation.

Dietary and Supplementary Nucleotides and Performance

The precise influence of dietary nucleotides on human health and performance is far from fully understood, but the evidence does seem to point to them having some benefits. I’m not for one minute suggesting that these will be revolutionary supplements.

Let’s face it, there is a massive long list of ingredients used in bodybuilding and sports supplements which are marketed to morph our bodies and boost our performance to never previously seen levels, which in reality do no more than waste our hard earned cash.

In an industry desperately looking for anything to sell, it actually surprises me that there is so little data on the effects of dietary nucleotides on sports performance parameters, because there is credible information that they may be beneficial in helping us absorb our food and improve our immune systems; both of which are crucial in our quest to become bigger and stronger and to perform better.

Let’s hope we see more research very soon.


  • Carver J (1999). Dietary nucleotides: effects on the immune and gastrointestinal systems. Acta Paed Suppl 88:430, 83-8
  • Dancey C, et al (2006). Nucleotide supplementation: a randomised double-blind placebo controlled trial of IntestAidB in people with irritable bowel syndrome. Nutr J 5, 16
  • Gil A (2002). Modulation of the immune response mediated by dietary nucleotides. Europ J Clin Nutr 56:S 3, S1-S4
  • Kulkarni A, et al (1994). The role of dietary sources of nucleotides in immune function: A review. J Nutr 124:8, 1442S-1446S
  • Loades C & Denby N (2008). Nucleotides: Do they have a role in human health? NHD 37, 10-13
  • Lopez-Navarro A, et al (1996). Morphological changes in hepatocytes of rats deprived of dietary nucleotides. Br J Nutr 76, 579-589
  • McNaughton L, et al (2006). The effect of a nucleotide supplement on salivary IgA and cortisol after moderate endurance exercise. J Sports Med & Phys Fit 46, 84-89
  • McNaughton L, et al (2007). The effects of a nucleotide supplement on the immune response to short term, high intensity exercise performance in trained male subjects. J Sports Med & Phys Fit 47:1, 112-119
  • Nieman D (2007). Marathon training and immune function. Sports Med 37:4-6, 412-415
  • Sanchez-Pozo A & Gil A (2002). Nucleotides as semi-essential nutritional components. Br J Nutr 87:1S, S135-S137
  • Singhal A, et al (2008). Dietary nucleotides and fecal microbiota in formula-fed infants: a randomised controlled trial. Am J Clin Nutr 87:6, 1785-1792
  • Yu V (2002). Scientific rationale and benefits of nucleotide supplementation of infant formula. J Paed Child Health 38, 543-549
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James Collier

James first started bodybuilding as a teenager back in the 1980s and obtained his degree in Nutrition and Dietetics from the University of Surrey back in 1995. After qualifying he worked as a clinical Dietitian for the NHS in various UK hospitals.

Having competed several times during the 1990s, his passion now lies in helping other bodybuilders, strength and fitness trainees reach their goals.

He is a Registered Nutritionist and a full member of The Nutrition Society in the UK. James is also co-founder and developer of Huel, nutritionally complete food.

1 thought on “Dietary Nucleotides and their Role in Human Health, Sports Nutrition and Muscle Gain”

  1. Interesting article. A follow up would be great. Amino acids and nucleotides are able to reprogram cells and metabolic pathways.

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