Nucleotides and the Paleo Diet

by Mark Connell August 15, 2009

Fresh liver--a rich source of nucleotides[/caption]

This article originally appeared in  The Paleo Diet Update, v5, #33 - Nucleotides and the Paleo Diet (August 14, 2009), published by and Loren Cordain, Ph.D. It was written by Mark Connell of nuBound and is reprinted with permission.

The Paleo Diet Update newsletter is a great nutrition resource. Subscribe to The Paleo Diet newsletter to begin building your own archive!

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Nucleotides are small molecules that are the building blocks of DNA and RNA. They are composed of a nitrogen-containing base bonded to a sugar and one or more phosphate groups. Nucleotides occur in all foods of animal or vegetable origin as free nucleotides or nucleic acids. Their concentration depends on cell density, which explains why organ meats are such a rich source.

Traditionally, nutritionists have dismissed any dietary need for nucleotides arguing that the body can produce them itself. This view has begun to change over the last two decades as a mounting body of research has demonstrated that dietary sources of nucleotides play several key roles.

One hint to the larger story is that the preponderance of foods with high concentrations of nucleotides are Paleo foodstuffs, such as game, organ meats (heart, liver, spleen, lungs and sweetbreads) and whole fish. /1-2 Human milk also contains high levels of nucleotides. /3

Research has uncovered multiple roles for dietary nucleotides, including growth and repair of the intestinal lining and liver, /4-5 modulation of the immune system, /6-7 and protein synthesis, /8 among other functions.

While the body is able to synthesize nucleotides from scratch, dietary sources of nucleotides are now considered semi-essential nutrients /9 under stressful conditions (which hamper the body's synthesis of nucleotides), such as rapid growth, malnutrition or infection. Additionally, certain tissues, such as the gut, which have a low capacity to produce nucleotides on their own, utilize salvage of dietary nucleotides to meet much of their need.

The long recognized superior health of breast-fed babies /10 is now attributed in part to the presence of nucleotides in mother's milk. /11 Several infant formula makers now add nucleotides to their cow's milk-based infant formula in an attempt to more closely mimic nature.

The lining of the gut is subject to rapid turnover with complete replacement occurring in less than one week. /4 Nucleotides assist both the continuous proliferation of cells and promote the development of the folds (villi), which allow proper absorption of nutrients. /12 Maintaining the integrity of the gastrointestinal tract is key in avoiding the complications arising from leaky gut.

Immune suppression is well documented in both endurance and strength/power athletes. /13 Recent studies of athletes supplementing their diet with nucleotides have suggested an improvement in immune function and faster recovery. /14-15

The Paleo Diet offers an abundance of nucleotides in comparison to a Neolithic diet, which includes the newer grains, dairy, and sugar never eaten by our Paleolithic ancestors. Basing your meals on the Paleo Diet, mainly lean meat, seafood, fruits, and vegetables, can help with intestinal permeability, immune function, and other functions that dietary nucleotides have been found to enhance.


1. Siegfried Souci, W. Fachmann and Heinrich Kraut. 2008. Food Composition and Nutrition Tables, 7th Edition. Medpharm.

2. Rodney Grahame, H. Anne Simmonds and Elizabeth Carey. 2003. Gout: Answers at Your Fingertips. London: Class Publishing Ltd.

3. Agget P, Leach JL, Rueda R and MacLean WC. Innovation in infant formula development: A reassessment of ribonucleotides in 2002. Nutrition. 2003; 19:375-384.

4. Carver JD. Dietary nucleotides: effects on the immune and gastrointestinal systems. Acta Paediatr Suppl. 1999; 430: 83-88.

5. Grimble GK. Dietary nucleotides and gut mucosal defense. Gut. 1994; 35: Suppl S46-S51.

6. Gil A. Modulation of the immune response mediated by dietary nucleotides. European Journal of Clinical Nutrition. 2002; 56:Suppl 3, S1-S4.

7. Maldonado J, Navarro J, Narbona J and Gil A. The influence of dietary nucleotides on humoral and cell immunity in the neonate and lactating infant. Early Human Development. 2001; 65 Suppl: S69-S74.

8. Sanchez-Pozo A and Gil A. Nucleotides as semiessential nutritional components. British Journal of Nutrition. 2002; 87:Suppl. 1 S135-S137.

9. Grimble GK. Why are dietary nucleotides essential nutrients? British Journal of Nutrition. 1996; 76:475-478.

10. Dewey KG, Fleming J, Nommsen-Rivers LA. Differences in morbidity between breast-fed and formula-fed infants. J Pediatr. 1995; 126:696-702.

11. Schaller JP, Kuchan MJ, Thomas DL, Cordle CT, et al. Effect of dietary ribonucleotides on infant immune status. Pediatric Research. 2004; 56:883-900.

12. Ortega MA, Nunez MC, Gil A and Sanchez-Pozo. Dietary nucleotides accelerate intestinal recovery after food deprivation in old rats. Journal of Nutrition. 1995; 125:2090-2095.

13. Nieman DC. Marathon training and immune function. Sports Medicine. 2007; 37(4-5): 412-415.

14. McNaughton L, Bentley DJ and Koeppel P. The effects of a nucleotide supplement on salivary IgA and cortisol after moderate endurance exercise. J Sports Med and Physical Fitness. 2006; 46:84-89.

15. McNaughton L, Bentley DJ and Koeppel P. The effects of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performed in trained male subjects. J Sports Med and Physical Fitness. 2007; 47:112-118.

Mark Connell
Mark Connell


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