DNA (deoxyribonucleic acid), the molecule that comprises the genome, and RNA (ribonucleic acid) are marketed as nutritional supplements. DNA, which makes up the genetic material, is comprised of units called nucleotides. A nucleotide consists of a base, a sugar and a phosphate group. The major bases in DNA are the purines adenine and guanine and the pyrimidines cytosine and thymine. The sugar moiety of the nucleotide is 2′-deoxyribose. RNA, which is more abundant in tissues than DNA by about an order of magnitude, is also comprised of nucleotide units. In the case of RNA, the major bases are again the purines adenine and guanine, and the pyrimidines are cytosine and uracil. One of the major differences between DNA and RNA is the presence of uracil in RNA and of thymine in DNA. The other major difference is in the sugar moiety. In RNA, the sugar moiety of the nucleotide is ribose, whereas in DNA it is deoxyribose.
For years, nucleic acids and nucleotides were not considered essential nutrients. It was thought that the body can synthesize sufficient nucleotides to meet its physiological demands via de novo nucleotide synthetic pathways. Some research during the last several years indicates that this may not be completely correct. There are certain conditions in which the body requires dietary nucleic acids/nucleotides to meet its physiological requirements. These conditions include rapid growth, limited food supply and metabolic stress. Under these conditions, metabolic demand exceeds the capacity of de novo synthesis. Under these conditions, dietary nucleosides, nucleotides and nucleic acids become conditionally essential nutrients. Dietary nucleotides may spare the energetic cost of de novo synthesis of nucleotides.
Dietary nucleic acids are found in plant and animal foods. The dietary intake of RNA is typically about an order of magnitude greater than DNA. The nucleotide salts disodium inosinate and disodium guanylate are present in many food products as seasoning substances, contributing to the dietary nucleotide intake. Interestingly, mother's milk is a rich source of nucleic acids, especially RNA, and nucleotides. There are a few medical foods and enteral supplements containing RNA and nucleotides, which are used for immune-enhancement under conditions of metabolic stress. RNA and nucleotides are sometimes referred to as immunonutrients. Nutritional supplements of RNA, DNA, nucleotides, nucleosides and bases are also being marketed.
Actions & Pharmacology
Nucleic acids and nucleotides may have immune-enhancing and tissue-regenerating activities.
Mechanism of Action
Nucleotides have been demonstrated to affect a number of immune functions, including reversing malnutrition and starvation-induced immunosuppression, enhancing T-cell maturation and function, enhancing natural killer cell activity, improving delayed cutaneous hypersensitivity, aiding in resistance to such infectious agents as Staphylococcus aureus and Candida albicans, and modulating T-cell responses toward type 1 CD4 helper lymphocytes or Th1 cells. Mice fed a nucleotide-free diet have both impaired cellular and humoral immune responses. Addition of dietary nucleotides restores both types of responses. Both RNA, which can be considered a delivery form of nucleotides, and ribonucleotides were used in these studies. The mechanism of the immune-enhancing activity of nucleic acids/nucleotides is unclear.
RNA and nucleotides have been shown to have stimulatory effects on recovery from hepatectomy in animals. They have also been shown to stimulate intestinal repair, in animals. The mechanism of the tissue-regenerating effects of RNA and nucleotides is unclear. Possibly the regenerating activity may be explained, in part, by the nucleotides serving as precursors of nucleic acid synthesis via the salvage pathways of nucleotide synthesis. Utilization of the salvage pathways may spare the energetic cost of de novo nucleotide synthesis.
RNA is digested in the small intestine via the action of the pancreatic enzyme ribonuclease to the nucleotides adenosine-5′-monophosphate (AMP), guanosine-5′-monophosphate (GMP), cytidine-5′-monophosphate (CMP) and uridine-5′-monophosphate (UMP). These nucleotides are then hydrolyzed to the nucleosides adenosine, guanosine, cytidine and uridine, respectively, via the action of the enzymes alkaline phosphatase and nucleotidase. The nucleosides may be further hydrolyzed to the purine bases adenine and guanine and the pyrimidine bases cytosine and uracil.
The nucleosides are transported in the enterocytes by both facilitated diffusion and sodium-dependent carrier mediated processes. Under normal conditions, that is, under conditions where the body is not under metabolic stress, the nucleosides undergo extensive catabolism in the enterocytes. The end product of purine catabolism is uric acid. An end product of pyrimidine metabolism is beta-alanine. Nucleosides and bases that are not catabolized in the enterocytes are transported via the portal circulation to the liver, where they are also catabolized. A small percentage of ingested RNA and nucleotides reach the systemic circulation and is transported to various tissues of the body.
Even under normal conditions, a small percentage (from 2% to 5%) of dietary RNA and dietary nucleotides is incorporated into nucleic acids, especially in the small intestine, liver and skeletal muscle. This occurs via the salvage pathways of purine nucleotide and pyrimidine nucleotide synthesis. During conditions of metabolic stress, including trauma, rapid growth and limited food supply, there is apparently greater conversion of dietary RNA and nucleotides into tissue nucleotides and nucleic acids.
DNA is digested in the small intestine via the action of the pancreatic enzyme deoxyribonuclease to deoxynucleotides; these, in turn, are hydrolyzed to deoxynucleosides and finally to the pyrimidine bases cytosine and thymine and the purine bases adenine and guanine. The deoxynucleosides and bases are absorbed by the enterocytes and processed as described above for the nucleosides.
Indications & Usage
The nucleotides appear to be effective in boosting immune response in some circumstances. They may also promote tissue repair in some conditions. Claims that they are an effective treatment for Alzheimer's disease, depression, skin disorders, sexual dysfunction, fatigue and aging are unsubstantiated.
Medical foods are available containing RNA as a delivery form of nucleotides/nucleosides, sometimes along with L-arginine and fish oils. These medical foods are used to support the immune system under conditions of metabolic stress.
RNA and DNA nutritional supplements are available, with RNA supplements being more popular. Typical doses range from 0.5 to 1.5 grams daily.
Brewer's yeast is a rich source of RNA (see Brewer's Yeast). Inosine is a nucleoside (see Inosine).
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Research & Summary
Numerous studies have shown that nucleotides can help restore immune function in malnourished animals, can enhance the activity of T-cells and natural killer cells, and can increase resistance to some pathogenic agents. Infants fed formulas supplemented with nucleotides had a lower incidence of diarrhea, higher natural killer cell activity and higher antibody titers following Haemophilus influenzae type b vaccination, compared with unsupplemented controls. In another study, post-operative immune response, evidenced by several measures, was enhanced in patients with upper-gastrointestinal cancer who were given supplements of RNA, arginine and omega-3 fatty acids.
Nucleosides have promoted tissue repair in a number of animal studies. They have shortened recovery time in animals with liver injury and have enhanced healing of experimental intestinal ulcers. They have shortened recovery time following small and large bowel injuries.
Contraindications, Precautions & Adverse Reactions
Supplemental RNA, DNA, nucleotides and nucleosides are contraindicated in those hypersensitive to any component of products containing these substances.
Pregnant women and nursing mothers should avoid nucleic acid and nucleotide supplements unless recommended by their physicians.
Those with a history of hyperuricemia should be extremely cautious about use of nucleic acid and nucleotide supplements.
No reports of adverse reactions.