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ATB
This a general thread on the subject of nucleotides as supplements and dietary components.

Nucleotides and Nucleosides, which are slightly altered, and related molecules are the subject here, and we may inclode the sugar ribose as well as its part of RNA.

To those who are not familiar with them, nucleosides are ntrogen containing molecules similar to amino acids in that they form the building blocks of many molecules in the life, but they may be found in simple molecules, on their own, or as more complex polymers.

It seems they may have beneficial effects as supplements.

Humans have an estimated 10, 000 taste receptors and 5 major taste sensations, which includes sweet, bitter and 'umami' which to me sounds vaguely sexual! This is the one that MSG hits and is the savoury ' brothy' receptor. Guanosine, the G in genetic code, is a nucleoside that also hits the savoury receptors and is used commercially as a flavour enhancer along with MSG.

Inosine, which is produced in the body from the nucleotide Adenosine, is also a stimulator of this sensation, and is also available as sodium inosinate as a food flavour enhancer. Keen spotters ammongst you may recall that inosine was the substance that had the best brain-regenerating effects following injury ever seen in animal studies, when it induced long distance rewiring in the brain. The potential seems great therefore, however, supplemental inosine does not reasdily pass into blood and brain, so it so far has to be injected directly.

AMP, adenosine mono-phosphate is part of the energy production system in the body. AMP is a 'bitter blocker' having very strong effects on elinating unpleasant astringent flavours. It is present in breast milk and it is hypothesised that this is a 'bitter blocker' that helps infants find the calcium rich milk more appetising. AMP is according to WIKI approved now as a bitter-blocker in America. This could make many fruits and natural substances much more appealing additives (i.e. pomegranates as sweetners).

This could be the biggest deal in the food sector for a long time, since normally fat, sugar and salt are used to hide undesirable ingredients and these flavours therefore directly drive the food processing industry in this direction, towards more calories and less micro-nutrients. Bitter-blockers, and a humble nucleotide, could be the most important weapon against this.

Nucleotides used as supplements are not well researched, but what is known seems favourable; boost on lifespan, immune cell and digestive benefits.

Ribose, which has many biological roles, although a sugar, is also a general fatigue fighter and health promotoer. These substances may together have potent health promoting effects.

Uridine, the U in genetic material, altered naturally to make Urisine, a nucleoside, is found in neurons and when combined with choline and DHA, was recently found to have profound brain growth enhancing effects in laboratory animals. Nucleotides too, could have similar synnergies.

Since many cells are reliant on their exogenous medium for nutrition, whilst under extreme growth stress - i.e. gut cells, and immune cells, and neurons, these seem to particularly benefit from enriching that medium with basic cell building blocks, whereas, less strained cells, in more sedentary roles, or which are dividing and growing / moving less vigourously, are probably more able to meet their demand endogenously by synthesising the various components themselves. Additionally, stress and disease may increase the demand for external sources of cell nutrients.

This is certainly what I think, and it is becomming clearer that in order for the cell to benefit from exogenous normally non-essential molecules, that all the key rate limiting components are needed at the same time. This is why food, biochemically complex and extremely bioactive, in a diverse diet, is associated with no toxicity and good health, whereas individual nutrients often have an associated toxicity profile.

With the nucletides, I am intrigued as to the possibility of obtaining nucleotide rich food sources as ingredients - as free nucleotides rather than buond RNA and DNA, or enriched RNA food supples, to see what promise they may hold in formulas and nutrient enriched foods.

For example, RNA enriched yeast powders are available.

Urisine is found in sugar extracts and one commercial supplement is available. Choline is easy to add to foods, and other nutrients and antioxidants can be easily added as food additives.

Going back to our taste perception, why do these components work so well? The answer is probably that they are healthsome, and we evolved to sense them through breast milks. Foods that may seek to be eaten, may employ these amino-acid and nucleotide tricks to make them more flavoursome. For example, glutamate is used by tomatoes as a natural flavour enhancer. These substances are cell building blocks and it makes sense that our taste buds look for them. In this way, macro-nutrients and bulk calories may not be the only influencer on the evolution of taste sensations, as previously thought. For example, umami is basically a sense for the complex nutritional value of a food, looking at its actual content rather than pure calorie contribution, being stimulated by nucleic acids and nucleotides.

And of course, its not only sugars that stimulate sweetness - but the amino acids glycine, glutamine and serine are extremely sweet agents.

With the nucvleotides there are other considerations, such as uptake and bioavailability with are not the same for each type, nor for polymers versus free nucleotides or nucleosides. IF a nucleotides is not readily taken into plasma and brain, it may however be possible to alter endogenous production favourably.

Anyway, some food toxicology data on flavour enhancers; http://www.inchem.org/documents/jecfa/jecmono/v32je06.htm

I'm looking at general data on health effects of nucleotides; here's a start

Nucleotides and IBS http://www.nutritionj.com/content/5/1/16

Adenosine and heart health, use as drug http://www.ashp.org/mngrphs/ahfs/a304010.htm

Adenosine, ATP, neurotransmission, aneathesia http://bja.oxfordjournals.org/cgi/content/full/94/5/556

"Based on the evidence from both animal and clinical studies performed during the last 20 years, ATP could provide a valuable addition to the therapeutic options in anaesthesia and intensive care medicine. In particular, its use in pain management, modulation of haemodynamics and treatment of shock seems promising. Further research is required, particularly on the issue of ATP–MgCl2, to clarify the exact role of ATP, magnesium and the combined compound.
"

patent http://www.freepatentsonline.com/5008251.html

list of RNA claims; http://www.vitaminexpress.com/encyclopedia.php/topic/RNA.php
Heavy_Lifter85
PA's company produces 6-methyl uracil:

http://www.giantnutrition.net/store/produc...;products_id=55

I don't believe I've ever seen any feedback on it.
liorrh
(by Michael Clive Price, author of the longevity report)
QUOTE
During digestion RNA is broken down into, and absorbed as, nucleotides and nucleosides. Nucleotides and nucleosides have a direct metabolic action, independent of their role in RNA, and are precursors to a number of coenzymes. The energy-supplying coenzyme ATP is a nucleotide, for instance, critical to our metabolism. There are other nucleotide coenzymes, such as UDP and CDP, required for biosynthesis of glycosaminoglycans, lipids and glycogen. (NAD and CoA are also nucleotide coenzymes, but are not derived from dietary nucleic acids.) Ribozymes, enzymes constructed from nucleotides instead of amino acids, are another example of the role of nucleotides.

RNA has a high turnover, being required for all gene expression and protein synthesis. We are capable of synthesising nucleotides from scratch (via the de novo pathways) but this is very expensive, in terms of the energy required. To ease the burden of de novo synthesis we have evolved the so-called salvage pathways which process nucleotides & nucleosides available both from our diet and from the natural turnover and breakdown of cellular RNA.

The amount of RNA in foodstuffs varies widely. Sardines, one of the most RNA rich foods, are between 0.5% – 1% by weight. To ingest the 250mg of RNA required for the life extension effect, we need only eat 12 – 25 g of sardines per day.

Summary: RNA enriched diets are beneficial to health, and in particular the immune system24, 26, 60, 61, and have extended lifespan1, 2.

[1a] The Use of Drosophila Melanogaster as a Screening Agent for Longevity Factors. I. Pantothenic Acid as a Longevity Factor in Royal Jelly. Thomas S Gardner, Journal of Gerontology 1(3) (1948): 1-8.

[1b] The Use of Drosophila Melanogaster as a Screening Agent for Longevity Factors. II. The Effects of Biotin, Pyridoxine, Sodium Yeast Nucleate, and Pantothenic Acid on the Life Span of the Fruit Fly. Thomas S Gardner, Journal of Gerontology 1(3) (1948): 9-13

[2a] The Effect of Yeast Nucleic Acid on the Survival Time of 600-Day-Old Albino Mice. Thomas S Gardner, Journal of Gerontology 3(?) (1946): 445-452. This reproduces the work of Robertson2b on lifelong administration of nucleic acid enriched diets, at a lower dosage.

[2b] Influence of Nucleic Acids of Various Origin upon the Growth and Longevity of the white mouse. TB Robertson in the Australian J of Experimental Biology and Medical Science, 5, (1928): 46-67

16% mean life span extension. Maximum lifespan (last 10%) extended by approximately 8-16%.

24a] Nucleic Acid Therapy in Aging and Degenerative Disease. Benjamin S Frank, MD. (1968) Library of Congress Catalog Card # 68-59227
[26a] Dietary nucleotides and gut mucosal defence. Grimble GK in Gut 1994 Jan;35(1Suppl):S46-S51

[26b] The role of dietary sources of nucleotides in immune function: a review. Kulkarni AD, Rudolph FB, Van Buren CT in J Nutr 1994 Aug;124(8 Suppl):1442S-1446S

[60] Nucleotides as immunomodulators in clinical nutrition. Grimble GK, Westwood OM in Curr Opin Clin Nutr Metab Care 2001 Jan;4(1):57-64

"supplementation of infant formula milk leads to improved growth and reduced susceptibility to infection. Animal studies have confirmed some of these data." … "Nucleotide supplementation has also been shown to improve some aspects of tissue recovery from ischaemia/reperfusion injury or radical resection." … "We propose that dietary nucleotides should be considered within a pharmacological and metabolic framework."

[61] Dietary nucleotides prevent decrease in cellular immunity in ground-based microgravity analog. Yamauchi K, Hales NW, Robinson SM, Niehoff ML, Ramesh V, Pellis NR, Kulkarni AD in J Appl Physiol 2002 Jul;93(1):161-6

"These results suggest that exogenous nucleotide supplementation, especially uracil, of normal diet is beneficial in the maintenance and restoration of the immune response".

Heavy_Lifter85
Benefits for IGA and corticol, not lactate or LDH.


The effects of a nucleotide supplement on the immune and metabolic response to short term, high intensity exercise performance in trained male subjects

Author: Mc Naughton, L; Bentley, D Koeppel, P Source: Journal of Sports Medicine & Physical Fitness 47, no. 1 (Mar 2007): p. 112-118 ISSN: 0022-4707 Number: 1273055311 Copyright: Copyright Edizioni Minerva Medica Mar 2007


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Aim. The aim of this work was to determine the ergogenic effects of a nucleotide supplement on the metabolic and immune responses to short term high intensity exercise in volunteer, trained, male subjects.

Methods. Thirty moderately trained male subjects were randomly divided into 3 equal sized groups, control ©, placebo (P) or experimental (E). Each subject undertook a 2 min maximal exercise test prior to, and after 60 days, on either a nucleotide (E) or placebo supplement. Prior to exercise testing unstimulated saliva samples and blood samples were taken. Saliva was analysed for cortisol and IgA, while blood was analysed for lactate, lactate dehydrogenase and creatine kinase.

Results. The postexercise C value was significantly higher than the pre-exercise concentration (P<0.0001; for C, P, and E). In the postsupplement C analysis, the E postexercise group was significantly lower than either the C (P<0.005) or the P group (P<0.05). In the pre- and post supplementation periods, the pre-exercise SIgA values were significantly higher than the postexercise values (P<0.0001). However, in the postsupplementation period, the SIgA value in the E group was significantly higher than either the P (P<0.05) or C (P<0.05) groups. There were no significant changes in blood lactate, lactate dehydrogenase, or creatine kinase concentrations post supplementation.

Conclusion. We concluded that a chronically ingested nucleotide supplement blunts the response of the hormones associated with physiological stress.




Results

There was no difference in the amount of work completed by the subjects in the pre- or postsupplementation tests and neither was there any difference between the 3 groups.

There was a significant Time^sub *^Group interaction effect (F(^sub 6,81^) = 2.58, P<0.03, Power = 0.83) for salivary cortisol. There was also a significant main effect of Groups (F(^sub 2,27^) = 3.29, P<0.05, Power = 0.57) as well as for Time (F(^sub 3,81^)= 168.1, P<0.0001, Power = 1.0). A comparison of the presupplementation, pre- and postexercise cortisol values, indicated that in all 3 groups, the postexercise value was significantly higher than the preexercise concentration (C<0.0001; E<0.0001; P<0.0001). In the postsupplement analysis, the postexercise values were again significantly higher than the respective preexercise concentration (P<0.0001). However, the E postexercise group was significantly lower than either the C (P<0.005) or the P group (P<0.05). Salivary cortisol responses are shown in Figure 1.

The repeated measures analysis for salivary IgA, indicated that there was no significant Time*Group interaction effect (F(^sub 6,81^) = 0.46, P>0.83, Power = 0.18) nor any group effect (F(^sub 2,27^) = 0.76, P>0.48, Power = 0.1). The time effect was however, significant (F^sub (3,81)^=143.8, P<0.0001, Power = 1.0) The Fisher's post-hoc ANOVA conducted on the date indicated that for all groups, in the pre- and postsupplementation periods, the pre-exercise values were significantly higher than the postexercise values (P<0.0001). However, in the postsupplementation period, the SIgA value in the E group was significantly higher than either the P (P<0.05) or C (P<0.05) groups. The salivary IgA responses can be seen in Figure 2.

The blood lactate response is shown in Figure 3. The repeated measures ANOVA showed no interaction (Time*Groups) effect (F^sub (6,81)^ = 0.24, P>0.96, Power = 0.11) nor any effect of groups (F(2,27) = 0.21, P>0.81, Power = 0.10). There was however a significant effect of Time (F^sub (3,81)^ = 476,4, P<0.0001, Power = 1.0), and the post-hoc analysis indicated that in all cases, the postexercise blood lactate concentration was significantly higher than the pre-exercise concentration (P<0.0001).

Neither LDH (Figure 4) or CK (Figure 5) was affected by the nucleotide supplement in pre- or postexercise measures after supplementation. LDH did not change either pre- or postexercise, or on the basis of the supplement, and the ANOVA conducted was not significant (P>0.42). The ANOVA performed on the CK values was not significant (P>0.3) but post-hoc analysis indicated that there was a significant time effect (P<0.001) and that all postexercise levels were significantly higher than their corresponding pre-exercise level (P<0.05).
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