The authors of this article [Herrick et al., 2009: (http://linkinghub.elsevier.com/retrieve/pii/S0306987709000061)] suggest that people could combine D-ribose with caffeine to augment the effect of caffeine and conceivably decrease the adverse effects associated with caffeine intake. The authors are essentially saying that ribose could augment ATP production and either decrease or increase the export of adenosine and its nucleotides from cells, meaning neurons, that have been stimulated by caffeine, etc. There's some validity to this suggestion, but, in my opinion, using purines or uridine as a source of small amounts of ribose would be a safer and more effective approach in the long term. Inosine monophosphate is ~43 percent ribose, and some similar percent of adenosine and guanosine are ribose. I don't feel like looking up the molar masses. In my opinion, high-dose ribose is not really a good idea, but I suppose one approach would be to combine small doses of ribose with purines and uridine or cytidine (uridine has been shown to elevated the cytidine and uridine nucleotide pools to significant extents, and so one doesn't need to take cytidine, really), etc. Barsotti and Ipata (2002) [Barsotti and Ipata, 2002: (http://www.ncbi.nlm.nih.gov/pubmed/11841784)] note that ribose has been shown to more effectively augment ATP repletion, following ischemia, when purines or purine bases are given along with the ribose (references 2 and 4, p. 130). Other articles have also shown that to be the case [Smolenski, 2000: (http://www.actabp.pl/pdf/4_2000/1171-1178s.pdf)(http://www.ncbi.nlm.nih.gov/pubmed/11996106)].
One major reason I say that ribose from purines would, in my opinion, be safer is that ribose has been shown to increase the export of purine nucleotides and nucleosides from skeletal muscle cells and other cell types (including cells in the liver, etc.). The "purine-wasting" effect is not nearly as large as the effect of xylitol (I've cited much of this research in postings in December and early January) or fructose, but there is the potential for that to occur, in my opinion. That essentially means, in my view, that there would be short-term export of purines that would appear to be beneficial and long-term sequalae that would not be desirable. A similar effect occurs with something like zinc, which shows all these apparent "antidepressant" effects in short-term animal studies. Zinc increases the export of adenosine and other purines, partly by serving as a cofactor for a number of nucleotidase enzymes that degrade intracellular and extracellular nucleotides. That can produce short-term benefits, but the articles showing neurotoxicity from excessive zinc supplementation or from derangements in zinc homeostasis, in the absence of supplementation, are almost endless in numbers and are just absolutely appalling to see. I collected about a hundred of them in a list, and I'll try to link to a large number of them one of these days. They're not pleasant to look for or to read. That's an extreme example, in any case. Also, adenosine is exported from neurons in a generalized manner in response to neuronal activity, and that would be part of the rationale for providing actual exogenous purines instead of ribose. This is basically the same thing I've been saying over and over again, and there are almost innumerable articles showing that purine export is a generalized response to the excitation of neurons, either by electrical stimulation or pharmacological manipulations that increase excitatory neurotransmission. This effect, again, to the extent that it would be therapeutic, might not be long-lived in the absence of some attempt to address the resulting deficit in the intracellular purine pools. I came across a reference to an old article suggesting that antidepressants may exert some of their effects by increasing adenosine availability (this was discussed in the context of the capacity of low levels of adenosine to produce activation, rather than inhibition, of adenylate cyclase) [cited as reference 7 on p. 598 in Cooper et al., 1980: (http://www.ncbi.nlm.nih.gov/pubmed/6162091)]. I'm not sure if that cited article is talking about a reduction in the export of adenosine or about the export of adenosine from astrocytes leading to the import of adenosine into neurons. But I have multiple articles showing that either exogenous guanosine, adenosine, or inosine can elevate cAMP in various cell types, and I don't feel like linking to them right now. cAMP signaling is really complex, though, and an increase in the activities of cAMP-dependent protein kinases can be "pathological" or undesirable under some circumstances, and adenosine exerts a very complex set of effects on cAMP signaling.
Ribose mainly would contribute to the pool of intermediates in the nonoxidative pentose cycle, and this would mainly assist, to some extent, in the salvage of purines and in the provision of ATP by glycolysis, etc. (the activities of the enzymes of the de novo purine biosynthetic pathway are very low in the brain, and any increase in de novo inosine monophosphate formation from exogenous ribose alone would, in my opinion, be fairly minimal).
This suggestion about ribose is actually sort of minimally interesting in the context of the bizarre formulation of some of these well-known energy drinks advertised heavily on tv. I'm not going to say the brand, but I looked up the ingredients to see what was supposed to be so special about one of them. I see nothing very special about it and don't see the appeal of it. But an ingredient that stands out, in combination with caffeine, as being unusual is glucuronolactone. This is metabolized into glucuronic acid, and some of labeled glucuronolactone is converted into L-xylulose and then ribose [Hiatt, 1958: (http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1062823&blobtype=pdf)(http://www.ncbi.nlm.nih.gov/pubmed/13575548)]. So, in my opinion, glucuronolactone is like a third-rate substitute for ribose (the conversion of L-xylulose into xylulose-5-phosphate is ATP-consuming, and this ATP consumption and phosphate sequestration is basically the mechanism whereby xylulose produces more purine depletion than ribose, etc.). These types of differences in the point of entry into the pentose cycle have been shown, fairly clearly, in my opinion, to produce surprisingly significant effects on ATP levels and phosphate sequestration, and it's partly because of the large amounts of the sugar(s) entering cells at one time.
Another advantage of providing the actual purines, as a source of ribose, would be, in my opinion (apart from the peroxynitrite scavenging effect of uric acid), the capacity of uric acid (urate) to influence purine metabolism indirectly (also, oral inosine has been shown to elevate plasma hypoxanthine and xanthine in humans, and the contribution of those elevations in hypoxanthine to the effects associated with inosine should not be underestimated). Hunter et al. (1990) [Hunter et al., 1990: (http://www.ncbi.nlm.nih.gov/pubmed/2345757)] found that elevating uric acid in the blood of rats decreased the density of A1 adenosine receptors in the striatum, a site of action of caffeine. In contrast, caffeine upregulated the A1 adenosine receptor density. This basically shows that uric acid elevations decreased the tolerance to caffeine by downregulating the chronic caffeine-induced upregulation of A1 adenosine receptor density [caffeine is a nonselective adenosine receptor antagonist, but its acute blocking effect on (antagonism of) A1 adenosine receptors figures prominently into its stimulant effects]. Thus, in a person who has never taken caffeine, the antagonism is robust, but the receptor density becomes gradually upregulated in response to the presence of the antagonism by caffeine. Increases in extracellular or intracellular uric acid may oppose that, but Hunter et al. (1990) found that uric acid was not a direct A1 adenosine receptor antagonist at physiologically-relevant concentrations. One mechanism could be feedback inhibition of xanthine oxidase activity [cited as reference 16 in Kroll et al., 1992: (http://www.ncbi.nlm.nih.gov/pubmed/1539702)]. I've never heard anyone talk about that mechanism, and it could be really important for understanding purine metabolism. There's research showing that the Ki for the feedback inhibition of xanthine oxidase by uric acid (urate) may be as low as 200 uM, a physiologically relevant concentration. This could spare ATP, given that xanthine oxidase is an ATP-consuming reaction and consumes reducing equivalents. I saw that the articles showing feedback inhibition of xanthine oxidase by endogenousl purines and purine-based drugs haven't been cited very many times, but, if that effect occurs in humans, it would be a really important mechanism, in my opinion. An excess of intracellular urate can obviously be detrimental, and one would want to discuss any of this with one's doctor and have one's uric acid checked. There's evidence that urate can inhibit glycogen phosphorylase, and caffeine can also inhibit glycogen phosphorylase. That would be counterproductive to any supposed therapeutic effects, and the levels of plasma urate at which those undesirable effects might begin to occur are not well-known. But there's research showing, for example, that hyperuricemia induced by excessive inosine supplementation (in a study in athletes whose urate levels were already high-normal) can worsen exercise performance, and inhibition of glycogen phosphorylase could account for that.
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