by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS, CFT
A Little Logic
Imagine crashing your car into a tree and sustaining massive damage to the front end. Along comes some guy and says, “Here’s your hubcap, now that should take care of the problem.” You would be pretty upset with this fool, because it’s going to take a lot more than a hubcap to fix your car. This simplistic, single-minded approach is exactly what many supplement companies use in their ads. “Take this and get bigger, stronger or recover faster.” The latest supplement that everyone is hyping is ribose. It has been touted as “The Great Genetic Equalizer” in terms of its ability to increase post-exercise recovery. This article reviews some of the claims made for ribose along with the science behind them. It concludes with some practical recommendations that will help you to decide for yourself if you want to try the product now or wait until more research is available and the price comes down.
A Simple Sugar
Ribose is a naturally occurring simple sugar. Structurally, ribose is important because it can serve as the basis for making glycogen precursors, nucleic acids, nucleotides (energy rich compounds), and ATP (adenosine triphosphate). The key pathway where these events start is called the Pentose Phosphate Pathway, which occurs in a variety of mammals [1]. The fact that ribose can be converted into a form of glucose and stored as glycogen is hardly newsworthy. However, its other roles are. Nucleic acids include ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). DNA serves as the storage site for genetic information. RNA translates genetic information into biological products, like more RNA or proteins. The proteins are then used structurally, like keratin, which makes your nails hard, or functionally, like enzymes catalyzing reactions. Interesting, but no evidence exists to indicate that we need more ribose to synthesize nucleic acids. Long before ribose came out everyone has been synthesizing these molecules just fine. Any impact ribose has in this area would be minimal, at best.
ATP Production
What does make ribose appealing though, is that it can be converted (through a series of reactions) into a glucose metabolite, pyruvate, or nucleotides, all of which can be used to make ATP. ATP is the high-energy molecule that provides the chemical energy for us to do mechanical work such as running and lifting weights. The idea that ribose could increase ATP levels would certainly make one speculate that ribose could increase performance. But before jumping the gun and rushing out to buy some, we first have to examine the ways by which ribose could elevate ATP.
Ribose can be used to make ATP through the Pentose Phosphate Pathway. To understand this better, we have to cover a little biochemistry. Realize that the body is a very dynamic organism. The main purpose of the Pentose Phosphate Pathway is to take a five-carbon sugar (pentose) like ribose, add other molecules to it, and make nucleotides. The energy rich nucleotides are then used to make adenosine monophosphate (AMP). AMP is then used to make adenosine diphosphate (ADP) and then ATP. The simple version of this pathway would therefore look like this:
Understand that these are not necessarily direct conversions and that there may be multiple steps between the components above (for more details consult a biochemistry text such as Zubay’s or Harper’s). Ribose-5-phosphate can be converted into PRPP (phosphoribosyl pyrophosphate). PRPP can then serve as the precursor to making nucleotides (like IMP) and this part of the Pentose Phosphate Pathway is referred to as the de novo Pathway (because nucleotides are synthesized). PRPP can also stimulate the production of nucleosides, which are then converted into nucleotides as part of the salvage pathway (because normally these nucleosides are leaked out of the cell into the blood). In healthy people at rest, the body is quite capable of recycling AMP into ATP. However, when someone is unhealthy, the above pathway is impaired. For this we’ll need to analyze the pathway in some more detail.
Ribose For Impaired Health
Ribose is not a magical supplement that will cure everything. It does appear to have some application for diseases where the body can not make sufficient ATP. In 1984, the Annals of Surgery published a review of the different interventions that could improve myocardial recovery following ischemia (lack of oxygenated blood) [2]. When blood flow to myocardial (heart) tissue is impaired, ischemia can result. The pain in the heart is clinically termed a myocardial infarction and is commonly known as a heart attack. Without oxygen the cardiac (heart) cells can no longer produce ATP from fatty acid oxidation and must rely on recycling ATP metabolites like ADP and AMP. As the oxygen-deprived cells generate more AMP and nucleosides, the cells become less able to resynthesize ATP. The result is that nucleosides and nucleotides leak out of the cell into the blood making less precursors for ATP synthesis available.
The production of PRPP as part of the de novo Pathway is the weak link in the Pentose Phosphate Pathway to producing ATP [3]. Research on rats has established that supplemental ribose can increase PRPP levels [4-7]. Ribose administration was also shown to improve nucleotide synthesis in dogs [8, 9], and in vitro (outside the body) research indicates that it is not species specific and can also do the same in humans [1]. It can elevate nucleotide levels in certain disorders, thus lending support to the notion that it can increase ATP levels via the Pentose Phosphate pathway in humans [10]. In addition, research on people afflicted with coronary artery disease indicates that high dose ribose therapy (60 grams in four divided doses for 3 days) [11] can be beneficial during exercise. Certain diseases such as myoadenylate deaminase deficiency may be successfully treated by treatment of 4 grams of ribose every 10-30 min during exercise [12]. Other studies also indicate that ribose may have a therapeutic role in specific situations, but can ribose benefit healthy people?
Ribose For Healthy People
Besides the fact that most of the research to date was done on rats or dogs, there is another important point that should be made. In general, ribose is shown to have a therapeutic effect when it is infused or given orally in multiple dosages. The point here is that around 20-60 grams per day appears necessary in order to have some benefit. One could speculate that healthy people may not need as much ribose, but more research is needed to know conclusively. What we do know is that ribose is absorbed fairly well across the small intestine and avoids first pass catabolism by the liver [13]. In an isolated guinea pig heart model, ribose elevated ATP, ADP and nucleotide levels after the tissue was deprived of oxygen [14]. It did this without affecting creatine phosphate stores. Since we know creatine works and that ribose also works for a variety of species, it certainly makes one hope that there is an additive effect between ribose and creatine monohydrate. There isn’t any research data available yet on creatine and ribose mixtures in humans. It is quite possible that there won’t be an additive effect, but even though there is a limited amount of data on ribose, it is conceivable that high dosages of ribose (around 20 grams per day or more) would have an additive effect with creatine.
Despite the potential for ribose to improve exercise performance in patients suffering from a variety of disorders, little has been done to see if it can improve athletic performance. Research indicates that adenine nucleotides are decreased under a variety of exercise conditions, from sprinting to endurance training [15-20]. While subjects in these studies did not lift weights, it can be safely assumed that nucleotide levels are depleted as well during resistance exercise. Since ribose can increase both nucleosides and nucleotides leading to the production of AMP, ADP, and ATP, it certainly holds promise. What we don’t know is just how much improvement one could expect.
The side effects of ribose reported in the literature appear to be limited to diarrhea when excessive dosages are consumed. This is expected and, in general, when simple sugars such as fructose or ribose are consumed alone in excess of 50 grams, diarrhea can occur. Another area of concern is the potential for gout to be exacerbated by excessive PRPP levels [21]. This doesn’t mean that you will get gout from ribose, only that if you have gout you may wish to rethink your supplement strategy. Another approach to maintaining ATP precursors is to simply ingest some type of sports drink containing about 8% carbohydrate [22, 23]. Carbohydrate ingestion during prolonged exercise also increases ATP precursors. Perhaps the next workout drink of choice will contain creatine, ribose, and glucose. For now if you plan on trying ribose, make sure you take some before and after your workout. Keep track of your dosages and a training journal, which should include your body weight. Don’t expect ribose to turn you into a world champion, but you should notice an improved ability to come back and train hard again. Anecdotal reports sent to me so far have been mixed. This is expected given the number of different ribose products tried and dosages used. The favorable reports claim that users could lift more weight or the same weight for more repetitions. So far no one has reported any weight changes after taking ribose. Feel free to email me with your results.
References
1. Zimmer, H.G., et al., Ribose intervention in the cardiac pentose phosphate pathway is not species-specific. Science, 1984. 223(4637): p. 712-714.
2. Pasque, M.K. and A.S. Wechsler, Metabolic intervention to affect myocardial recovery following ischemia. Ann Surg, 1984. 200(1): p. 1-12.
3. Sperling, O., et al., Regulation of de novo purine synthesis in human and rat tissue: role of oxidative pentose phosphate pathway activity and of ribose-5-phosphate and phosphoribosylpyrophosphate availability. Adv Exp Med Biol, 1977: p. 481-487.
4. Zimmer, H.G., The oxidative pentose phosphate pathway in the heart: regulation, physiological significance, and clinical implications [editorial]. Basic Res Cardiol, 1992. 87(4): p. 303-316.
5. Zimmer, H.G., Significance of the 5-phosphoribosyl-1-pyrophosphate pool for cardiac purine and pyrimidine nucleotide synthesis: studies with ribose, adenine, inosine, and orotic acid in rats. Cardiovasc Drugs Ther, 1998. 12 Suppl 2: p. 179-187.
6. Zimmer, H.G., Regulation of and intervention into the oxidative pentose phosphate pathway and adenine nucleotide metabolism in the heart. Mol Cell Biochem, 1996. 160-161: p. 101-109.
7. Pasque, M.K., et al., Ribose-enhanced myocardial recovery following ischemia in the isolated working rat heart. J Thorac Cardiovasc Surg, 1982. 83(3): p. 390-398.
8. St. Cyr, J.A., et al., Enhanced high energy phosphate recovery with ribose infusion after global myocardial ischemia in a canine model. J Surg Res, 1989. 46(2): p. 157-162.
9. Mauser, M., et al., Influence of ribose, adenosine, and “AICAR” on the rate of myocardial adenosine triphosphate synthesis during reperfusion after coronary artery occlusion in the dog. Circ Res, 1985. 56(2): p. 220-230.
10. Wagner, D.R., U. Gresser, and N. Zollner, Effects of oral ribose on muscle metabolism during bicycle ergometer in AMPD-deficient patients. Ann Nutr Metab, 1991. 35(5): p. 297-302.
11. Pliml, W., et al., Effects of ribose on exercise-induced ischaemia in stable coronary artery disease. Lancet, 1992. 340(8818): p. 507-10.
12. Zollner, N., et al., Myoadenylate deaminase deficiency: successful symptomatic therapy by high dose oral administration of ribose. Klin Wochenschr, 1986. 64(24): p. 1281-1290.
13. Gross, M., S. Reiter, and N. Zollner, Metabolism of D-ribose administered continuously to healthy persons and to patients with myoadenylate deaminase deficiency. Klin Wochenschr, 1989. 67(23): p. 1205-1213.
14. Seifart, H.I., U. Delabar, and M. Siess, The influence of various precursors on the concentration of energy-rich phosphates and pyridine nucleotides in cardiac tissue and its possible meaning for anoxic survival. Basic Res Cardiol, 1980. 75(1): p. 57-61.
15. Tullson, P.C. and R.L. Terjung, Adenine nucleotide metabolism in contracting skeletal muscle. Exerc Sport Sci Rev, 1991. 19: p. 507-537.
16. Sahlin, K. and S. Broberg, Adenine nucleotide depletion in human muscle during exercise: causality and significance of AMP deamination. Int J Sports Med, 1990. 11 Suppl 2: p. S62-S67.
17. Stathis, C.G., et al., Influence of sprint training on human skeletal muscle purine nucleotide metabolism. J Appl Physiol, 1994. 76(4): p. 1802-1809.
18. Hellsten-Westing, Y., et al., Decreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity training. J Appl Physiol, 1993. 74(5): p. 2523-2528.
19. Putman, C.T., et al., Effects of short-term submaximal training in humans on muscle metabolism in exercise. Am J Physiol, 1998. 275(1 Pt 1): p. E132-E139.
20. Sahlin, K., M. Tonkonogi, and K. Soderlund, Plasma hypoxanthine and ammonia in humans during prolonged exercise. Eur J Appl Physiol, 1999. 80(5): p. 417-422.
21. Sperling, O., et al., Superactivity of phosphoribosylpyrophosphate synthetase, due to feedback resistance, causing purine overproduction and gout. Ciba Found Symp, 1977. 48: p. 143-164.
23. McConell, G., et al., Muscle metabolism during prolonged exercise in humans: influence of carbohydrate availability. J Appl Physiol, 1999. 87(3): p. 1083-1086.
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