What’s the Big Idea?
Your body has sloshing around inside it, right now, about half a pound of adenosine triphosphate. ATP, the coin of the bioenergy realm, is your body’s molecular energy currency. ATP is the magnetic strip on your ATM card: if it’s worn out, you might have oodles of money, stored energy (in the form of glucose or fat), but you can’t access it. We use our bank cards continuously, since every metabolic process, every cellular signal, is powered by ATP that transfers money—energy—from one place to another in the body, and that magnetic strip is always getting worn out. Since it’s so important, the body recycles old, broken-down ATP into shiny new ATP—like a re-magnetized strip on an ATM card. It’s a massive operation (the body recycles its own weight in ATP every day(1)) and some of us are better at it than others. Athletes have the capacity to recycle their ATP quickly, and so they can push themselves harder than most. A normal person, subjected to intense physical exertion demands, can take up to 72 hours to recover normal ATP levels.(2) And a person suffering from Chronic Fatigue Syndrome or fibromyalgia is like someone with a perpetually worn-out ATM card: they have the money in the bank, the metabolic energy (in available glucose or fat), but they just can’t access it.(3)
ATP is composed of adenosine with three phosphate groups. Adenosine, in turn, is made up of adenine with D-ribose.(4) (The L-form is not found in nature, so D-ribose is sometimes abbreviated as simply, ribose.)
Ribose isn’t found in food: the body makes ribose from glucose. But in a state of high energy demand, or compromised energy production, glucose gets shunted into lactic acid, another source of energy; this leaves ribose production lagging behind what’s needed for ATP recycling.
The big idea is that by taking D-Ribose you’re giving your body what it needs to make ATP without having to wait on slow endogenous ribose production. The main benefits of taking ribose add up, to close out our metaphor, to continually refreshing the magnetic strip on your body’s ATM card—giving you access to your stored energy.
Real-world benefits are said to include speeding muscle recovery after intense exercise, limiting post exercise fatigue—and supplying cardiac,(5) CFS and FMS patients, as well as some aging adults, with a new zest for life.(6)
D-Ribose (IUPAC designation: (2S,3R,4S,5R)-5-(hydroxymethyl)oxolane-2,3,4-triol) is a simple (non-caloric) sugar, a monosaccharide containing five carbon atoms with the chemical formula C5H10O5 and the molar mass 150.13 g/mol. The body produces it from glucose.
Mechanism of Action
Ribose provides a substrate for ATP synthesis.
The function of ribose as a supplement is to aid ATP recycling, that is, the synthesis of new ATP from ATP breakdown products. The implications of this functionality is that while it does produce subjectively-felt dramatic improvement in CFS and FMS patients, as well as in patients recovering from cardiac surgery or congestive heart failure,(7,8) in healthy adults its functionality will mostly be felt in the process of recovering from intense physical exertion.
In cardiac patients, the ATP-recycling effects of ribose supplementation can rescue heart tissue that is dying, particularly in combination with creatine.(9) In CFS and FMS patient, ribose supplementation increases general vitality.(3) In healthy adults, perceptible benefits from ribose supplementation will take the form of faster recovery from intense exertion, rather than greater performance.(2)
There are also indications that ribose can aid general well-being and reduce fatigue in aging adults.(10)
Many of the negative results in the literature on ribose appear to be due to looking for the wrong effect at the wrong time. Ribose does not appear to have a consistent effect on athletic performance.
Ten grams a day for four weeks did slightly improve one measure of strength in a study of male recreational body-builders (though this was in a low-rated journal and the treatment group started out weaker).(11) Many other groups have tried to show an athletic-performance increment from ribose and failed. In an animal study, short-term follow-up of maximal exercise tests in thoroughbreds failed to show any benefit of ribose.(12) In human studies, 3 g before an intense cycling exercise had no effect.(13) Ten grams a day for 5 days had no effect on sprinting and recovering from sprinting.(14) Thirty-two grams in healthy males had a weak and inconsistent effect on sprinting performance.(15)
Eijnde and colleagues found no effects of ribose at 24 h after intense exercise with healthy adults.(16) However, in a pivotal study for our understanding of the role of ribose supplementation, Hellsten and colleagues found a significant effect of ribose 200 mg/kg bodyweight (i.e. 15 grams for a 175-lbs person) at the 72-hour mark after intense exercise. (2) Mean and peak power outputs were the same for both ribose and placebo groups in that study, both at the start and 72-hour after the intense exercise challenge.
The Hellsten et al study supports the mechanistic explanation that ribose supports ATP regeneration after intense exercise. By extension, it provides a MOA for ribose’s benefits in a sick population. In general, in healthy adults, ribose seems best for preventing a post-exercise “wiped-out” feeling (which can last several days in the non-athletic) rather than for increasing performance above baseline, or for preventing fatigue-related performance decrements.(17) The potential of ribose for reducing fatigue in aging adults, while poorly supported experimentally, is strongly supported by an uncontrolled study(10) and by extension from its known MOA and its function in cardiac, FMS, and CFS patients.
Some in vitro and animal studies have suggested deleterious effects of high-dose ribose. Intraperitoneal ribose injection impaired cognition in mice, and induced protein glycation in vitro. Protein glycation in humans is associated with cellular damage and aging-associated diseases including Alzheimer.(18,19)
Countering those concerns, a physician who has spent most of his career treating chronic fatigue syndrome and touts the virtues of D-Ribose for enhancing mitochondrial function(3) is also currently recruiting for a study of D-Ribose for Alzheimer.(20) In addition, a study in horses concluded that ribose supplementation was safe and does not cause glycation in vivo.(21)
In humans, 20 g a day over a two-week period was found to be safe, with no biochemical changes suggesting toxicity, except for mild transient asymptomatic hypoglycemia.(22)
Bioenergy has received a “no objection” letter from FDA for its GRAS self-determination for D-ribose.(23)
Ribose is a safe and useful supplement that can work wonders in certain people. It will not increase athletic performance, or if so, in inconsistent and unpredictable ways. For people who exercise, it should help with recovery over 3 days after the exercise. For aging adults, it may add vim and vigor to their lives. For general use, doses of about 5 grams three times a day appear reasonable. For recovery from athletic performance, the total dose, up to 20 g, should be consumed just before the event. Personally, I add about 5 g to my morning coffee, and 10 g to the coffee I take before weightlifting, and feel it helps me feel less wiped afterwards. It's always good to finish a workout feeling refreshed rather than empty.
1. Tornroth-Horsefield S, Neutze R. Opening and closing the metabolite gate. Proc Natl Acad Sci U S A. 2008 Dec;105(50):19565–6.
2. Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J Physiol Regul Integr Comp Physiol. 2004 Jan;286(1):R182–8.
3. Teitelbaum J. Enhancing Mitochondrial Function With D-Ribose. Integrative Medicine. 2008 Apr 2;7(2):46–55.
4. Herry L. Why does ATP contain Adenine and Ribose? [Internet]. 2013 [cited 2016 Jul 29]. Available from: https://www.quora.com/Why-does-ATP-contain-Adenine-and-Ribose
5. Wagner S, Herrick J, Shecterle LM, St Cyr JA. D-ribose, a metabolic substrate for congestive heart failure. Prog Cardiovasc Nurs. 2009 Jun;24(2):59–60.
6. Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006 Nov;12(9):857–62.
7. Pauly DF, Pepine CJ. D-Ribose as a supplement for cardiac energy metabolism. J Cardiovasc Pharmacol Ther. 2000 Oct;5(4):249–58.
8. Omran H, McCarter D, St Cyr J, Luderitz B. D-ribose aids congestive heart failure patients. Exp Clin Cardiol. 2004;9(2):117–8.
9. Caretti A, Bianciardi P, Sala G, Terruzzi C, Lucchina F, Samaja M. Supplementation of creatine and ribose prevents apoptosis in ischemic cardiomyocytes. Cell Physiol Biochem. 2010;26(6):831–8.
10. Flanigan R, MacCarter D, Shecterle LM, St Cyr JA. D-ribose aids fatigue in aging adults. J Altern Complement Med. 2010 May;16(5):529–30.
11. Van Gammeren DFDAJ. The effects of four weeks of ribose supplementation on body composition and exercise performance in healthy, young, male recreational bodybuilders: a double-blind, placebo-controlled trial. Current Therapeutic Research. 2002;63(8):486–95.
12. Kavazis AN, Kivipelto J, Choe HS, Colahan PT, Ott EA. Effects of ribose supplementation on selected metabolic measurements and performance in maximally exercising Thoroughbreds. J Anim Sci. 2004 Feb;82(2):619–25.
13. Kerksick C, Rasmussen C, Bowden R, Leutholtz B, Harvey T, Earnest C, et al. Effects of ribose supplementation prior to and during intense exercise on anaerobic capacity and metabolic markers. Int J Sport Nutr Exerc Metab. 2005 Dec;15(6):653–64.
14. Kreider RB, Melton C, Greenwood M, Rasmussen C, Lundberg J, Earnest C, et al. Effects of oral D-ribose supplementation on anaerobic capacity and selected metabolic markers in healthy males. Int J Sport Nutr Exerc Metab. 2003 Mar;13(1):76–86.
15. Berardi JM, Ziegenfuss TN. Effects of ribose supplementation on repeated sprint performance in men. J Strength Cond Res. 2003 Feb;17(1):47–52.
16. Eijnde BO, Van Leemputte M, Brouns F, Van Der Vusse GJ, Labarque V, Ramaekers M, et al. No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis. J Appl Physiol (1985). 2001 Nov;91(5):2275–81.
17. Kreider RB, Melton C, Greenwood M, Rasmussen C, Lundberg J, Earnest C, et al. Effects of oral D-ribose supplementation on anaerobic capacity and selected metabolic markers in healthy males. Int J Sport Nutr Exerc Metab. 2003 Mar;13(1):76–86.
18. Han C, Lu Y, Wei Y, Liu Y, He R. D-ribose induces cellular protein glycation and impairs mouse spatial cognition. PLoS One. 2011;6(9):e24623.
19. Wu B, Wei Y, Wang Y, Su T, Zhou L, Liu Y, et al. Gavage of D-Ribose induces Abeta-like deposits, Tau hyperphosphorylation as well as memory loss and anxiety-like behavior in mice. Oncotarget. 2015 Oct;6(33):34128–42.
20. Teitelbaum J. Treating Alzheimer's and Dementia With D-ribose [Internet]. clinicaltrials.gov. [cited 2016 Jul 29]. Available from: https://clinicaltrials.gov/ct2/show/NCT02260141
21. Sinatra ST, Caiazzo C. (D)-Ribose supplementation in the equine: lack of effect on glycated plasma proteins suggesting safety in humans. J Am Coll Nutr. 2015;34(2):108–12.
22. Seifert J, Frelich A, Shecterle L, St Cyr J. Assessment of Hematological and Biochemical parameters with extended D-Ribose ingestion. J Int Soc Sports Nutr. 2008;5:13.
23. FDA OK with Bioenergy’s GRAS D-Ribose. 2008 Nov 20. Available from: http://www.naturalproductsinsider.com/news/2008/11/fda-ok-with-bioenergys-gras-d-ribose.aspx