by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS
ATP
ATP stands for adenosine triphosphate. It is the molecule that provides the energy for muscles to contract and relax. Physiologically this is an extremely important molecule because every cell in the body is dependent upon it in order to function. It makes sense then that researchers are concerned with ways to maintain ATP levels in our body since it is crucial to life itself. As it turns out there are supplements that can potentially increase ATP levels and perhaps increase performance. These types of supplements include agents that can increase or maintain ATP (adenosine 5’-triphosphate) levels.
Chemically, ATP is a purine nucleotide that is found in every mammalian cell. Most people are aware of its role in cellular energy metabolism. However, extracellular ATP (and its breakdown product adenosine) can affect a variety of biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation, and liver glycogen metabolism. The rationale to increase ATP levels in order to improve performance is based on the assumption that declining ATP levels may be rate limiting for performance. While there is some research evidence that ATP levels are reduced during activity, it would be unlikely that reduced ATP levels represent the sole reason for fatigue. The effect of physical exertion on intramuscular ATP levels depends on the intensity and duration of the activity. If you think that your workouts are suffering from a lack of energy, then this may be the type of article you’ve been waiting for.
Adenosine Triphosphate
Clinical studies have demonstrated that ATP itself may have potential therapeutic potential for patients with neuropathic pain, ischaemic pain, haemorrhagic shock, pulmonary hypertension, tachycardia, cystic fibrosis, lung cancer, radiation tissue damage, and coronary artery disease [1]. However these studies administered ATP via injection. Studies documenting the effects of ATP on exercise performance have also used clinical populations and delivered the agent via injection. Oral doses of 40 to 300 mg daily appear to be well tolerated in patients [2, 3].
Various products have appeared in the supplement market claiming to contain ATP. The methods of delivery include oral tablet or capsule, liposomal (spheres of fatty acids), intraoral (sublingual sprays), and transdermal (creams, gels, or sprays applied to skin). Based on clinical studies, it appears that both oral and liposomal ATP exert physiological effects. Oral ATP is usually a salt and appears fairly stable. The use of liposomes as a delivery method for supplements has been questioned due to the unstable nature of liposomes, though. Intraoral delivery of ATP may not be ideal because the buccal cavity contains enzymes that breakdown ATP [4]. Transdermal delivery is also not ideal because ATP causes a dose-related pain response in human skin [5].
Given the lack of exercise-related data in healthy people, using ATP as a supplement would be premature. The areas of concern include dose-response effects and physiological adaptations to elevated ATP levels.
Creatine
Creatine is an amino acid that can be used by the body to make creatine phosphate and ATP. From Figure 1 we see that creatine (Cr) combines with inorganic phosphate (Pi) inside our cells to produce creatine phosphate (CrP). CrP combines with adenosine diphosphate (ADP) to yield ATP. Numerous studies have investigated the effects of oral creatine monohydrate on physical performance. While some acute studies have shown no benefit of creatine on anaerobic performance, the majority of studies do show an improvement. Long-term studies indicate that creatine ingestion increases the gains in strength and lean body mass provided by resistance exercise [6-8]. The ingestion of substances that can elevate insulin appears to improve the acute ergogenic effects of creatine [9]. In practice, this is often accomplished by ingesting creatine with a protein/carbohydrate drink after exercise. It is thought that creatine provides its ergogenic benefits by increasing the total intramuscular pool of creatine, thereby increasing the ability to make ATP. There is some debate over the mechanisms of action of creatine, however there is general agreement among research studies that creatine is chronically safe when ingested in doses of 10 grams or less per day [10, 11].
Various forms of creatine have appeared on the market. Most of the research has been done using creatine monohydrate ingested either as capsules or powder. Other creatine products include suspensions, liquids, and candy. Different labs have tested one type of liquid creatine and found no evidence of creatine. Given the instability of certain liquid creatine products, creatine powders appear a more prudent choice.
Many guys will try to load up on high doses of creatine to maximize the results. Unfortunately there is a limit to how much creatine our cells can store. Taking more than 3-5 grams per day is unnecessary, unless one is trying to “load” on creatine. In that case, loading is done with doses of 20-25 grams for 3-5 days. After the loading period, one would reduce the dose of creatine down to 3-5 grams. The powdered form of creatine is about fi to one whole level teaspoon.
Ribose
Ribose is a five-carbon sugar that can be used by the body to make ATP via the pentose-phosphate pathway. This pathway is of interest to researchers because it does not require oxygen for ATP production and therefore may be of use during conditions of impaired or inadequate blood flow. Exercise studies using patients with cardiovascular disease indicate that it can improve performance [12]. Oral does as high 50-60 grams per day were well tolerated without side effects [13]. However this was administered in smaller amounts of four grams each. Doses at 10 grams or more may cause hypoglycemia.
While several studies have been conducted on ribose in healthy subjects, most of this information has appeared primarily as abstracts presented at scientific conferences. The results from these abstracts overall appear to support the theoretical strategy that ribose supplementation before and during exercise may improve physical performance. However recently a double-blind randomized study was performed to evaluate the effect of oral ribose supplementation on knee extension performance and ATP recovery (14). Ten subjects ingested four grams of ribose four times each day for six days, while another 9 subjects ingested a placebo. Each group performed the same training protocol. There were no significant differences in knee extension performance between the two groups. In another part of the study, muscle biopsies were taken and ATP levels were analyzed. Ribose did not affect ATP levels. At this point the only peer-reviewed publication on ribose and exercise in healthy subjects indicates that ribose doesn’t work. This is contradicted by various abstracts indicating that ribose does work. It seems like the studies are from different labs and used different experimental designs. It will be interesting to read the peer-reviewed publications when they are published and compare them with the aforementioned study. Until then if you decide to try ribose, keep track of your performance so you can determine if it is helping you or not. One important aspect of ribose ingestion is the timing of administration. Unpublished observations indicate that approximately five grams should be ingested every 30-45 minutes of activity.
Summing it Up
Various herbs such as Schisandra, and supplements such as NADH have also been touted to increase ATP levels in the body. Unfortunately these agents often lack the supporting research to confirm these claims. At this point it looks like creatine is the best option that one would have for indirectly increasing ATP levels. The direct ingestion of ATP appears to have promise for clinical situations, yet research on exercise in healthy subjects is lacking. Ribose has theoretical support behind it, yet the most recent peer-reviewed evidence doesn’t indicate it works in healthy subjects. Stay tuned and we’ll keep you up-to-date on future developments on this exciting topic.
References
1. Agteresch, H.J., et al., Adenosine triphosphate. Established and potential clinical applications. Drugs, 1999. 58(2): p. 211-232.
2. Wang, J. and G. Bu, Clinical observation of oral adenosine triphosphate in treating rhinitis medicamentosa. Chinese Medical Journal, 2000. 113(4): p. 349.
3. Mizukoshi, K., et al., Clinical evaluation of medical treatment for Meniere’s disease, using a double-blind controlled study. American Journal of Otology, 1988. 9(5): p. 418-422.
4. Dabelsteen, E. and S. Kirkeby, ATP-ase positive cells in human oral mucosa transplanted to nude mice. Scandinavian Journal of Dental Research, 1981. 89(5): p. 433-5.
5. Hamilton, S.G., et al., ATP in human skin elicits a dose-related pain response which is potentiated under conditions of hyperalgesia. Brain, 2000. 123(Pt 6): p. 1238-46.
6. Becque, M.D., J.D. Lochmann, and D.R. Melrose, Effects of oral creatine supplementation on muscular strength and body composition. Medicine & Science in Sports & Exercise, 2000. 32(3): p. 654-8.
7. Volek, J.S., et al., Performance and muscle fiber adaptations to creatine supplementation and heavy resistance training. Medicine & Science in Sports & Exercise, 1999. 31(8): p. 1147-56.
8. Vandenberghe, K., et al., Long-term creatine intake is beneficial to muscle performance during resistance training. Journal of Applied Physiology, 1997. 83(6): p. 2055-63.
9. Green, A.L., et al., Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiologica Scandinavica, 1996. 158(2): p. 195-202.
10. Poortmans, J.R. and M. Francaux, Long-term oral creatine supplementation does not impair renal function in healthy athletes. Medicine & Science in Sports & Exercise, 1999. 31(8): p. 1108-10.
11. Schilling, B.K., et al., Creatine supplementation and health variables: a retrospective study. Medicine & Science in Sports & Exercise, 2001. 33(2): p. 183-8.
12. Pliml, W., et al., Effects of ribose on exercise-induced ischaemia in stable coronary artery disease. Lancet, 1992. 340(8818): p. 507-510.
13. Zollner, N., et al., Myoadenylate deaminase deficiency: successful symptomatic therapy by high dose oral administration of ribose. Klinische Wochenschrift, 1986. 64(24): p. 1281-1290.
14. Op, T.E.B., et al., No effects of oral ribose supplementation on repeated maximal exercise and de novo ATP resynthesis. Journal of Applied Physiology, 2001. 91(5): p. 2275-2
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