Punch ‘ribose’ and ‘athlete’ into any internet search engine and you’ll marvel at the number of companies that now promote supplemental ribose as an ergogenic aid. Given that ribose forms part of the adenosine triphosphate (ATP) molecule and that ATP, the universal currency of energy in the body, is what makes our muscles work, the claims that ribose supplementation can deliver more power and energy and faster recovery seem pretty plausible, especially when they’re apparently supported by numerous scientific references.

Dig a little deeper, however, and it soon becomes evident that all is not as rosy as it seems in the ribose garden.

Like most naturally occurring compounds ending in ‘ose’, ribose is a sugar; and like many of the more familiar sugars in the body and in the foods we eat, such as glucose, fructose and galactose, it consists of a carbon ring-like structure to which oxygen and hydrogen atoms are bonded.

However, unlike these other sugars, ribose is actually synthesised in the body from glucose by means of a process called ‘oxidative carboxylation’, in which another critically important compound called NADPH is generated. In crude terms, enzymes chop out a molecule of carbon dioxide (CO²) from a six-carbon glucose ring to generate ribose and NADPH, and this explains why ribose is a five-carbon sugar. Once ribose has been formed, it can either be recycled back to glucose or incorporated into other larger molecules that use ribose as building blocks. These include DNA and RNA, which store and translate genetic information during cell division, and, of course, ATP, whose job is to act as the universal energy currency within the body.

Although ribose is an integral part of the ATP molecule, it is important to understand that it is the phosphate groups of ATP that store and donate energy to working muscles; in particular, it is the bond between the end and middle phosphate that breaks to release energy, when ATP is broken down to ADP (adenosine diphosphate) and phosphate. The other end of the molecule (the adenosine part) consists of two building blocks joined together (adenine and ribose) and serves merely as an inert framework upon which the ‘action’ part of the molecule is hung (see figure 1).

Under normal conditions, when we speak of ‘breaking down’ ATP to release energy, we are referring only to the breaking of the end phosphate bond, since the rest of the molecule stays perfectly intact. Taking extra ribose, therefore, cannot be expected to increase the rate at which broken down ATP is resynthesised from ADP and phosphate (unlike creatine, of which more below). Rather it is thought that ribose helps the body to manufacture more adenosine frameworks – ie to actually increase the number of ATP molecules – or to slow down any decrease in ATP concentration that might occur under very strenuous training conditions, when small amounts of ATP can be completely destroyed (rather than just broken down to ADP and phosphate).

The new creatine?

There is no disputing the ergogenic potential of supplemental creatine. By boosting levels of muscle creatine, athletes can increase their stores of a substance called phosphocreatine, which acts as an emergency high-energy reservoir of phosphate. This phosphate pool is able to rapidly donate a high energy phosphate group to ‘spent’ ATP (known as ADP), thereby regenerating ATP in muscles when it is being used up more rapidly than it can be regenerated via the ‘normal’ aerobic pathway. The net effect of creatine is to help athletes sustain high-intensity bursts for longer, while speeding recovery between bursts.

Given that ribose forms an integral part of the structure of ATP, it was only a matter of time before scientists began to consider whether supplementary ribose would translate into an increased rate of ATP synthesis from its constituent building blocks, leading to higher muscle concentrations of ATP and thence to improved athletic performance.

Scientific interest in the potential benefits of ribose supplementation escalated rapidly after a number of studies carried out in the early 1990s indicated that supplementary ribose improved cardiac energy metabolism in patients with chronic heart disease, thereby significantly improving their quality of life^(1,2,3).

However, when researchers studied the effects of ribose supplementation on other conditions involving disorders of energy metabolism, the results were less impressive. These conditions included Duchenne dystrophy⁽⁴⁾, a progressive disease causing generalised weakness and muscle wasting, and McArdle’s disease⁽⁵⁾, where the ability to break down stored muscle glycogen to glucose, so generating ATP, is severely impaired.

Nevertheless, reports of the benefits of supplementary ribose for patients with chronic heart disease continued to accrue, supported by animal studies. Indeed, just last year a randomised double-blind crossover study (considered to be the most rigorous type of clinical trial) found that supplementing ribose in patients with congestive heart failure for three weeks significantly improved heart function and work output during a submaximal cycling test⁽⁶⁾. Moreover, the patients in question also demonstrated improved ‘quality of life’ scores.

The current scientific consensus is that in certain pathological heart conditions, significant amounts of ATP can be destroyed completely (not just broken down to ADP and phosphate) and lost from the heart. The heart’s ability to re-synthesise ATP may then become limited by the supply of ribose, one of the building blocks of the ATP molecule.

Studies on heart patients are well and good, but what does ribose have to offer those with normal cardiac function and, more particularly, what can it do for athletes? Unfortunately, this is where marketing-driven claims part company with reality; for when you look at the scientific evidence that has emerged from properly conducted placebo-controlled trials, the fact is that there is very little evidence to support these claims. Indeed, when you consider the most recent clinical trials on ribose supplementation in athletes, there’s almost complete agreement that it offers few, if any, significant benefits in practice.

Ribose and intense exercise

One study published last year examined the effects of ribose supplementation on a one-week period of intense intermittent exercise⁽⁷⁾. In a randomised double-blind crossover experiment, eight athletes performed cycle training, comprising 15 sets of 10-second all-out sprinting, twice daily for seven days. At the end of the study period, the subjects took either ribose (200mgs per kg of body weight) or a placebo three times a day for three days, after which an exercise test was carried out and muscle ATP measured. After a washout period, the groups changed places and the experiment was repeated.

Analysis of the results showed that three days after the training period those taking ribose had regenerated their ATP to pre-training levels, while those taking placebo did not recover their ATP quite as rapidly. However, mean and peak power outputs observed in the post-training exercise test did not differ between the groups; in other words, the slower ATP regeneration seen in the placebo group made no difference to their actual performance.

In another double-blind randomised clinical trial carried out last year, 19 trained men were initially tested for their anaerobic power by performing two 30-second sprint tests on a cycle ergometer, separated by three minutes of rest⁽⁸⁾. At the end of these practice sessions, blood samples were taken, and subjects were then matched for body mass and anaerobic capacity and assigned to ingest capsules containing either a dextrose placebo or ribose twice daily for five days, repeating the same tests on the sixth day.

No effect on anaerobic capacity

Although there was some evidence that total work performed in the second post-supplementation sprint was less in the placebo group than in the ribose group, further analysis showed that there were no significant differences in peak power, average power, torque, fatigue index, blood lactate or other blood metabolites between the groups. The researchers concluded that that oral ribose supplementation did not increase anaerobic exercise capacity or affect any of the measured metabolic markers.

Another recent study appears to provide some weak evidence that ribose can enhance sprinting performance⁽⁹⁾. In this randomised controlled double-blind clinical trial, subjects were asked to perform two bouts of repeated cycle sprint exercise in a single day, each bout consisting of six 10-second sprints, separated by 60-second rest periods. After the second bout, the subjects ingested either 32g of ribose or cellulose (an inert placebo) over the next 36 hours, then returned to the lab to repeat the sprinting test.

After a five-day washout period, the groups changed places and the whole procedure was repeated.

The results showed a statistically significant increase in mean and peak power in sprint 2, and higher absolute values – although too small to be statistically significant – in sprints 1, 3 and 4. The researchers concluded that, because supplementation did not show reproducible increases in performance across all six sprints, ribose did not have a consistent or substantial effect on anaerobic cycle sprinting.

Yet another recent randomised double-blind controlled trial appears to pour cold water on the notion that ribose supplementation can enhance performance⁽¹⁰⁾. In this study, muscle power output was measured during dynamic knee extensions on an isokinetic dynamometer before and after a six-day training period, during which subjects were supplemented with either ribose (16g per day divided into four doses) or placebo. The exercise protocol consisted of two bouts of maximal contractions, separated by 15 seconds of rest. Each bout consisted of 15 series of 12 contractions each, separated by a 60-min rest period, and the subjects performed the same exercise protocol twice daily, with 3-5 hours of rest between sessions.

At the end of the test, knee extension power outputs were approximately 10% higher in both groups, but there were no differences between the groups. Neither were there any differences between the groups in blood lactate and plasma ammonia concentrations.

Some ribose advocates point to animal studies for evidence of efficacy, but even here recent research seems to draw a blank. A study published earlier this year⁽¹¹⁾ examined the effect of ribose supplementation on thoroughbred gelding racehorses undergoing treadmill training (yes, racehorses really can be trained on treadmills!). The objective was to investigate the effects of ribose supplementation on blood ammonia and lactic acid, plasma glucose, oxygen consumption and heart rate during a standardised maximal treadmill exercise test and, in particular, to see whether ribose supplementation would decrease ammonia and lactic acid accumulation, thereby improving performance.

The horses were assigned randomly to either ribose or placebo, both provided at the same dose (0.15g per kg of body weight) as a twice-daily top-dressing to their feeds. After 14 days of supplementation, a standardised exercise test was performed. After a 10-day washout period, the horses switched groups and the protocol was repeated. In both placebo and ribose groups, blood ammonia and lactic acid increased with the duration of exercise and reached a peak 15 minutes after exercise. Peak blood glucose was observed 15 minutes after exercise, and peak heart rates and oxygen uptakes were recorded at highest speed during the test. In fact, there were no differences at all between the groups, leading the researchers to conclude that ribose supplementation had no effect.

Researchers drew a blank

These results appear to confirm those of an earlier study by the same group, in which lower levels of supplemental ribose (0.06g per kg) were used⁽¹²⁾. In this study, the researchers detected a faint non-significant trend towards a reduced post-exercise level of blood lactate and ammonia. By increasing the dose from 0.06 to 0.15g per kg, the scientists had expected to detect a clearer trend. But instead they drew a blank.

While there are plenty of anecdotal and testimonial-type claims for the efficacy of ribose to be found, if you take a long hard look at rigorous placebo-controlled peer-reviewed scientific trials, the evidence is at best very weak and at worst virtually nonexistent. Yes, it’s true that ribose is a building block of the molecular structure of ATP, but claiming that consuming extra ribose will therefore boost ATP production and energy is as logically naïve as saying that a car engine that needs four pints of oil for smooth operation will run twice as smoothly with eight pints!

It is true that with certain heart conditions supplemental ribose can help cardiac energy metabolism, but this is almost certainly because, in these rare circumstances, there is abnormal destruction and loss of ATP, and the heart’s ability to resynthesise ATP becomes limited by the supply of ribose available.

Human metabolism is an enormously complex and intricate system of closely coupled biochemical pathways, rigorously controlled by various feedback systems. For example, production of ribose in the body is tightly coupled to NADPH, a vital carrier of electrons in numerous biochemical reactions. Each molecule of ribose formed produces two molecules of NADPH, but the fact that unwanted ribose is readily recycled back to glucose suggests that the biochemical priority in this reaction is to produce NADPH, and that under normal conditions there is more than enough ribose for ATP synthesis.

Moreover, the ribose that is produced in the body in this way is in the form of ribose-5-phosphate, which has a phosphate group on the fifth carbon. This makes it a biochemically different and more energetic species than the plain ribose used for supplements (which doesn’t contain this phosphate group). There is no clear evidence that the ribose contained in supplements can be independently phosphorylated (the process of adding a phosphate group to a molecule) without first undergoing some kind of biochemical transformation. And even if this were to occur, it would require the input of energy via donation of a high-energy phosphate group. This is, of course, the exact opposite of what ribose supplementation is designed to achieve – ie to increase the availability of ATP and its high-energy bonds!

Even if extra ribose can help to regenerate any degraded ATP more rapidly (as suggested in one of the above-mentioned studies) or even increase the number of ATP molecules, this may still make no difference to energy reserves. This is because when ATP releases energy it can be very rapidly regenerated again from ADP and phosphate, either by means of aerobic metabolism or from the high-energy phosphate pool described above.

Remember that this energy-releasing process is completely reversible, unlike the complete destruction of the ATP molecule. Although the average human can store only about 3oz of ATP in total, during intense exercise as much as 15kg of ATP is broken down and reformed per hour. To put it another way, a typical ATP molecule in the active exercising muscles will be cycled back and forth between ATP, ADP and phosphate hundreds of times a minute!

What matters in terms of energy production is less to do with how many units of ATP there are to start and more about how efficiently ATP can be regenerated back from ADP and phosphate. This is exactly why supplementing creatine works: it boosts the size of the available pool of high-energy phosphate for ATP regeneration. Creatine supplementation turned the world of sports nutrition on its head precisely because it served as an extremely rare example of putting more of an energy-producing metabolic precursor into the body and getting more energy out!

Ribose supplementation may not be completely without merit, especially if, in certain circumstances, it can enhance the resynthesis of whole ATP molecules from its constituent building blocks. However, the sports supplement industry is notorious for taking a random substrate from an extremely complex metabolic pathway and marketing it as the next performance-enhancing pill; and the fact remains that, to date, there is just not enough scientific evidence to recommend its use.

This situation may change as future research studies roll in, but in the meantime athletes looking to enhance their performance should save their pennies for supplements that are known to work!

Andrew Hamilton

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