Ribose The Key to Cellular Energy

by Jerry Brainum

On an elemental level, all the size and strength gains you can possibly make come down to one thing: energy. While it's obvious that you won't be able to train with maximum intensity if you don't feel energetic, you'll also make less bodybuilding progress because of the lack of cellular energy available. Your body needs cellular energy to power such essential reactions as glycogen and protein synthesis within muscle, as well as innumerable other biochemical recovery reactions that occur after exercise.

The most elemental energy source in the body is a compound called adenosine triphosphate, or ATP The adenosine portion is made up of one molecule each of adenine and a five-carbon sugar, or pentose, known as ribose. As the name implies, the triphosphate portion of ATP consists of three phosphate molecules. When one of those phosphates is broken off from ATP, energy is released and the compound becomes adenosine diphosphate (ADP), which consists of adenosine (including its ribose base) and two phosphate molecules.

All sources of food energy—carbohydrates, fats and proteins—are eventually converted into ATP in the parts of the cell called the mitochondria. Every move you make and every chemical reaction that occurs in your body is powered by ATP.

Nevertheless, the body's stores of ATP are quite limited—about three ounces, or 90 grams. That's enough to supply maximum energy for all of 10 seconds. The body works around the limited ATP storage by using various recycling mechanisms. For example, after a phosphate bond is split from ATP, releasing tremendous energy and leaving ADP, the body, through a series of quick enzymatic reactions, adds a phosphate to the ADP to re-form ATP. That process works efficiently in the presence of oxygen, or aerobic metabolism, using fats and glucose as substrates, or starting molecules.

The situation changes during periods of decreased oxygen availability, or anaerobic metabolism, which is the type of energy cycle used in high-intensity training, such as bodybuilding workouts. Under those conditions the cells get their donated phosphate for re-forming ATP from creatine phosphate stored in muscle. That explains the primary ergogenic effect of creatine as a food supplement. It acts as a second battery in cells to help reconvert ATP by passing over a phosphate molecule. Even though the system sounds efficient, however, the ATP-creatine energy cycle can only supply about 30 seconds of maximum energy, as the creatine is rapidly used up under such conditions.

When that happens, the body relies on still another energy pathway to help resurrect ATP, a system called the myokinase reaction after the enzyme that catalyzes it. It involves using two molecules of ADP and one molecule of AMP, or adenosine monophosphate, which contains just one phosphate molecule, to form one molecule of ATP. The myokinase reaction helps supply necessary ATP when the creatine stores aren't sufficient. The reaction also balances ATP and ADP levels in the cell.

While the myokinase reaction helps to keep the cellular motor running, a problem arises because of the buildup of AMP in the cell. The body deals with it by turning on other enzymatic reactions that downgrade the AMP, which is then eliminated from the body. The problem is AMP's role as a substrate in the recirculation of ATP. If it's eliminated, the existing ATP stores may not be sufficient to supply maximum energy.

Once again, the body has ways of dealing with the problem. Two primary pathways exist to help use AMP in the creation of ATP. One is called the salvage pathway, a system in which the body tries to salvage AMP breakdown products. The good news is that when it works, it works well in helping to maintain ATP stores. That's where ribose enters the picture. Ribose promotes this more efficient salvage pathway, thus allowing better ATP recycling and consequent increased muscular recovery after training.

If the body doesn't use the salvage pathway—for example, when ribose is insufficient—it must

Ribose Glucose Arabinose

make ATP from scratch in a pathway called the de novo, or new, pathway. That occurs when the body has excreted too much of the metabolic byproducts of AMP that serve as precursors for ATP. While having enough ribose available favors the more efficient salvage pathway, the fact is that ribose is also required for the de novo pathway.

Both processes begin when ribose is converted into a molecule called 5-phosphoribo-syl-1-pyrophos phate (PRPP).

The cells make the conversion whenever PRPP is needed, but, once again, under conditions of strenuous exercise or poor blood circulation (as in cardiovascular disease) the PRPP stores are used up in the salvage or de novo pathways. Using supplemental ribose maintains PRPP, which in turn maintains the ATP salvage pathway. So the real limitation is the availability of ribose.

In truth, the body can synthesize PRPP from glucose, but it's a long, slow process that may take several days. In the meantime the existing muscle ATP stores aren't sufficient to support maximal energy for high-intensity exercise or sports. Ribose is made from glucose in a process called the pentose phosphate pathway, which metabolizes glucose into ribose-5-phosphate. That, in turn, is converted into the active PRPP. Taking supplemental ribose bypasses the two rate-limiting enzymes in the pentose phosphate pathway, leading to quicker production of PRPP, which helps to conserve nucleotides, or AMP metabolites, essential for ATP synthesis.

Another vital use of ribose ii in the formatk of nucleotides, which, in turn, are needed for energy production; foi synthesis of protein, glycogen and nucleic acids; and for the formation of cyclic nucleotides, such as cyclic AMP, a substance that needed for fat oxidation and hormone-cell interactions.

Taking supplemental ribose increases ATP manufacture in skeletal muscle by 340 to 430 percent. In the ATP salvage process supplemental ribose increases the cell's ability to reuse ADP and AMP by up to 700 percent.

The enzyme that controls the conversion of glucose into ribose is glucoses-phosphate dehydrogenase (G-6-PDH). The problem is that the supply of it in both skeletal and heart muscle is low. Even so, using supplemental ribose bypasses the enzymatic process, enabling the ribose to take an express route directly to the active substance that promotes ATP recovery, PRPP. The bottom line is faster and more efficient restoration of ATP stores in the body.

Since the body only contains about 1.6 milligrams of ribose for every 100 milliliters of blood and since most foods, such as meat products, contain barely discernable amounts of it, you can clearly see the necessity of taking extra ribose.

The body uses ribose in several important ways. It's used to make glucose, the most elemental sugar in the body, which circulates in the blood. Ribose may also be enzymatically converted into pyruvate, which enters the cell in an energy-producing process using oxygen that's called the Kreb's, or citric acid, energy cycle. Still another vital use of ribose is in the formation of nucleotides, which, in turn, are needed for energy production; for synthesis of protein (i.e., messenger RNA), glycogen and nucleic acids (RNA and DNA); for enzymatic control of electrolyte metabolism; and for the formation of cyclic nucleotides, such as cyclic AMP, a substance that's needed for fat oxidation and hormone-cell interactions.

Ribose is used in the manufacture of the B-complex vitamin riboflavin, or vitamin B2, which among other things makes your urine bright yellow. Ribose is also used in the manufacture of several antiviral drugs, such as Ribaviran, which prevents virus replication by inhibiting RNA and DNA synthesis.

Taking supplemental ribose increases ATP manufacture in skeletal muscle by 340 to 430 percent. In the ATP salvage process supplemental ribose increases the cell's ability to reuse ADP and AMP by up to 700 percent.

Although scientists have been aware of ribose metabolism since 1930, its importance didn't become apparent until the 1950s. Since then ribose research has burgeoned, having mostly to do with the effect of ribose protection against cardiovascular problems. When the heart doesn't get enough blood flow, a condition called ischemia, or when it's under low oxygen conditions, or anoxia, ATP stores in the heart are rapidly degraded. The heart's inability to rapidly restore the ATP loss leads to a buildup of AMP in the heart. Many studies have shown that supplying supplemental ribose restores ATP in the heart. A forthcoming study from the University of Maryland uses ribose to treat cardiac ischemia, which is typically manifested as the pain of angina pectoris in people suffering from coronary artery disease.

In fact, any disease that results in decreased blood flow to tissues and subsequent lowered oxygen delivery can lead to a depletion of ATP. That can cause symptoms of severe pain, cramping, stiffness and soreness. In one genetic enzyme deficiency called myoadenylate meami-

nase deficiency (MADD), muscle cells cannot conserve nucleotides. When that happens, AMP is degraded to inosine and hypoxanthine and leaves the body. The lack of ATP substrates makes a person suffering from MADD very weak, with stiff, sore muscles.

The same lack of adequate blood flow and oxygen can temporarily occur during intense muscular contractions, again leading to a loss of the nucleotides needed to rebuild ATP in the cells. When that happens, you won't feel fully recovered from workout to workout, and your strength gains will suffer. Research shows that the loss of vital nucleotides during intensive exercise can be as high as 20 to 28 percent. Most of such loss occurs during anaerobic exercise, since the high oxy -gen levels typical of aerobic exercise conserve nucleotides.

At present more than 150 peer-reviewed published studies attest to the fact that ribose effectively increases ATP and total nucleotide (TAN) recovery while improving performance in heart and muscle cells during periods of lowered blood flow or low oxygen. Those conditions can occur in the heart with coronary artery disease or during certain surgical procedures. As noted above, ischemia can also occur during intense anaerobic exercise.

Several studies have illustrated the severity of nucleotide loss during either intense exercise or ischemia. A Swedish study focused on two groups of exercising men, in which 11 healthy men performed high-in-tensity exercise three times a week for six weeks, followed by another week of twice-daily sessions. Another group of nine men rested for the first six weeks, then trained twice a day with the first group during the final week.

Muscle biopsies, which are small bits of muscle tissue taken for analysis, showed that ATP levels in the thigh muscles of the first group

Peak power was 9.9 percent higher and mean, or average, powe was 9 percent higher in the subjects who took the actua ribose supplement. Muscle biopsie of the subjects showed that those taking the ribose more effectively used their energy stores and recovered quicker after exercise.

Ribose supplements are particularly synergistic with creatine, which works by supplying a phosphate molecule after ATP is broken down to ADP to release energy.

dropped 13 percent during six weeks of training but did not decrease further during the final week of twice-daily sessions. Even after three days of rest ATP still hadn't returned to pretraining levels in the muscles of the first group and was 10 percent lower than the pretraining levels.

In the second group ATP levels dropped 25 percent right after the final workout. Even after three days of rest those men still showed ATP levels that were 19.5 percent less than when they started. This study showed that ATP levels dropped considerably with exercise and were not restored in the trained muscles even after three days of rest. Another study showed a 19 percent drop in muscle ATP levels after seven weeks of sprint training.1

Still another study showed that perfusion, or supersaturation, of skeletal muscle with ribose for 30 minutes increased de novo synthesis of nucleotides by 340 to 430 percent, depending on which type of muscle fiber was tested.2 A more recent study done by scientists from the University of Missouri is being presented at the 1999 meeting of the American College of Sports Medicine. It examined the role of ribose in the adenine nucleotide salvage pathway and involved mixed plantaris, or leg, muscles in rats. The results showed that providing ribose to the exercising rats—who did anaerobic exercise, which leads to the greatest breakdown and loss of nucleotides needed for ATP synthesis—led to a significant increase in nucleotide salvage. For example, the dose that some rats received, which translates to a human dose of 2.5 grams of ribose, led to a 244 percent increase in nucleotide salvage over baseline, and an amount that translated to a human dose of 15 grams led to a whopping 639 percent increase.

Another new, unpublished study from Ball State University in Indiana investigated the use of supplemental ribose on performance and recovery during and after high-intensity exercise. As noted above, previous reports showed that it takes as long as 72 hours to significantly restore ATP and TAN after intensive exercise.

In the new study two subjects took ribose and another two took a placebo, or inactive substance, in this case glucose, for three days before doing sprint cycling for three days of two sessions daily. Each session consisted of 15 10-second sprints with resistance at 7 percent of body mass, with 50 seconds' rest between sprints. Both the ribose and placebo were given in three 10-gram doses.

The results showed that peak power was 9.9 percent higher and mean, or average, power was 9 percent higher in the subjects who took the actual ribose supplement. Muscle biopsies of the subjects showed that those taking the ribose more effectively used their energy stores and recovered quicker after exercise. They also showed greater recovery after 48 hours than the placebo group. The researchers believe that occurred because of increased de novo synthesis of adenine nucleotides in the ribose group. As you'll recall, ribose supplementation allows the body to bypass various slower enzymatic conversion processes.

The authors noted that while subjects took 30-gram doses of ribose, that amount is in excess of what's required to maintain optimal ATP and TAN levels. While the amount needed relates to activity and intensity of exercise, doses greater than or equal to 2.2 grams a day of ribose should maintain peak ATP and TAN levels. One researcher found that ribose may increase the salvage of nucleic acids by up to 700 percent!

These studies show that ribose can benefit anyone engaged in intensive exercise. A good daily dose is around three to five grams, and the more you train, the more you should take. Ribose is slightly sweet (it is, after all, a sugar) and can be taken in various forms. You should avoid using it in hot protein drinks, however, since ribose, when heated, may react with the amino acids in protein and lose effectiveness.

Ribose supplements are particularly synergistic with creatine, which works by supplying a phosphate molecule after ATP is broken down to ADP to release energy. But creatine doesn't replace the ATP that's lost during intense exercise. When there isn't sufficient ATP in the cell, creatine throws the phosphate ball, but there's no one to catch it. Adding ribose will help to conserve the vital adenine nucleotides needed to replenish ATP through both the more efficient salvage system and the slower de novo pathway. The net effect is that when you use creatine and ribose, you maximize cellular energy production.

Ribose should also increase the effectiveness of other supplements that require an optimal supply of ATP, such as pyruvate and carnitine, among others.

In terms of safety, doses of up to 60 grams of ribose have led to few complications. Some people who take in more than 25 grams per dose may get diarrhea, while others in rare cases experience mild, transient hypoglycemia, perhaps due to an insulin reaction. Most excess ribose, however, is simply excreted in the urine.

In the past the manufacture of ribose was an expensive process, which explains why it wasn't sold commercially. Now, however, a new company has developed a bacterial fermentation process involving the conversion of corn syrup, a form of glucose, that makes mass production of ribose simpler, so it can be sold at a reasonable price. Some types of ribose, though, may contain impurities in the form of contaminating sugars, such as arabinose or glucose, and other metabolites.

Based on its established metabolic attributes, ribose may well prove to be the next supplement superstar. Who knows—ribose may turn out to be the nutrient of the millennium!

References

1 Stathis, C., et al. (1994). Influence of sprint training on human skeletal muscle purine nucleotide metabolism. J Applied Physiol. 76:1802-09.

2 Tullson, P., et al. (1991). Adenine nucleotide synthesis in exercising and endurance-trained muscle. American J Physiol. 261:C342- C347.

These studies show that ribose can benefit anyone engaged in intensive exercise. A good daily dose is around three to five grams, and the more you train, the more you should take.

Ribose:

Super Recovery and More Muscle Energy Through Creatine Synergy

It seems as if every time a new compound is released in the supplement marketplace, it's touted as the greatest breakthrough of all time. That can be a good thing, as it makes us all somewhat skeptical, but it can be a bad thing in that when a true breakthrough does come along, we miss it. "Yeah, yeah," we mutter as we turn the page, "another breakthrough."

If you said something similar when you saw the article on ribose by Jerry Brainum in this book, you may have glossed over a true supplement breakthrough that could change your workouts and recovery ability forever. Ribose may be the greatest supplement innovation since creatine—and that's not hype but fact backed by more than 150 peer-reviewed studies.

As you may or may not know, creatine works because it fortifies ATP, the compound your muscles use for energy. When you do a set, ATP is broken down rapidly, but creatine regenerates it by donating a phosphate to the depleted ATP (now ADP). The result is you get re-formed ATP and more anaerobic work capacity, which can result in more muscle growth stimulation. That's why creatine works.

Ribose also fortifies muscle ATP but through a different pathway—and perhaps even more critical, it bolsters muscle recovery after you train. Here's the way Brainum explained it: "Two primary pathways exist to help use AMP [adenosine monophosphate] in the creation of ATP. One is called the salvage pathway, a system in which the body tries to salvage AMP breakdown products. The good news is that when it works, it works well in helping to maintain ATP stores. That's where ribose enters the picture. Ribose promotes this more efficient salvage pathway, thus allowing better ATP recycling and consequent increased muscular recovery after training. If the body doesn't use the salvage pathway—for example, when ribose is insufficient—it must make ATP from scratch."

Making ATP from scratch is not a very efficient process and can compromise gains, so you don't want to be ribose deficient. Unfortunately, most hard-training bodybuilders are deficient because they don't get enough recovery time to regenerate ribose, which means they eventually run out of gas, plateau and more than likely fall victim to overtraining. One study showed almost a 20 percent drop in muscle ATP after only seven weeks of sprint training. Now imagine what happens to overall muscle ATP in bodybuilders after a few weeks of training all of their muscle groups. It's no wonder overtraining is so prevalent and the sport is filled with so-called hardgainers. (Perhaps hardgainers are simply not recovering due to ribose depletion.) Ribose supplementation could prevent that, or at least significantly slow the onset of overtraining by speeding the recovery process and ATP formation. Muscle biopsies of subjects taking ribose showed that they used their energy stores more effectively and recovered quicker after exercise. The hard numbers say that supplemental ribose increases ATP manufacture in skeletal muscle by 340 to 430 percent. In the ATP-salvage process supplemental ribose increases the cell's ability to reuse ADP and AMP by up to 700 percent. We're talking major muscle energetic upticks here along with a significant boost in muscle recovery between training sessions.

Brainum also discussed ribose's vital role in the formation of nucleotides, which are "needed for energy production; synthesis of protein (i.e., messenger RNA), glycogen and nucleic acids (RNA and DNA); enzymatic control of electrolyte metabolism; formation of cyclic nucleotides, such as the cyclic AMP needed for fat oxidation and hormone-cell interactions." Are you beginning to see the ribose-break-through connection?

Could ribose be the missing link that speeds recovery and puts an end to the hardgainer tag forever? Possibly. One thing is certain, however: All bodybuilders can benefit from better recovery and more efficient muscle energetics during a workout, and ribose is proving to be the new breakthrough in muscle regeneration supplementation as well as ATP-creatine synergy for more workout intensity.

—Steve HoJman

Fast Fitness

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