Carbohydrates stored in the muscle and liver are important for both anaerobic and endurance performance. The form of carbohydrate stored in the tissue is glycogen, a polysaccharide of glucose stored with phosphates and water in a 1:3 ratio. Muscle glycogen provides the necessary fuel for energy metabolism in striated muscles, while liver glycogen supplies glucose to other cells and maintains blood glucose levels for brain function. During exercise, muscle tissues begin to use glycogen while the liver releases glycogen into the blood at a proportional rate to thwart hypoglycemia. Fatigue during endurance events or prolonged anaerobic activity has been associated with low glucose levels in the muscle and in the blood. However, the body does not simply “run out” of glycogen and then “turn off” like a car running out of gas. If that were the case, active muscle would fall into a state of rigor-mortis as glycogen depleted from the system. Rather, fatigue has an onset characteristic that yields signs and symptomatic evidence as it increases in magnitude.

Fatigue during exercise is influenced by a complex interaction between peripheral and central nervous system factors. However, the duration of exercise maintained at a given intensity is related to the relative level of glycogen stores in the active tissue. For example, if a person runs at an 8-minutes per mile pace, eventually the run feels more difficult, even without alterations to pace or terrain resistance due to the energy contributions from carbohydrates. In this regard, scientists have found a linear relationship between a person’s perceived exertion (RPE) and their level of muscle glycogen. As muscle glycogen is depleted during a training bout, exercise will “feel” more difficult, and RPE will increase.

Concurrently, other fatiguing factors contribute to performance decline, such as signals which turn off enzymes that convert glycogen to energy and signals that increase the liver’s ability to make glycogen from other sources such as proteins. The drop in the blood levels of branched chain amino acids has been linked to altered brain chemicals (i.e. serotonin and dopamine). Some studies suggest that this drop in branched chain amino acids will alter one’s mood in favor of “relaxation” over feelings of “excitation.” Therefore, an athlete would rather stop exercising at this point and rest than continue, often called “hitting the wall”. A higher ratio of the chemical serotonin to the chemical dopamine in the brain is associated with feelings of tiredness and lethargy, hastening the onset of fatigue, whereas a low ratio favors improved performance through the preservation of arousal and motivation. Moreover, fatigue has been shown to occur when glycogen levels experience further diminution and the pain associated with exercise exceeds the reward of continuing the activity, a condition ultimately leading to the cessation of training. Finding a way to keep glycogen levels elevated in the muscle allows for a delayed onset of fatigue, whether it be due to reduced pain with exercise (peripheral), preserved balance of brain chemicals (central), or a combination of both.

Given this information, much attention has been focused on methods to increase glycogen stores prior to prolonged exercise (~ >90 minutes). Since the mid-1900s various methods have been employed by athletes and investigated by scientists. The “classical method” involved an initial phase of approximately 3 days of glycogen depletion by eating an Atkins-type (low carb) diet and exercising to exhaustion. This phase is followed by a period of high carbohydrate intake and reduced activity (~3 day taper). The newer methods do not involve a depletion phase, just reduced training and increased carbohydrate intake during a taper. Although the newer methods typically lead to less glycogen loading than the depletion-first methods, some believe that increase is sufficient to improve performance, without the potential side effects associated with the depletion phase (mood swings, symptoms of overtraining, potential of reduced immune function, etc…). As a result, many scholars/coaches/dieticians have recommended the newer methods in recent years.

Anecdotal performance evidence comparing the classical and new carbo-loading techniques has lead to a split decision by some practitioners. The preference of the older method may be attributed to the difference that sometimes exists between people who discuss exercise physiology and those who practice it; or the difference between scientific findings that are “statistically significant,” and those that are “practically significant.” Indeed, the subjective evidence is abundant; many athletes have migrated back to the classic method after finding the new method to not be as effective. Likewise, bodybuilders who practice the depletion method followed by carbo-loading to gain muscle mass for competitions have used the classic method for decades and claim such obvious and successful results that performing carbo-loading without depletion is rarely debated. Clearly, by just increasing carbohydrate intake alone without depletion-first they fail to see nearly the same amount of increases in body mass (remember for every 1 gram of glycogen stored there is almost 3 grams of water stored with it).

Interestingly, practice-based outcomes have led some investigators to revisit the traditional method of carbo-loading once again providing support of the classical depletion-first method. This may be due to advances in the means by which we can measure muscle carbohydrate levels. Many studies measure glycogen using muscle samples drawn via a needle called muscle biopsies. Some problems with these studies is that there are typically a small sample-sizes of participants, and involve a small number of biopsies taken (~3-4 times per subject). Moreover, biopsies taken from a muscle, even a small area (< 10cm2 ) reduces the muscle’s ability to store glycogen. This is a major and ironic confounding variable when the aim of such studies is to quantify muscle glycogen stores in response to dietary and training strategies.

Alternatively, new studies use a technique called nuclear magnetic resonance spectroscopy which exploits the magnetic properties of certain cell nuclei. This technique can identify carbon atoms in an organic molecule and has become an important method for understanding aspects of organic chemistry such as fuel levels in muscle. In contrast to the biopsy technique, this method allows for frequent, repetitive and non-invasive measurements which will not traumatize the muscle being studied.

Recent studies using this technology have clearly shown that a depletion phase promotes greater glycogen storage which lasts for a longer period of time than carbo-loading without a depletion phase. In support of earlier research, it appears that the depletion phase increases glycogen stores via 3 main pathways: 1) increased ability to uptake glucose; 2) increased storage rate; and 3) preferential fat metabolism and reduced glycogen oxidation (usage) rates. Recent research demonstrates that glycogen-depletion directly increases the capacity of a muscle to uptake glucose by increasing the expression of glucose transporters. It has been found that muscle contraction occurring when glycogen stores are low, increases an enzyme (AMPK alpha 2 isoform) which moves to the muscle cell nucleus to increase the synthesis of specialized transporters of glucose inside the muscle cell. Basically, the muscle gets better at pulling glucose out of the blood in an attempt to restore glycogen content. A concomitant increased glycogen storage rate occurs due to increases in the activity of the enzyme that stores glucose as glycogen in your cells (glycogen synthase). This enzyme is activated by low levels of its substrate (glycogen). The depletion phase lowers glycogen stores, causing the enzyme to be more active. The increased activity can dramatically increase the rate of glycogen storage in the subsequent carbo-loading phase (supercompensation). Thirdly, glycogen depletion may also evoke a shift in fuel oxidation, favoring fat over carbohydrate metabolism during prolonged exercise. This effect seems to involve up- and down-regulation of key regulatory enzymes in the pathways of skeletal muscle fat and glycogen metabolism, respectively. For example, after glycogen depletion the activity of enzymes that harness fat from storage (hormone-sensitive lipase) increase while the activity of enzymes which harness energy from glycogen in the muscle (pyruvate dehydrogenase) decrease. This adaptation may be preserved over the course of a brief taper period during carbo-loading and may ultimately help preserve glycogen levels for a longer period of time during endurance exercise.