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science nutrition blog

science nutrition <strong>blog</strong>

By Michael J. Rudolph, Ph.D.


One of the more popular axioms in sports science advocates drinking plenty of fluids to support optimal workout performance, as dehydration tends to significantly deplete muscular strength, power and endurance. Taking in fluids to avoid systemic dehydration only defines some of the advantages hydration provides, as sufficient fluid intake provides only some of the benefits of hydration. At the cellular level, adequate hydration within the muscle cell provides added benefits that can improve muscular size and strength. In fact, muscle cell hydration directly influences muscle growth by altering muscle cell volume. More specifically, improved cellular hydration can increase muscle cell volume, triggering muscle protein synthesis while decreasing muscle protein breakdown1,2, ultimately resulting in muscle growth.

The swelling of the muscle cell is ostensibly perceived by the cell as a threat to its structural integrity. This causes the cell to increase the synthesis of certain structural proteins while reducing the breakdown of others within the cell, boosting cellular stability as well as muscle size. The primary force driving volume changes within any cell, including muscle cells, is osmotic.3 In the body, osmosis normally involves the passage of water across the cell membrane, suggesting the best way to increase muscle cell volume, and thus muscle hydration, is to simply drink more water. Unfortunately, it is not that simple.

For starters, drinking more water will likely result in increased urine production by the kidneys, and not much else. On the other hand, consuming more water with glycerol will increase water retention by the kidneys, providing more water throughout the body (a process known as glycerol hyperhydration). Yet, even with more water retained in the body from glycerol intake, water will still not optimally flow into the muscle cell. To achieve maximal muscle hydration, water must be pulled into the muscle cell by osmotically active molecules within the muscle cell. Even though glycerol does function osmotically, pulling some water into the cell, advanced muscle cell hydration requires ingesting glycerol in combination with other powerful osmolytes like creatine or betaine that pull even more water into the muscle cell – maximizing muscle cell hydration that boosts muscle growth, strength and performance.

Boost Muscle Cell Hydration With Creatine

Perhaps the most effective osmolyte is the compound creatine, which is also one of the most effective muscle-building supplements on the market. Numerous studies over the years have shown the positive influence of creatine use on high-intensity exercise performance. This heap of evidence unmistakably shows creatine use increases power output during intense exercise while also stimulating muscle hypertrophy.4 The extraordinary capacity of creatine to boost size and power arises from creatine functioning as a primary energy storage molecule that rapidly reverses the depletion of muscle cell energy (in the form of ATP) during muscular contraction. Energy maintenance in the muscle cell prolongs the capacity for muscular contraction, promoting superior exercise performance and greater muscle growth.5 Creatine further stimulates muscle growth triggering several cellular mechanisms that include the stimulation of muscle cell formation6 and increased muscle protein synthesis.7 Research also shows creatine uptake into the muscle cell increases cell volume by attracting water into the cell causing the cell to swell, an affect most likely contributing to the outstanding muscle-enhancing effects of creatine.8,9

Enhancing Creatine's Volumizing Effect

Betaine is another powerful cellular osmolyte that also raises cellular water retention. Betaine’s muscle-hydrating function plausibly enhances muscle hypertrophy by also causing the muscle fiber to swell. In fact, a recent study showed subjects taking betaine while lifting weights gained up to 4 pounds of muscle mass.10 Other studies have shown betaine ingestion can also significantly amplifies anaerobic power in the bench press and squat11, suggesting the muscle-hydrating influence of betaine likewise augments muscle size and power. Betaine also appears to indirectly improve muscle hydration by improving creatine function, as betaine has the capacity to improve insulin function. The insulin-enhancing effect of betaine escalates creatine uptake into the muscle cell as insulin signaling drives creatine into the muscle cell.12 As a result, betaine supplementation not only functions as an osmolyte itself, improving muscle cell hydration, but also appears to amplify creatine uptake into the muscle cell – encouraging even greater cell swelling that conceivably bolsters a greater anabolic state within the muscle cell.

Hyperhydrate With Glycerol

The consumption of osmolytes creatine and betaine to drag water into the muscle cell improves considerably when co-ingested with the hyperhydrating compound glycerol. Glycerol hyperhydration is characteristically employed to induce fluid retention before exercise, offsetting dehydration – as loss of body fluids from sweat tends to reduce bodily functions like cardiac output, negatively influencing exercise performance. Doses of 70 grams of glycerol dissolved in around 2 to 3 liters of water several hours before exercise provides the hyperhydrating effect that increases water retention, improving endurance exercise performance.13

Glycerol’s capacity to rehydrate after exercise requires much less glycerol, which for many may be a better approach as 70 grams of glycerol provides a considerable calorie count at 280 calories – and this much glycerol may increase the likelihood of the rare side effects associated with glycerol use which include nausea, gastrointestinal discomfort and lightheadedness. Nevertheless, consuming around 9 grams of glycerol in one half a liter of water while exercising should delay dehydration.13 Finally, adding a similarly high amount of glycerol (70 grams) to 1 liter of water post-workout will speed up the hydration process.13

While the research on glycerol clearly shows a significant influence on hydration status, the effect of glycerol on aerobic and anaerobic performance is much more uncertain, with some investigations showing glycerol improved aerobic and anaerobic performance14 while other studies showed no affect whatsoever on aerobic or anaerobic capacity.15

Maximize Cell Volume Combining Glycerol With Creatine

Though it is uncertain whether glycerol can build strength and muscle, combining glycerol intake with creatine seems a logical progression toward enhanced muscle size and strength. The combined use of glycerol with creatine has been shown to have an additive effect on hydration, as the intake of glycerol with creatine for seven days significantly increased body fluid volumes 40 percent more than creatine alone and almost 50 percent more than just glycerol.16 Additional studies have also found the combined use of glycerol with creatine successfully attenuated the rise in body temperature and heart rate while test subjects exercised in hot temperatures, indicating greater hydration throughout the body and within the muscle cell from the combined use of these two compounds improves exercise performance.17,18 Naturally, these results have important implications for the potential influence of a glycerol-creatine blend on muscle hypertrophy, as more water in the muscle cell from creatine and glycerol ingestion should drive more muscle growth. Regrettably, no studies to date have investigated this effect. So, stay tuned to MD as we’ll be sure to report on this as soon as this data becomes available.

Despite the theoretically potent anabolic outcome of enhanced muscle cell hydration from this hydrating stack, there is one major potential drawback with the significant water retention caused from this approach. This will likely make many decide not to use these compounds for peak muscle hydration, especially the bodybuilder, as holding additional water would most certainly diminish the physique especially during contest preparation. Nonetheless, due to the potential effectiveness of this unique muscle-building method, the bodybuilder should reconsider the use of glycerol with creatine/betaine as a worthwhile option during off-season training, when gains in muscle size and strength take priority over getting ripped and shredded.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biological effects of exercise as a fellow at Harvard Medical School and Columbia University. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK – leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a Senior Scientist working at the New York Structural Biology Center where he investigates the molecular nature of human illness and disease.



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