The hydration state (cell volume) of muscle cells is an important determinant of protein anabolism. Increasing muscle cell volume or hydration status acts as an independent anabolic signal as it initiates the cellular mechanisms needed to preserve and create net gains in muscle1.  Muscle cell hydration is a determining factor in muscle growth.

Very small alterations in cell volume act as separate and potent signals of cellular metabolism. They not only serve to re-adjust cell volume but also profoundly modify a wide variety of cellular functions2. The effects of cellular hydration are intriguing as an increase in cellular hydration (swelling) acts as an anabolic, proliferative signal, whereas cell shrinkage is catabolic and anti-proliferative1-3.

Cell volume is dynamic and changes within minutes under the influence of substrates, hormones, amino acids, glucose and oxidative stress. Increasing cell volume triggers a number of anabolic reactions such as an increase in amino acid transport and protein synthesis and a decrease in protein catabolism2-4. Muscle cell volume dictates protein synthesis.

GL3 L-Glutamine 1200 Grams - Best Glutamine SupplementWater does not simply reside inside a muscle cell. Osmotic substrates are transported into the cell, and this is paralleled by respective water movement across cell membranes and subsequent alterations in cell volume. Pioneering work by several research groups in the 90’s provides evidence that glutamine is the most potent amino acid in its affects on cell swelling and the influence on muscle cell volume4-6.

Glutamine is the primary substrate of the insulin-sensitive Na+-dependent transport system Nm the fastest of all amino transporters in the sarcolemma7. At both basal and insulin-stimulated capacities, glutamine transport into muscle dramatically influences cell volume. Haussinger et al. (1995), using perfused muscle and demonstrated that as long as glutamine concentration remained high, cell volume (and anabolism) remained elevated.

An inverse relationship between protein synthesis rates and cell volume has been established. Using hospital patients with various catabolic conditions, researchers established that the extent of nitrogen wasting correlated closely with muscle glutamine content. Thus, muscle glutamine levels are shown to directly affect cellular volume [Low 6], cell volume is shown to affect protein synthesis rates4,5 and intramuscular glutamine levels also appear to affect protein synthesis8. Only 6-7% of muscle cell glutamine is within bound proteins,9 therefore, changes in cellular hydration state may be the variable linking muscle glutamine content to protein turnover in skeletal muscle, and because of the large mass of skeletal muscle, to whole body nitrogen balance.

See Also:
Carbohydrate Timing - How to Time Your Carbohydrate Intake For Maximum Muscle-Growth and Fat Loss

How to us this science for greater muscle gains . . .

Certain proteins and supplements can affect muscle cell volume and the anabolic/catabolic responses to training.

Increasing cell volume is an independent and powerful anabolic signal. It can be initiated by amino acids such as glutamine and creatine.

Therefore promoting cell hydration with muscles with strategic supplementation before and in the hours immediately following intense exercise can enhance muscle anabolism and dramatically increase results from heavy resistance training.

Cell volumizing strategy during intense training programs:

5-10 grams GL3 L-Glutamine in the hour before workouts – can be mixed with one serving of VP2 Whey Isolate.

Note: Micronized Creatine should also be used here as creatine is also a known cell volumizer – 5 grams.

5-10 grams GL3 L-Glutamine within the hour after workouts – can be mixed with one serving of VP2 Whey Isolate.

5-10 grams GL3 L-Glutamine within the 3-hour post workout window – can be mixed with one serving of VP2 Whey Isolate or Raptor-HP.

Non-training days: to maintain elevated cell volume & anabolism, 1 serving (5-10 grams) GL3 L-Glutamine per day.


1. Haussinger D, Hallbrucker C, vom Dahl S, Lang F, Gerok W. Cell swelling inhibits proteolysis in perfused rat liver. Biochem J 272: 239-42, 1990.
2. Stoll B, Gerok W, Lang F, Haussinger D. Liver cell volume and protein synthesis. Biochem J 287:217-22, 1992.

3. Haussinger D, Roth E, Lang F, Gerok W. Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 341:1330-1332, 1993
4. Haussinger. D. Regulation of metabolism by changes in cellular hydration. Clin.Nutr 14:4-12, 1995.
5. Vom Dahl S, Haussinger D. Nutritional state and the swelling-induced inhibition of proteolysis in perfused rat liver. J Nutr 126:395-402, 1996.
6. Lang F, Busch GL, Ritter M, Volkl H, Waldegger S, Gulbins E, Haussinger D. Functional Significance of Cell Volume Regulatory Mechanisms Physiol Rev. 78:247-272, 1998.
7. Low SY, Taylor PM, Rennie MJ. Response of glutamine transport in cultured rat skeletal muscle to osmotically induced changes in cell volume. J Physiol 492:877-885, 1996.
8. Cribb PJ, Williams AD, Hayes A and Carey MF. The effect of whey isolate on strength, body composition, and plasma glutamine. In J Sports Nutr Exerc Metab, 2006.
9. Curi R, Lagranha CJ, Doi SQ. Molecular mechanisms of glutamine action. J Cell Physiol 204: 392-401, 2005.


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Muscle Cell Volume: The Forgotten Anabolic (Muscle-Building) Stimulus

by Paul Cribb Ph.D. CSCS. time to read: 4 min