Cell Volume and Muscle Growth – Implications for Nutritional Supplementation

Gym “experts” – When most gym rats talk about getting bigger they are obviously referring to muscle growth or hypertrophy. Often, however they don’t really have a clue as to what’s happening within their muscles in order to make them bigger and stronger. For all they know little muscle fairies sneak into their rooms at night and when they wake up in the morning, voila, they’re bigger. Without fail, though, this never seems to stop the most ignorant of them from throwing around their lack of information with poorer form than the 20 lb dumbbells they use for “cheat” curls. And although I’m not the most brilliant guy in the world, I consider myself fairly knowledgeable at the iron game. For some reason, though, I seem to be a target for these gym “experts” as they are continually instructing me as to how to train and diet!

One comment that I hear pretty often that never ceases to amaze me is the comment many gym “experts” make regarding creatine. Perhaps you have heard it too. It goes something like this “So whaddya think about that creatine stuff? I tried it and yea it’ll put some pounds on ya, but it’s all water weight and I don’t like to feel bloated. Besides, you lose it all when you go off anyway”. (Its amazing how the statement they wish to make is always posed in the guise of a question as if they really wanted my opinion). Well at this point rather than respond to the “question” I usually thank them for the info and let them know that they just saved me a lot of wasted time and money on such a worthless supplement.

As an educator, I should be a little more understanding, but when I’m in the middle of a squat workout in which I am taking 60 second rest periods between sets, I really don’t have time to reprogram Biff and his anti-creatine chronies.

In all honesty Biff is right (god I hate to admit it) about one thing; the first few pounds gained when taking creatine are probably just a result of increased water weight. BUT the bloated feeling Biff is referring to is probably not a result of his creatine intake but probably from his 6 Budweiser and his Bucket o’ ribs at Sizzler last night. The reality of the situation is that an increase in water weight from creatine isn’t such a bad thing. In fact if that water weight happens to be intracellular fluid (which it often is) not only should that water weight lead to increased strength, but it should also lead to increased protein synthesis, increased muscle mass, and long term growth. Let me explain:

What exactly is muscle growth? Hypertrophy vs Hyperplasia

To begin, I’d like to cover the two main ways for an individual to increase overall muscle size. The first, muscle fiber hypertrophy, refers to the increase in the diameter of the individual muscle cells. The larger the cells, the larger the overall muscle, it’s that simple. Muscle fiber hypertrophy = Big muscle fibers.

The second, muscle fiber hyperplasia, refers to the splitting of muscle fibers in the interest of creating new fibers. Obviously this would be of interest to anyone pursuing size or strength due to the fact that and if an individual has more fibers, their overall size potential is greater. Therefore when looking at hyperplasia, Muscle fiber hyperplasia + Muscle fiber hypertrophy = Many big muscle fibers.

At this point, I know that you’re all supercharged to learn how to both make more fibers and to make them bigger, but I’m going to have to put the breaks on and be the bearer of bad news. The problem with hyperplasia is that no one really knows exactly how to promote it. Once we are born, some experts believe, muscle fiber number remains fixed for our lifetime. Therefore under normal circumstances muscle fiber hyperplasia seems nearly impossible.

nterestingly, though, experts have begun to speculate that under abnormal circumstances hyperplasia can contribute to overall muscle growth. For starters, recreational or even moderately intense weight training will probably NOT do it. Unfortunately there has not even been any evidence that very intense weight training will promote hyperplasia. One proposed link to hyperplasia, though is anabolic steroid use. A recent article in the American College of Sports Medicine’s Medicine and Science in Sport and Exercise found evidence for muscle fiber hyperplasia in anabolic steroid using powerlifters(1). This however, is pretty much the first evidence of a mechanism for hyperplasia in humans. The bottom line is that unless we are ready to boatload anabolic steroids into our systems, neither you nor I are going to be enjoying the benefits of muscle fiber hyperplasia any time soon. So what about hypertrophy? Well that, my friends, is a reality.

Two types of hypertrophy?

Let’s address the 2 main forms that muscle fiber hypertrophy can take. Muscle fiber hypertrophy can be accomplished by either increasing the volume contained within the muscle cell or by increasing the actual amount of muscle contractile protein making up the muscle cells. To give a simple analogy to help differentiate between the two types of hypertrophy, one can think of the muscle cell as a water-filled balloon. To make the balloon bigger (hypertrophy), one can either add more water to the balloon, thereby stretching it to its maximum capacity (increase cell volume) or one could theoretically add more balloon material to make the overall size of the balloon larger (increase in contractile protein). Although the mechanisms that cause increased cell volume and increased contractile protein content may be different, both are affected by weight training and there seems to be a link between the two that bodybuilders may be able to exploit in order to cause lasting muscle growth

First and foremost, when we talk about hypertrophy, we are most often referring to the second type mentioned above – an increase in contractile protein (adding more material to the balloon). This type of hypertrophy is the most lasting since it constitutes a remodeling of the muscle fibers, making them permanently bigger than before (assuming you continue to train, of course). Muscle increases of this type are not only asthetically pleasing, but also contribute significantly to strength. The more fibers available to contract, the more weight can be lifted!

But what about the other type of hypertrophy? Well let’s put it this way; how many of you wish that your muscles looked as good outside of the gym as they do in the gym after a great skin-stretching “pump”? I know that when I was younger, I wouldn’t even take one step out onto to the beach without doing some pushups first in order to “get a little blood into the muscle”. This phenomenon, the infamous “pump”, is a short-lived example of increased cell volume. Fluid moves into the cell thereby causing it to stretch, take up more space, and make you look pretty darn good. Unfortunately, such increases in cell volume disappear almost as quickly as they came. The good news is that there are other ways to increase cell volume for longer periods of time.

The increases in cell volume and their contribution to muscle growth that I wish to address are brought about by naturally by increases in cellular water; increases in the cellular storage of substrates such as carbohydrates, lipids, or amino acids; and increases in the cellular movement of ions like sodium and potassium. Research has shown that supplements like creatine, glutamine, and ribose can also lead to increases in cell volume by both increasing their own content within the cell but also by attracting water into the cell, causing cell swelling (2,3,4,5).

What’s the big deal with increased cell volume or cell swelling?

If you’ve read any of my previous articles, you know that I’m big on citing research, for without quality research, our attempts at finding out the truth about how our universe operates are merely stabs in the dark. (Kind of like Biff’s attempt at rational thought.) This research focus applied to the cell volume question has produced quite a bit of very interesting research that has and is bound to continue to dramatically impact the fitness and sports nutrition industry. Initially cell volume studies focused on the cells of the liver since the liver is the most important organ for whole body metabolic regulation (3,5,6).

What these studies found was that independent of hormone influence or substrate influence, decreased cell volume (cell shrinking) lead to cellular catabolism or protein breakdown, while increased cell volume (cell swelling) led to anabolism or protein synthesis. In this regard, the original authors of such papers concluded that cell swelling or shrinking acted as a “second messenger to tell the cell what to do about protein synthesis. Basically, the hormones tell the cell to swell or shrink and it is this swelling or shrinking, not the hormone’s action, that leads to changes in protein metabolism.

These findings were particularly exciting for muscle physiologists because this link could be explored in many clinical populations such as burn victims who are extremely catabolic and the elderly who tend to lose large amounts of muscle mass. Although the muscle research has mostly focused on catabolism rather than anabolism, a few important “take home” findings are evident. First is that decreased body water and intracellular nutrients can lead to cell shrinking and as we now know, increased muscle protein breakdown (7). Therefore by maintaining normal hydration and maximal substrate storage with ample fluid consumption and nutrient intake, an individual can easily prevent a great deal of protein breakdown. Also, although experimentally unproven, increased cell volume above normal hydration may lead to increases in muscle protein content. This is where supplements, especially those consumed immediately after bouts of intense exercise, come into play.

As I stated last month, maintaining a normally hydrated or volumized cell is crucial for preventing muscle loss. In addition, increasing the cell volume beyond “normal” may be a strong signal for muscle growth. Insulin, for example, leads to both increased cell volume and substrate uptake (9,10,11). And we all have heard how anabolic insulin is.

Using this information, how can we ensure adequate cell volume and even tip the cell volume scales in our favor? In other words, enough of the theory, lets talk getting BIG.

1.) Drink plenty of water daily. I like to recommend 50-70 oz of water per day for practical purposes although I try to get at least a gallon myself (oh yea, I have my very own urinal with a gold name plate on it). One of the many symptoms of dehydration (which include fatigue, poor performance, etc) is cell shrinking. Cell shrinking signals cell protein loss and muscle catabolism (9,10,11). Stay hydrated.

2.) Maintain a normal sodium intake. 2000-3000 mg of sodium is a reasonable level. If you train intensely, more may be necessary to replace what has been lost during activity. Sodium is an important cellular regulator and far too many people focus on eliminating sodium from their diets. The impact of this is beyond the scope of this article, but suffice it to say, don’t go oveboard in eliminating sodium intake. Adequate (but not excessive) intake will probably help you grow.

3.) Ensure liver and muscle glycogen stores are full. Low carbohydrate intakes, especially during intense training will leave muscles flat and glycogen depleated. Since water travels with carbohydrate, low carbohydrate stores in the muscle can lead to decreased cell volume and muscle breakdown. Interestingly, this phenomenon seems to work in reverse as well, as low cell volume adversly affects glycogen synthesis (12). Normal to high intra-muscular stores of glycogen can cause cell swelling as carbohydrates bring water with them. If you have ever seen a bodybuilder after a contest, then you’ll know what I’m talking about here. After a show, their muscles are super-compensated with high intra-muscular levels of glycogen and water. It is no surprise, then, that this also happens to be the most anabolic time for these bodybuilders. To ensure high muscle and liver glycogen stores, be sure to consume a high carbohydrate and high protein meal immediately after exercise and one about two hours later. In terms of numbers, we’re talking carb to protein in a three or four to one ratio with carbohydrate intake being determined using 0.5 – 0.8 grams per pound (13). Using these numbers, a 200 lb bodybuilder will consume one 100 -160 grams of carbs immediately after training along with 25 – 40 grams of protein. Associated with this high consumption of carbs and protein is an increase in insulin levels, which I’ve already stated is very anabolic (14).

4.) Creatine Monohydrate has been proven to increase intracellular fluid. Intra-muscular stores of creatine have been shown to increase by about 20-50% after 5 days of oral creatine supplementation (15). This increase in creatine content has been shown to increase anaerobic power and muscular strength by increasing cellular energy potential. In addition creatine, like glucose and glycogen, attracts water into the cell and can increase intracellular fluid by about 2-3% (16). These increases can lead to marked cell swelling and possibly an anabolic state within the muscle.

5.) Glutamine has both anabolic and anti-catabolic properties, some of which result from its effect on cell volume. Glutamine is a conditionally essential amino acid, meaning that is essential during certain times like times of high stress, disease, or intense training (17). It also has profound effects on cell volume and amino acid metabolism. The literature has implicated low intracellular glutamine concentrations in overtraining syndrome, chronic fatigue syndrome, muscle catabolism, immune dysfunction, and cell shrinking (18). Since glutamine is released from the muscle to fuel gut cells and immune cells, oral glutamine supplementation has been shown to have a muscle sparing effect, allowing muscular glutamine stores to remain high and allow cell volume to remain normal. In this case, the glutamine you ingest is used to feed the gut and the immune system. This enables the muscle glutamine to remain high and to prevent the cell from shrinking and going into a catabolic state.

Back to the gym

If I were a nicer guy I would have explained all of this preceeding information to Biff and his groupies between my sets of squats. Who knows, I might have lead him to a new path of enlightenment. Instead me and my volumized cells climbed under the squat bar and proceeded to knock out 12 more intense reps, swelling my legs to painful proportions. After the workout, I made a big vanilla protein shake with lots of carbs, protein, creatine, and glutamine in an attempt to swell my cells and promote some muscle hypertrophy. Maybe next time I’ll let Biff know about this article so perhaps he too can reap the rewards of increased cell volume.


(1) F Kadi, A Eriksson, S Holmner, LE Thornell. Effects of anabolic steroids on the muscle cells of strength-trained athletes. Med Sci Sports Exerc 1999 Nov; 31(11):1528-34.
(2) Tim Ziegenfuss, Lonnie Lowery, and Peter Lemon. Acute fluid volume changes in men during three days of creatine supplementation. JEPonlineVol 1 No 3 1998.
(3) Dieter Hauussinger, Florian Lang, Kathrin Bauers, and Wolfgang Gerok. Interactions between glutamine metabolism and cell-volume regulation in perfused rat liver. European Journal of Biochemistry 1989; 89: 1153.
(4) Dieter Hauussinger, Erich Roth, Florian Lang, and Wolfgang Gerok. Cellular hydration state: an important determinant of protein catabolism in health and disease. Lancet 1993; 341: 1330-1332.
(5) Ingwall, J.S., C.D. Weiner, M.F. Morales, E. Davis, and F.E. Stockdale. Specificity of creatine in the control of muscle protein synthesis. J Cell Biol 1974;63:145-151.
(6) Deiter Haussinger and Florian Lang. Cell volume in the regulation of hepatic function: a mechanism of metabolic control. Biochemica et Biophysica Acta 1991; 1071: 331-350.
(7) Barbera Stoll, Wolfgang Gerok, Florian Lang, and Dieter Haussinger. Liver cell volume and protein synthesis. Biochemical Journal 1992; 287: 217-222.
(8) S.M. Hughes, and S. Schiaffino. Control of muscle fiber size: a critical factor in ageing. Acta Physilogica Scandinavica 1999; 167 (4): 307.
(9) Stephan Dahl, Christian Hallbrucker, Florian Lang, DieterHaussinger. Regulation of cell volume in the perfused rat liver by hormones. Biochem J (1991) 280, 105-109.
(10) Siegfried Waldegger, et al. Effect of Cellular Hydration on Protein Metabolism. Mineral Electrolyte Metabolism 1997; 23: 201-205.
(11) Dieter Haussinger, F Lang, W Gerok. Regulation of cell function by the cellular hydration state. Am J. Physiolo. 267 (Endocrinol. Metab. 30): E343-E355, 1994.
(12) SY Low, MJ Rennie, PM Taylor. Modulation of glycogen synthesis in rat skeletal muscle by changes in cell volume. J Physiol (Lond). 1996 Sep 1;495 ( Pt 2):299-303.
(13) JL Ivy. Glycogen resynthesis after exercise: effect of carbohydrate intake.Int J Sports Med. 1998 Jun;19 Suppl 2:S142-5.
(14) KM Zawadzki, BB Yaspelkis, JL Ivy. Carbohydrate-protein complex increases the rate of muscle glycogen storage after exercise. J Appl Physiol. 1992 May;72(5):1854-9.
(15) PL Greenhaff, A Casey, AH Short, R Harris, K Soderlund, E Hultman. Influence of oral creatine supplementation of muscle torque during repeated bouts of maximal voluntary exercise in man.Clin Sci (Colch). 1993 May;84(5):565-71.
(16) Tim Ziegenfuss, Lonnie Lowery, and Peter Lemon. Acute fluid volume changes in men during three days of creatine supplementation. JEPonlineVol 1 No 3 1998.
(17) M Rennie, A Ahmed, et al. Glutamine metabolism and transport in skeletal muscle and heart and their clinical relevance. The Journal of Nutrition 1996; 126: 1142S -1149S.
(18) D Rowbottom, D Keast, A Morton. The Emerging Role of Glutamine as an Indicator of Exercise Stress and Overtraining. Sports Medicine. 1996, Feb 21 (2); 80-97.

Of course, if you want a complete guide to doing this yourself, I strongly recommend you pick up a copy of Precision Nutrition, where I’ll show you in great detail exactly what to do.

About the Author Dr. John M. Berardi PhD, CSCS

Dr. Berardi’s philosophy is simple: people from all walks of life, from soccerstars to soccer coaches to soccer moms, should have access to the most recentdevelopments in health, exercise, and nutrient science. Dr. Berardi and his company,Precision Nutrition, Inc. have one purpose: to take the latest in advanced nutritionresearch and teach it to others in a way that doesn’t take an advanced degree tofigure out. Dr. Berardi has earned a doctoral degree from the University of WesternOntario (2005) with a specialization in the area of exercise biology and nutrientbiochemistry. Prior to his doctoral studies, Dr. Berardi studied Exercise Scienceat Eastern Michigan University (Masters program; 1999) as well as Health Science,Psychology, and Philosophy at Lock Haven University (Undergraduate program; 1997).Currently, Dr. Berardi is an adjunct professor of Exercise Science at the Universityof Texas at Austin. Through his company, Precision Nutrition, Inc., Dr. Berardi hasworked in the exercise and nutrition arena for over a decade, working with individualsfrom all walks of life, from the sedentary to athletes at the highest level of sport.www.Precision-Nutrition.com