How you can increase your cell volume for rapid muscle growth

Here is a brief summary:

1. Cell volume is critical when it comes to transporting amino acids into cells. Increasing cell volume is also a fundamental property of compounds such as creatine.
2. Cell volume and pump, although related, are not the same thing. Cell volume refers to the fluid within the muscle cells, while pump has to do with the fluid between the muscle cells.
3. Even though cell volume and pump are different things, an increased pump can promote an increase in cell volume and lead to increased growth.

Nothing is more satisfying after a training session than a pump that literally bursts through your skin. This feeling lets you know that you have accomplished your task during training. The trained muscle is so "full" that even small movements become a challenge and you can literally feel the blood rushing through your arteries.

The fact that your muscles tend to feel extra full during periods of increased growth - even between training sessions - is no coincidence. A full muscle is an anabolic muscle, and increased cell volume works backstage to drive anabolic muscle growth.

It's widely believed that the best way to increase cell volume is to get a great pump in the gym. However, even though cell volume and pumps are related, they are not the same thing. While cell volume refers to the volume of water within the muscle cells, a pump - also known as reactive hyperemia - represents increased volume in the areas between and around the muscle cells, also known as the interstitial area.

Despite this distinction, an excellent pump can promote increased cell volume under the right circumstances. If you have not yet considered this variable as part of your training nutrition strategy, you should do so in the future. Cell volume is crucial when it comes to transporting amino acids into cells, activating protein synthesis and suppressing catabolic protein breakdown during the critical window of opportunity around your workout.

The anatomy of the muscle pump

In response to high-intensity exercise, the local blood supply to hard-working muscles increases, increasing the delivery of oxygen and the removal of waste products. This reactive hyperemia, also known as pumping, results in an increase in the amount of blood plasma in the areas between and around the muscle cells (interstitial area).

The combination of an increased amount of blood plasma and an accumulation of lactate and other metabolic waste products increases the osmolality of the interstitial fluid (1). This generates a concentration gradient that draws additional water from the bloodstream (2, 3) and causes a phenomenon we all know as the pump.

Since the pump is generally considered synonymous with cell volume, it may surprise some that the osmotic forces that conspire to induce the pump actually promote shrinkage instead of volumization.

This makes sense - at least on paper. Increase the concentration of a solute on one side of a semipermeable membrane and water will diffuse across the membrane in the direction of the concentration gradient until the solution reaches equilibrium. In the same way, in muscle tissue experiencing a pump, the increased osmolality of the interstitial fluid will cause water to diffuse out of the muscle cells in the direction of the concentration gradient, which would ultimately reduce cell volume.

Fortunately, skeletal muscle is well equipped to deal with this. Through a process known as regulatory volume increase (RVI), muscle cells are able to maintain or even increase their cell volume despite the increased osmolality that occurs during a skin bursting pump (4).

Understanding how this works is not just of academic interest - it's fundamental if you want to harness the anabolic power of cell volume to your advantage. Cell volume increases during a muscle pump via a coordinated activity of two transport proteins located in the cell membrane (4).

In the first step, the sodium-potassium (Na+/K+) ATPase pump transports three sodium ions out of the cell in exchange for two potassium ions. Since the concentration of sodium outside the cell is typically 10 to 20 times higher than inside the cell, energy in the form of ATP is required to pump sodium out of the cell against the concentration gradient.

In the second step, another pump associated with the membrane, known as the sodium-potassium-chloride co-transporter pump (NKCC for short), simultaneously transports one sodium, one potassium and two chloride ions from outside the cell into the cell.

If we do our math homework, we find that the coordinated action of the Na+/K+ ATPase and the NKCC pump results in a net influx of charged ions into the cell, which increases intracellular osmolality. When intracellular osmolality increases relative to the osmolality of the interstitial fluid, water is drawn into the muscle where it increases cell volume.

The increase in cell volume mediated by the NKCC pump is driven by the sodium gradient generated by the Na+/K+ ATPase pump (4). You can see exactly how this works in the figure above.

Cell volume and amino acid transport

The extracellular sodium gradient generated by the Na+/K+ ATPase pump is not only important for increasing cell volume - amino acid uptake is also driven by this sodium gradient. In order to repair damaged muscle tissue, we need to transport amino acids into the cell to activate protein synthesis. Although all amino acids activate protein synthesis to some degree, leucine is the most potent activator.

Leucine is transported into the cells via a tertiary active transport mechanism. For our purposes here, the exact molecular details of this process are less important than the big picture.

In order to activate muscle growth and the repair process after an intensive training session, we need to transport leucine into the cell. Leucine uptake is driven by cell volume and is dependent on the sodium gradient induced by the Na+/K+ ATPase (5).

At this point, you may have already noticed a trend: just like an increase in cell volume, amino acid uptake is also dependent on sodium, potassium, ATP and water.

Cell volume, protein synthesis and protein degradation

Cell swelling inhibits protein degradation and stimulates protein synthesis in a number of cell types (6-8) including skeletal muscle cells (9, 10). Since hard training stimulates both protein synthesis and protein breakdown (11), we are essentially fighting protein breakdown after every single training session.

If we consistently shift the balance towards protein synthesis and away from protein breakdown, then we win the battle for muscle growth and will build new muscle mass and strength. Since protein turnover increases substantially during the minutes and hours following exercise (11), maximizing cell volume with optimal training nutrition is critical to long-term progress.

A cell volume action plan

Now that we understand how all of this works, there are a number of things we can do to harness the anabolic power of cell volume.

1 - Increase hydration

This goes without saying. At the most basic level, adequate hydration is needed for optimal cell volume. The ability to activate protein synthesis and suppress protein breakdown during the window of opportunity around training is dependent on this. Even if you are only slightly dehydrated, your performance and recovery ability will be impaired.

2 - Optimize your electrolyte balance

To get water into the cells and increase cell volume, we need osmolytes - osmotically active molecules that draw water into the cell. For this reason, it is important to maintain optimal levels of sodium, magnesium and potassium. (Other important osmolytes would be chloride, calcium and phosphorus).

As we learned above, sodium and potassium are needed for cell volumization and amino acid uptake. For this reason, you should not shy away from sodium before and after training. Blood volume is highly dependent on sodium levels and if you are deficient in sodium, the pump you get during exercise will be almost non-existent.

You should also make sure to consume potassium-rich foods. Potatoes, broccoli, bananas and pumpkin are excellent sources of potassium. The function of the Na+/K+ ATPase (12) and NKCC (13) pumps is also dependent on magnesium, which is why your cell volumization will be impaired if you suffer from a magnesium deficiency. Regular ZMA® supplementation can prevent such a deficiency to help you keep the machinery of cell volumization running like a well-oiled machine.

3 - Creatine monohydrate - the original cell volumizer

It's hard to write about cell volume without mentioning creatine, which is stored in muscle cells in the form of phosphocreatine and provides a phosphate group to regenerate ATP during high-intensity contractions.

Creatine supports cell volumization via direct and indirect mechanisms. As an important muscle osmolyte, creatine increases cell volume directly by drawing additional water into the cell when it is ingested.

Creatine also increases cell volume indirectly. We learned above that the Na+/K+/ ATPase pump uses energy in the form of ATP to transport sodium out of the cell against the concentration gradient. This function is so important for life itself that more than 30% of total cellular ATP is used to keep the Na+/K+ ATPase pump running.

Creatine therefore indirectly increases cell volume by providing the supply of energy-rich phosphate to regenerate ATP. Five grams of creatine per day is sufficient to increase cell volume.

4 - Correctly timed training nutrition

Your ability to regenerate and improve your development depends on the timing of nutrients during the training phase. When it comes to nutrient timing from a macronutrient perspective, the best approach is usually what is considered best practice. Amino acids are in themselves osmolytes, which when transported into the cell draw additional water into the cell and increase cell volume.

Insulin not only activates amino acid transport, but also further increases cell volume by inducing glucose uptake. But even though macronutrient timing is important, there are additional factors you can consider to maximize your cell volume:

Pre-workout (45 minutes before):

Consume functional carbohydrates such as highly branched cyclic dextrins in combination with a fast-acting protein hydrolysate to keep insulin levels stable. To maximize cell volume, sodium, water and to a lesser extent potassium, magnesium and calcium are important.

As mentioned above, the Na+/K+ ATPase pump generates the extracellular sodium gradient that makes cell volumization, amino acid uptake and even glucose uptake possible in the first place. In addition, you should already be well hydrated before training and therefore increase your water intake during this time.

Before training (15 minutes before):

Continue to consume functional carbohydrates and fast-acting protein hydrolysates in liquid form. During this phase and during the actual training session, the intake of water and electrolytes (sodium, potassium, magnesium and calcium) is crucial for maximum nutrient absorption and maximization of cell volume. To eliminate the guess work, it is recommended to use a product that is specifically designed for this purpose and includes functional carbohydrates, fast-acting peptides and all the required electrolytes in the right proportions.

Creatine is also useful at this point and in vitro studies suggest that this may be the optimal time to take creatine. Creatine uptake efficiency may increase in response to the increased interstitial osmolality that induces a muscle pump during exercise (14).

Post-workout:

After an intense training session, you need protein, water and rest. Another boost of protein hydrolysate will promote continued protein synthesis. In terms of cell volume, you should continue to drink water with electrolytes. (This is when many drop the ball, as the last thing you tend to think about after a brutal training session is drinking large amounts of water).

5 - Maximize mechanical tension

Although cell volumization is a fundamental driver of muscle growth and recovery, the real magic happens when the volumized muscle is subjected to a large amount of mechanical tension.

Part of the mechanism by which cell swelling activates protein synthesis is increased cytoskeletal tension, which directly increases protein synthesis via an increase in translational mRNA efficiency (15, 16). Mechanical tension in response to high-intensity muscle contractions also directly activates amino acid uptake (17), based in part on activation of the Na+/K+ ATPase pump (18).

By now you should have realized how intense training of a volumized muscle generates a highly anabolic state. Expose a volumized muscle to a heavy load with sufficient time under tension and you will increase amino acid uptake and protein synthesis. Add to this a perfectly planned training diet and you get an anabolic orgy.

References:

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2. Lundvall J, Mellander S, Sparks H. Myogenic response of resistance vessels and precapillary sphincters in skeletal muscle during exercise. Acta Physiol Scand 1967;70:257-68.
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5. Baird FE, Bett KJ, MacLean C, Tee AR, Hundal HS, Taylor PM. Tertiary active transport of amino acids reconstituted by coexpression of System A and L transporters in Xenopus oocytes. Am J Physiol Endocrinol Metab 2009;297:E822-E829
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10. Low SY, Rennie MJ, Taylor PM. Signaling elements involved in amino acid transport responses to altered muscle cell volume. FASEB J 1997;11:1111-7.
11. Drummond MJ, Dreyer HC, Fry CS, Glynn EL, Rasmussen BB. Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. J Appl Physiol 2009;106:1374-84.
12. WHANG R, WELT LG. Observations in experimental magnesium depletion. J Clin Invest 1963;42:305-13.
13. Flatman PW. The effects of magnesium on potassium transport in ferret red cells. J Physiol 1988;397:471-87.
14. Alfieri RR, Bonelli MA, Cavazzoni A, Brigotti M, Fumarola C, Sestili P, et al. Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress. J Physiol 2006;576:391-401.
15. Kimball SR, Farrell PA, Jefferson LS. Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise. J Appl Physiol (1985 ) 2002;93:1168-80.
16. Goldspink DF. The influence of immobilization and stretch on protein turnover of rat skeletal muscle. J Physiol 1977;264:267-82.
17. Vandenburgh HH, Kaufman S. Stretch-induced growth of skeletal myotubes correlates with activation of the sodium pump. J Cell Physiol 1981;109:205-14.
18. MacKenzie MG, Hamilton DL, Murray JT, Taylor PM, Baar K. mVps34 is activated following high-resistance contractions. J Physiol 2009;587:253-60.

Source: https://www.t-nation.com/supplements/increase-cell-volume-for-fast-muscle-growth

From Bill Willis, PhD