by Bill Willis PhDc and John Meadows, CSCS, CISSN T-Nation
How do you structure the diet to build muscle without getting fat, or lose bodyfat while gaining or maintaining muscle? There are plenty of strategies available that seek to address these goals, but so far the reviews have been mixed. Unfortunately there's no cookie-cutter, one-size-fits-all approach that works for every metabolism.
The good news is that all effective dieting strategies have one thing in common: they make the best use of insulin.
Insulin is a potent inducer of amino acid uptake and protein synthesis, making it the most "anabolic" hormone in the body. But insulin also has a darker side, as a potent inducer of fat storage.
First Law of Thermodynamics
The first law of thermodynamics states that, "The energy within a closed system remains constant." This means that energy can be transformed (changed to one form or another) but can't be created or destroyed. To lose weight, you need to take in less energy than you burn. To gain weight, you need to take in more energy than you burn. Eat too much and you'll get fat, no matter where the calories are coming from.
It's that simple. There's no "magic" combination of macronutrients, micronutrients, meal timing, supplements, or even drugs to get around this. If you're the type that needs someone or something to blame, start with evolution, the universe, or the GOP.
However, a calorie is not just a calorie in the long run. Different macronutrients produce different long-term effects hormonally and metabolically.
Nutrient Partitioning: Macronutrients Matter
While we can't alter the laws of the universe, we do have some say how energy from the food we eat is used. Nutrient partitioning determines what the body does with energy from the diet. Calories are either burned and used for immediate energy or stored for future considerations. Given our druthers, all our extra energy would be used to fuel new muscle growth and build up muscle glycogen stores, not stored as bodyfat. After all, as athletes, we want to be lean, muscular, and full, not fat and flat.
However, unlike the first law of thermodynamics, macronutrients matter for nutrient partitioning. So how do we maximize muscle glycogen stores and minimize bodyfat, while gaining or maintaining muscle?
Nutrient partitioning is regulated by many tissues, a coordinated action of the liver, gut, brain/CNS, adipose tissue, and muscles, along with a symphony of hormones, secondary messengers, and ion channels. Scientists aren't even sure exactly how it all works. Nutrient partitioning becomes dysfunctional in the obese and diabetics, who also happen to be insulin resistant. This isn't a coincidence; insulin plays a huge role in nutrient partitioning. The more insulin "sensitive" you are, the better nutrients are partitioned in your favor.
Crash Course in Insulin Signaling
All dietary carbohydrates are broken down into glucose in the small intestine, which is then absorbed into the blood stream. This will either be used as an immediate energy source for ATP synthesis or will be stored, as directed by insulin.
Glucose is stored as glycogen in the liver and muscle tissue, or is converted to triglyceride and stored as body fat.
Obviously we want to maximize muscle glycogen storage and protein synthesis in muscle tissue while minimizing fat gain. Yet the popular belief that carb intake above a certain point "spills" into fat cells is not correct. Insulin isn't selective. It constantly stimulates fat cells to take up glucose where it's converted to glycerol or fatty acids, both of which are required to form triglycerides which are stored as body fat.
This means that we're always storing bodyfat after a meal, although this isn't as bad as it sounds. Under normal conditions muscle accounts for 85-90% of insulin-stimulated glucose disposal, while fat only accounts for 5-15%.
But eat too many carbs (or the wrong kind), and things can change. Glucose will only be deposited into muscle and liver tissue until glycogen stores are full, the rest of this excess energy will be turned into fatty acids and stored as triglycerides in adipose tissue.
Enter Insulin Resistance
This is where insulin resistance comes into play. Check out the diagram below. Notice the insulin receptor on the cell membrane. When insulin contacts the receptor, it starts a series of events ultimately leading to GLUT 4 translocation to the cell membrane.
Insulin is just the messenger. The real action occurs with GLUT4, which allows glucose to enter the cell.
For those who are insulin resistant, it's like they get the "knock at the door" (insulin receptor on cell membrane), but nobody answers. There's no "go" signal given to the GLUT4 proteins. Now nutrient partitioning gets tricky. In this case there will be little or no GLUT4 translocation, and the glucose and other nutrients can't get into the cell. This is a problem as glucose at high levels in the blood is toxic, the reason the body is set up to dispose of glucose as it enters the bloodstream.
So what happens when you knock on a door and nobody answers? Well, you knock harder. This is what happens with insulin resistance; insulin is increasingly released to activate GLUT4.
How Insulin Resistance Causes Fat Gain
The larger the insulin response, the more the insulin signaling machinery will become resistant to the effects of insulin, particularly in muscle tissue. This insulin signaling machinery desensitizes acutely even in healthy people.
Eat too many or the wrong type of carbs at the wrong time, and they'll be converted to fat by a process called denovo lipogenesis. This is by design, because we only have the capacity to store so much glycogen. When these stores are topped off, insulin sensitivity decreases to signal that glycogen stores are full. But any glucose remaining in the bloodstream still needs to be disposed of.
To accomplish this, more insulin is released, causing excess glucose to be converted to triglyceride by denovo lipogenesis. These triglycerides are then stored as fat in adipose tissue.
Improving Insulin Sensitivity: A Refresher
Pay attention to carb type and timing. A loose recommendation is to consume 70% of your carbs during the pre, intra, and post workout phase. The other 30% should be added to your breakfast, and/or the second post workout meal. If you train in the morning, then your lunch would be a better choice for the additional carb intake.
This isn't a universal guideline – everybody has different carbohydrate needs based on their metabolism, type of training, and supplements they take such as Indigo-3GTM, which seemingly allows you to ingest more carbs than you ordinarily could. It's an effective rule of thumb that does a good job of getting people leaner without compromising gains in muscle/lean tissue.
So if you consume 300 grams of carbs on days you train extremely hard, consume 200 grams during the pre, intra, and post workout phase.
Pre-workout: 1 cup of oats and 1 cup of blueberries. (54 + 22 = 76 grams)
Intra: 2 scoops of Surge® Workout Fuel.(64 grams)
Post: 8 ounces of sweet potato. (56 grams)
Total = 196 grams of carbs
The other 100 grams or so would be placed in your breakfast (50 grams), and second post-workout meal. Structuring carb intake this way gives them "purpose," and provides better nutrient partitioning.
Use glucose disposal agents. You can drive more nutrients into muscle by using exogenous insulin. I do not endorse this option, as a pancreas is a terrible thing to mess around with. There are safer supplements that mimic the effects of insulin and/or dispose of glucose without the harmful side effects. ReceptormaxTM is an excellent example as it contains r-ALA and cinnamon extract to increase insulin sensitivity. This means that it takes less insulin to trigger GLUT4 and glucose uptake into the cell. The less insulin needed to get the job done, the leaner you will be!
Limit overall carb intake. Excessively high carb diets decrease insulin sensitivity. The relationship between insulin levels and insulin sensitivity is nonlinear, meaning that high carb intake, even within normal ranges of insulin release, can cause a large decrease in insulin sensitivity. Increased insulin levels cause the metabolism to get "stuck" in carbohydrate-burning mode by activating the expression of genes for carb metabolism and down-regulating the expression of genes for fat-oxidation.
The average person has around 350-400 grams of glycogen reserves in muscle tissue, and another 100 grams or so in the liver. If the extra carbs are not burned for immediate energy, they're converted to triglyceride and stored as bodyfat.
Don't misinterpret this as a "carbs are bad message." Again, excess carbs are the culprit.
Improving nutrient partitioning by combating insulin resistance
Limit inflammation. You've no doubt heard about omega-6 to omega-3 ratios for general health. Lo and behold, it also helps fight insulin resistance.
Inflammation has a negative affect on insulin sensitivity, so controlling it is an important part of the nutrient partitioning equation. Chronic inflammation is a common denominator for obesity and type 2 diabetes, so if we connect the dots, poor insulin sensitivity means you'll be prone to gain fat and partition nutrients less efficiently.
Note: The overall level of inflammation in the body is determined by the ratio of omega-6 to omega-3 fats in cell membranes.
Omega-6 and omega-3 polyunsaturated fatty acids are precursors to potent signaling molecules called eicosanoids that play an important role in the regulation of inflammation. Omega-6 fats promote the formation of inflammatory eicosanoids while omega-3 fats promote the anti-inflammatory versions. This does not mean that we don't want any of the "bad" inflammatory eicosanoids; they're needed for things like wound healing. Again, it comes back to the ratio.
The human body can produce all the fatty acids it needs except for linoleic acid (LA), an omega-6 fat, and α-linolenic acid (ALA), an omega-3 fat. These fats are essential, and it's critical that we include these in the diet in the correct ratios to limit inflammation.
The typical "western diet" causes the overproduction of inflammatory eicosanoids, resulting in chronic inflammation and reduced insulin sensitivity. The "ideal" omega 6:3 ratio of 4:1 optimizes insulin sensitivity by balancing the production of pro-and anti-inflammatory prostaglandins.
Note. Only 8-20% of ALA in the body is converted to EPA, while conversion of ALA to DHA is even less, around 0.5-9%. This means that it's tough to get enough EPA and DHA to limit inflammation and achieve optimal levels of insulin sensitivity by ALA consumption alone.
The good news is that fatty fish such as salmon, trout, and herring are loaded with EPA and DHA. You can also boost EPA and DHA with fish oil or supplements such as FlameoutTM.
Scientists have recently discovered that the inflammatory response that causes insulin resistance and diabetes is linked to adipose tissue. Until recently, adipose tissue was considered to be "passive" storage for lipid energy, but we know now that fat stores also function to control whole body insulin sensitivity.
Scientists started taking a closer look at adipose tissue when it was found that over-expressing GLUT4 in adipocytes actually improved whole-body insulin sensitivity. Several years afterward, it was discovered that knocking out the GLUT4 gene specifically in adipose tissue caused insulin resistance in muscle and liver, proving that adipose tissue significantly affects how insulin works in the rest of the body.
Fat is really more of an endocrine organ, secreting a number of hormones called "adipokines" which control whole-body insulin sensitivity and inflammation.
More than 50 different adipokines have been identified to date, which can have either positive or negative effects on insulin sensitivity. The "good" adipokines including leptin and adiponectin are potent nutrient partitioning agents. Together, leptin and adiponectin increase fat burning, decrease fat storage, and increase insulin sensitivity.
The "bad" adipokines including resistin, TNFα and other cytokines such as IL-6 increase cause insulin resistance by increasing inflammation. Fortunately, we have some say over the type-and level of adipokines that are secreted from fat cells. The omega 3 fats EPA and DHA promote the production of the "good" adipokines, which increase insulin sensitivity and optimize nutrient partitioning.
EPA and DHA on Insulin Sensitivity and Inflammation
Reduce inflammation by promoting the formation of anti-inflammatory eicosanoids.
Directly increase the production of the "good" adipokines adiponectin and leptin by fat cells.
Increase insulin sensitivity by directly stimulating a receptor that limits the production of inflammation and "bad" adipokines in adipose tissue.
Next: Don't Stress!
Do everything else right and this one can still get you. Stress has a powerful negative effect on insulin sensitivity and the way we partition nutrients. Researchers discovered that the autonomic nervous system (ANS) is also a master at regulator insulin signaling. The ANS regulates involuntary vital functions, consisting of the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS).
The SNS is more commonly known as the "fight or flight" system. It responds to stress by speeding up the heart rate, constricting blood vessels, raising blood pressure, and reducing digestive activity; basically, everything you need to fight or run from danger. The PNS counteracts the SNS by inducing a relaxation response (blood pressure and heart rate are reduced, digestive activity is increased, etc.). It's the overall balance between PNS and SNS activity that determines how much insulin is released and insulin sensitivity.
PNS decreases energy expenditure and potentiates the effects of insulin in target tissues by increasing insulin sensitivity, activating glucose uptake and glycogen storage.
SNS increases energy expenditure, decreases insulin sensitivity, and triggers lipolysis in adipose tissue. The overall effect of the SNS is to increase the use of fats for fuel while in fight or flight mode to preserve muscle glycogen.
This system served us well in our ancestral days. When confronted by a saber-toothed tiger or angry club-wielding cavewoman, the SNS system kicked in, preparing us to fight or flee. If we managed to survive, ANS activity returned to normal once the stress abated.
But today, stress tends to be chronic instead of acute, such as deadlines, taxes, traffic jams, angry broom-wielding wives, etc. This put us in a constant state of stress, resulting in an imbalance between the SNS and PNS branches of the autonomic nervous system.
Chronic/ high levels of stress cause the ANS to become unbalanced by over-activating the SNS system. This can lead to insulin resistance, adrenal fatigue, high blood pressure, and increased muscle breakdown.
Left unchecked, stress can be a killer. We can't state the importance of this enough. High stress levels are poison to a great physique.
Optimize insulin signaling by balancing PNS and SNS activity
Don't worry about things you can't control.
Get enough sleep.
Avoid the life suckers. You know who they are.
Learn to relax. Relaxation promotes ANS activity, increasing insulin sensitivity (muscle growth, glycogen storage, etc).
Train hard! Training is the type of acute stress we were designed for. A combination of intense training and rest keeps the nervous system in just the right state of balance for lean muscle gains.
Under normal circumstances, insulin sensitivity is precisely controlled to maintain the balance point called energy homeostasis. As athletes, our goal is to drive maximum glucose into muscle tissue and minimum glucose into fat tissue. This requires optimal insulin sensitivity, a matter of nutrient partitioning.
The goal of nutrient partitioning is to strike a balance where nutrients are diverted primarily to muscle mass and glycogen storage while losing or maintaining low bodyfat levels. This is a subtle place, but just as the body balances countless factors to maintain energy homeostasis, our nutrient partitioning efforts need to be "balanced" as well.
Under normal conditions the system is self-regulating, but by following the guidelines we've laid out in this article you'll be well on your way to a leaner, more muscular, healthier physique.
Bill and John
Kahn BB. Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes 1996;45:1644-54.
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840-6.
SchutzY. Concept of fat balance in human obesity revisited with particular reference to de novo lipogenesis. Int J Obes Relat Metab Disord 2004;28 Suppl 4:S3-S11.
Schwarz JM, Linfoot P, Dare D, Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, low-carbohydrate and low-fat, high-carbohydrate isoenergetic diets. The American Journal of Clinical Nutrition 2003;77:43-50.
Parks EJ. Dietary carbohydrate's effects on lipogenesis and the relationship of lipogenesis to blood insulin and glucose concentrations. Br J Nutr 2002;87 Suppl 2:S247-S253.
KoltermanOG, Greenfield M, Reaven GM, Saekow M, Olefsky JM. Effect of a high carbohydrate diet on insulin binding to adipocytes and on insulin action in vivo in man. Diabetes 1979;28:731-6.
Roberts R, Bickerton AS, Fielding BA, Blaak EE, Wagenmakers AJ, Chong MF, et al. Reduced oxidation of dietary fat after a short term high-carbohydrate diet. Am J Clin Nutr 2008;87:824-31.
SemenkovichCF. Insulin resistance and atherosclerosis.J Clin Invest 2006;116:1813-22.
Calder PC. n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 2006;83:1505S-19S.
SerhanCN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med 2002;196:1025-37.
Schwab JM, Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature 2007;447:869-74.
SimopoulosAP. Importance of the ratio of omega-6/omega-3 essential fatty acids: evolutionary aspects. World Rev Nutr Diet 2003;92:1-22.
BurdgeGC. Metabolism of alpha-linolenic acid in humans. Prostaglandins Leukot Essent Fatty Acids 2006;75:161-8.
DeFilippisAP, Sperling LS. Understanding omega-3's. Am Heart J 2006;151:564-70.
WellenKE, Hotamisligil GS.Inflammation, stress, and diabetes. J Clin Invest 2005;115:1111-9.
ShoelsonSE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest 2006;116:1793-801.
Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature 2006;444:847-53.
GnudiL, Tozzo E, Shepherd PR, Bliss JL, Kahn BB. High level overexpression of glucose transporter-4 driven by an adipose-specific promoter is maintained in transgenic mice on a high fat diet, but does not prevent impaired glucose tolerance. Endocrinology 1995;136:995-1002.
Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001;409:729-33.
TrayhurnP. Endocrine and signalling role of adipose tissue: new perspectives on fat. Acta Physiol Scand 2005;184:285-93.
Havel PJ. Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004;53 Suppl 1:S143-S151.
Wall R, Ross RP, Fitzgerald GF, Stanton C. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev 2010;68:280-9.
Murata M, Kaji H, Takahashi Y, Iida K, Mizuno I, Okimura Y, et al. Stimulation by eicosapentaenoic acids of leptin mRNA expression and its secretion in mouse 3T3-L1 adipocytes in vitro. Biochem Biophys Res Commun 2000;270:343-8.
Perez-Matute P, Marti A, Martinez JA, Fernandez-Otero MP, Stanhope KL, Havel PJ, et al. Eicosapentaenoic fatty acid increases leptin secretion from primary cultured rat adipocytes: role of glucose metabolism. Am J Physiol Regul Integr Comp Physiol 2005;288:R1682-R1688.
ItohM, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M, et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol 2007;27:1918-25.
Oh DY, Talukdar S, Bae EJ, Imamura T, Morinaga H, Fan W, et al. GPR120 is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell 2010;142:687-98.
KreierF, Fliers E, Voshol PJ, Van Eden CG, Havekes LM, Kalsbeek A, et al. Selective parasympathetic innervation of subcutaneous and intra-abdominal fat–functional implications. J Clin Invest 2002;110:1243-50.
RobidouxJ, Martin TL, Collins S. Beta-adrenergic receptors and regulation of energy expenditure: a family affair. Annu Rev Pharmacol Toxicol 2004;44:297-323.
Schwartz MW, Woods SC, Porte D, Jr., Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature 2000;404:661-71.