By Andrew Abbate, Driven Sports

Last night I struggled tossing and turning with excitement for today’s musings on the versatility and evolving reinvention of modern glucose disposal agents, but then I stopped and thought, “Shit tomorrow’s only Tuesday”. With that came unequivocal inspiration for the mundane, so here comes the prequel, a generalized, demystifying portrait of human metabolism.

Just for clarity, the proceeding isn’t riding entirely on a whim: there is simply too much prerequisite background knowledge in metabolism necessary to appreciate the wonders of insulin manipulation, especially considering the prevalence of both obesity and cardiovascular disease here in The States. My goal here, therefore, is to provide insight for strength athletes first and help galvanize the general health discussion second, so we’ll keep it as brief as possible to prevent the rise of boredom as an equally formidable epidemic.

Where’d Ya Get These Numbers?

If you’re here, you likely have had the very basics beaten into your memory irrevocably, but for completeness, note that the three macronutrients carbohydrates, fats, and proteins provide four, nine, and four kcal/g in energy respectively. How we know is probably something you’ve never encountered unless you’re formally trained in paying attention in class.

These numbers are linked directly to the ubiquitous breakdown process called oxidative phosphorylation, from which fats provide more energy in short because they go through another oxidative process first – beta oxidation – which provides 5 extra ATP. 4+5 = 9 isn’t just simple enough for the scope of this article; it’s pretty much that simple on the whole. If you care to know more about the middlemen e.g. electron carrier NADH feel free to scan the intergoogle for my article on the TCA cycle.

It’s Mine; I Spend It

Energy expenditure also embraces the magic number, three, by taking on three forms, basal metabolic rate, the thermic effect of food, and physical activity. If Alan Aragon is reading this, sorry for making you cringe at the middle one. The thermic effect of food (TEF) is any avant-garde nutritionist’s bane because broscientists and daytime TV hosts have been pushing meal frequency as a fallacious metabolic edge for years on the brossumption that more frequent meals brings more calorie expenditure via TEF. Well, there is absolutely no evidence of this.

In reality, less than 10% of thermogenic energy expenditure comes from TEF, which we’ll distinguish for academic purposes as obligatory, because it’s not your choice and facultative, because it depends on how much energy your meal contained. (Becker et al., 1999 pp. 1148-49) Intuitively, it’s apparent that meal frequency couldn’t influence energy expenditure to any significant degree, but media pushed researchers to prove what they already knew anyway, for which I refer you to Mr. Aragon’s musings “A Critique of The ISSN Position Stand on Meal Frequency”. He also provides brief commentary on another important note, which is connected to hormonal control of satiety, the effect of meal frequency on daily satiety. Basically, in a 2010 study, six daily meals provided less satiety than three daily meals composed of equal energy. (Leidy et al., 2010) The reason I mention hormonal control is because we are dealing with the tandem pancreatic hormones insulin and glucagon, coming and going with fluctuating serum glucose levels.

The biochemical evidence for Leidy et al.’s results begins with glucose tolerance; that is, frequent eating takes glucagon, which we’ll generally consider a fat burning hormone so I keep you on the hook, somewhat out of the picture.

Eating every few hours is essentially titrating glucose into your bloodstream, which influences insulin secretion and downstream neuropeptides to essentially keep you hungry. Epinephrine, an energy utilization hormone, and glucagon work together and against insulin. Spacing out your meals keeps them at bay to a degree. As Alan alludes and as I’d like to complete, these effects are more widely observable in longer-term studies, likely because cellular adaptation and building hepatic (liver) glycogen propagates the unfavorable energy homeostasis. All things considered, we can throw away convictions of increased meal frequency as a metabolic advantage.

Hard and Fast

Nutritional research inspired by the obesity epidemic and subsequent editorials from the strength athlete community have cooperatively motivated recently accelerated interest in a dieting strategy dubbed, appropriately, intermittent fasting (IF). The skeptic in me wants to spit on all theories that aren’t mine and rub them in the dirt; however, finding IF through the plunder for physiological flaw was a serendipitous godsend. First of all, it works wonders for fat loss, and that’s anecdotal commonplace. Amongst my other academic circle I call it the economist’s favorite diet, because economists tend to, by obligatory academic contradiction, take ideas that work in real life and test them to see if they work in theory.

Well, in theory, we turn back to insulin and glucagon. The other side of the coin we draw from obesity and insulin resistance. For brevity, consider that a hypercaloric diet and a sedentary lifestyle combine to propagate insulin secretion irregularly, which causes cells to respond to it less and less fervently over time. The endgame is cardiovascular disease and type-II diabetes, which plagues national healthcare costs, but I digress. Increased insulin secretion not only causes decreased cellular sensitivity to insulin, but it decreases the cells’ ability to take up glucose in the absence of insulin. It’s not a popular distinction, but you can herein see how insulin sensitivity and glucose tolerance are not the same, although absence of the former precedes onset of the latter. That is, hyperinsulinemia causes insulin resistance first and glucose insensitivity second.

The whole glucose disposal and anabolic insulin window spike (or whatever) debate is thankfully a dead horse, but it is still important to note that 80-95% of glucose is stored in skeletal muscle at high serum insulin concentrations and in animals about 25% of intravenous glucose is stored in skeletal muscle with 60 seconds of infusion. (Becker et al.,1999, p. 1198) This percentage and speed is likely much higher in athletes, especially post exercise when insulin sensitivity is heightened. The whole misconception about meal timing, however, is insurmountably tenuous because it overvalues insulin secretion (and overstates the amount of PRO/CHO necessary to maximally stimulate muscle protein synthesis [MPS]) and undervalues physiological metabolic adaptations that occur over long periods of intense training and good eatin’. For simplicity’s sake, there is substantial evidence that post-workout carbohydrate + whey increases MPS no more than does whey alone, demonstrating that either insulin secretion from protein alone is enough to maximize MPS post-exercise or further insulin secretion is of no anabolic benefit. (Staples et al., 2011)

Although I’d love to continue right here with an in-depth analysis of fasting versus MPS, I’ll choose to reserve an analysis for a future article because it takes away from my pancreatic hormone lecture, which glows with intrigue and really makes you want to continue reading.

Fasting in essence provides a cellular amorousness for energetic efficiency and insulin sensitivity, since insulin secretion comes less frequently and low blood sugar spurns glucagon-influenced fat oxidation throughout the day. Less frequent insulin secretion means greater cellular sensitivity, more favorable cardiovascular parameters, improved general health, and more appropriate utilization of hereditary metabolic machinery. Fortunately, human research supports the notion that fasting improves insulin sensitivity, and the full text is open access, so check it. (Halberg et al., 2005)

If Insulin is Beta, Glucagon is Alpha

It’s obvious in human physiology that satiety and consequently body weight is under hormonal control. For example, a 1% overstimulation of caloric intake by defective central nervous system satiety control would result in an annual three-pound fat gain. (Becker et al., 1999, p. 1159) Satiety and body weight is indubitably subject to strict regulation in both the short-term and the long-term, and for the former I don’t believe glucagon receives nearly enough attention in the health and fitness community (at least relative to insulin).

To begin, in case it is unclear thus far, note that glucagon is just insulin’s “evil twin” (less the pejorative, because neither is evil). In other words, insulin stimulates glucose uptake in the liver and skeletal muscle while glucagon stimulates glucose release into the blood stream from the liver and glucose utilization within skeletal muscle. Glucagon also stimulates fat breakdown and works in tandem with catecholamines, adrenal hormones that stimulate a myriad of cellular processes in adipose tissue, skeletal muscle, and the cardiovascular system. In adipose tissue, it does the same thing as epinephrine; it activates a protein (that activates a protein) that takes stored fat and begins converting it into a usable energy source.

While there is no evidence that glucagon is necessary for survival in humans, there is reason to believe that it plays an important function role in metabolism, especially in athletes. For example, amino acids stimulate glucagon release, and strength athletes would likely suffer crippling hypoglycemia following a high protein meal without glucagon counteracting the mass insulin secretion. (Becker et al., p. 1195)

Regarding short-term blood glucose control, researchers have used a central nervous system hormone called somatostatin (read: if this looks familiar it’s because it’s the same hormone that inhibits growth hormone release) to elucidate glucagon’s role in glucose homeostasis. Turns out that when fasting humans are given a somatostatin infusion, both insulin and glucagon release is inhibited, resulting in a significant drop in blood glucose and providing evidence that glucagon is more important than insulin in short-term glucose homeostasis. (Becker et al., 1999, p. 1195) While this information doesn’t necessarily help us get bigger/stronger/faster directly, it certainly helps us understand why Dr. Oz and his cohort of overweight women can suck it.

Now That We Know…

We can use fasting in conjunction with pharmacological intervention to maximize the fat burning potential of glucagon and epinephrine. It is known that catecholamines stimulate glucagon release, so in a fasted state when insulin is minimized stimulants like ephedrine work super-effectively. The whole “empty stomach” thing has just as much to do with insulin as it does glucagon, since glucose inhibits glucagon secretion. As it garners more attention, I think intermittent fasting and similar diets are due for more in-depth examination especially with respect to BCAA/EAA supplementation. While it can definitely be a kick in the nuts for the first week or so, there’s no reason to believe that IF can’t be implemented in a behaviorally healthy manner that maximizes glucagon/epinephrine utilization, enhances insulin sensitivity, and torches fat without stimulating skeletal muscle proteolysis (which is energetically expensive and really doesn’t happen in strength athletes, believe it or not). The ground is certainly fertile for further research in a clinical setting, but for now I’ll sleep soundly knowing that what works in practice makes sense in theory.

References:

Becker K, Bilezikian J, Wellington H et al. Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia: J.B. Lipponcott Company, 1999.

Leidy HJ, et al. “The influence of higher protein intake and greater eating frequency on appetite control in overweight and obese men.” Obesity (Silver Spring). 2010 Mar 25.

Staples AW, et al. “Carbohydrate does not augment exercise-induced protein accretion versus protein alone.” Med Sci Sports Exerc 43, no. 7 (July 23, 2011): 1154-61.

Halberg. “Effect of intermittent fasting and refeeding on insulin action in healthy men.” Journal of Applied Physiology 99, no. 6 (July 28, 2005).