The Overfeeding Overview: High Fat, Carb, Protein, MCTs, Leptin, Testosterone, T3 & Reverse T3 - Get an Overview of the Consequences of Short- & Long-Term Overfeeding

High fat + high carbohydrate foods like mini doughnuts are exactly what you should not eat on a refeed day, let alone during weeks of bulking.

Do you want to know what happens during days and weeks of gluttony? How the effects "bulking" will have on your body weight and composition, depending on where those extra calories come from? Have you wondered what the optimal nutrient composition on refeed days may look like. And are you concerned about the potential the health consequences of bulking?

Yes? In this case, I would suggest you take a closer look at the following overview of the research. An overview that is probably not complete, but it should suffice to provide preliminary answers to the aforementioned questions.

Learn more about the effects of your diet on your health at the SuppVersity

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Carbohydrate Shortage in Paleo Land

• The amount of weight you gain depends on your genes: They are not the only determinant. That's for sure. A 1990 study by Bouchard et al. still leaves no doubt that your genes are one of the most important determinants of the quantity of weight you gain.
  
  In said study the researchers from the Laval University fed 24 sedentary young male twins 1,000kcal extra for six out of seven days of the week. In that the study is not the first to investigate the effects of overfeeding on weight gain in twins. It is yet the first and only one that did this over a period of 100 days and thus with a total energy excess of 84,000 kcal on a diet that contained 50 percent carbohydrate, 35 percent fat, and 15 percent protein.
  

  

  Figure 1: Comparison of the weight (left) and visceral fat (right) gains in twin pairs; high correlations were observed for both, but the correlation was significantly more pronounced for the unhealthy visceral fat than it was for the mere body weight (Bouchard. 1990).

  The data in Figure 1 does probably not need any extra explanations. In view of the fact that similar results have also been observed in previous studies like Poehlman et al. (1986), it should be obvious that the difference between the weight (left) and visceral fat (right) two identical twins gained was significantly smaller the difference between one twin from pair A and one twin from pair B. The statistical analysis of body fat and waist circumference data revealed similar correlations which were most significant for the visceral fat mass and the waist hip sizes, i.e. those quantities that predict the ill health effects of weight gain best.
  
  According to Ukkola, et al. (2001), the genetic differences may partly be mediated by differences in the genetic make-up of ones beta-2 adrenoreceptors with specific variants being associated with greater increases in insulin resistance, body weight and subcutaneous fatness. Other candidates are the cholesterol ester transfer protein (CETP) gene which appears to affect adiposity in response to long-term overfeeding (Terán-García. 2008). Other scientists use similar genetic polymorphisms to explain a general resistance to weight gain during overfeeding via genetically determined variations in nonexercise activity thermogenesis (Vanltallie. 2001).
• Overfeeding fat, carbohydrate or protein, does it make a difference? Studies that compare isocaloric overfeeding are quasi non-existent. What we do have are studies like the one by Horton et al. (1995) that compared high fat vs. high carbohydrate diets (see Figure 2 for macronutrient composition), where the additional energy came from fat or carbohydrates.
  
  In the Horton study this was a 50% extra that was added in form of fat or carbohydrates on top of the baseline diets of the normal-weight and obese subjects. A 50% extra that lead to significant weight gain.
  

  

  Figure 3: Weight gain (left) and increase in energy expenditure (right) in obese and lean subjects in response to carbohydrate and fat overfeeding (Horton. 1995).

  As you can see in Figure 3, both diets led to a rapid increase in body weight, but the trajectory was different. The main and maybe practically relevant difference, though, was that the rapid increase in water and glycogen in the high carbohydrate group was less resilient weight loss in the post-overfeeding period.

No! Carbs are not necessarily more fattening in the obese. It's a commonly held prejudice that carbohydrates are more readily coverted to fat and stored in the obese, but a study by Minehira et al. that investigated just this found that there was not just no difference in de novo lipogenesis with carbohydrate overfeeding between lean and obese individuals, there was also no increase in de novo lipogenesis, at all, when the when the obese subjects were overfed with a high carbohydrate diet for one day (Minehira. 2004).

• 

  Figure 4: Proportion of the energy that was stored as body fat (Horton. 1995).

  If we take a look at the proportion of energy that was stored as body fat in Figure 4, it is obvious why the fat gains lasted longer than the carbohydrate gains. Why? Well, simply because the 14-day overfeeding on fat lead to a significantly higher relative increase in body fat.
  
  Last but not least, it may also be worth mentioning that the the fat gain in the obese group was 89% and 57% higher in the carbohydrate and fat overfeeding group, respectively. An intriguing result that appears to stand in line with dieting studies, where high fat diets are superior to high carbohydrate diets in the obese, but not in lean individuals.
  
  What was not different for obese and lean individuals, though, was the the fact that the carbohydrate overfeeding lead to higher gains in lean mass than the fat overfeeding. A result that should remind you of a previously reported study here at the SuppVersity, in which a no fat bulk lead to significantly greater muscle and significantly lower fat gains than a low fat bulk (see "If You Go "High Carb", You Better Go Really High!" | more). Overall, "bulking", i.e. eating more than you need on any mixed diet, has repeatedly been shown to produce significant increases plasma Somatomedin-C/Insulin-like Growth Factor (SM-C/IGF-l) and testosterone concentrations as well as insulin, of which Forbes et al. speculate that they promote the lean mass increases that are particularly pronounced when overfeeding is combined with resistance training.
  
  In a more nutrient-type specific study b by Dirlewanger that did not focus on the weight gain or anabolism, but on the leptin response and the increase in resting energy expenditure the subjects experienced a significant increase in leptin (+28%) and resting energy only in the high carbohydrate, yet not in the fat overfeeding arm of their study in young, lean individuals (Dirlewanger. 2000). Other studies, without clear distinction between high carb and high fat overfeeding, indicate that fast food like burgers or fries is an effective short-term leptin stimulator, too - at least if it's consumed in a single binge (Kolaczynski,. 1996).
  

  

  Figure 5: Energy partitioning in young men upon overfeeding with ~5,000kcal per day - mostly carbohydrates, i.e. 1% protein, 3% fat, and 86% carbohydrate (Acheson. 1988).

  In the short run, like on refeed days, for example, carbohydrate overfeeding has another advantage over fat overfeeding, because it takes roughly 500g of carbohydrates (that's 2,000kcal) before even a single gram of those carbs is converted to fat and potentially, but not necessarily stored as body fat (Acheson. 1988) - at "only" 400kcal extra from carbs for one day there was no net lipogenesis at all (see Figure 5). This result is corroborated by data from McDevitt et al. (2000) who observed that the fat gain with fat overfeeding starts with day 1, while there is a time gap in the increase in body fat with carbohydrate overfeeding (McDevitt. 2000).

If you consume sugar on a refeed, should you prefer glucose, sucrose of fructose? In view of the fact that I don't suggest you refeed more than 1-2 days and considering the fact that you want to get the majority of your carbs from starches on a true bulks, it does not really matter. In fact, studies show no difference in de novo lipogenesis in 96h overfeeding studies between pure glucose and sucrose, which is a 1:1 combination of fructose or fructose in two studies in lean and obese women by (McDevitt. 2000 & 2001). In the long run, consuming amounts of fructose you could only get by drinking a couple of bottles of coke everyday, will yet not be favorable for your health - even if taking fish oil can blunt the increase in hepatic de novo lipogenesis, it won't blunt the insulin resistance (Faeh. 2005).

• 

  Figure 6: Schematic representation of the main lipid metabolic pathways affected in skeletal muscle during 4 weeks of fat overfeeding. Genes indicated in white boxes were down-regulated during the dietary study, whereas genes indicated in gray boxes were up-regulated (Meugnier. 2007).

  Fat overfeeding, on the other hand, has been show to favor fat storage not just because the dietary fat can be stored without being converted to triglycerides, but also because metabolic and genomic investigations show that the lipid oxidation rate tends to decrease, and 55 genes in the skeletal muscle were modified.
  
  Modifications of which Meugnier et al. show that they stimulate the synthesis of triacylglycerol, inhibit lipolysis and reduce the oxidation of fatty acid oxidation, while promoting the development of adipocytes with an excess of only ~550kcal/day from fat per day (see Figure 6).
  
  Another potential explanation is the change in thyroid hormones, of which the data in Figure 7 from an overfeeding study by Danforth Jr., et al. (1979) tells you that the high protein overfeeding despite a 29.8% lower total energy intake triggered the most, the carbohydrate diet the 2nd most favorable (=in favor of greater energy expenditure) effects on the thyroid hormone.
  

  

  Figure 7: Effects of overfeeding with carbohydrates, fats, and protein on thyroid hormones (Danforth, Jr. 1979).

  Accordingly, high protein diets, of which we know for sure that they are the most satiating hypercaloric diets (followed by high carb and high fat | Johnstone. 1996) and have the highest thermogenic effect (see Figure 8) and can help dieters avoid the yoyo effect after a diet (Lejeune. 2005), should have the least negative impact on your physique.
  

  

  Figure 8: Estimates thermic effect of carbohydrates fats, protein, and alcohol in % energy of the energy that's ingested in form of the respective nutrients (Joosen. 2006).

  And in fact, Jose Antonio et al. (2014) have recently been able to show that a diet that contains fivefold more protein than the FDA recommends (4.4g/kg | 307g/day) is not just benign but will, in conjunction with exercise, will have significant beneficial effects on the physique of healthy resistant trained men (learn more). Furthermore studies indicate that a high protein content may also ameliorate negative effects such as an increase in intrahepatocellular lipid deposition in humans (Bortolotti. 2009).

Beware of bulking the way you did in your twenties! It's almost certainly going to make you fat, because studies indicate that age correlates with a decreased increase in energy expenditure in response to overfeeding (Roberts. 1996). Since the difference is particularly pronounced on day 1 of the respective overfeeding period (see Figure on the left), I would also refrain from excessive "refeed days" if I were 60+ years old, like the subjects in the study by Roberts et al. from which I grabbed the graph that displays the energy expenditure on a diet that contained 956kcal extra per day (phase II in this study).

• Classic overfeeding studies with protein as a single nutrient are yet unfortunately rare. Even less, namely nothing, is known about the effects of ketogenic diets, which is why it's at the moment impossible to tell whether a hypercaloric high fat diet that is devoid of carbs and low enough in protein to actually induce ketosis will have the same negative effects as a high fat diet that still contains 15-30% carbohydrates and some protein.
  Based on the studies we have, it's yet quite certain that the combination of some carbs and a high amount of fat is the most obesogenic variety of "bulking" you could possibly select. Therefore - with the exception of ketogenic diets, where corresponding data is still missing, the rule of thumb is: The more fat in the diet, the more rapid the body fat, but not necessarily the body weight gain.

• MCT overfeeding is less obesogenic - The reason that rodents that are overfed with medium-chain triglycerides (Geliebter. 1983) and assumable human beings store less fat than on long-chain triglycerides as you will find them in your bacon, sausages, dairy & co is an increase in thermogenesis that has been observed in both rodent and human studies.
  

  

  Figure 10: Metabolic rate in healthy men after the ingestion of isocaloric fat meals containing MCTs or long chain triglycerides (Hill. 1989).

  As you can see in Figure 10, this effect does not diminish over time - at least, when only the effect of the infusion of MCTs versus long-chain fatty acids is concerned. In view of the rodent study by Geliebter et al. (1983) and the results of the study by Hill et al. (1989), it appears to be quite obvious that MCTs constitute a valuable addition to hypercaloric diets. The often-heard claim that they cannot be stored as fat is yet misleading - even if they are oxidized in the liver, the increase in available energy will increase the storage of energy from other nutrients. The dream of eating as much as you want without gaining weight does therefore remain a dream - at least for all of us who don't harbor a gene defect that blunts the storage of fat.
  
  Still, in theory it would appear as if using MCTs in a dieting context makes sense. In reality, studies have shown that using MCTs as a major source of your dietary fats does not lead to significant long-term improvements in  fat or general weight loss - even if 27% of an 800kcal/day starvation diet were pure MCT oil (Yost. 1989).

Fivefold More Than the FDA Allows: Extreme High Protein Diet (4.4g/kg | 307g/day) Benign & Non-Obesogenic. Plus: Macronutrient Prescription & Changes in Food Quality | more

Alright, so what's the bottom line, then? I guess, in view of the fact that we still have few studies on high protein overfeeding and no studies on overfeeding on ketogenic diet, a conclusive bottom line cannot be reached, yet. What appears to be true, though is that a diet containing some carbohydrates and a large amounts of fat is the worst choice you can make, when you are bulking.

A protein and a high(er) carbohydrate, as well as a correspondingly low(er) fat content on the other hand, appear to be the way to go at least in the short run. In the long(er) run, on the other hand, the differences between higher fat and higher carbohydrate overfeeding appears to disappear - albeit with a small, but potentially practically significant difference in terms of the amount of body fat you will gain (see Figure 4) | Comment on Facebook!

References:

• Acheson, K. J., et al. "Glycogen storage capacity and de novo lipogenesis during massive carbohydrate overfeeding in man." The American journal of clinical nutrition 48.2 (1988): 240-247. 
• Antonio, Jose, et al. "The effects of consuming a high protein diet (4.4 g/kg/d) on body composition in resistance-trained individuals." Journal of the International Society of Sports Nutrition 11.1 (2014): 19.
• Bouchard, Claude, et al. "The response to long-term overfeeding in identical twins." New England Journal of Medicine 322.21 (1990): 1477-1482. 
• Danforth Jr, E., et al. "Dietary-induced alterations in thyroid hormone metabolism during overnutrition." Journal of Clinical Investigation 64.5 (1979): 1336.
• Dirlewanger, M., et al. "Effects of short-term carbohydrate or fat overfeeding on energy expenditure and plasma leptin concentrations in healthy female subjects." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 24.11 (2000): 1413-1418.
• Faeh, David, et al. "Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men." Diabetes 54.7 (2005): 1907-1913.
• Forbes, Gilbert B., et al. "Hormonal response to overfeeding." The American journal of clinical nutrition 49.4 (1989): 608-611.
• Geliebter, Ae al, et al. "Overfeeding with medium-chain triglyceride diet results in diminished deposition of fat." The American journal of clinical nutrition 37.1 (1983): 1-4.
• Hill, James O., et al. "Thermogenesis in humans during overfeeding with medium-chain triglycerides." Metabolism 38.7 (1989): 641-648.
• Horton, Tracy J., et al. "Fat and carbohydrate overfeeding in humans: different effects on energy storage." The American journal of clinical nutrition 62.1 (1995): 19-29. 
• Johnstone, A. M., R. J. Stubbs, and C. G. Harbron. "Effect of overfeeding macronutrients on day-to-day food intake in man." European journal of clinical nutrition 50.7 (1996): 418-430. 
• Joosen, A. M., and Klaas R. Westerterp. "Energy expenditure during overfeeding." Nutr Metab (Lond) 3 (2006): 25.
• Kolaczynski, JERZY W., et al. "Response of leptin to short-term and prolonged overfeeding in humans." The Journal of Clinical Endocrinology & Metabolism 81.11 (1996): 4162-4165.
• Lejeune, Manuela PGM, Eva MR Kovacs, and Margriet S. Westerterp-Plantenga. "Additional protein intake limits weight regain after weight loss in humans." British Journal of Nutrition 93.02 (2005): 281-289.
• McDevitt, Regina M., et al. "Macronutrient disposal during controlled overfeeding with glucose, fructose, sucrose, or fat in lean and obese women." The American journal of clinical nutrition 72.2 (2000): 369-377.
• McDevitt, Regina M., et al. "De novo lipogenesis during controlled overfeeding with sucrose or glucose in lean and obese women." The American journal of clinical nutrition 74.6 (2001): 737-746.
• Meugnier, Emmanuelle, et al. "Changes in gene expression in skeletal muscle in response to fat overfeeding in lean men." Obesity 15.11 (2007): 2583-2594. 
• Minehira, K., et al. "Effect of carbohydrate overfeeding on whole body macronutrient metabolism and expression of lipogenic enzymes in adipose tissue of lean and overweight humans." International journal of obesity 28.10 (2004): 1291-1298.
• Poehlman, Eric T., et al. "Genotype-controlled changes in body composition and fat morphology following overfeeding in twins." The American journal of clinical nutrition 43.5 (1986): 723-731. 
• Roberts, Susan B., et al. "Effects of age on energy expenditure and substrate oxidation during experimental overfeeding in healthy men." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 51.2 (1996): B148-B157.
• Terán-García, Margarita, et al. "Effects of cholesterol ester transfer protein (CETP) gene on adiposity in response to long-term overfeeding." Atherosclerosis 196.1 (2008): 455-460.
• Ukkola, Olavi, A. Tremblay, and C. Bouchard. "Beta-2 adrenergic receptor variants are associated with subcutaneous fat accumulation in response to long-term overfeeding." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 25.11 (2001): 1604-1608.
• Vanltallie, Theodore B. "Resistance to weight gain during overfeeding: a NEAT explanation." Nutrition reviews 59.2 (2001): 48-51.
• Yost, Trudy J., and R. H. Eckel. "Hypocaloric feeding in obese women: metabolic effects of medium-chain triglyceride substitution." The American journal of clinical nutrition 49.2 (1989): 326-330.

Starving Yourself Makes You Fat, Regardless of Whether You Overeat Or Not. Study Finds Obesity Promoting Effects of Ghrelin Unrelated to Orexia.

Image 1: Starving + indulgence, even without
over-indulgence, leads to obesity. (Image from
Hieronymus Bosch's The Seven Deadly Sins
and the Four Last Things)

Do you know that grumbling? This strange feeling you get, when you are "running on empty" - not the appetite or desire you feel when you pass by the ice cream parlor. I am talking about hunger, real physiological hunger, the one where you start towards your fridge and, regardless of what is in there, stuff it down your pie-hole. This ravenous desire for food is the direct psycho-physiological response to surges of the "hunger-hormone" ghrelin.

So, if high ghrelin levels make you eat everything that cannot escape fast enough, it seems quite obvious that this would be the underlying reason for obesity in rats injected with exogenous ghrelin.

This, however, was not the case in a recently conducted study by Perez-Tilve et al. from the Department of Internal Medicine at the University of Cincinnati (Perez-Tilve. 2011).

Figure 1: Food intake of ghrelin injected or control rats on low fat or high fat diets.
(data adapted from Perez-Tilve. 2011)

The scientists had administered intracerebroventricular ghrelin injections to two groups of rats. One group received a low-fat chow, while the other was on the famous high-fat diet scientists use to emulate our modern westernized gluttony (cf. yesterday's news, fig. 1). As expected, the rats that were fed the low-fat chow significantly increased their food intake (cf. Figure 1). Unexpectedly, though, ghrelin failed to statistically significantly increase food intake in the high fat diet group, yet ...

in rats fed the HFD, ghrelin nonetheless increased adiposity [fat mass increase of 14±2 g (ghrelin+HFD) vs. 1±1 g (saline+HFD), P<0.001] up-regulating the gene expression of lipogenic enzymes in white adipose tissue.

These results are of great interest, because they clearly show that your typical "fast", where you diet really hard for a few days (and thus increase your ghrelin levels), until you get so ravenously hungry that you end up (deliberately or not) "refeeding" yourself with pizza and ice-cream set the scene for further undesirable fat gain by setting your body's metabolic switches to fat storage mode.

Leucine Supplementation Exemplifies Potential Downsides of Non-Specific Insulin Sensitizers on a Hypercaloric Diet / Bulk

Adelfo's latest progress pics speak for themselves. Maybe that consoles you for the missing update!?

Another Thursday and ... no post from your's truly Adelfo Cerame. In fact, Adelfo shot me an email earlier today, that he won't be able to submit a blogpost this week if he wanted to get some sleep this night (remember we are living in different time zones) And while this was in fact a problem for me, since I am pretty pressed on time, today and did actually allocate the time I usually spend writing these blogposts, I agreed to cover his a** and step into the breach (so please ignore the surplus of typos, mistakes an missing words, please ;-). I mean, what could I say? We all know about the importance of sleep to bring in your best physique possible and I don't want to be the one who could be blamed in the very unlikely case that he won't finally take away his pro-card on his upcoming competition in March, right?

SuppVersity Science Round-Up Sneak Peak

Apropos sleep, I guess sleep is going to be one of the topics Carl and I are going to talk about on today's SuppVersity Science Round-Up (check out all previous installments and the respective Seconds, here), other topics I've got on my list here, are the Aspartame causes cancer study that resurfaced as of late on the pertinent "science websites" as if it had been released yesterday, and a couple of other news, e.g.

• The thrifty phenotype - Is it an effect of "healthy calorie restriction" during gestation?
• Fish protein & glucose metabolism - More evidence that a little can go a long way
• Eat more fruits & vegetables! - Why "more" is not specific enough
• Vitamin D - Convincing evidence that the obesity connection is a one-way street
• BPA and prostate cancer - Changes in aromatase and 5α-reductase increase malignancy
• Night shift & breast cancer - Meta analysis finds 30%+ increased risk

Even if you are not interested in any of these (btw. there will be more on obesity & healthy eating than the first two ;-), you should know by now that there are usually side-tracks, follow up an "on the other hands" that often lead the discussion into a completely new direction. So make sure you don't forget to tune in live - 1PM (EST) on the Super Human Radio Network. As usual, a podcast and the Seconds with everything that did not make it into the show will be available tomorrow.

Chronic leucine supplementation + hypercaloric diet = ???

The subheading actually summarizes pretty well, what the scientists from the School of Public Health at the Huazhong University of Science and Technology, the Department of Nutrition at the University of North Carolina at Chapel Hill and one colleague from the Hubei University of Medicine in the People's Republic of China wanted to find out, when they bought a group of male Sprague-Dawley rats, and kept them in eight groups of 10 animals for 24 weeks on one of the following dietary regimen

normal chow diet (3.78 kcal/g)	hypercaloric "high fat"(54%) diet  (5.20 kcal/g)
+ 0%, 1.5%, 3.0% or 4.5% leucine	+ 0%, 1.5%, 3.0% or 4.5% leucine

The animals had free access to food and water. The body weight and average food intake were recorded once a week. And if you take a peek at the graph on the left hand side of figure 1 it does not take a rocket scientists to recognize that any effects the supplementation may have had was "negligible" at best, with higher weight gain in the high leucine (3% an 4.5%) and minimally lower weight gain in the medium leucine supplementation group (1.5%) for the normal diet and higher weight gain for all leucine supplemented diets in the HFD group (1.5% > 3.0% > 4.5%)

Figure 1: Body weight development (remember the food intake was identical) and perirenal fat depot weight at the end of the study (Lee. 2013)

In view of what leucine is hailed for in the fitness and bodybuilding community, the explanation should be obvious: "Of course are those glutenous rodents simply gaining more muscles." The anabolic prowess of leucine makes it possible. They are ..." I am not going to repeat the superlatives with which the supplement industry is going head over heels to explain why they have just ramped up their BCAA product from a 2:1:1 to a  5:1:1 and from there to whatever ratio, as you will by now already have realize that what the rodents gained was not mere muscle, but a significant amount of body fat. So much in fact that the total boy weight to fat ratio was skewed (in other words, the body fat % increased):

[T]he perirenal white adipose tissue was −1.20% of the total body weight in animals on ND [nromal diet]. HFD alone increased the perirenal fat to 1.62% (p<0.05). Chronic supplementation of leucine (1.5 and 3.0%) increased the percentage of the perirenal white adipose tissue to 2.01–2.03% in animals on HFD (p<0.05). [...] These results show that chronic supplementation of leucine increases the ratio of white fat over total body weight in rats on HFD." (Li. 2013)

Interestingly, this increase in adiposity went hand in hand with a decrease in the expression of TNF-alpha and various inflammatory cytokines in the adipose tissue of the rodents. The picture of leucine that emerges here is therefore one of a "healthy growth factor". unfortunately one that obviously does not make a difference between muscle and fat tissue.

Leucine as a non-selective growth promoter and insulin sensitizer

Whether the decrease in inflammatory cytokines is the chicken or the egg here cannot be said for sure. What is pretty certain though is that the combination of decreased inflammation → increased adipose tissue insulin sensitivity → increase energy uptake by the fat tissue may lead to a healthier, but certainly not smaller adipose organ and does thus go against what the usual muscle head would be looking for, when he or she buys a product that claims to provide lean mass gains.

Figure 3: HOMA-IR and Area Under the Curve (AUC) of the glucose response in a glucose challenge (Lee. 2013)

In fact, the data in figure 2 hints at a classic dilemma I have alluded to in various contexts before. Many of the purported insulin mimetics or insulin sensitizers are non-tissue specific, which means that the increase in insulin sensitivity happens in the adipose tissue as well. This allows for lower blood glucose levels, but only because the energy can be stashed away in the fat cells. For a diabetic that probably does not matter much, as his or her first concern would be to get the blood glucose levels back in check. If that happens at the cost of yet another midriff bulge that may be unaesthetic, but better than the progression from type II to type III diabetes aka Alzheimer's or the advent of other side effects of chronically elevated blood glucose levels.

Figure 3: Plasma insulin response to the ingestion of 0.7g/kg CHO, 0.7g/kg CHO + 0.3g/kg WPH, and the former with additional 0.1g/kg leucine in type II diabetics and healthy controls (Manders. 2006)

What's more from previous human trials in type II diabetics, we already know that the addition of leucine to a whey protein hydrolysate does not augment its beneficial effects on postprandial glucose clearance. While statistically non-significant, the data from a 2006 study by Manders et al. rather suggests that it has a negative effect on the benefits of the 0.3g/kg whey protein hydrolysateof which the scientists were able to show that it reduced the plasma glucose response by 15% (vs. only 12% with 0.3g/kg whey + 0.1g/kg leucine; cf. Manders. 2006). Moreover, this was no diabetes specific "problem". In fact, the unnecessary insulin overshoot from the added leucine was even more pronounced in the healthy controls of the Manders study (see data in figure 3).

---

Bottom line: You could in fact argue that leucine works much like the diabetes drug rosiglitazone. While the underlying mechanism it totally different, the outcome is very similar. Both increase the insulin sensitivity by reducing adipose tissue inflammation and allowing for greater energy storage in the fat tissue. Good or bad thing? Well, I guess for the majority of SuppVersity readers of whom I hope that they are not type II diabetics an only battling with one or another unaesthetic, but totally healthy pound of body fat, this is bad news.

Even if it was not for the non-specific and potentially obesogenic insulin sensitizing effects of leucine, the increased protein anabolic response to whey hydrosolate compared to free form amino acids is another thing that speaks against the use of leucine or other free-form amino acis in isolation. After all, you would be missing out on the anabolic effects of the peptides in whole proteins (read more).

When you are dieting and there is no energy surplus to stored, you don't have to bother. When you are bulking, on the other hand, and trying to do yourself a favor by adding some "highly anabolic" leucine to each and every meal, you better watch out what it is you are "building" here - is it going to be the intended lean mass or is it going to be a pot belly? I obviously don't have an answer to that question, but in view of the fact that previous trials with "leucine only" supplementation (Balage. 2010) and the provision of leucine as part of an already leucine rich protein shake (Koopman. 2008) did fail to produce superior gains, it's actually not worth trying.

If you also take into consideration the latest SuppVersity post on the non-insulin dependent increase in skeletal-muscle glucose uptake from isoleucine, the #3 in the original branch-chain amino acid concert (leucine, valine, isoleucine; read more), you better keep away from bulk supplies of l-leucine and "superior high leucine BCAA powders" and stick to the tried and proven.

References:

• Balage M, Dardevet D. Long-term effects of leucine supplementation on body composition. Curr Opin Clin Nutr Metab Care. 2010 May;13(3):265-70.
• Koopman R, Verdijk LB, Beelen M, Gorselink M, Kruseman AN, Wagenmakers AJ, Kuipers H, van Loon LJ. Co-ingestion of leucine with protein does not further augment post-exercise muscle protein synthesis rates in elderly men. Br J Nutr. 2008 Mar;99(3):571-80. Epub 2007 Aug 13.
• Li X, Wang X, Liu R, Ma Y, Guo H, Hao L, Yao P, Liu L, Sun X, He K, Cao W, Yang X. Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin-target tissues. Mol Nutr Food Res. 2013 Feb 13.
• Manders RJ, Koopman R, Sluijsmans WE, van den Berg R, Verbeek K, Saris WH, Wagenmakers AJ, van Loon LJ. Co-ingestion of a protein hydrolysate with or without additional leucine effectively reduces postprandial blood glucose excursions in Type 2 diabetic men. J Nutr. 2006 May;136(5):1294-9.