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.

Leucine & Phenylalanine Enriched YoYo-Diets Ameliorate Fat Gain, Protect Muscle & Maintain T4→T3 Conversion

Too little leucine & phenylalanine in O.'s diet?

Actually it is quite counter-intuitive that the "YoYo"-diets competitive boydbuilders adhere to (diet vs. bulking phase) are capable of producing such amazing physiques. I mean, when Mr. and Mrs. Average "diet down" and "bulk", the result will usually be neither aesthetic nor healthy, right?

A recent study from the University of Sao Paulo does now provide some insights into the important role the high amount of essential amino acids (leucine and phenylalanine, to be precise) in the typical bodybuilding diets may play with respect to its moderating effects on the lean muscle loss and body fat gains of Opra-esque ups and downs in body weight.

Leucine + Phenylalanine + diet and refeed = ???

I guess the details in the headline to this paragraph are not actually detailed enough to get an idea of what Donato Jr. et al did in their latest rodent study, are they? I see. I will still try to stick to the most important facts.

Contrary to the beliefs of many mostly female victims of life-long dieting, never eating to satiety is NOT going to promote a bikini body - quite the contrary (learn more)

Donato and his colleagues fed a group of adult Wistar rats diets that differed only in their amino acid make-up. Both the control and the experimental diet were based on the same synthetic standard chow (remember what you've learned about synthetic chow lately?). What was different, though was the form of protein / amino acids the scientists used to replace 8.55g of the cornstarch (per kg) of the original diet. The final diets did thus contain either...

• 8.55g of casein (control), or
• 5.45g l-leucine + 3.1g l-phenylalanine (LP)

... as replacements for the cornstarch. Since both were still isocaloric and had an identical protein content (12%) this modification would allow Donato et al. to see if the different amino acid profiles would have nay effects on the weight development of the rodents.

I guess by now you may be asking yourself about the connection to Oprah and boydbuilding diets, right? Well, the 28-day experiment actually had 2 phases a dieting and a maintenance phase. Both cycles were 14 days long. In the first one, the rodents dietary intake was cut in half, while they were allowed to eat as much as they wanted (ad-libitum feeding) in the second 14-day cycle.

YoYo or not - is that the question?

Now, what would you guess happened? I mean, remember: Both diets had an absolutely identical amount of calories and protein - so, the rodents in both groups "hit their macros", right? The logical answer - at least to an increasingly popular, but over-simplistic dietary paradigm - must be: "Nothing! Both groups will end up at an identical body composition.", right!? A brief glance at the data in figure 1 does however suffice to tell you the IIFYM prognosis was not exactly correct - at least not if we take the changes in body composition into account.

Figure 1: Effects of weight cycling with casein (control) and leucine + phenylalanine (L+P) on body composition (left), feed efficiency (=how much weight do you gain per gram of food) and weight (Donato Jr. 2013)

So what can we conclude based on the results in figure 1? Firstly, the small figure on the bottom right goes to show you that weight cylcing per se does not make you "heavy" as in "having a higher BMI than somebody who does not weight cycle". The large figure on the left, on the other hand informs us that weight cycling can cost you muscle and make you fatter - 4% fatter to be precise. Skinny fat, so to say. Notwithstanding, the data from the Donato Jr. study does also tell us that the provision of a low amount of additional leucine and phenylalanine minimized the fat gain in the bulking phase and had beneficial effects on amount of lean mass the rodents maintained and build during the 4-week study. The net result is a higher body weight in the L+P group, at an almost identical body composition.

Leucine + phenylalanine also blunt the reduction of T4 → T3 conversion

If we look closer we do yet see another related, but non-negligible advantage: The typical downregulation of the conversion of the "inactive" thyroid hormone T4 to the "active" thyroid hormone T3 in response to long-term dieting was significantly reduced by the provision of leucine and (I will just go on a limb here and say "more importantly") the neurotransmitter precursor phenylalanine.

Figure 2: Effect of weight cycling of markers of glucose and thyroid metabolism (Donato Jr. 2013)

This did yet not translate into a significant amelioration of the highly significant (>50%) deterioration of the blood glucose metabolism, and the triglyceride levels (not shown) were actually 20% lower in the casein yoyo group (CON) than in the non-weight cycled control group. From a health perspective, the addition of leucine and phenylalanine is thus "only" useful, because it will help you retain or actually build muscle mass (with the data we have, it's difficult to say which effect was the dominant one, but I'd suspect it's the anti-cabatolic one).

Bottom line: You need to be careful about mis- and over-interpreting the results of the study at hand - and that's not just because it's "only a rodent study".

If there was one "take home message" from the study at hand, I guess it would be very similar to the one from the one of the December 2012 post I borrowed this figure from: "Make sure to get at least 10g of EAA with each of your meals"... ah well, "... and avoid 'classic' YoYo dieting à la Oprah, whenever possible - of course!" ;-)

The alleged "lean mass gains" on the L+P diet come at the expense of a non-negligible increase in body fat. Overall the lean mass to fat mass ratio is thus not better than in the continuously fed rodents. And unless your beauty ideal is all about being "massive", this is not necessarily going to be an improvement to your physique.

If you take another look at figure 1 you will also see that the feed efficiency, i.e. the amount of weight you gain per kcal you consume was not reduced but increased by the addition of leucine and phenylalanine. This may be a result of the pro-insulinogenic and "anabolic" (Nuttall. 2006; Iverson. 2013), as well as the anti-cabatbolic effects of these amino acids and is thus not necessarily "bad".

It would nevertheless be highly unwarranted to believe that supplementing your diet with leucine + phenylalanine on a a "lean bulk" would yield significant advantages - this hypothesis is clearly not supported by the study at hand. The same goes for the usefulness of supplementing isolated amino acids, in this case leucine and phenylalanine, on top of a high protein diet, in general. In fact, I can refer you directly to an older article of mine that confirms that you better make sure to get the full dose of 20g+ of whole protein than trying to make up for it by adding additional aminos (learn more)

References:

• Donato, J. et al. Effects of leucine and phenylalanine supplementation during intermittent periods of food restrictionand refeeding in adult rats. Life Sciences. 2007 [epub ahead of print]
• Iverson JF, Gannon MC, Nuttall FQ. Ingestion of leucine + phenylalanine with glucose produces an additive effect on serum insulin but less than additive effect on plasma glucose. J Amino Acids.
• Nuttall FQ, Schweim KJ, Gannon MC. Effect of orally administered phenylalanine with and without glucose on insulin, glucagon and glucose concentrations. Horm Metab Res. 2006 Aug;38(8):518-23.