Metabolic Damage in Biggest Losers: Will Diet & Intense Exercise Make You Fat, While Surgery Will Make You Lean? Plus: How to Avoid / Correct Diet-Induced REE Reductions

If you start to work out when you are already obese, it'll still help you lose weight, but if you'd been active the years before chances are you'd not have such weighty problems and wouldn't have to fear metabolic slow down.

Let me answer the question in the headline of today's SuppVersity Article right away, 'cause the answer short and easy: "No!" If you compare the body composition of the Biggest Losers who were included in a recent study by scientists from the National Institutes of Health in Bethesda and the Pennington State Biomedical Research Center, the Vanderbilt University School of Medicine and the University of California-Los Angeles to that of their bariatric surgery patients, the "Biggest Losers" (BLC) had lower body fat and higher lean mass percentages than their peers who took the easy way out (Knuth. 2014). What is non-debatable, though, is the fact that the thirteen "Big Losers" also exhibited significantly more reduced resting metabolic rates - a phenomenon that caused quite a stir in two Facebook groups I am frequenting regularly.

You can learn more about the biggest losers and related topics at the SuppVersity

Weight Cycling & Reduced Metabolic Rates

Biggest Weight Loss Lowest RMR?

You Can't Gain Sign. Amounts of Fat in 3 Days!

Whey Works "Wheytloss Wonders"

Sweeteners Mess W/ Sweet Tongue

Pastured vs. regular Dairy for Leaner Waists?

If you know the exercise drill and "diet" regimen on the TV show, you are probably not surprised to hear that the calorie restriction along with vigorous exercise in BLC participants resulted not just in a higher preservation of fat free mass (FFM), but also in a significantly more pronounced "metabolic adaption" compared to RYGB subjects.

Now, the fact that this happened despite comparable weight loss clearly suggests that we are dealing with "metabolic damage", right? Well, this is exactly what neither I, nor Nicolas D. Knuth and his colleagues who published the results of their NIH funded research in the peer-reviewed journal "Obesity" would say.

Figure 1: Changes (%) in BMI, lean mass and body fat (%) after 7 (BLC) and 6 months, respectively (Knuth. 2014)

The thing we are dealing with is not "damage", it's adaptation and it's an adaptation process that occurred during the weight loss intervention (30 weeks; see Johannsen. 2012), not after an appropriate reintegration to a normal life.

Things to keep in mind: The study at hand confirms what Pourhassan et al. report in another recent study. Reductions in muscle, plasma triiodothyronine and kidney masses explain only 34.9%, 5.3%, and 4.5% of the reduction in RMR (Pourhassan. 2014). And with respect to the false notion that it would be better not to work out, to avoid "metabolic damage", I can only say that DeLany's recent study into the effects of exercise on the reduction in energy expenditure during weight loss interventions is only the latest in a long line of studies that confirm that working out will not just keep the energy expenditure from dropping, it will also improve the dieters' adherence to a given prescribed caloric restriction (DeLany. 2014).

Against that background and in view of the fact that recent studies show that the contribution of body fat and other organs to the resting metabolic rate may have been significantly underestimated it is questionably how significant this comparison is. A comparison, by the way, that's not exactly fair:

• 

  Sugar + phosphate can limit the reduction in T3 during diets in women (read more)

  6 months in the RYGB patients vs. 7 months in the BL competitors, 
• being sedentary vs. working out vigorously, 
• not being able to cheat vs. being able to stick to a diet and exercise regimen, 
• type II diabetic w/ HOMA-IR >8 vs. still pretty healthy w/ HOMA-IR = 2.0 

Where's the level playing field, here? And how significant are the reductions in leptin (tells the hypothalamus that there is still enough body fat left) and T3 (is the active thyroid hormone and a main determinant of resting metabolic rate) that suggest that the Biggest Losers competition ruined their metabolism temporarily, when they came with significant reductions in blood pressure, andimproved HDL and C-peptide levels, which did not occur in the bariatric surgery group?

If you are sitting in the diet trap your situation is similar to the one of the boys and girls suffering from Athletes's Triad and so is the solution!

What can a "Big Loser" do to get back to normal REEs fast? Based on the contemporarily available evidence, the best thing they could do was to inject leptin (Rosenbaum. 2005; Kissileff. 2012). Other strategies that may work are strategic overfeeding (for 2-3 days; on a high(er) carbohydrate diet) and intake / supplementation of foods and agents that have been shown to increase leptin in normal-weight or reduced obese individuals. The effects should be similar to those scientists observed with leptin injections - albeit much less rapidly: So be patient if you are going to try any or all of the following tweaks.

Possible means to restore leptin to normal would include: Lower omega-3 (Hariri. 2014), total fat (Havel. 1999) and fructose (Teff. 2004), but higher dairy (Wennersberg. 2009) and carbohydrate (Romon. 1999) meals and / or  zinc supplements (Chen. 2000) or sugar + phosphate (learn more) and nicotine (Eliasson. 1999) to increase leptin and leucine / EAA-rich proteins (Binder. 2014) or, again, nicotine (Li. 2003) to increase leptin sensitivity. Ah! And don't forget not to overtrain (Jürimäe. 2003) and, of course, to sleep enough (~8h) - sleeping less will lower leptin by >20% (Spiegel. 2004).

Moreover, if you look at my plot of the data in Figure 1, you will see that the that it is a perfectly normal adaptations to exuberant caloric deficits (>50%).

Figure 2: The metabolic "damage" is rather a metabolic "adaptation" (y-axes; in kcal/day) in response to significant energy deficits (x-axes; calculated energy expenditure (includes exercise induced energy expenditure, therefore it can approach 100%) expressed relative to calculated RMR) - the problems begin with intakes >50% below maintenance.

Whether or not the exercise component made things worth, is something that cannot be said based on the data from this study. What it certainly did, though, was to protect the lean mass of the subjects - a vital requirement to achieve what most people are dieting for: Health and being happy with what they see in the mirror.

In conjunction with the previously cited health benefits (reduced blood pressure, increased HDL, ...) it would thus be idiotic to use the study at hand as evidence against the repeatedly proven usefulness of exercise for weight loss and health improvements in obese and non-obese individuals.

Weight loss does not have to cost muscle and ruing your metabolism - learn more about the science-based "art" of losing weight

Bottom line: The study at hand ain't the evidence the lazy ones have been waiting for. It's not a free ticket to the surgeon and it does not provide convincing evidence that diet + exercise are not far superior ways of losing weight (compared to bariatric surgery).

What the study does show, though, is that the recommendations I made in my previous article "Losing Weight Doesn't Have to Ruin Your Metabolism: No Unexpected Reduction in Energy Expenditure With Sane Weight Loss. Plus: 9 Simple Rules Every Dieter Must Follow" (read more) are spot on: Never (!) stay at a caloric deficit that's >40% of what you'd need on a daily basis for more than maybe a week and take breaks, instead of increasing the calorie deficit, when you feel you're hitting a plateau (read all 9 tips, here) | Comment on Facebook!

Ah, and by the way, it's also a myth that formerly obese individuals have necessarily lower resting and total energy expenditures. As Hume et al. found the RMR of ever-lean and formerly overweight women is identical and the ostensibly lower energy expenditure during physical activity is an artifact that's caused by over-reporting of physical activity in the formerly overweight women (Hume. 2013).

References:

• Chen, Ming-Der, Yuh-Min Song, and Pi-Yao Lin. "Zinc may be a mediator of leptin production in humans." Life sciences 66.22 (2000): 2143-2149.
• DeLany, James P., et al. "Effect of physical activity on weight loss, energy expenditure, and energy intake during diet induced weight loss." Obesity 22.2 (2014): 363-370. 
• Eliasson, Björn, and Ulf Smith. "Leptin levels in smokers and long‐term users of nicotine gum." European journal of clinical investigation 29.2 (1999): 145-152.
• Hariri, Mitra, et al. "Does omega‐3 fatty acids supplementation affect circulating leptin levels? A systematic review and meta‐analysis on randomized controlled clinical trials." Clinical endocrinology (2014).
• Havel, Peter J., et al. "High-fat meals reduce 24-h circulating leptin concentrations in women." Diabetes 48.2 (1999): 334-341.
• Hume, David John, Jacolene Kroff, and Estelle Victoria Lambert. "Resting and activity-related energy expenditure: Do formerly overweight women differ from their ever-lean counterparts?." International Journal of Nutrition and Metabolism 5.8 (2013): 134-139.
• Johannsen, Darcy L., et al. "Metabolic slowing with massive weight loss despite preservation of fat-free mass." The Journal of Clinical Endocrinology & Metabolism 97.7 (2012): 2489-2496.
• Jürimäe, Jaak, Jarek Mäestu, and Toivo Jürimäe. "Leptin as a marker of training stress in highly trained male rowers?." European journal of applied physiology 90.5-6 (2003): 533-538.
• Kissileff, Harry R., et al. "Leptin reverses declines in satiation in weight-reduced obese humans." The American journal of clinical nutrition 95.2 (2012): 309-317.
• Knuth, N. D., Johannsen, D. L., Tamboli, R. A., Marks-Shulman, P. A., Huizenga, R., Chen, K. Y., Abumrad, N. N., Ravussin, E. and Hall, K. D. "Metabolic adaptation following massive weight loss is related to the degree of energy imbalance and changes in circulating leptin." Obesity.  (2014) doi: 10.1002/oby.20900 
• Li, Ming D., and Justin K. Kane. "Effect of nicotine on the expression of leptin and forebrain leptin receptors in the rat." Brain research 991.1 (2003): 222-231.
• Pourhassan, Maryam, et al. "Impact of body composition during weight change on resting energy expenditure and homeostasis model assessment index in overweight nonsmoking adults." The American journal of clinical nutrition (2014): ajcn-071829.
• Romon, M., et al. "Leptin response to carbohydrate or fat meal and association with subsequent satiety and energy intake." American Journal of Physiology-Endocrinology And Metabolism 277.5 (1999): E855-E861.
• Romon, Monique, et al. "Postprandial leptin response to carbohydrate and fat meals in obese women." Journal of the American College of Nutrition 22.3 (2003): 247-251.
• Rosenbaum, Michael, et al. "Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight." Journal of Clinical Investigation 115.12 (2005): 3579-3586. 
• Teff, Karen L., et al. "Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women." The Journal of Clinical Endocrinology & Metabolism 89.6 (2004): 2963-2972.
• Wennersberg, Marianne Hauge, et al. "Dairy products and metabolic effects in overweight men and women: results from a 6-mo intervention study." The American journal of clinical nutrition (2009): ajcn-27664.

Less Frequent Large(r) Meals & Caffeine - Proven Ways to Increase Your Energy Expenditure & Conserve Your Resting Metabolic Rate While Dieting | Part I of A Multipart Series

Whether you want to lose or gain weight, never forget to "Eat to live!"

To lose weight, you must create a negative energy balance.It is however unrealistic to expect your body not to do everything it can to conserve energy, when you've been eating 50% below maintenance for weeks (e.g. you need 2,000kcal, but eat only 1,000). Not to reduce your energy intake by more than 40% (for max. 2 weeks) and going with 20-25% if you plan to diet for 4-6 weeks would thus qualify as rule #1; a rule of which I can only say that I highly recommend you stick to it, because if you don't even the five tips below are not going to save your metabolism from crashing (learn more about the nine rules that can help avoiding metabolic shut-down).

There is evidence of effects of coffee & CGA on your gut microbiome (Jaquet. 2009)

Fiber for Female Fat Loss

Sweeteners & Your Gut

Foods, Not Ma- cros for the Gut

Lactulose For Gut & Health

Probiotics Don't Cut Body Fat

The Macrobiotic MaPi2.0 Diet

Ah, and before I forget to mention it. If you don't control your dietary energy intake, chances that any of the following tricks (in that case magically) help you lose weight without the need to diet are anywhere between "slim" and "zero".

• Eat large meals less frequently: It may go against the longstanding recommendation, but due to the fact that meal size, not macro composition is the main determinant of the post-meal increase in thermogenic effect.

  

  Figure 1: Increase in metabolic rate above basal metabolic rate (BMR) (kJ/min) after ingestion of
  four different test meals by human subjects (Kinabo. 1999)

  And considering the fact that the latter lasts for 5h+ (see Figure 1) the idea that you have to eat a small meal every hour "to stoke the furnace" is fundamentally flawed. No wonder, people all over the world are successfully using weight by intermittent fasting.

Thermic effect of food (in kcal/3h), when it's consumed at rest or after a workout in lean vs. obese (fat, not just heavy) subjects (Segal, 1985)

The thermic effect of food is reduced with obesity: A review of 49 pertinent studies by researchers from the Pennington Biomedical Research Center clearly indicates "the reduction of TEF in obesity is related to the degree of insulin resistance, which may be influenced by a low level of sympathetic activity." (Jonee. 1997). A study by Segal et al. measured a difference of 42% at rest and 64% if the meal was consumed after a workout (see figure on the left). Accordingly those of you who are still carrying more than "some" extra weight should be careful not to overestimate the benefits of food induced increases in thermogenesis. Don't misinterpret this as "you got to eat more often", though! This could make things even worse.

• You have to be careful, though, long arduous workouts during the fast or fasting for more than 12-16h could nullify the thermogenic benefit of being able to eat to satiety once or twice a day. And no! The Kinabo study is not a statistical outlier, it's just like a study with almost identical results by Tai et al. (1991) real vs. broscience which dictates that you "got to stock the furnace" - a practice of which the latest controlled studies show that is has "no significant effect on 24-h fat oxidation, but may increase hunger and the desire to eat." (Ohkawara. 2013)

• Use 4mg/kg caffeine per day - You will certainly have expected to see caffeine on the list of agents that help. Unfortunately, caffeine is significantly more effective for lean vs. overweight individuals. In a study from the Institute of Physiology at the University of Lausanne, David Bracco and colleagues were able to show that the thermogenic effect of caffeine coffee (4mg/kg body weight) was 35.6% more pronounced in the lean vs. obese female subjects (Bracco. 1995) - similar results have been reported by Belza et al. (2007), Hollands et al. (1981) increases of 15% in the two hours after the ingestion of caffeinated vs. decaffeinated coffee.
  

  

  Figure 2: Relative increase in resting metabolic rate, energy expenditure during exercise and sleep in lean and obese women in response to the ingestion of 4mg/kg of caffeine (vs. placebo | Bracco. 2014)

  In addition to the overall effect size, the data in Figure 2 does also indicate that an "over night" effect, as well as the increase in energy expenditure during workouts were likewise only observed in the lean, not in the obese women (since the lack of thermogenesis has been associated with decreased insulin sensitivity using 300-500mg of alpha lipoic acid, as I have suggested in a recent article, may ameliorate the reduction in postprandial thermogenesis).

Remember not to go overboard on caffeine (here's why): Stick to 600mg/day and take it in three to four doses of 200mg or 150mg respectively; and, if possible, get some of it from coffee, for the added benefits of chlorogenic acid & co (McCarty. 2005). In fact, a recent study from the Technische Universität Kaiserslautern shows that coffee consumption 250ml 3x per day (vs. decaffeinated coffee as placebo) will even induce body fat loss(es) in the absence of deliberate restrictions of food intake in 84 healthy subjects... and on top of it, the coffee consumption protected the study participants DNA (Bakuradze. 2014).

• Now 4mg/kg may seem like quite a high dosage for some of you. In contrast to the usual SuppVersity mantra that "more won't help more", those 4mg caffeine per kg of body weight are yet well necessary. In a 1999 study from the University of Geneva, for example, the administration of only 50mg of caffeine had no effect on the resting energy expenditure of 10 healthy male volunteers (Dullo. 1999).
  
  

  

  Figure 3: Substrate utilization (mg/min) before (filled bars) and after (empty bars) the ingestion of a complex test meal with either coffee (4mg/kg caffeine) or decaffeinated coffee (Acheson. 1980).

  Furthermore, caffeine has also been shown to increase the thermic effects of a meal and to shift the fuel utilization towards fatty acids (Acheson. 1980; see Figure 3). The latter will not necessarily help you to burn more body fat, but it will spare liver and muscle glycogen, when you're dieting and reduce the chances that your liver resorts to amino acids from your musculature to cover the glucose requirements of your body.
  
  In conjunction with the net increase in energy expenditure Dullo et al. quantify in the range of 150 kcal in lean volunteers and 79 kcal as a response to the bi-hourly consumption of 100mg of caffeine in the post-obese subjects, there is little doubt that
  

  "Caffeine at commonly consumed doses can have a significant influence on energy balance and may promote thermogenesis in the treatment of obesity." (Dullo. 1989)

  Studies by Yoshida et al. support this notion and confirm that the addition of caffeine to the weight loss equation will be particularly effective in overweight individuals with reduced baseline metabolic rate (Yoshida. 1995) and more recent experimental data from the University of Maastricht confirms that high caffeine intakes are associated not just with increased weight loss through thermogenesis and fat oxidation, but also with reduced fat mass, and waist circumference in overweight and moderately obese subjects (Westerterp‐Plantenga. 2005).

Suggested: Many Small Meals Suck - Especially for Diabetics | more

You already knew those two? Well in that case you've probably been following my articles here at the SuppVersity for quite some time, now. I have, after all, written about caffeine, coffee, intermittent fasting and meal frequencies, before. And in case you didn't find at least a couple of additional new figures, you haven't seen before, I can comfort you: There will be follow ups in the course of the next weeks.

It would thus be a stroke of bad luck if you didn't find at least one new agent or trick in one of the next installments of this series or spend your time commenting on Facebook!

References:

• Acheson, K. J., et al. "Caffeine and coffee: their influence on metabolic rate and substrate utilization in normal weight and obese individuals." The American journal of clinical nutrition 33.5 (1980): 989-997. 
• Bakuradze, Tamara, et al. "Four weeks coffee consumption affects energy intake, satiety regulation, body fat, and protects DNA integrity." Food Research International (2014).
• Bracco, David, et al. "Effects of caffeine on energy metabolism, heart rate, and methylxanthine metabolism in lean and obese women." American Journal of Physiology-Endocrinology and Metabolism 32.4 (1995): E671. 
• Dulloo, A. G., et al. "Normal caffeine consumption: influence on thermogenesis and daily energy expenditure in lean and postobese human volunteers." The American journal of clinical nutrition 49.1 (1989): 44-50.
• Dulloo, Abdul G., et al. "Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans." The American journal of clinical nutrition 70.6 (1999): 1040-1045.
• Hollands, Marjorie A., J. R. Arch, and M. A. Cawthorne. "A simple apparatus for comparative measurements of energy expenditure in human subjects: the thermic effect of caffeine." The American journal of clinical nutrition 34.10 (1981): 2291-2294.
• Jonee, Lilian, and George A. Bray. "The thermic effect of food and obesity: a critical review." Obesity research 5.6 (1997): 622-631.
• Kinabo, J. L., and J. V. G. A. Durnin. "Thermic effect of food in man: effect of meal composition, and energy content." British Journal of Nutrition 64.01 (1990): 37-44. Segal, Karen R., et al. "Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight." Journal of Clinical Investigation 76.3 (1985): 1107.
• McCarty, Mark F. "A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk." Medical hypotheses 64.4 (2005): 848-853.
• Ohkawara, Kazunori, et al. "Effects of increased meal frequency on fat oxidation and perceived hunger." Obesity 21.2 (2013): 336-343.
• Segal, Karen R., et al. "Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight." Journal of Clinical Investigation 76.3 (1985): 1107.
• Tai, Mary M., Peter Castillo, and F. Xavier Pi-Sunyer. "Meal size and frequency: effect on the thermic effect of food." The American journal of clinical nutrition 54.5 (1991): 783-787. 
• Westerterp‐Plantenga, Margriet S., Manuela PGM Lejeune, and Eva MR Kovacs. "Body weight loss and weight maintenance in relation to habitual caffeine intake and green tea supplementation." Obesity research 13.7 (2005): 1195-1204.
• Yoshida, T., et al. "Relationship between basal metabolic rate, thermogenic response to caffeine, and body weight loss following combined low calorie and exercise treatment in obese women." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 18.5 (1994): 345-350.

Evidence From the Metabolic Ward: 1.6-2.4g/kg Protein Turn Short Term Weight Loss Intervention into a Fat Loss Diet

2x-3x higher than RDA protein intakes work equally well for men and women, to get and stay lean and lose fat and build / maintain muscle.

There are very few principles I believe are set in stone and valid regardless of your age (maybe not for toddlers), your training goals and your nutritional "orientation" (paleo, low carber, low fat eater, or whatever), and among these the "Have at least 30g of quality protein (eggs, meats, dairy, fish, etc.) with every major meal" (this assumes you eat 3meals+ per day) probably is king. It is the recipe to success and I actually don't feel as if it was necessary to convince you of the advantages this high(er) protein intake will have on your physique and - although the medical establishment is still reluctant to admit that - your health, as well. Still, the most recent study from the Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine in Natick, Massachusetts, USA; have much more to offer than "just" some additional evidence to the superiority of high(er) protein diets on a cut.

It's more than high time to revise the RDA

The study was designed to assess the effects of different dietary protein (RDA = 0.8g/kg, 2x RDA = 1.6g/ kg and 3x RDA =2.4g/kg) intake on body composition and postabsorptive and postprandial muscle protein synthesis on a 21-day cut (-30% energy restriction phase; ED). The latter was preceded by a 10-day weight maintenance (WM) period.

To up the calculated energy deficit to 40% the physically active (physical activity 3– 4 d/wk), weight stable ( 2 kg; for a minimum of 2 mo before the study), 39 volunteers [32 men (11 military, 21 civilians) and 7 women (7 civilians)] with a body mass index (BMI) between 22 and 29 kg/m² and a sufficient baseline fitness had to exercise daily:

"You told me to eat more protein and this burger has both meat and cheese!" - This and other mishaps are the rule, not the exception in uncontrolled dietary interventions (learn more). The fact that the study at hand took place in the metabolic ward of the U.S. Department of Agriculture Grand Forks Human Nutrition Research Center really is a HUGE PLUS.

"To isolate the effects of the diet and minimize the potential of an exercise training stimulus, physical activity during WM was prescribed at levels comparable to those reported in prestudy 7-d physical activity records. Volunteers performed low-tomoderate-intensity (40 – 60%Vo2peak) treadmill and cycle ergometry steady-state physical activity sessions daily. Intensity was based on pre-study Vo2peak
measurements obtained during a progressive intensity treadmill test and verified during
familiarization trials using indirect calorimetry (ParvoMedics) and corresponding heart rate. Workloads during steadystate physical activity sessions were adjusted accordingly to
ensure accuracy using the heart rate reserve method and portable heart rate monitors." (Pasiakos. 2013; my emphasis)

The study took place in the metabolic ward (so there was no cheating involved here => HUGE PLUS; cf. ) at the U.S. Department of Agriculture Grand Forks Human Nutrition Research Center. All volunteers were required to abstain from nutritional supplements, alcohol, smoking, and all medications, unless acetaminophen-containing products were provided by the investigator or study physician. Volunteers were also required to be in their assigned rooms with lights out by 11 P.M. (possibly very important; learn why) to ensure adequate and similar levels of sleep.

Don't worry this was not "cardio only"

To maintain prestudy muscular fitness levels, the volunteers also performed resistive-type physical activity 3d/wk. However, "to minimize the potential of an unaccustomed, anabolic stimulus influencing study outcome measures, the intensity and volume of the resistive-type exercise was low" (Pasiakos. 2013):

Table 1: Energy / macronutrient content of the diets (updated on June 21; previously there was a copy + paste error in the table)

"Specifically, volunteers performed one single-joint movement per major muscle group (3 sets of 15 repetitions) using workloads determined during the prestudy period. Frequency, intensity, mode, and volume of resistive-type activities did not change during the 31-d study. Research staff who were blinded from dietary assignment supervised all physical activity sessions for safety and accuracy". (Pasiakos. 2013)

The body weight, was recorded in two day intervals and the body composition was quantified using a  dual-energy X-ray absorptiometry (DXA) during WM (day 9) and ED (day 30). To elicit the underlying mechanisms, the resting metabolic rate, protein synthesis, nitrogen balance and the expression of intracellular signaling proteins were tested, as well.

Figure 1: Change in body composition and protein synthesis (Pasiakos. 2013)

As you can see in figure 1, there was a baseline and dose-dependent effect on the changes it total weight and body composition, respectively.

Body weight during WM was similar between dietary treatment groups and remained stable from d 1 (group mean, 77.5 1 +/-5 kg) through d 10 (77.1 1 +/-5 kg). Overall, volunteers lost 3.2 0 +/- 2 kg during the 21-d ED; 3.5 0 kg for RDA, 2.7 0 kg for 2 -RDA, and 3.3 0 kg for 3 -RDA (P < 0.05). Independent of dietary protein, percentage body fat decreased (P < 0.05) from 19.8 1% during WM to 18.1 1% during ED, and the change in percentage body fat was similar between RDA (1.3 0 +/- 3%), 2 -RDA (1.8 0 +/- 4%), and 3 -RDA (1.9 0 +/- 3%)." (Pasiakos. 2013)

What's worth taking a closer look at, is yet the proportion of total weight loss due to changes in fat mass (FM) and FFM, which differed across dietary protein levels.

• the percentage of total weight loss attributed to reductions in fat mass (FM) was higher (P < 0.05) for 2 -RDA (70.1 7%; 1.9 0 +/- 3 kg) and 3 -RDA (63.6 5%; 1.9 0 +/- 2 kg) than for RDA (41.8 5%; 1.6 0+/-2 kg)
• the percentage of total weight loss due to a loss of fat free mass (FFM) was lower for 2 -RDA (29.8 7%; 0.8 0 +/- 2 kg) and 3 -RDA (36.4 5%; 1.2 0. +/- 3 kg) as compared to RDA (58.2 5%; 2.3 0 +/- 3 kg)
• the fat to lean mass loss ratio was 30% higher in the medium protein intake group, in other words, the increase in protein intake in the 3xRDA group did not protect the lean mass any better than the 1.6g/kg in the 2xRDA group

While the latter change did not reach statistical significance, the trend is clear and I suspect with a higher number of participants, the scientists would have been able to show that the 3x RDA intake is not just worthless, but actually contra-productive, if your goal is stable ongoing fat loss.

No inter-group differences in the majority of signaling proteins

All the changes took place in the absence of statistically significant inter-group differences in the changes in anabolic intracellular signaling and gene expression [ignore the following list if you are no geek ;-], i.e.

• postprandial Akt (Ser 473) phosphorylation was increased 1.4-fold higher (P < 0.05) compared to postabsorptive levels
• postprandial p70 S6K1 (Thr 389), eIF4E Ser (209), and rpS6 (Ser 235/236) phosphorylation status was 16, 1.9, and 15.5-fold higher (P < 0.05), respectively, compared to postabsorptive phosphorylation levels
• phosphorylation status of eEF2 (Thr 56) was lower (P < 0.05) after feeding

The more important general observation was yet that the upregulation of these signals 3 h after consuming a protein-containing meal, demonstrated a main feeding effect for all proteins of interest (P < 0.05). On the other hand, their expression was not influenced by energy status or the level of dietary protein intake (and let's be honest, what would an increase be worth if the data in figure 1 already told us what the real-world implications are?)

Figure 2: Changes in postabsorptive muscle protein synthesis-associated mRNA expression levels during the diet phase (-40% energy intake) of the study (Pasiakos. 2013)

Additionally, the energy deficit increased the mRNA expressions of a couple of other proteins implicated in the intracellular regulation of muscle protein synthesis:

"Transcription of Vps34, a protein involved in amino acid sensing and amino acid-mediated stimulation of mammalian target of rapamycin (mTORC1) signaling, was 1.2-fold higher (P < 0.05), while expression of mTORC1 inhibitors REDD1 and REDD2 were both 1.3-fold higher (P < 0.05) after ED compared to WM. Increasing dietary protein intake increased Vps34 mRNA expression, with 1.2-fold higher levels for 3x-RDA than RDA (P 0.05). MAP4K3, LAT1, and SNAT2 mRNA levels were not influenced by energy and dietary protein manipulations." (Pasiakos. 2013)

In view f the slight advantage of the 3xRDA diet in terms of the stimulation of protein synthesis, you may want to come back to the statistical insignificance of the superiority of the 2xRDA diet to keep indulging the same hilarious amounts of protein that have probably not gotten yourself anywhere near contest shape in the past, well, let's take a look on a couple of other observations, then:

• While the nitrogen balance remained negative (meaning the body was burning more protein than it stored) over the whole trial in the 0.8g/kg group, it returned to baseline (weight maintenance levels) first in the 1.6g/kg (=2x RDA) group (day 17!). This restoration of to pre-diet levels was observed only on day 30 in the high protein group (2.4g/kg) and the that without any significant advantage of the 3xRDA over the 2xRDA intake (if anything it was lower in the high protein group; see figure 3)
• There was no "thermogenic advantage" - or whatever people usually like to call the purported beneficial effect that comes with the ingestion of higher amounts of protein; in fact, the resting metabolic rate was identical for all three groups over the whole 21-day diet period. 
• With a diet that was high in carbohydrates and low in fat (see table 1), the conversion of protein to glucose, was likely relatively limited and the potential downsides of high protein + low carb diets, where most of the protein will be broken down in the liver to supply your body with glucose and any temporary increase in insulin due to fast acting protein sources were not an issue.

In the end, the increase in postprandial protein synthesis in the 3x RDA group is therefore worthless, because it went hand in hand with an increase in wastefulness due to which the absolute protein retention did not differ all that much and the differences in lean mass loss 0.1kg) are clearly insigificant- plus: If you simply do the math, the ratio of fat free to fat mass loss, is still 31% higher in the 2x RDA group.

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Irrespective of how many supplements you take - you cannot out-supplement a bad diet, laziness and a lack of motivation & determination. Still, especially for the elderly HMB with it's pronounced anti-cababolic effec could help - particularly on a diet (learn more; leucine vs. HMB)

So what's the optimum then? If we reconcile the results of the study at hand, the "optimal" protein intake would thus probably be somewhere between 1.6g/kg and 2.0g/kg an thus in the <200g range for the vast majority of people. If you also consider that this value includes all protein even that from rice, and other "non-quality" protein sources, the study at hand does not confute my previous recommendation to stick to a 1.5g/kg-2.0g/kg (per total body mass) protein intake from quality protein sources, to discount the additional protein you will be getting from "low protein food" (too much counting will only make you neurotic) and to do that irrespective of whether you are bulking and or dieting  .

One thing you may want to keep in mind though, is the fact that the overall calorie deficit of ~40% may still have been a little to high - it was not enough to elicit a significant reduction in the resting metabolic rate, but still enough to induce a loss of at least 30% of lean mass. A lower caloric deficit 20-30%, a little more patience and a focus on hypertrophy-specific weight lifting are thus probably a way more significant difference, than whether you consume 1.6g/kg or 2.4g/kg body weight.

References: 

• Pasiakos SM, Cao JJ, Margolis LM, Sauter ER, Whigham LD, McClung JP, Rood JC, Carbone JW, Combs GF Jr, Young AJ. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 2013 Jun 5. [Epub ahead of print]