"Just One More Set" (1/2): Metabolic Response to 10,000kg vs. 20,000kg Regimen. EPOC: Do Reps and Loads Both Figure? And What About Elite Athletes Do They Need More?

"Ah come on, just another set!" ... "I don't know man, we've already pumped away 100,000kg today... do you really believe that's going to be productive, I mean, yeah, we are cuttin', but still... I mean I don't dig this epic!", "EPOC man, it's called EPOC!" *shakes his head* "Call it whatever you want, bro, I am out!"

If you want, you can think of today's SuppVersity post as an extension to yesterday's "Bigger, Stronger, Faster" special of the On Short Notice series; to be more precise: As a practically more relevant version of the rodent study on hypertrophy vs. strength training that was part of the aforementioned post. Yep, we are "talking volume" today. How much is too much?  And though this is never-ending debate, it appears that at least as far as research goes, a little more debating certainly would not hurt. Therefore I am happy to have not one, but two studies for you which don't just address this issue, but have also been conducted with human subjects!

In view of the fact that these are no "short notices", I will discuss one today and the other tomorrow - yep, that means that you can already make a mental note to come back tomorrow ;-)

"Just one more set, ..." - how productive can that be?

Today's study comes from the Human Performance Laboratory at the Florida State University and deals with the energetic side of things - specifically the often-cited EPOC (excess post-exercise oxygen consumption), which is often touted as one of the most important aspects why strength training in general and higher volume / intensity strength training, in particularly, would have the edge over cardio training. The reasoning is easy: You don't burn so much energy while you work out, but in the time after, your body will (a) still expend more energy per minute / hour and (b) has the advantage of emptied glycogen stores, which will force it to tap into its body fat stores the source for the required energy.

All of you who have read the complete Athletes' Triad series, will by now already know that at least argument (b) is pretty idiotic, because it wouldn't allow you to replenish your muscle and liver glycogen after workouts and thus pave the way into the dreaded vicious circle of the athlete's triad. The former argument, on the other hand has - on a way more general level - only been confirmed a couple of days ago (see "Scientists resolve the paradox of stable muscle metabolism but greater mitochondrial respiration in muscle of inactive vs. active subjects", read more), the question still remains: How much weight do you have to lift to set the 'afterburner' into full gear? 

10 metric tonne or 20 metric tonnes? What do you say?

I see, you are laughing, but basically the above question is what the George J. Abboud and his colleagues tried to find out, when they recruited 8 healthy men aged19-29 yrs who had 

"at least 12 months of RT experience with no more than 2 wks rest at a time, less than a total of 4 wks off within the last 6 months, or 9 wks off within the last 12 months [and] reported no prior or current use of illegal performance enhancing substances." (Abboud. 2013)

Suggested read "Three is More Than One: Higher Volume Increases Strength Gains in Legs, and Satellite Cell Recruitment and Fiber Size in Legs & Traps."

As usual the subjects had to fill food logs for the three days before the testing and were instructed to replicate the same eating pattern on the second occasion in which they were randomly assigned to perform a standardized resistance training (RT) regimen consisting of 4 exercises performed on a non-counterbalanced smith machine so that the range of motion during

• bench press, 
• squat, 
• bent-over row and 
• Romanian deadlift 

could be controlled for easily. Other than the equipment and the exercises, which were identical on both occasions, the volume of the training sessions varied and if you express this volme in kg or metric tons, it was a competition of 10,000 kg (10 metric tonnes) vs. 20,000 kg (20 metric tonnes) of weight. 

"The loads were divided between the 4 exercises as follows: 35% to squats, 30% to bench press, 20% to bent-over rows and 15% to Romanian deadlift. For each set, subjects lifted approximately 85% of their 1RM for 6-8 repetitions. If 6 repetitions could not be completed at any point, the load was reduced by 10% for the subsequent set." (Abboud. 2013)

Both sessions were supervised by three testers : One monitored the metabolic cart, one made sure the proper range of motion was used and one monitored the proper lifting form. The subjects had to perform the concentric portion of each lift with maximal speed and ensure a controlled eccentric descent. A specific time interval was not dictated. Sets were stopped if "subjects broke form" (Abboud. 2013) and 2 minutes of rest were given between sets. In this fashion the subjects simply kept lifting set after set until the volume prescription for the respective trial was reached.

Figure 1: Resting metabolic rate (RMR) per kg body weight, 30min energy expenditure and respiratory exchange ratio (RER; lower values = higher fat, lower glucose  oxidation)  after low and high volume trial (based on Abboud. 2013)

As you can see in figure 1 there were differences as far as the effects of the high (20,000) vs. low (10,000kg) regimen on the resting metabolic rate, 30 min energy expenditure, and the respiratory quotient (lower values = higher fat, lower glucose oxidation), but in view of the fact that the high volume group moved 2x more weight and should thus (at least theoretically) have expended twice the energy (assuming they performed all reps with perfect form and identical speed), those differences are more than disappointing. 

The minuscle effect size is yet not the most "disappointing" (or "surprising" ?) result

In fact, contrary to the low volume workout the 20,000kg workout did not produce any increases in resting metabolic rate and 30min energy expenditure, at all - put simply: There was no EPOC after the high volume training. And this did not change over the whole 48h period (and I know you guys, you won't rest longer anyway ;-).

Now you may say that this was a crazy protocol, but let's do the math, let's assume the guys did squat 100kg, benched and rowed their own body weight of ~80kg and deadlifted 125kg. With 10 reps per set thats 1,000kg + 2x800kg + 1,250kg per set respectively. If they did three sets per exercise they would thus already be up to 9,950kg! If you still think that's crazy, let's hear what the scientists have to say:

"As subjects in the present study were well adapted to RT, the training stimulus needed to elicit increases in EPOC arguably needed to be much higher compared to that used in previous research  Two studies using intensities of 70% 1RM report significant increases in RMR. Melby et al. had subjects perform 6 setsof 10 different exercises for a total of 60 sets. The repetition range for this protocol was 8-12 repetitions per set. This amounts to approximately 600 repetitions performed during the course of the exercise bout. The range of load-volume lifted by these subjects was 15,000-38,000 kg. [...]" (Abboud. 2013)

The list goes on and you just have to go to your gym and I guarantee you, no matter how few people are on the floor you will see a guy who (often without noticing is) will be pounding away much more word within a single workout. Moreover, the the subjects in the present study completed their trials
with a drastically lower number of repetitions -  a mean of 199. Had they performed the crazy rep-volume of the Melby study, they would probably have come close to 50,000 kg. This raises an interesting question is "volume" correctly defined by giving the total amount of weight you lift? Or is the number of reps maybe more important as far as the after-burner EPOC is concerned?

Too much of a good thing? But what if you are a highly trained athlete?

A previous study, by Hackney et al. would support the notion that heavy lifting is an obligatory part of the EPOC equation. In the latter study, EPOC trained individuals who used a lower load-volume than the trainees in the study at hand  had increased resting metabolic rates for up to 72h (Hackney. 2008). Since the Hackney study also put an emphasis on eccentric contractions and will thus probably have lead to even greater muscle damage than the protocol of the study at hand (CK(10,000kg) = 729U/L vs.CK(20,000kg)  = 1,159IU/L), Abboud et al. speculate that ...

"[a]s protein synthesis required for repair is energetically expensive, it is logical that untrained subjects will show greater and longer alterations in EPOC post-RT. Judging by training history, strength levels and CK responses, subjects in the present study had most likely reached a higher level of adaptation than ones in previous studies, and therefore were less sensitive to the metabolic effects of recovery from RT." (Abboud. 2013)

In other words, for you, probably a seasoned strength trainee, the 'more is more' principle is not going to yield better results - even if your goal is to shed body fat. And ...

"Although RT is an important component in any weight loss program to attenuate the loss of fat free mass and therefore better preserve RMR, it is unlikely that the total energetic cost (during and post-exercise) of a typical duration workout will be adequate for significant weight reduction in highly trained recreational lifters without caloric restriction and/or additional aerobic or high intensity interval training." (Abboud. 2013)

And since I rarely encounter a conclusion that's so to the point, I'll leave you with that for today and remind you to come back tomorrow to learn, when and for which body parts doing somewhat more may still be beneficial - read me tomorrow ;-)

References:

• Abboud GJ, Greer BK, Campbell SC, Panton LB. Effects of Load-Volume on EPOC after Acute Bouts of Resistance Training in Resistance Trained Males. J Strength Cond Res. 2013 Oct 18.
• Hackney KJ, Engels HJ, and Gretebeck RJ. Resting energy expenditure and delayed-onset muscle soreness after full-body resistance trainingwith an eccentric concentration. J Strength Cond Res. 2008; 22: 1602-1609.
• Melby C, Scholl C, Edwards G, and Bullough R. Effect of acute resistance exercise on postexercise energy expenditure and resting metabolic rate. J Appl Physiol. 1993; 75: 1847-1853.

Predictive Value of Equations to Calculate Your Resting Metabolic Rate (RMR) Flawed: Results Can Be 14-29% Off

Would she still look so happy, if she knew that thee treadmill just lied to her?

I have written, said and, in person, even shouted it out often enough: Once you start to rely on the figures certain formulas generate (and this includes what your treadmill, your heart rate monitor etc. will produce, 'cause they use the same flawed formulas), you are lost.

The message of today's SuppVersity article is therefore by no means a new one. What's pretty new, though, is the study by V. Bonghana and colleagues from University of Campinas who have compared five predictive equations that are supposed to predict your and everyone else's basal (=excluding physical activity) energy demands (Bonghana. 2013).

"Start with a 15% energy deficit" - based on what?

The above, i.e. to start dieting by consuming ~15% less energy than you usually do, is my usual suggestion for anyone who's not in the "so fat that your health is in danger" zone, someone like you, maybe - someone who wants get rid of his/ her belly to finally see a at least the uppermost portion of his / her abs.

Table 1: The five equations the researchers used to calculate the predicted resting metabolic rate (RMR) that was then compared to the measured RMR (indirect calorimetry by respiratory gas analysis) of the 43 participants (Bonganha. 2013)

Now, what do you think would happen if this person was a postmenopausal women (of whom many, as we all know, love to "diet" exactly as they are told to, counting calories and what not) who is too lazy to follow my even more important advice to track her caloric intake for 2 weeks in order to get a "baseline reading"? What would happen if this woman, instead of doing just that simply used one of the calculators on the Internet and build her diet right according to the number the machine vomits out?

Figure 1: Comparison of the predicted resting metabolic rates and the mean difference to the "real" (=measured) RMR of the 43 healthy postmenopausal women who participated in the study (Bonghana. 2013)

Actually a cursory look at the data in figure 1 should suffice to tell you what the result would be. If she was lucky and the calculator used the rather uncommon Mifflin-St Jeor equation she would not lose a single pound, because she would end up right at the 1,063 kcal/day she, a 52-year young women, who's 159cm small has a totally age-appropriate BMI of 25kg/m², but a slightly high body fat level of 33%, just like the "average subject" in our experiment, needs to fuel her most basic metabolic demands (measured those are 1063.8 kcal/day). The former obviously implies that she did also take into account that she spends a few extra calories, even when she does not exercise.

Use the WHO calculation and you are lost

Guess how she got in in shape? Right! The EDC Program (learn more)

If she was not just as lucky and used the WHO equation as a baseline, she would not only overestimate her basal energy requirements by more than 30%. No, even with the 15% reduction she would be continuously gaining gaining wait... now, imagine she had also started to work out and had for once heard received some good advice, which is not to freak out about the weight gain, because it's all muscle. What? Right, she would be working away instead of towards her goal to lose weight and fat, 'cause one thing is sure.

Unless you expend more energy than you eat it is almost impossible to get rid of the belly. Unfortunately, simplistic calories in vs. calories out calculations won't help you find out whether this is the case..

The notion that exercise "alone" can, especially for those who are pretty chubby to begin with, have a "repartitioning effect" may still hold here, but it is more  likely that our imaginary post-menopausal training rookie is - if anything - gaining more muscle than fat and that's certainly not going to give her the look she is aspiring. In fact the situation would probably not be much different from the one in the study I had in the Facebook News a couple of days ago (Tibana. 2013).

Adding exercise on top of a proven (your N=1 experience) obesogenic diet rarely helps

In the course of this 8-week intervention study, the subjects, a group of 14 middle-aged (33.9 ± 8.6 years) overweight/obese women (body mass index - BMI 29.6 ± 4.1 kg/m²) underwent 24 sessions (3 times per week) of a whole body RT program with 3 sets of 8–12 repetitions maximum (RM). Unfortunately, for them without any dietary advice / incentive to modify the baseline diets that were obviously to blame for the extra-weight they were carrying.

Figure 2: Body mass, waist, hip, neck circumference, body adiposity index and visceral fat volume in middle-aged women before and after an 8-week 3x/week full body weight training intervention (Tibana. 2013)

The net result of this "intervention" was thus by no means representative of what you can achieve, when you really commit. If you discard the diet component, or even worse, fall for the common idea that you've worked out for an hour and could thus "afford" that piece of pizza, pie or panacotta, you are effectively bulking. Therefore, you should thus not be surprised, if you got strong and bulky, but don't see improvements in your body fat level, your waist line and any of the biochemical variables, i.e. fasting glucose, HbAIc, insulin,  triglycerides, HDL, and the TG/HDL ratio (not shown in figure 2), your doctor will be eyeballing.

---

Without taking a "baseline reading" and accessing where you want to go, you ain't going to succeed (read more)

Bottom line: In conjunction, the results of the Bonghana and Tibana papers only underline the necessity to (a) make a baseline assessment of your current, individual food quantity and quality(!), before you embark on any kind of diet and (b) that the notion of "exercising the fat away" is only useful when you are not making the mistake to chart your dietary intake up against whatever you believe your exercise induced energy expenditure would look like. Even if it's not pizza, pasta and panacotta you are thinking of, when you look at the figure your treadmill or heart rate monitor calculated based on similarly whacky formulas as those used for the RMR, you are still lost whenever you put more faith into a impersonal arithmetics than the signals of your own body... and this, gentleman, is true irrespective of your age and sex.

If you still insist on calculating something, you may also want to take a look at Part III / III of the Female(?) Athlete Triad Series, but please be aware that I am not liable for the damage this type of calorie counting is going to do to your physique and your psyche.

References:

• Bonganha V, Libardi CA, Santos CF, de Souza GV, Conceição MS, Chacon-Mikahil MP, Madruga VA. Predictive equations overestimate the resting metabolic rate in postmenopausal women. J Nutr Health Aging. 2013;17(3):211-4.
• Tibana RA, Navalta J, Bottaro M, Vieira D, Tajra V, Silva AD, de Farias DL, Pereira GB, de Souza JC, Balsamo S, Cavaglieri CR, Prestes J. Effects of eight weeks of resistance training on the risk factors of metabolic syndrome in overweight /obese women - "A Pilot Study". Diabetol Metab Syndr. 2013 Feb 28;5(1):11.

Fiber Up Your Foods, Omega-3 Preload For Female Fat Loss, 50+ Ways to Treat Constipation, Serotonergic Peptides in Milk, Weight Cycling & Reduced Metabolic Rates, Exercise & 102% Weight Loss From Fat - Plus: More Short News

Inulin enriched foods are good for your gut, your waistline and your pancreas (anti-diabesity effect) and what's more inulin is also on the list of anti-constipation agents,

100g that's this week's SuppVersity figure of the week and that despite the fact that it is the amount of fat you are going to gain within one year when your metabolic rate is 100kcal below where it should be (Piaggi. 2013)... Where it should be? Yeah, ok I know that's idiotic, but if you read today's news-item about the down-regulation of the metabolic rate due to YoYo-dieting the picture that emerges is that of yet another vicious cycle that leads directly into a weight spiral that knows but one direction: upwards!

Another one of today's news-items does however hint at a solution: Just lose 102% fat! What? I see I got you interested. So what are you waiting for? Lot's of good stuff today. So much in fact that let's spend no time and get right to the news-business ;-)

"Fiber up" you foods with prebiotics (inulin in particular)

Pretty obvious that these Spanish Christmas confections take a toll on your HbA1c ;-)

(Capriles. 2013; Garcia-Garcia. 2013) -- You've read about the benefits of "feeding the good guys" a couple of days ago. Now, aside from being a substrate for the purportedly beneficial gut bacteria fiber also changes the feel, taste and most importantly digestive properties of foods. A couple of recently published studies confirm that this can have pretty profound and in most cases highly desirable consequences.

Garcia-Garcia, for example, added some inulin (5%) to Turon, a traditional Spanish sweet treat that's made of toasted almonds, honey and sugar and fed 30g of the Christmas nougat-type confection to 32 healthy, normal-weight volunteers.

While the subjects in the "regular" Turon group had a slight but significant increase in HbA1c (long-term measure of blood glucose management) the blood glucose management of the 17 subjects in the active group did not budge. And while most subjects (64%, specifically those who conumed Turon as a Christmas snack on a regular basis) preferred the "classic" variety, at least 24% did actually like the inulin Turon better (Garcia-Garcia. 2013)

Gluten will interact with PPARs & gut bacteria and can thus precipitate insulin resistance (read more).

In a similar study, scientists were able to show that the addition of prebiotic inulin-type fructans to gluten-free bread (4 g of fructans per 50 g bread serving size) did

"[...] provide structure and gas retention during baking, thus improving GFB quality by yielding better specific volume, softer crumb, improved crust and crumb browning with enhanced sensory acceptance" (Capriles. 2013)

 and decreased the glycemic index and glycemic load of the gluten-free bread by 34% (from 71 to 48) and 33% (from 12 to 8), respectively.

Omega-3 loading improves weight loss in obese women

(Munro. 2013) -- According to a recently published study, a 4-week preload with 6 × 1 g capsules per day LC ω-3PUFA (fish oil) each comprising 70 mg EPA and 270 mg DHA, increased the amount of weight the female (and only the female!) participants of a very low calorie weight loss intervention lost in the subsequent 8-weeks.

Despite being statistically significant, the 1.4% increase in bod weight loss is yet not so pronounced that anyone whose been dieint with LC-PUFA preload in the past should now be fretting about having missed out on this great chance of getting ripped. If you are a man, the protocol would have been useless, anyways.

Constipated? Review offers three types of "solutions" - in some cases a literal sense

(Gelinas. 2013) -- If you are one out of five, chances are you belong to the 20% of the world's population who suffer from constipation on a regular base. If that's the case, you may want to consider one of the following "treatment" strategies, Pierre Galinas mentions in his latest review of the literature:

• 

  Table 1: Relative laxative potential of 50 food ingredients for the prevention of constipation

  Bulking agents  - They soften the stool by binding water; examples are psyllium seed husk, wheat bran, methylcellulose, calcium polycarbophil; are considered "mild" and are not habit forming, but may cause abdominal pain and bloating because of gas formation
• Osmotic agents - They also soften the stool but ba a dfferent mechanism than the bulk fiber, they create an osmotic gradient, which will distend the intestines and stimulates a contractile response; examples are lactulose, sorbitol, mannitol, polyethylene glycol (PEG), magnesium hydroxide (milk of magnesia), sodium phosphate; side effects are gas, and the offensive taste (of some)
• Softeners and lubricants  - They  lubricate (oil) and soften (detergent) the stool; examples are sodium docusate and various mineral oils; pretty milk
• Stimulants - Just like the stims in a fat burner get you going, these get your colon going; examples are epson salts (magnesium sulphate heptahydrate), bisacodyl, sodium picosulphate, sodium sulphate, magnesium oxide, phenolphthalein; they taste offensive, but don't produce gas
• Herbal teas - Provide water and can increase bowel frequency; examples are anthracenes derivatives (senna; aloe; cascara, Frangula bark); unfortunately they taste offensive and work almost immediately; moreover tolerance builds up pretty fast

As you can see there are different ways to get going with the bulk agent aka an increase in fiber intake being the only healthy long-term solution.

Even unhappy cows produce "Happy Milk"

"Mutant Milk" is homogenized milk a potential threat to your health (learn more)?

(Nongonierma. 2013) -- Three days ago a paper by Alice Nongonierma and her colleagues was published ahead of print on the website of the Journal of Food & Function. In the said paper, the researchers describe an experiment, in the course of which they were able to proof that hydrolyzed milk proteins contain a peptides that "behave as serotonin 2C (5-HT2c) receptor agonists" (Nongenierma. 2013). According to the scientists, the bioactive peptides have a relatively low molecular mass (< 1 kDa) and are hydrophobic in nature. With the 5-HT2c receptor being more than just a pharmacological target for the treatment of depression and anxiety, but also a trigger of neurogenesis (growth of new neurons) in the hippocampus (Millan. 2005), this certainly is good news for all the milk junkies out there - or could the serotonine-like effects make you fat?

Magic anti-diabetic mushrooms

(Su. 2013) -- Not what you are thinking now, folks! That's Traditional Chinese Medicine. After all, mushrooms such as Coriolus versicolor and Grifola frondosa have been used in TCM for centuries now. As a recent study by Scientsts from Kang Jien BioTech confirms rightly, so. Extracts from both mushroom had potent inhibitory effects on the carbohydrate digesting enzymes α-amylase and α-glucosidase. With Coriolus being a better inhibitor of the former and Grifola a more potent inhibitor of the latter enzymes.

How this relates to glucose control? Easy: If you don't disentangle the complex carbs your body cannot access their sugar content and if you do it only very slowly even "high" GI starches suddenly turn into low GI foods.

Weight cycling does not forestall future weight loss, but it makes it harder

Geoffrey Cannon's "Dieting Makes You Fat" was first published in 1983 but is that true? Does dieting always make you fatter and would it be better so simply surrender   (learn more)?

(Bosy-Westphal. 2013) -- While the ups and downs in body weight so many dieters are experiencing on a regular basis do not, as it was long suspected, ruin your body composition. A paper that has been published roughly a week ago in the International Journal of Obesitysuggests that another often touted downside, namely the long-term creeping down-regulation of the basal energy expenditure is unfortunately very real.

According to the analysis of the researchers from the Christian-Albrecht University in Kiel, Germany, the 27 "weight regainers" (after ~30% of loss) showed a reduced REE adjusted for changes in organ and tissue masses after weight loss that was not present in the 20 previously weight stable, yet likewise overweight / obese subjects in the control group of the researchers' 13-week dietary intervention study.

It is however not sure, whether this actually is a result of previous weight cycling or vice versa; meaning that the people with the ups and downs in body weight are the ones whose metabolism shuts down the easiest. The study at hand was obviously not able to exclude this possibility.

More than 100% weight loss from fat? How is that supposed to work?

(Hall. 2013) -- Actually this study was published late in the year 2013, that it still made it to On Short Notice has two reasons. Reason #1 is that it was an Epub way ahead of print. Reason #2 is that the figures the author reports appear to be pretty nonsensical. I mean how on earth can the projection K.. Hall from the National Institute of Health in Bethesda made based on data from the Biggest Loser camp yield a net weight loss of 24kg of which more than 100% (102% to be precise) came from the exuberant body fat stores of the (>70kg for the average participant) of the "big losers"?

For the researchers who worked with the Biggest Losers the highly successful TV show was a fluke. Having a TV station pay for their "research" certainly is something extraordinary and against and the study at hand is only the latest publication based on data from the Biggest Loser camp (read up on a previous news item)

The answer is actually pretty straight forward and underlines the efficacy of exercise as a weight loss tool that won't leave you skinny fat, but lean and more muscular. After all, the initially counter-intuitive +2% extra came from the increase in lean mass the Big Losers experienced despite being on a 1,300kcal-1,600kcal diet and working out at a "vigorous intensity" for 3.1h and 1.1h per day in phase 1 and phase 2 of the boot-camp intervention (the simulation of a diet only intervention yielded a slightly larger total weight loss yet with only 65% of the weight coming from the fat stores).

The one thing I am a bit skeptical about is whether Hall's prediction that the weight loss will be sustainable with no more than 20min/day of, once again, "vigorous" exercise per day. I mean that probably would be true in the sheltered environment of the weight loss camp. In a real life scenario, on the other hand, the super size menus, family pizzas and cosy TV couches are probably too much of a temptation for the many of the Big Losers.

---

Wine was yesterday! Chocolate liqueur is the future of healthy alcohol consumption (learn more)

That's all for today, at least as far as On Short Notice is concerned. By now the majority of you should yet be aware that there's always more... correct, the Facebook News - not sure if you notices, but you can actually see the latest items in the side-bar of the SuppVersity. To make sure you don't miss any of them it would yet be wise to simply "like" the SuppVersity on Facebook and/or register as a follower to my Twitter Account. It's hard-wired to the Facebook page, so if you are into tweeting.. maybe you prefer being notified this way.

Whatever your social media service provide of choice may be, I am pretty sure that you don't want to miss news such as the one on the total phenols, flavonoids, flavan-3-ols and proanthocyanidins of chocolate liqueur and how this may make it a better choice for your daily dose of "healthy" alcohol than wine ;-)

References:

• Carpiles VD, Aréas JADG. Effects of prebiotic inulin-type fructans on structure, quality, sensory acceptance and glycemic response of gluten-free breads. Food & Function. 03 Oct 2013 [Epub] 
• Garcia-Garcia E., Narbona E, Carbonell-Barrachina AA, Sanchez-Soriano J, Roche E. The effect of consumption of inulin-enriched Turrón upon blood serum lipids over a 5-week period. International Journal of Food Science & Technology. 2013; 48(2):405–411.
• Gelinas P. Preventing constipation: a review of the laxative potential of food ingredients. International Journal of Food Science & Technology. 2013; 48(3):445–467. 
• Hall KD. Diet versus exercise in "The Biggest Loser" weight loss competition. Obesity (Silver Spring). 2013 Oct 3. doi: 10.1002/oby.20065. [Epub ahead of print]
• Lai MN, Ng LT. Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase – enzymes related to hyperglycemia. Food & Function. 2013 [Epub ahead of print].
  
• Millan MJ. Serotonin 5-HT2C receptors as a target for the treatment of depressive and anxious states: focus on novel therapeutic strategies. Therapie. 2005 Sep-Oct;60(5):441-60.
• Munro IA, Garg ML. Prior supplementation with long chain omega-3 polyunsaturated fatty acids promotes weight loss in obese adults: a double-blinded randomised controlled trial. Food & Function. February 2013 [Epub ahead of print].
• Nongonierma A,  Schellekens H, Dinan T,  Cryan JF, Fitzgerald D. Milk protein hydrolysates activate 5-HT2c serotonin receptors: influence of the starting substrate and isolation of bioactive fractions. Food & Function. 2013 [Epub ahead of print]
• Piaggi P, Thearle MS, Bogardus C, Krakoff J. Lower Energy Expenditure Predicts Long-Term Increases in Weight and Fat Mass. JCEM. 2013; jc.2013-3529;

Forgotten Dieting Aids: Choline, Carnitine, Caffeine and the Anti-Weight-Loss Plateau Effects of Sugar and Phosphates

I bet both Flex Wheeler (left) as well as Serge Nubret (right) still knew what choline is. Something you probably cannot say of many of today's gymrats.

In view of the fact that the brief "Oldie but Goldie" post on the efficiency of a stack of carnitine, choline and caffeine as a weight loss adjuvant on the SuppVersity Facebook Wall caught so much attention, I thought that especially those of you who have not yet "liked" the SuppVersity on Facebook and have thus missed this brief reminder of these "classic" fat loss helpers would appreciate if I devote a whole post to this issue as well as another "Oldie but Goldie", I came across recently: The anti-plateau effects of succrose (plain sugar) and phosphates during phases of (very) intense dieting.

ECA was yesterday and so was CCC ;-) 

Let's start with the CCC stack, though. In the year 2000, Hongu et al. published a paper describing a rodent experiment in which they were able to show that the combination of choline, carnitine and caffeine had similar beneficial effects on the body fat and leptin levels of sedentary rodents as exercise (Hongu. 2000).

Figure 1: Fat pad weight (in g) and serum glucose, lactate, triglycerides, free fatty acids and leptin levels expressed relative to sedentary rodents on standard chow (Hongu. 2000)

With statistically highly significant reductions in the weight of the epididymal, inguinal and perirenal fat tissue and corresponding decreases in leptin, the net fat (not simply weight!) loss the 7-wk-old male Sprague-Dawley rats exhibited in face of an unaltered basal energy intake at the end of the 5-weeks study period was yet so pronounced that the question, whether these results would be replicable and, more importantly, whether they could be reproduced in human beings should already be preying on your mind.

"So you are saying it's unlikely this will work in humans, right?"

For a follow up study, the scientists recruited 19 healthy non-obese women with no history of diabetes, or cardiovascular disease (18–54y; body weight, 47.5–92.7 kg; body mass index (BMI), 18.9–35.9kg/m²; body fat, 17.9–37.8%) and repeated the experiment (Hongu. 2003); yet with a slightly different design (see figure 2) that would allow the researchers to differentiate the individual effects of choline and carnitine - unfortunately, without the third "C", i.e. the caffeine.

Figure 2: Study design of the follow up human study three years later (Hongu. 2003).

In the absence of caffeine, the combination of choline and carnitine lost its congenial partner in crime, whose job it is to squeeze the lipids out of the fat cells (lipolysis). But that's not all, the dosages used in the human trial were also significantly lower than the human equivalents of those the rodents had coonsumed three years before (see infobox to the right of the next paragraph). With appropriately high doses, the caffeine may even not have been necessary to elicit the desired fat loss effects. What is unquestionable though is thatthe caffeine induced lipolysis would have amplified any existing effect, because you obviously need enough fatty acids to be transported to the mitochondria in order to make optimal use of the increase in oxidative capacity from the other "C"s in the CCC stack.

What we have here is not a fat loss study

What were the dosages of choline, carnitine and caffeine that were used in the studies? The human equivalent doses for the rodent study from 2000 were 98mg/kg choline, 52mg/kg carnitine and 1mg/kg caffeine. In the human study from 2003 the scientists used much lower dosages of 15mg/kg choline bitartrate and only 1mg/kg l-carnitine l-tartrate per day (!) no wonder the effects on the body composition were completely absent in the human trial.

Against that background the results of this follow up study are of greater theoretical than practical value for us, as they allow some insights into the underlying mechanisms which are responsible for the profound fat loss effects the researchers observed in the rodent trial. As far as this mechanism is concerned the researchers write in the discussion of their paper:

"The mild exercise routine enhanced fat utilization as energy substrate in both supplemented groups, but not in the placebo group [This went hand in hand with a 21–27%] loss of acylcarnitines in urine [that] has not been found in individuals subjected to low or high intensity exercise without supplement. [...] It may thus be argued that increased demand for energy by exercise in choline/carnitine-preloaded individuals increases rates of fatty acid oxidation, albeit incomplete, resulting in sustained loss of acyl groups in urine." (Hongu. 2003)

I willingly admit that this hardly sounds like an explanation, so let's briefly recap the main points.

Firstly, there is the increase in fat utilization in response to the ingestion of choline and carnitine. Secondly, therese there is the loss of acetylcarnitines, i.e. a complex of carnitine + the short-chain fatty acid acetyl in the urine of the women who participated in the study.

 "Choline promotes carnitine conservation and accretion by tissues that favor incomplete oxidation of fatty acids and disposal of fatty acid carbons in urine as acylcarnitines." (Hongu. 2003)

As the scientists point out, the reason for the latter is an incomplete oxidation of long(er)-chain fatty acids and the net result is a non-negligible loss of energy in the urine. With the addition of caffeine to the equation, the total amount of fat that is available for oxidation during exercise, but more importantly also at rest (not just during exercise) would have increased, the same would apply to the amount of fat that is shuttled into the mitochondria and the amount of fat that will leave the mitochondria only partially oxidized. And what happens if you use more stored fat and use it less efficiently? Correct! The fat depots on your hips, buttocks and abs and if you still have some, the nasty inter-organ fat will be gone faster than without the use of the "CCC" stack. Will it disappear magically overnight and without any dietary and lifestyle changes? Probably not overnight, but maybe over several weeks and months.

Add sugar & phosphate to ameliorate the downregulation of the metabolic rate on a diet

YoYo-Dieting or Constant Gluttony? What Happens During Weight Cycling? And Why Does Every Diet Make You Fatter? I have answered these and related questions in a previous blogpost, already (read more)

Sounds too good to be true? Well in a way it in fact is. After all, this requires a 100% constant food intake and presumes that your body does not adapt its caloric expenditure to achieve a new steady state. That the latter is not very realistic, is probably something many of you have already learned the hard way. after all, those new steady states are actually the underlying reasons of the nasty weight loss plateaus this 2nd part of today's SuppVersity post is dealing with.

"Sugar, orange juice, carrots, ..." does this ring a bell? Yeah, I see you have heard or read about this combination before on the Internet.  No idea yet? Well another hint, then: You usually complement those foods with egg shells, which are a good source of calcium, but not in the form of calcium phosphate, but rather as the simple white powdery calcium carnbonate and thus certainly not what the results of a 1996 study by Nazar et al. would suggest the sugars should be complemented with.

In the said study the results of which were published in the Journal of Physiology and Pharmacology 16 years ago, the researchers from the Polish Academy of Science write that the addition of a phosphate supplement containing non-disclosed amounts of calcium, potassium and sodium phosphate to a 1,000kcal, high viscose fiber diet ameliorated the diet induced reduction in basal metabolic rate in the 30 female overweight study participants (+15 / +19% depending on whether the supplement was taken from week 1-4 or week 5-8 of the 8-week dietary intervention). As Nazar et al. point out, the

"[p]hosphate supplementation ameliorated also a decrease in plasma triiodothyronine level and a decrease in thyroxine to triiodothyronine ratio. [While t]here were no differences between groups in the plasma insulin, catecholamine, growth hormone, cortisol and testosterone levels[,] plasma lipids or blood glucose concentration." (Nazar. 1996)

With the thyroid hormone concentration marking the only statistically significant hormonal difference between the supplementation and placebo phases of in the Nazar studies, the similarities to Dr. Ray Peat's previously alluded highly controversial "sugar for thyroid health protocol" should be obvious.

"Ok, but if it's phosphates instead of calcium, then it must be fat instead of sugar, right? "

Often a picture says more than 1000 words: Normal (left) and repeatedly hypoglycemic rodents (learn more about the obesogenic effects of hypoglycemia)

I bet the above question is now preying on the minds of some of you. "Sugar, really?" It may sound hilarious, but as I've pointed out several times before: An energy deficit, specifically a pronounced one, is a game changer. Things that would usually precipitate weight gain suddenly don't matter, when - at the end of the day - your body has used more energy than it has been able to acquire from the foods you  ate.

Unfortunately your body hates nothing more than having to fight to fulfill his acute energy demands by tapping into its body fat stores and will therefore after a couple of days start to save energy, this is particularly true, when your brain realizes that it's beloved glucose is becoming scarce and there is no abundance of ketone bodies to use instead.

Basically this is exactly the situation that arises on a HCG-like very low calorie (800kcal/day) high protein (95% protein, 4% fat, 1% carbohydrate) such as the one the obese women in a study by Hendler et al. were following at thne Yale Clinical Research Center in the late 1980s (Hendler. 1986). The exact study protocol was a bit complicated (and nonsensical ;-) with half of the patient starting out on what I would prefer to call a 'protein only' diet and not, as the scientists do a "high protein" diet, for 15 days followed by another 15 days on a "sucrose diet" with reversed macronutrient ratios, but identical energy content. The other half dieted for 15 days, only, on the sucrose regimen (I wonder why they did not switch those to the protein regimen afterwards...?!). And one miserable wretch "consumed the high-protein diet for 30 days to serve as a control for the sequential protein-sucrose diet"

HCG like dieting: Don't do this at home!

I guess, I don't have to mention that dietary interventions like these are meant to be used in clinical settings and in very obese individuals. So, don't be bamboozled by the 9kg of body weight the subjects lost within those 30 days and try something similarly stupid at home. Our interest in this study is merely related to the effects on the resting metabolic, which were (I will list the main effects and quote excerpts from the results):

• 

  Figure 3: Effect of the sequential protein-sucrose diet on resting metabolic rate (RMR), serum triiodothyronine (T3) and plasma norepinephrine concentra- tions (Hendler. 1986)

  significant reductions in resting metabolic rate during the protein phase: "After 15 days of the hypocaloric protein diet, resting metabolic rate decreased by 354 kcal/day, or 21 percent of control values (p < 0.01)"

• restorative effects of the sucrose diet in the subsequent 15 days: "Sucrose substitution significantly increased the resting metabolic rate (+228 kcal/day, p < 0.05) to values approaching those in the control period (p = NS)."

• metabolic shut-down in the poor wretch who followed the protein only diet for 30 days: "In contrast, the single patient given the protein diet continuously for 30 days showed a progressive decline in resting metabolic rate (2,165, 1,822, and 1,628 kilocalories per day at baseline and after 15 and 30 days of the protein diet, respectively)." 

• Plummeting levels of the active thyroid hormone T3 that were only partly restored in the sucrose phase: "Changes in serum triiodothyronine levels followed the pattern of diet-induced changes in resting metabolic rate. The serum triiodothyronine level fell by 41 percent (p < 0.02) after the protein diet and then rose (by 28 percent, p < 0.02) after sucrose substitution, reaching values intermediate between control and protein diet levels. 

• Significant correlations between the drop in T3 levels and the lowered metabolic rate: "There was a significant correlation between the changes in the serum triiodothyronine level and resting metabolic rate during the sequential diets (r = 0.701, p < 0.01).

• Only minimal signs of a reduced sympathetic tone in the protein phase, none in the succrose phase: "Supine norepinephrine concentrations were slightly, but not significantly, reduced by the protein diet (10 percent) and failed to change significantly when sucrose was substituted. 

• No correlation between epinephrine and the resting metabolic rate: "There was no correlation between changes in the supine norepinephrine concentration and resting metabolic rate."

Interestingly, no significant changes in any of the measured parameters, i.e. serum triiodothyronine (T3) levels, epinephrine and, most importantly, the reductions in metabolic rate were observed in the patients who followed the succrose diet.

---

 Does it make sense to eat carbs on a lean bulk as well, or will they just make you fat *scary sound*? Learn more in a previous SuppVersity post.

So what's the take home message, here? Don't worry, as I've already pointed out, I am neither suggesting that you should follow a pure sugar nor a 800kcal diet. And you can be sure that the negative effects on the resting metabolic rate are "diet dose depend" (meaning the harder and imbalanced you diet, the more pronounced they will be). What I am suggesting is that there is reason I keep repeating my mantra "you cannot live on protein alone", both here, as well as on the SuppVersity Science Round-Up. So if you insist on going on a "low carb diet" you better do it right and turn to a  high fat diet (<15% protein), use regular really high carb (including sugar!) refeeds or periods of normal high(-ish) carb intake to keep your metabolism chugging along nicely.

A final note on a possible CCC protocol: I actually did not want to write that down, but I know you will be asking anyways. Please keep in mind though, that I cannot tell you the optimal dose and that I have more than just second thoughts about taking high amounts of choline (see potential side effects next to the respective bullet point below).

• Max. (!) 3g choline: Take the choline (bitartrate or citrate, no funky GPC or similar junk) with meals split across the day, but refrain from taking the human equivalents (HED) from the rodent study, I suppose 3g could already make you smell like a fish. Watch out for potential side effects, such as cramps, nausea, vomiting, dizziness, high blood pressure, or acne-like skin rash. Stop the supplement immediately, if you experience any of those. Also make sure to get adequate amounts of potassium and magnesium.
• 3-5g of carnitine: Stick to the l-tartrate or regular form of carnitine. Take the carnitine in 3 doses best on empty (learn more about in the Amino Acids for Super Humans Series). 
• 200mg sevings of caffeine: Use the caffeine whenever you are fasted for at least 90min or before you are working out. Don't take more than 400mg, max. 600mg per day and - needless to say - don't take it before bed.

Again keep an eye on side effects and don't expect any miracles! This is a supplement to help you lose fat, not to make you lose fat.

Once you've got these fundamentals right you may want to consider adding in the CCC stack and a phosphate supplement to promote - not to induce - fat loss.



References:

• Hendler RG, Walesky M, Sherwin RS. Sucrose substitution in prevention and reversal of the fall in metabolic rate accompanying hypocaloric diets. Am J Med. 1986 Aug;81(2):280-4.
• Hongu N, Sachan DS. Caffeine, carnitine and choline supplementation of rats decreases body fat and serum leptin concentration as does exercise. J Nutr. 2000 Feb;130(2):152-7.
• Hongu N, Sachan DS. Carnitine and choline supplementation with exercise alter carnitine profiles, biochemical markers of fat metabolism and serum leptin concentration in healthy women. J Nutr. 2003 Jan;133(1):84-9.
• Nazar K, Kaciuba-Uściłko H, Szczepanik J, Zemba AW, Kruk B, Chwalbińska-Moneta J, Titow-Stupnicka E, Bicz B, Krotkiewski M. Phosphate supplementation prevents a decrease of triiodothyronine and increases resting metabolic rate during low energy diet. J Physiol Pharmacol. 1996 Jun;47(2):373-83.