Losing Weight Is Easy. Staving It Off Ain't: A Lesson in High vs. Very High Energy Restrictions - What's More Effective?

If you tried to follow all the "good advice" you can find on the Internet and in the myriad of diet books and ebooks, I can guarantee that you are going to get fatter, not leaner. When it comes to dieting, there is after all nothing worse than doings things by halves... but is this also true for cutting your energy intake by half?

Ok, I freely admit that I have tricked you. Despite the fact that the study at hand is a randomized human study, it is possible that it is not 100% relevant for all of you. After all, the subjects in Lisa M. Nackers, Kathryn R. Middleton, Pamela J. Dubyak, Michael J. Daniels, Stephen D. Anton and Michael G. Perri's latest experiment were not exactly as lean as I would expect most of you are (this reminds me that I wanted to put up a questionnaire).

In other words, the subjects were obese. Whether the fact that they were also female is as grave a difference is something I cannot tell, but in view of the fact that this makes weight loss even harder, I would say it's probably not much of a problem if you are a man (and let's be honest, don't we all have a female friend who is constantly complaining about her weight, guys?)

Inspite of a mean BMI of 37.84kg/m², the relative results of this study will probably apply to a lean person, as well. In other words, if the women in the study at hand were randomized to consume either 1,000 or 1,500 kcal/day per day, I would suggest that a lean man / woman with much lower fat reserves to draw on should never go below 1,500 / 1,200 kcal/day.

So, this is not you, but the results are still intriguing

The important question was and still is now: What's more effective? A high, or a low caloric deficit? As a seasoned SuppVersity student, you will be aware that the "grazing approach to lose weight" in the course of which you reduce your calorie intake by only 5%, to make sure that (a) it's not getting to hard for you, or (b) you are not losing any muscle, will fail miserably and can result in serious deteriorations of your body composition (learn more). But what about the alternatives? Which of them, i.e. the -50% or the -25% diet, is appropriate for the obese ladies and which could be a model for yourself?

No exercise = not necessarily negligence: I know, for physical culturists like you and me, it sounds hilarious that the subjects were not encouraged to actually work out. If we are honest, we all know that this would have been the first thing the participants dropped in the unsupervised phase II of the study. I was thus not negligent to tell the subjects to simply follow the 10,000 steps per day approach as it is recommended by Donelly et al. in their often-cited 2009 ACSM Position Stand.

We know from previous research that lifestyle interventions are capable of inducing weight reduction of 7-10% and corresponding decreases in risk factors for heart disease and diabetes within weeks (DPPRG. 2002; Look AHEAD Research Group. 2010; Butryn. 2011).

"Get Your Protein, Veggies & Fruits and Get Them Regularly: High(er) Meal Frequency (6 à Day) + High(er) Protein Diet Support Weight & Fat Loss on a Diet " | learn more

"Nonetheless, behavioral changes initiated during lifestyle treatment often are poorly maintained and regaining of lost weight is common, thereby diminishing health benefits of weight loss. As a variety of biological and environmental influences make it difficult to maintain large dietary changes, a number of researchers and professional organizations have proposed a ‘‘small change’’ approach to weight management, arguing that small sustainable changes will produce better long-term weight control than larger changes that are unlikely to be sustained.

Alternatively, other researchers have observed that larger initial dietary changes, and the greater, more rapid weight losses they produce, are more likely to reinforce the weight-change process and lead to better long-term weight-loss outcomes." (Nackers. 2013)

In other words, as of now, it's mostly a question of faith, not one of scientific evidence, whether you answer my previous question in favor of the "small change" or the "massive reduction" approach.

Fast and hard, or slow and steady? How would you like it?

Ah, well... this is of course before you've taken a look at the results of this 12 months dietary intervention, of which the researchers speculated that it would demonstrate greater short- and long-term weight losses, and higher rates of weight loss in the metabolically relevant >5% body weight region in the 1,000kcal/day vs. 1,500kcal/day group.

If you do now finally take a peak at the actual results after 6 months with group-care (supervision) and the subsequent unsupervised 6 months "weight maintenance" (mind the inverted commas ;-) phase, what would you tell your chubby female friend she'd do? Cut back drastically or moderately?

Figure 1: Weight loss in the supervised (0-6m) and unsupervised (7-12m) of the study; the %-values indicate the relative difference between the 1,000kcal and the 1,500kcal diets (Nackers. 2013)

If we go by the results of the study at hand, the answer probably is: "Cut back drastically." Someone who is, unlike the ladies in the study at hand, not putting his health at risk if he maintains his current body weight, would yet probably be better off running a "moderate" caloric deficit of 25-30%. This could help him or her minimize the dreaded "fat rebound".

I mean, despite the fact that the post-diet weight gain in the study at hand was less pronounced than the average Internet craze about "yoyo"-dieting would suggest, any form of uncontrolled weight gain after weeks or months of serious dieting could potentially raise your body fat levels to previously unexpected new heights.

You can learn more about dieting at the SuppVersity

Chronic Dieting
➫ Fat Athletes

Diet Down to Below 5% BF

Overtraining & Undereating

Calculate your Energy Intake!

Half As Heavy, Twice As Fat!

5% Energy Deficit Makes You Fat!

For someone who was lean, when he or she started out dieting, the endless circuits of "cut back drastically" <> "gain fat rapidly" certainly entail the risk of making the highly undesirable transition from having a small gut, but enough muscle to make up for that (metabolically), to having the same or even a bigger gut, but no muscular metabolic currency to balance it. That this is very bad news for both your health and sex-appeal is something I shouldn't have to tell you, right (learn more about skinny fats).

 You cannot program weight loss for all!

Even in the study at hand, we can find evidence for one of the fundamental messages researchers who are dabbling with diet and nutrition appear to be too afraid to tell their financiers: There is no magic formula. It is thus not surprising that Nackers et al. observed that a "subset of participants may not benefit from this level [1,000kcal only] of, baseline caloric" (Nackers. 2013) intake.

When we look more closely at the underlying reasons, it becomes clear that the baseline energy intake, which is - even in the morbidly obese - a(n allegedly unreliable) gauge of the basal energy requirements of an individual determined, whether the high caloric deficit worked, or sucked: 

"Breakfast Keeps You Lean" Myth or Mystically True?" | find out

"Participants with 'high' baseline caloric intake ( 2,000 kcal/day) regained more weight during months 7-12 if assigned 1,000 kcal/day than those with 'low' baseline caloric intake (<2,000 kcal/day).

For individuals who consumed 'high' levels of baseline calories, the prescribed intake of 1,000 kcal/day required a reduction in energy consumption of 50% or more — a level that may be unsustainable long term." (Nackers. 2013)

In their discussion of the results, the authors rightly point out that "this findind holds important treatment-matching implications" - implications, every Suppversity reader has been aware of for years:

"At the start of lifestyle interventions, participants reporting 'high' baseline calorie levels may benefit from energy prescriptions based on either a percentage of their baseline intake (e.g., 25-50% reduction) or a projected amount of weight change per week (e.g., 0.50-0.75 kg) rather than a fixed energy intake, such as 1,000 kcal/day." (Nackers. 2013)

With their last suggestion, i.e. the formulation of a "less restrictive calorie goal" for a phase of "extended care treatment" that would be "gradually moving participants from 1,000 to 1,250 to
1,500 kcal/day" that would also allow for one or another "cheat" by providing "acceptable intake goals" instead of inflexible calorie values, Nackers, Middleton, Dubyak, Daniels, Anton, and Perry eventually formulate a bottom line to their study that should look vaguely familiar to all of you for whom this is not the first visit to the SuppVersity.

I am not sure, if you all remember that, but the energy deficit Adelfo Cerame Jr. ran during the contest preps he logged, here at the SuppVersity (read them), was always in the 15-30% range. His success would confirm my previous statement that the "radical approach" (-50%) is only appropriate for those of you who still have a very long way to go.

Bottom line: If you asked me if we can learn something new from the study at hand, I am reluctant to say "Yes, we can!". The notion that obesity requires rapid weight loss even if that implies a larger post-intervention weight (re)gain should after all not be news to any of you.

The experimental confirmation that the weight rebound does not (necessarily) ruin an obese individual's weight loss success, on the other hand, is news. It would argue in favor of an aggressive dietary intervention and - as the scientists point out in their discussion of the results - a staggered return to a lower caloric deficit in the months to come. I mean, despite the upheaval about  Abercrombie & Fitch not offering "plus size" clothes, one thing should be 100% clear: 90kg, which is the average weight of the ladies in the 1,000kcal group after 6 months, is not a normal body weight for a 145cm tall 52 year old woman, right?

References:

• Butryn ML, Webb V, Wadden TA. Behavioral treatment of obesity.Psychiatr Clin North Am. 2011;34:841-859.
• Donnelly JE, Blair SN, Jakicic JM, Manore MM, Rankin JW, Smith BK. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc. 2009;41:459-471.
• Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002;346:393-403.
• Nackers LM, Middleton KR, Dubyak PJ, Daniels MJ, Anton SD, Perri MG. Effects of prescribing 1,000 versus 1,500 kilocalories per day in the behavioral treatment of obesity: A randomized trial. Obesity (Silver Spring). 2013 Dec;21(12):2481-7. 
• The Look AHEAD Research Group. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus. Arch Intern Med. 2010;170:1566-1575.

Leucine, Insulin & Vitamin D*: A Hypertrophy Boosting Triplet That Does Not Make It From the Dish to the Gym? Evidence & Counter-Evidence from Human Trials

If you could simulate a workout at the beach in the petri dish, its beneficial health effect would be all the rage ;-)

I am pretty sure all of you still remember the recent post about the literal muscle building effect of vitamin D, right (see "Vitamin D Builds Muscle")? Me too, and so I was almost tricked to believe I was looking at the Girgis study, when I scanned the contents of the latest issue of Molecular Nutrition & Food Research, in which you'll with the telling title: "1,25(OH)2-vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes". Ah, ok, I see that's not exactly easy to understand. Well, in plain English this means as much as...

Calcitriol boosts the anabolic effect of leucine & insulin

If your read the "Vitamin D Builds Muscle" article, you should actually remember the dichotomous nature of the effects vitamin D had on muscle cell hypertrophy (which goes up) and proliferation (which goes down). This was after all the most intriguing result of the Girgis study (go back). The new data from the paper at hand, which is likewise dealing with in-vitro effects of vitamin D, does now provide us with some additional information on the underlying mechanisms of the hypertrophy effects.

Figure 1: Protein synthesis, insulin receptor expression and the levels of p-AKT, p-mTOR, and p-70S6K, all regulators of skeletal muscle protein synthesis in muscle cells with and without additional 1,25(OH)2D3 in a leucine + insulin filled Petri dish (Salles. 2013)

If we go by the data in Figure 1 it's obvious that the latter is driven by a direct amplifying effect of 1,25(OH)2D3, the active form of vitamin D, aka calcitriol, on the leucine and insulin induced increase in muscle protein synthesis. Unfortunately, this does not tell us a word about the potential consequences of the anti-proliferative effects of vitamin D on long-term increases in muscle size and the repair of damaged muscle fibers.

Vitamin D and health - What the latest systematic review says: As long as you look at things at the population level or sit in your well-climatized lab next to the Petri dishes, vitamin D is king. When you look at the real world, of which I still believe that it is populated by individuals, the excitement appears to be unwarranted. The most recent systematic review that has been published today in the (most) prestigious medical journal The Lancet says: "The discrepancy between observational and intervention studies suggests that low 25(OH)D is a marker of ill health. Inflammatory processes involved in disease occurrence and clinical course would reduce 25(OH)D, which would explain why low vitamin D status is reported in a wide range of disorders." (Autier. 2013) -- in other words: Being sick will lead to reduction ins 25(OH)D and not vice versa.

It is nevertheless intriguing to see, how the myotubes that had been cultured in 1,25(OH)2D3 solutions at 0, 1, or 10 nM for 72 h reacted to the leucine and insulin challenges. 14–16% increases in fractional protein synthesis rates (FSR) and an increased expression of insulin receptors, of which we can hope that it would also translate into increased glucose uptake into the cells. Assuming that similar effects occur in vivo and in a normal vs. high vitamin D environment, these benefits would be more than just statistically significant.

Ok, that's an in vitro study, so why do you discuss it at all?

If the above is what you've just been thinking, you know me quite well by now. I would indeed not have wasted a whole SuppVersity article on this vitamin D paper, if it would not contradict the real-world results of a recent randomized, double-blind, placebo-controlled study from the University of Oslo so "nicely".  In this paper, a group of Swedish researchers probed the effects of provision of 1,000IU and 400IU of vitamin D3 per day on 251 healthy adult men and women (age 18-50 years; Knutsen. 2013). 

Despite the fact that the vitamin D levels of the subjects almost doubled, none of the strength and performance parameters, i.e. jump height, handgrip strength and the chair-rising test, showed pre vs. post differences that differed from those in the control group.

Figure 2: Relative pre vs. post changes in jump height, grip strength and the time it took the subjects to complete the chair test; no statistically significant inter-group differences were observed (Knutsen. 2013) vs. relative increase in strength (no inter-group differences) in obese, vit D deficient resistance trained individuals (Carillo. 2013)

This in turn raises the question, whether all our new enthusiasm about 'vitamin D' (in the broad sense, i.e. D3, 25(OH)D3 and 1,25(OH)2D3) was misplaced. That's unquestionably a tricky question and if those "enthusiasm" was triggered by the idea that vitamin D would have independent anabolic or ergogenic effects, the answer is probably "Yes". If we are yet talking about the general role of vitamin D in the complex concert of muscular health, the answer must be "No!" There are, after all exceptions to the "vitamin D does not build muscle rule" that applies so nicely to the Knutsen study - there aren't many, but they are there.

The study Carillo et al., for example (Figure 2, right). If you take a look at the results , it's easy to see that for the twenty-three overweight and obese (age: 26.1±4.7 y; BMI: 31.3±3.2 kg/m², body fat: 43%) subjects with insufficient vitamin D levels (25-hydroxyvitamin D: 19.3±7.2 ng/ml) the researchers from the Purdue University recruited for their experiment the 4000IU of supplemental vitamin D each of them received on a daily basis had the expected effect on the resistance training induced increase in peak power and reduction in waist-to-hip ratio (not shown). The effect size is however is pathetic and the only thing that was "significant" - imho statistically, only - was the peak power in the vitamin D group.

A brief note on 25(OH)D vs. 1,25(OD)2D3: I know that it may sound as if it sucks that taking D3 supplements won't increase the amount of calcitriol in your veins, but if it did, I know more than a handful of people whose trust in some gurus would already have cost them a kidney or even their lives. There is a good reason that calcitriol is a prescription drug, because a dysregulation of the 1,25(OH)2D3 levels in the blood will increase the calcium deposition in the organs and vasculature (Bas. 2006) and would thus have the opposite effects most people expect from their high dose vitamin D3 supplementation regimen.

Bottom line: On paper, the real world-evidence from vitamin D deficient obese individuals in Carillo's recent study does supports the notion that vitamin D is an important facilitator of skeletal muscle protein synthesis, what it does not do, though is provide the missing conclusive evidence that being in the upper tertile of the physiological range (not restoring deficiencies as in Ceglia. 2013, for example) has beneficial real-world effects on muscle strength or size.

If you take another look at the doses the vitamin D enthusiasts from the Girgis study bathed their cells in, that the Swedes used active vitamin D, i.e. 1,25(OH)2D3 and that there is no direct relation between vitamin D3 intake, the serum levels of 25(OH)D3 and the amount of calcitriol (1,25(OH)2D3) your cells are exposed to, it's actually not surprising that the muscle building effects don't translate from Jérôme Salles' calcitriol saturated Petri dishes into the real world of the 251 participants of the Knutsen and the majority of the other vitamin D3 supplementation studies, is it?

References:

• Autier, P. et al. (2013) Vitamin D status and ill health: a systematic review. The Lancet Diabetes & Endocrinolog, Available online 6 Decembee
• Bas, A., Lopez, I., Perez, J., Rodriguez, M., & Aguilera‐Tejero, E. (2006). Reversibility of Calcitriol‐Induced Medial Artery Calcification in Rats With Intact Renal Function. Journal of Bone and Mineral Research, 21(3), 484-490.
• Ceglia, L., Niramitmahapanya, S., Morais, M. D. S., Rivas, D. A., Harris, S. S., Bischoff-Ferrari, H., ... & Dawson-Hughes, B. (2013). A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women. Journal of Clinical Endocrinology & Metabolism, jc-2013.
• Knutsen, K. V., Madar, A. A., Lagerløv, P., Brekke, M., Raastad, T., Stene, L. C., & Meyer, H. E. (2013). Does Vitamin D Improve Muscle Strength in Adults? A Randomized, Double-blind, Placebo-controlled Trial Among Ethnic Minorities in Norway. Journal of Clinical Endocrinology & Metabolism, jc-2013.
• Salles, J., Chanet, A., Giraudet, C., Patrac, V., Pierre, P., Jourdan, M., ... & Walrand, S. (2013). 1, 25 (OH) 2‐vitamin D3 enhances the stimulating effect of leucine and insulin on protein synthesis rate through Akt/PKB and mTOR mediated pathways in murine C2C12 skeletal myotubes. Molecular nutrition & food research.

Weightloss Supplements Exposed: Green Tea & Probiotics. Fat Loss, Energy Expenditure, Fat Oxidation, Sex & More

Yesterday at Starbucks: "I just ordered a bottle of probiotics!"

In view of the fact that all the feedback I got in response to the re-installment of the Short News was positive, I guess you won't mind if I use the chance and bundle the two soon-to-be-published weight loss studies from the British Journal of Nutrition into a Weight Loss Supplement Mini-Special of the SuppVersity Short News.

If you were actually sitting next to you, I would probably ask you, whether you'd prefer the good, or the bad news, first!? Well, I guess I'll start with the bad one, then: Green tea sucked - again!

ZERO effect of EGCG supplementation in overweight women

To examine the effects of green tea epigallocatechin-3-gallate (EGCG) on the changes in body composition (! not just weight), energy and substrate metabolism, cardiometabolic risk factors and liver function enzymes after an energy-restricted diet intervention in obese women, a group of researchers from the University of the Basque Country in Spain recruited a group of 83(!) obese (BMI 30-40 kg/m2) pre-menopausal women (Mielgo-Ayuso. 2013).

The women were randomly assigned to consume either 3x100 mg/d of EGCG or placebo (lactose) with each of their three main meals for 12 whole weeks. During those twelve weeks, all women followed a specifically designed low-energy mixed (55 % carbohydrates, 30 % lipids and 15 % proteins) diet that provided ca. 600 kcal/day energy less than the women would need to maintain their body weight. The energy content and macronutrient composition of diets were designed to achieve a weight loss of 0.5 to 1 kg per week, as it was observed by Davis et al. (2006) and Bantle et al. (2008) on very similar regimen. As the scientists point out, the "dietary instructions were reinforced weekly by a dietitian" (Mielgo-Ayuso), to optimise compliance.

Figure 1: Changes in body composition, energy expenditure and fat oxidation, left; changes in glucose, cholesterol metabolism and inflammation, right (Mielgo-Ayuso. 2013)

I am not sure how compliant the participants actually were, but in view of the fact that the women were advised not to change their physical activity habits during the energy restriction program, the relatively meager and statistically non-significant changes in body weight (-0·3 kg, p > 0.05) and fat mass (-0·7 kg, p > 0.05) are probably not really surprising. It is nice to see, though, that the women lost more fat than total mass - muscle loss was thus not an issue for the ladies.

What was not to be expected, though, - at least if you believe a single word of the hype about green tea supplements - were the non-existent effects of the purported weight loss supplement on  energy expenditure, fat metabolism, HOMA-IR (insulin sensitivity), total cholesterol, LDL-cholesterol, or triglycerides. In fact, the only good thing about the whole EGCG intervention was that the recently observed negative effects on the liver did not occur, either.

SIGNIFICANT Effect W/ 16 Million CFU of Nestlé's Lactobacillus rhamnosus strain

Want to check out the patent?

Despite the fact that the overall results are much more exciting than those in the previously discussed green tea study, I'd advise you to keep calm. We are after all dealing with another Nestlé study on a patented strain of Lactobacillus rhamnosus (LPR), i.e. "CGMCC1.3724" (date patented: 2012-05-10; #20120114622), and cannot tell how many never published negative study results the Nestlé guys had to dispose of, before Marina Sanchez et al. finally produced study results that pleased the marketing division of this multinational corporation.

What? Ok, ok... let's get back to the facts: The scientists from the Laval University and the Nestlé Research Center randomized a group of one-hundred fifty-three 18 to 55 year-old obese men and women to receive either a placebo or the said LPR formulation with 1·6 × 10⁸ colony-forming units of LPR and additional oligofructose and inulin per cap for a total of 24 weeks.

In the course of the first 12 weeks (phase 1), each participant received a personalised diet plan that would have him or her consume 500 kcal/d less than he or she'd need for weight maintenance (just as an aside, that's 100kcal more than for the subjects in the green teas study). During phase 2, each participant received a personalised diet plan without energy restriction. The good thing, the resting energy expenditure (REE) was actually measured: after a 12 h overnight fast in subjects having had rested for at least 15 min in a standardised supine position. This procedure was repeated thrice: (1) At baseline, (2) after the weight-loss and (3) after the second phase weight-maintenance periods using indirect calorimetry.

Figure 2: Changes in body composition (all data in kg) in men (left, blue) and women (right, orange) after weight loss (ΔW12) and weight maintenance (ΔW24) phase (Sanchez. 2013)

The data in figure 2 confirms what the abstract says: "The intention-to-treat analysis showed that after the first 12 weeks and after 24 weeks, mean weight loss was not significantly different between the LPR and placebo groups when all the subjects were considered."

Figure 3: Changes in metabolic parameters, i.e. energy intake (kcal/day), resting energy expenditure (REE, kcal/day) and respiratory quotient (RQ, remember: low RQ = high fat, low carb oxidation) after 12 and 24 weeks (Sanchez. 2013)

It does yet also confirm - and that there was a significant treatment × sex interaction, observed with the women in the treatment group losing significantly more weight than those in the placebo group (P= 0·02). More importantly, though...

"[...w]omen in the LPR group continued to lose body weight and fat mass during the weight-maintenance period, whereas opposite changes were observed in the placebo group."

For the unlucky men, on the other hand, the (unquestionably expensive) supplement didn't do sh*t: Their "changes in body weight and fat mass during the weight-maintenance period were similar" irrespective of whether they received the placebo or the active treatment.

Whether this was the reason or a consequence of the fact that the the men didn't show similar significant reductions in circulating leptin, as the women is questionable. Based on the fact that the relative abundance of bacteria of the Lachnospiraceae family in faeces increase only in women, we do yet have to assume that the missing reduction in leptin, as well as the absence of the significant body fat reductions, the researchers observed in their female subjects was simply a results of ...

• under-dosing - the same the 1·6 × 10⁸ colony-forming units of LPR that was sufficient for the average woman (body weight ~89kg) could have been too low for the guys (body weight ~104.3kg) 
• dietary interference - there could have been something in the diets of the guys that ruined the effects of the supplementation (lactobacilli are not exactly friends of meats and we all know that men love their meat ;-)
• different baseline gut microbiome - it goes without saying that you cannot place a group of rabbits in forest full of predators and expect them to survive; similarly the LPR spores may have come off second in the guts of the men, because they have a less "LPR-friendly" baseline colinization
• fundamental sex differences - at the moment I am not sure what the underlying reasons could be, but it's not impossible that hormonal difference could have played a role as well

I am pretty sure that I could come up with a whole host of additional, increasingly bizarre ad-hoc explanations for the null-effect Marina Sanchez and her colleagues from the Laval University and the  Nestlé Research Center in Lausanne observed in their male study but would rather conclude this news-item with the scientists own funky, but not unlikely explanation: Men are simply too good at dieting!

True: Women have a harder time losing weight even with high protein | more

As the authors point out, we know from previous trials (and corresponding SuppVersity posts, read more) that men are generally more prone to respond to a negative-energy balance intervention than women - and that's true irrespective of whether it is an exercise-training programme (Tremblay. 1984), a diet– exercise programme (Doucet. 1999), or a session of exercise and of mental work (Pérusse-Lachance. 2013). Plus, if you look at the data in figure 2, you'll see that this is actualy "concordant with the results of the present study that shows higher weight loss in men in the placebo group than in the women". Sanchez et al. do now believe that the high baseline success "abolished this difference" (Sanchez. 2013).

In view of the fact that there was a difference in a single low-abundance taxonomic group  (Prevotellaceae) between the baseline gut microbiome of the male and female study participants, I would still not exclude that the different baseline gut microbiomes could at least have added to the 'effect abolishing effect' of the sex-specific ease of weight loss in men. I mean, why wouldn't the feces of the men show an increase in lactobacillus spores, if the supplement worked?

Bottom line: Today's installment of the short news is very characteristic of the dilemma with weight loss supplements. We are just realizing that the classic thermogenic 'rodent fat burner' don't really work in humans. Against that background the rise of supplements that target the gut microbiome and exert much more complex body recompositioning effects comes in the nick of time.  Unfortunately, our understanding of the complex interactions between the gut microbiome and our immune system in the context of the emerging science of immunonometabolism is so incomplete (Mathis. 2011) that we are more or less groping in the dark, whenever we supplement subjects, patients or even ourselves with allegedly healthful bacteria.

All alleged benefits aside,  "specificity", the 2nd Principle of Sensible Supplementation, should keep you away from the next best GNC or online supplement store. The two studies at hand do after all not warrant the use of either green tea or lactobacillus supplements as weight loss aids in lean, healthy and active  men or women.

Accordingly, the observation that green tea supplements won't help sedentary over-weight women to lose weight appears to be much more reliable than the allegedly impressive weight loss effects of the probiotic during the "maintenance phase" of the Sanchez study.

We must however not forget the respective constraints of the research design and irresponsibly over-interpret the results of the EGCG study to (a) the potential benefits of regular 'whole' tea consumption in the average, non-obese individual (Wu. 2003) or (b) visceral fat loss in diet + exercise interventions in obese individuals (cf. Maki. 2009). Similarly, the fact that obese women will lose weight on a LPR supplemented maintenance diet is very unlikely going to translate to lean, athletic folks like you and me. According to the 2nd Principle of Sensible Supplementation, which is "specificity" (learn them all), I don't see you or me heading over to the next best online shop to buy LPR or EGCG supplements - irrespective of the promising results of the Sanchez trial.

References: 

• Bantle JP, Wylie-Rosett J, Albright AL,et al.(2008) Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. Diabetes Care31, Suppl. 1, S61– S78.
• Davis NJ, Emerenini A & Wylie-Rosett J (2006) Obesity management: physician practice patterns and patient preference. Diabetes Educ32, 557 – 561. 
• Maki, K. C., Reeves, M. S., Farmer, M., Yasunaga, K., Matsuo, N., Katsuragi, Y., ... & Cartwright, Y. (2009). Green tea catechin consumption enhances exercise-induced abdominal fat loss in overweight and obese adults. The Journal of nutrition, 139(2), 264-270.
• Mathis, D., & Shoelson, S. E. (2011). Immunometabolism: an emerging frontier. Nature Reviews Immunology, 11(2), 81-83.
• Mielgo-Ayuso J, Barrenechea L, Alcorta P, Larrarte E, Margareto J & Labayen I (2013). Effects of dietary supplementation with epigallocatechin-3-gallate on weight loss, energy homeostasis, cardiometabolic risk factors and liver function in obese women: randomised, double-blind, placebo-controlled clinical trial. British Journal of Nutrition, available on CJO2013. 
• Tremblay, A., Despres, J. P., Leblanc, C., & Bouchard, C. (1984). Sex dimorphism in fat loss in response to exercise-training. Journal of obesity and weight regulation.
• Wu, C.-H., Lu, F.-H., Chang, C.-S., Chang, T.-C., Wang, R.-H. and Chang, C.-J. (2003), Relationship among Habitual Tea Consumption, Percent Body Fat, and Body Fat Distribution. Obesity Research, 11: 1088–1095.

Protein Wheysting?! No Significant Increase in PWO Protein Synthesis W/ 40g vs. 20g Whey, But 100% Higher Insulin, 340% More Urea & 52x Higher Oxidative Amino Acid "Loss"

No, I don't think the results would have been different, if the subjects had been young women. For older guys and gals, on the other hand, I am not 100% sure.

It has been a while since we've been taking a look at one of the two or three dozen "whey increases muscle protein synthesis" studies and, officially, we would have to wait not just for Santa, but actually until January 2014 to take a glimpse at the results Oliver C Witard, Sarah R Jackman, Leigh Breen, Kenneth Smith, Anna Selby, and Kevin D Tipton present in their soon-to-be-published paper in the journal of the American Society for Nutrition (Witard. 2014).

The intention of the researchers was (yet again) to "characterize the dose-response relation of postabsorptive rates of myofibrillar MPS to increasing amounts of whey protein at rest and after exercise in resistance-trained, young men", (Witard. 2014). This is nothing new, but still right up the average SuppVersity reader's alley, I suppose.

So what about the study design

The design of the study was simple. The 48 healthy volunteers consumed a standardized, high-protein
(0.54 g/kg body mass) breakfast. Three hours later, they all performed a standardized bout of unilateral exercise, consisting of 8x10 leg presses and leg extensions at 80% of their individual, predetermined one-repetition maximum. "Immediately" (max. 10min) after they were done with the leg workout the volunteers consumed

• 0g, 10g, 20g, or 40g whey protein isolate

as a post-workout protein shake, of which I don't have to tell you that it was likewise... standardized, right! The subjects were then hooked up with the necessary instruments and tools to measure their

• postabsorbtive rates of myofibrillar protein synthesis (MPS) , 
• whole-body rates of phenylalanine oxidation and 
• urea production 

over a 4-h period (the stopwatch started ticking the very moment the subjects had ingested the protein shake) in all four arms of this parallel research design, single-blind study with 7 subjects in each of the 0, 10, 20, and 40g whey protein isolate groups.

Change (%) in myofibrillar and sarcoplasmic protein synthesis after ingestion of 25g whey at rest (FED) and resistance exercise (FED-EX) after 3h and 5h (Moore. 2009a)

Just a reminder: You do remember that there is another muscular compartment where we can measure protein synthesis? Right? The sarcoplasma, i.e. the zone around the myofibers, where the satellite cells reside. At least for the exercised leg, in the study at hand, this may not be that important, though, because "in contrast [to protein feeding at rest], resistance exercise rapidly stimulates and sustains the synthesis of only the myofibrillar protein fraction after protein ingestion" (Moore. 2009; my emphasis). The word "only" is slightly misplaced. If you look at the figure on the left, it's obvious that "mainly" or "more significantly", would probably be more accurate.

Now that you know all the important details about the study design, it's almost time to take a look at the results. Before we finally do that, let's just briefly recapitulate the results of (Cuthbertson. 2005) who observed that 10 g EAAs at rest and (Moore. 2009b) who observed that 20 g egg protein after exercise were "optimal for the maximal stimulation of MPS in young adults". This is after all, what the researchers hypothesis that "20 g of whey protein (~10 g EAAs) would be sufficient for the maximal stimulation of myofibrillar-MPS rates at rest and after resistance exercise in trained, young men" (Witard. 2014) was based on.

Figure 1: Post-exercise serum insulin (AUC, µmol/ml x 4h) and leucine peak (mmol/ml), total phenylalanine oxidation (AUC µmol/ml x 4h x 100), urea production (AUC µmol x 4h) and plasma urea (AUC mmol/l x 4h), as well as myofibrillar protein synthesis (MPS) in the 4h after the workout (Witard. 2014).

As you can see, the actual study results confirm the scientists suspicion: The 20g of whey protein did maximized the myofibrillar protein synthetic response to a hypertophy-oriented leg training workout (see bottom line for an explanation of why I chose to underline the word "leg") in rested and exercised muscle of ~80-kg resistance-trained, young men.

We are talking about statistical significance here: I know what you are going to tell me, now. And yes, you are right. The protein synthesis was in fact higher, but that's more of a matter of how sustained the increase was and not a matter of a "faster" protein synthesis. In other words, with 20g of a fast absorbing whey protein and a whole meal with slow absorbing proteins 30-40min after you will achieve the same - if not higher muscle protein synthesis rates in the long(er) run (>2h)... ah, and by the way: The response in the untrained leg confirms: There is not additional MPS stimulus from 40g vs. 20g of whey (much contrary to the insulin spike, by the way ;-).

The side-finding that this in medical terms "high" amount of whey also lead to significant increases in urea production is - at least in my humble opinion not surprising. The increased ammonia production due to higher protein oxidation rates does after all have to be cleared from the body. Against the background that this process is facilitated by the urea cycle, anything but the observed increase in urea production would have been startling.

"Confirmed: All Wheys, Not Just Hydro Whey Boost Glucose Uptake and Liver + Muscle Glycogen Supercompensation. Plus: How Can Taurine help?" | more

The fact that this increase in urea production and plasma concentrations did occur in the first place, on the other hand, is a clear cut sign for the onset of "wastefulness" with higher protein consumption - or as Selby et al. put it:

"Indeed, in the current study, urea production rates , as well as plasma urea concentrations, were markedly raised with the ingestion of 40 g protein.

Thus, instead of incorporation into muscle protein, the metabolic fate of excess exogenous amino acids contained in the 40WP was predominantly the oxidation or excretion as an indication that a state of amino acid excess was reached." (Selby. 2014)

Whether you consider this a "waste" of valuable dietary protein or not is probably a matter of your personal concept of protein nutrition.

If you are on the "protein worshipper" side of the devide, you will probably argue that you better "burn" protein for energy than carbs or fats, because otherwise you would have to eat less protein and  more carbohydrates + fat and would "become fat". It goes without saying that this is bullshit - not to mention that anyone who is interested in performance and the sanity of his doctor. The poor guy would freak out, when he'd see the elevated AST and ALT levels the combination of "protein only" diets + intense physical exercise are going to produce.

Your doctor's mental sanity or the excited calls of his receptionist are probably not really your concern, but I would still not discard the performance and, in the long run, metabolic and psychological detriments from running on protein only. From an (bio-)energetic perspective it's the least effective of the three macronutrients and thus not exactly a suitable fuel source for high performance athletes.

"So what would you put into a post-workout shake, Adel?" Personally, I have ~30g of whey protein and some fruit, like 1-2 bananas, a ton of water melon, or whatever else I have lying around. If no fresh fruit is available, I just grab some instant oats. And while I know that the carbs won't help with protein synthesis (Koopman. 2007), there is hardly any better timepoint to use the massive isulin spike and shuttle the glucose into the muscle than after the workout (van Loon. 2000). For me personally, the addition of carbs also prevents the brainfog, I get due to low blood sugar after an intense leg-workout and a protein shake without carbs. So, if you feel like you're not thinking straight or would have to go to bed after your shake, I would try to fix that by adding some carbs to the equation.

Bottom line: With the study at hand we (will) get further confirmation of the existence of a protein threshold of ~20g of whey protein, beyond which we won't see additional increases in acute myofibrillar protein synthesis after having a high protein breakfast and the completion of a standardized hypertrophy-oriented leg workout in young, healthy, male individuals.

If you wonder about the many underlined words in this conclusion, I may remind you of the fact that all these words describe boundary conditions that won't be fulfilled for everyone: There are more than enough people who don't have a high protein breakfast. There are people who train their whole body in a single session and would thus upregulate the protein synthesis in more than just the leg muscles. Not everyone is still young (and there is albeit inconclusive evidence that older individuals need more protein). For long-term muscle gains the sarcoplasmic protein synthesis may and the long-term (not acute) net protein balance definitely is more important than the acute increase... I could go on, but I guess you see, where this is heading: Theoretically, we'd have to do another 100 studies, but I am not sure whether Glaxosmith Kline who support Tiptons research would want to finance all of these ;-)

Reference:

• Cuthbertson, D., Smith, K., Babraj, J., Leese, G., Waddell, T., Atherton, P., ... & Rennie, M. J. (2005). Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. The FASEB journal, 19(3), 422-424.
• Koopman, R., Beelen, M., Stellingwerff, T., Pennings, B., Saris, W. H., Kies, A. K., ... & Van Loon, L. J. (2007). Coingestion of carbohydrate with protein does not further augment postexercise muscle protein synthesis. American Journal of Physiology-Endocrinology And Metabolism, 293(3), E833-E842.
• Moore, D. R., Tang, J. E., Burd, N. A., Rerecich, T., Tarnopolsky, M. A., & Phillips, S. M. (2009a). Differential stimulation of myofibrillar and sarcoplasmic protein synthesis with protein ingestion at rest and after resistance exercise. The Journal of physiology, 587(4), 897-904.
• Moore, D. R., Robinson, M. J., Fry, J. L., Tang, J. E., Glover, E. I., Wilkinson, S. B., ... & Phillips, S. M. (2009b). Ingested protein dose response of muscle and albumin protein synthesis after resistance exercise in young men. The American journal of clinical nutrition, 89(1), 161-168.
• van Loon, L. J., Saris, W. H., Kruijshoop, M., & Wagenmakers, A. J. (2000). Maximizing postexercise muscle glycogen synthesis: carbohydrate supplementation and the application of amino acid or protein hydrolysate mixtures. The American journal of clinical nutrition, 72(1), 106-111.

Fructose-Nation: No Change in Fructose Availability in the US Since the Early 1970s. So Why Are We Fat, Then?

From fat to Fructose - just another scapegoat for a fundamental problem?

Over the past 5 years or so, the idea that that fructose is to blame for the ever-increasing rates of diabesity has become so popular that hypotheses such as "the fructose consumption has exploded over the past decade" are usually accepted as scientifically verified facts.

A recent paper from the Department of Nutrition and Health Sciences at the University of Nebraska did now remind me that not all things that appear logical and consistent with our believes are necessarily true.

Do we even consume that much fructose?

As Trevor J Carden and Timothy P Carr point out, "the consumption pattern of fructose and other key nutrients" in the past 4 decades, "remains a topic of debate" (Carden. 2013). To determine whether fructose consumption in the US has increased sufficiently to be a casual factor in the rise in obesity prevalence Carden and Carr analyzed the USDA Loss-Adjusted Food Availability Database.

The researchers found that the food availability of glucose and fat, but not fructose, increased in the US between 1970 and 2009.

To calculate the percent change in energy from food groups and individual nutrients, Carden and Carr started initially compiled the available data on the per capita loss-adjusted food availability for 132 individual items were. In a second step they analyzed the corresponding nutrient profiles and used their findings to determine the availability of energy as well as macronutrients and monosaccharides during the years 1970-2009. By comparing the values for a given year to the baselinen in 1970, they did eventually determine the percent change in energy from food groups and individual nutrients.

Figure 1: Change in food energy availability per capita, 1970-2009 (Carden. 2013)

If you take a glance at the data in Figure 1 it's easy to see that their findings indicate that during this 40 year period the total energy availability increased by +10.7%. In that, the main "offenders" were grains and oils, the net change in total fructose availability, on the other hand was 0% - in other words, the added sweeteners (1%) were not even fructose based. Furthermore, Carden and Carr observed that the ...

"[e]nergy available from total glucose (from all digestible food sources) increased 13.0% [and ended up being] more than 3-times greater than fructose." (Carden. 2013)

With 14.6%, the amount of fat increased to a very similar extend as that of glucose. That's a 3x higher increase than for protein (+4.7) and am 1.6x higher increase in energy availability than for carbohydrates ,in general (+9.8).

So, it's the fat and sugar that's to blame? Not the fructose?

Despite the fact that I am not particular fond of the "fructose theory of everything evil", I believe that we got to be cautious about the significance of Trevor J Garden's and Timothy P Carr's conclusion, that their data would "suggest" that fructose is "unlikely to have been a unique causal factor in the increased obesity prevalence". If you take a look at the supplemental data they provided you will find, that their list of 132 foods used to calculate USDA food availability, i.e.

• Head Lettuce
• Kale
• Lima Beans
• Whole flavored milk
• Buttermilk
• Lowfat flavored milk
• Plain 1-percent milk
• Plain 2-percent milk
• Skim milk
• Eggnog and Half and Half (dairy and fat share of)
• Sour cream
• Yogurt
• Cheeses
• Lowfat cottage cheese
• Reg. cottage cheese
• Frozen yogurt and other misc
• Ice cream
• Lowfat ice cream
• Condensed bulk and canned skim milk
• Condensed bulk whole milk
• Condensed canned whole milk
• Dry buttermilk
• Dry whole milk
• Nonfat dry milk
• Barley products
• Corn flour and meal
• Corn hominy and grits
• Corn starch
• Durum flour
• Oat products
• Rice
• Rye flour
• White and whole wheat flour
• Beef
• Lamb
• Pork
• Veal
• Chicken
• Turkey
• Fish and Shellfish
• Eggs

• Great N. Beans
• Butter
• Edible beef tallow
• Lard
• Margarine
• Other edible fats and oils
• Salad and cooking oils
• Shortening
• Beer
• Wine
• Distilled Spirits
• Garlic
• Frozen Veggies
• Mushrooms
• Mustard Greens
• Navy Beans
• Okra
• Onions
• Canned Veggies
• Other Dry Beans
• Peas and Lentils
• Pinto Beans
• Potatoes
• Pumpkin
• Radishes
• Red Kidney Beans
• Lettuce
• Snap Beans
• Spinach
• Squash
• Sweet Corn
• Sweet Potatoes
• Tomatoes
• Turnip Greens
• Peanuts
• Tree Nuts
• Coconuts
• Refined sugar
• Dextrose
• Glucose
• HFCS
• Edible syrups
• Honey
• Plain whole milk
• Green Peas

• Collard Greens
• Avacado
• Bananas
• Blackberries
• Blueberries
• Canteloup
• Cherries
• Cranberries
• Dates
• Figs
• Grapefruit
• Grapes
• Honeydew
• Kiwifruit
• Lemons
• Limes
• Mangos
• Olives
• Oranges
• Frozen Berries
• Papayas
• Peaches
• Pears
• Pineapple
• Plums and Prunes
• Raisins
• Raspberries
• Stawberries
• Tangerines
• Watermelon
• Artichokes
• Asparagus
• Bell Peppers
• Black Beans
• Broccoli
• Brussel Sprouts
• Cabbage
• Carrots
• Cauliflower
• Celery
• Cucumbers
• Eggplant
• Apples
• Apricots
• Chili Peppers
• Escarole & Endive

... is representative of the variety of foods US citizens eat, but it does not tell you which of these foods, they will eventually select. Let's take apples, coconuts, and white and whole wheat flour as an example triplet. I guess if you had to rank them according to their contribution to the total energy intake of the average US citizen, none of you would hesitate to give me an answer like this: "White and whole wheat flour > apples > coconuts". Without the corresponding "weights" that would tell the scientists that white and whole wheat flour has a 10x higher impact on the average macronutrient composition of the average American diet, we be talking about the nutrient and fructose availability, not the actual intakes.

Better treat the data with the appropriate caution

Unfortunately, the scientists provide only rudimentary information about the impact of food choices, i.e. how much of the items listed above, the average US citizen actually consumes, namely:

• The food categories that increased the most during this time were grains and fats/oils, having increased 24.2% and 25.3%, respectively. 
• Caloric sweeteners (including both sucrose and HFCS) increased a modest 1.3%. 

With respect to the sweeteners Carden and Carr emphasize that the "sugar" availability, or as they put it the "monosaccharides available for metabolic absorption" is more than 3x higher than that of fructose.

In other words: Despite the fact that fructose appears to have become ubiquitous, overeating on plain sugar is still 3x easier. That this does not imply that you cannot do so, is the main and in my humble opinion crucial problem Carden and Carr fail to address. The result of their study do after all not exclude that a significant parts of the US population increased their fructose intake, in spit of the fact that its availability remained essentially the same.

The availability of a given nutrient on the shelves of US supermarket may provide a realistic image of the diets of a society of identical clones, who wheel their carts back and forth through the whole supermarket and buy foods from all each and every shelf. The "real" American, however, is no clone. On the contrary! He has his preferences and for a large part of the society these preferences can be found in the "highly processed, high sugar, high fat"-shelves of the super market. He does not care about the coconuts, apples, kale, mushrooms, olives and all the other foods in the "whole foods" section of the supermarket. They are available, but not what he is looking for.

Figure 2: The increase in total energy intake is one of the most fundamental contributers to the obesity epidemic (adapted from Carden. 2013)

Bottom Line: Despte the disconnect between availability and consumption you will be hard pressed to debate the scientists' conclusion that "increased total energy intake, due to increased availability of foods providing glucose (primarily as starch in grains) and fat" are the major contributors to the increased obesity in the US.

What is annoying, though, is the fact that a vast majority of the researchers fails to realize that their studies already account for the obesogenic effects of nutrient density. The average "high fat diets are bad for ..." is after all based on experiments, where animals or humans are fed diets that are high in both fat and carbohydrates.

Despite the fact that these studies provide a realistic portrayal of the average Western diet, the messages people infer, when they read about these results in the mainstream media is flawed.

It's not about eating less, fat, fructose, sugar or whatever scapegoat the author of the corresponding article believes was to blame for our misery. It's about nothing else than turning our whole way of eating upside down. It's about the right foods, not the right macros and it's about moderation and mindfulness.

References:

• Carden, T. J., & Carr, T. P. (2013). Food availability of glucose and fat, but not fructose, increased in the US between 1970 and 2009: analysis of the USDA food availability data system. Nutrition journal, 12(1), 130.

Vitamin D Builds Muscle: 70% Reduction in Myostatin, 45% Increase in Myotube Size in 10 Days - So, What's the Catch? Plus: Where Could Retinoic Acid (Vitamin A) Figure In?

If rely on the results of the most recent study from Australia, the answer to the above question probably reads "Yes, to a certain degree it does".

It has been a while that a vitamin D study has made it into the SuppVersity news (see previous articles). The reason for that is simple. I am not interested in study no. 9235235 that discusses random associations of low vitamin D with whatever ailment is plaguing us or review no. 89359252 that presents a selection of papers and concludes: "Man, there are vitamin D receptors everywhere, so it must be the f*** most important vitamin in your body!" The upcoming publication of a paper in the scientific journal Endocrinology did yet appear to be a good reason to stop the vitamin D radio silence. It's an in vitro study, I know, but it could answer a question many of will be interested in.

Does vitamin D build muscle?

I guess all of you will tell me that, in view of the results of pertinent studies (cf. Girgis. 2013a), the answer is "no, it doesn't, but deficiency seems to hamper muscle growth and impair skeletal muscle function". This conclusion is hard to debate, especially in view of the fact that we don't even know what exactly vitamin D does in human muscle cells.

Exactly this, i.e. the question "what exactly happens, when muscle cells are exposed to vitamin D" must have been bother Girgis et al., too. Therefore they devised a very simple yet interesting in-vitro study in the course of which they treated C2C12 cells, which are a commonly used model (see bottom line for a comment on this) for human skeletal muscle with both, the active 1,25(OH)2D and inactive 25(OH)D form of 'vitamin D' and observed the effects on cell proliferation and growth.

Figure 1: Number of live cells (10^4/dish; middle) and images of the cells w/out & w/ 25(OH)D2 (Girgis. 2013b)

The first intriguing finding the scientists present in their paper is yet not related to the growth or proliferation of the cells, but to their ability to convert active into inactive vitamin D and vice versa. What we are talking about here, specifically, is the increased expression of CYP24A1. This enzyme is responsible for the 'deactivation' of active vitamin D into calcitriotic acid. This supposedly inactive metabolite (you never know with these vitamin Ds ;-) is then excreted in the urine. The reason that I mention this ostensibly unimportant observation is that the expression of CYP24A1 and CYP27B1, which will convert 25OHD into the active 1,25(OH)2D is evidence of the presence of an auto-regulatory vitamin D-endocrine system in muscle cells.

Ok, enough of the enzymes what about "getting big"?

Let's briefly forget about the mechanisms and return to the actual effects on growth and proliferation. Effects such as the 30-50% increases in G0/G1, a gene that's responsible for arresting the cell cycle, and the 30% and 20% decreases in Myc and Cyclin-D1 the scientists observed in response to both 25(OH)D and 1,25(OH)2D.

In view of the fact that these genes are necessary for the progression of the cell cycle, it is not surprising that the exposition to both forms of vitamin D brought the cycle to a screeching halt. In the end, this is yet a long-known phenomenon. The antiproliferative effects of 1,25(OH)2 D in muscle cells were first described in 1985 and are, as Girgis et al. point out, ...

"[...] they are consistent with antiproliferative effects of 1,25(OH)2 D in a number of other cells and tissues including skin, cancer cells and immune cells ." (Girgis. 2013b)

What's news though, is that the researchers were able to confirm that even 25OHD, the "prohormone" (Girgis. 2013b) to 25(OH)D2, displays antiproliferative effects in C2C12 cells.

Don't forget the "Underestimated Vitamin D Sources: Especially Eggs, But Also Chicken, Pork, Fish & Dairy Contain an Overlooked, Physiologically Relevant Amount of Ready-Made 25OHD" | read more

In that, it's important to acknowledge that these effects are not necessarily brought about by direct receptor interaction. They could also be mediated by the 'activation' of 25OHD via the previously mentioned CYP27B1. With CYP27B1 and its counterpart CYP24A1 the cells would thus be able to produce and clear active vitamin D on demand - and in this case the muscle cells were using it for anti-proliferative purposes.

"What? Vitamin D kills muscle growth?"

At first sight the cell-cycle arrest really suggest that high, and not the often cited low vitamin D levels should have anti-anabolic effects. Since muscle does not necessarily depend on proliferation, or more specifically cell devision, to grow this is yet not the case. At least up to a volume time-point your muscle cells and with them your total muscle volume can grow by simply taking up more protein. This process is called hypertrophy and it works quite nicely until a certain threshold is reached and myostatin pulls the emergency break (if you read my previous article "Getting Big Means Growing Beyond Temporary Physiological Limits" you will know that this is the point, when the activation and incorporation of satellite cells becomes important; learn more)

Figure 2: There may be less live cells, but once the cell cycle arrests, the cells that are bathed in serum with high amounts of acvite vitamin D 1,25(OH)2D grow like crazy, but probably only until they are 'ready to burst' (Girgis. 2013b)

Irrespective of all growth limits, it is thus no irreconcilable contradiction that the data in Figure 2 confirms that 'vitamin D builds muscle. Since proliferation and hypertrophy are independent (or rather mutually exclusive processes) the individual cell growth, while the total cell mass remains the same (remember: cell cycle arrest does not mean that the cell dies).

So, is this good or bad news? Whether the cell cycle arrest is a problem that could haunt you, in the long term, i.e. whence the limits of natural growth are reached (learn more) is something this study can't tell us, because...

... firstly, the cells the researchers used cells express proteins necessary for muscle contraction and display the morphology of individual fiber unit, but C2C12 cells are not adult muscle cells. With a varying degree of maturation, and mode (Langelaan. 2011) of glucose transport (Kotliar. 1992), even Girgis et al. have to admit that "effects in C2C12 cells do not always translate to adult muscle." (Girgis. 2013b) and ...

Figure 3: Primary C2 cells (chicken & mouse) were either untreated (A,C,E) or treated w/ 10 µM RA (B,D,F). A + B panels display satellite cells incubated w/ or w/out RA for 24 hr. C,D and E,F panels show satellite cells and C2 cells, respectively, after 48hr of incubation.

... sedondly, as with every in-vitro study, we cannot tell if the effects that are observed under direct exposition of cells to pharmacological doses of 1,25(OH)D will correspond with those of physiological levels of vitamin D - even high ones.

In the end, we are thus as clueless as before. Even if everything works as it does in the  model, the data in Figure 2 would suggest that after a couple of days of increased hypertrophy, the myostatin levels are identical and the D-advantage disappears.

When this 'growth limit' is reached it would require proliferative effects and new cells, or rather myonuclei, to grow further (learn more). With vitamin D alone, that's not going to happen. What could help though, is the villain of the average vitamin D enthusiast: Retinoic acid (RA) aka vitamin A. The latter has after all been shown to "induces adult muscle cell differentiation mediated by the retinoic acid receptor‐α", ten years ago (see Figure 2 from Halevy. 1993).

Now you tell me: Isn't it funny how we always end up with vitamin A (learn more), whenever we realize that 'vitamin D, without vitamin A' sucks? That cannot be mere coincidence, can it?

References:

• Girgis, Christian M., et al. "The roles of vitamin D in skeletal muscle: form, function, and metabolism." Endocrine reviews 34.1 (2013a): 33-83. 
• Girgis, Christian M., et al. "Vitamin D Signaling Regulates Proliferation, Differentiation and Myotube Size in C2C12 Skeletal Muscle Cells." Endocrinology (2013b): en-2013.
• Halevy, Orna, and Orna Lerman. "Retinoic acid induces adult muscle cell differentiation mediated by the retinoic acid receptor‐α." Journal of cellular physiology 154.3 (1993): 566-572.
• Kotliar, N., and P. F. Pilch. "Expression of the glucose transporter isoform GLUT 4 is insufficient to confer insulin-regulatable hexose uptake to cultured muscle cells." Molecular Endocrinology 6.3 (1992): 337-345. 
• Langelaan, Marloes LP, et al. "Advanced maturation by electrical stimulation: Differences in response between C2C12 and primary muscle progenitor cells." Journal of tissue engineering and regenerative medicine 5.7 (2011): 529-539.

Are You Overtraining? Two Scientifically Proven Methods to Test Yourself - Method 1: Heart Rate Variability Analyses

It may sound like the invention of the heart rate monitor industry, but it's a matter of scientific "fact" that HRV analyses are a great tool to monitor and manage training and recovery.

Overtraining, its existence, consequences and detection is and has always been one of the hottest topics in the fitness community. While some practitioners and trainers claim that it does not even exist, others fear it so much that they constantly undertrain. The result? Stagnation.

In the highly competitive world of the average iron-willed gymrat, it's however pretty rare that the gains ain't coming, 'cause he or she is under-training. I would guesstimate that the exact opposite is the case for at least 75% of the self-proclaimed hard-gainers. Overtraining, undereating and/or  a lack of consistency are the stumbling blocks of 99% of the trainees.

I know that you know all that, ...

... so I'll cut this short and get right to the point. Within the past two weeks I hit upon two interesting papers that describe very different, but - in both cases - effective methods to determine whether you are overtraining, or not. While I originally wanted to tackle both in one article, I had to realize that the day has only 24h for my to write and you to read SuppVersity articles. Therefore, I decided to tackle heart rate variability monitoring today and postpone writing about the other to next week's follow up (stay tuned!).

You can learn more about overtraining at the SuppVersity

Heart Rate Variability

ABEL Test

Overtraining & Undereating

Calculate your Energy Intake!

There Are No Magic Macros!

Reinvent Your Training!

I guess you may have heard about the usefulness of the latter on my buddy Carl Lanore's Super Human Radio, already and are thus familiar with the idea that your heart’s ability to produce fluctuations in the beat-to-beat interval in response to different situations. According to José Morales and his colleagues from the Laboratory of Sport Sciences a the Ramon Llull University in Spain,

Don't turn into the guy on the left, don't overtrain & undereat | learn more

"the use of heart rate variability (HRV) as a training tool has progressively increased and deserves attention as a tool to monitor the possible states of overtraining and recovery after a training process. [...] Several studies suggest that the quantification of HRV can be used as a non-invasive method for assessing autonomic  cardiovascular  control  via  the  impact  of  HRV  on  beat-to-beat  heart  rate  modifications." (Morales. 2013)

The relationship between autonomic modulation and HRV is different during exercise and immediate recovery compared to rest periods. This makes the HRV a viable tool for the non-invasive assessment of the autonomic cardiovascular control and a comparatively objective measure of your training status (Camm. 1996; Seiler. 2007; Bosquet. 2008) .

Hold on: What exactly is my HRV? Actually it's much less complicated than terms like fourier-transforms and frequency domain suggest. If you say "my heart rate is 60 beats per minute", this is an average you measured over a certain timespan. If you counted every beat for 60s, for example, the iterval between the beats probably was not exactly 1s. One beat may have been "premature", another took a little more than one second to finally come. The HRV is a measure for the variation in the time interval between heartbeats. In other words, if your heart beats 60 times per minute 24/7, your HRV would be zero and you're probably a cyborg ;-)

The HRV responds particularly to heavy loads / intense workouts. The magnitude of the workout-induced stress is thought to be proportional to the activation of the sympathetic arm of the autonomic nervous system and thus the variations in autonomic balance, which can be indirectly assessed using HRV analysis (Seiler. 2007). A significantly lowered HRV days after a heavy workout is thus a signal that your central nervous system is still recovering. It tells you that you'd better insert a light cardio day or spend the time with friends instead of getting back onto the grind for another torturous 5x5 session.

Technology vs. psyche - HRV vs. RESTQ-Sport

Compared to psychological tests like the Recovery Questionnaire for Athletes (RESTQ-Sport), which is frequently used in research to observe the balance between stress and recovery during training processes, the physiological data you evaluate with the HRV method is obviously more objective. It is yet still debated whether it is also reliable and can / should replace or complement the classic psychological testing procedures.

Table 1: Overview of the training weeks of the two groups (Morales. 2013)

For Morales and his colleagues this doubt was among the most important reasons to conduct a study that would integrate both methodologies. To this ends, the researchers recruited 14 male national-standard judo players (age 22.85 years; height 174.08 cm; body mass 76.85 kg) and randomized them to four-weeks of...

• high training load (HTL - 8 sessions per week ➙ short recovery periods)
• moderate training load (MTL - 4 sessions per week ➙ long recovery periods) 

For the detection of the HRV at the beginning of the first and last session in weeks 1 and 4, the researchers used a Polar S810 cardiotachometer which provided the scientists with the following parameters either directly or the corresponding data to calculate them:

Figure 1: A wide spread (green ellipse) of the poincare plot indicates full recovery.

• the mean inter-beat (RR) interval,
• the standard deviation of the inter-beat (RR) interval , 
• the heart rate & its standard deviation
• the square root of the mean squared difference of successive RR intervals, 
• the number of consecutive RRs that differed by more than 5 ms each, and 
• the percentage of consecutive RRs that differed by more than 5 ms each

That sounds extremely complicated, but in the day and age of automated data acquisition and immediate processing (including fourier transformation to get the frequency data, etc.), there are lot of tiny little gadgets and apps that can do all the hard math-work for us.

HRV + RESTQ-SPORT + HTL vs. MTL = reliable training analysis

The next thing they did was to to simply plot pairs of inter-beat intervals, e.g. 1/60 vs. 1/64, 1/64 vs. 1/76, etc. the resulting graph is a so-called poincare plot (see Figure 1) and the spread of the point in this graph can tell you whether you are well-rested (wide ellipse) or overtrained / need rest (narrow ellipse)

Figure 2: Changes in selected HRV variables, left; performance, as well as stress + recovery values in the RESTQ-Sport, right; all differences expressed relative to values at the beginning to study (Morales. 2013)

The data in Figure 2 (left) does yet demonstrate - the poincare plot of the inter-beat variables characterizes the decreased heart rate variability (HRV) quite well.

"The multivariate test indicated that there was an interaction effect between the testing time and group on HRV variables. [...] the HTL group showed lower square root of the mean squared difference for successive RR intervals, very low frequency, high frequency, short-term variability and short-range scaling exponent in the post-test than in the pre-test (p < 0.05). The HTL group showed higher low/high frequency ratio in the post-test than in the pre-test. Finally, there were no differences between the pre-test and post-test in the MTL group." (Morales. 2013)

In other words: While the HTL group showed the expected increase in HRV, the judo players in the MTL group did not experience any significant changes in heart rate variability.

The question that remains - at least until you take a look at the data in Figure 2 (right) - is: Do these abstract figures really tell me that I am overtraining? The answer the comparison to the data from the RESTQ-Sport questionnaire gives us is YES, it does!

Don't be that guy or girl who works his / her ass off for nothing. Learn how to identify and combat the Athlete's Triad | read all articles.

Bottom Line: The accumulating scientific evidence and the ever-increasing number of practitioners (trainers and trainees) who rely on heart rate variability analyses to judge whether or not they are over-training clearly suggest that a heart rate monitor and the appropriate software (usually part of the bundle) would make a valuable addition to any (over-)ambitious athlete's Christmas gift list.

If there is still room for another present on your wishlist, I'd suggest you come back next week for part II of this series, to learn about another, maybe sexier method to find out whether your perception that training 1h-2h with no sweat every day won't have you overtrain (note: not sweating or feeling cold in the gym can be signs of severe or chronic overtraining).

Reference:

• Bosquet, L, et al. "Is heart rate a convenient tool to monitor over-reaching? A systematic review of the literature." British journal of sports medicine 42.9 (2008): 709-714.
• Camm, A. J., et al. "Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology." Circulation 93.5 (1996): 1043-1065.
• Morales, J., Álamo, J. M., García-Massó, X., López, J. L., Serra-Añó, P., & González, L. M. (2013). The Use Of Heart Rate Variability In Monitoring Stress And Recovery In Judo Athletes. Journal of strength and conditioning research/National Strength & Conditioning Association. 
• Seiler, Stephen, Olav Haugen, and Erin Kuffel. "Autonomic recovery after exercise in trained athletes: intensity and duration effects." Medicine and Science in Sports and Exercise 39.8 (2007): 1366.