Vitamin D for Athletes: 20,000 & 40,000IU / Week Bring Low Levels Back Up, Yet W/Out Measurable Performance Effect

Jumpstart low vitamin D-levels with 2,000 - 3,000 IU/day - but don't expect that to jumpstart your performance...

Most of you will probably remember the vitamin D news from the Short News on Saturday. And yes, I have to admit that as of now - the usefulness of known that both genetic polymorphisms and your vitamin D binding protein levels (which are incidentally higher in obese than lean individuals), are not exactly useful, when it comes to pick an appropriate dosage of supplemental vitamin D to bring your levels up into upper region of the normal range.

In this respect, a study like the one that has been published in the latest issue of the British Journal of Sports Medicine may in fact be more useful. After all, the study was designed to investigate two doses of vitamin D supplementation (20,000 vs 40,000 IU/week vs placebo) on serum 25[OH]D concentration in club-level male athletes over 6 and 12 weeks.

Note: If you read the Short News Update from Saturday, you will be aware that due to certain genetic polymorphisms you can be "vitamin D3 non-responder" (in the study by Nimitphong 40% of the subjects would could be considered low/no-responders due to the small scale of the study (N=20) this is yet not representative and may also be subject to inter-ethnic differences between Asians vs. Caucasians; learn more), if that's the case you may need 10,000-20,000IU à day or more - another reason to TEST not to supplement blindly!

Boring? Well, what if I tell you that the second aim of the study was to elucidate whether this protocol or rather the respective changes in vitamin D levels would have effects on the physical performance of the 30 21-year old athletes who were all competing for university athletics clubs (mostly rugby and soccer) in the UK (=low sun exposure)? ...I see, now you're listening. 

The research design was actually pretty straight forward: (0) Make sure none of your subjects has been popping vitamin D supplements of fish oil in the past; (1) Test the baseline performance and vitamin D levels of your study participants; (2) assign them via block randomization (to ensure there are no sign. inter-group differences in the baseline 25OHD levels) to three groups; (3) make them swallow either 20,000 or 40,000 IU vitamin D3 (cholecalciferol) or a visually identical placebo (PLB) (100 mg maltodextrin) once a week for 12 weeks; and (4) retest physical performance and vitamin D levels after 12 weeks.

Figure 1: The non-existent effects of vitamin D supplementation on the physical performance; neither the increments nor the decrements reached statistical significance (Close. 2013)

The study outcomes, at least as far as the performance increases are concerned could hardly be more unambigous. Despite the fact that 7/30 individuals (57%) had concentrations less than 50 nmol/l (=inadquate according to the US Institute of Medicine standards from 2011) and 6/30 (20%) were downright deficient (12-30 nmol/L) or severely deficient (<12 nmol/L) and irrespective of the fact that the subjects with the lowest D3 levels saw the most rapid increases in 25OHD levels, the research did not observe any significant improvements in the standardized performance tests. They do yet point out that

"[t]o further ascertain whether vitamin D status does affect skeletal muscle function in young
healthy participants, it may now be pertinent to also adopt more sensitive measurement techniques (eg, single muscle fibre measurements)." (Close. 2013)

Although I'll leave it up to you whether you want to ascribe a higher value to the corresponding gene essays that would be used in such an "advanced" study or the real world performance gains, I personally am not really interested in this kind of follow up study. It would make more sense to assign the subjects (preferable athletes and not yet another bunch of sick people, or even rodents) to a standardized exercise regimen and re-test, whether or not there would be any benefits of vitamin D supplementation in a more controlled training scenario.

Now that we've left the disappointing part behind, let's briefly take a closer look at the changes in v25OHD levels in figure 2. You will also realize that the higher dosage protocol produced a steeper incline in vitamin D levels, but was likewise unable to raise the vitamin D levels to the >120 nmol/ml range, where Heaney and other researchers would like to see it.

Figure 2: 25OHD levels in nmol/ml after 3 weeks and 6 weeks of supplementation (left), regression analysis demonstrating the dependence of serum total 25[OH]D increases on baseline levels (Close. 2013).

What's more, the way in which both supplementation regimen approach the 90-100 nmol/ml mark after 12 weeks of continuous supplementation suggests that it is probably not even feasible to bump your vitamin D levels into that region without taking even higher amounts of vitamin D on a daily basis to abrogate the natural regulation process which does not appear to favor "vitamin D council levels" in the >120 nmol/ml range. Even the Maasai and Hadzabe who live, as Luxwolda et al. put it in the "cradle of makind" have vitamin D levels that are approaching, but not surpassing the magic 120 nmol/ml margin (Luxwolda. 2012).

To get your levels in the recommended >75 nmol/ml range it should yet suffice to take ~2,000-3,000IU per day - or, for those with really low levels who are in a hurry to get them up into the normal range twice the amount.

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Table 1: Prevalence of low(ish) vitamin D levels in athletes (based on overview in Close. 2013)

Talking about really low levels: I have not changed my mind about the importance of getting your vitamin D levels tested before you embark on a supplementation regimen with anything more than ~1,000IU/day. And if you take a second look at the dose-response relationship in figure 2, you will notice that you would only be wasting money if you took vitamin D supplements, when your levels are already in the optimal range.

Considering the fact that previous studies have revealed surprisingly high levels of vitamin D deficiency in athletes (see table 1), the money a bi-annual test may cost you is yet certainly well-spent. If not in terms of immediate performance increases then certainly with respect to your overall health. After all, contrary to the questionable benefits of brining your vitamin D levels into the >120 nmol/ml range, the evidence for (long-term?) detrimental effects of vitamin D deficiency is unambigous.

References:

• Close GL, Russell J, Cobley JN, et al. Assessment of vitamin D concentration in professional athletes and healthy adults during the winter months in the UK: implications for skeletal muscle function. J Sports Sci 2012.
• Bescos Garcia R, Rodriguez Guisado FA. Low levels of vitamin D in professional basketball players after wintertime: relationship with dietary intake of vitamin D an calcium. Nutr Hosp 2011. 26:945–51. 
• Ducher G, Kukuljan S, Hill B, et al. Vitamin D status and musculoskeletal health in adolescent male ballet dancers a pilot study. J Dance Med Sci 2011.15:99–107.
• Halliday TM, Peterson NJ, Thomas JJ, et al. Vitamin D status relative to diet, lifestyle, injury, and illness in college athletes. Med Sci Sports Exerc 2011. 43:335–43.
• Hamilton B, Grantham J, Racinais S, et al. Vitamin D deficiency is endemic in Middle Eastern sportsmen. Public Health Nutr 2010. 13:1528–34. 
• Heaney RP. Assessing vitamin D status. Curr Opin Clin Nutr Metab Care 2011;14:440–4.
• Lehtonen-Veromaa M, Mottonen T, Irjala K, et al. Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls. Eur J Clin Nutr 1999. 53:746–51.
• Lovell G. Vitamin D status of females in an elite gymnastics program. Clin J Sport Med 2008. 18:159–61. 
• Luxwolda MF, Kuipers RS, Kema IP, Dijck-Brouwer DA, Muskiet FA. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/l. Br J Nutr. 2012 Nov 14;108(9):1557-61.  
• Morton JP, Iqbal Z, Drust B, et al. Seasonal variation in vitamin D status in professional soccer players of the English Premier League. Appl Physiol Nutr Metab 2012. 37:798–802.
• Wilson G, Fraser WD, Sharma A, et al. Markers of bone health, renal function, liver function, anthropometry and perception of mood: a comparison between Flat & National Hunt jockeys. Int J Sports Med 2012.

Aspartame, a Cancer Protective Brain Toxin? Is There a Hormetic Threshold for the Consumption of the Dreaded Artificial Sweetener? Plus: What Do We Know, Anyway?

The beauty ideals have changed over the years. Coke, however, is still there. But are we going to say the same about the aspartame in diet coke 50 years from today? I don't think so - regardless of what the science says...

Artificial sweeteners are one of the "hot topics" here at the SuppVersity and I am already looking forward to the upheaval today's post on aspartame is probably going to cause - and that despite the fact that the bottom line is probably going to satisfy both the critics and "not so critics" (I actually don't know any real aspartame enthusiasts ;-) among the SuppVersity readers...

But let's not fast forward too much and rather take a peak at the review Karol Rycerz & Jadwiga E. Jaworska-Adamu from  University of Life Sciences in Lublin (Poland) recently published in a special issue of Folia Neuropatholgica (Rycerz. 2013).

Actually their paper starts out like one of the countless "aspartame is the devil" articles you would expect to see when you type the words "aspartame" and "cancer" into a search engine. Yet despite the fact that they refer to aspartame as a "widespread sweetener used in many food products" that is considered "a highly hazardous compound" (Rycerz. 2013), the abstract to their review also mentions that

 "[...] the action of astrocytes during aspartame poisoning may be advantageous for neuro-protection." (Rycers. 2013)

This statement is not just surprising it does also conflict with the authors' self-declared aim to "demonstrate the direct and indirect role of astrocytes participating in the harmful effects of aspartame metabolites on neurons" (Rycerz. 2013) and reminds you of the literal fish out of water.

The authors leave no doubt: They think aspartame is dangerous

The results of a study from the University of Western Sidney  to suggest that you could keep your insulin levels at bay, if you mixed your sugary intra-workout supplement with aspartame-laden diet coke instead of water (learn more)

You may remember from an older episode of the Science Round Up on the Super Human Radio Network that a more recent rodent study by Iyyaswamy & Rathinasamy suggested that we may have overlooked the negative effects of aspartame on the human brain in previous rodent trials due to differences in the way the methanol which comprises 10% of the breakdown products of aspartame, is metabolized in the human vs. the rodent body (Iyyaswamy. 2012). The Indians tried to mimic the slow(er) turnover rates by the provision of methotrexate and observed a significant increase in oxidative stress in the brain at much lower doses of aspartame than they have been used in any of the previous rodent studies, the majority of which support the notion that aspartame is totally benign unless it is consumed in amounts as high as you would find in a whole truckload of diet coke.

Despite the fact that we are thus still not 100% sure how dangerous aspartame actually is, it is probably not as benign as the pre-2012 data may have suggested. Against that background Rycerz' and Jaworska's elaborations shouldn't be discarded as totally irrelevant. It does after all appear logical that ...

• ... the reduced levels of dopamine and serotonin in response to the aspartame induced presence of excess amounts of phenylalanine that blocks the transport of important neurotransmitter precursors (tryptophan, l-tyrosine & co) to the brain, as well as the
• ... the neuronal hyper-excitability that's caused by the high aspartic acid concentrations in the presence of other excitatory amino acids like glutamates

may be detrimental to the brain, even in the absence of the previously mentioned brain toxic effects of methanol, which may "cause CNS depression, vision disorders and other symptoms leading ultimately to meta-bolic acidosis and coma" (Rycers. 2013).

Hyperexcitatory, toxic, dangerous and protective?

   Figure 1: Graphical illustration of the break down and down stream effects on GABA, dopamine, serotoine & co that are induced by high amounts of aspartame in the brain - keep in mind that "high" is more than the occasional glass of diet coke (Rycers. 2013)

In view of all these horror stories and accumulating evidence that dike-topiperazine (DKP) a metabolie of aspartame that is formed during prolonged storage of artificially sweetened foods ant is accordinly particularly high in (diet) energy drinks and cola (Roj. 2009) promotes the formation of brain tumors (Roberts. 1991; note: the incidence for lymphomas due to DKP consumption is much higher than that for brain cancer), it is hard to believe that "[...] the action of astrocytes during aspartame poisoning may be advantageous for neuro-protection." (Rycers. 2013)

While it is a matter of fact that the activation of the glia by the presence of smaller amounts of glutamate, aspartate and other excitatory neurotransmitters in response to aspartame consumption may exert hormetic effects by inducing corresponding autoregulatory effects that re-establish normal neurotransmitter levels and reduce the potential (over-)expression of the cancer promoting pro-inflam-matory cytokines IL-1, IL-6, TNF-α, PGE2. This is up to now nothing but a hypothesis.

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Questionable "brain health effects": While you may remember that Carl and I talked about the beneficial effects / necessity of inflammation, when it comes to getting rid of  degenerate cells in several of the recent episodes of the Science Round Up (read up on hormesis, as well), I highly doubt that you will be able to hit that "sweet spot" of maximal hormesis, where a minimal amount of aspartame toxicity is going to give you an increase in your brains endogenous defense system that would not just negate the potential downsides, but exert the "neuroprotective"effects Rycers et al. imply in the abstract of their review.

Suggested Read: "Coke vs. Diet Coke vs. Milk - The Unhealthy Beverage Shoot-Out: Milk Reduces, Coke Increases Visceral Fat. Dreaded Diet Coke on Par With Plain Water" (read more)

That being said, it is not exactly likely that the occasional cup of diet coke or the consumption of a pre-workout, protein or other supplement with minor amounts of aspartame in it, will reach your brain in those amounts that would be necessary to elicit either beneficial or negative effects on your neurons.

For the true aspartame junkies, on the other hand, the sheer amount of other potentially health threatening agents, like citric acid, phosphor, carmine coloring and co may eventually be so high that they become a much greater thread to your health than the comparatively minor amounts of aspartame in the chemical cocktails that are marketed as healthy alternatives to regular sodas.

References:

• Iyyaswamy A, Rathinasamy S. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats. J Biosci. 2012 Sep;37(4):679-88.
• Roberts HJ. Does Aspartame Cause Human Brain Cancer? J Adv Med 1991; 4: 231-241.
• Rój A, Stasiuk E. Oznaczenia  jakościowe w zakresie zawartości aspartamu i jego metabolitów w napojach gazowanych bezalko -holowych z zastosowaniem techniki HPLC. Bromat Chem Toksykol 2009; 3: 543-547.
• Rycerz K, Jaworska-Adamu JE. Effects of aspartame metabolites on astrocytes and neurons. Folia Neuropathol. 2013;51(1):10-7.

Intramuscular Fat & High Energy Expenditure + Fatty Acid Oxidation. Vigorous Exercise & Feto-Protection. Genetics, Binding Proteins, Phosphorus & Low Vitamin D

Jogging or Tai Chi!? You have the choice - longevity-wise it may not make much of a difference.

20% that's the average risk reduction for all-cause mortality among those of the 61,477 Chinese men in the Shanghai Men's Health Study who practice Thai-Chi regularly.

And what's more, in view of the fact that this is hardly less than the 23% risk reduction the researchers from the Vanderbilt University School of Medicine in Nashville, Tennessee, calculated for  men who walked regularly and only 7% less than the reduction in all-cause mortality Na Wang et al. observed in regular joggers, it is also the SuppVersity Figure of the week (Wang. 2013) - a figure that's not much different for cancer and cardiovascular mortality, by the way. 

Before you go exploring your Qi and prolong your life, I'd still suggest you meditate over the other On Short Notice items for a couple of minutes ;-)

Feto-Protective Effects of Vigorous Exercise in Pregnant Women

Another interesting observation of the study at hand was that the pregnant women did perform the same amount of work during their 40 min workouts, despite the fact that they had to carry significantly more weight and were clearly disadvantaged from a kinetic point of view, theoretically that is to say.

Being pregnant should be a reason to get going, not to "slacken off". After all, the chances a women is already pre-diabetic, when she becomes pregnant is unpleasantly high already. Against that background it is certainly not a good idea to reduce your daily "exercise" from "almost zero" to "minus 1".

Recent evidence for the notion that pregnancy is a reason to exercise, not to "slacken off" comes from a soon to be published study by Michelle F. Mottola et al. who found that 40 minutes of vigorous exercise at 95% ventilatory threshold (for most active individuals that would be a fast jog) yielded significant improvements blood glucose levels and better outcomes in a subsequent glucose challenge (75 g) that was conducted after the workout -- changes of which the researchers say that they are "fetoprotective" and did not lead to adverse effects on birth outcome (Mottola. 2013).

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Listen up fathers-to-be: That you should not  have your pregnant wives or girlfriends do heavy deadlifts in the gym or with the water canisters at home, does not mean that you have to featherbed them - that would be detrimental to both, your loved one and your unborn child.

Gentics, Vitamin D2, D3 and Vitamin D Binding Proteins, Phosphorus & Low Vitamin D

Figure 1: If you don't have the "standard" genes you may in fact be better off supplementing with vitamin D2 to bring your total 25OHD levels up into the >20nmol/ml zone (Nimitphong. 2013)

You still think it's all just about how much vitamin D you have? Well, at least in multiple sclerosis it is probably more important how much of it is bound to vitamin D binding protein... you did not even know that existed? Well, that's the result of too much hype and too little science, which are the main characteristics of the mainstream coverage of vitamin D.

And to get back to the important stuff: If you have MS and want to benefit from vitamin D supplementation, you should try find out what your vitamin D binding proteins are like. After all high levels of VDB did totally blunt the beneficial effects of vitamin D supplementation in a recent study from China (Yang. 2013).

Ah, talking about vitamin D, you may also be intrigued to hear that at least in the 99 women and 41 men (age, 66-96 years) who participated in a recent study from the Justus-Liebig-University in Giessen, Germany (Jungert. 2013), the nutritional intake of vitamin D showed no relation to the amount of circulating vitamin D levels (25OHD3), at all.

It is possible that the high dietary intake of phosphor plays a role in the etiology of the low vitamin D epidemic (learn more)?

And while the same was true for the average calcium intakes, the statistically significant association between the dietary intake of phosphorus and the subjects' parathyroid hormone (PTH; its logarithmic value, to be precise) in the lean study participants. In view of the fact that the levels of PTH correlate negatively with the levels of vitamin D, this should remind you of a previous SuppVersity article about the potential involvement of the overtly high amounts of phosphorus in the standard western diet (cf. "Hypothesis: Does Vitamin D 'Deficiency' Protect Us From Phosphorus Overload? 1,25OHD Production Drops By 19pg/dL With Each 1mg/dL Increase in Phosphorus" | read more...).

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I am convinced... we are far from understanding how vitamin D actually works. Aside from our incomplete understanding of the role the vitamin D binding protein (e.g. is VDB like SHBG for testosterone necessary for the interaction with certain tissues, while blunting the interaction with others), our concept of its interactions with vitamin A is incomplete and the mainstream paradigm of a general antagonism simply flawed. Therefore I am confident that this was not the last mini-update on vitamin D that goes beyond the hoopla of what vitamin D is supposed to be involved in, here at the SuppVersity.

The schizophrenic effects of intramuscular fat (IMTG)

Depending on the way you aquire it, the fat "within" the muscle (intra-muscular triglycerides; IMTG) appears to have very different effects. While it is generally associated with insulin resistance in the morbidly obese (a causal effect has never been proven), it has likewise been shown to increase in response to exercise (Shaw. 2010), where it serves as a readily available endurance substrate.

Things to remember about IMTG:

(1) In lean active individuals, the IMTG pool is regularly depleted during exercise and is replenished during subsequent feeding. Supercompensation is possible.

(2) Reduced IMTG oxidation appears to contribute to the reduction in fat oxidation during exercise in sedentary individuals, where it is accompanied by the accumulation of lipid metabolites and insulin resistance in skeletal muscle.

(3) The IMTG stores are a readily available substrate during workouts.

(4) A high IMTG synthesis rate is a major determinant of IMTG content and keeps lipid metabolite concentrations low and insulin sensitivity high.

(5) IMTG synthesis rates can be increased by exercise, dietary interventions, and combined dietary and exercise interventions. (based on Shaw. 2010)

Van Loon et al. (2003) for example observed a 60% reduction in IMTG content in type 1 muscle fibers following two hours of cycling exercise performed at 60% maximum oxygen uptake (VO2max) and Shaw, Clark and Wagenmakers point out that

"the specific depletion of IMTG in type 1 muscle fibers is a consistent finding and is in line with the greater capacity for IMTG storage and fatty acid oxidation in these fibers. The use of IMTG as a fuel source does not appear to be limited to endurance exercise either, as several studies have also demonstrated a significant reduction in IMTG content after a single bout of resistance exercise." (Shaw. 2010)

Against that background, it is maybe no longer that surprising to hear that a group of Harvard researchers found that those of the overweight children in their study who did not just receive "standardized healthful lifestyle advice" for 8 weeks, but were also randomized to an in-home supervised exercise intervention exhibited increases in both fitness and intramuscular triglycerides ( McCormack. 2013).

Figure 2: Overview of some of the main results of the Harvard study (McCormack. 2013)

What I am pretty sure, though, is going to surprise you is the fact that these increases in the amount of fat in the musculature of the kids (average age 13y) showed a highly significant correlation with greater resting energy expenditure (r = 0.78, P = 0.005) and a decrease in fasting respiratory quotient (r = -0.70, P = 0.02). Or to put is simply: The more intramuscular fat, the more energy your burn sitting around and the more of this energy is going to be from fat.

Against that background, studies investigating the role of ITMG in both obesity and exercise performance begin to appear in a very different light. Let's take insulin's inhibitory effect on adipose tissue lipid oxidation, as an example. Logically you should assume that this effect was a major bummer for any endurance athlete and guzzling glucose containing drinks before or even during a workout would be stupid.

Different rules for glycogen loading and re-pletion (more on the latter)

As Shaw et al. point out in their review, this insulin-induced inhibition of adipose tissue lipolysis could yet lead to an increase in IMTG utilization that would mirror the increase in IMTG utilization seen after pharmacological suppression of adipose tissue lipolysis by Acipimox (= a special form of niacin; van Loon. 2005a, 2005b). In fact, the use of IMTG has been shown to increase ∼twofold when high-GI-index meals are eaten the day preceding exercise.

Moreover, Shinora et al. were able to show that the increase in intra-muscular lipids after a 7-day glycogen loading protocol as it is commonly used by endurance athletes increased the amount of IMTGs and bumped up the fatty acid oxidation rate by 5-6% (Shinohara. 2010)

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Still much to be learned: It remains to be seen how this relates to the increases in energy expenditure the Harvard researchers just observed. What appears to be certain, though is that the common vilification of IMTG is another instance of hilarious over-generalization that does not stand the test of science.

Facebook News Round-Up

As far as the official Short News are concerned, that's it for today. If you want more, I suggest you head over to the SuppVersity Facebook Wall and check out one of the following news items that appeared in the course of the week:

• 

  Some supplements are for drag queens and wanna-be eunuchs, only: "Study Finds 17x Elevated Estrogen, High Progesterone + Reduced DHEA Levels in 65% of Ecdysteroid, Tribulus, Phytoestrogen, Phytosterol and/or Soy Protein Users!" (read more)

  Caffeine stops cirrhosis of the liver -- That's at least what a recent paper from the Department of Gastroenterology, Hanyang University Medical Center in Korea would suggest | read more...
• GH is an abdominal fat annihilator -- While most of you will have seen this news already, you may want to take a peek at the additional information on the "optimal" dosing regimen, I posted, yesterday | lean more...
• Dairy & vitamin B6 decrease, green tea & co increase homocysteine -- Good to know, yet what's even more important to know is that homocysteine is not even associated with an increased risk of CVD | read more...
• Improved body composition w/ DHEA supplementation -- Review of RCTs w/ 1353 elderly male participants says the effects are mediated by the conversion to testosterone and estrogen | learn more...

You've digested them all? Well, in that case you've two options left: (A) You begin practicing Thai-Chi or (B) you start right into an exciting weekend... whatever your choice may be, I hope you enjoy the rest of the day and come back tomorrow for more news from the realms of nutrition, exercise and supplementation sciences.

References:

• McCormack SE, McCarthy MA, Harrington SG, Farilla L, Hrovat MI, Systrom DM, Thomas BJ, Torriani M, McInnis K, Grinspoon SK, Fleischman A. Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents. Pediatr Obes. 2013 Jun 25
• Mottola MF, Inglis S, Brun CR, Hammond JA. Physiological and metabolic responses of late pregnant women to 40 minutes of steady-state exercise followed by an oral glucose tolerance perturbation. J Appl Physiol jap.00487.2013; published ahead of print June 27, 2013.
• Nimitphong H, Saetung S, Chanprasertyotin S, Chailurkit LO, Ongphiphadhanakul B. Changes in circulating 25-hydroxyvitamin D according to vitamin D binding protein genotypes after vitamin D₃ or D₂ supplementation. Nutr J. 2013 Apr 4;12:39.
• Shaw CS, Clark J, Wagenmakers AJ. The effect of exercise and nutrition on intramuscular fat metabolism and insulin sensitivity. Annu Rev Nutr. 2010 Aug 21;30:13-34. 
• Shinohara A, Takakura J, Yamane A, Suzuki M. Effect of the classic 1-week glycogen-loading regimen on fat-loading in rats and humans. J Nutr Sci Vitaminol (Tokyo). 2010;56(5):299-304.
  
• van Loon LJ, Koopman R, Stegen JH, Wagenmakers AJ, Keizer HA, Saris WH. Intramyocellular lipids form an important substrate source during moderate intensity exercise in endurance-trained males in a fasted state..J. Physiol. 2003. 553:611–25.
• van Loon LJ, Manders RJ, Koopman R, Kaastra B, Stegen JH, et al. Inhibition of adipose tissue lipolysis increases intramuscular lipid use in type 2 diabetic patients. Diabetologia. 2005a, 48:2097–107.
• van Loon LJ, Thomason-Hughes M, Constantin-Teodosiu D, Koopman R, Greenhaff PL, et al. Inhibition of adipose tissue lipolysis increases intramuscular lipid and glycogen use in vivo in humans. Am. J. Physiol. Endocrinol. Metab. 2005b. 289:E482–93.
• Wang N, Zhang X, Xiang YB, Li H, Yang G, Gao J, Zheng W, Shu XO. Associations of Tai Chi, Walking, and Jogging With Mortality in Chinese Men. Am J Epidemiol. 2013 Jun 27. [Epub ahead of print]
• Yang M, Qin Z, Zhu Y, Li Y, Qin Y, Jing Y, Liu S. Vitamin D-binding protein in cerebrospinal fluid is associated with multiple sclerosis progression. Mol Neurobiol. 2013 Jun;47(3):946-56.

The Glucose Repartitioning Effects of Exercise: Moderate Beats High Volume Training When It Comes to Shuttling Glucose Away From Fat and Right into the Muscle

"Are 2h of cardio each day still too little!?  It must be my thyroid! Yeah, that's it. It must be the thyroid!" Could be bro, but if it is probably self-inflicted hypothyrodism

In the context of my dissertations on the unwarranted vilification of insulin as a "fattening agent" (go back to "The "Pro-Insulinogenic" Effects of Non-Nutritive Sweeteners + Mechanisms & Consequences" if you have not read the article already), I presented data from a rodent study to make a point that insulin's fattening effects depend on two closely related and highly familiar factors.

One is the over-consumption of energy that is the norm, not the exception here in the Western Obesity Belt. In conjunction with the lack of glucose depleting exercise this "ensures" that the intra-muscular and hepatic liver stores of the average Westerner are always topped off and the only change to get rid of the glucose that's floating the system of the coke-guzzling convenient generation on a day-to-day basis is to pack it away in the adipose organ.

That being said, it is only logical to assume that working out would help mitigate the problem by restoring the "normal" state of partly if not fully depleted glycogen stores and allowing insulin to do its original "glycogen anabolic". It is this process of insulin induced glucose partitioning towards the emptied glycogen stores of the skeletal musculature and the influence of (a) sedentarism (control), (b) aerobic exercise worth 300kcal/day, and (c) aerobic exercise worth 600kcal/day a group of scientists from the University of Kopenhagen in Denmark (Reichenkendler. 2013) investigated in their most recent study.

300kcal or 600kcal does it even make a difference?

For the experiment on which this paper that is supposed to be published in one of the upcoming issues of the American Journal of Physiology, Endocrinology and Metabolism, the researchers recruited 27 moderately overweight men (BMI: 28.1(1.8); age: 30(6) years; no diabetic relatives, weight stable for the last 6+months), randomized them to one of the three previously mentioned conditions.

According to which group the subjects had been randomized to, the participants either continued their sedentary lifestyle (CON) or performed daily aerobic exercise of 300 kcal/day (MOD) or 600 kcal/day (HIGH) for 11 weeks. The workouts were performed

• at a higher intensity (>70% of VO2max), three times per week, and
• at a low-medium intensity on the other three workout day

As you can see this is more of a chronic "general activity" + exercise study, than your average acute (let's save some money) trials and thus highly relevant to the aim of investigating the effect of chronic

"[...] moderate or high dose aerobic physical exercise on insulin-stimulated glucose uptake in individual femoral muscle groups, intra- and retroperitoneal VAT, abdominal (both anterior and posterior) and femoral SAT [subcutaneous adipose tissue] in sedentary, young and moderately overweight men." (Reichenkendler. 2013)

Moreover, the use of DEXA scan and non-invasive FDG PET/CT + hyperinsulinemic, isoglycemic clamp tests by the means of which the researchers assessed the body composition and glucose uptake of the study participants before and after the 11-week intervention ensured that Reichenkendler et al. would get accurate results.

Figure 1: Change in skeletal muscle (left) and body fat (right) glucose uptake from pre- to post-interverion (Reichenkendler. 2013)

Speaking of results, in view of the fact that the participants had not been been engaged in  in regular exercise, before the study was conducted and considering the fact that their maximal oxygen consumption [VO2max] of ≤45 ml O2/kg body mass/min mirrors their sedentary lifestyles, it is actually not really surprising that the unaccustomed exercise led to decreases in abdominal subcutaneous, visceral and leg fat masses in the two intervention groups - what may be surprising, though is the fact that those were not statistically different in the medium vs. high volume group.

On the other hand, only the high, yet not the moderate volume exercise (600kcal/day) led to significant increases in fat free mass in the legs (with the difference between the moderate and high volume achieving borderline significance; p = 0.06).

1:0 for 600kcal/day and high volume training!?

The additional muscle building benefit from the high(er) volume in the study at hand appears to conflict the results of a previous study by Rosenkilde et al. On the other hand, the most important message still remains: Working out twice as much is not going to double your fat loss! If anything it will make you feel miserable. Remember that and spread the word!

The muscle building advantage of the high volume endurance exercise is interesting. After all it appears to contradict data from a previous study by Rosenkilde et al. who observed detrimental effects of doubling the exercise volume from 300kcal/day to 600kcal per day in their study from August 2012 (read more).
If we scrutinize the different protocols, this could be a result of an ostensibly small, but physiologically relevant difference in the exercise prescriptions:

While the subjects in the study at hand had the four low intensity days to recover, the Rosenkilde study did not deliberately implement intensity differences like that - the subjects were just told "you burn 600kcal/day - no matter what!" In view of the still prevalent notion that this would be most beneficial if you achieved it by "training in the zone" (the non-existent "fat burning zone"), it is not unlikely that for Rosenkilde's subjects every day ended up a "high" intensity day and the constant exercise induced stress ended up backfiring.

If we go by the body composition data this this was not necessarily the case in the study at hand.The increase in fatloss every noob believes would come out of simply doubling your cardio workouts was not present either and that despite the fact that the exercise induced total body glucose disposal rate was increased  only in the high volume group (p = 0.03). In the moderate intensity group this effect did nor reach statistical significance.

Figure 2: The overall greater GLUT-4 response to insulin (signifying improvements in insulin sensitivity) probably explains the advantage of the medium volume training (Reichenkendler. 2013)

Much contrary to the total body glucose intake, where both the liver and the adipose tissue are greatfully sucking up the glucose your muscles are not snatching from under their nose, the total skeletal muscle glucose uptake rate increased in both, the moderate (p = 0.007) and high (p = 0.002) volume groups.

And now for the real surprises...

Did you know that high intensity, muscle damaging workouts reduce the post-exercise glycogen repletion rate and could thus impair the general glucose repartioning effects of exercise? It cannot be said for sure whether an increase in muscle damage was partly to blame for the lower glucose repartitioning effects in the medium vs. high volume groups in the study at hand, but the long-lasting (10 days) defect in glycogen resynthesis Kevin P. O'Really et al. observed in their 1987 study in response to 45min of eccentric cycling should remind you that "go heavy of go home" does not imply that you go home only, when your muscles hurt so much that even going light is not possible any longer.

Much contrary to what you may expect, though, the increase in muscle specific glucose uptake was more pronounced in the moderate (difference to control p = 0.02) than in the high volume group, where only a trend (p = 0.06) was observed.

And while the total glucose uptake rate of femoral adipose tissue did not change significantly in either of the intervention groups, the amount of glucose that ended up in the abdominal subcutaneous fat stores decreased. Just like the muscle specific glucose repartitioning, this effect did yet occur only in the moderate, yet not in the high volume groups.

Similarly the glucose repartitioning away the visceral adipose tissue of the midsection was statistically significantly only for the moderate volume group. For the subjects in the high volume group, the researchers observed a non-significant tendency (p = 0.09) for a decrease in the amount of glucose that was taken up by the visceral fat depots in the abdominal region.

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What do we make of these counter-intuitive results: First of all, I would like to emphasize that any form of exercise is going to have a measurable repartitioning effect and whether the latter is "statistically significant" or not may in the end be of secondary importance. Moreover, the overall greater energy expenditure in the high volume regimen resulted in greater improvements in body composition than its low volume counterpart - irrespective of its "non-significant" or "borderline significant" glucose repartitioning effects (so much about "calories don't count", and "it's all about insulin and the fattening carbohydrates" ;-)

These abs were not sculpted by 600kcal/day workouts check out some more promising routines

On the other hand, the results of the study at hand to eventually confirm what the previously cited study by Rosenkilde et al. (click on the image with the mouse) already suggested: Doing more is not necessarily beneficial. Even in the presence of what you may call "light intensity recovery days", the daily hour (on the light days you will need way more than an hour to burn 600kcal) of the ever same, non-challenging exercise is not going to cut it - in the literal sense; or, to put it differently: doing low intensity training just to burn calories everyday is not yield the fat burning, muscle building or maintaining results you are looking for.

If you are looking for better alternatives, check out the fatloss support workouts in the Step By Step Guide to Your Own Workout.

References:

• O'Reilly KP, Warhol MJ, Fielding RA, Frontera WR, Meredith CN, Evans WJ. Eccentric exercise-induced muscle damage impairs muscle glycogen repletion. J Appl Physiol. 1987 Jul;63(1):252-6.
• Reichkendler MH, Auerbach P, Rosenkilde M, Christensen AN, Holm S, Petersen MB, Lagerberg A, Larsson HB, Rostrup E, Mosbech TH, Sjödin A, Kjaer A, Ploug T, Hoejgaard L, Stallknecht BM. Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: A randomized study using FDG PET imaging. Am J Physiol Endocrinol Metab. 2013 Jun 25. [Epub ahead of print]
   

Carnitine Loading Revisited: 3g Carnitine per Day Ward Off Vitargo Induced Fat Gain by Increasing Fatty Acid Oxidation and Total Energy Expenditure in 12 Week Human Study

Figure 1: With highly bioavailable carnitine in meat it is 100% paleo (unlike coke, obviously ;-)

I am not sure, whether its ten, twenty or maybe two-hundred ;-) years ago that the first carnitine supplement was introduced to the sport supplement market (from a paleo perspective it has always been there - in the form of meat!); and honestly I am too lazy to google it up. What I do know, however is that carnitine has been around ever since I first started working out. Incidentally, the same can be said about the debate whether or not supplementing with one or another form of this endogenously synthesized amino acid (your body can make carnitine from the amino acids lysine and methionine) would actually or just theoretically be beneficial for the average trainee.

Years have passed and I still hesitate, whenever someone asks me whether or not I'd recommend trying this or that form of l-carnitine to increase his or her performance. After years of being inclined to answer: "Very unlikely." The publication of a handful of promising studies over the past months makes me question, whether "May be worth a try" would not be a more appropriate response to this sixty-four-thousand dollar question.

Sixty-four-thousand dollars for l-carnitine?

The most recent of these studies is going to be published in the Journal of Physiology in a couple of weeks. It was conducted by researchers from the MRC/Arthritis Research UK Centre for Musculoskeletal Ageing Research, School of Biomedical Sciences at the University of Nottingham in the UK, and investigated the effects the provision of 2x1.36g of carnitine per day had on the energy
metabolism, body fat mass, and muscle expression of fuel metabolism genes.responses of 12 men who exercised at 50% VO2max for 30 min once before and once after 12 weeks twice daily feeding of

• 80 g carbohydrate from Vitargo (Control, n=6) or 
• 1.36 g L-carnitine + 80 g carbohydrate (Carnitine, n=6). Maximal

Contrary to what you may expect, the activity of the "fatty acid carnitine shuttle" or rather the corresponding mitochondrial enzyme, namely carnitine palmitolytransferase 1 (CPT1) remained similar in both groups over the course of the 12-week study period.

Suggested read: "Meaty "News": Choline, Carnitine & "Bacteria Poop" Make (Red) Meat Unhealthy. Learn Why the Latest Revelations Are Neither New, Nor Meat-Specific And Still Made the News" (read more)

Still, the additional carnitine did prevent the statistically significant weight and fat gain (1.9kg and 1.8kg, respectively) the scientists observed in the the control group. It also ...

• increased the muscle total carnitine concentration by +20%
• ramped up the activity of long-chain acyl-CoA, an enzyme that is crucially involved in the mitochondrial oxidation of long-chain fatty acids by +200% and
• upped the whole body energy expenditure by a comparatively small, but statistically significant +5%

Moroever, the researchers found 73 out of 187 genes relating to fuel metabolism to be upregulated in the subjects who had been randomized to the active arm of the study.

What mechanisms are at work and what do they do?

Now it is unquestionably not straight forward how these results relate to the one and only practically relevant outcome of the study - the lack of weight gain. Therefore it does appear prudent to take a look at what the researchers say about the relationship between the total carnitine levels, the expression of long-chain acyl-coa and the overall increase in energy expenditure on the decreased weight gain.

Their reasoning that the"20% increase in muscle carnitine content prevented the 1.8 kg increase in body fat mass associated with daily ingestion of a high carbohydrate beverage." Does yet not have large explanatory power imho. If the participants had been following a regular workout routine and the whole body energy expenditure hat been increased in all of these sessions to the same degree it was in the post-intervention test (+5%), this would probably make sense.

Table 1: Amount of carnitine in selected foods (learn more)

If we take a look at the other parameters the scientists measured, it is likely, yet by no means dead certain that this increase took place. After all, the changes in energy expenditure  were accompanied by...

"[...] an increase in fat oxidation, and a marked adaptive increase in the expression of gene networks involved in insulin signalling, peroxisome proliferator activated receptor (PPAR) signalling, and fatty acid metabolism over and above the decline observed in Control." (Stephens. 2013)

If we do assume that exercise does not thwart (maybe even promote) these effects, it could thus in fact make sense to answer the sixty-four-thousand dollar question by stating that it may at least be worth a try for those with unlimited funds.

And that despite the fact that the "mechanism underlying the increase in energy expenditure is not entirely clear" (Stephens, 2013) and the researchers can only speculate that it may be the result of carnitine driven increases in the rate of fac oxidation.

"Muscle free carnitine content was not measured after 20 min of exercise in the present study, but in our previous study (Wall. 2011) a 20% increase in skeletal muscle total carnitine content following 24 weeks of daily L-carnitine and carbohydrate feeding resulted in a striking 80% greater availability of muscle free carnitine following 30 min of low intensity exercise compared to Control, which was associated with a 30% reduction in PDC [pyruvate dehydrogenase complex] activation and 55% reduction in muscle glycogen utilisation." (Stephens. 2013)

For these changes to become practically relevant they would yet, as Stephens et al, suggest have to be present at reast, And while the 4-fold increase in resting muscle long-chain acyl-CoA content, of which the authors have shown previously (Stephens. 2006) to be consistent with an increase in muscle carnitine content and a switch in fuel metabolism at rest, would suggest that this is the case, I am not yet inclined to back off of my "probably not worth the extra bucks".

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Carnitine may also ramp up anabolic and shut down catabolic signals in trainees and I'd say this is probably a better argument to supplement than the "anti-cok(e)obesity effect" (learn more)

Bottom line: Despite the accumulating evidence of real world benefits of carnitine supplementation it would be cheaper and way easier to simply not guzzle an additional 4x servings of coke a day if you want to avoid weight gain.

And if you are really looking for arguments in favor of carnitine supplementation I'd suggest you'd rather base your decision to invest into a bag of bulk l-carnitine on the IGF-1, p-AKT and mTOR boosting and and atrogin, murf and fox-o inhibiting anabolic and anti-catabolic effects study by Keller et al. reported in their March 2013 study you've read about here at the SuppVersity on March 18, 2013 (read more).

References:

• Keller J, Couturie A, Haferkamp M, Most E, Eder K. Supplementation of carnitine leads to an activation of the IGF-1/PI3K/Akt signalling pathway and down regulates the E3 ligase MuRF1 in skeletal muscle of rats. Nutrition & Metabolism. 2013; 10:28 
• Stephens FB, Wall BT, Marimuthu K, Shannon CE, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL. Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks, and prevents body fat accumulation in humans. J Physiol. 2013 Jul 1. [Epub ahead of print]
• Wall BT, Stephens FB, Constantin-Teodosiu D, Marimuthu K, Macdonald IA, Greenhaff PL.
  Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol 2011. 589:963-973.

Cut the Weight, Add the Vibe: Squatting on Vibration Plates - A Valuable Tool in Your HIIT & Conditioning Repertoire or Just Plain Out Embarrassing?

Disclaimer: This article contains prejudiced references to the way women train. Please don't take it personally, ladies; take it as a challenge to show us guys that you know better than that ;-)

I know, it is embarrassing to even think of joining the mostly older ladies on the whole body vibrators in your gym. According to a recent study from the Florida International University (Serravite. 2013), it may yet really be worth to grab the Olympic Bar, load it with ~50% of your usual squatting weight, check if no trainer is there to freak out that you + the weight on your back may damage the expensive workout equipment and hop right onto the Whole Body Vibration Plate next to the nice older lady who is staring at you (a heretic) with awe.


Now, aside from being talked about at the gym, the main reason to actually take my advice and relocate your squat workouts to the the whole body vibration plates is the increased energy expenditure you can achieve, when you're performing your squats on shaky grounds.

Good vibrations, bad vibrations?

In fact, according to the data, Daniel H. Serravite, David Edwards, Elizabeth S. Edwards, Sara E. Gallo and Joseph F. Signorile recorded, while their 10 active male graduate and undergraduate students (26.50 ± 5.06 years old, weight 83.18 ± 9.46 kg, height 184.0 ± 8.95 cm) without prior lifting experience were fidgeting on the vibration plates, clearly shows that the added "resistance" due to the constant vibrations decreases the energy efficacy and doubles the energetic demands of the exercise.

Now, while this will certainly not give you the bragging rights, a new PR on the bench or in the squatting rack would give you, the combination of light-weigh squats and full-body vibration could in fact be turned into a highly effective, compared to regular squats less injury prone (you will need much less weight) staple exercise in a HIIT-esque cardiovascular and fat burning workout.

How exactly did that work?

In the study at hand, the subjects performed 30 s sets of active squatting, using a range of motion from slightly below full extension to 1.57 rad, were performed at a speed of one squat per 3 s (controlled by a metronome).

No you don't have to wear a mask, as well - that was just necessary to ensure that the researchers would be able to measure energy expenditure and substrate utilization correctly.

The angle was controlled by setting a horizontal stick as a limit at the lower end of the motion for subject reference. A one  min period of passive recovery was provided between sets.

The nine training protocols represented different combinations of external load applied at shoulder level  using a backpack (0%, 20%, and 40%BW) and vibratory condition (see Figure 1). Vibratory conditions ranged from no vibration (NV) to 35Hz at 2–3 mm (35L; 1.89g) and 50Hz at 5–6 mm (50H; 7.7g) (Pel. 2009). The vibratory conditions reflect the frequency–displacement relationships found to maximize neuromuscular performance in our earlier study (Adams. 2009).

The equipment the scientists used was a synchronous WBV plate (Model Pro-5, Power Plate North America, Northbrook, IL).

And if you take a peak at the picture above (no not the in the head of the article, guys!) you'll notice that the external load was not, as I humorously implied in the introduction loaded an Olympic bar with 2x 25kg and 2x12.5kg weights on both sides, but rather put into sandbag containing backpack.

So how exactly would that look like in practice?

Let's take an example. If your 1-RM max on the squat were 200kg and you were usually squatting 40% (=80kg) of those for 10x10 with minimal rest in-between sets to turn your leg training into a fat burning, mitochondrial burning HIIT workout, you'd expend the "exact" same amount of energy if you performed those squats with only 20% of your 1-RM max on a vibration plate.

Figure 1: Oxygen consumption during squats with different loads (0%, 20% and 40% of the body weight) at different  frequencies and amplitudes (NV - no vibration; 35L - 35Hz at 2-3 mm, 1.89g; 50H 50Hz at 5-6 mm, 7.7g; Serravite. 2013)

Ok, in essence, it would warrant further investigation, whether the results of the study at hand, in the course of which the subject squatted with only 16kg / 32kg on their backs would translate to a situation in which you are squatting with 40kg or 80kg, respectively.

Figure 2: Oxygen consumption during recovery; * indicates sign. diff. from no vibration (Serravite. 2013)

If you take a closer look at the data in figure 1 & figure 2 you will yet notice that squatting on the full body vibrator without additional weight, as the previously mentioned older ladies and the "I hope there is no fat in that salad dressing"-gals who don't want to risk breaking their freshly manicured fingernails love to do it, is not going to yield any significant benefits over regular squats. It would therefore appear likely that you are going to benefit from using even higher loads, as well. Whether the effect size will be significantly greater is yet another question; a question that cannot be answered based on the study at hand, only.

This does not mean that it won't benefit the activation of stabilizer muscles that would not be activated to the same extend during the regular squat on stable ground).

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If the rowing machine is not already part of your personal repertoire of HIIT compatible workout equipment, I highly suggest you go back to the "Eight HIIT Sessions on the Rowing Ergometer Cut Body Fat, Increase Adiponectin, VO2Max & Performanc"-post from December 2012 (read more)

So what? In view of the fact that neither the respiratory exchange ratio, nor the heart rate did vary significantly between the testing conditions, the use of one of the often sneered at vibration plates could actually make a viable addition to a HIIT-esque squatting workout. You'd get the same metabolic bang for your buck, but could use significantly lower weights. The latter entails a lower risk of injury and could shorten the recovery times.

And as an added bonus you will be activation muscles, of which many of you may not even have been aware that you had them.

This does not mean that you should forget about your previous HIIT workout regimen all-together. For those who don't care about being stared at at the gym the proposed combination of a high(er) rep, short rest squatting workout could yet become a new tool in their (hopefully already versatile) cardiovascular exercise repertoire.

References: 

• Adams JB, Edwards D, Serravite DH, Bedient AM, Huntsman E, Jacobs KA, Del Rossi G, Roos BA, Signorile JF. Optimal frequency, displacement, duration, and recovery patterns to maximize power output following acute whole-body vibration. J Strength Cond Res. 2009 Jan;23(1):237-45.
• Pel JJ, Bagheri J, van Dam LM, van den Berg-Emons HJ, Horemans HL, Stam HJ, van der Steen J. Platform accelerations of three different whole-body vibration devices and the transmission of vertical vibrations to the lower limbs. Med Eng Phys. 2009 Oct;31(8):937-44.
• Serravite et al. Loading and Concurrent Synchronous Whole-Body Vibration Interaction
  Increases Oxygen Consumption during Resistance Exercise. Journal of Sports Science and Medicine. 2013 [epub ahead of print].

Protein Timing Reloaded: A Reminder on the Importance of Repeated 20g Pulses for Optimal Protein Synthesis

Protein timing & dosage matter for protein synthesis in the PWO window.

"30g+ of quality (=leucine rich) protein per meal." I am not really sure how often I have been writing and saying this here, on facebook and on the Science Round Up at SuperHumanRadio in the past months, but I hope that it's been enough for you to remember this simple rule; a rule that will also help you to distribute your protein intake somewhat more evenly across the day and thus - as a recent study that was conducted by researchers from the School of Medical Sciences at the RMIT University, in Melbourne, the Australian Institute of Sport in Canberra, the Department of Kinesiology at the  McMaster University in Hamilton, Ontario and the Nestlé Research Center in Lausanne, Switzerland - maximize the protein induced increase in protein synthesis.

Note: This paper is actually an almost identical clone to a previous paper by the same groups of researchers (Moore. 2012). Since I've discussed that back in 2012 already, I still decided to include it in this week's SuppVersity line-up, because it fits in perfectly with the previously discussed study on the benefits of protein intakes >2x RDA and that simply eating more protein is not really gonna cut it. If you want to read up on the corresponding SuppVersity article discussing the 2012 study, you can do this right here.

More is only more if it's adequately timed & distributed

The scientists knew from countless previous experiments that a single bolus of∼20 g of protein after a bout of resistance exercise would provide a maximal anabolic stimulus during the early post-exercise recovery period (∼5 h). The "effect of various protein feeding strategies on skeletal muscle protein synthesis during an extended recovery period (12 h)" (Areta. 2013) was yet largely  unknown. In order to shed some light onto the protein-anabolic response in this "post-post-workout window", the researchers compared three different patterns of ingestion of 80 g of protein during 12 h recovery after resistance exercise and the associated anabolic response in human skeletal muscle:

• 10, 20 or 40 g feedings using a pulsed, intermediate or bolus ingestion regimen, respectively
• consumed after 4x10 reps @  80% of the 1 RM with 3 min rest between sets

 In accordance with the hypothesis that protein timing would directly influence the expression of "anabolic" signalling proteins in the muscle, the researchers observed significant hierarchy with BOLUS > INT > PULSE in the magnitude of phosphorylation of p70S6K and p-AKT on an individual base.

Figure 1: Fractional protein synthesis expressed relative to mean protein synthesis at the respective timepoint (left); corresponding levels of the "anabolic" signaling proteins p70S6K (right, top) and p-akt (right, bottom; Areta. 2013)

However, despite the fact that the immediate response was maximal in the BOLUS group, both the actual amount of protein that was shuttled into the muscle was still significantly higher in the INT trial, in the course of which the subjects ingested 20g of protein every three hours.

So what's the deal, then?

The "anabolic window" turns out to be more of a barn door, which is unlocked by the key of exercise and nutrition science (learn more)

In their discussion of the results, the researchers point out that this is the first study to confirm the long-touted notion that ...

"[...] rates of myofibrillar protein synthesis (MPS) remain elevated above rest throughout 12 h of recovery when a single bout of resistance exercise is followed by the partitioned ingestion of 80 g of high quality protein. Furthermore, we show that daily rates of protein synthesis were highest with regular (i.e. every 3 h) intake of a moderate (20 g) quantity of rapidly digested whey protein." (Areta. 2013)

Areta et al. specifically emphasis that the acute stimulation of the nutrient and contraction-sensitive intracellular signalling network is thus not the main determinant of net protein synthesis in the huge post-anabolic window.

A word of caution: Before you freak out totally about how big you're going to be next week, now that you follow the optimal protein supplementation regimen, I suggest you take a look at Alan Aragon and Brad Schoenfelds paper on the purported and real benefits of protein timing and its real-world implications | read more ...

The anabolic effects of the intermediate supplementation do yet only appear to be. Over the whole study period, they are not statistically different and the superiority in terms of the actual fractional protein synthesis (FSR) persists, even when using a mean intracellular enrichment from the other groups. Thus an increase in intracellular enrichment cannot be the underlying mechanism for the increase in  fractional synthesis rates in the intermittent supplementation trial (INT) the researchers ascribe to an optimized interplay between resistance exercise, time between ingestion, and the total quantity (20g = at the critical threshold) of each (whey) protein feeding. The optimally timed and adequately dosed ingestion of 4 servings of 20g of whey could thus have

Figure 2: Plasma EAA concentration following a bout of leg extensions and subsequent whey ingestion during a 12 h recovery period (top); timing and dosage of supplementation (bottom); p < 0.05 for pulse *, intermittent †, and bolus ‡ at equivalent time point (Areta. 2013)

"[...] resulted in a cyclical plasma AA profile that might be considered ideal to stimulate MPS [...] While the temporal resolution of time points selected for quantifying plasma amino acid concentrations failed to clearly show distinct amino acid profiles throughout the 12 h post-exercise period a hierarchical response was observed for leucine concentration early in recovery indicative of an initial divergence in branch-chain amino acid availability between feeding patterns [figure 2]. Thereafter, the continuous hyperaminoacidaemia or lack of postprandial periods of relative hypoaminoacidaemia over the 12 h period with PULSE feeding most likely resulted in some suboptimal stimulation of the protein synthesis machinery similar to that observed with continuous amino acid infusion." (Areta. 2013). 

Now, this may appear counter-intuitive at first, after all the aminoacedemia in the intermediate trial does not appear to be more pronounced than that in the pulse trial and certainly inferior to the one of the bolus trial. This is in fact true, but it is a mere consequence of much greater %-ual absorption of the amino acids in the intermittent trial compared to both the bolus and pulse supplementation, of which the former are 'protein wasting' and the latter simply insufficient to fully trigger the protein synthetic response.

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One thing to keep in mind, when you look at the results of the study at hand is the fact that this is just another acute resistance training study that employs an unrealistic (leg extensions only) workout. In other words, we cannot simply take for granted that statistical significant difference in short term protein synthesis (12h is still short) will also translate into measurable, let alone visible improvements in muscle hypertrophy. Still following the protocol outlined to the left is certainly not going to hurt you.

Bottom line:  It should not really be necessary that I actually formulate another bottom line. If you stick to my basic recommendations (outlined among others in my interview with my buddy Sean Casey) you will do something very similar with your 3-5 meals with 30+g of quality protein each. The only thing that may be worth adding to it is a re-emphasis on the interaction of timing and dosing. 

You need at least 20g of leucine-rich protein to kickstart protein synthesis and - as of now - it looks like those will not sustain maximal protein synthesis for longer than ~3h before you have to 'refuel' the amino acid pool and (probably more imporatantly) 'reignite" the protein synthetic machinery with another 20g+ bolus of whey.

In view of the fat that proteins with a low(er) leucine content will probably need to be ingested in higher amounts I would still stick to the '30g+ rule' - after all, I assume you won't want to live off whey protein supplements and Quest Bars, only - do you?

Important additional read: "Evidence From the Metabolic Ward: 1.6-2.4g/kg Protein Turn Short Term Weight Loss Intervention into a Fat Loss Diet" | read more...

References: 

• Areta JL, Burke LM, Ross ML, Camera DM, West DW, Broad EM, Jeacocke NA, Moore DR, Stellingwerff T, Phillips SM, Hawley JA, Coffey VG. Timing and distribution of protein ingestion during prolonged recovery from resistance exercise alters myofibrillar protein synthesis. J Physiol. 2013 May 1;591(Pt 9):2319-31. doi: 10.1113/jphysiol.2012.244897. Epub 2013 Mar 4. 
• Moore DR, Areta J, Coffey VG, Stellingwerff T, Phillips SM, Burke LM, Cléroux M, Godin JP, Hawley JA. Daytime pattern of post-exercise protein intake affects whole-body protein turnover in resistance-trained males. Nutr Metab (Lond). 2012 Oct 16;9(1):91.

Sugar Sweetened Beverages, Bottled Water & the Obesity Epidemic: Evidence, Counter-Evidence & Scapegoatism

SSBs worse than an obesity pill?

It is a given fact that neither I nor any sane researcher is going to debate the over-consumption of sugar sweetened beverages are part of the reasons why we are fat. The way they are currently portrayed as the worst invention since trans fats, could however fire back on us. You do just have to look how willingly the oil refiners are bashing the corn refiners, how the fruit "juice" industry claims that their "healthy 100% fruit juices were less obesogenic" than a coke (which is clearly not the case) and how consumers are standing in the line at their local fast-food outlet thinking about taking the diet coke with their menu to be able to have an additional "healthy fruit smoothie" as a dessert.

I had all that in the back of my head already, when I hit on a related "Pro v Con Debate" in the early views (articles that are not yet available in the print edition) of the Obesity Reviews and thought that you might be interest in some of the arguments F.B. Hu and K.A. Kaiser et al. are presenting in their "debate" (in fact we are talking about to separate position papers) on the "Role of sugar sweetened beverages in Obesity", as well.

Point: Sugar sweetened beverages, obesity & diabetes - Scientist says the evidence is there

(Hu. 2013) I would assume that the vast majority of you is not going to have to be convinced by rational or irrational arguments that sugar sweetened beverages will increase your risk of obesity and diabetes. Still, F.B. Hu, a scientists from the Departments of Nutrition and Epidemiology at the Harvard School of Public Health in Boston must have thought of the rest of the public and the bribed, ah... pardon "mislead" policy makers, when they compiled their latest paper with the tell-tale title "Resolved: there is sufficient scientific evidence that decreasing sugar-sweetened beverage consumption will reduce the prevalence of obesity and obesity-related diseases". According to Hu,

Figure 1: Relative risk of the development of obesity per increment of 10 risk alleles, according to intake of sugar-sweetened beverages; data based on the Nurses’ Health Study (NHS) and Health Professionals + follow up (HPFS), the Women’s Genome Health Study (WGHS) and the three cohorts together (Hu. 2013)

"Consumption of SSBs has increased markedly across the globe in recent decades, tracking closely with the growing burdens of obesity. These beverages are currently the largest source of added sugar intake and the top source of daily energy in the U.S. diet. The cumulative evidence from observational studies and experimental trials is sufficient to conclude that regular consumption of SSBs causes excess weight gain and these beverages are unique dietary con- tributors to obesity and T2D. Compelling evidence indicates that reducing SSBs will have significant impact on the prevalence of obesity and its related diseases, especially T2D. [...] Although reducing SSB consumption alone is unlikely to solve the obesity epidemic entirely, limiting intake of SSBs is one simple change that could have a measurable impact on weight control and prevention of T2D and other metabolic diseases" (Hu. 2013; my emphasis)

Hu also points to the "strong resistance from the beverage industry" and the few, but increasingly numerous  public policies and regulatory strategies to reduce intake of SSBs that are already in place or being developed. The importance of a grass-roots approach, on the other hand appears to escape him. After all, it often does not look like this, but in the end the US is still a free country: You don't have to drink Pepsi, Coke and Mountain Dew, folks and neither do your friends and family.

Counterpoint: Sugar sweetened beverages are bad - in theory, but what about the reality?

(Kaiser. 2013) Now that your conviction that sugar sweetened beverages are bad, has been confirmed. let's shake the evidence and take a peak at what K. A. Kaiser, J. M. Shikany. K. D. Keating and D. B. Allison have to say about the question whether reducing sugar-sweetened beverage consumption will reduce obesity and why they feel that "[The e]vidence supporting conjecture is strong, but evidence when testing effect is weak".

Theory vs. experimental evidence: In fact the theoretical slope of the line depicting the increase in weight gain due to the consumption sugar sweetened beverages is more than 10x steeper than the one that has been observed in scientific studies (see figure 3).

What is particularly interesting is that the theoretical prediction is accurate only in the lowest 10-15% of the SSB intakes investigated in the study, for the "real SSB junkies" the gab widens significantly.

Figure 2: Rise in obesity rates (round markers) and bottled water consumption (square markers) in the US (Kaiser. 2013)

If you take a look at the graph to the right (figure 2) you will notice right away: We can as well blame the obesity epidemic to the increase in bottled water consumption (or the decrease in tap water consumption?) - the epidemioloical "evidence" is conclusive!

This figure is yet not the only thing Kaiser at al. enlist to make you at least reconsider how conclusive the evidence of which Hu just argued that it is "there" actually is. The most important factors Kaiser, Shikany, Keating and Allison want to remind us of, when it comes to the interpretation and evaluation of the hitherto available studies are...

• the risk of bias -- Most scientists start out with the same conviction we do: "Sugar sweetened beverages make you fat!" Against that backround it is even more detrimental that  "some study designs failed to adequately isolate treatment effects from the attention researchers paid to some groups." (Kaiser. 2013) The researchers also point out that not all studies had an objective measure of participant compliance (returned containers, urinary sucralose measures) and did not report whether the people who accessed the effects were blinded as well (10 out of 15 studies did not). Publication bias, on the other hand, did not appear to be a factor to skew the results (Kaiser. 2013)
• missing / insufficient sensitivity analysis -- In their re-analysis the researchers found sign. differences in the obesogenic effects of SSBs on young vs. old, male vs. female and lean vs. obese participants, yet the majority of the studies does not accordingly differentiate the outcomes.
  

  

  Figure 3: Observed (30,34,40–42,62) versus theoretical (63) weight gain effect of mandatory sugar-sweetened beverage (SSB) consumption (Kaiser. 2013)

  "[...] we evaluated the overall summary effects by excluding the studies referenced above. The overall SMD for the added SSB studies (adults only) increased by 0.06 (to 0.34; 95% CI: 0.15 to 0.54). The overall SMD for the reduction of SSBs in children of all weight categories was reduced by 0.01 (to 0.07; 95% CI:  -0.01 to 0.15). The overall SMD for the reduction studies in children only who were overweight or obese at baseline increased by 0.05 (to 0.30; 95% CI: 0.13 to 0.46)." (Kaiser. 2013)

  The general heterogenity (all variables included) is yet not another contributor to significant changes in the study outcomes.
• data interpretation / analysis - The scientists suggest that analyzing only absolute weight / BMI levels is not an adequate measure and propose two different methods to evaluate the data
  
  1. Asking the question, whether a person that is in the "SSB" group would increase or decrease weight / BMI if he or she switched to the other group - This analysis yielded a +2% and +7% change of weight / BMI reduction.
  2. Using the correlation data as basis to calculate the explanatory value of SSB consumption - This analysis showed that only 1.92% of the variance in body weight or BMI change is explained by SSB consumption, for the variance weight reductions in persons of all weight categories the figure is a hilariously irrelevant 0.09%
  As you can see, looking at the data from a marginally different angle can easily make all the difference. 

I know what you are thinking now "but XY said..." or "but what about..." and obiously Kaiser et al. must also have thought about objections like these and added a brief adjunct to their paper in which they point towards three major reasons that explain why the influence of sugar sweetened beverages is perceived as larger than life by the public:

1. 

   Don't get me wrong, I love the "ads" of the NYC Dept. of Health & Mental Hygiene campaign against sugar sweetened beverages, and used it as title picture for a previous post on the fattening effects of SSBs, but they are part of the problem Kaiser et al. are pointing at in their paper. People will sit next to them think about the gym and say: "Well I drink diet coke, so I don't have to go to the gym today - after all sugar is the problem!"

   Emotion-raising language - Emotion-raising language has often been used in discussions of SSBs and obesity. Some authors have used words like ‘plague’, ‘toxic’, ‘hazardous’ (4,53) and ‘deadly’ when describing SSBs or the sugars they contain and have tried to promote perceived connections between SSB marketers and the worst behaviour of tobacco marketers . Although such words may help to advance an agenda, they do not educate or inform the public.
   
   Moreover, they likely raise emotions and impair logical reasoning. As Kersh and Morone wrote, ‘Scientific findings never carry the same political weight as does a villain threatening American youth.
   
   If critics successfully cast portions of the industry in this way, far-reaching politi- cal interventions are possible, even likely. When an industry becomes demonized, plausible counterarguments (privacy, civil liberties, property rights, and the observation that “everyone does it”) begin to totter.’
2. Distortion of scientific information - A second factor that has likely contributed to misperceptions in this area is the distortion of scientific information by some authors and commentators. [...] Clearly, such practices mislead and have likely contributed to misperceptions in the scientific and lay communities about the strength of the evidence regarding the proposition debated here.
3. The mere exposure effect - The final factor that we believe has led to the erroneous perception that the evidence showing that the proposition of this debate has been unequivocally proven is the ‘mere exposure effect.’
   
   The mere exposure effect is the label psychologists use for the phenomenon that the more a person is exposed to an idea, the more they come to like and accept it. As the Nobel Prize-winning economist Daniel Kahneman described, ‘A reliable way to make people believe in falsehood is frequent repetition, because familiarity is not easily distinguished from truth. Authoritarian institutions and marketers have always known this fact. But it was psychologists who discovered that you do not have to repeat the entire statement of a fact or idea to make it appear true’
   
   The number of articles on SSBs and obesity and the number of statements that SSBs are especially problematic in obesity are extraordinary, especially in comparison to the modest amount of probative data. Thus, opinions about SSBs may have been offered so often that these opinions have become accepted as fact by many in the scientific community, media and lay public.

I probably could quote addtional parts of the excellently written paper here, but I guess you are getting the notion and will be able to understand that neither my nor the scientists who wrote the original paper intend to support the position of the SSBs industry that have long realized that this war cannot be won on the scientific stage and have long focused all their efforts having their "lifestyle" drinks being marketed by the "cool and hip" celebrities, athletes and super models to the "wanna be cool and hip" normals.

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Bottom line: I am well aware that some of you are now probably already dialing the Dr. Lustig's phone number or calling the blogosphere's vice police to accuse me of making a pact with the Coca Cola company.

You all know I am an opponent of the consumption all sugar & HFCS sweetened drinks and foods and well aware of the "fat consequences" (learn more), but overemphasizing the roles of SSBs or HFCS, is not going to help us solve the global obesity problem.

But let's be honest, you all know that I neither drink nor recommend anyone to drink sugar sweetened beverages. My interest is in understanding the contributions each and every of the myriad of dietary, behavioral, endocrine, paracrine, neurological, environmental, social, ... to the obesity epidemic and if you take a look the 1.92% explanatory value of SSBs consumption in terms of body weight and BMI, it is clear that sugar sweetened beverages are a major contributor to the obesity epidemic.

Still it is not warranted and would be a consequential mistake to expect that by taking them off the market the whole issue would be solved. We all know that this won't be the case and you just have to look at the non-existent long-term effects switching to diet sodas had on the waist lines of the obese to know that we have to do more than remove all sugar sweetened beverages from the displays of the supermarket.

Does this mean we should not tell people they are bad for them? Try to tax or ban them? No. What it does mean, though, is that the war against obesity is not a war against SSBs, only.

References:

• Hu FB. Resolved: there is sufficient scientific evidence that decreasing sugar-sweetened beverage consumption will reduce the prevalence of obesity and obesity-related diseases. Obes Rev. 2013 Jun 13.  
• Kaiser KA, Shikany JM, Keating KD, Allison DB. Will reducing sugar-sweetened beverage consumption reduce obesity? Evidence supporting conjecture is strong, but evidence when testing effect is weak. Obes Rev. 2013 Jun 7.