Artificial Sweeteners Mess W/ Gut Biome & Induce Insulin Resistance in Rodents - What about Man? Plus: Sucralose & Saccharin, Not Aspartame Induce the Effect

Could diet coke really be more obeso- genic than regular coke? There is no evidence to prove that and still the mainstream interpretation of the latest rodent study in Nature says just that.

In contrast to some other experts, I believe in the usefulness of rodent studies as preliminary, easily available way to investigate general physiological processes. Still, when I look at a study that has to use germ-free mice to produce an effect, I begin to doubt that the results are relevant for someone with an intact gut microbiome (no matter if it's "perfectly healthy", or not).

Before I go on with my criticism of a recently published study in Nature (Suez. 2014), I would suggest we'll first take a look at study design and outcome, to make sure not just Steven and Conor, both of whom asked my opinion on the study on Facebook, know what we are talking about.

You can learn more about sweeteners at the SuppVersity

Unsatiating Truth About Artif. Sweeteners?

Will Artificial Sweeteners Spike Insulin?

Sweeteners & the Gut Microbiome Each is Diff.

Sweeter Than Your Tongue Allows!

Stevia, the Healthy Sweetener?

Sweeteners In- crease Sweet- ness Threshold

Suez et al. claim that their study, a 10-week study in the course of which germ-free mice (no bacteria in the gut at the onset of the study) were fed standard chow and supplied with unlimited access to

• saccharin (artificially), sucralose or aspartame sweetened drinking water,
• naturally sweetened drinking water with either sucrose or glucose as a sweetener, or
• plain water as a control,

would demonstrate that the consumption of commonly used non-caloric artificial sweeteners (NAS) formulations, in this case , drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. In that, they probably rightfully point out that

"[...t]hese NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS," (Suez. 2014)

but they don't tell the reader without full-text access that the negative effects occurred only in four of the animals, were saccharin- and sccralose exclusive and did not occur with the often (falsely) derided sweetener aspartame (see Figure 1, right hand side).

Figure 1: Changes in the bacterial make-up (left) and consequences for the glycemic response after 11 weeks on regularly or artificially sweetened drinking water and antibacterial treatment (Suez. 2014).

Scientific fraud? No, I would rather say a clever way to draw everyone's freakin' attention to a problem that (even if it exists), is not one of all artificial sweeteners and maybe not even be one everyone is susceptible to.
You, as a SuppVersity reader know that this is not the first study to show significant effects of alternative sweeteners on the gut microbiome of the host.

Previous experimental evidence shows that NAS promote, not hinder weight loss | learn more

Experimental evidence vs. observational statistics: As a SuppVersity reader you will also remember that experimental evidence from human studies shows that "Artificial Sweetened Foods Promote, Not Hinder Fat(!) Loss. 1.2kg Body Fat in 70 Days By Eating Artificially Sweetened Products." In the corresponding study by Sørensen et al. I wrote about in May 2014, the artifical sweetener group also had lower hunger ratings, and higher fat oxidation rates compared to the subjects on sucrose sweetened diets. Similar results have been reported by Chen et al. in a study, where subjects replaced part of their regular SSB consumption with diet drinks (Chen. 2009) and de Ruyter et al. who recorded sign. reductions in fat and weight gain in youths after masked replacement of regular SSBs with diet coke & co (de Ruyter. 2012).

In April 2014, I already wrote about a corresponding study by Daly et al. which found that "[d]ietary supplementation with lactose or artificial sweetener enhances swine gut Lactobacillus population abundance," and shows that this effect can be beneficial, as well (at least atm, we still believe that lactobacilli were among the "good guys").

Table 1: Human gut-associated microbial species capable of metabolizing fructose, sugar alcohols, artificial sweeteners (left) and rare sugars and host metabolism and potential implications of consuming various dietary sugar compound (right; HFCS = high fructose corn syrup | Payne. 2014)

Likewise earlier this year, Payne et al. (2014) published a review on the gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols and the implications for host–microbe interactions contributing to obesity (see Table 1), which suggests both, positive and negative effects depending on the type of sweetener that's used. In this context, it's yet worth mentioning that previous reviews of the literature clearly indicate that the role of artificial sweeteners in the gastrointestinal tract in humans vs. rodents may be fundamentally different (Brown. 2012).

Accordingly, the results Suez et al. present in their latest paper would hardly be considered significant evidence of the existence of a similar problem in human beings, if there weren't the results of an on-going study the scientists are doing. A study that clearly indicates that "similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects." (Suez. 2014)

Alright, but there is one caveat: The previously mentioned human study, the data of which has unfortunately not yet been published has a built-in selection bias with the subjects that meet the criterion of long-term NAS consumption usually being those who have all the reason, namely weight problem, to avoid sugar-sweetened products.

Table 2: Data from the unpublished ongoing observational human study by the same researchers -- Correlates of chronic sweetener (ab-)use; In red: parameters directly related to glycemic control (Suez. 2014)

Still, the significant positive correlations between NAS consumption and several metabolic-syndrome-related clinical parameters (Table 1), including increased weight and waist-to-hip ratio (measures of central obesity); higher fasting blood glucose, glycosylated haemoglobin (HbA1C%) and glucose tolerance test (GTT, measures of impaired glucose tolerance), and elevated serum alanine aminotransferase (ALT, measure of hepatic damage that is likely to be secondary, in this context, to non-alcoholic fatty liver disease) are unquestionably disconcerting and should make us all revisit the amount and frequency with which we are using artificial sweeteners, if the results are eventually corroborated by experimental, not observational, evidence.

Ah, and did the other Internet sources you looked at mention that only saccharine and sucralose, but no allegedly worst of all artificial sweeteners, aspartame, lead to changes in glucose homeostasis? No, well I thought so and I guess they didn't mention either that less than 50% of the mice even developed measurable decreases in insulin tolerance, right? In that case, the fact that stevia has anti-microbial properties (Goyal. 2010; Subudhi. 2010) and could thus also mess with the gut microbiome, wasn't mentioned either, right? Comment on Facebook!

References:

• Brown, Rebecca J., and Kristina I. Rother. "Non-nutritive sweeteners and their role in the gastrointestinal tract." The Journal of Clinical Endocrinology & Metabolism 97.8 (2012): 2597-2605.
• Chen, Liwei, et al. "Reduction in consumption of sugar-sweetened beverages is associated with weight loss: the PREMIER trial." The American journal of clinical nutrition 89.5 (2009): 1299-1306.
• Daly, Kristian, et al. "Dietary supplementation with lactose or artificial sweetener enhances swine gut Lactobacillus population abundance." British Journal of Nutrition 111.S1 (2014): S30-S35.
• de Ruyter, Janne C., et al. "A trial of sugar-free or sugar-sweetened beverages and body weight in children." New England Journal of Medicine 367.15 (2012): 1397-1406. 
• Goyal, S. K., and R. K. Goyal. "Stevia (Stevia rebaudiana) a bio-sweetener: a review." (2010).
• Payne, A. N., C. Chassard, and C. Lacroix. "Gut microbial adaptation to dietary consumption of fructose, artificial sweeteners and sugar alcohols: implications for host–microbe interactions contributing to obesity." obesity reviews 13.9 (2012): 799-809.
• Sørensen, Lone B., et al. "Sucrose compared with artificial sweeteners: a clinical intervention study of effects on energy intake, appetite, and energy expenditure after 10 wk of supplementation in overweight subjects." The American journal of clinical nutrition (2014): ajcn-081554. 
• Subudhi, E., et al. "In vitro antimicrobial study of plant essential oils and extracts." Int. J. Microbiol 8.1 (2010): 1-6.
• Suez et al. "Artificial sweeteners induce glucose intolerance by altering the gut microbiota." Nature (2014). Ahead of Print.

Melatonin the Anabolic On-Switch!? Is Supplementation Necessary for Older and Beneficial for Younger Trainees?

Whatever sleeping position you and your partner prefer, you better make sure you do get some sleep. There'll still be time for life's other pleasures, don't worry  ;-)

If you are - as I would highly suggest - following the 6-12 SuppVersity Short News on Facebook, you will be aware of the accumulating evidence suggesting that a lower resistance to the inflammatory assault of exercise is at the heart of the age-induced decline in muscle gains.

We all know that especially those of us, who are still in good shape in their 60s and beyond are already having a hard time to keep the status quo, and only a handful of them appears to be able to make constant progress. But is this something you just have to accept or can the latest research help you overcome or at least lower the "anabolic" resistance? And if so, could young(er) individuals benefit from the same or similar interventions?

Age, inflammation, recovery and supercompensation

In a soon-to-be-published study from the University of Alabama at Birmingham an analysis of the vastus lateralis muscle gene expression and protein cell signaling of the IL-6 and TNF-α pathways in myoblasts from young (AGE28) and old (AGE64) donors, which have been pre-treated with TNF-α revealed that ...

"[i]ndices of activation for the pro-inflammatory transcription factors STAT3 and NFκB were highest in AGE76. Resistance loading reduced gene expression of IL-6 receptor, MuRF1, and atrogin-1, and increased TWEAK receptor expression. Donor myoblasts from AGE64 showed impaired differentiation and fusion in standard media, and greater NFκB activation in response to TNF-α treatment (compared to AGE28)".(Meritt. 2013; you know it already, if you are following www.facebook.com/SuppVersity)

These findings show for the first time that the aging process alone is associated with a hightened susceptibility to muscle inflammation.

Graphical illustration of what you should have learned by now, if you read the previous installments of the Intermittent Thoughts; note: while I have used the arrows rather indiscriminately (they do not necessary mean "causes"), the stops at the end of other lines indicate an inhibition, eg. the line from exercise to myostatin indicates that exercise inhibits myostatin, which would inhibit increases in myonuclear domain sizes, if it was not "switched off" by exercise... (learn more)

In view of the importance of "controlled inflammation" in the context of muscle damage, repair and supercompensation (learn more in the Intermittent Thoughts on Muscle Building, spec. this episode), the goal should thus be to (a) lower the inflammatory load to a level that allows the aging body to cope with it and (b) improve your body's ability to cope with a certain (yet to be determined) amount of inflammation that's necessary for the hormetic response to exercise to take place.

As alluded to in the introduction to this article, the same 500mg+ of vitamin C + 400IU+ of mixed tocopherols per day that are - at best - useless for a young trainee could in fact make a smart and valuable addition to the supplement stack of an older physical culturist, who is more reliant on exogenous ROS scavengers than the young grasshopper, for whom the exercise-induced inflammation is part of the training: A training for his endogenous defense system and a potential prerequisite for the structural remodeling process of the muscle (check out the figure on the right and learn more).

Melatonin: Protection beyond ROS scavenging

At least for the well-educated SuppVersity student you are ;-) It should be obvious that the "classic" anti-oxidants like vitamin C and E are not the only venues molecules to control inflammation. In fact, the emerging science shows that alternatives to these "Kamikaze"-inhibitors (ROS scavengers) can, in this, as well as other contexts, deliver much better results.

As a SuppVersity reader you'll know that melatonin is also an Alzheimer protectant, can help you shed body fat, could be the goto-supplement for ultra-marathon runners, figures in the cardio-protective and controls the circadian rhythm, the disturbance of which is involved in "all things bad" ranging from metabolic syndrome over diabetes to cancer.

Think of DHEA, for example. The adrenal hormone, which happens to decrease from year to year once you've passed your late 20s can even help young men to cope with the muscle damage of 5 days of concomitant combined endurance, strength and HIIT training in young men (read the whole story).

Or - and now we are finally zoning in on the actual news - think of melatonin, which has been shown to boost your anti-oxidant defenses, reduce the oxidaton of the lipids in your cell walls and modulate the immune response to intensive training, when it is supplemented in relatively high amounts of 6mg (learn more; don't forget to check out the links in the infobox to the right, as well).

It will therefore only come as a minor surprise for a diligent SuppVersity reader like yourself that a recent rodent study that has just been accepted for publicaton in the Journal of Pineal Research comes to the conclusion that..

[...a]dequate levels of circulating melatonin are [...] necessary to improve energetic metabolism efficiency, reducing body weight and increasing insulin sensitivity [in aging animals]. (Mendes. 2013)

Ah, and just to make that clear, I am not willing to start the "mice are no little men"-debate, here, but will take it for granted that you keep in mind that results, I have plotted for you in figure 1 have to be verified in future human trials (personally, I am confident, they will).

Figure 1: Relative levels of visceral fat, triglycerides, change in distance covered from month 0-2, running speed, citrate synthase activity, muscle & liver glycogen and glucose AUC during tolerance test; all data expressed relative to sedentary (S-) unsupplemented (-C) control, SC (Mendes. 2013)

So what are we seeing here in figure 1? Well, first of all there is a surprisingly significant (compared to the SC group) decrease of total, but more importantly visceral fat weight in both, the sedentary (SM), as well as the trained (TM) rodents. The latter goes hand in hand with

• 

  Expression of the muscle anabolic enzymes PI3K, p-AKT, as well as AMPK and GLUT4 in muscles of the supplemented (SM & TM) and non-supplemented (SC & TC) rodents in arbitrary units (Mendes.2013)

  significant improvements of the amount of triglycerides (a if not the no1 risk factor for CHD) even in the absence of exercise (compare the SC vs. SM groups)
• a mind boggling increase in the distance covered and the running speed of the animals in both the trained and the sedentary rodents "on" melatonin (in view of the fact that this increase remains statistically significant even when you compare it to the baseline levels, similar effects may even occur in young animals)
• almost 3x respectively 4x elevations in citrate synthase activity, a maker of fatty acid oxidation in the sedentary and trained melatonin treated rodents
• a 6x and 12x increase in muscle glycogen levels and an ameliorative effect on the exercise induced glycogen increase in the liver, both of which could not just explain the massive increase in exercise tolerance, but the previously observed beneficial effects on glucose tolerance, as well
• a 30-40% reduction in the glucose AUC that corresponds with the increased glycogen storage mentioned in the previous bulletin point

and lastly and for many of the physical culturists in the posterior half of their lives maybe most importantly, highly significant increases in the activity of the pro-anabolic PI3K, MAPK and AKT that were not increased at the expense of the fat-burning, anti-cancer, anti-diabetes AMPK energy switch (see figure 2).

---

Bottom line: It is beyond doubt that the small amount of exercise corresponding to the four to five sessions at 0.3 – 0.5 km/h running on a 0% grade treadmill [questionable whether this is a typo on the speed, by the way] for 10 min/day in the study at hand alone are good for aging individuals. It's also almost certain that the addition of supplemental melatonin ameliorates these exercise-induced benefits and induce benefits on their own.

Don't forget t take appropriate time off, otherwise even 15g of melatonin are not going to help you overcome a growth plateau. Why? Well "Chronic Resistance Training Reduces the Anabolic Signaling in Response to Exercise - 12 Days of Detraining Restore It" (read more)

What is yet highly questionable still is the optimal dosage. The 1mg/kg body weight that were used in the study at hand would translate to roughly 0.16mg per kg for a human being and thus ~13mg for an adult (male) human being. Personally, I don't think this is exorbitantly high, but I know that real and pseudo-experts would be bashing me, if I even remotely suggested that you consume similar as much supplemental melatonin on a regular basis... what all of us would probably agree on is the fact that future human studies are necessary, and if you asked me not so much to avoid potential harm, but rather not to miss what Mendes et al. believe would be an outstanding chance to "improve the beneficial responses induced by regular exercise in aging individuals, promoting a better quality of life and a healthier aging process" (Mendes. 2013).

 References:

• Mendes C, de Souza Lopes AM, Gaspar do Amaral F, Peliciari-Garcia RA, de Oliveira Turati A, Massao Hirabara S, Scialfa Falcão JH, Cipolla-Neto J. Adaptations Of The Aging Animal To Exercise: Role Of Daily Supplementation With Melatonin. Journal of Pineal Research. 2013 [accepted manuscript]
• Merritt EK, Stec MJ, Thalacker-Mercer A, Windham ST, Cross JM, Shelley DP, Tuggle SC, Kosek DJ, Kim JS, Bamman MM. Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans. J Appl Physiol. 2013 May 16.

90 Min Sleep Restriction - How Bad is It Really? Changes in Insulin Resistance Last For One Week - Until the System Adapts. Plus: Subjects Even Reduce Weight & Waistline

In general it's certainly a good idea to rise, when the cock crows on the dung heap, but what if that means you miss 90 min of your precious sleep?

"Tell me how and how long you slept last night and I'll tell you something about your chances of getting / staying lean and healthy!" It sounds more straight forward than the stupid AM vs. PM system you, my American friends, are still sticking to: If you consistently miss just one hour of sleep, you are messing with your insulin sensitivity, body weight and your plasma concentrations of leptin. But is this actually accurate and "how much messing" does it actually take? A close analysis of a recent study by a group of researchers from University of Surrey in Guildford, UK (Robertson. 2013), does at least raise some questions in how far smaller deviations from your usual 24/7 x 365 consistency will mess with your physique and health.

Can you "wake your way" towards obesity?

"Mild sleep restriction" is what scientists call it, when you miss 'only' one hour of your regular 7-8h of sleep every night and "mild sleep restriction" is also what the 19 healthy young normalweight men in the Robertson study have been exposed to over a three-week period.

Just in case you have forgotten about it, you can do the Munich Chronotype test for free (including personal evaluation) right at the website of the University of Munich (click here to be redirected)

Healthy male students, aged 20–30years, BMI 19–26kg/m² were recruited for this randomized–controlled sleep intervention study [...] those with a self-reported sleep length of 7.0–7.5h were invited for more detailed screening.[...] According to self-report, volunteers were not taking prescription or over the counter medication and had a stable weight for >3months. Specific exclusion criteria also included (i) shift-work and travel beyond 2 time zones in the preceding 2months, (ii) high intake of caffeine and alcohol, (iii) extreme morning or evening preference assessed with the Munich Chronotype and Horne Östberg Questionnaire, (iv) a self-reported sleep problem (Pittsburgh Sleep Quality Index global score≥6) and (v) daytime naps in the preceding 4weeks.

Before the actual study began, the habitual sleep patterns were assessed by actigraphy and sleep diary information collected during a two week baseline period. The subjects were then  randomized to either the

• restricted group spending their regular time-in-bed minus 1.5h per night, or the
• habitual group who simply followed their habitual sleeping patterns

The participants had to fill out sleep logs in order to assure compliance. Moreover, participants were instructed not to take naps during the day . The actual acquisition of the weight, blood pressure and adiposity data, as well as the leptin and adiponectin levels, and information about  arterial stiffness took place after a 12h overnight fast, at the Centre for Endocrinology Diabetes and Research (the oral glucose tolerance used to evaluate the effects of sleep deprivation on insulin sensitivity took place at the CEDAR, as well). The procedure was conducted four times, initially following the 2-week baseline period and in weekly intervals for the 3 weeks of the intervention, thereafter.

Figure 1: Relative changes of insulin sensitivity (HOMA-IR), fasting blood glucose and adiponectin levels in the course of the three-week study period (Robertson. 2013)

If you simply went by the absolute data and the short but concise summary of the main results the researchers provide in the abstract it would in fact seem as if the provocative statement I at the very beginning of this article would be spot on and you would add a pound of fat to your frame and lose a full week of your precious life-time with each minute of sleep you are missing. If you put things into perspective by calculating the relative changes, you cannot but realize that sleeping 90min less may not be ideal, but it's "medium term"  effects are probably overrated.

Figure 2: Illustrated and annotated version of the graph depicting the change in insulin sensitivity in the habitual (open circles) and sleep restricted (closed circles) group (Robertson. 2013)

In fact, the plot of the changes in insulin sensitivity in figure 2 clearly suggests that there is something like an adaptation process that compensates for the initial reduction in insulin sensitivity once a new 'sleep steady state' is achieved. In the absence of data from the following weeks, we cannot however exclude that the in an even longer-term scenario the reduction of sleep duration from below the 5h mark would not have had a negative impact on the overall and metabolic health of the subjects. In this context, Robertson et al. point out that

"[...] some of the effects of sleep restriction appear transient, i.e. we have beenunable to confirm a change in insulin sensitivity beyond one week of sleep restriction [and that t]he data clearly indicate that the effects of a reduction in sleep duration may change in the course of the exposure to sleep reduction, [which renders any] extrapolation from single visit laboratory studies to epidemiological data problematic." (Roberston. 2013)

If we would yet discard the epidemiological findings and simply ignore the constant increase in fasting blood glucose and rely on the fact that the insulin tolerance returned to baseline after an initial drop, we could even (ab-)use the data from the study at hand to argue in favor of sleep "deprivation" (I am deliberately using quotation marks, because the previously mentioned adapation process would suggest that the subjects were not actually "deprived") as a means to reduce the obesity epidemic. After all the subjects in the sleep restricted group did lose some body weight and reduced their adiposity index, the waist equivalent to the BMI (higher values = higher ratio of waist to body height), by meager, but at least measurable 0.8%.

Believe me: Fridge raiding is your least problem if you don't sleep at night. If you want to know more about the profound metabolic, psychological and even carcinogenic effects of having or not having a regular sleeping rhythm, why a dark room is important and more, read up on the Circadian Rhythm Series

Sleep does not necessary equal sleep: It should also be mentioned that "sleep" data we are talking about is actually data spent in bed and if you take a look at the sleep latency, you will realize that the subjects in the restricted group made up for 4-8 minutes of their 90min sleep debt by simply falling asleep more readily. Another factor to keep in mind is that, at least in my humble opinion, the actual sleep duration of the young men who participated in the study was to low to begin with. This is just my personal N=1 experience, but whenever the demands of life (or my own stupidity) forced me onto a <7h sleeping schedule, I ended up gaining body fat - not necessarily weight, but fat. So if there is something like a "break even" and the subjects were below that already, the effects could be much more pronounced in someone like you, who is (hopefully) getting is 7h of sleep in a pitch black, quiet room every night.

And what's more, in the correlation analysis the scientists conducted, the only parameter with a statistically singnificant correlation with sleep duration was - you won't guess that - body weight! With a positive correlation of +0.271 indicating that shorter sleep durations exhibited - at least in the study at hand - statistically significant correlations with decreases in body weight.

So what? You cannot 'wake yourself lean', can you?

No, probably not. The evidence from epidemiological studies is too overwhelming to throw the insufficient sleep = diabesity hypothesis over board. On the other hand, the results of the study at hand are interesting, as they clearly suggest that (a) our bodies are able to adapt to a news steady state within a certain window of suboptimal to optimal sleeping time and (b) that the short term effects of what I would like to identify as an actue stressor, namely 1-2 weeks of reduced sleep will lead to similarly transient weight loss.

Previous study showed: When you are dieting 40min extra sleep can help you 1lbs extra fat (read more).

increases in cortisol levels do the exact same thing. In the short run, they will spike you up (Lance Armstrong has admitted using corticosteroids to outperform the competition only days ago). Used intermediately, they will begin to gnaw on your body fat and muscles and in the long run they will totally mess up your metabolism (this assumes chronic low level exposure). To cut a long story short: The study at hand clearly suggests that someone without pre-existing health problems, a young man or woman in the prime of your life, won't risk becoming diabetic during the exam preparations or during any other period in his / her life, where he / she has to reduce the habitual and natural sleep durations by 90min for a <1 month in order to cope with external circumstances he or she has no bearing on.

Bottom line: Now, does this mean that we have been overrating the importance of sleep hygiene before? Certainly not. What we may have underestimated, however, are short-term compensatory effects which allow for a brief, but non-negligible time window, in which neither the acute very short-term effects - nor the chronic (very) long-term effects of sleep deprivation will harm you. And though we don't know anything about the size of this window, one thing appears to be certain: It's large enough for exam preparations, but not for years of drinking, partying and doing all sorts of things but sleeping ;-)

References

• Robertson MD, Russell-Jones D, Umpleby AM, Dijk DJ. Effects of three weeks of mild sleep restriction implemented in the home environment on multiple metabolic and endocrine markers in healthy young men. Metabolism. 2012 Sep 15.

Pomegranate for Statin Users, Magnesium for Cancer-Free Colons, Cialis for Diabetic & Healthy Women and Protein Supplementation for 0.81kg More Muscle & 13.5kg More Strength Gains Than Placebo (Data From Meta-Analysis)

As the data in the graphs at the bottom shows, only vigorous physical activity (right), yet not moderate (middle), let alone light physical activity (left) will help kids to stave off the bad visceral body fat, which increases their waist line from year to year. The photo in the background was by the way taken in 1989 on Orchard Beach, in the Bronx. If I remember correctly that's 6 years before the release of Nintendo's first "Game Boy". And yeah, I got one and it really doubled if not tripled my sedentary time!

7 minutes! That's the SuppVersity figure of the week and a number that should actually ring a bell with everyone of you who is following my advice and pays a daily visit to the SuppVersity Facebook Wall. "Seven minutes" that's what scientists from the University of Alberta and their Canadian colleagues believe would be the amount of "vigorous physical activities" our kids should get (Hay. 2012). I am not sure, if those scientists are still youths, but assuming they are not, I wonder if they cannot remember the amount of "vigorous activity" (which was back in the day simply called "play") they themselves or at least their parents or grand parents got, in the days when you still had to physically kick a ball, if you wanted to play soccer with your friends.

I mean, it's already bad enough that today's kids spend 70% of their time with sedentary activity, only 23% with light activity (like walking from the sofa to freezer ;-), 7% with modest and only 0.6% with vigorous physical activity, wouldn't it be wise then, to rather shoot for the stars and work towards a much higher amount of vigorous activity? After all, even Hay's own study shows that only vigorous activity was associated with a reduced waist circumference and lower markers of metabolic disease (see illustration on the right).

Even if the kids don't make it to the moon, but over to the neighbor's basketball hoop or a public playground that would be a major improvement over the 'exhausting' walks from the Playstation to the fridge and back, wouldn't it?

• Pomegranate the better statin? Adding pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) to a statin and reduce adipose tissue ROS production by a whopping 73%!  In their most recent paper Mira Rosenblat, Nina Volkova, Michael Aviram report that the administration of Simvastatin (15 μg/ml) to macrophages in the petri dish did only only "modestly decreased macrophage reactive oxygen species (ROS)" (Rosenblat. 2012), the presence of punicalagin (15 or 30 μM) almost 'extinguished the fire' cutting back inflammation dose-dependently by another 61% or 79%.
  
  

  

  As a regular here at the SuppVersity yo will still be aware that Pomegranate does also contain a potent plant version of CLA, called CLnA, no? Well then go back and read the full article!

  Intriguingly, β-sitosterol alone showed had minor pro-oxidant activity, when it was administered to the J774A.1 macrophages cell line the researchers from The Lipid Research Laboratory in Haifa (Israel) were analyzing,
  

  "the combination of simvastatin, β-sitosterol and punicalagin, clearly demonstrated a remarkable 73% reduction in ROS production."

  So what's the use of the statin, then? After all the scientists also found (but rather not mention in their abstract) that the combination of β-sitosterol and punicalagin actually suppressed macrophage cholesterol synthesis as effectively as low dose Simvastin or high dose Pravastatin (Click here to read about pomegranate in the SuppVersity news)
• Organo-Magnesium stops colon cancer in its tracks by inhibiting inflammation, and the findings a group of researchers from the Gifu University Graduate School report in a soon-to-be published paper are not surprising. After all many epidemiological studies studies like Folsom & Hong (2006), for example, have already shown that there is a -23% reduced risk of developing colon cancer for 55-65 year-old Swedish women in the highest vs. lowers quantile of magnesium intake. Earlier this year Wark et al. conducted a randomized trial and meta-analysis of the hitherto published studies and found:
  

  "Our findings support the hypothesis that higher intakes of dietary magnesium are associated with lower risk of colorectal tumors. The consumption of magnesium-rich foods may be a new avenue to explore further in the search for cancer-prevention strategies." (Wark. 2012)

  Tabs or capsules? A 2010 study has the answer to the question which form of supplemental minerals is the best for you. Roswitha Siener and her colleagues from the University of Bonn in Germany found that magnesium oxide from effervescent tablets is better absorbed than from capsules and you can be pretty sure that similar results will be found for other forms of magnesium. My advice would yet be: Save the money and just go for plain magnesium citrate powder.
  The meta analysis yielded 13% lower risk of colorectal adenomas and 12% lower risk of colorectal cancer for every additional 100mg of magnesium per day. This does yet not mean that by eating pounds of magnesium you could render yourself 'cancer proof', but it is good evidence to make sure to get at least the into the 380-500mg range. And if you want to supplement, you really won't need the organ-magnesium Kuno et al. produced by mixing magnesium oxide (0.22 g), citric acid (0.55 g), malic acid (0.55 g), and glycine (0.22 g) - unless you can't tolerate it, cheap magnesium citrate will do just as well.
  
• Taldalafil for insulin resistant and healthy post-menopausal women?! (Murdolo. 2012) A group of European scientists have found that the administration of 10mg of Taldalfil (the notorious PDE-5 inhibitor in Cialis) to both diabetic and healthy controls led to
  
  • an increase in permeability surface area product for glucose , and
  • skeletal muscle interstitial lactate levels r
  The forearm glucose uptake, as well as the arterial lactate levels showed differential responses, while there was a trend for increased glucose uptake in the healthy controls, the latter was absent in the diabetic group. The profound decrease in arterial lactate levels in the diabetic patients, on the other hand, was not present in the healthy controls, whose lactate levels had already been in the normal range (see figure 1).
  
  

  

  Figure 1: Effects of 10mg of Taldalafil on arterial and intramuscular lactate concentration (Murdolo. 2012). The increase in intramuscular glucose oxidation (evidenced by the lactate that is generated during this process) could even be of interest to healthy women (and men?).

  Based on these findings, Guiseppe Murdolo and his colleagues argue that the results would suggest that acute Tadalafil administration can increase the capillary recruitment and nonoxidative glucose metabolism, without having consistent effects on forearm blood flow and regional lipolytic rate. However...
  

  "[...] notwithstanding the lack of measurable changes on forearm glucose uptake, the microvascular response to tadalafil emerged as an independent predictor of muscle glucose disposal in both T2D patients and insulin-sensitive controls."

  Well, and if those effects don't reach statistical significance, maybe 'others' will. After all a 2003 study by Caruso et al. suggests that Taldalafil can also increase "the frequency of sexual fantasies and of sexual intercourse, and enjoyment" (Caruso. 2003) in a group of  53 pre-menopausal women (age 22–28) years affected by arousal disorders. Maybe we should simply put Taldalfil into the drinking... ah, I am just kidding ;-)
• Finally! Scientists determine 'exactly'*rofl* how much more muscle you can gain with supplemental protein (Cermak. 2012). I hope I do not have to point you towards the irony in the headline of this On Short Notice item. If this ain't your first visit to the SuppVersity you should by now be aware that calculations like add 1g of protein per day and gain x-amounts of lean muscle mass per month, year or whatever timespan are nonsensical and will provide, if anything, a very general orientation.
  
  That said, it is still interesting to see the actual results Naomi M Cermak et al.'s quantitative meta-analysis of 22 studies, of which 77% were conducted with untrained individuals (64% with young trainees) produced. Most studies, which had a duration of 6-24 weeks (median: 12 weeks), used 3-5 x whole body workouts / splits coupled with milk (mostly whey) protein supplementation in amounts that ranged from 10g to 106g - keep that in mind when you think about how 'exact' the following figures can actually be:
  

  • 

    Size-wise and even more so strength-wise Arnold could still benefit from a protein shake after a workout. When it comes to the increases in type I and type II fiber CSA, his age could however put a spoke in his wheel.

    Fat free and fat mass - Compared with the placebo, protein supplementation significantly augmented the gain in FFM during prolonged resistance-type exercise training (weighted mean difference: 0.69 kg). A subgroup analysis for age showed that protein supplementation was beneficial for both the young and the old trainees, but that the total effect size in terms of fat free mass gains were ~1.7x higher in the young subject (+0.81 kg) than in the older ones (+0.48 kg;) subjects.
    
    What I find particularly surprising is that the subgroup analysis also revealed that training status had no significant and what's more, if anything a beneficial effect on the effect sizes in the young untrained (+0.75 kg) and trained subjects (+0.98 kg), respectively.
    
    As far as fat loss is concerned the scientists did not record any statistical significant differences compared to placebo and that despite the fact that the placebo in most of the 22 studies was a sugary carbohydrate drink.
  • Muscle fiber cross sectional area - As the gains in lean mass already suggest, the cross sectional area (CSA) of the muscle fibers increased: By ~ 212µm² in the type I fibers and 291µm² in type II fibers. Unfortunately, both the increases in type I and type II fibers were statistically significant only in the young trainees.
  • 1-RM Strength - The performance for the one-rep maximum (1RM) on the leg press improved across the board (+13.5kg more than in placebo) and that did work almost equally well for younger (+14.4kg) and older trainees (+13.1kg).
  I will leave it up do you what you want to do with this data and whether you think that studies like this are actually useful for the individual practitioner who does not - contrary to way too many dietitians - have to be convinced of the benefits of protein supplementation on top of the low 0.8g per body weight the dietary guidelines recommend.

That's it another saturdaily installment of On Short Notice and in case you feel that you could use some more educative news, tomorrow is another day ;-)

References:

• Caruso S, Intelisano G, Lupo L, Agnello C. Premenopausal women affected by sexual arousal disorder treated with sildenafil: a double-blind, cross-over, placebo-controlled study. BJOG. 2001 Jun;108(6):623-8.
• Cermak NM, Res PT, de Groot LC, Saris WH, van Loon LJ. Protein supplementation augments the adaptive response of skeletal muscle to resistance-type exercise training: a meta-analysis. Am J Clin Nutr. 2012 Nov 7.
• Folsom AR, Hong CP. Magnesium intake and reduced risk of colon cancer in a prospective study of women. Am J Epidemiol. 2006 Feb 1;163(3):232-5.
• Hay J, Maximova K, Durksen A, Carson V, Rinaldi RL, Torrance B, Ball GD, Majumdar SR, Plotnikoff RC, Veugelers P, Boulé NG, Wozny P, McCargar L, Downs S, Lewanczuk R, McGavock J. Physical Activity Intensity and Cardiometabolic Risk in Youth. Arch Pediatr Adolesc Med. 2012 Sep 10:1-8. doi: 10.1001/archpediatrics.2012.1028.
• Kuno T, Hatano Y, Tomita H, Hara A, Hirose Y, Hirata A, Mori H, Terasaki M, Masuda S, Tanaka T. Organo-Magnesium Suppresses Inflammation-Associated Colon Carcinogenesis in Male Crj: CD-1 Mice. Carcinogenesis. 2012 Nov 3.
• Murdolo G, Sjöstrand M, Strindberg L, Lönnroth P, Jansson PA. The Selective Phosphodiesterase-5 Inhibitor Tadalafil Induces Microvascular and Metabolic Effects in Type 2 Diabetic Postmenopausal Females. J Clin Endocrinol Metab. 2012 Nov 1.
• Rosenblat M, Volkova N, Aviram M. Pomegranate phytosterol (β-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis. Available online 31 October 2012.
• Siener R, Jahnen A, Hesse A. Bioavailability of magnesium from different pharmaceutical formulations. Urol Res. 2011 Apr;39(2):123-7.
• Wark PA, Lau R, Norat T, Kampman E. Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis. Am J Clin Nutr. 2012 Sep;96(3):622-31. doi: 10.3945/ajcn.111.030924. Epub 2012 Aug 1.

Sleep to Grow, Train to Sleep: How Strength and Endurance Training Effect Your Sleep Patterns & Exercise Performance and May Help or Hinder Fat Loss & Muscle Gains

Image 1: As a toddler you already knew - "Sleep is the most anabolic agent there is"; Sleep - Train - Eat, repeat! Remember that ;-)

If you like Dave Palumbo's Heavy Muscle Radio, you will probably have heard an advertisement that (a few other questionable statements aside) contains a real gem of wisdom: "Sleep is the most anabolic agent there is!" But how come? Well, if you remember the comments I made on the way your muscles grow by both, increasing mononuclear domain sizes (protein synthesis) and the accumulation of new myonuclei, you will probably also remember that, next to estrogen, nitric oxide and a handful of other factors, growth hormone, in general, and the IGF-1 (and MGF-1) that is locally released in response to its secretion, are the primary drivers of satellite cell driven muscle hypertrophy (and possibly hyperplasia)... now, guess when your body produces the lion share of growth hormone (and downstream IGF-1?) in a given day?

You got it, in those cosy (hopefully) ~8 hours you are snorkeling away in between your sheets (Cauter. 1998) - it is in these hours, that your GH levels spike at 600% of their daytime average and your cortisol levels plummet into the abyss. As studies show, this is yet not the only thing on which you are missing out if you do not get your share of quality sleep day in, day out: Even short-term (let alone chronic) sleep deprivation has been shown to significantly increase rates of perceived exertion in athletes and - and this may be even more detrimental - decrease insulin sensitivity and glucose tolerance (VanHelder. 1989). So that after nights and nights of low-quality or insufficient sleep, your secret weapon against tiredness, your pre-workout high-carb-get-me-going shake will no longer get you going in the gym, but rather out of the gym and right to your doctor to ask him for a script for some Metformin to get your blood sugar levels back to normal.

Assuming that I now got your full attention, I want to share the results of two very recent studies with you. One on the differential effect of strength and endurance training in the morning (10am) on sleep quality and duration in 15 healthy trained men (Roveda. 2011) and a second one on the beneficial effects even a single session of resistance training (at 60%RM) has on the sleep pattern of 22 65-85 year old men (Viana. 2011).

Always remember: Sleep is the most anabolic agent there is

One thing upfront: A reasonable amount of physical activity will - regardless of your age and fitness level - make it easier to fall asleep, lengthen the time you spent in bed actually sleeping and not tossing and turning, and contribute to an overall improvement in sleep quality.

Figure 1: Relative changes (compared to baseline) in assumed and actual sleep on day 1 and day 2 after a 10am strength (bench press 4x80RM + 10 min warm up)or endurance training (10min warm-up, 30min 80%VO2max, 10min cool-down) session in 15 healthy young men (data calculated based on Roveda. 2011).

As figure 1 goes to show there was a distinct effect of both strength and endurance training on the time spend in bed (assumed sleep) and the actual sleep time on the first day after the physical activity. In that, it is particularly noteworthy that the actual sleep time increased by +8% and +12.5% and thusly ~2% more than the time the subjects spent in bed. This increase in sleep quality is something we also see in the older subjects of the Viana study, whose REM latency, i.e. the time it took them to enter into the valuable rapid eye movement phase of their sleep, decreased by a whopping -48%, on days on which they had performed their 3 sets of 12 reps (60%RM) of chest presses, leg presses, vertical tractions, leg curls, biceps curls, abdominal crunches, arm extension, and lower back exercises.

Figure 2: Relative changes in sleep efficiency and sleep latency on day 1 and day 2 after a 10am strength or endurance training session in 15 healthy young men (data calculated based on Roveda. 2011).

Now, while we see a "rebound" effect (a decrease in sleep time) in the 2nd night after the morning exercise in the young subjects (comparative data were not collected in the Viana study), the increase in sleep efficiacy, i.e. the amount of time the young men spent in bed vs. the amount of time they actually sleep persisted (cf. figure 2)! And the sleep latency, i.e. the time it took the subjects to fall asleep was still significantly reduced on day 2 after the respective physical activities.

Although there probably is no doubt that physical activity may benefit sleep quality and sleep quality in turn may benefit not only the performance during the former, but also its effects on your metabolic health and body composition (cf. image 1), it is still a matter of constant debate how much, is too much - after all, both forms of overtraining, the sympathetic form, which puts you into a chronic fight and flight mode and will wreak havoc on both your sleep quality and its duration (usually associated with higher intensity training than the bench pressing session 10min warm-up + 4x80%RM the Rovenda subjects performed) and the parasympathetic form, which is what people usually refer as "burnout syndrome" and will have you sleep hours after hours waking totally unrefreshed, produce quite distinct, yet of many athletes carelessly overlooked sleeping patterns, which - and here lies the culprit, still appear to be one of the best, yet by far not "objective" measures of whether you are "hitting your sweet spot" or are just digging a deep black hole by keep pushing and pushing, when your batteries have long run out of energy (Urhausen. 2002)... but this, my friends is a topic for another blog post ;-)