First Dates - This is How They Work: Cliches, Prejudices & Scientifically Verified Dating Scripts

Holding each other's hand is part of the dating scripts of both men and women.

No, you did not enter the wrong URL - this is  the SuppVersity! And yes, I know this does not sound like a SuppVersity topic, but let's be honest: a satisfactory love-life (spiritual and physical) is in as much part of a healthy lifestyle and as a healthy diet and a reasonable amount of exercise. Against that background I thought it's warranted to write an article about the Rules of Engagement and what men and women expect from a first date - and yes, I willingly admit I was sort of fed up with "diabesity", muscle and performance "gainz" and wanted to write about something else, today.

The corresponding research is unfortunately already 5 years old, but I guess most of it is still valid (although there is no information about Facebook, Twitter and general smartphone use on the first date included - for me, personally, a total turnoff, by the way). That being said, the Mary Claire Morr Serewicz and Elaine Gale did a pretty decent job, when they analyzed the first-date scripts of  209 college students in the Midwestern United States.

Don't forget: Dating is an art! I truly believe in science, but when it comes to interpersonal relationships and love, all the science in world can - at best - prepare you for what's going to happen. So don't take this as a blueprint and rather trust your instincts than the stats, when you stand in front of your date's door and think about what today's SuppVersity post taught you about "polite leave-taking" ;-)

You have no idea what kinds of results this research could possible deliver? Well, here are a couple of examples:

• Women are more creative than men: Men’s scripts will show greater redundancy than will women’s scripts.
• Men are wired to think about how to score with their dating partner: Men’s scripts will include more sexual behavior than women’s scripts.
• Women know what they want: Female-initiated dates will include more sexual behavior than male-initiated dates.

All these are actually prognoses the researchers formed based on results from previous studies. The same goes for the hypotheses that

• keg parties a good place to date if you want to get down and dirty after your date, while
• coffee-shops are the right locations for intimate communication

I guess all that is not actually surprising to you - unless you have been spending most of your live on Facebook and don't even know what a keg party is, obviously. That's you? Well, the following information may be particularly valuable for you; that is if you ever plan to leave the secure and cosy light / dark blue world of fake friends and faked profile pictures and go on a real date.

So let's see what men and women have on their minds when they're dating

The first-date script the Mary Claire Morr Serewicz and Elaine Gale constructed based on their interviews and questionnaires contained 23 actions, 20 of which were unique actions. Two actions, get ready and talk, were repeated. Ten actions were mentioned by at least 50% of participants: get ready, pick up date, go to movie, pay, talk, go to café/party, talk(2), walk/drive home, kiss, and future plans.

Included in the following list are all items that were mentioned by at least 25% of the study participants. Practically speaking, this means for example that whenever you go on four subsequent dates (at least) one of your dating partners will have "holding hands" on his / her mind.

Male	Female
GET READY PICK UP DATE (M) Feel nervous GO TO MOVIE Pay (M) TALK Get something to eat Flirt Hold hands GO TO CAFÉ/PARTY TALK Touch/hug (M) Drink alcohol Deep conversation Evaluate relationship (M) Talk Leave party Invite the other in More than kissing WALK/DRIVE HOME (M) KISS FUTURE PLANS (M) Walk/drive home (M)	GET READY PICK UP DATE (M) Feel nervous Talk to friends (W) GO TO MOVIE PAY (M) TALK Pay (M) Hold hands GO TO CAFÉ/PARTY Smile/joke/laugh Nonverbal closeness TALK Drink alcohol Touch/hug Mingle with others Deep conversation Talk Leave party WALK/DRIVE HOME (M) Polite leave-taking KISS FUTURE PLANS Part for the night (M)

Ok, I see you are (rightly) confused; and honestly, I did feel the same, when I saw this table. Let's first get the meaning of the CAPITAL and bold items straight. As I already mentioned, the table lists only those items that have been mentioned by at least 25% of the respondents. The items in CAPITAL LETTERS were even more frequent. They have been mentioned By at least 50% of the participants. Actions in bold, on the other hand, are sex specific that means they were mentioned only by men or women, but not by both sexes.

Some things you would, some things you wouldn't expect

12 Things Everyone Should Know Before His / Her Next Date

• He should not buy new clothes for a date, woman don't expects that.
• Ladies & gents, you better shave / use make-up! Your date expects you to do so.
• The car is his job. The same goes for making sure it does not break down!
• He pays! And ladies, don't take that away from him: He actually wants to pay!
• She loves flowers. 79% of the women wouldn't mind a long-stemmed rose.
• He picks her up. That's something men and women agree upon.
• Be prepared to meet the parents guys, 58% of the ladies expect that of him.
• He opens the door for her. Well, unless she is one of the 11% of the women who do not expect that.
• He takes the first step. More than 50% of both men and women agree even initiating a hug is his job.
• She loves "deep conversations". They are in the toplists of 50% of the women but only 43% of the men know that.
• It's his duty to take her home. 88% of the ladies and 90% gents believe that.
• Women will call a friend after the date.  54% of the guys know that.

These "facts" are based on a study by Laner & Ventrone from 2000.

I guess few of you will be surprised that "get something to eat" is a male exclusive, right? I mean that's caveman speaking here ;-) What may be more surprising is that "evaluate relationship" is likewise a male exclusive. With the (M) signalling that the men expected of themselves to do that, it would appear that a statement like "I just wanted to see where we are at" is rather to come from the male date partner than from his female counterpart who will be less concerned about "being invited in" and "receiving more than a kiss" (yes, I know ladies, we are Neanderthals ;-) than about a possibility to "tell her friends about the date".

Apropos women, the results Mary Claire Morr Serewicz & Elaine Gale present in their paper do not suggest that you must sit 10 meters apart from your date, guys. Quite the opposite, as long as you "smile, joke and laugh" you are welcome to "keep eye contact" and even "sit close" to your inamorata (both "keeping eye contact" and "sitting close to each other" belong to the nonverbal closeness category). In most cases you may also take and hold her hand, but you should be aware that your are not only expected to "pay the bill", but also to "drive her home" and once you are there you  may - if you are lucky - "kiss her" before you "leave politely" and "part for the night".

I hope this short tale of the all-American standard date (as Sereictz' and Gale's subjects see it) did promote your understanding of how you can read the results in the tabular overview. Before I leave you to your own interpretation, I do however want to take a departing look at the difference between male vs. female initiated dates.

Influence of the gender of date initiator

Traditionally it's up to us (men) to ask you (ladies) out and, as we have already seen, to pay for the bills. With the emancipation, though, things have changed... well, at least as far as the initiation of the date goes (not so sure about paying the bills, to be honest). From a 'date-scientific-perspective' it's thus important to understand the difference between male and female initiated scripts. And I bet you will be surprised what the researchers found ... no, the guy is still expected to pay the bill, so that's not the surprise!

While the male initiator scripts follow the classic "smile, laugh, joke"-"go to the cinema"-"talk"-"take her home and leave"-script, a female initiated date is much more laden with Neanderthal expectations: Aside from "getting something to eat" and "drinking alcohol", female-initiated dates are way more often expected to end on "invite the other in" and "more than kissing" than male-initiator scripts... hmm, I guess my grandma was right, then: "You better beware of those women" ;-)

What's the use of all this? In case this is what you are just asking yourself, it probably did not hurt you that you've just been thinking about something else but optimal protein intakes, macronutrient ratios and ergogenic supplements.

Believe it or not: There is a world out there, where looking good naked may come very handy and is still not all that counts. Don't forget that!

References:

• Laner MR, Ventrone NA. Dating Scripts Revisited. Journal of Family Issues. 2000; 21:488.
• Serewicz, MCM, Gale E. First-date scripts: Gender roles, context, and relationship. Sex Roles. 2008; 58(3-4): 149-164.

Sweet, But Not Innocent!? The Fattening Effects of the Non - Nutritive Sweeteners Erythritol & Aspartame Are On Par With Equally Sweet Sugar Water

I just hope that today's SuppVersity article is not going to cause scenes like this, because when it all said and done it may be less likely, but not impossible that it is (for whatever vexed reason) still aspartame that caused the negative effects observed in the study at hand.

It is one of the recurring motifs here at the SuppVersisty and at the same time one of the most popular issues of dispute in the health and fitness community: The Obesogenic Effects of Artificial Sweeteners. Or, in plain English, the question  

"Can I use Sucralose, Aspartame and Acesulfam-K without taking the risk of getting fatter - not leaner, as I actually intended?"

For all three of the explicitly mentioned agents human studies clearly suggest that the answer is "Yes, you can!" And I will now dare saying that the of the most recent study from the Oita University in Japan are not going to change that - as long as you use them instead of carbs in your diet the said zero-calorie sweetener are going to help not block weight loss.

So why did the mice in the Mitsutomi study get obese then?

By anticipating the most important conclusion, I have made things easy for us, after all the only questions we still have to answer are:

• Why did the mice in the Mitsutomi study get obese?

• Is it possible that this is an erythritol-specific effect?

It would appear as it it could not be all too difficult to answer the first question. It was after all part of the research interests of the Japanese scientists, so that you would expect it to be answered in the discussion of their result. Well, let's see then, ...

Exactly what the energy drinks promise, the sugar water got the rats "on sucrose" going: They were >40% more active than their peers - without caffeine as you may notice (Mitsotomi. 2013)

"Compared with sucrose supplementation, NNS supplementation decreased the serum glucose level. Interestingly, compared with the control treatment, NNS supplementation increased the serum insulin level in mice with DIO. In addition, NNS administration influenced glucose tolerance compared to controls.

These observations suggest that NNS supplementation induced insulin resistance by increase of tissue triglyceride, although some NNSs are used to control hyperglycemia.

NNS supplementation increased the WAT leptin level in DIO mice in the present study.

It is possible that the high leptin level was related to body adiposity. Indeed, NNS administration increased the weight of epididymal fat. Thus, it is possible that the high leptin level was related to the influence on body adiposity." (Mitsotomi. 2013)

No, I don't see an explanation, rather a concise summary of the results, that tells us that the addition of plain sugar (33%)  to the drinking water did - as the scientists already expected - lead to a decrease in food intake and an increase in obesity and its nasty unhealthy side effects.

Figure 1: Differences in food intake & body composition of mice with 33% sucrose and 4% erythritol + aspartame in the drinking water (left) expressed relative to control w/ plain water, histology of lover (top) and white adipose tissue (WAT, bottom) of mice with regular (control) and sucrose respectively NNS drinking water (Mitsotomi. 2013)

Much to their own surprise, Mitsotomi et al. did also observe that the group that received the "non-nutritive sweeteners" as a 4% solution (99% of which were erythritol and 1% was aspartame) in their drinking water got exactly as fat (see Figure 1), had a slightly less pronounced increase in adipocyte size, and experienced a similar fatty acid deposition in the liver (NAFLD). And as if that had not been bad enough, there were also pathological changes in the "fat burning brown adipose tissue" (BAT) of the rodents in the NNS group - a physiological deterioration, Mitsotomi et al. observed exclusively in the erythritol + aspartame goup.

Figure 2: Leptin resistance (in WAT) and the major downregulation in UCP-1 (in BAT; both left) are candidates of which the researchers believe that they were responsible for the visible defect (right) in the BAT architecture (Mitsotomi. 2013)

Let's be honest, if you take another look at the BAT histology in Figure 2 (right) even you as a non-expert will see that there is a major difference between the meshed BAT in the rodents on the control diet and the messy BAT of the NNS group, compared to which the brown fat cells of the sugar guzzlers still look very healthy.

Remember: All this mess happened in the absence of an increase in calorie intake

Just to make this clear: This is not the first study to show that artificial sweeteners can have obesogenic effects in rodent models. In contrast to Naismith et al. (1995) and Blundell & Hill (1986) who observed a "pradoxical effects" of  artificial sweeteners on the appetite of their lab rodents, the rats in the study at hand did not overeat, though! They also moved about as much as their peers in the control group and still got fat and sick.

Want to change your "Fat-o-type"? Work out! | read more

In other words, the weight gain the Japanese researchers recorded was neither a result of a mismatch between energy intake and expenditure nor the consequence of a promotional effect of artificial sweeteners on the "sweet tooth" of the rodents. Rather than that it was either brought about or accompanied and promoted by the impairment of the thermogenic capacity of the brown adipose tissue, of which you can argue, based on histologies in Figure 2 that the brown adipose tissue of the furry "subjects" of this study was not just functionally, but also structurally compromised by the ingestion of the non-nutritive sweeteners.

The defective brown adipose tissue (BAT) and the correspondingly reduced UCP 1 expression (UCP increases mitochondrial uncoupling in BAT and burns off energy to increase the body temperature), led to a significant reduction in oxygen consumption. With the latter being a direct marker of fatty acid oxidation the it is difficult to say which came first, the defect in BAT or the onset of obesity. What we can say for sure, though, is that the defective BAT had its share in the rapid weight gain and the corresponding metabolic deterioration.

This could be an erythritol specific effect

Despite the fact that Mitsotomi et al. did not address the potential influence the type of artificial sweetener they used, it is not unlikely that the use of erythritol, of which I have seen dozens of toxicity studies, but no long(er) term feeding studies in a potentially obesogenic diet scenario, could explain the unexpected study outcome. So: "Is this an erythritol specific effect?"

An advantage of erythritol is that it has almost the same sweetness profile as sugar (sucrose), but is 30-40% less sweet (de Cock. 2012)

Without further studies, it is obviously not possible to answer this question, it does however not appear to be unlikely that it were the 99% of erythritol in the commercial erythritol + aspartam mixture the researchers used in their study that's to blame for the obesogenic effects. If this was a general NNS effect, a similar impairment of the brown adipose tissue and corresponding increases in body, muscle and liver fat should after all have been observed in previous studies, already. To my knowledge these studies do not exist - specifically not for aspartame. Without speculating about unpredictable interactions within the two we are thus left with erythritol as out only culprit.

While erythritol has only 60% to 70% of the sweetness of sucrose (comparing 10% solutions in water; this means you need much more of it to achieve a similar sweetness) it has an almost identical sweetness profile (no "off" tastes; cf. de Cock. 2012). This is not the only reason both scientists and the food industry are fond of the low-calorie sweetener. It's rather the combination of its gut- and tooth-friendliness that makes it such a valuable addition to everything sweet. So, despite the fact that it does share the the anti-caries effects with sugar alcohols like xylitol, it is so easy on the gut that its use is not restricted to chewing gums and other "food" items that need only marginal amounts of sweeteners to achieve the desired degree of sweetness. If you want to sweeten larger amounts of foods / beverages, erythritol is thus the sugar alcohol of choice

There is evidence that suggests aspartame reduces insulin - at least during workouts | learn more

Why don't you suspect aspartame? The reason that I am scrutinizing erythritol and not aspartame is simple. Despite or rather because of all the hoopla around potential toxic effects of aspartame it is one of the best researched artificial sweeteners and evidence for obesogenic effects in the absence of increases in food intake are simply non-existent. It may thus make this article more popular among the high number of aspartame haters out there, but it would not help us understand the experimental results,if I started lamenting about how Coke and Pepsi are trying to kill us.

If you take a peak at the Wikipedia article and many scientific papers, you will learn that erythritol has been shown to be mostly (90%) absorbed before the chyme enters the colon (Bernt. 1996). The non-negligible rest of the erythritol  (10%), on the other hand, is said to pass through the short and long intestine, where it is generally believed not to fermented by the gut bacteria (Arrigoni. 2005).

The cholesterol increase scientists observed in response to a high sucralose diet is another of the many yet not fully understood side effects of artifical sweeteners | learn more

In view of a more recent study by Beards et al. (2010) it is however more than questionable that this assumption for which researchers usually cite the in vitro results Arrigoni et al. presented in a 2005 paper is accurate.

Beards and her colleagues from the University of Reading in the UK were after all able to show that erythritol is not simply excreted undigested. Rather than that it is fermented and leads to changes in the bacterial composition and a 6.25x increase in acetate production.

In view of the beneficial effects of SFCA (acetate, propionate and butyrate) on the production of satiety hormones this certainly appears to be a good thing. From studies by Patil et al. we do however know that chronically high SCFA levels and decreased relative bacteroides levels are characteristic of features of human obesity (Patil. 2012; see Angelakis. 2012, as well).

If we include the comparatively short timespan (24h) in the course of which the said changes in the bacterial composition and acetate production in the Beards study occured and assume that this may, after days of constant erythritol exposure have destabilized the previous "ecosystem" in the gut, it does not appear too far fetched to assume that the rodents may have suffered from weight gain and all sorts of metabolic deterioration as a consequence of the potential lactobacilli + Atopobium overgrowth in response to the erythritol in their drinking water.

By now it should no longer appear totally odd to assume that neither artificial sweeteners per se, nor the "bad bad" aspartame are to blame for the "fat effects" the researchers observed in the study at hand, right? I mean, of all the three short chain fatty acids, butyrate, acetate and propionate, acetate is the one with the weakest antiobesogenic effects (Lin. 2012) and in view of the fact that it is preferentially used as a substrate for de novo lipogenesis (=deposition of fat) in colonocytes, hepatocytes and adipocytes (Samuel. 2008), both the fatty liver and the 172% increase in body fat could be explained by the constant influx of acetate from a dysbiotic gut - right?

Suggested Read + Podcast: "he Pro-Insulinogenic Effect of Artificial Sweeteners + Mechanisms & Consequences" | read more

Reason to be afraid - yes or no?"It could be possible...", these are the four little words that would have to go before each and every of the sentences in this conclusion. It could be possible that the interaction of erythritol with the gut microbiome of the rodents drove the accumulation of lipids in the liver, which would in turn have lead to the development of insulin and leptin resistance and could have compromised the function of the "fat burning brown adipose tissue" of our furry friends. The latter could have sped up the weight gain and may eventually explain why the mice in the "non-nutritive sweetener" group were by no means better off than their similarly obese peers in the sucrose group.

Despite the fact that it could also be possible that similar negative effects on the accumulation of liver and whole body fat would be observed in humans, the failure of the brown adipose tissue wouldn't be much of a problem for us, a species that has long lost most of its brown fat stores (learn more). Against that background and in view of the fact that I'd hope that no one of you follows a 60% fat, 20% carbohydrate diet and tries to sooth his / her sweet tooth with 2-3l of erythritol + aspartame sweetened water per day, I'd suggest you refrain from freaking out until we do have more compelling evidence that the stress hormones you will be producing are not more harmful than the few mg of sugar alcohols in your protein bars.

References:

• Angelakis E, Armougom F, Million M, Raoult D. The relationship between gut microbiota and weight gain in humans. Future Microbiol. 2012 Jan;7(1):91-109.
• Arrigoni E, Brouns F, Amadò R. Human gut microbiota does not ferment erythritol. Br J Nutr. 2005 Nov;94(5):643-6. 
• Beards E, Tuohy K, Gibson G. Bacterial, SCFA and gas profiles of a range of food ingredients following in vitro fermentation by human colonic microbiota. Anaerobe. 2010 Aug;16(4):420-5.
• Bernt WO, Borzelleca JF, Flamm G, Munro IC. Erythritol: a review of biological and toxicological studies. Regul Toxicol Pharmacol. 1996 Oct;24(2 Pt 2):S191-7. Review.
• Blundell JE, Hill AJ. Paradoxical effects of an intense sweetener (aspartame) on appetite. Lancet 1986;1(8489):1092–3.
• de Cock P. Erythritol. In "Sweeteners and Sugar Alternatives in Food Technology". 2nd edition. Ed. O'Donnell & Kearsley. Wiley. 2012.
• Lin HV, Frassetto A, Kowalik EJ Jr, Nawrocki AR, Lu MM, Kosinski JR, Hubert JA, Szeto D, Yao X, Forrest G, Marsh DJ. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLoS One. 2012;7(4):e35240. 
• Mitsutomi K et al. Effects of a nonnutritive sweetener on body adiposity and energy metabolism in mice with diet-induced obesity. Metabolism. Oct. 2013 [ahead of print]
• Naismith DJ, Rhodes C. Adjustment in energy intake following the covert removal of sugar from the diet. J Hum Nutr Diet 1995;8:167–75.  
• Patil DP, Dhotre DP, Chavan SG, Sultan A, Jain DS, Lanjekar VB, Gangawani J, Shah PS, Todkar JS, Shah S, Ranade DR, Patole MS, Shouche YS. Molecular analysis of gut microbiota in obesity among Indian individuals. J Biosci. 2012 Sep;37(4):647-57.
• Samuel BS, Shaito A, Motoike T, Rey FE, Backhed F, Manchester JK, Hammer RE, Williams SC, Crowley J, Yanagisawa M, Gordon JI. Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16767-72.
• Sell H, Deshaies Y, Richard D. The brown adipocyte: update on its metabolic role. Int J Biochem Cell Biol 2004;36: 2098–104.

DOMS - Delayed Onset Muscle Soreness: No Pain, No Gain? Is DOMS Necessary to Build Muscle?

Are stretch, tear and DOMS what makes concentration curls an effective biceps builder? Can we use the soreness as a gauge for the efficiency of our training?

An article by Alex Leaf (CPT)

In last Sunday's first installment of our discussion on delayed onset muscle soreness (DOMS), we looked at what causes DOMS as well as treatment methods and supplements for relieving its symptoms. This led us to today’s big question:  Is DOMS necessary for muscular adaptations to exercise? No pain, no gain, right?

Before we can discern whether DOMS may benefit muscle growth, we need to look at what muscle growth is and what causes it, so that we may see if DOMS is in fact a piece of the puzzle.

Taking a Second Look at Muscular Hypertrophy

During muscle fiber hypertrophy, contractile proteins proliferate, and the muscle fibers enlarge to support this growth (Vierck. 2000). While there are many factors regulating this process, from gene expression to hormones and other growth factors, the two necessities for hypertrophy are some form of increased muscular tension, damage, or stress (Goldberg. 1975), and a positive net protein synthetic response with adequate energy availability (Miyazaki & Esser. 2009).

Beware of too much "good" ROS scavengers. NAC will effectively block the recruitment of new satellite cells | learn more

Through exercise, the former is accomplished and paves the way for the repair processes that require the latter to occur. In other words, without a need to increase muscle size and strength, hypertrophy will not happen. Likewise, even if there is a need, without proper nourishment hypertrophy simply cannot happen.

So with exercise being the trigger and nutrition the ammo, what is left to play the gun? Skeletal muscle does not undergo significant cell replacement once mature (Chargé & Rudnicki. 2004), and thus a repair mechanism for any microtrauma is essential.

This medic is the satellite cell, a type of stem cell found only within mature muscle tissue. After microtrauma, satellite cells activate, proliferate, and ultimately fuse to one another and existing muscle fibers to form new myofibrils (Toigo & Boutellier. 2006).

All parts of this regenerative weapon rely on one another. The satellite cells mediate the hypertrophic process, but without a need (the exercise) they will not start, and without the nourishment (energy availability) they cannot function. All else that impacts the accuracy of the gun can be thought of as the factors influencing satellite cell efficiency. Hormones could be wind speed, gene expression the user’s accuracy, and perhaps DOMS is the distance to the target (or not ;-).

Muscle Damage

Suggested Read: "Understanding Muscle Hypertrophy - Study Sheds More Light on Process of Satellite Cell Recruitment" | read more

The hypertrophy process begins with microtrauma and an ensuing accumulation of calcium within the damaged muscles (Sorichter. 1999). This is shortly followed by a rapid stimulation of satellite cells via hepatocyte growth factor (HGF) and nitric oxide (NO), both of which rely on the changes in calcium levels within the muscle tissue (Tatsumi, 2010), and satellite cells may even be activated by the calcium flux itself (Hara, et al., 2012).

Furthermore, HGF secretion is proportional to the extent of the muscle damage (Tatsumi, et al., 1998). Therefore, it seems plausible that greater muscle damage leads to greater satellite cell recruitment, especially since the activation of satellite cells is exclusive to the fiber that has become damaged and satellite cells of one muscle fiber will not respond to injury of adjacent muscle fibers (Chargé & Rudnicki, 2004).

As it just so happens, DOMS inducing eccentric contractions disrupts muscle integrity more so than concentric or isometric contractions (Faulkner, 1993).  What may seem odd, however, is that EMG activity has been shown to be lower in eccentric loading compared to concentric loading (Westing. 1991), suggesting less fiber recruitment.

Part I	Part II

Just a reminder: This is a twp-part series on Delayed Onset Muscle Soreness. You can switch back and forth between part I "What Is DOMS & How Can It Be Managed? Science, Strategies, Supplements" & part II "No Pain, No Gain? Is DOMS Necessary to Build Muscle?" by clicking on the images to the left.

In their study, (Westing. 1991) measured the torque and EMG activity of the quadriceps muscle at different movement speeds between a knee angle of 30° and 70° on the leg extension for both the concentric and eccentric portions of the exercise. The participants were 14 highly trained athletes that were accustomed to performing maximally during training. As you can see in Figure 1, average torque of the eccentric activity was significantly greater than that of the concentric activity across all movement speeds, but the EMG activity was significantly lower and continued to lower as movement speed increased. The fact that the EMG values of the eccentric activity are below 100% shows that the activation during the concentric phase was higher, even at lower speeds and despite “maximal” effort.

Figure 1: Exemplary data from Westing (1991) showing the mean and SEM torque- and EMG-velocity relationships during the eccentric (open symbols) and concentric (filled symbols) tests.

Actually, this gives support the idea that eccentric exercise is more damaging. It is hypothesized that neural drive to the working muscle is reduced under conditions of extreme muscle tension (i.e. less EMG but more torque) to protect the muscle from injury that could result if it became fully activated (Moore. 1984). Regardless, single bouts of eccentric contractions have been shown to increase the satellite cell content and activation status in Type II muscle fibers (Cermak. 2013).

Inflammation - Friend or Foe of Muscle Growth?

Learn more about eccentric training and satellite cell recruitment and how even fat cells can become muscle.

Once the damage has been done, the repair process may begin. As mentioned in "DOMS - Delayed Onset Muscle Soreness: What Is DOMS & How Can It Be Managed? Science, Strategies, Supplements" (read article), an acute inflammatory response follows microtrauma.

This is also the time that DOMS normally makes it move. During this time, the damaged muscle releases several cytokines, while white blood cells such as neutrophils and macrophages invade the damaged tissue and release several growth factors, all of which may regulate satellite cell activity (Toigo & Boutellier. 2006). Creatine kinase, for example, is a standard indirect measurement of muscle damage (Banfi. 2012).

As stated above, several cytokines and growth factors are involved in the anabolic response to muscle damaging exercise. The list is quite extensive but a few notable players are:

• The cytokine interleukin-6 (IL-6) appears to be an essential regulator of satellite cell mediated hypertrophy, and genetic loss of IL-6 blunts the hypertrophic response (Serrano, et al. 2008). There also appears to be a close association between cytokine concentrations and muscle damage (Pedersen, Ostrowski, et al. 1998), with (Bruunsgaard, et al. 1997) showing that IL-6 concentration is higher after eccentric cycling compared with concentric cycling.  Likewise, interleukin-15 (IL-15) is another highly anabolic player in the inflammatory response to muscle damage (Furmanczyk and Quinn 2003), and is elevated following resistance exercise but not treadmill running, suggesting a need for microtrauma in its stimulation (Pedersen, Akerström, et al. 2007).

• 

  Learn more about the different splice variants of IGF-1 and how they figure in the process of muscle hypertrophy and why systemic measures may mislead us.

  Insulin-like growth factor 1 (IGF-1) has also received much attention due to its ability to increase muscle mass via muscle protein and DNA augmentation (Chakravarthy, Davis and Booth 2000). These effects are at least in part attributed to the activation of satellite cells and increased protein synthesis within the muscle fibers (Barton-Davis, Shoturma and Sweeney 1999). And guess what? Damaging exercise increases IGF-1. A study by (Bamman, et al. 2001), for example, showed that eccentric exercise increased IGF-1 gene expression by 62% while decreasing inhibitory genes by 57%. Oh, and concentric exercise produced non-significant changes in the above markers, suggesting that it was indeed the structural damage responsible for the IGF-1 expression.
• Lastly, the aforementioned HGF acts as a chemo-attractant for satellite cells (Bischoff 1997), effectively stimulating satellite cells to migrate to the place of injury, where it then has a direct effect on satellite cell proliferation and differentiation (Vierck, et al. 2000). Oddly enough, abnormally elevated concentrations of HGF actually inhibit muscle regeneration via up-regulation of myostatin (Yamada, et al. 2010). Since HGF is secreted by regenerating muscles for the first three days following injury (Jennische, Ekberg and Matejka 1993), its accumulation could act as a regulatory “stop” mechanism that marks the end of muscle repair via satellite cells (Chazaud 2010).

A final indirect notion of the importance of DOMS is the idea that NSAIDs – a common treatment method – reduce the hypertrophic response. Recall that both NO and HGF are responsible for activating satellite cells in the early stages of the repair process. This process appears to be partially regulated by the cyclooxygenase (COX)-2 pathway, which releases various prostaglandins known to stimulate satellite cells (Bondesen, et al. 2004). The problem is that NSAIDs inhibit this pathway and thus may impair the hypertrophic response (Schoenfeld 2012). Indeed, studies have shown NSAID usage following eccentric exercise reduced satellite cell activity for up to eight days (Mikkelsen, et al. 2009).

Summary: Hypertrophy involves a complex array of anabolic and catabolic processes working in a downstream manner to favor protein synthesis over degradation. DOMS is not necessary,  may however present itself during the early stages of exercise. What is necessary is a mechanical overload of the muscle resulting in microtrauma. So train hard, train smart, and may the growth be with you.

So is DOMS necessary? DOMS can be thought of as a sign of muscle damage, but it is the damage itself and the subsequent inflammatory response that are responsible for hypertrophy. DOMS is actually a rather poor indicator of muscle damage and will not always reflect the magnitude of the damage (Nosaka, et al., 2002). Nor will it always be present.

Studies have shown that even a single bout of eccentric exercise reduces and may negate DOMS in subsequent bouts (Nosaka. 2001), and these effects persist for at least several weeks (Clarkson. 1992). This would explain why soreness is common in the beginning of a new routine full of unaccustomed damaging exercise, but fades as time progresses. And in fact Flann (2011) showed that using a three week acclimation protocol prior to beginning an eight week eccentrically loaded leg press protocol significantly reduced DOMS and markers of muscle damage compared to beginning the routine cold turkey.

References

• Bamman, M M, et al. "Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans." American Journal of Physiology - Endocrinology and Metabolism 280, no. 3 (2001): E383-E390.
• Banfi, G, A Colombini, G Lombardi, and A Lubkowska. "Metabolic markers in sports medicine." Advances in Clinical Chemistry 56 (2012): 1-54.
• Barton-Davis, E R, D I Shoturma, and H L Sweeney. "Contribution of satellite cells to IGF-I induced hypertrophy of skeletal muscle." Acta Physiologica Scandinavica 167, no. 4 (1999): 301-305.
• Bischoff, R. "Chemotaxis of skeletal muscle satellite cells." Developmental Dynamics 208, no. 4 (1997): 505-515.
• Bondesen, B A, S T Mills, K M Kegley, and G K Pavlath. "The COX-2 pathway is essential during early stages of skeletal muscle regeneration." American Journal of Physiology - Cell Physiology 287, no. 2 (2004): C475-C483 .
• Bruunsgaard, H, H Galbo, J Halkjaer-Kristensen, T L Johansen, D A MacLean, and B K Pedersen. "Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage." The Journal of Physiology 499, no. Pt 3 (1997): 833-841.
• Cermak, N M, et al. "Eccentric exercise increases satellite cell content in type II muscle fibers." Medicine and Science in Sports and Exercise 45, no. 2 (2013): 230-237.
• Chakravarthy, M V, B S Davis, and F W Booth. "IGF-I restores satellite cell proliferative potential in immobilized old skeletal muscle." Journal of Applied Physiology 89, no. 4 (2000): 1365-1379.
• Chargé, S B, and M A Rudnicki. "Cellular and molecular regulation of muscle regeneration." Physiological Reviews 84, no. 1 (2004): 209-238.
• Chazaud, B. "Dual effect of HGF on satellite/myogenic cell quiescence." American Journal of Physiology - Cell Physiology 298, no. 3 (2010): C448-C449.
• Clarkson, P M, K Nosaka, and B Braun. "Muscle function after exercise-induced muscle damage and rapid adaptation." Medicine and Science in Sports and Exercise 24, no. 5 (1992): 512-520.
• Faulkner, J A, S V Brooks, and J A Opiteck. "Injury to Skeletal Muscle Fibers During Contractions: Conditions of Occurrence and Prevention." Physical Therapy 73 (1993): 911-921.
• Flann, K L, P C LaStayo, D A McClain, M Hazel, and S L Lindstedt. "Muscle damage and muscle remodeling: no pain, no gain?" The Journal of Experimental Biology 214 (2011): 674-679.
• Furmanczyk, P, and L S Quinn. "Interleukin-15 increases myosin accretion in human skeletal myogenic cultures." Cell Biology International 27, no. 10 (2003): 845-851.
• Goldberg, A L, J D Etlinger, D F Goldspink, and C Jablecki. "Mechanism of work-induced hypertrophy of skeletal muscle." Medicine and Science in Sports 7, no. 3 (1975): 185-198.
• Hara, M, et al. "Calcium influx through a possible coupling of cation channels impacts skeletal muscle satellite cell activation in response to mechanical stretch." American Journal of Physiology - Cell Physiology 302, no. 12 (2012): C1741-C1750.
• Jennische, E, S Ekberg, and G L Matejka. "Expression of hepatocyte growth factor in growing and regenerating rat skeletal muscle." The American Journal of Physiology 265, no. 1 Pt 1 (1993): C122-C128.
• Mikkelsen, U R, et al. "Local NSAID infusion inhibits satellite cell proliferation in human skeletal muscle after eccentric exercise." Journal of Applied Physiology 107, no. 5 (2009): 1600-1611.
• Miyazaki, M, and K A Esser. "Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals." Journal of Applied Physiology 106, no. 4 (2009): 1367-1373.
• Moore, J C. "The Golgi tendon organ: a review and update." American Journal of Occupational Therapy 38, no. 4 (1984): 227-236.
• Nosaka, K, K Sakamoto, M Newton, and P Sacco. "The repeated bout effect of reduced-load eccentric exercise on elbow flexor muscle damage." European Journal of Applied Physiology 85, no. 1-2 (2001): 34-40.
• Nosaka, K, M Newton, and P Sacco. "Delayed-onset muscle soreness does not reflect the magnitude of eccentric exercise-induced muscle damage." Scandinavian Journal of Medicine & Science in Sports 12, no. 6 (2002): 337-346.
• Pedersen, B K, K Ostrowski, T Rohde, and H Bruunsgaard. "The cytokine response to strenuous exercise." Canadian Journal of Physiology and Pharmacology 76, no. 5 (1998): 505-511.
• Pedersen, B K, T C Akerström, A R Nielsen, and C P Fischer. "Role of myokines in exercise and metabolism." Journal of Applied Physiology, 2007: 1093-1098.
• Schoenfeld, B J. "Does exercise-induced muscle damage play a role in skeletal muscle hypertrophy?" Journal of Strength and Conditioning Research 26, no. 5 (2012): 1441-1453.
• Schoenfeld, B J. "The use of nonsteroidal anti-inflammatory drugs for exercise-induced muscle damage: implications for skeletal muscle development." Sports Medicine 42, no. 12 (2012): 1017-1028.
• Serrano, A L, B Baeza-Raja, E Perdiguero, M Jardí, and P Muñoz-Cánoves. "Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy." Cell Metabolism 7, no. 1 (2008): 33-44.
• Sorichter, S, B Puschendorf, and J Mair. "Skeletal muscle injury induced by eccentric muscle action: muscle proteins as markers of muscle fiber injury." Exercise Immunology Review 5 (1999): 5-21.
• Tatsumi, R. "Mechano-biology of skeletal muscle hypertrophy and regeneration: possible mechanism of stretch-induced activation of resident myogenic stem cells." Animal Science Journal 81, no. 1 (2010): 11-20.
• Tatsumi, R, J E Anderson, C J Nevoret, O Halevy, and R E Allen. "HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells." Developmental Biology 194, no. 1 (1998): 114-128.
• Toigo, M, and U Boutellier. "New fundamental resistance exercise determinants of molecular and cellular muscle adaptations." European Journal of Applied Physiology 97, no. 6 (August 2006): 643-663.
• Vierck, J, et al. "Satellite Cell Regulation Following Myotrauma caused by Resitance Exercise." Cell Biology International 24, no. 5 (2000): 263-272.
• Westing, S H, A G Cresswell, and A Thorstensson. "Muscle activation during maximal voluntary eccentric and concentric knee extension." European Journal of Applied Physiology and Occupational Physiology 62, no. 2 (1991): 104-108.
• Yamada, M, et al. "High concentrations of HGF inhibit skeletal muscle satellite cell proliferation in vitro by inducing expression of myostatin: a possible mechanism for reestablishing satellite cell quiescence in vivo." American Journal of Physiology - Cell Physiology 298, no. 3 (2010): C465-C476.

The Fallacy of Working Out To "Burn Calories" + Exercise Shuts Down the Carb Cravings: Bench Press, Leg Press HIIT & LISS Are Not Meant to Incinerate the Junk You Eat

If you work out to be able to allow yourself to eat, you know you have a serious problem.

So, what was that about the bench pressing consuming as much energy as leg presses and the "exercise just makes you hungry myth" on the last installment of the Science Round-Up? If that's what you have been asking yourself this morning, when you showered I am impressed - or should I be worried?

If you have not done so already, this would be the right time to download + listen to the Science Round-Up - I promise there is much to learn and not all of it is going to be repeated here.

Whatever... in the end it does not matter how urgent you were waiting to take a look at the data that supports my argument that (a) exercise does not just make you hungry, and that (b) the notion to work out primarily to burn energy is hilarious.

Chest vs. legs what's energetically more costly?

While I could imagine that the comparison would have yielded a different result if the 10 healthy young men (>1 year of resistance training experience; BMI ~24kg/m²) had performed squats instead of regular leg presses, I have to admit that I was still surprised to see that Magossoa et al. actually found no difference in the total energy expenditure between 3 sets of 10 reps (70% 1RM) of bench vs. leg presses (Note: The researchers determined the total energy expenditure using the oxygen uptake (aerobic component) the EPOC and lactate production (anaerobic component)).

Table 1: Workload, energy expenditure total, per minute per weight lifted (Magosso. 2013)

If you look at the data in Table 1, you will have to concede: The only difference between the energy expenditure during the leg and the leg press was the inferior energy consumption per kg of weight on 'the bench'.

If you were one of the lazy (and mostly ignorant) buggers who "already have big enough legs", you could probably use these results to argue that leg presses and the rest of the leg workout was a pretty unnecessary undertaking - I mean, if you don't want bigger legs it should at least help you with that sixpack by burning a couple of calories, right?

Only a fool will work out to "burn energy"

Suggested Read: "Busting the 3,500kcal = 1lbs Weight Loss Myth! Debunking the rule of thumb with the power of science" | read more

Once they're there, it does usually you not take very long until people will remember this ingeniously simply (and about s flawed) rule of thumb that says: To lose 1lbs of fat you got to burn 3,5000kcal. Here, in our concrete example, that would mean that it would not matter if you did another 228 sets of bench presses or leg presses to lose 1lbs of pure body fat.

Once you've gotten caught in calculations such as the above, i.e. 229 sets x 46kcal / 3 sets  > 3500kcal, or in words "I got to do 228 sets of bench presses to burn one pound of body fat!", you are lost.

Firstly, the equation 3,500kcal caloric deficit = 1lbs fat loss if flawed (learn more).

Secondly, and even more importantly, doing more, which is what all the "I workout to lose fat" weekend warriors do, is not going to yield superior results. If you don't believe that, I suggest you go back to my "How to Burn 27,300 Kcal Extra W/out Losing a Single Extra Pound of Fat!"-article and take a look at the results of the Rosenkild study from 2012 (figure 3).

Gary is ... no, not a fool, but he is still wrong

Now, I obviously cannot forbid workout extra and luckily even Gary Taubes can't because even if you insisted to burn 600kcal, instead of just 300kcal, you can at least console yourself that this is not going to increase your appetite (learn more). Especially if we are talking about relatively intense exercise for similarly "relatively obese" individuals, working out will not only reduce your window of opportunity to eat (for some people even that may make a difference, believe me), but rather work like a gastric bypass - one that won't allow you to hit your obesogenic macros on the subsequent meals.

Figure 1: Macronutrient intake (lunch + dinner in g) on control vs. exercise day (David. 2013)

Those of you who have not listened to the podcast yet will now probably be wondering what I am talking about, right? Well, take a look at the 3D bars in Figure 1. They represent the results of a study David et al. conducted earlier this year. A study that involved both lean and obese kids and a study that demonstrates that a relatively short (3x10 min) but comparably hard workout (75% VO2max) is not going to make the sugar junkies crave for more - quite the opposite, it will reduce their apperite for carb(age) to a normal level [similar appetite-reducing effect were observed by Sim et al. (2013) in adult men and Rosenkilde (2013; already discussed at the SuppVersity].

I mean, a voluntary 35% reduction in carbohydrate intake during lunch and dinner and a total reduction in energy intake of 475kcal are impressive ballpark figures considering the fact that exercise is often said to "just make you hungry" - wouldn't you agree?

EPOC should not determine your choice of exercise either

If you are sprinting because of the increase in EPOC, you are a fool.

From the article I referenced in yesterday's write-up ("More Than 3x Higher EPOC Induced Energy Expenditure With HIIT vs. LISS! But Does That Really Matter?" | read more) you already know that  HIITing it hard on Wingate tests will yield a pretty pathetic increase in EPOC of ~20kcal over a casual 30min jog.

So even if it was about burning calories the jog would be far superior because the increase in Excess Post-Exercise Oxygen Consumption (EPOC) is not going to compensate the additional kcal the subjects in the Townsend study burned during the steady state exercise.

The latter is by the way not much different if you compare two different HIIT regimen - a very intense short one (HIIT1) and a somewhat longer slightly less intense alternative regimen (HIIT2):

• HIIT1: 10 x 1min, 1min pause between intervals; cycling at 80-90RPM at 90% of the HRmax

• HIIT2: 10 x 4min, 2min pause; cycling at 60-80RPM and without a prescribed minimal heart rate

In their trial that involved 9 lean, healthy male subjects, Kelly et al. obeserved that the HIIT2 trial was more than two times more energetically costly (675kcal vs. 275kcal) - the EPOC effect on the other hand did not lead to any significant differences in post-exercise energy expenditure, so that the HIIT1 group was stuck with their ~400kcal inferior energy expenditure... now, that sounds as if it was a bad thing, but if we consider that they spent less time on the ergometer and were rewarded with a greater stimulus for mitochondrial expansion and even muscle growth (see "The Anablic Effects of HIIT" | read more), I would not say that they came off second best - would you?

Practical suggestions for your workout week...

• health focus - 2-3x resistance training + daily LISS as in walking (min. 30-60min)
• performance focus - 3x resistance training + 1-2x HIIT + 6x LISS as in walking (30-40min)
• physique focus - 3-4x resistance training + 1x HIIT +  6x LISS as in walking (30-40min)

Don't forget that the reason you do the LISS training is not because you want to burn calories, but rather because you want to spend some time doing what you actually would have to do everyday: Walking from place A to B; and if you belong to the few of us who don't sit on a desk all day, you may skip the walk in the park.

So what's a good reason to work out, then? Health! I know that does not sound as sexy as six-pack abs and bigger sleeves, but there is not denying it: Exercise is your vaccine and magic pill. It's what's going to make you feel good, look good and age well and unless you want to end up debilitated in a nursing home it is not optional even if you follow an energy restricted diet for the rest of your life. What is optional, though, is exercise as a means to increase athletic performance or influence the shape of you body withing your individual very specific limits.

Within this health ↔ performance ↔ looks triangle you will often encounter conflicts, where the optimization of one compromises the realization of another. I am nevertheless convinced that classic light intensity steady state (to make up for our modern sedentary lifestyle), en vogue high intensity interval training (to increase your VO2max) and classic and modern forms of resistance training (to build and maintain muscle mass) all have their place in a routine that does not lose sight of any of the vertices of the triangle.

What? How you can ever lose weight without doing endless hours of cardio? Well what about dieting?

References:

• David T, et al. Obese but not lean adolescents spontaneously decrease energy intake after intensive exercise. Physiol Behav. 2013 [epub ahead of print]
• Kelly B, King JA, Goerlach J, Nimmo MA. The impact of high-intensity intermittent exercise on resting metabolic rate in healthy males. Eur J Appl Physiol. 2013 Oct 6. [Epub ahead of print]
• Magosso et al. Energy Expenditure during Multiple Sets of Leg Press and Bench Press. Journal of Exercise Physiology online. October 2013.
• Rosenkilde M, Auerbach P, Reichkendler MH, Ploug T, Stallknecht BM, Sjödin A. Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise--a randomized controlled trial in overweight sedentary males. Am J Physiol Regul Integr Comp Physiol. 2012 Sep 15;303(6):R571-9.
• Rosenkilde M, Reichkendler MH, Auerbach P, Toräng S, Gram AS, Ploug T, Holst JJ, Sjödin A, Stallknecht BM. Appetite regulation in overweight, sedentary men after different amounts of endurance exercise - a randomized controlled trial. J Appl Physiol (1985). 2013 Sep 19. [Epub ahead of print]
• Sim AY, Wallman KE, Fairchild TJ, Guelfi KJ. High-intensity intermittent exercise attenuates ad-libitum energy intake. Int J Obes (Lond). 2013 Jun 4. doi: 10.1038/ijo.2013.102. [Epub ahead of print]

Science Round-Up Seconds - GABA & Exercise: Both Can Improve and Mess With Your Sleep. Plus: Natural GABA Alternatives and Sleep As An Overtraining-Gauge

Don't forget that and prioritize proper sleep hygiene over pills and powders.

Let me make get this straight, yesterday's episode (please note that at the minute I post this article, the download is not yet working, should go up within the next hour, though) of the Science Round-Up on Super Human Radio was not only ultra-long (120min+), it was also largely speculative. If you already listened to the show, you will know that Carl and I took up on a discussion Dan Rollins triggered on his, Carl's and my Facebook page(s). Contrary to what you would expects Dan felt that gamma-Aminobutyric acid aka GABA would not help him calm down and let him sleep. For him GABA turned out to have stimulative rather than sedative effects.

I am not going to repeat all the potential explanations I went through in the first ~40min of the show here. Instead, I'd suggest you simply download the podcast and listen to the various hypothesis which range from (a) the general issue of whether or not GABA even crosses the blood-brain-barrier, over (b) the possibility that the GH spike, the sedative (low blood glucose) and the agitating effect (catecholamine + cortisol release with very low blood glucose) could all be brought about by a GABA induced increase in insulin production and a corresponding reduction in blood glucose levels to (c) potential confounding factors such as caffeine consumption (Roca. 1988; Desaulles. 1991; Mukhopadhyay. 1995), interactions with beta alanine, taurine or glycine (Tiedje. 2010; El Idrissi. 2013; Kletke. 2013), (d) genetic differences as with the tingling for beta alanine (Macphee. 2013) or (e) the influence of exercise on the density of GABA receptors in the brain (Dishman. 1990).

Enough of the speculations: What are proven alternatives

Against the background that we still don't really know why Dan and others don't seem to benefit from GABA supplementation the way Carl and Alisa do, we do know that there are other natural alternatives:

• Valerian [dosage: 400-900mg] - inhibits breakdown of GABA in the brain; assuming that GABA makes it across the blood-brain-barrier, valerian would thus work synergistically with oral GABA 

• 

  Due to its anti-PPAR-gamma effect ginseng also made it into the list of "agents that may help you to stay lean" I posted earlier this year. Want to know about the other "20 Anti-Obesity Agents Have the Potential to Inhibit Fat Gain Right at the Cellular Level"? Here you go!

  Ginseng [1-2g crude root extract or 200-600mg of extract] - ginsenoids compete with GABA on both the GABA-A & GABA-B receptor and are thus thought to exert their calming (only in low! doses) effects on the CNS via direct GABA-ergic effects; sedative effects have been observed for Panax ginseng (Korean or Asian ginseng), Panax quinquefolius (American ginseng), and Panax vietnamensis (Vietnamese ginseng); if you feel agitated, reduce the dosage
• Kava kava [180-210mg of kava lactones] - the active agents in Kava kava belong to a group of resinous compounds known as kava lactones or kava pyrones, they bind to the benzodiazepine binding site of the GABA receptor, which could reduce the risk of unwanted excitatory effects
• Passion flower (Passiflora incarnata) [4-8g as a tea] - has been used as a sleeping aid for centuries; chrysin, a mild anti-estrogen appears to be the active ingredient (GABA-A binding; cf. Zhai. 2008); warning: must not be consumed by pregnant women (!) PI can initiate uterine contractions

• 

  I know you don't want to hear that, but(!) don't forget that it could also be your BCAA product that keeps you you from falling asleep and makes you wake up several times during the night by blocking the uptake of tryptophan and thus depleting your brain of the raw material for serotonin (read more).

  Hops (Humulus lupus) [0.5g of dried herb] - has binding affinities to both the melatonin and serotonine receptor (Abourashed. 2004) and can increase GABA in the brain (Franco. 2012); warning: must not be consumed by women with a (family) history of breast cancer (!) hobs has mild, but distinct pro-estrogenic activity (Hajirahimkhan. 2013)
• L-tryptophan [1g] / 5-HTP [100mg] - both will increase serotonin and could thus be stacked with agents that act on GABA; incidentally, there is paucity of research on the efficacy of either of the two as sleep aid
• Melatonin [1-10mg] - as both Carl and I pointed out on the show, melatonin is not an acute sedative, but a signal that it's time to "shut down", don't expect it to actively "send you into sleep", like a sleeping pill

Aside from these agents, Carl and I talked about accupuncture and low energy emission therapy (LEET), as well. While the mechanisms of the former are still not fully understood (e.g. Kwok. 2013), the amplitude modulated high frequency fields the LEET mouthpiece emits right into your brain have been shown to modify the release of GABA and the concentration of benzodiazepine receptors in the rat brain. In addition, low level electromagnetic fields can directly induce the release of melatonin in mammals (Reiter. 1993).

If you are sprinting because of the increase in EPOC, you are a fool.

Read more about exercise and energy expenditure tomorrow! With the info on energy expenditure also crammed into this article it would have been too packed. Therefore you will have to live with a 24h deleay until you learn about the energetic costs of bench pressing, the laughable EPOC effects of HIIT and the evidence that exercise does not just make you hungry. If you feel that's not tolerable, you can already learn about the pathetic EPOC effects of HIIT and exercise & hunger in previous articles.

I already hinted at the physiological (side?) effects of chronic endurance training on the expression of the GABA receptors in rodent brains early in the show (and this article). It should thus not surprise you that exercise can have major impacts on the onset, quality and duration of your sleep - both positive and negative ones, obviously [based on data from Youngstedt (1997; published online 2003)]:

• 

  "90 Min Sleep Restriction Changes in Insulin Resistance Last For One Week"

  Timing of your workouts: While working out 4-8h before bed will have you fall asleep easily, you may experience problems if you have to ignore the onset of tiredness, because you have been exercising more than 8h before you go to bed or to close to hitting the hay. Incidentally, working out 4-8h before bed another advantage: It will help you to sleep through.
• Working out outdoors: The light exposure, the fresh air all that makes working out outdoors so healthy for you (as long as you are not living in Beijing ;-) will energize you and could keep you from falling asleep.
• Duration of your workout: There is a U-shaped dose-response curve for the negative effects of working out on your REM sleep. As Carl rightly pointed out during the show the negative effects of short exercise durations (<1h) is probably in as much a question of intensity / exhaustion (you train intense, when you train short) as the cumulative effects of "exercising" for more than 2h straight (which is by the way more than twice as detrimental for your sleep quality than the <1h exercise)
  
  Aside from its effect on the workout duration will also affect your overall sleep needs with both exercises in the 1-2h and exercises in the >2h range having a major impact on the amount of time you got to spend in bed to recover.
• Exercise intensity*: With a high propensity of low intensity exercise to help you sleep through, a walk on a treadmill in the evening is not going to compromise a good nights sleep, the HIIT workout that would improve your postprandial triglyceride response on the next day (I used this SuppVersity Facebook News as a discussion starter in the live-show), on the other hand may have you wake up several times during the night (*note: I used the studies on the post-exercise heat load in Youngstedt et al. as a proxy for intensity).

If you wanted to distill some practical advice on how you can / should exercise to avoid that your workouts will interfere with your sleep, you should (a) leave at least 4h between any intense workout and hitting the hay (HIIT, weight lifting, etc.) and (b) make use of the beneficial effects of moderate duration (20-40min) light intensity workouts (walking on an incline treadmill, cycling etc.) on sleep onset and quality.

Did you know that...

there are other agents that can "spike" GH temporarily?

• intravenous (iv) insulin 0.2 IU/kg - 50x increase
• intramuscular (im) glucagon 1 mg - 21x incr.
• iv. arginine 20 g/m² as an infusion over 30 minutes - 11x incr.

All observed in a human study involving 18 perfectly healthy young men(Rahim. 1996).

In view of the effect GABA has on the release of insulin from the pancreas, it is not unlikely that my previously voiced hypothesis that the "relaxation" and the "agitation" are responses to low and very low glucose levels would also explain the increase in GH as a response to the hypoglycemic effects of insulin.

What can you take away from the first part of this installment of the Science Round-Up Seconds?

• GABA does not work for everyone
• esp. in higher doses GABA can have excitatory, instead of calming effects
• the exact reasons that this happens is not clear; temporary hypogylcemia is albeit not the least likely candidate
• the hypoglycemia would also explain the GH release which is yet very unlikely to have beneficial effects on muscle growth (GH & gains don't correlate) or fat loss
• among the GABA alternatives, those with a specificity for the benzo docking site on the GABA receptor could work for people for whom GABA itself is excitatory
• working out too late / too intense can compromise sleep
• being "tired but wired" indicates sympathetic overtraining (too much intensity)
• constant fatigue + an increased sleep demand, but light and ineffective sleep is more indicative  parasympathetic overtraining (too much volume)

References:

• Abourashed EA, Koetter U, Brattström A. In vitro binding experiments with a Valerian, hops and their fixed combination extract (Ze91019) to selected central nervous system receptors. Phytomedicine. 2004 Nov;11(7-8):633-8.
• Desaulles E, Boux O, Feltz P. Caffeine-induced Ca2+ release inhibits GABAA responsiveness in rat identified native primary afferents. Eur J Pharmacol. 1991 Oct 2;203(1):137-40. 
• Dishman RK, Dunn AL, Youngstedt SD, Davis JM, Burgess ML, Wilson SP, Wilson MA. Increased open field locomotion and decreased striatal GABAA binding after activity wheel running. Physiol Behav. 1996 Sep;60(3):699-705.
• El Idrissi A, Shen CH, L'amoreaux WJ. Neuroprotective role of taurine during aging. Amino Acids. 2013 Oct;45(4):735-50. doi: 10.1007/s00726-013-1544-7. Epub 2013 Aug 21.
• Kletke O, Gisselmann G, May A, Hatt H, A Sergeeva O. Partial agonism of taurine at gamma-containing native and recombinant GABAA receptors. PLoS One. 2013 Apr 30;8(4):e61733.
• Kwok T, Leung PC, Wing YK, Ip I, Wong B, Ho DW, Wong WM, Ho F. The effectiveness of acupuncture on the sleep quality of elderly with dementia: a within-subjects trial. Clin Interv Aging. 2013;8:923-9.
• Macphee S, Weaver IN, Weaver DF. An Evaluation of Interindividual Responses to the Orally Administered Neurotransmitter β -Alanine. J Amino Acids. 2013;2013:429847.
• Mukhopadhyay S, Poddar MK. Caffeine-induced locomotor activity: possible involvement of GABAergic-dopaminergic-adenosinergic interaction. Neurochem Res. 1995 Jan;20(1):39-44.
• Rahim A, Toogood AA, Shalet SM. The assessment of growth hormone status in normal young adult males using a variety of provocative agents. Clin Endocrinol (Oxf). 1996 Nov;45(5):557-62.
• Reiter RJ. Electromagnetic fields and melatonin production. Biomed Pharmacother. 1993;47(10):439-44.
• Roca DJ, Schiller GD, Farb DH. Chronic caffeine or theophylline exposure reduces gamma-aminobutyric acid/benzodiazepine receptor site interactions. Mol Pharmacol. 1988 May;33(5):481-5.
• Tiedje KE, Stevens K, Barnes S, Weaver DF. Beta-alanine as a small molecule neurotransmitter. Neurochem Int. 2010 Oct;57(3):177-88.
• Youngstedt SD, O'Connor PJ, Dishman RK. The effects of acute exercise on sleep: a quantitative synthesis. Sleep. 1997 Mar;20(3):203-14.
• Zhai K, Hu L, Chen J, Fu CY, Chen Q. Chrysin induces hyperalgesia via the GABAA receptor in mice. Planta Med. 2008 Aug;74(10):1229-34.

Melato Cola™ or What? Fructose for Improved Glucose Metabolism and Melatonin to Counter Fructose Overload

There was a time, when Coke still contained "coke"... so why not add some melatonin for health benefits? I am obviously just kidding here, but a combination of fructose + melatonin may actually make sense.

The title of today's SuppVersity article is confusing, I know. Firstly, it contains the almost heretical notion that fructose could actually improve instead of impair your glucose metabolism and secondly it does not appear to make sense that you would have to use melatonin to counter the pro-diabetic effects of fructose, if the latter is in fact so good for you.

Before you are getting totally confused, let me clarify how the improvements in glucose metabolism and the melatonin-powered diabesity protection go together: Both have been observed in a recent study from the Pontificia Universidad Católica Argentina in Buenos Aires, Argentina (Cardinali. 2013), in the course of which the improved glucose metabolism was nothing but a side-finding of a study Cardinali et al. conducted to  examine the effect of melatonin when it is administered to rodents simultaneously with fructose in the drinking water.

This is the Coke + sufficient sleep study ;-)

Obviously this is not as the subheading would suggest the "coke + sufficient sleep study", but in light of the fact melatonin is after all the "sleep" hormone and in view of the results of a recent study by Senador et al. who observed that fructose had a negative effect on glucose management only, when it was available during the light phase (which is the inactive phase for a rodent; cf. Senador. 2012), it comes close; and that despite the fact that fructose timing was yet not an issue in the study at hand. Instead of modifying the timing, Cardinali et al. used different amounts of fructose with half of the rodents in the experimental arm of the study having a 5% and the other half having a 10% fructose solution as their main water supply.

Figure 1: Glycemia (mg/dL) 0-140min after 2g/kg body weight  glucose tolerance test (Cardinali. 2013)

If we trust the nutritiondata.com information about the average fructose content of a "carbonated beverage, cola, with higher caffeine" ...

• the rodents in the 10% fructose group were consuming the total carbohydrate equivalent of coke, but with a 100% instead of ~50% fructose content, while
• the rodents in the 5% fructose group were consuming less total carbohydrates, but roughly the same amount of fructose someone would ingest if he drank nothing but coke.

A direct comparison of either of the groups to the "coke only"-drinking human being is thus not warranted.

It is nevertheless intriguing that the 5% fructose group showed a significantly higher glucose tolerance - not just compared to the 10% fructose group, but also compared to the control group that was fed with water, only (see figure 1).

"Meta-Analysis: Lower Glucose, Insulin and HbA1c Levels From 'Catalytic' Dose of 36g Fructose" | read more

"But isn't fructose the reason you develop diabetes?" Before we get on to the effects of melatonin, I want to emphasize that this is by no means an outlier, in fact, I have written about the catalytic effects of 36g of fructose in a previous post "6x Bananas a Day!? Meta-Analysis: Lower Glucose, Insulin and HbA1c Levels From 'Catalytic' Dose of 36g Fructose" (learn more).

Previous studies have also shown that a 2:1 mixture of glucose + fructose is at least up to the regular glucose only drinks in terms of post-workout glycogen repletion (learn more) - partly because the fructose will keep the liver occupied, while the muscles suck up the glucose.

As previously mentioned the main research interest of the Argentinian scientists was not the effect of fructose on the glucose sensitivity of their rodents, but rather if the administration of 25 μg/mL of melatonin in the tapwater the rodents received would lead to significant changes in the study outcomes.

Figure 2: Effects of melatonin in drinking water with or without 5% [left] and 10% [right] fructose on body weight, systolic blood pressure and glucose response to glucose tolerance test (Cardinali. 2013)

As you can see in figure 1 it did: Melatonin did ameliorate the weight gain, and the increase in blood pressure that was observed even with only 5% fructose in the drinking water. It did not improve the glycemic response of the rats in the 5% fructose group even more, though, but it bulnted the negative effects of the 10% fructose solution had on the glycemic response in the glucose tolerance (figure 2, right).

SuppVersity Suggested Read: "Circadian Rhythmicity - Sunlight, Bluelight, Backlight & Co Mess Learn How THey W/ Your Internal Clock. Plus: Tips & Tricks to Prevent Negative Side-Effects" | read more

Is a melatonin solution the solution? If we also consider the negative effects of 10% fructose feeding on LDL (the rodents on 10% + Mel had even lower LDL than the control), the normalization of triglycerides and the potential therapeutic reduction in uric acid (-30% even vs. control), of which Cardinali et al. point out that it could have therapeutic effects in people with gout and other uric acid related metabolic disorders, it would appear smart that do dissolve the human equivalent dose of 21-35mg melatonin in your drinking water in the morning and keep guzzling it all day long.

Well, as I said, it "would appear to be" smart, but is it really smart? I wouldn't be too sure about that. Despite the fact that that you probably won't die, the chronically increased systemic melatonin levels could have long-term negative consequences on your circadian rhythm that could undo all potential benefits.

Restricting your fructose intake to fructose from fruit, only, getting enough sleep and using melatonin timely, i.e. 20min before bed would thus appear to be a more prudent approach to improve / maintain optimal blood glucose levels and insulin sensitivity. And if you are more into hard facts than "erring on the side of caution", you may consider the acute decrease in glucose tolerance, Cagnacci et al. observed in postmenopausal women, when they participated in a blood glucose test after the administration of 1 mg melatonin more convincing (Cagnacci. 2001).

References:

• Cagnacci A, Arangino S, Renzi A, Paoletti AM, Melis GB, Cagnacci P, Volpe A. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf). 2001 Mar;54(3):339-46. 
• Cardinali DP, Bernasconi PA, Reynoso R, Toso CF, Scacchi P. Melatonin may curtail the metabolic syndrome: studies on initial and fully established fructose-induced metabolic syndrome in rats. Int J Mol Sci. 2013 Jan 25;14(2):2502-14.
• Senador D, Shewale S, Irigoyen MC, Elased KM, Morris M. Effects of restricted fructose access on body weight and blood pressure circadian rhythms. Exp Diabetes Res. 2012;2012:459087.