BDNF-Driven Athletic Brain Optimization For Wise Guys: Better Hard, Than Long, But Always Without Interruptions

Believe it or not, a "smart" brain is not necessarily a healthy brain. Nevertheless, if Einstein had worked out regularly and lived a couple of years (better decades ;-) longer, he may have had a change to figure out the missing link between his Theory of Relativity and the Quantum Theory ;-)

"Workout for your brain!" If you were a member of the club of sedentary couch-potato, you would probably be thinking of Dr. Kawashima or similar IQ games on one of your beloved gaming devices. As a diligent student of the SuppVersity and life-long follower of physical culture, you will yet be aware that the imperative "Work out for your brain!" has to be understood quite literally. After all, there have been dozens of studies to show how exercise benefits the brain of young and old, sick and healthy, lean and obese individuals.

In this context scientists often measure a peptide that goes by the name brain-derived neurotrophic factor, or short BDNF, which has been recognized as an important tropic hormone in the regulation
of neuron morphology and survival. With exercise being one of the stimuli that triggers its production BDNF it is not surprising that working out has been shown to improve cellular development and growth, exert beneficial effects on mood regulation, and cognitive functions such as learning and memory - all of these things are after all influenced by this important hormone.

Low circulating BDNF levels, on the other hand, have been associated with a widerange of neuropsychiatric disorders including depression (Karege. 2002), bipolar disorder (Cunha. 2006), schizophrenia (Zhang. 2007) and neurodegenerative diseases (Yu. 2008). And despite the fact that a definitive causal relationship between low BDNF levels and the said pathologies has yet not been established, researchers are confirmed that elevated BDNF levels can lead to improved brain health.

So if exercise is good, how much is optimal?

As mentioned before, we do already know that chronic exercise training - endurance exercise in particular - will promote the production of this important neurologically active peptide, what we do not know, however, are the dosage and intensity that would yield "optimal" effects... well, I should say we did not know that until a group of researchers from the Department of Psychology, Neuroscience Program, and the Department of Health Promotion and Human Performance at the Weber State University in Odgen gave us a first glimpse on what this "optimal" dose / intensity ratio may look like.

In their latest paper Matthew T. Schmolesky, David L. Webb and Rodney A. Hansen report the results of a study involving 45 healthy human adult males aged 18-25, who were assigned to one out of six exercise conditions that varied in both, intensity (80% or 60% of heart rate reserve, or control) and duration (20 or 40 min). To elucidate whether circadian or other effects would influence the response to the long and short vigorous and moderate intensity exercise, three subjects were excluded to serve as a sedentary control.

Figure 1: Changes in s-BDNF levels relative to baseline (Schmolesky. 2013)

If you discard the inter-group differences and focus on the effect size in general, first, you will notice that any type of aerobic exercise will result in significant increases in BDNF levels (30% on average). Once you look closer, it does yet become apparent that there is a non-significant tendency for higher changes in BDNF levels with higher intensities and longer durations.

For the study at hand this implies that the Vig40 trial, in the course of which the subjects cycled for 40 min at an intensity of 80% of their maximal heart rate, yielded the greatest total increase in BDNF. If you do yet take a look at the non-significant difference to the Vig20 trial, the additional 25% increase in BDNF is paid for with an additional 20 minutes on the cycle ergometer. Now taking into account that this was still more effective than the high dose bout (40min) of moderate intensity exercise, the 20 min of vigorous exercise provide the most BDNF-bang for your bucks and should thus be considered the "optimal" training regimen to promote your brain health.

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Exercise specific news: "Bigger, Stronger, Faster: CoQ10 for Brain & Muscle. The Optimal HIIT Regimen for Fun & Fat Loss - 8s at 100% 60s Idling! Protein Power From Oats? Plus: Rest Times, Clusters, Form & Hypertrophy Training" (read more)

"Hold on that's not optimal"... Ok, you are right, it is not just questionable, but in fact highly unlikely that the scientists actually found these 20 minutes of vigorous activity are actually the non-plus-ultra among the unlimited number of potentially BDNF-boosting exercise regimen.

In fact, the existing bias towards higher intensities and shorter durations. Yet while this would suggest that high intensity interval training could be the true "optimum" in terms of BDNF-boosting exercise. There are as of now no human studies to support this notion and a previously published study in which the researchers tested the effects of exercise on the regeneration of axons in injured peripheral nerves clearly suggests that the BDNF response to interval training is inferior to its continuous counterpart (Wood. 2012).

Whether these results are applicable to human beings and / or whether the 5x2min intervals the rodents in the Wood study were exposed to may have been "too much of a good thing", will yet have to be elucidated in future trials.

References:

• Cunha AB, Frey BN, Andreazza AC, Goi JD, Rosa AR, Gonçalves CA, Santin A, Kapczinski F. Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes. Neurosci Lett. 2006 May 8;398(3):215-9.
• Karege F, Perret G, Bondolfi G, Schwald M, Bertschy G, Aubry JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res. 2002 Mar 15;109(2):143-8.
• Schmolesky MT, Webb DL, Hansen RA. The Effects of Aerobic Exercise Intensity and Duration on Levels of Brain Derived Neurotrophic Factor in Healthy Men. Journal of Sports Science and Medicine. 2013. 12 [epub ahead of print]
• Wood K, Wilhelm JC, Sabatier MJ, Liu K, Gu J, English AW. Sex differences in the effectiveness of treadmill training in enhancing axon regeneration in injured peripheral nerves. Dev Neurobiol. 2012 May;72(5):688-98.
• Yu H, Zhang Z, Shi Y, Bai F, Xie C, Qian Y, Yuan Y, Deng L. Association study of the decreased serum BDNF concentrations in amnestic mild cognitive impairment and the Val66Met polymorphism in Chinese Han. J Clin Psychiatry. 2008 Jul;69(7):1104-11.
• Zhang XY, Tan YL, Zhou DF, Cao LY, Wu GY, Xu Q, Shen Y, Haile CN, Kosten TA, Kosten TR. Serum BDNF levels and weight gain in schizophrenic patients on long-term treatment with antipsychotics. J Psychiatr Res. 2007 Dec;41(12):997-1004.

Capsaicin - 2.56mg to Keep Your Metabolism Running on a Diet. Cold Thermogenesis - 5°C for 6kcal/h. Mobile Phones - 0.853 W/kg Pulsed EMR to Mess Up Neurotransmitters

You don't have to worry, the "guidelines" do not require you to perform either your 150 minutes of moderate cardio, or your 75 minutes of vigorous-intensity aerobic activity, and not even your two weekly full-body workouts in these shorts.

24% that's the SuppVersity Figure of the Week and it is actually not so low as I would have expected it to be, after all those 24% describe the ratio of US adults who meet the Physical Activity Guidelines for muscle-strengthening physical activity. Which guideline? Ah, you are the US guys and gals, so you should know that you are advised to

"perform muscle-strengthening activities that are moderate or high intensity and involve all major muscle groups on 2 or more days a week, because these activities provide additional health benefit" (2008 Physical Activity Guidelines for Americans)

Additional benefit? Well, it goes without saying that the 150 minutes of moderate aerobic training and the reduction of salt, as well as the use of healthy vegetable oils are the primary object for every 'true American'.

Not That Hot: Cold Thermogenesis

Figure 1: An avg. effect size of 6kcal/h, non-responders + "negative-responders"; it doesn't work for those past the 30y mark - how on earth is cold thermogenesis going to help us solve the obesity pandemic?

(Chen. 2013) In a single-blind, randomized crossover intervention 24 volunteers (14 men, 10 women) were exposed to a 5°C temperature reduction (from 24°C to 19°C). During that treatment they wre sitting in a whole-room indirect calorimeter to measure their energy expenditure and lay in a positron emission tomography (PET) scanner afterwards (results, see image to the right).

Now, based on previous SuppVersity articles on the matter, you'll know that it is not exactly easy to find people who actually harbor a "significant" (and in this case this means "any at all") amount of metabolically active brown adipose tissue to get the thermogenesis going.

And with 23cm³ and 35cm³ for the men and women participating in the study at hand, the amount of the "good fat" they were carrying around is still pretty stingy. No wonder ...

• there was no thermogenic response in the male participants, but a
• 10% increase in energy expenditure in the female participants

I already see your eyes glow in the cold, ladies, but you crow too soon - those 10% were 6kcal/h, I repeat in full words "six additional calories per hour". Or roughly as much energy as a single set of body weight squats would be burning .

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If you are looking to shed 18% fat in 21 days, increase your health and your physical appearance, turn up the heat during your workouts, clean up your diet and don't move into the fridge (learn more)!

Bottom line: Against the background that there were neither significant changes in the hormonal profile (thyroid, adrenal, etc.) and considering the fact that the effect declined with age and was hardly measurable for 5 and negative (=lower energy expenditure in the cold) for 4 subjects, I stick to previous assessment: cold thermogenesis as a means of "expending more energy to get rid", is about as stupid as the whole concept of expending more energy to lose fat and it certainly does not, as the scientists state "represent a novel environmental strategy in obesity treatment".

If you want a "environmental strategy in obesity treatment", ban all the junkfood, switch off the elevators, hand out bikes and increase the health insurance cost for everyone who refuses to get his or her ass off the couch on a regular bases. Zealous? Unrealistic? Yeah, it is - but not more unrealistic than the hilarious notion that cooling the overweight majority of the inhabitants of the Western Obesity Belt down by 5°C would solve the obesity problem.

Mobile phones mess with neurotransmitter levels

Andreassen et al. have already developed a "Facebook Addiction Scale" and found that Facebook junkies tend to be

neurotic and extraverted, but lack a reasonable amount of conscientiousness (Andreassen. 2012)

(Aboul Ezz. 2013) I am well aware that many of you don't want to hear this and will discard the results researchers from the Cairo University present in their latest paper in the European Review forMedical and Pharmacological Sciences as "just another worthless rodent study" and I freely admit, you may be right.

It is well possible that rodents are more susceptible to the pulsed electromagnetic radiation from mobile phones than humans are, but I gather you will have to agree that the chance that there are still residual effects in human beings is by no means zero... and based on my personal observations, I would even argue that you see certain abnormalities in mobile phone junkies, already. Ok, those could have psychological and behavioral roots, but ...

Before I digress even further into the abyss of the "I cannot live without my mobile" virus that has already befallen many of my real world students, let's rather take a look at the outcome of Aboul Ezz et al.'s latest experiment.

Table 1: While the first six are actually the TOP (=low SAR) phones that are currently on the market, the others are random picks of mine from the data on SARdatabase.com

In the course of the latter, the scientists exposed a group of adult rats to the pulsed electromagnetic radiation of a mobile phone having a power density of 0.02W/cm² and an average specific absorption rate (the notorious SAR-value) of 0.843W/kg for 1h/day (that happens to be a little less of what your neat iPhone5 is pumping into your brain day in and day out) and measured the monoamine levels after one, two and four months, as well as on a follow-up one month after the last exposure and found:

The exposure to EMR resulted in significant changes in DA [dopamine], NE [norepenephrine] and 5-HT [serotinine levels] in the four selected areas of adult rat brain" (Aboul Ezz. 2013)

And the Egyptian researchers add, these chance could well explain the adverse effects that have been reported in conjunction with chronic "low level" exposure to pulsed electromagnetic radiation, which are usually related to memory problems and chronic stress.

What they don't mention in the abstract though is that the changes were not really consistent. It appeared as if there was some cyclicity involved with an initial increase in 5HT, a concomittant decrease in dopamine a newly established "balance" between the two leading to an increase in norepinephrine (=chronic stress) in months four.

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Bottom line: That being said, I can only repeat that even in the absence of direct physiological effects of the EMR exposure, the constant state of "being available" to whoever wants to reach you, as well as the addictive potential of being in contact with all your (often fake) facebook friends alone should be reason enough to re-evaluate your own mobile phone use.

Capsaicin keeps fatty acid oxidation & total energy expenditure up, when you're dieting

No this is not Liza Oz after taking Mehmet's beloved RK supplements - and it is not one of the subjects from the "Kitchen Sink Approach to Fat Loss study"... although, who knows? (learn more about that study)

(Janssens. 2013) Right from the Department of Human Biology, School for Nutrition, Toxicology and Metabolism (NUTRIM) at the Maastricht University in The Netherlands comes a new study that confirms that capsaicin a long-touted "fat burner" and anti-obesity agent  that's also turning up your heat, when you consume hot peppers, will maintain your energy balance and fatty oxidation rates in the normal zone, when you are dieting.

The 15 healthy Caucasian subjects underwent four 36 h sessions in a respiration chamber, which allowed the scientists to accurately measure their energy expenditure, the ratio of glucose / fat oxidation and blood pressure after receiving a dose of 2.56mg (1.03g of red chili pepper worth 39,050 Scoville heat units (SHU)) with every meal.

Now, this wouldn’t be something we have not seen in previous studies, already. With the study at hand, however, the capsaicin intake, was not the only controlled variable. In addition to simply checking what happens, when you consume one serving of capsaicin with each meal, the scientists also assessed the influence of the baseline energy intake of the subjects, with them being randomly assigned to receive adequate amounts of energy (= 100% of the daily energy requirements), or a calorically reduced diet (=75% of the daily energy requirements) during the tests.
 
The first noteworthy observation the scientists made is the adaptiation induced amelioration of the energy deficit. Contrary to what the simply calories in vs. calories out equation would suggest, the participants who received 25% less energy than they would need ended up having an effective energy deficit of only 20.5% - in other words, the missing 4.5% were simply conserved by the dreaded metabolic downregulation that’s one of the most important reasons for weight loss plateaus.

Figure 2: Changes in energy expenditure at rest, during sleep in response to food intake and activity, as well as substrate oxidation in 15 healthy Caucasian subjects (seven women, eight men) during the supplemented (CAP) and non-supplemented (PLA) energy sufficient (100) and restricted (75) conditions (Janssens. 2013).

Now this is where the capsaicin comes into play, as the results of the study at hand clearly demonstrate, the additional provision of 2.56 mg of the hot spice with every meal can negate the reduction in diet-induced thermogenesis and restore the lowered sleeping metabolic rate the 25% caloric reduction has brought about.

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Suggested read for those looking to stacking different ingredients to propel their weight loss efforts: "Forgotten Dieting Aids: Choline, Carnitine, Caffeine and the Anti-Weight-Loss Plateau Effects of Sugar and Phosphates" (read more)

Bottom line: In view of the fact that the capsaicin supplement also increased the fat oxidation during both the calorically reduced and the normal dieting conditions, it may in fact be that we've hot a pretty "hot" fat burner here... unfortunately, just with any other "fat burner", you still got to give your body the chance to actually burn the fat. Without sweat and a slightly reduced energy intake (25% does by the way make a good rule of thumb) this is yet not going to work.

Moreover, it is also questionable, whether the effects will be that noticeable after 1-2 weeks of chronic usage. I'd bet money they will either disappear completely or be drastically reduced, but that would be the topic for another study ;-)

All that's left are... *drumrolls* the Facebook news and an awesome weekend!

You know what's coming now, right? Correct, first I will enumerate a couple of Facebook News you may or may not have seen on the SuppVersity Timline (ha! I did not write "wall", am I now going to be rewarded, Mark Zuckerberg?)

• SuppVersity Highly Suggested Read - Part II of Sean Casey's summary of the ISSN conference | read more...
• Science for Science Sake - In the current scientific environment many scientists turn to biased reporting, intrinsically flawed study design & the like to produce "break through" results that are at best irrelevant, in the worst case threaten the live of participants in follow up studies | learn more... 
• Moderate Drinking Probably Lacks Life-Extending Effects - Sociologists argue: The lifestyle and not the booze of moderate drinkers is what prolongs their lives | learn more...
• Barefoot Running is Good for Your Knees: Take your shoes off to reduce patellofemoral joint stress during running | read more ...
• Can Supplements Precipitate Headaches? At least in a recent study from China the researchers observed correlations between isoflavone-supps in men and B-complex, vitamin C and green algae supplements in women | read more...

And afterwards I am telling you to have a nice weekend and reminding you of the fact that Sunday is no "off day" here at the SuppVersity ... although, for many of you it appears to be, which is why I am actually thinking about dropping the Sunday posts completely. Whatever... enjoy your weekend!

References:

• Aboul Ezz HS, Khadrawy YA, Ahmed NA, Radwan NM, El Bakry MM. The effect of pulsed electromagnetic radiation from mobile phone on the levels of monoamine neurotransmitters in four different areas of rat brain. Eur Rev Med Pharmacol Sci. 2013 Jul;17(13):1782-8.
• Andreassen CS, Torsheim T, Brunborg GS, Pallesen S. Development of a Facebook
  Addiction Scale. Psychol Rep. 2012 Apr;110(2):501-17.
• Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, Herscovitch P, Millo CM, Remaley A, Lee P, Celi FS. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013 Jul;98(7):E1218-23. 
• Janssens PL, Hursel R, Martens EA, Westerterp-Plantenga MS. Acute effects of capsaicin on energy expenditure and fat oxidation in negative energy balance. PLoS One. 2013 Jul 2;8(7):e67786.
   

High Intensity Resistance Training to RESOLVE Weight & Health Problems. Hitting the Weights Hard + Walking Yields Better Results Than Endless Jogging & Light Weights

After 90min of cardio at 70% of your HRmax your body tells you that this is not beneficial - why don't you just listen to it?

You may remember a recent Facebook post of mine in which I wrote about a recent study that showed that sedentary primary care physicians are less likely to prescribe exercise as a treatment to their overweight patients than those who work out, themselves.

Well, according to a recent study from the Gordon and Leslie Diamond Health Care Centre in Vancouver, it appears as Canada would be in store for seriously more exercising overweight patients in the future... well, that's probably a little too optimistic, but in view of the fact that "fourth-year UBC [University of British Columbia] medical students engage in more strenuous PA [phycical activity] than average age-matched Canadians" (Holtz. 2013), there is still hope that the next generation of obese patients is not going to get their scripts that effortless any longer.

Exercise? Yeah, but what is the ideal exercise prescription?

What remains to be seen, though is whether or not this new generation of MD is willing and able to prescribe anything but the moribund standard protocols. Something like the high intensity resistance, moderate endurance exercise protocol (HRME) European scientists dared to test against the way more prevalent moderate intensity resistance, moderate endurance exercise (MRME), and moderate intensity resistance, high intensity endurance exercise (MRHR) protocols in their most recent ramdomized trial.

When I see this stupid protocol, I wish the scientists had read my article "How to Burn 27,300 Kcal Extra W/out Losing a Single Extra Pound of Fat!" (read it), before starting the study.

"The participants were coached daily individually, within the context of their assigned group. The same time (15–20 h/week) was spent by all groups in endurance (90 min daily) plus in resistance (90 min four days a week). Exercises differed only in intensity, from 30% to 70%. Participants' heart rate was monitored by Polar™ S810 with instantaneous recording and storage of heart rate values. Endurance training included aquagym, cycling and walking. Resistance training consisted of 8 exercises with free weights and traditional muscle building equipment. Each exercise [e.g. bench press, leg extension, biceps curl] was performed for three sets of 10 repetitions." (Dutheil. 2013; my emphasis)

The experiment was part of the so-called REverse metabolic SyndrOme by Lifestyle and Various Exercises (RESOLVE) trial, and consisted of a combined dietary + exercise intervention, in the course of which 100 participants, aged 50–70 years, underwent a diet restriction (protein intake 1.2 g/kg/day) with a high exercise volume (15–20 h/week).

When you start out with 3kg of pure fat around your wasteline, ....

Too much volume for the real world! Just in case you are one of the future doctors mentioned in the introduction you can take my word for it: your patients are not going to be 85% compliant to an insane workload like this. If you get your patients to complete 4 resistance training workouts with subsequent 15min of cardio training lasting for a total of 60 min each and have them take the stairs instead of the elevator that would be more than enough, anyway.

... how much can be lost on a -500kcal/day diet with a minimal protein intake of 1.2g/kg per day and an exercise program on a daily endurance (90min) and four times a week (90 min) resistance training regimen?

"Exercises differed only in intensity, from 30% to 70%. Participants' heart rate was monitored by Polar™ S810 with instantaneous recording and storage of heart rate values. Endurance training included aquagym, cycling and walking. Resistance training consisted of 8 exercises with free weights and traditional muscle building equipment. Each exercise was performed for three sets of 10 repetitions." (Dutheil. 2013)

While this was not the exact research question the scientists put into their paper, it is essentially what the study that has been funded by the Heart and Diseases Foundation was designed for. Whether or not it is realistic to assume that anyone would actually do 90 minutes of cardio everyday is yet questionable and since that was not controlled for during the 1-year at-home follow up, I hardly doubt any of the participants was stupid enough to do that.

Apropos, the dropout rates of the individual groups were 10/34 for the HRME, 8/32 for the MRHE and 4/34 for the MRME groups. In other words, the less intense the training program the more likely the subjects were to stick to it.

Figure 1: Changes in central fat, lean and fat mass; expressed relative to baseline (Dutheil. 2013)

If you look at the actual study outcomes in figure 1 it should yet be clear that it would make more sense to cut back on the training volume to increase the adherence to the protocol, than to cut back on the intensity. After all, the latter appears to be the main determinants of the success of the exercise intervention in both the high intensity resistance training (blue) and endurance training (yellow) groups...

Figure 2: Fat/lean mass ratio, changes in HbA1c (longterm blood glucose marker), and strength (maximum load of 10 repetitions from three prescribed exercises, i.e. bench press, leg extension, biceps curl) over the course of the study (Dutheil. 2013)

..however, after taking a look at figure 2 there is no debating that the high intensity endurance program is significantly inferior to its weight lifting training counterpart: greater strength gains, persistent improvement in HbA1c even at the end of the 12 months follow up and, most importantly, the largest fat-to-lean-mass ratio loss of all three protocols.

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Bottom line: You do really want to know the bottom line? Well, eat clean, hit the weights hit the weights hard combine that with yet by no means so much moderate cardio training as the subjects in the study and the nasty blubber and the associated health problems are problem of yesteryear... ah, and when I write "yesteryear" this implies it may well take a year or longer to reach your goals.

Don't be afraid to take a week off, it will reset the protein anabolic response to your training (learn more)

Persistence is key, but just as you've learned in Wednesday's SuppVersity article with the telling title "Do Chronic Energy Deficits Make Athletes Fat? The Longer & More Severe You Starve, the Fatter You Are. Irrespective of What the Calories-in-VS-Calories-Out Formula May Say, going all out day in and day out will, just like dieting hard, day in and day out, knock you out.

Make sure you get adequate rest and take a week off every 6 weeks, when you are switching from one iteration of your training program to another one.

And if you really have to make it happen fast, do it as the subjects did, make sure you get your 1.5g/kg protein (or better 30g+ with every meal) ramp up the volume, overreach for three weeks, look great at your high-school reunion, photo shoot, wedding or whatever the reason for the urgency was and resume your training at a low volume after a full week of binge-free rest.

References:

• Dutheil F, Lac G, Lesourd B, Chapier R, Walther G, Vinet A, Sapin V, Verney J, Ouchchane L, Duclos M, Obert P, Courteix D. Different modalities of exercise to reduce visceral fat mass and cardiovascular risk in metabolic syndrome: the RESOLVE* randomized trial. Int J Cardiol. 2013 May 25.

Eight Meals Instead of Three Keep Leptin & Insulin Stable and Shift the Nigh-Time Leptin Peak Towards the Early Morning - Impressive? Well, What is That Good For, Then?

All at once, in three or eight equal portions? That is the question... well, I guess these days no one would even dare saying that you should eat all the three "meals" in the middle column individually in order to make it to the 8 meals a day line, but in 2004, when this study was published things, were still a little different. For good reason?

It has become very quiet in the "eat as many meals as possible" camp in the last couple of years. In fact even the majority mainstream dietitians who have long been promoting 6 meals or more per day are now recommending three square meals and no more than "healthy" snacks in-between.

Against that background the recent study from the Leiden University Medical Center in the Netherlands appears to come right from the nutritional Middle Ages and that despite the fact that it was conducted "only" 9 years ago. I mean, the scientists did not compare three to two or one meal, deal with intermittent or alternate day fasting, but found it pretty natural to see beneficial effects in the hormonal profile of their five healthy obese female subjects (BMI 25–35 kg/m²; stable body weight), when they would feed them eight instead of three meals.

What the scientists were interested in were the insulin, leptin & cortisol responses

... of the ladies to the two dietary regimen. To this ends all subjects had to follow identical diets consisting of of a "normal quantity of macronutrients" (approximately 71 g of protein, 30% of calories as fat, and 55% of calories as carbohydrates) from common foods. The diet had an average coloric content of 2400-2500kcal per day and was consumed in either

• three equally sized servings - breakfast at 08:15, lunch at 13:30 and dinner at 18:30, or
• eight equally sized servings - eaten every 3 h (09:00, 12:00, ... 24:00, 03:00, 06:00) 

Since this is a cross-over study it is important to note that the diets of the first and of the second phase were completely equal in composition and content. What could be a potential problem, though, is the fact that the subjects did not stay at the lab, but ate their food at home. If you take a peak at the results, it does yet appear as if no one has been cheating badly. Otherwise, the pattern would have had unexpected troughs and spikes.

Figure 1: 24h profile of leptin (left) and insulin (right) during the 3x and 8x feeding condition (Fogteloo. 2004)

Apropos troughs and spikes, if you take a look at the results the differences look pretty profound. A cluster analysis did yet reveal that neither the insulin nor the leptin levels showed significant differences in terms the area under the curve, the mean 24h concentration, the burst frequency and interval, etc.

What did however differ significantly were the size of the amplitudes and the time at which the acrophase (maximally elevation) for the leptin levels occurred. With a 50% lower amplitude the leptin levels on the eight-meal condition were much more stable and the acrophase was shifted from ~1 o'clock AM to ~3:40 AM. In conjunction with the lower insulin levels in the waking hours could indicate a higher propensity to oxidize fat as the main fuel source, but as mentioned in a couple of previous articles, this does not necessarily have to be beneficial.

Fine, so we can postpone the leptin peak, but what's that good for?

While it is certainly interesting that we can influence the peak time and amplitude of the leptin levels by the way we eat, I highly doubt that there are physiological benefits associated with the decrease in irregularity, the 160min time-shift of the 24h peak and the overall lower leptin amplitude in the 8 feedings per day trial.

Figure 2: Aside from the missing cortisol "spike"at 10 PM the cortisol profiles during the two interventions look virtually and are statistically identical. So if there were any advantages to one of the feeding strategies it is probably not related to cortisol.

I know that one of the mechanisms by which the researchers in the "Carbs Past 6PM Studies" tried to explain the beneficial effects of their "eat your carbs before bed" approach were increased leptin levels during the day, this shift was much more pronounced in response to the macronutrient-timing approach vs. the food frequency approach in the study at hand (go back and look at figure 1).

Similarly, missing cortisol "mini spike" at 10pm (see figure 2) could be a disadvantage, when you think about the recently discovered relation between the presence of a natural up and down in cortisol and metabolic health (learn why). On the other hand it is a statistically non-significant difference in otherwise identical cortisol profile - a difference that appears to be way too small to actually make a difference.

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Bottom line: Talking about differences, in the end, it would seem that it does not really make a difference in terms of your cortisol, insulin and leptin levels whether you eat three or eight meals. If you are insulin resistant you may argue that you could benefit from the lower absence of insulin spikes with the eight meal strategy, but in view of the fact that it is a pain in the ass to carry food around all the time and considering the fact that these mini-meals won't be satisfying for the majority of individuals, the study at hand does not provide any reasonable argument to consume eight instead of just three meals a day.

References: 

• Fogteloo AJ, Pijl H, Roelfsema F, Frölich M, Meinders AE. Impact of meal timing and frequency on the twenty-four-hour leptin rhythm. Horm Res. 2004;62(2):71-8.

Do Chronic Energy Deficits Make Athletes Fat? The Longer & More Severe You Starve, the Fatter You Are. Irrespective of What the Calories-in-VS-Calories-Out Formula May Say

This is not an "anti-gymanstics" or "anti-runners" article, this is an anti-ruin-your-life-post for the average female and male gymrat.

Maybe you've read about the results Deutz, Bernardot, Martin and Cody published in their 1999 paper on the "Relationship between energy deficits and body composition in elite female gymnasts and runners"... in fact, it may be possible that I already mentioned it in the "Athletes Triad Series" (read more), but even if I did, the fact that I get messages like "I eat 1,100kcal/day and still gain, not lose fat" or "my girlfriend eats 900kcal/day and maintains that this is normal", tells me it does not matter if I mention one or two of the figures the authors compiled in this unfortunately highly "under-cited" paper (only 72 citations are referencing this article) twice.

If that makes just one of the victims of their own ambition rethink what he or she is doing, it was well worth... wouldn't you agree?

Can the elite be wrong?

Usually you would assume that elite athletes are doing everything right, they are the epitome of our modern understanding of "health". As a SuppVersity reader you are yet well aware that there is a disconnect between optimal health and performance and with the latter being in part dependent on having a certain look as it is the case for bodybuilding, figure competitions and the like this disconnect can be so huge that being successful may eventually require a non-genetically gifted athlete to sacrifice his or her health on the altar of a misinterpretation of "physical culture".

That being said there is a way more traditional and, contrary to bodybuilding, officially Olympic sport where similar rules apply: Gymnastics! Especially among the female competitors the paradigm still is - the thinner the better. And to make things even worse, in this case "thin" actually means "thin" as in "being able to hide behind a straw". Now, this is obviously not the case in any of the aforementioned disciplines and yet they claim way more victims of life-long dieting than those sports, where "being thin" is actually part of the game - and what's almost sarcastic, the tortures some professional and many hobby athletes subject themselves to are not even rewarded.

You will have to take the following figures with two grains of skepticism! One for the scientifically established bias due to under-reporting in female gymnasts (Jonnalagadda. 2000), and the other one for the discrepancy between factual and calculated energy expenditures, which is, due to the negative feedback chronic dieting exerts on the total energy expenditure, much narrower than the formulas suggest. And another thing, remember that we are talking about body-fat % not total body fat masses here!

Against that background you will probably not be surprised to hear that the vast majority of the elate female artistic (N=32) and rhythmic (N=11) gymnasts in the study at hand is consuming 1,002kcal less than they would actually need to satisfy their caloric demands.

Figure 1: Comparison of within-day energy balance in the four groups of elite athletes (left); largest energy deficit per hour and average 24h energy deficit in all athletes, gymnasts and runners (Deutz. 2000).

If you take a closer look at the data in figure 1 you will yet realize that the average medium- and long-distance runner is not much better off. Now, whether the latter is a necessary prerequisite to make it to the top or simply a result of being unable (for physical or psychological reasons) to compensate for the training induced increase in energy expenditure, is beyond the scope of this post and essentially irrelevant to the statistically highly relevant acorrelation between between energy balance and body fatness, I've plotted for you in figure 2.

Figure 2: Relationships (Pearson correlations) between energy balance factors and body fat percentage in all athletes, gymnasts, and runners (Deutz. 2000)

I hope that these results do not come as a surprise for the vast majority of those for whom this is not the first visit to the SuppVersity. After all, I have been trying my very best for years (hard to believe I am doing this "chronically" ;-) to scare you away from the chronic and towards the cyclic calorie reduction as a means to cut body fat and maintain muscle mass (note: with the relatively small study size not all effects reached statistical significance; for the parameters pertaining to the "energy out vs. energy in"-calculations the average dieter is so fond of, this was yet particularly noteworthy).

In athletes chronic "dieting" results in an increase in body fat percentage

The message is simple and so is the underlying mechanism. The chronic provision of an insufficient amount of energy leads to a metabolic downregulation that goes hand in hand with an increased disposition to store and a decreased disposition to let go of body fat.

Another note: This is not an anti-intermittent fasting article either. If you do IF to cut weight you will have an overall negative energy balance, just like on every other diet, but if you are doing it for life (for whatever reason), you should be meeting your daily energy demands. This means you would have a much higher energy surplus on the other hours - in essence the data simply don't apply to someone who is doing intermittent fasting on a maintenance diet.

The concomitant exercise induced physical stress lulls your body to believe that you are amidst a starvation period, where building muscle and/or maintaining more muscle than is absolutely necessary to sustain the regular exercise routines is a no go and each and every energy unit that that is not necessary to keep you from passing out will get stored to cover those hours with a per hour deficit of 750kcal (which is the average maximal deficit per hour in the rhythmic gymnast group).

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Bottom line: Don't get fooled by the "Don't worry. That's not you, starve yourself! It's good for you - don't you feel it?" the little gal or guy in your shoulder is now whispering into your ear. The rule "chronic starvation = increase in body fat percentage" applies to male and female athletes, gymnasts, runners, sprinters, cyclists, fitness junkies, bodybuilders, footballers, ... and across a wide range of energy deficits.

You don't have to eat burgers and French fries all day, to meet your energy requirements. Living on chicken breast & broccoli for the rest of your life is neither necessary nor conducive to your goals, and that's even true for such profane goals as "staying lean"! And by the way - how much do you need (learn more)?

So say good buy to the little guy with the hunger high and use your brains and acknowledge to yourself: "I am a junky. A starvation junky!"  You are not? Well then check this out:

Addiction is a persistent, compulsive dependence on a behavior or substance. [...] Addiction has been extended [...] to include mood-altering behaviors or activities." (Livingston. 2008; my emphases)

And the main criteria for being addicted are a loss of willpower, fear of harmful consequences, an unmanageable lifestyle, tolerance or escalation of use and withdrawal symptoms upon quitting. Well if all that is not you and you. Stop working out like mad and return to eating normal without going crazy whenever you feel satiated, now!

References:

• Deutz RC, Benardot D, Martin DE, Cody MM. Relationship between energy deficits and body composition in elite female gymnasts and runners. Med Sci Sports Exerc. 2000 Mar;32(3):659-68. 
• Jonnalagadda SS, Benardot D, Dill MN. Assessment of under-reporting of energy intake by elite female gymnast. Int J Sport Nutr Exerc Metab. 2000 Sep;10(3):315-25.
• Livingstone, C. "addiction." Dictionary of Sport and Exercise Science and Medicine. 2008. Elsevier Limited 14 Jul. 2013 http://medical-dictionary.thefreedictionary.com/addiction

You Eat What You Feed: How Much Omega-3s Can You Possibly Pack into a Single Steak? The Impressive Effects of a "Grass(+)" Diet on Raw Meat & Meat Products

Learn more about the fatty acid and nutrient composition of grass-fed vs. regular beef this SuppVersity article is for you... and make the first step to reduce your CVD risk by 20% irrespective of whether or not you're going to eat grass-fed in the future!

I remember that I wrote a previous post about the detrimental effects of growing salmon on a high omega-6 diet. The result is a fish with an omega-3 to omega-6 ratio that is totally different from that of the wild-caught salmon everyone is raving about. Bad news, I know and to be honest, I am fed up with bad news.

Luckily you can rely on the scientists over at the Leibniz Institute for Farm Animal Biology in Germany: Dirk Dannenberger and his colleagues have just published a paper that sheds some light on the beneficial side of this ostensibly nasty link between the fatty acid make-up of the feed and the fatty acid composition of the meat of the animals we eat.

N6 in N3 out, N3 in N6 out - you see, it works both ways!

In their quest to find a way to change the fatty acid composition of beef products (German Corned beef (GCB), tea sausage spread (TSS), scalded sausage (SS)) the scientists simply replaced the regular maize silage + concentrate  and soybean meal based diet with a diet containing grass silage + concentrate with added rapeseed cake (12%) and linseed oil (3%) and *surprise* the amounts of short chain and long chain omega-3 fatty acids increases by 160%, 130% (EPA) and 70% (total long-chain PUFA = EPA, DHA, DPA).

Figure 1: Detailed comparison of the fatty acid content (mg/100  g) in Longissimus muscle of German Holstein bulls fed the regular corn + soy based (control) vs. grass + linseed based (experiment) diets  a different diet (Dannenberger. 2013)

Now that's cool, but in view of the fact that the major part of beef products is not bought as a raw steak of in form of ground beef, etc. what really counts is the net omega-3 gain in the previously mentioned beef products and that did not work as well as the enthusiastic

"n-3  PUFA  from  beef were  found  to  be  product-specifically  transferred  into  the  corresponding  beef  products"(Dannenberger. 2013)

 would suggest. After all, the increase in short chain and total long-chain omega-3s in the corned beef was only 40% and 50% and thus 75% and 29% lower than the increase in the "raw material".

So where did the good omega-3s go?

Well, I guess some of you will already have got it. German Corned Beef if freakin' lean. With only 2% fat the reason for the absence of omega-3s is thus simply that the fatty cuts don't even make it into the end product.

Figure 2: While the "grass-fed + enhanced" meat has identical amounts of iron, copper, zinc and selenium (not shown) it lacks the additional "vitamin E"-s that are in the corn-based chow; furthermore both forms are devoid of the fat burning isomer of CLA, this does yet also imply they don't entail the corresponding diabetes risk (Dannenberger. 2013)

So, despite the success of the study at hand, we would initially have to take up eating the whole animal, or rather all the cuts instead of throwing away the fatty ones just to be take the lean parts, fry them in plant oils and drown them in soy- or sunflower-oil based sauces to "water" the dry meat and spice up the blatant taste (with the decrease in total fat content in grass-fed cattle this effect will be even more pronounced, by the way).

Once we have made that important step from thinking that all animal fat must be bad, a simple change in the ingredient profile of our animals' feed could make a big difference to our health... what? No, you can already buy meat like that... you must be kiddin' me, right?  ;-)

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This is not what you want: Farmed Atlantic salmon - raised with & fried in soy *yummy* (learn why)

Bottom line: I hope today's SuppVersity article did not just provide you with more information about the fatty acid profile of "grass fed, omega-3 pimped meat", but also made you smile. And if it did that I did already contribute to a 22% reduction your personal heart disease risk before you even ate one of the omega-3 steaks from the German cows.

How? Well, that's the CVD risk reducing effect of positive affect that was established in a large prospective study with 10 years of follow-up by Karina Davidson from the Department of Medicine, Center for Behavioral Cardiovascular Health at the Columbia University Medical Center in 2010 - I know I am so caring, but you don't have to thank me for that. I mean who would ready my stuff if it was not for you?

References:

• Dannenberger D, Nuernberg K, Herdmann A, Nuernberg G, Hagemann E, Kienast W. Dietary PUFA Intervention Affects Fatty Acid- and Micronutrient Profiles of Beef and Related Beef Products. Foods. 2013; 2(3):295-309.
• Davidson KW, Mostofsky E, Whang W. Don't worry, be happy: positive affect and reduced 10-year incident coronary heart disease: the Canadian Nova Scotia Health Survey. Eur Heart J. 2010 May;31(9):1065-70.

Bofu-Tsusho-San: Ephedrine Based Kampo Kitchen Sink Fat Burner Cuts 10kg Body Weight, Boosts Metabolism by +15% & Reduces Insulin of Diet-Resistant Woman by 50%

Is there a Japanese  weight loss wonder supplement not even Dr. Oz knows about? And could it be more effective than Oz's raspberry ketones?

Sometimes the most inconspicuous articles turn out to be the most interesting ones. I mean, who would have guessed that a case report titled "Japanese herbal medicine for weight loss in a morbidly obese patient: A case report" would make it into the SuppVersity news? Being as heavy as tall, in this case 154.8 kg distributed not very proportional on a 157 cm frame with an 155cm waist, is - as unfortunate as that may seem - not exactly uncommon these days - even for a 22-year old woman. The words "japanese herbal medicine" and the line "her resting metabolic rate (RMR) increased from 2260 to 2440 kcal/day" (Haruta. 2013) the abstract mentions right after discussing her 10kg weight loss peaked my interest.

How bad off was the subject?

The subject had obviously been yoyo-dieting for years, when she was as hospitalized in the researchers' department for the purpose of weight loss.

"Her heart rate was approximately 100 beats per minute and her blood pressure was 156/108 mm Hg. Upon initial admission, we performed blood work, abdominal ultrasonography (US), and a head computed tomography (CT) to exclude secondary adiposis."

A biochemical examination of her blood yielded

To eat or to diet, what's worse? Some people argue that "dieting just makes you fat" and we all know about the yoyo effect, but is that (a) true and (b) what effects does it have on your over and metabolic health? (learn more)

• marginally elevated ALT levels;
• marginally elevated uric acid, but 
• normal creatinine and BUN levels;
• low HDL levels (bottom of the range), and 
• high-normal LDL levels;
• elevated HbA1c and fasting blood glucose levels,
• highly elevated insulin levels (2.7x), and
• highly elevated (5.5x) CRP levels
• normal cortisol, normal growth hormone, but 
• slightly elevated ACTH levels
• slightly elevated testosterone levels, but 
• otherwise normal endocrine function

Although the  elevation of ALT was marginal and the other parameters of liver health appeared in range, a fatty liver and a left ovarian tumor were detected by abdominal ultrasound.Unfortunately both not exactly uncommon in subjects with full blown metabolic syndrome, which is - according to International Diabetes Federation criteria - defined as having...

• hypertension, blood pressure>130/85 mm Hg, 
• abdominal circumference > 80 cm

• HDL-C < 50 mg/dL, and 
• plasma glucose>100 mg/dL

The doctors at the Department of Psychosomatic Internal Medicine of the Kagoshima University Graduate School of Medical and Dental Sciences in Kagoshima, Japan, prescribed a reasonable exercise program and a calorically restricted diet containing 2,000kcal and thus ca. 12% less than the subjects resting metabolic rate (measured by respiratory exchange ratio; 2260 kcal/day). That did help her to lose ~5kg during her stay at the hospital, but at 150kg the weight loss stalled until....

Things changed, when the scientist prescribed bofu-tsusho-san

Bofu-tsusho-san  has been used in Kampo, the Japanese study and adaptation of Traditional Chinese medicine (TCM), for decades and though I have to admit I had not heard about it before, there is actually existing evidence for its efficiacy as a weight loss adjuvant:

Figure 1: Bofu-tsusho-san (BTO) does what you expect from a potent weight loss helper. It keeps your metabolic rate up - and even better BTO even increases it on a per lbs of body mass basis (Hioki. 2004)

• higher body fat loss, greater weight loss, no reduction in BMR + improved insulin response and lower homa-IR in 40 Japanese women (body mass index (BMI) 36.5 +/- 4.8 kg/m2) with IGT and insulin resistance (IR), who had been treated with a low-calorie diet (5016 kj/day: 1200 kcal) and an exercise regimen (1254 kj/day: 300 kcal) compared to 40 women in the placebo group (Hioki. 2004).

• blunts the weight gain patients on anti-psychotics (Zyprexa = olanzapine) often experience (Yamamoto. 2009).
   
• works by three distinct pathways, i.e. via the inhibition of triglyceride synthesis in the liver, and the enhancement of lipolysis in adipocytes and of thermogenesis in brown adipose tissue. At least that's what early studies in rodents suggest (Morimoto. 2001). 

The preparation has an overall favorable safety profile, with a tolerable intake of 2g/kg in rodents and thus ~325mg/kg in humans. Nevertheless, Bofu-tsusho-san is not totally devoid of side effect, there are two case reports of pneumonitis that occured after ~1 months of treatment with the drug and went away when the herbal was discontinued (Masushima. 2002; Suzuki. 2004).

For the subject in the study at hand, it may yet eventually turn out to be a life saver. After all the fat that had been coming back for more after each and every diet kept melting away, even after her stay at the hospital and when she reported back for the last examination before the paper was written, she had lost 10kg. That left her still morbidly obese, but with the initially mentioned +8% in resting metabolic rate (+15% if you express that relative to her body weight), improved fasting glucose levels (-31%) an HbA1c of 5.5.% (-17%) and immuno reactive insulin levels of 27.9 mU/mL (-45%!) she may not have been on her way to the cover of Shape, but (and this may be even a contrast) to a non-life-threatening body weight.

Let's look at the formula: Some old acquaintances in here

Did you know... that ephedrine HCL is not just a beta agonist, but also a potent anti-inflammatory? According to the results a group of scientists presents in the latest issue of Cellular & Molecular Biology, ephedrine HCL is "a new potential anti-inflammatory drug that can be useful for treating severe invasive Gram-positive bacterial infection"!? This conclusion is based on the observation that EHCL increases the levels of the anti-inflammatory interleukin-10 (IL-10) and decreases the release of proinflammatory cytokines (IL-6, TNF-alpha, IL-12 and IL-1beta) in immune cells that are stimulated with a component of the cell walls of gram-positive bacteria (Zheng. 2013)

Bofu-tsusho-san has also been shown (in vitro; Katoh. 2009) to inhibit beta-estradiol 3-glucuronidation, which is yet probably only a problem if you ingest it in very high amounts, an undertaking that could pose other problems even before you realize that its blocking your estrogen metabolism due to the sympathetic overactivation caused by ingredient #1 on the list below:

• Ephedrae herba (EH; contains ephedrine),
• Glycyrrhizae radix (GR; contains licoricidin), 
• Forsythiae fructus (FF; contains D-pinoresinol), and
• Schizonepetae spica (SS; inhibits phosphodiesterase enzymatic activities).

Looks pretty much as if it came right from the labs of an innovative supplement company, who've been following the SuppVersity news and articles pretty closely, right? Ok, everybody knowas about the beta-agonist qualities of ephedrine that may not have been important, but the fat-loss prowess of licorice (cf. "All about cortisol"), as well as the potential application of phosphodiesterase inhibitors to alleviate insulin resistance and promote fat loss (cf. Jansson. 2010; Murdolo. 2012) Carl and I mentioned on one of the past episodes of the Science Round Up would be something they may have picked up, here...

"Enough of the bragging, Adel!"

Ok, ok. I have to admit that it would have required some research on their part to come up with the additional Forsythiae fructus extract and the

• antihyperglycemic (Wikul. 2012), 
• antihypertensive (Greeneway. 2011),
• antifungal (Hwang. 2010) and 
• antioxidant effects - particularly in the gut (Jung. 2010; During. 2012) 

of its D-pinoresinol glycosoids, to come up with this ingenious invention, if it had not already been invented by an unknown Japanese Kampo practitioner decades ago, I should say ;-)

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The Kitchen Sink Approach to fat loss is surprisingly effective(learn more)

Bottom line: While I believe nobody will be arguing that the ephedra part of the formula is probably the most effective ingredient, it's interesting to see that traditional medicine has already come up with "drugs", or rather herbals, that make use of synergies such as the weight loss benefits of PDE inhibtors, the Western allopathic medicine starts to understand, only now.

That these synergies can do the trick in commercially available supplements, as well, is something we have seen about a week ago, with the "Kitchen Sink Fat Burner" (learn more).

And still, not knowing which of the ingredients are actually responsible for the observed benefits is an unquestionable downside. A downside due to which I can't tell you if the classic E+C stack would be as, less or even more effective than the "kambo version of ECA". What I can tell you, though, is that the addition of Schizonepetae spica to the legendary "fat loss classic" makes sense. The same would go for Glycyrrhizae radix and Forsythiae fructus, which appear to make particularly good match as the latter will counter potentially blood pressure elevations due to the former.

References:

• During A, Debouche C, Raas T, Larondelle Y. Among plant lignans, pinoresinol has the strongest antiinflammatory properties in human intestinal Caco-2 cells. J Nutr. 2012 Oct;142(10):1798-805.
• Greenway F, Liu Z, Yu Y, Gupta A. A clinical trial testing the safety and efficacy of a standardized Eucommia ulmoides Oliver bark extract to treat hypertension. Altern Med Rev. 2011 Dec;16(4):338-47. 
• Hioki C, Yoshimoto K, Yoshida T. Efficacy of bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance. Clin Exp Pharmacol Physiol. 2004 Sep;31(9):614-9.  
• Hwang B, Lee J, Liu QH, Woo ER, Lee DG. Antifungal effect of (+)-pinoresinol isolated from Sambucus williamsii. Molecules. 2010 May 14;15(5):3507-16.
• Jansson PA, Murdolo G, Sjögren L, Nyström B, Sjöstrand M, Strindberg L, Lönnroth P. Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes. Diabetologia. 2010 Oct;53(10):2205-8. doi: 10.1007/s00125-010-1819-4. Epub 2010 Jun 10. 
• Jung HW, Mahesh R, Lee JG, Lee SH, Kim YS, Park YK. Pinoresinol from the fruits of Forsythia koreana inhibits inflammatory responses in LPS-activated microglia. Neurosci Lett. 2010 Aug 23;480(3):215-20.
• Katoh M, Yoshioka Y, Nakagawa N, Yokoi T. Effects of Japanese herbal medicine,
  Kampo, on human UGT1A1 activity. Drug Metab Pharmacokinet. 2009;24(3):226-34.
• Lee MY, Shin IS, Seo CS, Kim JH, Han SR, Shin HK. Subchronic oral toxicity
  studies of the traditional herbal formula Bangpungtongseong-san in Crl: CD (SD)
  rats. J Ethnopharmacol. 2012 Dec 18;144(3):720-5.
• Matsushima H, Takayanagi N, Ubukata M, Tokunaga D, Mori S, Sato N, Kurashima K, Yanagisawa T, Sugita Y, Kawabata Y, Kanazawa M. [A case of pneumonitis induced by Bofu-tsusho-san]. Nihon Kokyuki Gakkai Zasshi. 2002 Dec;40(12):955-9.
• Morimoto Y, Sakata M, Ohno A, Maegawa T, Tajima S. [Effects of bofu-tsusho-san, a traditional Chinese medicine, on body fat accumulation in fructose-loaded rats]. Nihon Yakurigaku Zasshi. 2001 Jan;117(1):77-86.
• 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. 2013 Jan;98(1):245-54. 
• Suzuki S, Tanaka A, Arai T, Adachi M. [Case of interstitial pneumonitis induced by a Chinese herbal medicine, bofu-tsusho-san]. Nihon Kokyuki Gakkai Zasshi. 2004 Aug;42(8):777-81. Japanese.
• Yamamoto N, Inada T. Bofu-tsusho-san effectively attenuates the weight gain
  observed after receiving olanzapine. Psychiatry Clin Neurosci. 2008
  Dec;62(6):747.
• Wikul A, Damsud T, Kataoka K, Phuwapraisirisan P. (+)-Pinoresinol is a putative hypoglycemic agent in defatted sesame (Sesamum indicum) seeds though inhibiting α-glucosidase. Bioorg Med Chem Lett. 2012 Aug 15;22(16):5215-7.
• Zheng Y, Yang Y, Li Y, Xu L, Wang Y, Guo Z, Song H, Yang M, Luo B, Zheng A, Li P, Zhang Y, Ji G, Yu Y. Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via the PI3K/Akt/GSK3β pathway. Cell Mol Immunol. 2013 Apr 22.

Sucralose is for Diabetics Not, Scientists say. But How Significant is the Cholesterol Increase They Observed?

This way of consuming Splenda is quite certainly going to increase your cholesterol levels ;-)

I guess, all of you will still remember the show Carl and I did on the "Pro-Insulinogenic Effects of Artificial Sweeteners" (read more), right? The one where I tried to point out that even if there was a meager change in the insulin response, this would only be a problem if there was any truth to  narrow-minded condemnation of insulin as the deadly obesity hormone, so that, in the end, the whole hoopla turned out to be way less daunting than some scare-mongers would have it.

Yet while something deep inside of me is telling me that the latter is probably going to be the same with the recently published study that's at the focus of today's SuppVersity article, cannot refute that the data from that very rodent study that was published in the Journal of Nutrition Sciences does clearly suggest that...

...sucralose increases cholesterols!

That certainly doesn't sound so scary to you, as it does to someone who still adheres to the "cholesterol is the root cause of all evil" paradigm, yet still. The fact that the administration of  11 mg/kg body weight of SPLENDA® over the course of 6 weeks to "intensifie[d the already existing] hypercholesterolemia in STZ-induced diabetic rats" (Saada. 2013) does sound as if there must be something to the rumors about sucralose being one of the main ingredients of devil's excrements.

Would having your coffee with Splenda instead of sugar make this cookie even more hazardous to your glucose levels and what about your waistline? Read more about the effects of artificial sweeteners on glucose-management, insulin and obesity in a previous article.

Now 130-150mg of sucralose per day is unquestionably a whoppy dose of artificial sweeteners. After all, this stuff is approximately 600x sweeter than sugar. Sounds like a total overkill, but if you do the math, i.e. 150mg x 600 = 90,000 mg, you will realize that this is not more than the non-caloric sweetness equivalent of ~1.5 Snickers bars. And if the figures a Scivation rep mentions in a post on the most popular bodybuilding website on the planet are correct this would be exactly 10 servings of their highly popular BCAA formula. Considering the fact that for most people Xtend is probably not the only dietary source of sucralose in the diet it is thus not a totally unrealistic dose (especially for those diabetic or non-diabetic sugar addicts, who are using splenda as a means to sweeten their tea, coffee and whetever else, as well).

Good you've made it past the introduction

That being said the message that sucralose "intensifie[d the already existing] hypercholesterolemia in STZ-induced diabetic rats" (Saada. 2013) appears to be even more scary.

Fortunately (or unfortunately for the "sweeteners are devil's excrements"-faction out there), this is not your average "Pubmed-Warrior blog", where the authors read a headline copy and paste the conclusion of the abstract and try to sell it as "science news" and I do not leave you hanging with the inappropriately overgeneralizing conclusion of the author's that

"[...] diabetic people consuming high amount of sucralose must check their lipid profile to avoid diabetic complications" (Saada. 2013)

Now, it is obviously right that diabetics should "check their lipid profile" on a regular basis, but if you look at the actual study outcomes, it is hard to argue that this would be particularly important for those of them who use SPLENDA® on a regular basis.

Figure 1: Changes in blood glucose, insulin, triglyceride and total (TC), HDL, and LDL cholesterol, as well as the TC/HDL levels after 6 weeks on 150mg/day sucralose (Saada. 2013)

After all, the "dangerous" increase in cholesterol the scientists observed in their lab animals (remember: we are not even 100% sure the same is going to happen in human beings) is not just accompanied by highly desirable desirable reduction in glucose (-22%) and triglycerides (-22%), it also leaves the CVD-relevant ratio of total to HDL cholesterol literally unchanged (+2%, n.s.).

Moreover, if you look at the way statins help managing cholesterol, but increase diabetes risk, you could even speculate that there is a yin and yang connecting the two metabolic pathways, where a lower strain on the one side will precipitate a higher strain on the other. Within this paradigm, the increase in cholesterol, which is by the way something many people who are "going paleo" will see, as well, could be a totally normal part of a "balancing" process that has nothing to do with the pathological overprodcution (always remember this is not about eating too much cholesterol) of highly oxidizable small and very small density lipoproteins people fear like the plague.

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In addition to reductions in blood glucose and triglyceride compared to cornflakes & co, the regular consumption of whole eggs increases HDL's ability to carry lipids out of the macrophages. If these accumulate, they will turn the macrophage into pro-atherogenic foam cells (learn more).

Bottom line: At least in my humble opinion, the results of this study don't imply that diabetics should stay away from sucralose. In the end, the benefits of lower glucose & triglyceride levels will outweigh the "downsides". This is all the more true, in view of the fact that we (a) the total-cholesterol-to-HDL-ratio remained essentially the same and (b) don't have data on the changes in lipoprotein particle profile. After all, improved glycemia and reduced triglyceride levels often go hand in hand with heat-healthy changes in the particle size distribution that is still totally ignored by way too many researchers.

That being said, the reduction in 10% reduction in TBARs, a marker of oxidative damage, clearly indicates that the rats with "increased" cholesterol levels were less inflamed than their sugar guzzling peers.

Needless to say that the same applies for the healthy rodents, where the changes in blood glucose, triglycerides and total, HDL and LDL cholesterol were much less pronounced, but the tendencies identical.

References:

• Saada H, Mekky N, Eldawy H, Abdelaal A. Biological Effect of Sucralose in Diabetic Rats. Food and Nutrition Sciences. 2013; 4(7a):82-89.

Taurine Pumps Up Strength & Recovery in Response to Eccentric Curls. NAC Decreases Peformance & Boosts Fat Oxidation!? Exercise Reduces, Caloric Restriction Increases Inflammation. Carnitine Rescues Fast Twitch Muscle

Blood glucose alone would not last for 90s of running up the stairs.

80 minutes! That's the SuppVersity Figure of the Week and the impressive timespan you could (theoretically) fuel your energy demands during exercise at 70% of your VO2max from your muscle glycogen stores.

The latter hold the energetic equivalent of ~1,500kcal and are thus an almost 40x larger reservoir of energy than the tiny amounts of glucose that's floating around in your bloodstream (data based on Gleeson. 2008).

If you had to rely on that alone, you would pass out after 2 mins of the previously mentioned exercise at 70% VO2max.

Obviously no workout is going to be fueled 100% exclusively by glucose/glycogen, so that you can still use the amount of energy your body stores in the fat cells (~93,000kcal) and in form of tissue proteins (~49,000kcal) and keep running for another 7,400 minutes or 5.13 days... theoretically

Enough of the figures let's get to some recent research results

• 

  You want the boost without the buzz? Hit the right taurine / caffeine ratio to avoid the stim crash & sleeplessness (learn how)

  Taurine for increased strength and recovery during and after eccentric biceps curls (Acordi da Silva. 2013) In a recent study researchers were able to show that the provision of taurine for 14 days before a standardized eccentric exercise regimen comprising 3 sets of eccentric biceps curls on the Scott bench that were performed at  80% of the 1-RM to total failure resulted in significant increases in strength levels and thiol total content of the muscle, as well as a decrease in muscle soreness, lactate dehydrogenase level, creatine kinase activity and oxidative damage (xylenol and protein carbonyl) after the workouts.
  
  Since the activity of the antioxidant enzymes (superoxide dismutase, catalase, and gluthatione peroxidase) and inflammatory markers (tumor necrosis factor, interleukin (IL) -1 beta, and IL10) in the blood of the twenty-one participants (mean age of 21 ± 6 years, weight of 78.2 ± 5 kg) were not altered, decreases in muscle growth as they have been reported for NAC, only recently are not likely to occur. 

• 

  CLA in pomegranate? Not really, but the CLnA in the seeds of the fruit may be even more potent (learn more)

  NAC increases fat oxidation, but compromises performance during HIIT cycling (Trewin. 2013) Talking about NAC another recent study conducted by Adam J. Trewin, Aaron C. Petersen, Francois Billaut, Leon R. McQuade, Bernie V. McInerney, Nigel K. Stepto found that the provision of N-acetylcysteine (NAC) before a HIIT cycling exercise (6x5min HIIE bouts at 82 % PPO (316 ± 40 W) ) separated by 1min at 100W, then after 2min recovery at 100W) elevated the fat oxidation yet only during the last two bouts by 150%. It also reduced the makers of lipid oxidation (these are cell lipids not stored fat) and lactate levels after the time trial. However, the mean EMG activity was -7% and the mean power output 4.9% lower during the NAC trial.
  
  Now, whether that's a good or bad thing actually depends on your goals. If you are glucose tolerant and train to burn fat, it's a good thing. If you want to empty your glycogen stores to promote GLUT-4 or are a competing athlete whose main interest is maximal performance, though the changes would be detrimental.

• Exercise training vs. dieting - anti- vs. pro-inflammation (Auerbach. 2013) In a soon-to-be-published paper in the American journal of physiology. Regulatory, integrative and comparative physiology scientists from the University of Copenhagen report that contrary to their own expectations, the adherence to an endurance exercise program that would burn ~600kcal /day (LISS training of 65% of the heart rate reserve) that was interspersed by 3-4 days of high intensity workouts at 85% of the heart rate reserve ...
  

  "[...] increased the number of anti-inflammatory CD163⁺ macrophages (from 12.7 [2.1] (mean [SE]) to 16.1 [3.1] CD163⁺ cells/100 adipocytes, P=0.013), whereas diet-induced weight loss tended to decrease CD68⁺ macrophages in subcutaneous abdominal adipose tissue" (Auerbach. 2013)

  In that it is interesting to note that the most beneficial changes were observed in the group that compensated for the 600kcal extra energy expenditure per week.

  

  Figure 1: Effects of the 12 week diet + exercise / diet only / exercise only interventions on the body composition of caucasian overweight men aged 20-40 yrs w/ body fat >25% (Auerbach. 2013)

  Compared to the exercise + baseline diet and diet only (-600kcal energy reduction) group, they had a highly significant decrease in the TNF-alpha in the femoral adipose tissue ended and the greatest increase in anti-inflammatory CD163⁺ macrophage. 

• Carnitine rescues fast-twitch glycolytic macrofibers in a rodent study (Couturier. 2013) According to a recently published paper in Nutrition & Metabolism, the provision of carnitine as part of the diet did prevent the type-II-diabetes-induced transition of glycolytic to oxidative muscle fibers in obese Zucker rats.
  
  Now while you can never be sure if things that happen in a rodent model will also happen in man, it is not totally unlikely that these effects could be observed in human beings as well.
  

  

  Carnitine to prevent sugary fat gain

  "The results demonstrate that carnitine supplementation to obese Zucker a rat counteracts the obesity-induced muscle fiber transition and restores the muscle oxidative metabolic phenotype. Carnitine supplementation is supposed to be beneficial for the treatment of elevated levels of plasma lipids during obesity or diabetes. " (Couturier. 2013)

  The corresponding human equivalent dose to the 3g/kg of carnitine in the rodent chow would be would be roughly 16mg/kg or something between 1-2g per day for an adult human being (learn how to calculate HEDs). This is actually not really much and may well be worth a try, assuming that your own or your relatives' glucose burning, weight lifting musculature is endangered by diabetes.  

That's it for the short news!

In case you still have enough glycogen left in any of your major "tanks", or, alternatively, are depleted enough to have your body produce tons of ketones to fuel your brain for another 3-5 minutes you may yet want to take a brief look at the latest SuppVersity Facebook News...

• 

  With the relation of fish oil to prostate cancer (see facebook news) being based on high serum levels, I suggest you (re-)read this post about why fish oil supplements may fail to increase tissue levels, of way which previous studies have shown that they may protect against prostate cancer (read more).

  High or low fat for blood lipids? - Recent meta-analysis says: "The jury is still out there." The same appears to be the case for the type of fat, by the way | read more...
• Fish oil is bad for your prostate! - That's at least what the latest spin-off of the SELECT study (the one with selenium and vitamin E, you know?) says | read more...
• Green tea, butter and bread - Neither the most nutritious, nor the most yummy breakfast one can thing of, but way better for your triglyceride levels than water, butter and bread | learn why....
• Fat gains with saturated fats? Not if you pick the right ones - Study identifies interestification of saturated fat as a main determinant of its obesogenic effect. Regular palm oil, for example leads to lower fat gains than soy oil | read more...

... before you either eat, train sleep or have fun on the best day of the weekend: Saturday! ... What's so special about Saturday? Well easy, you can sleep late, shop, work out, party and whatever you like and sleep all the exertions and occasional "spiritual diversions" off on Sunday ;-)


References:

• Acordi da Silva et al. Effects of taurine supplementation following eccentric exercise in young adults. Applied Physiology, Nutrition, and Metabolism. 2013
• Auerbach P, Nordby P, Bendtsen LQ, Mehlsen JL, Basnet SK, Vestergaard H, Ploug T, Stallknecht BM. Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men. Am J Physiol Regul Integr Comp Physiol. 2013 Jul 10. [Epub ahead of print]
• Couturier A, Ringseis R, Mooren FC, Krüger K, Most E, Eder K. Carnitine supplementation to obese Zucker rats prevents obesity-induced type II to type I muscle fiber transition and favors an oxidative phenotype of skeletal muscle. Nutr Metab (Lond). 2013 Jul 10;10(1):48.
• Trewin et al. N-acetylcysteine alters substrate metabolism during high-intensity cycle exercise in well-trained humans. Applied Physiology, Nutrition, and Metabolism. 2013
• Gleeson, M. Biochemestry of Exercise in Maughan, Ronald J., ed. The Encyclopaedia of Sports Medicine An IOC Medical Commission Publication, Nutrition in Sport. Vol. 7. Wiley.com. 2008.