Health & Exercise Quickie: Vitamin D Deficiency, Taurine & Glycine. Multiple Sclerosis & Epstein-Barr. Paracetamol & Muscle Gains. Gender & Fatigue from Workouts. HIIT, LISS & Appetite. Plus: Scientists Debate: Light vs. Heavy Weights

While there is a positive trend in the percentage of US adults who meet the 2008 federal physical activity guidelines according to which they have to "devote at least 150 minutes/week to moderate, or 75 minutes/week to vigorous intensity exercise, or an equivalent combination", the number of people who have gotten the message that a combination of both strength and aerobic training (red line) is much more efficient than doing just aerobics (blue line) remains the same (CDC. 2013)

48%! That's the SuppVersity figure of the week and the percentage of US adults aged 18 and over who met the 2008 federal physical activity guidelines for aerobic activity in 2013 - that's 5% more than in 1997. It would be better to see it up in the 75%+ region, but it's nice to see that more and more people are devoting at least 150min/week to moderate intensity exercise, or 75 minutes/week to vigorous intensity exercise, or an equivalent combination.

What's not so nice is that people are still way too focused on aerobics and the number of US citizens that's combining resistance and aerobic training to reach their exercise goals is stagnating below 20%. Moreover, best-agers and baby boomers, who would probably benefit even more from some weight lifting than the 36% of the young men (age 18-24) who make up the lion's share of the 'real' physical culturists who know about the importance of both, 'weights' and 'cardio', are - if they work out at all - still sticking to the tried and disproven LISS only regimen.

On Short Notice, today: A Health & Exercise Quickie

Apropos "LISS" as the headline of today's On Short Notice news quickie already gave away, light intensity steady state aerobic training aka LISS is one of the exercise related topics today. We will however start out with the health related news... and don't wonder that the first post is about polar bear health. I promise you will be intrigued, when you've read it ;-)

• 'Westernized' polar bears' bones look as if they would need vitamin D supplements, in reality all they are probably missing is sufficient taurine in their diet. I don't know but maybe you've asked yourself before: "How on earth can a white bear survive in the Arctic, when his nose is the only part of his skin that's exposed to the sun and would thus be able to produce vitamin?" (Please mind that this is not a serious question ;-) He eats his vitamin D!
  
  

  

  Scientists speculate: Their cousins in captivity suffer from rickets and fractures due to secondary vitamin D deficiency in consequence of insufficient taurine intake.

  Ok, first question first answer, but what about question #2: "How come that the clubs of his brethren and cousins in captivity get rickets and fractures as if they were vitamin D deficient, although they get the exact same amount of vitamin D from mother's milk and their later diet (sometimes the latter is even supplemented) as their wild counterparts?" Answer? No idea? Well, if you ask the researchers from the The University of Tennessee Health Science Center the answer is (Cheesney. 2009): A lack of taurine in the diet.
  
  Taurine plays a fundamentally important role in the conjugation of ursodeoxycholic acid to TUDCA and facilitates the uptake of fatty acids and fat soluble vitamins. With insufficient taurine in the diet polar beers (and human beings) can probably drink as much vitamin D in olive oil or whatever other fat base they deem more appropriate then dry tabs without any effects on their 25-OHD => calcitonin levels and consequently bone health (suggested read "Fat D-Ficiency! Study Shows, Even 50.000 IU of Vitamin D3 Useless, When You Ingest It Without Fat").
  
  Moreover, a recent guinea pig study from Department of Internal Medicine at the Medical College of the National Cheng Kung University suggests that glycine could be another 'pro vitamin D amino acid' due to its beneficial effect on the liver and subsequent protection of disturbances in vitamin D metabolism and low 25-OHD levels (Chen. 2008) - now, what if any of these, i.e. taurine or glycine, or simply insufficient bile acid, which incidentally depends on the consumption of the "bad, bad" cholesterol (cf. Kern. 1994), is the actual reason of the rampant vitamin D deficiency in our meat-, fat- and cholesterol-o-phobic societies?
• "Low vitamin D and remote EBV infection may be associated with clinical MS breakthrough within 2-3 years." (Décard. 2013) Usually I don't simply copy the study titles, but this one says it all. Even before the first symptoms of multiple sclerosis occur, i.e. in the so-called pre-CIS (=clinically isolated syndrome) interval, patients with quiescent multiple sclerosis have 50% lower 25OHD levels than their healthy peers and - what could actually be the causal factor, here - three times higher Epstein-Barr specific IgG levels (EBNA1). Can these observations a group of scientists from the Department of Neurology at the St. Josef-Hospital of the Ruhr-University Bochum in Bochum, German, really be mere coincidence?
  
  

  

  Figure 1: While it would be best never to be infected with Epstein-Barr your risk of EP-related MS is more than twice as high if you are exposed late (Ascherio. 2010)

  At least as far as the Epstein-Barr relation goes the answer of a 2010 review of the literature would be 'no, probably no coincidence' (Ascherio. 2010). It appears to be established that Epstein-Barr (EB) plays a pivotal role in the etiology of MS. Based on the observation that people without EB are virtually MS free, and the fact that their own previous research has clearly shown that late infections with EP increase your risk to develop MS by more than 2x (compared to people who have been exposed in childhood; see figure 1), Ascherio et al. argue that it is very unlikely that EP is not at least the trigger, if not the ultimate cause of MS.
  
  The scientists also refer to the hygiene hypothesis which has been advanced by other authors before, unfortunately, however, getting rid of the 'cleanliness' and exposing your immune system to the training it needs by exposing yourself to the virus at an earlier age, is of little use, if not totally stupid. After all it would only reduce your risk to develop MS to a level that's still more than 1,000% higher than in people who have never been exposed to the virus in the first place (see figure 1).
  
  Due to the inconclusive data on the long and short term effects of Epstein-Barr infections on the B-cell and T lymphocyte response, the Ascherio et al. are not yet sure about the exact mechanism by which EP stimulates, triggers or drives the development of MS. All that can be said with relative certainty is that Epstein-Bar infections contribute to the increase in multiple sclerosis. Aside from the previously mentioned correlations the mere fact that those regions of the world where Epstein-Barr is quasi non-existent are virtually MS free is probably the best evidence of its involvement in autoimmune attacks on your brain. So if you want to protect yourself you better make sure you don't get infected!  Since EP is part of the herpes family and transmitted via saliva this is unfortunately not exactly easy...

• 

  Figure 2: Overall there is no statistical significant downside to chronic paracetamol supplementation, but there is a slight advantage for the NSAID free group in term of increases in lower body strength - the time course (not shown) of the strength gains was by the way identical for both groups, as well (Jankowski. 2013)

  Paracetamol does not interfere with muscle gains in elderly men. The issue whether or not NSAIDs will interfere with resistance training induced gains in skeletal muscle is certainly relevant for everyone. If there is one group of people for whom it could be of paramount importance, though, this would be the men and women in their best ages (>50 years) who have finally realized that muscle is not just metabolic currency, but a true life insurance.
  
  Against that background the most recent results from the College of Nursing at the University of Colorado Anschutz Medical Campus may be important news (Jankowski. 2013). I mean, if the use of N-acetyl-4-amniphenol (ACET) aka paracetamol would hamper or even forestall muscle gains, the training efforts of the men and women who take ACET would be to no avail.
  
  Now the good news is that the chronic use of paracetamol at a daily dose of 1,000mg did not reduce the lean mass gains in the 17 men (age >50y) who actually participated (instead of giving up) in all of the 3-5 days A/B resistance training sessions
  
  • workout A: R three sets of lateral pull down, bench ress, hip abduction and adduction, biceps curls, seated row, and ssisted chin ups
  • workout B: overhead press, leg press, triceps xtension, knee extension and flexion, heel raise, and shoulder external rotation
  • warm up / cool down: 10 min warm-up on the treadmill, a stair climing intermezzo after the first warm up sets and another 10 min cool down
  that were performed with at 80% of the 1-RM and with at least 1 day off in-between over a period of 16 weeks.
  
  
  The chronic ingestion of paracetamol is not advisable regardless of its negligible detrimental effects on skeletal muscle gain. Only recently, Kane et al. have shown that older people in are particularly prone to the hepatoxic effects of this (imho falsely OTC available) NSAID (Kane. 2013). If there is no way around it, because you cannot stand the pain, a safer (at least for the liver) and more effective medical approach could be the combination of tramadol (75 mg), a weak opioid analgesic, with low dose of paracetamol (325-650mg, max!; cf. Pergollizzi. 2013).
  In as much as the nonexistent negative effects are good news, they are likewise strange news, because according to the expression of proteins involved in the protein synthetic response to exercise, it should actually have hampered the gains:
  

  "[...] in the ACET group that the expressions of the anabolic gene p70S6K and the catabolic gene MAFbx were significantly reduced at week 16 of PRT. Given that the increases in FFM in response to PRT were not significantly different between the groups, it is possible that the suppression of catabolic signaling was sufficient to offset reductions in anabolic signaling in the ACET group." (Jankowski. 2013)

  As the authors point out future studies will have to elucidate the exact mechanism this at first sight contradictory results.
  
  In the mean time Jankowski et al. do yet speculate that the loss of prostaglandin signalling and supsequent increases in p70S6K, the protein that's responsible for muscle protein synthesis may be countered by the normalizing effects paracetamol exerts on the expression of Akt, the ameliorative effect on the overexpression of nitric oxide synthase (iNOS) and the reduction of the age-relatedly increased myocyte apoptosis.
  

• 

  Compared to Hope Solo or Serena Williams Olympian Brian Lochte, is probably a weakling - of course only as far as the fatigabilty of his skeletal muscle is concerned - as far as the risk do develop the Athlete's Triad is concerned, this may yet be advantage.

  Men and women tire differently - men (once more ;-) the weaker sex Let's face it guys,  we are weaklings. At least this is what Beth W. Glace and her colleagues from the Nicholas Institute of Sports Medicine and Athletic Trauma at the Lenox Hill Hospital in New York report in their latest paper. Other than the quadriceps muscles of our significant others, our muscles fatigue after 2h of cycling with intermittent one minute sprints every 20 minutes.
  
  In women, in this particular case just like their male counterparts trained cyclists or triathletes with a training load of at least 100km per week, on the other hand, it's solely the central nervous system fatigue that will keep them from cycling 'forever'. Unfair, right? Us men have to battle both, central as well as local muscular (=peripheral) fatigue.
  
  Now what seems nothing but advantageous can however turn against you. In a way the low fatigability of female muscle is also part of the reason why are way more susceptible to the athlete's triad (click here to learn more) than men: They are simply able to work their CNS into the ground, because their peripheral musculature is less prone to exhaustion.
• Recent study puts question mark behind assumed appetite reducing benefit of HIIT sprints vs. classic aerobics - but does that mean that aerobics is the way to go? Not yet in press, but already intriguing are the results of a recent study by  Kevin Deighton et al. from the School of Sport at the Loughborough University who say that they found that ...
  

  "[a]n acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise" (Deighton. 2013)

  

  Figure 3: Intentionally or not, based on the conclusion of the abstract you would probably not have expected to see these results (data adapted from Deighton. 2013)

  Now this sentence from the abstract certainly suggests that sprinting would have nothing but negative effects. The actual data you see in figure 3 does yet tell you something different. The sprinters may have had increased ghrelin and lower PYY levels with the expected downstream effects on perceived hunger, but this did not translate into significant differences in food intake. In other words, even longish sprint exercises like the ones in the study at hand won't put you at danger of overeating - despite transient increases in ghrelin levels.
  
  In fact, the increased ghrelin amplitude can actually be an advantage (see August 04, 2013) and the calories in vs. out calculation the scientists do is so irrelevant to the real world health and body composition effects of exercise that I refuse to repeat it here ("No, you cannot eat that extra piece of layer cake because you ran on the treadmill earlier today" ;-)
  
  In the end, comparisons like this always suggest you had to choose between doing one or another mode of "cardio", when a combination of both, i.e. cycling HIIT and LISS, yet not both in one session, would be the most productive way to go. And no, Mr. Taubes, none of them is "just going to make you hungry" (see "Every Dog Has His Day: Dr. Oz Was Right, Exercise Does Not "Just Make You Hungry", But Reduces Energy Intake!")
  
• Researchers debate the "low vs. high weight" conundrum. In the editorial to the next issue of the Journal of Applied Physiology Mark D. Schuenke, Jennifer Herman, and Robert S. Staron reject the criticism they received from Nicolas Burd et al. for the pro heavy weights arguments they put forward in their recently published study on the effects of high vs. low weight training (Schuenke. 2013a; covered on the SuppVersity on October 01, 2013). Now while this back and forth between the two groups does not deliver any new data, I believe that it is still interesting and highly educative to see how science is actually a matter of negotiated not set truths. So, let's see how Schuenke et al. respond to Burd's assertion that ...
  

  

  Figure 4: Changes in body composition (left) and changes in muscle fiber cross-sectional area in response do different training regimen (Schuenke. 2013a; this study was discussed here on the SuppVersity on October 01, 2013)

  "[t]he authors’ views continue to contribute to a resistance training doctrine that is incorrect, most notably the belief that heavier weights are better concept. This conclusion is likely due to the relative dearth of quality studies assessing the hypertrophy potential of lower load resistance training paradigms, in contrast to the large number of studies employing ‘traditional’ resistance training intensities (*70 % of maximal strength).

  Clearly, evidence exists to support the concept that light(er) loads can support training-induced muscle hypertrophy both independently and by comparison to heavy loads. We would propose that so long as the stimulus is an overload, performed with high effort (fatigue), and progressive then even the most seasoned lifters would see progression,  at the very least no regression, in strength or muscle mass." (Burd. 2013)

  I will briefly summarize the most important points the researchers from the University of New England College of Osteopathic bring forward to defend their "go heavy or go home" argumentation:
  
  • The list of previous studies which confirm the the efficacy of training with high(er) weight for "optimal" gains in hypertrophy and strength is extensive.
  • Low load training is not as Burd et al. suggest "simply a milder form of low-load blood flow restrictive exercise", of which the researchers state that it is "interesting".
  • Schuenke et al. specifically refer to a Y2k study by Takadara et al. which shows that without the cuffs light loads don't build anything (Takadara. 2000).
  • The researchers point out that the claim by Burd et al. that "maximal muscle fiber activation can be achieved in any circumstance as long as the effort is to failure is unwarranted and unsubstantiated".
  • The study by Mitchel et al. Bird et al. cite to prove their hypothesis may not report significant differences between knee extensions performed at 30 % of 1RM for 3 sets, 80 % of 1RM for 1 set, or 80 % of 1RM for 3 sets as far as the isometric strength and hypertrophy between the three types of training are concerned, but
    

    "[t]his result is not surprising considering the following: (1) no control group was used, (2) each subject trained each limb using a different protocol (cross-over effect), (3) only one single-joint exercise was used (low volume versus a much higher volume of training used, for example, in Schuenke et al.: 3 sets each of leg press, squat, and knee extension), and (4) only fiber types I and II were delineated (severely limiting interpretation of the results).

    In that the last parentheses is obviously another direct criticism of what Schuenke would probably call "cherry picking" studies and specific results to support an unwarranted hypothesis.
  Based on this line of argumentation, Schuenke et al. conclude their deliberations on the note:
  

  

  One should not forget that it's not only about light vs. heavy, but in as much about appropriate and inappropriate weights. If you go by the quantity of the evidence there is however no debating that those weights are too light - probably even for a Lady in her best years.

  "Low-load training appears to have some merit. How-ever, our data support the use of high-load, high-intensity resistance training to maximize fiber hypertrophy and strength. In addition, heavy loading of the muscle has an impact on bone and other connective tissues which are minimized/lacking using low-load training. Finally, Burd et al. appear to oversimplify the field of exercise physiol-ogy. To claim that any training load (light or heavy) con-fers the same physiological adaptations as long as the end point is volitional failure is shortsighted and similar to claiming that running for any distance or time will elicit the same effects as long as fatigue is reached." (Schuenke. 2013)

  If you asked me, both are right. While I personally tend to agree with Schuenke, the main reason that I do is that the heavy weights approach is tried and proven, while - just as Burd says - the sceintific evidence pertaining to low weights is scarce and ambiguous and the anecdotal evidence from 'big guys' is non-existent. I am still curious about the next move(s) on both sides of this divide. And by the way, conflicts like these have always been among the driving forces of scientific progress, so I am pretty sure that we as trainees can only benefit from this debate as well as potential follow-up studies, both groups will feel inclined to conduct in order to 'prove' their point.

That's all for today! I hope you enjoyed the stay, all have electricity and an intact water supply ... I mean it's nice if you have a fully charged iPhone to get your daily dose of SuppVersity news, but even I have to concede that some other things in live are way more elementary.

References

• Ascherio A, Munger KL. Epstein-barr virus infection and multiple sclerosis: a review. J Neuroimmune Pharmacol. 2010 Sep;5(3):271-7.
• Burd NA, Moore DR, Mitchell CJ, Phillips SM. Big claims for big weights but with little evidence. Eur J Appl Physiol. 2013 Oct 20. 
• CDC. Early Release of Selected Estimates Based on Data From the January–March 2013 National Health Interview Survey. September 2013
• Chen CY, Wang BT, Wu ZC, Yu WT, Lin PJ, Tsai WL, Shiesh SC. Glycine ameliorates liver injury and vitamin D deficiency induced by bile duct ligation. Clin Chim Acta. 2013 Oct 23-
• Chesney RW, Hedberg GE, Rogers QR, Dierenfeld ES, Hollis BE, Derocher A, Andersen M. Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity? Adv Exp Med Biol. 2009;643:325-31.
• Deighton K, Barry R, Connon CE, Stensel DJ. Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise. Eur J Appl Physiol. 2013 Oct 31.
• Décard BF, von Ahsen N, Grunwald T, Streit F, Stroet A, Niggemeier P, Schottstedt V, Riggert J, Gold R, Chan A. Low vitamin D and elevated immunoreactivity against Epstein-Barr virus before first clinical manifestation of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Aug 11.
• Kane A, Mitchell SJ, Carroll PR, Matthews S, Hilmer SN. Characteristics of older and younger patients with suspected paracetamol toxicity. Australas J Ageing. 2013 Sep;31(3):190-3.
• Kern F Jr. Effects of dietary cholesterol on cholesterol and bile acid homeostasis in patients with cholesterol gallstones. J Clin Invest. 1994 Mar;93(3):1186-94.
• Kappenstein O, Vieth B, Luch A, Pfaff K. Toxicologically relevant phthalates in food. EXS. 2013;101:87-106.
• Pergolizzi JV Jr, van de Laar M, Langford R, Mellinghoff HU, Merchante IM, Nalamachu S, O'Brien J, Perrot S, Raffa RB. Tramadol/paracetamol fixed-dose combination in the treatment of moderate to severe pain. J Pain Res. 2013;5:327-46.
• Schuenke MD, Herman JR, Gliders RM, Hagerman FC, Hikida RS, Rana SR, Ragg KE, Staron RS. Early-phase muscular adaptations in response to slow-speed versus traditional resistance-training regimens. Eur J Appl Physiol. 2013a Oct;112(10):3585-95.
• Schuenke MD, Herman J, Staron RS. Preponderance of evidence proves "big" weights optimize hypertrophic and strength adaptations. Eur J Appl Physiol. 2013b Oct 25.
• Sioen I, Fierens T, Van Holderbeke M, Geerts L, Bellemans M, De Maeyer M, Servaes K, Vanermen G, Boon PE, De Henauw S. Phthalates dietary exposure and food sources for Belgian preschool children and adults. Environ Int. 2013 Nov 1;48:102-8.
• Takarada Y, Takazawa H, Sato Y, Takebayashi S, Tanaka Y, Ishii N. Effects of resistance exercise combined with moderate vascular occlusion on muscular function in humans. J Appl Physiol. 2000; 88:2097–2106.

Pharmacological Starvation: 30% Increased Life Expectancy w/ Still to be Developed FGF21 Analog - The Royal Road To Longevity? Plus: Ground Yourself It's World Nutrition Day!

Do you really think this kid cares whether there is fructose in his/her banana? Think about that before you delve into the next religious discussion about whether or not food a is legit to eat, "not paleo" or "too high in carbs" *thank you*

It's World Food Day and I thought it may be nice to remind everyone about the hilariousness of such "important" first world problems as "eating X bananas a day is bad foryou", the notion of "non paleo" foods and the rest of the vitally important topics the blogosphere is so fond of, these days. Allegedly, neither the bloggers, nor the facebookers or forum posters, who spend so much time and energy debating these and similarly worldshaking issues, will be among the 24,000 human beings who are dieing each and every day from hunger, but maybe one or another of you, of whom I am sure that they don't belong to the group of real notorious nitpickers, will have a similar "grounding experience", from just being reminded of this figure, as me, when I heard it on the radio earlier this morning.

Don't get me wrong, I am not intending to point with a finger at anyone (if anything I would have to start with pointing at myself), but if one or another of you would pause for a second or two and have a similar "grounding experience" as I had, I would be happy.

From real starvation to starvation science
 
Although this prelude appears to segue quite nicely into today's science post, I am not sure if that's even a good thing... be that as it may, after listening to the news on the radio I was quite annoyed, when I read about a recent study by Zhang, Kliewer et al. on the wonderful effects of the "starvation hormone" FGF21 (fibroblast growth factor 21; the effects were observed in mutants who overexpressed FGF21, by the way) on yet another of those awful copy & paste items on Science Daily that are 99% hype and 1% science (in the scientists' defense it must be said that I am well aware of the fact that our, i.e. university or institutionalist, press offices are writing this stuff together in this way on purpose and are not really interested in the actual science background, though). With statements such as "[the mice] got the benefits of dieting without having to limit their food intake" (UT Southwestern Medical Center. 2013) the "article" tailors perfectly to the demands of the glutenous Westerner who applies his "the more the better" principle to all areas of his super sized life that people will probably already be emailing Dr. Kliever about the release date of the drug he surely must be working on.

And in fact, the actual results of the study (Zhang. 2013), the press release specifies by quoting Kliever who said "Male mice that overproduced the hormone had about a 30 percent increase in average life span and female mice had about a 40 percent increase in average life span" sound intriguing. After all this would mean that you would have a realistic chance of making it to the magic 100, when you would otherwise have died at the age of 77.

Starvation, real or hormonal is not the way to healthy longevity!

Nonetheless, the price you would have to pay to "starve yourself into this biblical age" - pharmacologically, of course since (a) otherwise no one could make money on it and (b) no one would want to do it - is high. And I am not sure any of you is willing to pay it.

Figure 1: What do you call it, when mice simply won't grow and end up as a small copy of their normal counterparts with identical body composition, but virtually no bone mass? Right! That's failure to thrive. Now, what do you call the same phenomenon, if the poor critters live 30% longer? Yeah, righ! That's a scientific break through!

I guess you could say you can cope with being a shrimpy weed (or a tiny version of yourself, which is actually what what you would be if you had half your current weight and the same totally average body composition; see figure 1), if that means that you can see your grand grand children rise, but your chances that this is going to happen outside of a wheelchair are not particularly high for men and the chance of seeing them at all is non-existent for women.

The combination of low bone mass and infertility should actually ring a bell with everyone who has been following the Athlete's Triad Series.

Why is that? Well, next to being a pathetic weed, your bone mass and density would be so low that the chances of literally breaking apart are probably way higher than the already low chance that any of these results do even translate to human beings.

And while men who like to gamble may want to make this bet with the pharmaceutical devil, the antifertility effect of FGF21 would not allow any women making the same bet to even have children. Which does obviously not make it very likely that they will ever get to see the children of their grand children - regardless of whether they become 200 years old, by the way.

I am therefore not so sure whether the mere fact that the FGF21 mutants' mobility was not effected is evidence enough of "living a nice, long life", as Kliewer is pointing out (UT Southwestern Medical Center. 2013).

There is no way this drug will be gluttony and thus "Western lifestyle" compatible 

Figure 2: Don't be fooled! The small "g/g body weight" makes all the difference! If you weigh half of a normal human being thanks to whatever patented FGF21 derivate you take, you better make sure you eat like half a human being, as well, if you don't want to shorten your life by 30%, instead of prolonging it!

And as far as the implicit promise of being able to eat "as much as you want" goes, it may be correct that "there were no differences in food intake, physical activity, oxygen consumption or respiratory exchange ratio" (see figure 2) but if you scrutinize the caption of the Y-axis you'll see the bad, bad letters "g/g body weight". And this label means nothing else than that whoever has written the press release has been trying to fool you, when he or she wrote

"The mice that overproduced FGF21 in this latest study were lean throughout their lives and remained lean even while eating slightly more than the wild-type mice, the researchers said." (UT Southwestern Medical Center. 2013)

The truth is, they ate almost half as much as the normal animals, so where on earth was this not a starvation diet? I mean, all of you who have read parts (better the whole) SuppVersity Athlete's Triad Series will be well aware that bone loss and infertility are hallmark features of in this case exercise induced "starvation".

And let's be honest, unless Mc Donalds is going to produce XXS Menues for people on FGF21, I can guarantee you that the only effect any future drug analog of this hormone is going to have is to make people's lives even more miserable than they already are... longevity? No way! After all, this is not going to correct the dietary induced failure of our natural satiety response that constantly drives us to overeat on all those things the people who are now probably lining up in front of Mr. Kliewer's office to be part of the earliest trial are not willing to give up, although they know that they are thus easily reducing their maximal life-expectancy by 30%!

The unsexy, since inconvenient truth is missing from the mainstream science breakdown

In view of the fact that neither the press guy (or girl) nor the scientists appear to have a wested interest to tell you that FGF21 activity is "paradoxically elevated in obese conditions" (Fletcher. 2013) and that something as awfully inconvenient (and moreover non-patentable!) as exercise is the best way to normalize not only the skewed FGF21 levels, but also to increase the expression of the "longevity factor" clotho (30-50% in a classic rodent model; cf. Fletcher. 2013), I consider it my duty to let you know that you neither have to resort to the exogenous provision of drugs, nor starve yourself and can still be sure to benefit from the effects of FGF21: Either by its modulation via exercise if you are obese as the aforementioned rodents or, more importantly, by its upregulation in normal weight individuals, like the 60 sedentary young women Cuevas-Ramos et al. put on a two week exercise regimen earlier this year, only to find that their

"[s]erum FGF21 levels significantly increased after two weeks of physical activity [and that this 66%! increment in FGF 21] correlated positively with clinical parameters related to the adrenergic and lipolytic response to exercise." (Cuevas-Ramos. 2013)

Now, I don't know about you, but I, for my part, would probably risk to make a bet with the devil (pharmacological or not) that anyone who is willing and able to appropriately fuel his workouts, get his share of anabolic and restorative sleep and refrain from overtraining, will get all the benefits, the press release aptly ties solely to the unquestionable pharmacological "separation of the hormone’s life span-extending effects", Kliever is cited for in the last paragraph of the copy & paste job, without any of the downsides.

The SuppVersity Approach to Longevity is therefore simple, cheap and 100% healthy: Work out, eat healthy and get your daily dose of SuppVersity news to know how you can optimize your training, nutrition and supplementation regimen ;-)

References:

• Cuevas-Ramos D, Almeda-Valdés P, Meza-Arana CE, Brito-Córdova G, Gómez-Pérez FJ, Mehta R, Oseguera-Moguel J, Aguilar-Salinas CA. Exercise increases serum fibroblast growth factor 21 (FGF21) levels. PLoS One. 2013;7(5):e38022.
• Fletcher JA, Meers GM, Laughlin MH, Ibdah JA, Thyfault JP, Rector RS. Modulating fibroblast growth factor 21 in hyperphagic OLETF rats with daily exercise and caloric restriction. Appl Physiol Nutr Metab.
• UT Southwestern Medical Center. Newsroom. Starvation hormone markedly extends mouse life span, without need for calorie restriction. Oct 16, 2013. < http://www.utsouthwestern.edu/newsroom/news-releases/year-2013/october/starvation-hormone-mangelsdorf-kliewer.html > retrieved Oct 16, 2013.
• Zhang Y, Xie Y, Berglund ED, Coate KC, He TT, Katafuchi T, Xiao G, Potthoff MJ, Wei W, Wan Y, Yu RT, Evans RM, Kliewer SA, Mangelsdorf DJ. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. elife. 2013;1:e00065. doi: 10.7554/eLife.00065.

Carbs Past 6PM Reloaded: Circadian Shifts in Leptin and Ghrelin + Rising Adiponectin During the "Carb-Fast" Could Explain the Efficacy of Eating All Carbohydrates at Night

Image 1: Paul Bart (Kevin James) in Mall Cop (Columbia) probably would be better off weight- and health- wise without his Segway, which is by the way among the "50 Worst Gadgets of the Decade" in the Business Insider hall of shame from 2009 (Barret, Brian. 2009)

The SuppVersity was the first place you read about the how "Carbs past 6pm Will Make You Lean" (at least about the non-anecdotal scientific evidence) and for 99% of you, this will probably be the first time you read about the "follow up paper" on the original study, which was originally intended to induce a shift in the circadian pattern of leptin secretion in order to make use of its fat burning effects over night. Exactly this is the focus of a follow up paper that's soon going to be published in Nutrition, Metabolism & Cardiovascular Diseases (Sofer. 2013).

Israeli Police Diet Acadamy Reloaded!

Now the bad news is that the news are only partly new. In other words, the Israeli scientists only reevaluated the original data which was based on 63 overweight police officers who finished the original "don't eat carbs before dinner study."

And if that was not already enough, the complete hormonal profiles which had been collected on days 0, 7, 90 and 180 of the study period were only available for 39 of them.

Figure 1: 24h leptin profile before and after the intervention in the control (left) and experimental (right) group
(graph adapted from Sofer. 2013)

Still, the data in figure 1 does support the original hypothesis that the mechanism due to which the participant on the experimental diets (composition see figure 3 in "Carbohydrates Past 6PM Will Make You ... Lean!") lost ~2% more weight, and ~4% more body fat was in fact a shift in the circadian expression of leptin:

I suggest you go back to the original "Carbs past 6pm Will Make You Lean" post to read up on the details; unless you're a longstanding reader and this reminder is enough for you.

"On day 0 both groups demonstrated typical concave diurnal leptin curves, including a fall throughout the hours of 08:00-16:00, reaching a nadir at the afternoon and a rise from 16:00. On day 180, leptin curves were lower compared to day 0 in both groups. In the experimental group, the curve became more convex with a nadir only in the evening and not in the afternoon (figure 1, right). A significant difference was observed within the experimental group between day 0 and day 180 in the morning and in the evening (p = 0.023 and p = 0.021, respectively). For subjects in the experimental group that had complete data, the change in evening measurements from day 0 to day 180 was significant(p = 0.024). Using these data, the change in evening measurements was significantly greater than the afternoon and the noon change (p = 0.009 and p = 0.014, respectively). In the control group, a significant difference was observed between day 0 and day 180 at noon (p = 0.042). This result was also found for subjects with complete data (p = 0.045)." (Sofer. 2013)

What's also noteworthy is that the sparse information the scientists had on the ghrelin levels of their participants (believe it or not, but the nurse or whoever took the blood samples must have messed up, so that much of the data was lost) would suggests that the "post 6pm group" (=experimental group) were freaking hungry in the evening (see figure 1, right), but this was not the case, contrary to the subjects in the control group which had carbs from AM to PM, they did rather expose an "enhanced daytime satiety" an observation based on which Sofer et al. rigthly state that

"[...] the alteration in ghrelin’s peak from daylight hours to the evening just before dinner was another cause for the elevated daylight hour satiety, improved persistence in the weight loss process and better anthropometric outcomes that were reported [16]." (Sofer. 2013)

Next to with the circadian shifts in leptin and ghrelin levels, the pronounced increase in adiponectin (see figure 2), a reliable marker for an improved glucose tolerance, the "carb binges" which as you will probably remember included desserts such as ice-cream and co (see figure 3 in "Carbohydrates Past 6PM Will Make You ... Lean!"), probably is the third pillar of the superiority of the past-6PM carb regimen over the conventional "eat small amounts of carbs all day" approach  the control group was following.

Figure 1: 24h Adiponectin profile before and after the intervention in the control (left) and experimental (right) group
(graph adapted from Sofer. 2013)

In conjunction those three made the "impossible possible": Eat all instead of no carbs past 6PM and lose weight! Now the unfortunate truth is that this works well for people with compromised insulin sensitivity and anywhere between 15-20% body fat to shed before they approach the level of leanness (<20%) most of you probably started out with, whether it will work similarly well for significantly leaner, physically active individuals, on the other hand, remains to be seen.

Video 1: I don't want to be a spoil, but the weight loss program of the Stadtwerke Cologne which works by simply skipping dinner (!) and without any caloric restriction got some series attention here in Germany. Why? Well, it simply works... so what does this tell you? Maybe it's more about helping AMPK come to it's own, instead of stuffing yourself with readily available energy 24/7, than about exact timing or meticulously calculating macro compositions?
(click here to watch Quarks & Co.)

Bottom line: Irrespective of my all doubts about the applicability of the very same diet principle in a context, where the goal is to get really ripped and not simply non-obese, the study at hand (and I am referring to the whole experiment, here not just the last paper) does confirm that there is more to dietary success than calories in vs. calories out that having breakfast like a king is not a necessity (nuts + coffee, which was the standard breakfast in the experimental group, or nothing, which is Adelfo Cerame's standard breakfast, work just as well) and that the influence of circadian rhythms goes far beyond our sleep-cycles... which reminds me that I'll do my very best to get into more details on that in the coming episode III of the SuppVersity Circadian Rhythm Series on Sunday. Until then, try not to lose the beat ;-)

References:

• Barret, Brian. The 50 Worst Gadgets Of The Decade. Business Insider. Dec 31, 2009. < http://www.businessinsider.com/the-50-worst-gadgets-of-the-decade-2009-12?op=1 > retrieved on Aug 24, 2013.
• Sofer S, Eliraz A, Kaplan S, Voet H, Fink G, Kima T, Madar Z. Changes in daily leptin, ghrelin and adiponectin profiles following a diet with carbohydrates eaten at dinner in obese subjects. Nutr Metab Cardiovasc Dis. 2013 Aug 14.

Y3K Fat Burners: Bile Acid Suppositories! Plus: How This Relates to Taurine, Cholesterol, Statins and Diabesity

Image 1: Is the US starving for sulfur amino acids and cholesterol?

You've learned in yesterday's post (cf. "Sodium-Alginate for 30-40% More Weight Loss and Body Fat Reduction on Mild Caloric Deficit") on the surprising fat-loss effects of seaweed extract, or sodium alginate, already that the "fat burner" of the future isn't going to be a stim, ... well, at least not necessarily or exclusively, but rather a compound that acts onto the GBA, the gut-brain axis by modulating your bodies response to food and fasting. Now, as gross as this may seem, a recently published study from the United Arab Emirates University does suggest that this fat burners may not even come in pill, but rather as a suppository!

A fat burning suppository? Wtf....

I see you are shocked, well so was I, but the alternative would be that you take a syringe and... ah, let's just assume they came out with a suppository which could deliver the same 0.66, 2.0, 6.66 and 20.0 mmol (0.36, 1.08, 3.58, 10.75 g) of sodium taurocholate the ten obese type II diabetic volunteers (!) in the study by Adrian et al. received rectally via a silastic cannula in 20 ml of 1% (wt/vol.) carboxymethyl cellulose over a period of 1 min after an overnight fast - a small injection with profound effects:

Figure 1: Response of insulin, blood glucose and GLP-1 to rectal administration of different doses of taurocholate to obese type-2 diabetics (based on Adrian. 2013)

As the data in figure 1 shows the injection of deliquescent yellowish crystalline bile acid, most people know for its involved in the emulsification and absorption of dietary fats and fat-soluble vitamins, exerted profound effects on hormonal peptides we have long believed to be produced mainly in response to the ingestion of specific nutrients or the gastrointestinal production of short-chain fatty acids from the latter (Tolhurst. 2013). In particular, the rectal administratoin of sodium taurocholate (the sodium stabilizes the molecule in water) lead to

• dose-dependent increases in plasma concentrations of active GLP-1 and total PYY (not shown in figure 1, but increase paralleled GLP-1) both of which were statistically highly significant (p<0.001) with the highest dose of taurocholate leading to a 7.2x increase in active GLP-1 and a 4.2x increase in PYY
• at the same time plasma insulin increased by 2.6x and the glucose levels decreased progressively over 60 min by up to 3.8 mmol/l

An impressive result which does yet beg the question: Is this good or bad? I mean a 2.6x increase in insulin? That must be bad, right? It certainly would - but if that's a 2.6x increase that does exactly what it's supposed to, i.e. reduce blood glucose levels in obese type II diabetics, it's unquestionably a good thing.

 Figure 2: Food intake 75min after taurocholate administration at different doses; subjects were provided with their favorite meals and advised to eat to satiety (based on Adrian. 2013)

What's yet even better are the downstream effects on subsequent food intake (see figure 2). 75min after the somewhat embarrassing treatment, the subjects had free access to a as much of their favorite food as they wanted. For 2h, their simple task was "eat as much until you are fully satisfied" and the subjects complied. On the occasions where their suppository contained the high dose of taurocholate, the chicken wings, hamburgers, fries and chocolate cakes or whatever these guys indicated were their favorite foods were almost twice as satiating! The 10mol dosage reduced the food intake by roughly 1/4 still and would be in the range of my recommended 'reduce your energy intake by ~20% if you want to maximize fat and minimize lean mass loss' recommendation - yet not as a result of pure willpower, but simply because more was not necessary and much more probably not even possible!
I can control my appetite I don't need these tools

I can see that some of you are now giving a sniff at those gluttonous fatsos who are not able to control their appetite and therefor simply cannot lose weight and I guess for a small minority of dieters that may actually be the case. The emerging research on the far-reaching metabolic effects  of the so-called "satiety hormones" PYY and GLP-1 does yet clearly suggest that gluttony is only part of the reason why the efforts of dieters all around the globe fail time and again. And it is therefore more than reasonable to assume that this satiety induced caloric reduction, contrary to the common will-power based mild to profound starvation,  will actually produce the expected weight loss results as long as it can be sustained over weeks and months.

Figure 3: It's as easy as can be - work against your body, starve yourself, never eat to satiety and lose (top) vs. work with your body, use gut-brain-axis (GBA) modulators and win (bottom)

Direct evidence for this hypothesis comes from yesterday's news, where the reduction in ghrelin, the hunger-inducing counterpart to GLP-1, PYY & co helped the dieters in the high algae fiber group to adhere to their diets, to lose weight and more importantly body fat at a constant rate over the whole 12-week study period (cf. "Sodium-Alginate for 30-40% More Weight Loss and Body Fat Reduction on Mild Caloric Deficit"). 

Taurocholate suppositories, taurine, cholesterol, statins and yet another reason we are fat

Image 2: What do panic buying and overeating have in common? In both cases the affected people or their bodies expect that there is going to be a shortage in the future and they got to squirrel goods or nutrients away.

It doesn't take a rocket scientist or SuppVersity student to figure from the name alone that a molecule which goes by the name "taurocholate" could contain taurine and cholesterol, right? Right! So what happens if you don't eat enough sulfur(-amino acids) which are necessary as a precursor for taurine biosynthesis (Brosnan. 2006), because those are mainly found in yummy high cholesterol foods such as eggs and co? Right! You will neither produce enough taurine nor have enough cholesterol to produce those amounts of taurocholate and other bile acids as would be necessary to reach the enteroendocrine cells in the distal colon, which would then release those peptides that will signal your consciousness that you are satiated and your metabolism to keep burning those damn love-handles because there is plenty of energy coming in and no sign of impeding famine.

The result, a mismatch between energy intake and energy sensing / satiety, will not just have you eat, eat and... eat! as if there was no tomorrow (see image 2), it will also have your body squirrel away every calorie it can save right into your evergrowing adipose tissue. You develop diabetes and hyperlipidemia and your doctor who beliefs in "medical standards" throws a bunch of statins at you. The statins reduce your cholesterol further. There is less substrate for bile acid production. The mismatch becomes even greater, your energy metabolism is tumbling and you are hungrier than ever before... the perfect storm, it's raging!

"Where is the evidence?"

Image 3: What happens when you feed rats 375x more cholesterol than usual, from whole eggs of course? Right, their lipid profile improves! How do you know, did you read my previous blogpost on the study by Yang et al. (Yang. 2013)? If you didn't click on the image to get there.

There is no evidence for a hilarious theory like that? Well let's start with what happened, when we stopped eating nutritious foods, began throwing away egg yolks and started replacing regular foods with cholesterol-free junk... we got fatter: Year by year! Let's go ahead and take a look at the host of scientific evidence for the beneficial effects of taurine on glucose and lipid metabolism (e.g. Park. 1998; Hansen. 2001; Mühlfeld. 2011; De la Puerta; 2010; Nardelli. 2011). And let's finally combine that with the still hushed up pro-diabetic effects of statins (cf. "With >50% Increased Risk to Develop New-Onset Diabetes, Statins are "Starter Drugs" for Post-Menopausal Women"). I guess that's not conclusive scientific evidence, yet and as so often only part of "why we get fat", but it is certainly a promising hypothesis that adds another piece to a puzzle where the gut-brain-axis or gut-endocrine-axis is occupying a place that can hardly be underestimated.

References:

1. Adrian TE, Gariballa S, Parekh KA, Thomas SA, Saadi H, Al Kaabi J, Nagelkerke N, Gedulin B, Young AA. Rectal taurocholate increases L cell and insulin secretion, and decreases blood glucose and food intake in obese type 2 diabetic volunteers. Diabetologia. 2013 Jun 14.
2. Brosnan JT, Brosnan ME. The sulfur-containing amino acids: an overview. J Nutr. 2006 Jun;136(6 Suppl):1636S-1640S.
3. De la Puerta C, Arrieta FJ, Balsa JA, Botella-Carretero JI, Zamarrón I, Vázquez C. Taurine and glucose metabolism: a review. Nutr Hosp. 2010 Nov-Dec;25(6):910-9.
4. Hansen SH. The role of taurine in diabetes and the development of diabetic complications. Diabetes Metab Res Rev. 2001 Sep-Oct;17(5):330-46.
5. Mühlfeld A, Kubitz R, Dransfeld O, Häussinger D, Wettstein M. Taurine supplementation induces multidrug resistance protein 2 and bile salt export pump expression in rats and prevents endotoxin-induced cholestasis. Arch Biochem Biophys. 2003 May 1;413(1):32-40. 
6. Nardelli TR, Ribeiro RA, Balbo SL, Vanzela EC, Carneiro EM, Boschero AC, Bonfleur ML. Taurine prevents fat deposition and ameliorates plasma lipid profile in monosodium glutamate-obese rats. Amino Acids. 2011 Oct;41(4):901-8.
7. Park T, Lee K. Dietary taurine supplementation reduces plasma and liver cholesterol and triglyceride levels in rats fed a high-cholesterol or a cholesterol-free diet. Adv Exp Med Biol. 1998;442:319-25.
8. Stephan ZF, Armstrong MJ, Hayes KC. Bile lipid alterations in taurine-depleted monkeys. Am J Clin Nutr. 1981 Feb;34(2):204-10.
9. Tolhurst G, Heffron H, Lam YS, Parker HE, Habib AM, Diakogiannaki E, Cameron J, Grosse J, Reimann F, Gribble FM. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes. 2013 Feb;61(2):364-71.
10. Yang F, Ma M, Xu J, Yu X, Qiu N. An egg-enriched diet attenuates plasma lipids and mediates cholesterol metabolism of high-cholesterol fed rats. Lipids. 2013 Mar;47(3):269-77. Epub 2013 Jan 11.