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

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

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

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

Enough of the speculations: What are proven alternatives

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

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

• 

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

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

• 

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

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

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

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

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

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

• 

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

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

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

Did you know that...

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

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

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

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

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

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

References:

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

Jump Squats 80% Type-II Fiber Activity, Cold Thermogenesis Better Fasted, Tuned Swiss Ball Crunch, 5-HTP vs. Asthma, HIIT Before Strength & High vs. Low GI Meal Pre Workout

Image 1: Few of the things the average trainee does in places that call themselves "fitness studios" has little to do have will actually promote fitness, as in being athletic. "Mr. check out my biceps", for example would be similarly lost ding this as the sedentary computer nerd "Mr. biceps" loves to laugh about.

I know from time to time I am not 100% in time when it comes to delivering promised articles, but after an exhaustingly hot day, I am pretty much in-time with the 2nd installment of "On Short Notice" for today and the third for this weekend. Since I felt that it looked awkward to have three posts with the "On Short Notice" in front posted one after the other, I did however decide to ditch that (at least for today) and get straight down to ... well, "business" with posts on the revealing type II fiber specific muscle-damage from jump squats, the reason why you better sit in your ice-tub fasted if you want to practice cold thermogenesis, the superiority of Swiss Ball Crunches with resistance bands over the classic ab machine, the surprising anti-asthmatic effects of super high doses of 5-HTP, the way women benefit equally from a progressive strength training regimen with or without HIIT or steady state cardio before the strength workout, and, lastly, the futility of fretting about the acute effects of high vs. low GI meals before a workout and how that relates to childhood obesity. And while I do, believe it or not, have material for at least another episode, I am not going to bore you with even more short news pieces for this weekend. Don't worry ;-)

• Plyometrics for type II muscle fiber(-damage) It probably depends on your individual take on the usefulness of muscle damage, if the headline to this "On Short Notice" got you excited about plyometric training or not. When I am now telling you that the participants in the recently conducted trial by Macaluso et al. were previously untrained (N=8; age = 22 ± 1 years, height = 179.2 ± 6.4 cm, weight = 78.9 ± 5.9 kg) and the creatine kinase levels (a marker of muscle damage and the subsequent leakage of the creatine kinase enzyme into the blood) peaked at only 529.0 ± 317.8 U/L (that's high, but way below the 1,000er range you often see in untrained subjects after nothing but a couple of eccentric biceps curls being performed to failure) after the exercise intervention, I'd guess that most of you will appreciate that the researchers observed significantly more severely damaged type II than type I fibers (on average 85% vs. 27% of the respective fiber type).

  

  Image 2: The effect of plyomtetrics on your fitness & physique is still  underrated by the most fitness enthusiasts; and that despite the facts that plyos are the bread and butter of many athletes whose physical feats they are admiring.

  If we now make the reasonable assumption that the ~60% higher rate of muscle damage in both the glycolytic and oxidative subtypes of the type II fibers was indicative of the fact that they were the ones which shouldered the main workload of the 10 x 10 jump squat regimen the young men had to perform, this is unquestionable good news for everyone trying to get big and buffed. After all, these fibers, which are also known as type IIa (86% severely damaged) and type IIx fibers (84.% severely damaged vs. just 27% of type I fibers), are the ones that allow bodybuilders to get lean and muscular - not just one or the other... if that got you intrigued about what plyometrics are and if there is more research on it, I suggest you take a(nother) look at my previous posts on "ploys", such as "Building the Jack-of-All-Traits Legs Workout With Squats, Jump Squats and Body Weight Plyometrics?" or even the "Turbo-Fire vs. Insanity ShootOut" from one of the previous installments of "On Short Notice".
• Cold thermogenesis is not for everyone, but if it works for you, better do it fasted! That the amount and in many cases even the presence of the metabolically active brown adipose tissue and with it the thermogenic response to cold exposure is a very individual thing, is something you, as a diligent SuppVersity student will be aware of after all you have already read my previous post of the matter (cf. "Cold Thermogenesis vs. Ephedra").

  

  Figure 1: Cold thermogenesis in postprandial (PP) vs. fasted state (FF); dark areas indicate high 18F-FDG uptake (=high metabolic activity; Vrieze. 2012)

  Since there are still way too many people who actually seem to believe that sitting in a cold bathtub for a couple of minutes everyday would be all it takes to get you ripped and jacked, I thought it prudent to give them the chance to make it actually work and advice them to do it fasted! According to a recently published study from the Department of Internal Medicine at the Academic Medical Center in Amsterdam, in the Netherlands (Vrieze. 2012), the metabolic activity of the brown fat in all 6/10 of the 10 healthy, lean male volunteers (18-32 y; body mass index, 20-24 kg/m²) who participated in the study was about twice as high when they sat in a room which was cooled down to 16-18°C for 2h fasted (13.1 g/mL glucose uptake) vs. in the postprandial state (6.8 g/mL).
  Aside from the usual non-responders (40%) and the huge heterogenity with respect to the thermogenic response (6.1 - 27.6g/L), which are typical for these experiments there is a similarly large intra-individual difference with respect to the increase in BAT activity in the fasted state with the highest responder going from 11g/L in the post-prandial to 27.6g/L in the fasted state and the "fasting non responder" with a statistically non-existent (the term "non-significant" would not be bold enough ;-) "increase" in cold induced thermogenesis from 5g/L to 6g/L.

• 

  Video 1 (askthetrainer.com): The Swiss ball crunch with resistance bands takes some "tweaking" to be done correctly. After all you usually don't have the equipment set up in the way you would need it at your gym (click image to watch).

  Swiss ball crunch with resistance bands effective and saver than ab machine While I am not sure how "effective" the ab-machine in the study by Sundstrup et al. actually was, I can tell you that done with resistance bands the allegedly hilariously looking swiss ball crunch is not just at least as effective in recruiting the musculature of the rectus abdominus (104±3.8 vs 84±3.8% nEMG, respectively) as one of those machines, where your legs are locked in a way that the rectus femoris will do take do way too much of the work (2x more activity than in the swiss ball crunch with resistance bands) and you thus set yourself up for future lower back (=lumbar pain).
  Against that background and in view of the fact that Sundstrup et al. found that "both men and women, younger and elderly, and individuals with and without pain benefitted equally from the exercises" (Sundstrup. 2012), it is probably well worth taking the 2-3 min to get the equipment in position and do 3-4 sets of this unquestionably unconventional exercise (check out the SuppVersity EMG Series and my post on "Integrated Core Exercises For 6-Pack Abs" for additional ab exercises).
• 

  A couple of statistics on the current asthma rates in the US
  

  • asthmatic adults: 18.7 million (8.2%)
  • asthmatic children: 7.0 million (9.4%)

  In 2010, most U.S. children aged 17 years and under had excellent or very good health (82%). However, 8% of children had no health insurance coverage, and 5% of children had no usual place of health care. Seven percent of children had unmet dental need because their families could not afford dental care. Fourteen percent of children had ever been diagnosed with asthma. An estimated 8% of children aged 3–17 years had a learning disability, and an estimated 8% of children had ADHD. (Bloom. 2011; based on data from 2010)
  5-HTP switches allergic asthma off No good news for the average Olympian athlete who would then lose his script for his beta-agonists (clenbuterol & co, see also SuppVersity Facebook news from Aug 01, 2012), but probably something those of you who suffer from allergic rhinitis or full-blown asthma will appreciate: The administration of 5-hydroxy-tryptophan an orally available precursor to serotonin over the course of  led to a profound reduction (70-90%!) reduction in allergic lung inflammation in a rodent model (Abdala-Valencia. 2012). While the supplement left all sorts of side-effect related parameters unchanged and did not lead to weight gain, which is an often touted side effect of SSRIs - mostly unjustly, by the way! - the hilariously high dosage of 5mg 5-HTP per kg body weight the rodents received did reduce the allergen-induced transglutaminase 2 (TG2) expression, the migration of immune cells into the lung tissue, the local synthesis of serotonin and the subsequent serotonylation of proteins (serotonin conjugation of proteins) which is a key feature of allergic asthma.
  Regardless of the fact that Abdala-Valencia explicitly point out that these effects "occured without systemic increases in serotonin" (Abdala-Valencia. 2012), which could have led to vasoconstriction and other negative side-effects, I strongly caution against the ingestion of a whole bottle of 5-HTP tabs per day... when the researchers from the Northwestern University Feinberg School of Medicine publish a follow up study on humans, I'll let you know, though - in view of the ever-increasing asthma (see infobox on the right) research in this area could not just offer a valuable new treatment strategy, but also insights into the underlying reasons of this epidemic.
• Young women can combine strength training with either steady state or HIIT and still make progress - Somewhat related to my post earlier this week on doing cardio before instead of after your strength workout are the results of a recent study by Silva et al. who found that young women (age ~23y) make identical strength gains, regardless of whether and which type (HIIT sprinting or steady state cardio on the cycle ergometer or classic jogging) they perform before with their twice a week full-body training (Silva. 2012). Just as in the Di Blasio study, the "cardio" sessions, which were performed in a 1 min all-out vs. 1 min active recovery (HIIT) or 95% of the ventilatory threshold (SST) fashion for 20-30min (progressing from 20-30 over the course of the 11 weeks), were performed before the weight training (note: changes in body composition were not evaluated in detail, but I would be very surprised, if the concomitant training regimen, and in that specifically the HIIT protocol, did not outperform the resistance training only protocol in this respect).

  

  Image 3 (rippedfitness.com): You will certainly remember Wednesday's news on doing cardio before weights, well, here you have more evidence that even doing 20-30 min of HIIT won't hamper the gains of fit female beginners on a twice a week full-body regimen with built-in progression regimen - neither will steady state cardio "in the zone", by the way.

  If you are a young, fit woman (or man) without years of competitive athletics under your belt and don't train all too often (~2-3 times per week), it does thus obviously not harm your strength gains on a classic strength training program with built in linear progression from 15-18RM to 8-10RM, if you concomitantly work on your conditioning - whether the results would be identical if the subjects were not just fit and healthy but had been training for years and were working out 5x instead of 2x a week, is yet questionable. On the other hand, it is very unlikely that seasoned athletes (and this goes out to the gentlemen, in particular) will lose muscle and ruin their strength gains, whenever they move further than the bench to the squat rack - it's all a matter of total volume and running out of puff due to bad conditioning can just as well keep you from pulling those additional 10kg off the floor as the exhaustion from doing too much cardio.
  This, by the way, brings me back to the notion of "fitness" vs. "being fit", I alluded to in the caption of image 1, already: If you want to exploit the 100 year credit your genes have granted you (see "Exercise for Life Extension" in today's first installment of "On Short Notice"), you better focus on "being fit". Try different things and don't get stuck in a rut.
• High GI, low GI, ... f*** GI! When you, a healthy, more or less well-conditioned individual are about to engage in a high intensity exercise protocol that simulates a football match (bouts of walking (31-39 s), jogging (41-46 s), cruising (41-45 s), sprinting (16-21 s) and standing), it make absolutely no difference whether you ingest a high (=80) or low (=44) pre-workout meal (total energy=377 kcal; CHO=79 g; Fat=3 g; Protein=13 g) 3.5h before your workout (Hulton. 2012).

  

  Image 4: Add Lucozade + Akash rice for high GI (80) or apple juice and basmati for low GI (44) and you have two isocaloric test pre-workout meals

  That's at least what the results of a recent study by Hulton et al. which did not find any differences in blood glucose, fatty acids (FA), glycerol, β-hydroxybutyrate, lactate and insulin (assessed before, during, and after the exercise bout), rates of CHO and fat oxidation (determined at 4 time points during the protocol) or 1 km time trial performance. It should be mentioned, though, that this was not a liquid meal, but consisted of either Lucozade + akash rice (high GI) or apple juice + basmati rice (low GI) with an identical chicken breast + tomato sauce "base" and identical macro-nutrient and calorie content.
  That the long-term consequences on your body composition may still be different is a different cattle of fish though and how "beneficial" liquid sugar, ah... I mean energy drinks, such as Lucozade are is something at least those of you who read my "Fat Content Per Energy Drink 0g, Body Fat Gain Per Energy Drink 18g!" post from June 30, 2012. Whether apple juice is much better is still debatable, though. Wojcicki & Heyman, for example, argue (finally, as I would like to add) in their latest paper that "excessive fruit juice consumption is associated with increased risk for obesity" and the ingestion of "sucrose [...]without the corresponding fiber, as is commonly present in fruit juice, is associated with the metabolic syndrome, liver injury, and obesity". Reason enough for the two pediatrics from the University of California to recommend that the "US Department of Agriculture's Child and Adult Food Care Program, which manages the meal patterns in childcare centers such as Head Start, promote the elimination of fruit juice in favor of whole fruit for children." (Wojcicki. 2012)

Before I eventually call it a week, I would like to remind everyone of the daily mini-news on the SuppVersity Facebook wall. Only few of them will also make it into the "On Short Notice" column (actually the "Exercise for Life Extension" in today's first installment was an exception), so that even the few of you who don't suffer acute short news withdrawal symptoms, may want to stop by from time to time ;-)

References

• Abdala-Valencia H, Berdnikovs S, McCary CA, Urick D, Mahadevia R, Marchese ME, Swartz K, Wright L, Mutlu GM, Cook-Mills JM. Inhibition of Allergic Inflammation  by Supplementation with 5-hydroxytryptophan. Am J Physiol Lung Cell Mol Physiol. 2012 Jul 27.  
• Bloom B, Cohen RA, Freeman G. Division of Health Interview Statistics Summary Health Statistics for U.S. Children: National Health Interview Survey, 2010. U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention National Center for Health Statistics. Hyattsville, Maryland December 2011. DHHS Publication No. (PHS) 2012–1578.
• Hulton AT, Gregson W, Maclaren D, Doran DA. Effects of GI Meals on Intermittent Exercise. Int J Sports Med. 2012 Jun 15.
• Macaluso F, Isaacs AW, Myburgh KH. Preferential Type II Muscle Fiber Damage From Plyometric Exercise. J Athl Train. 2012;47(4):414-20.
• Silva RF, Cadore EL, Kothe G, Guedes M, Alberton CL, Pinto SS, Pinto RS, Trindade G, Kruel LF. Concurrent training with different aerobic exercises. Int J Sports Med. 2012 Aug;33(8):627-34. Epub 2012 May 4.
• Sundstrup E, Jakobsen MD, Andersen CH, Jay K, Andersen LL. Swiss ball abdominal crunch with added elastic resistance is an effective alternative to training machines. Int J Sports Phys Ther. 2012 Aug;7(4):372-80.
• Vrieze A, Schopman JE, Admiraal WM, Soeters MR, Nieuwdorp M, Verberne HJ, Holleman F. Fasting and Postprandial Activity of Brown Adipose Tissue in Healthy Men. J Nucl Med. 2012 Jul 31. 
• Wojcicki JM, Heyman MB. Reducing childhood obesity by eliminating 100% fruit juice. Am J Public Health. 2012 Sep;102(9):1630-3. Epub 2012 Jul 19.

L-Tryptophan is Reduced While Dieting - Does This Make the Essential Amino Acid a Key to Succesfull Weight Loss?

Trp and it's metabolite 5-HTP may be particularly useful for female sugar cravings and binges.

Can l-tryptophan help you lose body fat? If you look at the results of the latest study from the University for Health Sciences, Medical Informatics and Technology it would seem that the answer to this question may be "Possibly, yes, but..." Before we come to the implications I would yet like to take a closer look at said study which shows that a lack of tryptophan (Trp) during diets does not just affect the biosynthesis of serotonin, but may also be associated with increased susceptibility for mood disturbances and carbohydrate craving. Accordingly, "strategies to supplement Trp while dieting could be highly useful in treating uncontrolled weight gain or in preventing neuropsychiatric symptoms" (Strasser. 2014).

Honestly, fasting and eating / skipping breakfast may be more promising weight loss tools

Breakfast and Circadian Rhythm

Does Meal Timing Matter?

Breakfast & Glucose Metab.

Breaking the Fast, Cardio & the Brain

Does the Break- Fast-Myth Break?

Fasting = Muscle- Loss - Always?

As Strasser et al. point out, both overweight and obesity go hand in hand with significant increases in low-grade inflammation. The latter is not just the reason that obesity increases the risk of cardiovascular disease, though. Recent evidence suggests that it is also associated with errors in the kynurenine (Kyn) pathway, in which tryptophan is broken down to kynurenine which in turn has been associated with increased risk of depressive symptoms, cognitive deficits in schizophrenia, Alzheimer's and, as mentioned before, cardiovascular disease. Weight loss, on the other hand,

"[...] has been shown to improve or prevent many of the aforementioned conditions. Bariatric surgical intervention in patients with adiposity was found not to improve tryptophan breakdown rates and other signs of immune activation and inflammation [4], whereas caloric restriction is known to be a strong activator of protective metabolic pathways, thereby leading to lower blood pressure, improved blood lipids, and reduced inflammatory markers, including CRP [9]. Still, little is known about the effects of an extreme short-term hypocaloric diet on Trp metabolism and changes in inflammatory biomarkers" (Strasser. 2014).

The study Barbara Strasser, Ken Berger and Dietmar Fuchs conducted was thus designed to assess the effect of a 2-week caloric restriction weight loss diet on Trp breakdown, leptin, and inflammatory biomarkers in over weight adults.

Taking tons of BCAAs can deplete your brain Trp and serotonin and leave you tired and depressed.

Beware of your beloved BCAAs,  Trp competes with the other large neutral amino acids (LNAA), namely valine, leucine, isoleucine, Tyr, and Phe for transport across the blood–brain barrier. In fact, scientists use large boluses of BCAAs to practically deplete tryptophan and thus reduce serotonin (Fernstrom. 2005). If you want to learn more about this unwanted side effects of BCAA, I'd suggest you take another look at my article "The Neurotransmitter Depleting Effects of Branched Chain Amino Acids (BCAAs) and Their Potential Ergolytic, Anxiogenic & Depressive Downstream Effects" | read more.

The scientists randomized 27 overweight and 11 obese participants (22 men and 16 women, mean age 52.8 ± 9.1 years) from the health center Lanserhof, Innsbruck–Lans, into two diet groups:

• a very low kcal diet group (VLCD; Ø 600 kcal/ day) and 
• a low kcal diet group (LCD; Ø 1,200 kcal/day). 

Only healthy subjects with BMI [25 kg/m²] between the ages of 35 and 70 years were accepted for the study. A physician performed physical examinations on all subjects before the study. Subjects were excluded if they consume any anti-inflammatory drugs (e.g., ibuprofen or aspirin) or supplements (such as antioxidants or fish-oil capsules). None from either group was involved in regular training programs.

Figure 1: Changes in body composition pre- vs. post (Strasser. 2015).

As the measurements of body composition, which were just like the energy intake and biologic markers conducted in all subjects before and after the 2-week energy restriction intervention period, indicate, both diets lead to significant reductions in body mass - and that almost exclusively in form of body fat.

Table 1: Biologic markers before and after a 2-week very low kcal diet (VLCD) or low kcal die (LCD) in 38 overweight subjects (mean ± SD)

"Data for biologic markers are shown in Table [1]. Fasting blood glucose declined significantly (P < 0.05) in the LCD group with no significant changes in insulin sensitivity in both groups after 2 weeks of caloric restriction. Weight loss diet lowered leptin levels in both groups, although not reaching the level of significance. Inflammatory biomarkers were not significantly altered during the trial, although there was a tendency toward an increase in IL-6 and TNF-a in the LCD group" (Strasser. 2015).

In contrast to what the researchers expected, both the Trp and Kyn concentrations decreased significantly by 21 and 16 % for VLCD and by 15 and 17 % for the LCD group, respectively, with no significant difference between groups. Practically speaking, this means that the ratio of Kyn/Trp concentrations did not change significantly in both groups.

Adding 900mg 5-HTP to the diet of obese women helps them to reduce their energy intake significantly (Cangiano. 1992).

5-HTP the better choice? While it makes sense to keep an eye on the Trp:LNAA ratio in your diet, it is questionable, whether supplementing with Trp on top of a Trp-sufficient diet will have significant beneficial effects. In this respect, 5-hydroxytryptophan aka 5-HTP a direct serotonin precursor appears to be the more promising supplement. Taken in dosages of 400-1,000mg/day it has been shown to (a) reduce food intake (up to 18% more than placebo in a 1989 study w/ obese women | Ceci. 1989), (b) increase weight loss in 12-week study with obese women (Cangiano. 1992) and (c) reduced the food and specifically carbohydrate intake in both male and female type II diabetics (Cangiano. 1998).

A significant reduction in Phe concentrations was only seen after VLCD. Neopterin and Tyr levels remained unchanged during the trial. Which leaves us with only one significant finding:

"Trp concentrations decreased significantly with a caloric restriction weight loss diet, and lowest Trp concentrations were observed in the group of individuals with the lowest calorie intake." (Strasser. 2015)

This reduction in Trp levels may well induce a disturbance in the biosynthesis of neurotransmitter 5-hydroxytryptamine (5-HT | Anderson. 1990), and appears to be associated with an increased susceptibility for depression (Widnet. 2002; Raison. 2009). Strasser et al. highlight:

Figure 2: The consumption of tryptophan-free amino acid supplements leads to highly significant increases in hunger ratings in healthy female subjects (Rieber. 2010).

"Because Trp is precursor in various biochemical pathways, e.g., it is hydroxylated by tryptophan-5-hydroxylase (T5H) into the intermediate product 5-hydroxy-tryptophan, which by decarboxylation is further converted to neurotransmitter 5-HT (serotonin), and because substrate saturation of T5H is only about 50 % (Dantzer. 2011), changes in plasma Trp levels may have an immediate impact on brain serotonin levels" (Strasser. 2014).

Experiments in which Trp was acutely depleted (in many studies by administering BCAAs | see red boy) support this assumption. Young et al. (2013), for example, confirmed that the acute depletion of tryptophan will lead to low serotonin and subsequently lower mood and increased aggression, although results vary somewhat between studies with similar participants.

Figure 3: Correlations between changes in tryp:LNAA ratio and appetite ratings (Gendall. 2000).

For the link to obesity, though, the correlation (r-values in Figure 3) between high Trp:LNAA (BCAAs, tyrosine, phenlylanine) and a reduction carbohydrate cravings, general hunger and binge eating is yet way more important - and that specifically for women, who appear more vulnerable than men both to the diet-induced reductions in Trp and to its consequences for brain serotonin function (Anderson. 1990).

Ah, and in case you are asking yourself why carbohydrate / sugar binges are a common consequence of low tryptophane:LNAA ratios, it's important to know that increases in glucose and insulin in response to high carbohydrate meals will trigger an increase in brain tryptophan and serotonin synthesis (Benton. 2002). This is why the effects of low tryptophan or high LNAA (BCAA, tyrosine, phenylalanine) levels are more pronounced if you avoid dietary carbohydrates.

There is evidence of direct effects of serotonine on metabolic rate, but there is no evidence that the administration of Trp will induce similar increases in fatty acid oxidation and thermogenesis as serotonin (Le Feuvre. 1991; Cui. 1993). It does therefore remain speculative whether the use of tryptophan supplements will have beneficial effects on the success of your next diet that go beyond an increased ability to stick to your predetermined caloric deficit due to reduced hunger and (CHO) cravings. Furthermore it's not 100% clear whether taking 5-HTP which is significantly closer to serotonin would have different and/or more pronounced beneficial effects compared to its precursor Trp.

This raises the question: Does supplementation help? It's one thing to observe correlations, it's another thing to have scientific evidence from controlled trials which support a causative link between higher tryptophan intakes and/or supplementation and increased adherence to calorically restricted diets and/or reduced cravings and binges.

Let's take the study by Rieber et al. (2010 | Figure 2), for example, in their study a tryptophan-free amino acid supplement like the ones people sell as muscle builders lead to significant increases in hunger scores in healthy young women. Only recently, scientists from the University of Barcelona were able to show that chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women. A result that suggests that chronic vs. acute treatments may have different effects, as well.

Direct evidence that tryptophan will also affect the reduction in energy expenditure, when dieting is yet not available from human trials. As of now, it's thus the reduction in appetite and cravings that is furthermore particularly pronounced in women that may considered among the scientifically warranted benefits of tryptophan supplementation and the avoidance of tryptophan depleting Trp-free amino acid supplements containing BCAAs, phenylalanine and tyrosine | Comment on Facebook!

References:

• Anderson, I. M., et al. "Dieting reduces plasma tryptophan and alters brain 5-HT function in women." Psychological medicine 20.04 (1990): 785-791. 
• Benton, David. "Carbohydrate ingestion, blood glucose and mood." Neuroscience & Biobehavioral Reviews 26.3 (2002): 293-308.
• Cangiano, Carlo, et al. "Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan." The American journal of clinical nutrition 56.5 (1992): 863-867.
• Cangiano, Carlos, et al. "Effects of oral 5-hydroxy-tryptophan on energy intake and macronutrient selection in non-insulin dependent diabetic patients." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 22.7 (1998): 648-654.
• Ceci, F., et al. "The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects." Journal of neural transmission 76.2 (1989): 109-117.
• Cui, Y., T. F. Lee, and L. C. H. Wang. "Thermoregulatory responses following injection of 5-hydroxytryptamine into the septohippocampal complex in rats." Pharmacology Biochemistry and Behavior 45.4 (1993): 935-939.
• Dantzer, Robert, et al. "Inflammation-associated depression: from serotonin to kynurenine." Psychoneuroendocrinology 36.3 (2011): 426-436. 
• Fernstrom, John D. "Branched-chain amino acids and brain function." The Journal of nutrition 135.6 (2005): 1539S-1546S.
• Gendall, Kelly A., and Peter R. Joyce. "Meal-induced changes in tryptophan: LNAA ratio: effects on craving and binge eating." Eating behaviors 1.1 (2000): 53-62. 
• Le Feuvre, R. A., L. Aisenthal, and N. J. Rothwell. "Involvement of corticotrophin releasing factor (CRF) in the thermogenic and anorexic actions of serotonin (5-HT) and related compounds." Brain research 555.2 (1991): 245-250.
• Nieuwenhuizen, Arie G., et al. "Acute effects of breakfasts containing α-lactalbumin, or gelatin with or without added tryptophan, on hunger,‘satiety’hormones and amino acid profiles." British journal of nutrition 101.12 (2009): 1859-1866.
• Raison, Charles L., et al. "CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-α: relationship to CNS immune responses and depression." Molecular psychiatry 15.4 (2009): 393-403.
• Rieber, N., et al. "Acute tryptophan depletion increases experimental nausea but also induces hunger in healthy female subjects." Neurogastroenterology & Motility 22.7 (2010): 752-e220.
• Strasser, Barbara, Ken Berger, and Dietmar Fuchs. "Effects of a caloric restriction weight loss diet on tryptophan metabolism and inflammatory biomarkers in overweight adults." European journal of nutrition (2014): 1-7.
• Widner, Bernhard, et al. "Neopterin production, tryptophan degradation, and mental depression—What is the link?." Brain, behavior, and immunity 16.5 (2002): 590-595.
• Young, Simon N. "The effect of raising and lowering tryptophan levels on human mood and social behaviour." Philosophical Transactions of the Royal Society B: Biological Sciences 368.1615 (2013): 20110375.