Friday, October 18, 2013

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)
  • Abourashed EA, Koetter U, Brattstr├Âm 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 ╬▓ -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.