Natural Migraine Prophylaxis & Treatment: Riboflavin, ALA, Magnesium, CoQ10, Feverfew, Melatonin, Butterbur & Co.

Natural migraine protection: Even if supps won't cure it, they can at least reduce the number of "bad days" and the severity of the attacks.

In the last installment of the "Short News" you've learned about the enormous costs chronic pain produces on an annual basis: Roughly $300 billion for its treatment and another $300 billion in form of economic damage. No wonder pain killers, Cox inhibitors and & co are among the top selling and drugs in the world.

Now, migraine is unquestionably among the most debilitating forms of chronic or rather cyclic chronic pain and while women are much often hit by the pain from withing (21.8% v.s 10.0% of the US citizens suffer; NHS 2009). And while I cannot tell you how much of the $2,000 bucks each of you is "spending" on an annual base on treating the pain of his / her fellow citizens, I believe that both of you, my dear mal and female readers, may benefit from the information in today's installment of "On Short Notice" with a comprehensive, but probably not all-encompassing list of promising supplemental agents for migraine prophylaxis and "treatment":

• magnesium: I have actually mentioned that in a previous SuppVersity post already (read more), but I guess it's well worth mentioning it again. Low brain magnesium levels have been reported in a whole host of observational studies in migraineurs. There have also been a couple of respective trials with overall inconclusive, but rather positive results for the acute treatment of patients with aura and, possibly, perimenstrual migraine prophylaxis.
  
  The magnesium formulation that has been used in these trials varied, and there is no large(r) scale comparison of different forms and dosing regimen as of now. Corresponding effects have been observed with 250mg of intravenous and 600mg of oral magnesium chelates (Cady. 1998; Mauskop. 1998), for example. Evans and Taylor additionally cite the following four randomized controlled trials (RCTs; my emphases):

  Take a form that does not give you diarrhea! If you look at the success rates it would appear as if  the organic formulas are superior to the inorganic ones. On the other hand, this may be a simple effect of the increased rates in diarrhea reported by many researchers using non-organic formulations. After all, this does not simply reduce magnesium absorption but will also have negative effects on the overall mineral and water balance. Both, dehydration and mineral imbalances could otherwise increase instead of decrease your risk to suffer from migraine attacks.

  "The first RCT of magnesium for migraine prevention involved only 20 subjects and was positive; the active therapy was 360 mg Mg++ pyrrolidone carboxylic acid divided TID. The second RCT, by Peikert et al, involved 81 adult women and 600 mg magnesium (trimagnesium dicitrate) daily demonstrated a 41.6% improvement with verum versus 15.8% for placebo. The third RCT for migraine prophylaxis, published by Pfafferath et al, involved 69 patients taking 486 mg magnesium; no benefit for magnesium was found; at the end of the 3-month treatment phase, the responder rate was 28.6%in the magnesium group and 29.4% in placebo subjects, according to the primary efficacy endpoint. [...] In a last trial, Wang et al gave magnesium oxide 9 mg/kg divided TID to subjects aged 3 to 17 years. Approximately three-quarters of eligible subjects completed the study, with a significant downward trend in headache days in the active treatment group versus placebo; the lack of any difference in the slope of treatment trends, however, was such that no significant superiority of magnesium over placebo could be documented." (Evans, 2006)

  While magnesium's acute effects are usually ascribed to increases in the circulating levels of Mg++ ions, it's efficacy as a prophylactic treatment is most likely a result of increasing tissue levels and requires a minimum of 3 to 4 months for measurable benefits to occur.
• CoQ10: As a student of the SuppVersity you are well aware of the beneficial (actually vital!) importance of CoQ10 on mitochondrial health. It is an endogenous enzyme cofactor that can be produced by your body. Unfortunately, there are certain conditions and medications that lead to the depletion of CoQ10 and subsequently impair the proton-electron translocation across the mitochondrial membranes.
  
  

  

  No headache, no problem, but not a reason not to consider CoQ10 supplementation. CoQ10 can also help if your exercise performance is what gives you headaches: "300mg CoQ10 Boost Peak Power Increases in Young Elite Athletes. Plus: 140ml of Beet Root Juice, That's all it Takes to Minimize the Oxygen Demands During a Workout" (learn more)

  Against that background and in view of the involvement of mitochondrial malfunction in the etiology of migraine, it is not surprising that Rozen et al. observed in a 2002 open label study in which 61%  of the 31 patients who consumed 150mg CoQ10 daily for 3 months had at least a 50% reduction in migraine days without experiencing any significant adverse events. Interestingly, the supplement took "only" 4 weeks to kick in (a follow up on whether or not it was necessary to stay "on" CoQ10 is not available, but I would consider it likely). In 2005 Sandor et al. conducted one of the few randomized controlled trials: In this particular study, the patients received 100mg of CoQ10 three times daily and saw significant decreases in the attack frequency, the number of headache days, and days with nausea.
  
  Interestingly the highly soluble version of CoQ10 (a liquid formulation of water dispersed nano-particles comprising a supercooled melt of CoQ10 with modified physicochemical properties; GuttaQuinone) that was used in the Sandor study had some side effects (gastrointestinal disturbances and cutaneous allergy that had not been reported in other studies). Overall, CoQ10 is yet perfectly safe (even if it's nano-sized) and may even yield benefits if you don't suffer from migraine.
• Tanacetum parthenium: Also known as Feverfew, the dried chrysanthemum leaves have a long history as an analgesic and one huge problem, according to the only available peer-reviewed report, preparations of feverfew have shown a >400% variation in dosage strength of the known active ingredient parthenolide (Rossi. 2005). According to evens Evans & Taylor, some experts even doubt if it can be generally assumed that parthenolide, which has some very promising research to back up its efficacy even is the active ingredient in the plant leaves.
  

  

  Feverfew does not look exactly, like powerful medicinal plant, right?

  "In a systematic review, Vogler et al reported on randomized controlled trials (RCTs) involving feverfew for migraine prophylaxis conducted prior to 1998. 11-16 Five studies qualified by Jadad score as adequate; 1 has been published in abstract form only, and only 216 subjects in total have been studied. Vogler et al concluded, “In view of the popularity of feverfew, perhaps the most striking finding was the paucity and low average quality of the existing RCTs on the subject.”

  If you wanted to cut it short you could thus say. It's popular, people swear by it, but according to our current knowledge it may as well be the placebo effect that keeps people coming back to this natural remedy for headaches.
  
  The latter would be nasty, since Feverfew does actually have a handful of side effects that range from a sore mouth and tongue (including ulcers), over swollen lips, loss of taste, abdominal pain, and GI disturbances, up to the occasional report of what Evans & Taylor call the "post-feverfew syndrome" of joint stiffness and aches that were accompanied by (guess what) increasing headaches! In the MIG-99 trials, which used an isolated and highly standardized 6.25 mg dose of parthenolide the number of adverse events were similar. It would thus seem very likely that many of the side effects are brought about either by the initially mentioned natural fluctuations in the active or - and this is even more likely - by other agents in the feverfew leaves.
• Riboflavin: Also and probably better known as vitamin B2, riboflavin has only few quality trials to support its efficiency with its importance in the mitochondrial energy chain and its role in the electron transport within the citric acid cycle, it does, however, appear to be likely that the otherwise often overlooked "yellow-green pee"-vitamin may actually help reduce the number of migraine attacks by >50% (that's 35% more than w/ 25mg/day; Schoenen. 1998), when it is consumed in doses of 400mg/day.

  

  This table shows the nutrient combination of a supplement that has been found to optimize mitochondrial function in a 2011 study (learn more) and it has not just riboflavin, but also lipoic acid and coQ10, both of which are also on the list of "anti-migraine supplements" - certainly no coincidence! Migraine is after all about mitochondrial health and disease.

  The only known side effects researchers observed in the few available randomized controlled trials were diarrhea and polyuria - and those were pretty rare. Evans & Taylor do yet point out that despite its non-toxicity and the non-existence of a tolerable upper intake level they wouldn't recommend high-dose riboflavin consumption to pregnant women, simply because the possible health effects on the unborn child are not known yet.
• Alpha lipoic acid: Certainly less known and not well-researched are the potential benefits of ALA (it is thus not necessary to buy R-ALA, which was in the formula of the supplement mentioned on the label of the table above). A double-blind, placebo-controlled trial by Magis et al. from the year 2007 was yet able to show a reduced monthly attack frequency with alpha lipoic acid at dosages of 600 mg daily after 3 months. It must be said, though that these results were not significantly different from those in the placebo group. Within-group analyses did yet reveal a significant reduction in attack frequency, headache days and headache severity in patient treated with alpha lipoic acid, but not in the placebo group (Magis. 2007)
• Buttebur:
  A note of caution: The Butterbur plant contains pyrrolizidine alkaloids which are
  hepatotoxic and carcinogenic, these compounds have to be removed before you can safely use this plant from the genus of Asteraceae  to counter / prevent headaches.
  Petasites hybridus or rather extracts of its root have gotten some attention as a potential migraine treatment, as well. Petasites is thought to act through calcium channel regulation and inhibition of peptideleukotriene biosynthesis. These cells are thought to play an important role in the inflammatory cascade associated with a migraine (Sheftell. 2000; Pearlman. 2001). A randomized, double-blind, placebo-controlled trial by Grossman & Schmidrams (2000) found that the consumption of 50 mg of butterbur twice daily yielded significantly reduced number of migraine attacks and migraine days per month. Similar results with 50mg of Petasites extract were also reported by Lipton et al. (2004). Finally, a multicenter prospective open-label study of butterbur in 109 children and adolescents with migraine resulted in 77% of all patients reporting a reduction in migraine frequency of at least 50% (Pothmann. 2005).
  
  Serious adverse events were not observed in any of the few hitherto published studies. Overall, butterbur was well tolerated and the most frequently reported adverse reactions were mild gastrointestinal events, predominantly eructation (burping). 
• Melatonin: Yep, you will be hard pressed to find anything melatonin the pineal sleep hormone is not good for. So it is probably not very surprising that it is on the list or rather the end of a list potential natural(*) anti-migraine supplements (some critics will probably say that supplementing with melatonin is not "natural").
  

  • 

    Sleep is good for everything and if you look back at the past SuppVersity articles on the pineal hormone this seems to apply to melatonin, as well.

    1999, Leone et al. were among the first to report beneficial effects of 10mg of melatonin on cluster headaches; yet while this worked magically in some, other patients did not appear to benefit at all (Leone. 1999)
  • melatonin appears to be an effective alternative for indomethacine in idiopathic stabbing headache (Rozen. 2003)
  • cluster migraine which often goes hand in hand with a lack of melatonin secretion has been shown to respond to 9 mg melatonin taken at bed time (Peres. 2001)
  In a 2005 review of the literature Peres does yet point out a multitude of mechanisms by which melatonin could help alleviate headaches, including "its anti-inflammatory effect, toxic free radical scavenging, reduction of proinflammatory cytokine up-regulation, nitric oxide synthase activity and dopamine release inhibition, membrane stabilization, GABA and opioid analgesia potentiation, glutamate neurotoxicity protection, neurovascular regulation, serotonin modulation, and the similarity of chemical structure to that of indomethacin" (Peres. 2005). Despite the fact that large(r) scale randomized controlled trials are absent, up to know. I personally would certainly give it a try.

Aside from "real medications" (I wonder where you can make the distinction between a supplement like thiotic acid aka ALA and a medicinal agent like aspirin?), there is also a "consistent level of evidence"for the usefulness of acupuncture, which has proven to be superior to no or placebo treatment and works as an adjunct to conventional treatment (Schiaparelli. 2010).

There is one thing left to mention that may even work better than any of the previously enumerated supplements: Prevention! While many people don't really know the cause of their migraine attacks there are a couple of known food triggers you may want to avoid or even test (Peatfield. 1984; Scharff. 1995):

• 

  MSG in fast food is a problem (learn more about MSG)

  Alcohol -- 29-35% of people with migraine are sensitive to mankind's most consumed poison
• Chocolate -- 19-22% of the migraine sufferers worldwide are sensitive to the sweet superfood
• Cheese -- 9-18% don't tolerate the tyramine which can also be found in other fermented foods
• Caffeine -- 14% of the patients report that the vasoconstrictive effects of caffeine make the headaches significantly worse
• MSG -- 12% of the migraine sufferers report that eating high mono-sodium glutamate foods gives them the "Chinese Restaurant Migraine"

Theoretically, each and every food item could trigger migraine attacks, therefore I would not suggest relying on this list all too much. Instead of just testing those 5 and resigning, when you are unable to trigger/avoid migraines by consuming/abstaining from them, I'd strongly advise to start a food diary, in which you log everything you eat, drink and supplement (nitrates are by the way notorious for triggering headaches, as well) + your migraine symptoms. Once you go through the notes you should be able to identify what causes the problem, if it has any dietary cause at all.

References:

• Cady RK, Farmer K, Altura BT, et al. The effect of magnesium on the responsiveness of migraineurs to a 5-HT1 agonist.Neurology.1998;50(suppl 4):A340. 
• Evans RW, Taylor FR. "Natural" or alternative medications for migraine prevention. Headache. 2006 Jun;46(6):1012-8. Review.
• Grossman M, Schmidrams H. An extract of Petasites hybridus is effective in the prophylaxis of migraine.Int J Clin Pharmacol Ther.2000;38:430–435.
• Leone M, D'Amico D, Moschiano F, Fraschini F, Bussone G. Melatonin versus placebo in the prophylaxis of cluster headache: a double-blind pilot study with parallel groups. Cephalalgia. 1996 Nov;16(7):494-6.  
• Lipton RB, Gobel H, Einhaupl KM, et al. Petsites hybridus root (butterbur) is an effective preventive treatment for migraine.Neurology.2004;63:2240–2244.
• Magis D, Ambrosini A, Sándor P, Jacquy J, Laloux P, Schoenen J. A randomized double-blind placebo-controlled trial of thioctic acid in migraine prophylaxis. Headache. 2007 Jan;47(1):52-7.
• Mauskop A, Altura BM. Role of magnesium in the pathogenesis and treatment of migraines.Clin Neurosci.1998;5:24-27.
• Pearlman EM, Fisher S. Preventive treatment for childhood and adolescent headache: role of once-daily montelukast sodium.Cephalalgia.2001;21:461
• Peatfield RC, Glover V, Littlewood JT, et al. The prevalence of diet-induced migraine.Cephalalgia.1984;4:179–183.
• Peres MF, Rozen TD. Melatonin in the preventive treatment of chronic cluster headache. Cephalalgia. 2001 Dec;21(10):993-5.
• Peres MF. Melatonin, the pineal gland and their implications for headache disorders. Cephalalgia. 2005 Jun;25(6):403-11. 
• Pothmann R, Danesch U. Migraine prevention in children and adolescents: results of an open study with a special butterbur root extract.Headache.2005;45:196–203.  
• Rossi P, Di Lorenzo G, Malpezzi MG, et al. Prevalence, pattern and predictors of use of complementary and alternative medicine (CAM) in migraine patients attending a headache clinic in Italy.Cephalalgia.2005;25:493-506. 
• Rozen TD, OshinskyML, Gebeline CA, et al. Open label trial of Coenzyme Q10 as a migraine preventive. Cephalalgia. 2002;22:137–141.
• Rozen TD. Melatonin as treatment for idiopathic stabbing headache. Neurology. 2003 Sep 23;61(6):865-6. 
• Sandor PS, DiClemente L, Coppola G, et al. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Neurology. 2005;64:713–715.
• Scharff L, Turk DC, Marcus DA. Triggers of headache episodes and coping response of headache diagnostic groups. Headache.1995;35:397–403. 
• Schiapparelli P, Allais G, Castagnoli Gabellari I, Rolando S, Terzi MG, Benedetto C. Non-pharmacological approach to migraine prophylaxis: part II. Neurol Sci. 2010 Jun;31 Suppl 1:S137-9.
• Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial.Neurology.1998;50:466-470 
• Sheftell F, Rapoport A, Weeks R, et al. Montelukast in the prophylaxis of migraine: a potential role for leukotriene modifiers.Headache.2000;40:158–163. 
• Srivastava KC, Mustafa T. Ginger (Zingziber officinale) in rheumatism and musculoskeletal disorder. Med Hypotheses.1992;33:342–348.
• Sun-Edelstein C, Mauskop A. Foods and supplements in the management of migraine headaches. Clin J Pain. 2009 Jun;25(5):446-52.

300mg CoQ10 Boost Peak Power Increases in Young Elite Athletes. Plus: 140ml of Beet Root Juice, That's all it Takes to Minimize the Oxygen Demands During a Workout

Athletes from various sports train at the Olympic Camp, where the CoQ10 study was conducted.

As unfortunate as it may sound, the number of "next big things" in the area of performance enhancing (legal) substances - at least in large parts - a line-up of supplemental non-starters. Against that background it is all the more surprising that today' SuppVersity article features not one, but two already available supplements that could in fact make a valuable contribution to your workout regimen. And while we are going to take a brief look at the latest research on the ergogenic effects of beet root juice later, we will start out with a study the results of which did actually surprise me - in a positive sense, that is.

• Reduced CoQ10 (ubiquinol) increases peak power in trained athletes (Alf. 2013) -- While previous studies on the efficiacy of CoQ10 demonstrated at best inconclusive and statistically, but mostly practically insignificant benefits, the latest study from the Olympiastützpunkt Rhein-Ruhr in Essen, Germany, reports a whopping +11% increase in peak power per kg body mass in the 53 males and 47 females young German athletes (average age 19.2 years, height 181 cm, weight 78 kg) who consumed 5x 60mg ubiquinol, the completely reduced form of CoQ10, which comes in three redox states, i.e. fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol), on a daily basis day as a supplemental adjunct to their 6-week training regimen.
  

  

  Figure 1: Progress of absolute peak power in the placebo and 5x60mg ubiquinol group (Alf. 2013)

  While it is not possible to tell, whether it was the comparatively long study period (CoQ10 needs week to build up in the tissue; cf. Cooke 2008), the high dose of ubqiuinol (previous studies with 150mg did not yield comparable results, cf. Svensson. 1999) or a combination of both thats responsible for the ergogenic effects you see in figure 1 cannot be said for sure. What is however certain and actually pretty remarkable, if you take into account that these young athletes were all training regularly at the Olympic Training Camp Rhein-Ruhr in Essen and that many of them have been competing at the Olympic Games 2012 in London., is that the supplemented athletes did make 2.5% more out of  their 6 weeks at the camp.
  Addendum: In view of the fact, that Rick just asked about potential side effects on facebook and I assume that, smart as you are, you will immediately spot the 2009 study by Sumien et al. talking about detrimental effects on cognitive function, I want to point out that the human equivalent of 2.6mg/g chow the high dose group received would exceed an ubiquinol intake of >6g even for the lightweights of you. With 1/4 of the dosage not producing any long-term negative sides in the same rodent study, you are thus probably on the save side w/ 300mg/day. This hypothesis is by the way backed by a 2008 review by Hidaka who report a no-observed-adverse-effect level (NOAEL) of 1200 mg/kg/day derived from a 52-week chronic toxicity study in rats that would translate to 720 mg/day for a person weighing 60 kg (Hidaka. 2008)
  Moreover, the way in which the gap between the supplement and placebo group widens only in the last weeks of the intervention seem to support the previously mentioned "pre-loading hypothesisand raises the hope that the ergogenic effects will persist for more than just 6 weeks.
  
  

  

  CoQ10 did work in previous studies, but affected mostly serum markers not performance (learn more)

  The researchers also speculate that "older athletes and “weekend warriors” might profit even more from CoQ10 supplementation than young, well-trained athletes", as both age and the lack of training are associated with a lower mitochondrial density, of which Alf et al. suspect that it may be compensated for by the provision of CoQ10. In view of it's purported beneficial effects on ATP and creatinine phosphate synthesis, this may well be the case. I would yet still refrain from buying a year-long supply of the ubiquinol before respective evidence from independent trials is available. I mean, with the current price tag on ubiquinol, even an N=1 experiment with a 6-weeks supply of 300mg of ubiquinol per day would cost you ~$60 which is not exactly cheap, but could be worth a try - assuming you have the patients to wait for the results.

• 280ml beet root concentrate have well-established ergogenic effects, more is not necessary (Wylie. 2013) -- Right from the Exeter University comes a new study on the ergogenic effects of beet root juice. While the main message of the paper is that beet root juice supplementation can effectively increase nitric oxide levels and physical performance, the real interesting part of the paper deals with the dose-response relationship.
  
  

  

  There are a couple of important confounding factors which will determine whether or not you or anyone else can benefit from nitrate supplementation. Sex is yet - as far as I know know - not one of them... ah, by the way, there may be other benefits to nitrates that are "sex-specific", but in this case the semantics are somewhat different (learn more in a previous post on beet root  juice here at the SuppVersity ;-)

  Lee J. Wylie and his colleagues found that the provision of 70, 140 or 280 ml of concentrated beet root juice (BR), with 4.2, 8.4 and 16.8 mmol NO3- on six separate occasions increased the plasma concentration of NO2- in a dose-dependent manner, with the peak changes occurring at ~2-3 h. Of the three dosing regimen,
  

  "[...] only the higher dosages (140ml and 280ml) reduced the steady-state VO₂ during moderate-intensity exercise by 1.7% (P=0.06) and 3.0% (P<0.05), whilst time to task failure was extended by 14% and 12% (both P<0.05), respectively" (Wylie. 2013)

  As the scientists point out, these results indicate that "there is no additional improvement in exercise tolerance after ingesting BR containing 16.8 compared to 8.4 mmol NO3-".
  
  The dreaded carb overload that may have popped in your head, whenever you heard about using a natural NO3- supplement should not keep you from taking advantage of nature's very own "nitric oxide supplement" ;-)

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Bottom line: In view of the fact that ubiquinol and beet root juice act via totally different pathways, a direct comparison of the two obviously doesn't make sense. A combination of both on the other hand would. I would not expect any synergistic affects, but it is relatively save to assume that the effects will add up.One thing you should keep in mind, thoug,h is that only the beets will have acute effects and provide the instant gratification everybody seems to be striving for, these days. The effects of coqu10 n the other hand will manifest only weeks after you started taking it, so that you will - for want of an independent control you will thus simply have to beleive that its working ... after all, you don't know how much progress you wouls make without it.

References:

• Alf D, Schmidt ME, Siebrecht SC. Ubiquinol supplementation enhances peak power production in trained athletes: a double-blind, placebo controlled study. J Int Soc Sports Nutr. 2013 Apr 29;10(1):24. 
• Cooke M, Iosia M, Buford T, Shelmadine B, Hudson G, Kerksick C, Rasmussen C, Greenwood M, Leutholtz B, Willoughby D, Kreider R: Effects of acute and 14-day coenzyme Q10 supplementation on exercise performance in both trained anduntrained individuals. J Int Soc Sports Nutr2008, 5:8.  
• Hidaka T, Fujii K, Funahashi I, Fukutomi N, Hosoe K. Safety assessment of coenzyme Q10 (CoQ10). Biofactors. 2008;32(1-4):199-208.
• Sumien N, Heinrich KR, Shetty RA, Sohal RS, Forster MJ. Prolonged intake of coenzyme Q10 impairs cognitive functions in mice. J Nutr. 2009 Oct;139(10):1926-32. doi: 10.3945/jn.109.110437.
• Svensson M, Malm C, Tonkonogi M, Ekblom B, Sjodin B, Sahlin K: Effect of Q10 supplementation on tissue Q10 levels and adenine nucleotide catabolism during high-intensity exercise. Int J Sport Nutr1999, 9:166–180. 
• Wylie LJ, Kelly J, Bailey SJ, Blackwell JR, Skiba PF, Winyard PG, Jeukendrup AE, Vanhatalo A, Jones AM. Beetroot juice and exercise: pharmacodynamic and dose-response relationships. J Appl Physiol. 2013 May 2.

Antioxidants For Lazy Rodents: Alpha Lipoic Acid + CoQ10 + Vitamin E Work Mitochondrial Wonders On Untrained Female Mice... And ONLY On Untrained Female Mice!

ACE!? Are alpha lipoic acid, coQ10 and vitamin E good for them or not?

With all the bad press on anti-oxidants, you could actually get the impression that performance and longevity should be a function of the amount of oxidative stress you're exposed to.

Despite the fact that this hypothesis may have it's merit, the "True or False" item on the negative side effects of eccentric training should probably have reminded you that keeping a balance between the constant oxidative assault from our environment (in the broadest sense) on the one hand and our bodies' continuously evolving defense system is what we should actually be aiming for.

Whether or not we will benefit from an increase in exogenous anti-oxidants like vitamins, will therefore always depend on both the stressor and the state and performance of our anti-oxidant defense system. A recent paper that has just been published in the peer-reviewed online journal PLOS-ONE does actually appear to confirm this notion of "stress management". In other words:

Adaptation occurs, when you expose yourself to stressors which are taxing, but won't obliterate your defense system = the "i + 1" / hormesis principle

We know from previous human studies that vitamin C and vitamin E (1g Vit C, 400IU Vit E; about as much as you will find in any of the useless "high performance multis") can blunt the hormetic effects of exercise-induced oxidative stress on insulin sensitivity and the concomitant adaptive response of the endogenous antioxidant defense system (Ristow. 2009).

Figure 1: TBARS in the supplemented (no improve in insulin sensitivity) and non-supplemented trainees (Ristow. 2009)

A quick note on how to interpret study results: Whenever you take a look at one of the "pro-antioxidant studies", you got to make sure the scientists don't base their assessment that the use of the respective molecule was beneficial on the observation of a reduction in exercise induced stress.

If the (mito-)hormesis theory holds, the amelioration of the latter in the 2009 study by Ristow (see figure 1) is in fact to blame for the absence of increases in insulin sensitivity, adiponectin, etc.

The results of the Ristow study have caused quite an upset within the scientific community and the world of physical culture. Especially within the latter the results of the researchers from the University of Jena were often misinterpreted as "all anti-oxidants are bad for you" and then prematurely dismissed on the basis of studies in which the researchers were able to observe mostly marginal and in terms of the explanations in the red info box above, highly questionable "beneficial" effects of anti-oxidant supplements.

Not all "antioxidants" are created equal

Suggested read: In a 2012 letter to the proponents of the mitohormesis hypothesis pick the results of a paper by Higishada et al. that's often cited in support of vitamin C + E supplementation to pieces and conclude "The vast majority of experimental evidence clearly advises against this supplementation. Thus, we unreservedly confirm the conclusions derived from our previous research and disagree with Higashida et al. In our opinion, antioxidant supplements are, at the least, useless" (Gomez-Cabrera. 2012). The letter should be accessible for all of you, so feel free to read up on the evidence they provide to support this conclusion... keep in mind, though no honest scientist will claim he would tell you the one and only truth. What they will give you is their assessment of the facts and the conclusion they believe should be drawn based on these facts.

In fact, the actual number of exercise interventions in which scientists observed real-world benefits from vitamin C and vitamin E, in particular, is often overestimated. Therefore neither of these most prominent members of a very broad class of molecules that carries the label "antioxidant" can be considered a "proven ergogenic" and it is therefore not very surprising that Nikolaidis et al. conclude their 2012 review of the literature on the words:

"Based on the contradictory evidence regarding the effects of higher intakes of vitamin C and/or E on exercise performance and redox homeostasis, a permanent intake of non-physiological dosages of vitamin C and/or E cannot be recommended to healthy, exercising individuals." (Nikolaidis. 2012)

Now, despite the fact that the acronym may be the same (ACE usually stands for beta carotene, vitamin C and vitamin E), the "antioxidant" supplement in the study at hand has a different makeup. While it does contain vitamin E, it does not contain the additional "kamikaze vitamin" ascorbic acid, which cannot distinguish between "good" and "bad" ROS formation and will - much like a fire extinguisher - quench both "smoke signal" that's telling your boy "the mitochondrial engine is running at full speed, it may be time for an upgrade", as well as the not so beneficial "sparking" that occurs when the engines are overheating.

Does the mix make the difference?

CoQ10 on the other hand, is more or less specialized on protecting the mitochondria. It is not a "fire extinguisher", but rather a fire-proof coating that protects the mitochondria from "leaking" reactive oxygen specimen into the circulation. In conjunction with the cell-membrane protecting effects of vitamin E and the "vitamin recycler" alpha lipoic acid, we get a highly specialized antioxidant stack of which the results of the study at hand show that it is beneficial in those situations, where the baseline protection against an imposed stressor is insufficient.

Figure 2: Differential effect of anti-oxidant supplementation on trained (8 wks treadmill running) (n = 12/group) and untrained (n = 24/group) male and female rodents' endurance performance; data presented in meters (Abadi. 2013)

If you do now take a peak at the data in figure 2 you will realize that the latter was the case in the female rodents who were not exposed to the chronic exercise regimen. Correspondingly the provision of the ALA + CoQ10 + vitamin E stack did improve the exercise performance and mitochondrial respiratory chain protein capacity. The same data plot does yet also reveal that these effects were sex and training specific and generally absent in the trained rodents.

Figure 3: Questionable (female) and non-existant (male) "benefits" of antioxidant supplementation on the relative expression of the mitochondrial builder PGC-1a, the satellite cell recruiting "stress" kinase p-38 MAPK and the well known glucose sensitizing AMPK (Abadi. 2013)

One of the many things, Abadi et al. don't mention, though, is the fact that the "reduced the activation of the stress kinase p38-MAPK following acute exercise in untrained" (Abadi. 2013, cf. figure 3) could also decrease the "repair" and supercompensation process that will take place after the unaccustomed (remember the data in figure 3 is from untrained animals after the 2nd exercise test). After all, the "stress kinase" is at the same time "a molecular switch for satellite cell activation" (Jones. 2005) and thus heavily involved in the recruitement of satellite cells.

"Voilà it works.... ahm, ok only in one out of four groups, but it works!"

Similarly, Arkan Abadi and his colleagues unfortunately forgot to mention is that they did not measure "THE" training-induced adaptations in the sense of "all training induced adaptations", but only a couple of mitrochondrial protein expressions. Against that background we cannot exclude that the insulin sensitizing effects of exercise Ristow et al. have been missing in their human subjects was not blunted in Abadi's C57Bl/J6 mice, as well.

Remember the case is not yet settled: This is an analysis of a single study and the fact that this suggests that CoQ10, ALA and vitamin E are worthless for the majority of trainees does neither negate that the provision of only on of them, e.g. 200mg/day CoQ10 in athletes taking statins (Deichmann. 2012), or the provision of respective supplements during specifically stressful training periods can have ergogenic effects.

The absence of more comprehensive data on the actual metabolic effects of the supplement regimen, as well as the unexplained confounding effects of gender and training status, specifically the non-significant, yet paradoxically opposed effects the scientist observed in the male rodents certainly warrant the question, why the abstract focuses almost exclusively on the already moderate benefits they observed in the untrained females. After all, the scientists declare that the

"study was undertaken to investigate the effects of dietary supplementation with vitamin E, a-lipoic acid, and CoQ10 in combination on basal and training-induced mitochondrial adaptations in mice." (Abadi. 2013)

In other words, their interest was in the effectiveness in mice in general and not in untrained female mice. Against that background, the most significant finding of the study would actually have been that there are confounding factors rendering the combination of these three mitochondrial antioxidants useless.

---

Figure 4: Health and longevity as a function of mitochondrial reactive oxygen species (ROS) formation.
Both too much and too little ROS are detrimental, due to either insufficient stimulus for or overtaxing of hormetic processes (this graph is a mere illustration and is not based on any existing experimental data and was first published in a previous SuppVersity article from May 2011)

Bottom line: I bet you will soon see the results, or rather excerpts of the results of this study referenced on the bottles and shiny adverts of the supplement industry. "Most recent studies show that the combination of alpha lipoic acid, CoQ10 and vitamin E in RippYouOffSupplements (ROS) newest product increases ..." You know the whole spiel and are probably not fooled by pseudo-scientific nonsense like that anyway.

Take a look at the data and use your gray matter: Are you rather an untrained female mouse? Or would you rather describe yourself as a devoted physical culturist?  If choose the 2nd option, you don't have to rack your brain any longer about the what ifs and maybes pertaining to potential reductions in the exercise induced increase in insulin sensitivity, because the "scientific evidence" ROS presents in favor of the efficacy of their newest "blockbuster product" is not relevant for you, anyway.

Now that I am done ranting, I should maybe add that I sill like this study. Not just as an educative example of how easily scientifically valid data can be abused to provide proof for whatever you want, by simply skipping on parts of the results, but also because it adds sex as a new confounding factor you have to keep in mind, when you compare studies on the useful an uselessness of antioxidant supplements. And that's not just in an exercise, but also in any other scenario (e.g. longevity, metabolic syndrome, etc.) - after all, the gender-difference was present only in the non-exercised rodents.

References:

• Abadi A, Crane JD, Ogborn D, Hettinga B, Akhtar M, Stokl A, MacNeil L, Safdar A, Tarnopolsky, M. Supplementation with a-Lipoic Acid, CoQ10, and Vitamin E Augments Running Performance and Mitochondrial Function in Female Mice.
• Deichmann RE, Lavie CJ, Dornelles AC. Impact of coenzyme Q-10 on parameters of cardiorespiratory fitness and muscle performance in older athletes taking statins. Phys Sportsmed. 2012 Nov;40(4):88-95.
• Gomez-Cabrera MC, Ristow M, Viña J. Antioxidant supplements in exercise: worse than useless? Am J Physiol Endocrinol Metab. 2012 Feb 15;302(4):E476-7; author reply E478-9.
• Higashida K, Kim SH, Higuchi M, Holloszy JO, Han DH. Normal adaptations to exercise despite protection against oxidative stress. Am J Physiol Endocrinol Metab. 2011 Nov;301(5):E779-84.
• Jones NC, Tyner KJ, Nibarger L, Stanley HM, Cornelison DD, Fedorov YV, Olwin BB. The p38alpha/beta MAPK functions as a molecular switch to activate the quiescent satellite cell. J Cell Biol. 2005 Apr 11;169(1):105-16.
• Nikolaidis MG, Kerksick CM, Lamprecht M, McAnulty SR. Does vitamin C and E supplementation impair the favorable adaptations of regular exercise? Oxid Med Cell Longev. 2012;2012:707941.
• Ristow M, Zarse K, Oberbach A, Klöting N, Birringer M, Kiehntopf M, Stumvoll M, Kahn CR, Blüher M. Antioxidants prevent health-promoting effects of physical exercise in humans. Proc Natl Acad Sci U S A. 2009 May 26;106(21):8665-70.

Grass-Fed Pork? Not Really. Still the Difference in Fatty Acid Composition & Micronutrient Content Are Profound & Not Accounted for by Food Databases - Let Alone Epidemiology

You often hear that pigs are pretty closely related to us humans, but "are all pigs created equal"? Or what may be a more appropriate question for the SuppVersity: Is all pork really created equal?

If you like databases like nutritiondata.com or the USDA's very own detailed nutrient database in order to evaluate whether your diet is actually delivering all the nutrients you need you are probably missing half of the picture. At least as far as the more sophisticated details go, a recent paper from the Instituto de Ingeniería de Alimentos para el Desarrollo at the Universidad Politécnica de Valencia clearly indicates that you would at least have to consider what the animals, in this case pork, were fed and from which muscle of the animal the piece of meat you are eating has been cut, in order to get an approximate idea of how much of unquestionably health relevant micronutrients, such as coQ10, carnosine, anserine, taurine, creatine glutamine or haem you get - and in some cases the differences can be way larger than 100%!

If pizza salami equals pork...

... in epidemiological studies, how can these studies on the fallacies and advantages of eating red meat, which usually get a hell lo of media attention, be accurate, given the fact that the amount of unquestionably beneficial coQ10, for example, would differ by 60 percent, even if you would only ignore the difference between loin that was cut from the trapezius (= high coQ10 content) and the longissimus dorsi (=low coQ10 content)?

Figure 1: Content of selected amino acids and micronutrients in cuts from different muscle; data expressed relative to respective mean (total value is given in mg/100g above the bars) of all tested muscle samples (data based on previous studies by the co-authors that have been compiled for Reig. 2012).

Moreover, if you take a look at the complete data in figure 1 it should be clear that coQ10 is only one of several micro-nutrients / amino acids that are highly dependent on which muscle your particular steak or whatever you are about to eat was cut from. Let's take taurine as yet another example. A prolonged low dietary intake of taurine has been observed to be linked to a number of disorders including retinal degeneration, retardation of growth and development, cardiovascular dysfunctions, CNS abnormalities, immune impairment and hepatic disorders (Abebe. 2011). If you eat meat (fish & other animal products) only occasionally and are therefore at risk of not getting adequate taurine in your diet, eating sausages from a butcher you trust would be a better choice than a piece of ham, since the former do include the high taurine meat from the masseter (cheeks) of the animals, while ham does not.

Let's get to the obvious: Grass-fed is... ah, wait a minute

"Grass fed is best" as you will people say about beef obviously won't be the case for pork, because pigs, just like humans, by the way, are omnivores. The simple formula, grass-fed = most beneficial fatty acid and micronutrient profile that may (in general) be valid for beef doesn't apply and we will have to take a closer look at the actual data first to decide what would be the "best" feed for pigs, if the goal was not a maximal yield of lean meat (in that case adding some clenbuterol, like the Chinese like to do it would be the least you should do; cf. The China Post. 2011), but rather to produce the meat with the most beneficial fatty acid  composition.

Figure 2: Fatty acid composition (primary axis) and omega-6 to omega-3 ratio of pork from pigs fed different diets (corrected version of data Reig et al. re-pupublished based on previous studies; spec. the figure for the n6:n3 ratio in the "standard feed" group that's based on Enser et al. was off - a ratio of 1.54 is obviously unrealistic)

I we define "most healthy" as having the lowest omega-6 to omega-3 ratio - a practice that seems appropriate given that 95% of the inhabitants of the so-called 'Westernized World' consumes way too much of the former and (comparably) way too little of the latter type of polyunsaturated fatty acids, the data in figure 2 clearly argues in favor of *surprise* the standard feed - at least if you define that by the feed the animals the meat of which (50 samples) Enser et al. bought in British supermarkets in 1996 (note: these values are still higher than for the conventional beef samples from the same study, which had a n-6:n-3 ratio of ~2.2; cf. Enser. 1996). There are however more intricate patterns that are not evident from the overview in figure 2, but could have implications as far as the direction into which "pork production" could or should head to in the future is concerned (summarized based on Reig. 2012):

Do you notice a pattern? I guess even based on the data in figure 2 you will already have noticed that the "grainier" the diet, or in other words, the more corn and soy there is in the diet of the swine the less favorable is the fatty acid composition of their meats going to be. Now, I am asking an outrageous question: If swine are such a good model for human metabolism, what do you believe your belly was going to be made of, if you copied the pigs' diets and lived on "healthy grains", their oils and the uber-healthy soy beans for the (probably pretty short) rest of your life?
• more food (yet no excess) can produce overall leaner muscle meat in the type II fibers, while the total body fat is increasing
• aside from local desaturation and elongination effects, the overall muscular fatty acid pattern does (much like in humans, by the way) mirror the dietary intake
• canola or linseed oils produce a substantial increase in the content of linolenic acid (C 18:3), and slightly increase the eicosapentaenoic (EPA, C 22:5) and docosahexaenoic (DHA, C 22:6) acid contents in pork mea
• soy, peanut, corn, and sunflower increase the content of linoleic acid (C 18:2; omega-6), increase the n-6:n-3 ratio and reduce the content of mono-unsaturated fats (MUFAs)
• fish oils or algae added to the feed substantially increases the content of EPA and DHA and thus reduce the n-6:n-3 ratio
• a high saturated fat content as in tallow (see figure 2) increases the levels of palmitic, palmitoleic, stearic and oleic acids in pork meat and reduces the PUFA:SFA ratio 
• CLA supplementation can increase the CLA content of the fatty portion of the meats (1% CLA results in 5.5 mg CLA/100g) and the adipose tissue (2% CLA yields 1,490mg CLA/100g fatty acids).

As you can see, the same rule applies for humans, pigs and, as you know from a previous SuppVersity post, mice who are fed inferior, since soy-fed salmon, as well: You are what you eat, folks!

Wallowing, roaming, routing: Work out like a pig

Since pigs make a pretty decent model of human metabolism and in view of the fact that - aside from our diets - the amount of exercise we get is one of the fundamental determinants of the total and relative levels of body fat, it should not be forgotten that "exercise" or rather the ability to range freely and be as active as any swine should be, is another determinant of the quality of the meat you are buying at the supermarket, grocery store, butcher or your local farmer. In this context, Reig et al. point out that

If you have no idea of the different cuts and location of the individual muscle, I suggest you download the "Meat Cuts Manual" from the website of the Canadian Food Agency. It's free and bilingual.

"[i]t has been reported that pigs maintained in free-range conditions in the Mediterranean forest had subcutaneous and intramuscular fats with higher monounsaturated fatty acids and lower saturated fatty acids than those pigs housed individually and receiving acorns as feed. The subcutaneous fat depth increases with exercise being 15.9 mm for exercised pigs in comparison to 11.5 mm depth for those kept in confinement. The same applies for the intramuscular fat content where 3.36% for extensive vs 1.44% for intensive raised pigs have been reported in the semimembranosus muscle." (Reig. 2012)

And if you really intend to overcomplicate things, you would also have to ask your butcher, whether the sausages you are about to buy were made of the meat of male of female pigs. After all, meat from barrows typically contain more fat and marbling and a thicker subcutaneous fat layer than meat from gilts (Armero. 1999). But let's face it: If you start stressing about things like this, the quality of your meat is probably your least problem.

If you want to know read more about epidemiological overgeneralization andthe effects of "pork" and red meat on your health (spec. the prostate) I suggest you go back to the Meat-Ology post.

So what's the bottom line, then: I guess the bottom line of the above insides is twofold. As far as you as an individual are concerned, it would be yet another argument for getting your meats (pork or whatever else) from a farm nearby, where you know what you are getting. It is yet also evidence of the fact that meticulous nutrient counting as I often see it in former calorie counters who have nor grasped the notion that "a calorie is not a calorie" is of little avail - at least if you expect to be able to calculate them as precisely as you can read them on the nutrition labels of the 90% artificial and 100% standardized convenient foods that's probably much more the answer to the question "Why are we fat?" than the non-descript statement "insulin".

In fact, the real significance of these results lies elsewhere. It concerns the way epidemiological studies are conducted (I may remind you of the metaphorical pizza salami being red meat or pork), their over-generalizing interpretations and the conclusions on what the optimal human diet should look like. So, once the next study is telling you "red meat" or "pork" is bad for you - you may want to remind yourself of some of the things you have learned in today's blogpost and ask yourself (and if you incidentally have the chance, the researchers as well): What kind of "pork" are we talking about?

References:

• Abebe W, Mozaffari MS. Role of taurine in the vasculature: an overview of experimental and human studies. Am J Cardiovasc Dis. 2011;1(3):293-311.
• Armero E,  Flores M,  Toldrá F,  Barbosa JA,  Olivet J,  Pla M,  Baselga M.Effects of pig sire types and sex on carcass traits, meat quality and sensory quality of dry-cured ham.  Journal of the  Science of  Food  and  Agriculture. 1999; 79:1147-1154.
• Enser M, Hallett K, Hewitt B, Fursey GA, Wood JD. Fatty acid content and composition of english beef, lamb and pork at retail. Meat Sci. 1996 Apr;42(4):443-56.
• Reig M, Aristoy MC, Toldra.Variability in the contents of pork meat nutrients and how it may affect food composition databases. Food Chemistry. 2012 [ahead of print]
• The China Post. Clenbuterol-tainted pork latest China food scandal. March 18, 2011. < http://www.chinapost.com.tw/china/national-news/2011/03/18/295146/Clenbuterol-tainted-pork.htm > retrieved Dec 06, 2012.

Bigger, Stronger, Faster: CoQ10 for Brain & Muscle in Young & Old. The Optimal HIIT Regimen for Fun & Fat Loss - 8s at 100% 60s Idling! Protein Power From Oats? Plus: Rest Times, Clusters, Form & Hypertrophy Training

I decided against calling this the "Get Big, Green and Look Like the Hulk Quickie" (img. Paramount Pictures)

In view of the fact that most of you apparently enjoyed the "Get Lean and Stay Lean Quickies" I posted in the last weeks, I thought you may also be inclined to read a "Get Big, Green and Look Like the Hulk Quickie", but then decided that the name was too long for the headline and "big, green" and maybe even "hulk" in conjunction with "quickie" may have had the SuppVersity turn up on google and other search engines in too close vicinity to websites I do not exactly want this blog to be associated with (just kiddin' ;-)

Be that as it may, enjoy the ride and let me know whether you do prefer this thematically structured approach over the classic news-potpouris ala On Short Notice.

I mean you can obviously argue in favor of both and since this is a place I want you to look forward to visit everyday, I would be inclined to hear whether "innovations" like this make it better or worse.

• CoQ10 supplementations could offer beneficial effects on brain and muscle in elderly individuals and could - at higher doses - work for youngsters, as well (Shetty. 2012) -- In a rodent trial the provision of a relatively high dose of CoQ10 as part of the diet effectively blunted age-induced 'cognitive decline' (whatever that may be in a mouse ;-) and protein breakdown in heart, liver and muscle tissue of the 17.5 months-old mice.
  
  

  

  Figure 1: Carbonyl levels in liver and muscle of young and old mice.

  This result is also interesting, because the mitochondrial protein breakdown in the brain was the one which was least beneficially affected. What's of greater importance, for this news quickie at least, is that the 2.81mg CoQ10 per gram of chow the high dose group received (the human equivalent would be roughly 33mg/kg or 2-3g per day!) elicited beneficial effects on the skeletal muscle carbonyl content, a marker of protein oxidation, in the young animals, as well (see figure 1).
  
  The notion that coQ10 in appropriate doses could be beneficial not just for statin users, but also for perfectly healthy people, even athletes, is also supported by the beneficial effects the administration of coQ10 had in a recent trial where it blunted the oxidative damage due to a high frequency endurance training program in rodents (Okudan. 2012). It does however stand in contrasts with a recent study by Bloomer et al., n which the supplementation of only 300mg (ca. 15% of the HED used in the study at hand) did not yield the desired effects on the exercise performance of 15 perviously individuals (10 men and 5 women; 30-65 years; Bloomer. 2012). Whether this really is just a matter of the correct dosing, or maybe a fundamental difference between mice and men will still have to be elucidated and I would not spent the bucks for anything that's only "maybe" going to work.
• Rats don't do well with hypertrophy training (Scheffer. 2012) -- According to a recently published paper by Scheffer et al., rodents who are afraid of increases in markers of oxidation should refrain from hypertrophy oriented muscle training and stick to lower volume resistance training.
  
  For their study, the Brazilian researchers had analyzed the effects of three different resistance training protocols, namely  muscular resistance training (RT), hypertrophy training (HT), and strength training (ST), which had to be performed twice a week for 12 weeks on muscle lactate and glycogen content, superoxide production, antioxidant enzyme content, and activities, as well as markers of lipid and protein oxidation.
  

  

  While you certainly don't want a fire inferno, doing too little is not going to yield the results you are looking for either (suggested read "The emerging role of an auto-/endocrine-immune axes")

  "Results showed increased superoxide production (UT = 5.348; RT = 5.117; HT = 8.412 ; ST = 6.354), SOD (UT = 0.078 ; RT = 0.101 ± 0.013; HT = 0.533 ± 0.109; ST = 0.388), GPx (UT = 0.290; RT = 0.348; HT = 0.529; ST = 0.384) activities, and content of GPx (HT = 3.8 times; ST = 3.0 times) compared with the UT group. CAT activity was lower (UT = 3.966; RT = 3.47; HT = 2.276 ; ST = 2.028) in HT and ST groups. Oxidative damage was observed in the HT group (TBARS = 0.082; carbonyl = 0.73; thiol = 12.78) compared with the UT group.

  The way in which the authors' conclusion that these "findings indicate that HT causes an imbalance in oxidative parameters in favor of pro-oxidants, causing oxidative stress in skeletal muscle" does implicitly suggest that this is a bad thing that has to be avoided at all cost, which is obviously totally beside the point - if you don't challenge your body he has nothing to adapt to and neither your conditioning, nor your strength or muscle mass are going to improve. The absence of statistically significant increases in oxidative damage in the low volume strength training routines, on the other hand supports the notion that you can use phases of very low volume training with heavy weights in between intense phases of overreaching to monetize on the muscular gains (which will probably keep coming in these 2-4 weeks) by taking all your lifts to another level and thus lying the foundation for future growth.
• Optimized HIIT regimen for overweight kids: 4s max sprinting + 60s active recovery do the trick - could work four you, as well! (Crisp. 2012) -- Either from the SuppVersity news or from listening to Super Human Radio you may remember that a recent study by Deighton et al. has found that sprinting will increase your appetite more and burn less calories than workload matched steady state cardio training. A novel study from Australia does now suggest that this may well be the case, but probably only as a result of doing it wrong - the sprinting, I mean.
  
  
  In their study Nicole A. Crisp and her colleagues from the School of Sport Science at the The University of Western Australia, describe how the combination of 8s all-out sprints on a cycle-ergometer with 60s of active rest easily outperforms its 30min steady state counterpart (30min moderate pace) and its "little brother" and "big" bother the 8s sprint, 120s active rest and the 8s sprint, 30s active rest protocol, respectively.
  
  

  

  This is not the first study to show the superiority of HIIT training in obese boys. In February 2012, I have already covered a very similar study where a brief HIIT session that burns "only" 360kcal was a major motor to teenage weight loos.

  In that, it's important to note that despite a linear increase in energy expenditure from the 60s to the 30s rest group, the latter failed to reach statistical significance (p = 0.076), ...
  

  "[...] likely as a result of decreased sprint quality as indicated by a significant decline in peak power output from SI₆₀ to SI₃₀ (p = 0.034)" (Crisp. 2012)

  In conjunction with the absence of the overcompensation effect at the following breakfast buffet (which was present in the 8/30s and to a lesser degree even the 30min steady state trial), this makes the 8/60s protocol the superior choice for everyone doing HIIT mainly to get or stay lean.
  
  And aside from its practical value, the 8/60s regimen was also the one the boys enjoyed the most.
  
  "And what about me?" I don't see why doing this very short sprints with large bouts of active recovery in between would not be right for you, as well. At least if the activation of your metabolism and / or fat loss during a diet is your primary goal and not an improvement in VO2 max., you would thus probably get many of the benefits at a smaller risk of overtraining. Just make sure you are actually sprinting all-out for the whole 8s and don't stop, when you are just about to get up to speed ;-)
• Long rest times necessary for high jumpers - with 8-12 min pause your performance on the next jump will increase not decrease (Gouvêa . 2012) -- In a recent meta-analysis that's soon going to be published in the Journal of Sports Sciences André Luiz Gouvêa and his co-workers report that the manipulation of rest intervals seems to affect post-activation potentiation magnitude and jump height.
  
  After analyzing fourteen studies, which met the criteria of having a crossover design, being randomised, or non-randomised and counterbalanced and observed the voluntary muscle action-induced post-activation potentiation on jumping performance, the scientists state that the...
  

  "[...]results demonstrated medium effect sizes for rest intervals 0–3 and 8–12 min (-0.25 for 0–3 min; 0.24 for 8–12 min) and a small effect for other ranges (0.15, CI: -0.08 to 0.38 for 4–7 min; for ≥16 min)." (Gouvêa . 2012)

  Since there was little to no evidence for heterogeneity among the sub-groups and no indication of publication bias, these results clearly suggest that rest intervals of 0–3 min have detrimental, rest intervals between 4-8 min neutral and rest intervals of 8-12 min beneficial impact on jump height. In that, the improvements are likely to be mediated by post-activation potentiation.
• The science of cluster training - Conventional wisdom prevails, 10 deep breaths would yield optimal rest time between reps (Hardee. 2012) -- At lest with respect to proper form, which may also have consequences for optimal muscle recruitment and hypertrophy, the optimal rest time between two reps in a cluster appears to be 20s, which is actually what the good old "10 deep breaths rule" would state, as well.
  
  
  What is a cluster? When you are "clustering" your sets you are doing one (sometimes also 2-3) rep(s), rack the weight, rest, do another rep etc. This is a very good technique to increase your strength and break through plateaus that's useful for powerlifters and bodybuilders alike.
  In order to examine the effects of three different cluster set configurations on power clean technique, the scientists recruited 10 male, recreational weightlifters who had to perform clustered or non-clustered power-cleasn: 3 sets of 6 repetitions at 80% of their individual repetition max with 0 (P0), 20 (P20) or 40 seconds (P40) inter-repetition rest.
  
  In the P0 (no cluster) condition, the scientists observed how the form suffered and got worse and worse from the first to the last rep (the catch and first pull were in a more forward position during repetition 6 as compared to repetition 1). With the long rest times in the P40 condition, on the other hand,  "differences in horizontal displacement were found between repetitions 1 and 6 for the second pull and the loop" (Hardee. 2012).
  
  In the P20 condition the researchers did not observe any differences in horizontal displacement between repetitions 1 and 6 during P20. Reason enough for the scientists to conclude that their results would demonstrate that cluster sets with greater tha 20s of inter-repetition rest would be useful to maintain appropriate form without significantly dropping the density of your workout - whether this did actually facilitate strength or size gains was yet not evaluated in the study.
  
  The evidence for the efficacy of this training regimen (aside from simply providing a novel stimulus, which is obviously always a good thing) does come from a 2011 study by  Hansen et al who compared the response of highly trained rugby players to on traditional vs. clustered leg training program and found the latter to be slightly superior with respect to the increase in peak velocity and strength , while the classic continouus set training had an edge as far as total power increases in the lower limbs were concerned (Hansen. 2011).
• Oats healthy car source with performance protein? (Xu. 2012) Who would have thought that, oats are not just an excellent source of slow digesting carbs and potentially fat-burning beta glucan (listen to the SuppVersity Science Round-Up from two weeks ago), they also contain a non-negligible amount of protein of which researchers from the College of Food Science and Engineering at the Northwest A&F University in Yangling, China, have now shown that it ameliorates the increase in lipid oxidation (MDA) and decrease in antioxidant activity (SOD) during an exaustive bout of swimming in 30 male mice.
  
  After the oat protein had been purified from oat meal thirty male Kun-ming mice were divided kept on either a normal control diet, a diet that was enriched with oatmeal and a diet that contained only the protein fraction of the oats. After 20 days, the rodents were subjected to swim to exhaustion. Their swimming endurance and the major metabolic substrates were measured from serum, liver and muscle.
  

  

  Figure 2: Antioxidant enzymes up, lipid oxidation down. That's the result of a comparison of the detrimental effects of an exhaustive swimming test in mice fed regular, oat enriched or oat protein pimped diets for 30 days (Xu. 2012). What the study cannot answer is however whether identical effects would have been seen w/ any other high quality protein as.

  "The results showed that no significant differences were observed in swimming endurance test between the normal control group and the oat protein group (P > 0.05). Mice in the oat meal group had significantly longer swimming endurance compared to the normal control group (P < 0.05). Furthermore, dietary oat protein increased the levels of liver glycogen, enhanced the activities of lactic dehydrogenase and superoxide dismutase, and decreased the levels of blood urea nitrogen and malondialdehyde in serum." (Xu. 2012)

  Now the good news certainly is that id did work. The "bad" or at least not so good news, on the other hand is that there is no adequate control group, since the addition of both the oats and the oat protein will have increased the amount of essential amino acids in the rodent chow significantly.

That's it! At least as far as news on getting bigger, stronger and faster is concerned. In case yo are also interested in something else, for example...

• how scientists have successfully transformed former breast cancer cells back to benign mammary epithelial cells by placing them in a non-carcinogenic environment like a healthy non-inflamed mouse
• that continously taking 25,000IU of supplemental vitamin A is at least not particularly healthy for young lean and obese women
• why Munuka honey, when Greek or Cypriot Honeys are the more potent antimicrobials?

and whatever else I will still be posting before tomorrow's SuppVersity news, you are alway welcome to visit the SuppVersity Facebook Wall.

References:

• Bloomer RJ, Canale RE, McCarthy CG, Farney TM. Impact of oral ubiquinol on blood oxidative stress and exercise performance. Oxid Med Cell Longev. 2012;2012:465020. doi: 10.1155/2012/465020. Epub 2012 Aug 23. 
• Crisp NA, Fournier PA, Licari MK, Braham R, Guelfi KJ. Optimising sprint interval exercise to maximise energy expenditure and enjoyment in overweight boys. Applied Physiology, Nutrition, and Metabolism, 10.1139/h2012-111. 
• Gouvêa AL, Fernandes IA, César EP, Silva WA, Gomes PS. The effects of rest intervals on jumping performance: A meta-analysis on post-activation potentiation studies. J Sports Sci. 2012 Nov 9.
• Hansen KT, Cronin JB, Pickering SL, Newton MJ. Does cluster loading enhance lower body power development in preseason preparation of elite rugby union players? J Strength Cond Res. 2011 Aug;25(8):2118-26.
• Hardee JP, Lawrence MM, Zwetsloot KA, Triplett NT, Utter AC, McBride JM. Effect of cluster set configurations on power clean technique. J Sports Sci. 2012 Nov 5.
• Okudan N, Revan S, Balci SS, Belviranli M, Pepe H, Gökbel H. Effects of CoQ10 supplementation and swimming training on exhaustive exercise-induced oxidative stress in rat heart. Bratisl Lek Listy. 2012;113(7):393-9. 
• Scheffer DL, Silva LA, Tromm CB, da Rosa GL, Silveira PCL, de Souza CT, Latini A, Pinho RA. Impact of different resistance training protocols on muscular oxidative stress parameters. Applied Physiology, Nutrition, and Metabolism, 10.1139/h2012-115
• Shetty RA, Forster MJ, Sumien N. Coenzyme Q(10) supplementation reverses age-related impairments in spatial learning and lowers protein oxidation. Age (Dordr). 2012 Nov 10. 
• Xu C, Lv J, You S, Zhao Q, Chen X, Hu X. Supplementation with oat protein ameliorates exercise-induced fatigue in mice. Food Funct. 2012 Nov 12.

CoQ10 for Ultra-Endurance Athletes: 150mg of Ubiquinone Reduce Stress & Inflammation and Stabilize Cell Membranes in 52.4 Mile Torture from 640m to 3,393m!

Image 1: Susan Kokesh, blogger and the Crazy Running Mum at the Sierra Nevada ultra-endurance run a 52.4 miles "double marathon"
  in September 2010; I probably would not even have survived this torture - respect!

As a health conscious physcial culturist, you are probably aware that the vitaminesque nutrient CoQ10, which, due to its ubiquitous presence in all living beings, is also known as ubiqinone, plays a fundamental role in cellular bioenergetics. It is a necessary cofactor in the mitochondrial electron transport chain (i.e. your cell's way of "breathing", its respiratory chain) and is therefore essential for the production of ATP, the fundamental energy unit your cells are operating on. In that, CoQ10 works as a mobile redox agent that shuttles electrons and, interestingly, also protons (those little blue and red balls from Bohr's atom model ;-) in the electron transport chain. Within the health and fitness community, it is however better known for its antioxidant value, as in its reduced form, ubiquinol, it is a potent lipophilic (which means that it does not combine with fats) antioxidant, which is able to recycle and regenerate other antioxidants, such as vitamin E and vitamin C (Ernster. 1995). Moreover, CoQ10 participates in cell signaling and gene expression and has been used as a dietary supplement (among others) for the treatment of neurodegenerative diseases and statin-induced myopathies.

In view of its pluripotent influence on mammalian metabolism (on a side note: the "-10" in CoQ10 indicates the length of the isoprenoid sidechain that is attached to the common benzoquinone ring structure; the latter is unique and can be found in humans and a few other mammals only), it should thus not surprise you that Chavier Díaz-Castro and his collegues from the University of Granada report that the intake of 150mg of the natural version of CoQ10 (2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone; natural = has trans configuration), profoundly modulated "the undesirable effects of the evoked oxidative stress and inflammation signaling during high-intensity" (Díaz-Castro. 2011).

Illustration 1: Supplementational protocol used in the study; CoQ10 was administered as 2,3-dimethoxy-5-methyl-6-decaprenyl-1,4-benzoquinone in powder form in 30mg capsules.

As you can see in illustration 1, the 20 highly trained male amateur athletes (all had run The Sierra Nevada ultra-endurance race in the previous 2 years), who participated in the study were not given the whole dose of 150mg of CoQ10 at once, but followed what I would like to call a "loading protocol" in the two days before the event. The placebo group received an identically looking product containing beer yeast, cellulose,
acacia, silica stearic acid, magnesium stearate, cellulose gum, and maltodextrin.

The total distance of The Sierra Nevada run is >50km. It is considered one of the hardest trials worldwide, mainly because the run, in the course of which the participants "climb" from 640m to a final altitude of  3,393m is almost on a continuous incline! A 5.5 hour torture, for which the CoQ10 supplemented athletes needed on average ~25min less than the subjects in the placebo group. In this study, the exercise performance was yet of negligible importance. What the scientists were really interested were the markers of oxidative damage and inflammation and as the following data shows, those were markedly influenced by the ingestion of this rather "mediocre" (compared to what you see some "health-gurus" advocate) amount of CoQ10.

Figure 1: Effects of CoQ10 supplementation of total bilirubin, triglycerides and urinary creatinine in 20 ultra-endurance runners (data calculated based on Díaz-Castro. 2011)

As you can see in figure 1, CoQ10 induced a significant reduction in urinary creatinine even before the race started (figure 1, left column). Moreover, there were significant differences in the bilirubin (indicates heme catabolism), triglycerides and (again) creatinine (indicates net protein catabolism):

Intense physical exercise resulted in an increase in net protein catabolism and an increase in
creatinine excretion in the PG after the physical test (p < 0.001); however, the urinary levels of creatinine were lower (p < 0.05 before and p < 0.001 after the physical test) in the CoQ10 treated group. Other interesting result was that although there was an increase in urinary creatinine in the CG, it was lower than in PG (38.77 ± 10.20 vs. 88.23 ± 11.21, p < 0.05). We also observed a decrease in the bilirubin concentrations in the CG after the run (p < 0.001) with lower values compared to PG group.

There were also significant differences in the inflammatory response, with (statistically significant, p<0.05) lower values of interleukin 6 (IL-6; -32%) and TNF-alpha (-23%) before the start of the race, and -22% lower TNF-alpha values after the "torture". Moreover, the basal hydroper-oxide content in the erythrocyte membranes, the scientists measured as an indicator of the degree of oxidative stress were lower before and after the exercise test, as the scientists call it.

Taken together, these results suggest that the addition of a small dose of CoQ10 to your supplemental regimen could induce unexpectedly profound cell-stabilizing benefits, of which it would yet be interesting to see how those translate into performance benefits, health and longevity, in the long run.

Mitochondrial Super Food: R-ALA, Acetyl-L-Carnitine, Biotin, Nicotinamide (B3), Riboflavin (B2), Pyridoxine (B6), Creatine, CoQ10, Resveratrol & Taurine Optimize Mitochondrial Function.

From China, the biggest (and cheapest) producer of raw materials for dietary supplements comes a study (Sun. 2011) on the effectiveness of a mitochondrial nutrient combination on performance and mitochondrial biogenesis in exhaustively exercised rats, which may well have consequences on the number of items on your next supplement shopping list.

For 4 weeks, Sun et al. supplemented exhaustively exercising rats with a combination of R-a-lipoic acid, acetyl-L-carnitine, biotin, nicotinamide, riboflavin, pyridoxine, creatine, CoQ10, resveratrol and taurine (cf. table 1)

Table 1: Ingredients of the "mitochondrial nutrient supplement";dosage used in rat study (data adapted from Sun. 2011); and calculated human equivalent doses 

This nutrient combination had beneficial effects on standard markers of exercise induced oxidative stress and muscular breakdown. Specifically, it "significantly inhibited the increase in activities of alanine transaminase, lactate dehydrogenase and creatine kinase". The supplementation protocol also had beneficial effects on antioxidant status reversing increases in malondialdehyde and inhibiting the decrease in glutathione S-transferase and total antioxidant capacity in plasma. It also suppressed the elevation of reactive oxygen species in the spleen and thus protected splenic lymphocytes from apoptosis [cell death].

These effects were accompanied / mediated by significant increases mitochondrial biogenesis, evidenced by increases in

[...] the protein expression of mitochondrial complexes I, II and III, mtDNA number and transcription factors involved in mitochondrial biogenesis and fusion in skeletal muscle.

Taken together these results underline that proper nutrition, not only on a macroscopic, but also on a microscopic level, is of paramount importance to exercise performance and metabolic health. Interestingly, the amount of the supplemental "mitochondrial nutrients" used in this study is not even exorbitantly high. In fact, the human equivalent doses (cf. table 1) would be easily attainable by a nutrient-rich diet and some cheap and readily available supplements.