Happy New Year Hangover Cures - 8 Cures That Work + Two Dozen Purported "Cures" That Have No Scientific Backup

Happy New Year! In case this guy looks anywhere similar to how you feel after yesterday's party night, today's SuppVersity article is for you!

"Happy New Year", health, love, ... you know the whole litany, so let's get over it and straight to the things that are really important, today. The hangover cures. In the following I have compiled an extensive yet probably by no means complete list of scientifically proven hangover cures that may help better than aspirin and plenty of water (Harvard Health Letter. 2006), alone.

Apropos aspirin, it's actually not too bad to start with 400-800mg of it, if you are having a hangover. It has after been shown to block the increased prostaglandin synthesis in response to alcohol ingestion and thus counter at least the inflammatory aspect of the hangover (George. 1979).

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The latter cannot be said of another common pain killer: Acetaminophen, which failed to inhibit ethanol-induced subjective effects in human volunteers in a 1992 study by Pickworth et al. The same study by George et al. would yet also suggest that aspirin may also prolong the time it takes for the alcohol to leave your system completely... and this may not be your only problem, because the coingestion of aspirin and alcohol has been associated with an increased risk of gastrointestinal haemorrhage (Needham. 1971).

So what do you do if water and aspirin are not enough? Well, here are a couple of suggestions - in a more or less random order, since there are hardly any studies that compare the efficacy of one to another.

• 

  Figure 1: Effects of 200mg tolfenamic acid on hangover symptoms in man (Kaivola. 1983).

  Tolfenamic acid - Tolfenamic acid is a very specific prostaglandin biosynthesis inhibitor that lead to significant reductions in hangover symptoms in a 1983 study by Kaivola, et al. (see Figure 1).
  
  The only problem is: The subjects consumed the 200mg of the anti-migraine drug tolfenamic acid before they started binge drinking. Whether the effects are similarly pronounced if you take it the day after remains to be elucidated.
• Gamma linoleic acid (GLA) - The omega-6 fatty acid from vegetable oils like rapeseed/canola oil and soy beans, walnuts, flax seed (linseed oil), perilla, chia, and hemp seed effectively reduced the hangover symptoms of human volunteers in a study the results of which have unfortunately never been officially published (Moesgaard; based on Pittler. 2005).
  
  In view of the fact that I have only 2nd hand access to the results I cannot tell you how much GLA you would need. Considering the effect that the supplement contained B officinalis aka Borage, which contains 26-36% GLA, if it's not specifically enriched, I would yet assume that 100-300mg should do.

Figure 2: Symptoms and possible contributers of hangover (Swift. 1998).

• Yeast + B-Vitamins: Another trial tested the efficacy of 250 mg dried yeast, 0.5 mg thiamine nitrate, 0.5 mg pyridoxine hydrochloride, and 0.5 mg riboflavin in participants who consumed vodka (40% volume alcohol) amounting to a total of 100 g absolute alcohol (Laas. 1999). The difference in the change for the symptoms discomfort, restlessness, and impatience was statistically significant in favor of the yeast preparation and appear to suggest that the corresponding supplement aka "Morning Fit" works.
  
  Moreover, corresponding research from the Chungnam National University in Korea shows that a preparation of combined glutathione-enriched yeast and rice embryo/soybean extracts constitutes a  "a promising candidate for improvements of alcoholic hangover" (Lee. 2009), as well.
• Oh!K - A hangover cure with green ginger, turmeric, pepper, and green tea extract, along with salt, citric and ascorbic acid and fructose as the carrier worked pretty well in a recent study by Gopi et al. (2014).
• Sprite! Or rather a sprite-like herbal drink - In the media you may have read about Sprite, when in fact the two drinks researchers from the Sun Yat-Sen University in China tested and found to be effective in increasing the production of the enzyme that helps our bodies to get rid of alcohol were xue bi, a fizzy lemon and lime drink of which the researchers did not declare that it was indeed Sprite and hui yi su da shui, probably a type of soda water (Li. 2014).
• After Affect(R): Another commercially available anti-hangover cure "proved" to be effective in a non-randomized non-controlled trial from the Utrecht University (Vester. 2012).
  

  

  Table 1: Rationale for the ingredients included in After-Effect©. 1 - Total dose of 5 capsules. 2 - Only those symptoms that showed a significant improvement during alcohol hangover are listed. GLA: gamma-linolenic acid, EPA: eicosapentaenoic acid (EPA), and DHA: docosahexaenoic acid (Verster. 2012).

  If it were not for the reasonable ingredient profile (see Table 1), I probably wouldn't have listed it, but with GLA, magnesium, B-vitamins & co it does contain a bunch of ingredients that may actually help.
• Party Smart (carbonate mix) - Yet another commercial preparation that contains calcium carbonate (615 mg) and vegetable carbon (345 mg) and has - unfortunately - to be consumed while you are drinking.
  
  More specifically, the subjects in the 2004 study by Manu et al. consumed their first serving of two caplets with first drink and two more caplets every 2 to 3 hours (or 5 to 6 drinks).
  

  

  Figure 3: Mean hangover score and mean blood alcohol 10h after drinking (Manu. 2004).

  The data in Figure 3 does yet indicate that this alkalization regimen worked pretty well (I wonder if sodium bicarbonate would to the same ;-) is a pretty effective means to (a) keep the hangover in check and (b) help your body clear the alcohol from your bloodstream.
• Aging! Ok, I know this does not really help you today, but maybe on New Year's Eve 2065! Tolstrup et al. found that hangover following engagement in binge drinking is much more common in the young than in the older age groups (Tolstrup. 2014). For women, similar results were obtained.
  
  As the scientists point out, "[t]his finding could not be explained by the usual amount of alcohol consumption, frequency of binge drinking, or the proportion of alcohol consumed with meals" (Tolstrup. 2014).

List of anti-hangover remedies from the Internet - all w/out scientific evidence that they work (Pittler. 2004).

You still feel like dying? If all these cures didn't help and you feel as if you were about to die, today, you may have inherited a special gene variant from of Aldehyde Dehydrogenase (ALDH2) an Asian ancestor that makes you extra susceptible to more severe hangovers (Wall. 2000).

And if you are totally desperate you may want to give C scolymus aka Artichoke leaves and O ficus-indica extracts a final try. While two randomized controlled trials did not intergroup differences for their main outcome measures (Pittler. 2003; Wiese. 2004), both are often hailed as natural hangover remedies. The same can be said of most of the other remedies you will find if you google anti-hangover cures on the Internet (see table on the right). As Pittler et al. highlight in their 2005 review of the literature, none of them has reliable scientific evidence that would confirm that they are working | Comment on Facebook!

References:

• George, Frank R., and Allan C. Collins. "Prostaglandin synthetase inhibitors antagonize the depressant effects of ethanol." Pharmacology Biochemistry and Behavior 10.6 (1979): 865-869.
• Gopi, Sreeraj, et al. "Studies on the effectiveness, safety and tolerability of two doses of Anti Hangover Drink in Reducing Alcohol Induced Hangover Symptoms in Adult Male Social Drinkers." Int.J.Cur.Res.Aca.Rev. 2.8 (2014): 125-131.
• Harvard Health Letter. How to handle a hangover: drinking fluids may help with the morning-after misery from getting drunk. Harvard Health Letter 31.3(2006):3. 
• Kaivola, S., et al. "Hangover headache and prostaglandins: prophylactic treatment with tolfenamic acid." Cephalalgia 3.1 (1983): 31-36. 
• Laas I. A double-blind placebo-controlled study on the effects of Morning Fit on hangover symptoms after a high level of alcohol consumption in healthy volunteers. J Clin Res 1999;2: 9-15. 
• Lee, Heon-Sik, et al. "Effects of a preparation of combined glutathione-enriched yeast and rice embryo/soybean extracts on ethanol hangover." Journal of medicinal food 12.6 (2009): 1359-1367.
• Li, Sha, et al. "Effects of herbal infusions, tea and carbonated beverages on alcohol dehydrogenase and aldehyde dehydrogenase activity." Food & function 5.1 (2014): 42-49. 
• Manu, M. B., and S. A. Kolhapure. "Evaluation of the Efficacy and Safety of “PartySmart” in the Prevention of Alcohol-induced Hangover: A Prospective, Randomized, Double Blind, Comparative, Phase III Clinical Trial." INDIAN JOURNAL OF CLINICAL PRACTICE 15.7 (2004).
• Moesgaard S, Hansen NV. GLA effectively reduces hangovers. Pharma Nord Research, unpublished report. 
• Needham, C. D., et al. "Aspirin and alcohol in gastrointestinal haemorrhage." Gut 12.10 (1971): 819-821. 
• Pickworth, Wallace B., et al. "Acetaminophen fails to inhibit ethanol-induced subjective effects in human volunteers." Pharmacology Biochemistry and Behavior 41.1 (1992): 189-194.
• Pittler, Max H., et al. "Effectiveness of artichoke extract in preventing alcohol-induced hangovers: a randomized controlled trial." Canadian Medical Association Journal 169.12 (2003): 1269-1273.
• Pittler, Max H., Joris C. Verster, and Edzard Ernst. "Interventions for preventing or treating alcohol hangover: systematic review of randomised controlled trials." Bmj 331.7531 (2005): 1515-1518.
• Swift, Robert, and Dena Davidson. "Alcohol hangover." Alcohol Health Res World 22 (1998): 54-60. 
• Tolstrup, J. S., Stephens, R. and Grønbæk, M. (2014), Does the Severity of Hangovers Decline with Age? Survey of the Incidence of Hangover in Different Age Groups. Alcoholism: Clinical and Experimental Research, 38: 466–470. doi: 10.1111/acer.12238.
• Verster, J. C., and O. Berthélemy. "Consumer Satisfaction and Efficacy of the Hangover Cure After-Effect©." Advances in preventive medicine 2012 (2012).
• Wall, Tamara L., et al. "Hangover symptoms in Asian Americans with variations in the aldehyde dehydrogenase (ALDH2) gene." Journal of Studies on Alcohol and Drugs 61.1 (2000): 13.

Removal of Amalgam Fillings Associated With Reductions in Memory Loss, Fatigue, Anxiety, Confusion & Other Health Problems, Observational Study from Canda Shows

Amalgam removed = health restored?

While there is little doubt that mercury vapor poses a known health risk, there is neither a clearly established safe level of exposure, nor evidence that similar ill health effects can occur with chronic low grade exposure to mercury vapor from dental amalgam fillings.

As you may know amalgam is not 100% but "only" 50% mercury, but is that enough to represent a significant health risk? The objective of a recent study from the University of Calgary was "to determine if mercury exposure from amalgam fillings is associated with risk of adverse health effects" (Zwicker. 2014).

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To this ends, Zwicker et al. conducted a large longitudinal non-blinded study involving participants from a preventative health program in Calgary, Canada. The goal was to assess whether (a) there was an association between having amalgam fillings, the amount of mercury in the urine and reported health issues and (b) whether the 14 previously self-reported health symptoms would improve in a sample of persons who had their fillings removed compared to a sample of persons who had not had their fillings removed.

Figure 1: Summary data for study sample with urine mercury measures (Zwicker. 2014)

A brief glimpse at the baseline data reveals that the presence of 18.4 and 23.7 amalgam fillings on the tooth surfaces of the subjects in the treatment (amalgam fillings will be removed) and the amalgam control group (amalgam fillings will not be removed) have higher amounts of mercury in their urine.

What do previous studies say? Oskarsson et al. (1996) fount that mercury from amalgam fillings was the main source of mercury in milk. In fact, the amount of mercury babies were exposed to from breast milk ranged up to 0.3 μg/kg/d, of which approximately one-half was inorganic mercury and which corresponds to approximately one-half the tolerable daily intake for adults recommended by the World Health Organization (Oskarsson. 1996). Other studies present opposing results, though, and claim that fish, not amalgam fillings was the major source of mercury in breast milk (Drexler. 1998). Still, evidence from other studies, such as Nylander (1987), which report mercury vapor from amalgam fillings to be the major source of mercury in the organs of human subjects, support the notion that at least the "first generation" amalgam fillings are a major source of human mercury exposure. The correlation with subjective health symptoms, on the other hand, is less obvious. Studies like Ahlqwist et al. (1988) and a twin study by Björkman et al (1996) clearly refute the existence of a significant correlation.

What is interesting, but not actually what the scientists wanted to investigate is the fact that the mercury levels in women are generally higher (may be a result of a comparatively lower body size and mass and similar mercury exposure).

What do you think happened one year after the fillings were removed?

Well, let's see. As the data in Figure 2 indicates, the mercury levels in both amalgam groups declined in comparison to the baseline measure (follow up data for the amalgam free group is not available)

Figure 2: Changes in mean urinary mercury level after one year after the amalgam fillings
were removed / not removed (Zwicker. 2014)

The effects are, I guess you will agree with me on that one, not exactly impressive. Against that background the obvious question is: "Are the self-reported measured improvements in headache, memory loss, depression, fatigue, anxiety & co a result of a placebo effect?" I mean, the subjects obviously knew that their amalgam fillings were removed (remember: it's a non-blinded study!) and you bet that they've read some of the horror stories about mercury on the Internet.

Table 1: One year odds of symptom improvement and worsening in the group of subjects who had the amalgam fillings removed, controlled for age and sex | Odds ratio coefficients are the odds of change in treatment group relative to the positive amalgam group. {P values}; * indicates coefficient is different from 1 at size 0.05; ^ represents statistical significance at size 0.10 (Zwicker. 2014).

So, can we tell whether the "improvements" you see in Table 1 are actually brought about by the removal of the amalgam fillings or simply by the subjects psyche? I would say we can't and that's why I have my doubts about the validity of the researchers conclusion that "that mercury exposure from amalgam fillings adversely impact health and therefore are a health risk" (Zwicker. 2014) - not necessarily because I believe they are harmless, but rather because the data the scientists evaluated does not prove this claim.

If avoiding mercury from fish is a good thing, avoiding mercury exposure from amalgam fillings is a good thing, too. Irrespective of the fact that the study at hand provides only insufficient evidence of its ill health effects.

Bottom line: I personally had my one filling removed back in the day, but rather the necessary result of the fact that it was in a baby tooth ;-)

That being said, I still subscribe to the researchers assertion that "a safer alternative materials for dental fillings should be encouraged to avoid the increased risk of health deterioration associated with unnecessary exposure to mercury" (Zwicker. 2014), yet not because of the data in the study at hand, though, but rather based on the notion that you would want to limit any unnecessary exposure to heavy metals, no matter how small the amount that's leeching from the amalgam fillings may be, though.

On a side note: A study investigating the commonly heard claim that the removal of amalgam would only increase the load of mercury (at least temporarily) indicates that - if it's done properly - "[t]he uptake of amalgam mercury in the GI tract in conjunction with removal of amalgam fillings seems to be low" (Björkman. 1997). So if you are considering this procedure, it's unlikely that it will make whatever symptoms you believe to have as a consequence of having amalgam fillings more severe | Comment on Facebook!

References:

• Ahlqwist, Margareta, et al. "Number of amalgam tooth fillings in relation to subjectively experienced symptoms in a study of Swedish women." Community dentistry and oral epidemiology 16.4 (1988): 227-231. 
• Björkman, Lars, Nancy L. Pedersen, and Paul Lichtenstein. "Physical and mental health related to dental amalgam fillings in Swedish twins." Community dentistry and oral epidemiology 24.4 (1996): 260-267.
• Drexler, Hans, and Karl-Heinz Schaller. "The mercury concentration in breast milk resulting from amalgam fillings and dietary habits." Environmental research 77.2 (1998): 124-129. 
• Oskarsson, Agneta, et al. "Total and inorganic mercury in breast milk and blood in relation to fish consumption and amalgam fillings in lactating women." Archives of Environmental Health: An International Journal 51.3 (1996): 234-241.
• Nylander, Magnus, Lars Friberg, and Birger Lind. "Mercury concentrations in the human brain and kidneys in relation to exposure from dental amalgam fillings." Swedish dental journal 11.5 (1986): 179-187.
• Zwicker, Jennifer D., Daniel J. Dutton, and John Charles Emery. "Longitudinal analysis of the association between removal of dental amalgam, urine mercury and 14 self-reported health symptoms." Environmental Health 13.1 (2014): 95.

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.

Caffeine - 3mg, 6mg or 9mg/kg? What's the Optimal Dosage for Lifting & HIT Cycling and What About the Side Effects?

Wouldn't a single 200mg caffeine be enough to elicit the desired ergogenic effects without side effect like increased urination, headaches and muscle aches on the day after?

Caffeine is not only the world's #1 it is probably also the most (ab-)used ergogenic on the planet and whatever you may think about the longterm consequences of its use, there is not debating that it is part of those few "supplements" that actually work "no hype, no *bs*" ;-)

That being said, you may have noticed with yourself that its effect are dose dependent, but not linearly and that some things, such as an increase in mental focus at work require much lower doses of C8H10N4O2 aka 1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione or 3,7-dihydro-1,3,7-trimethyl-1H-purine-2,6-dione than the elucidation of a major buzz before an intense strength workout.

So what's the perfect dose, then?

Without wanting to hurt your feelings, you may imagine that you are not the only one who has come to this realization. In fact, the very same thought must have occurred to Jesús G. Pallarés and his colleagues from the University of Castilla-La Mancha and the Spanish Antidoping Agency, as well. With a whole host of technological equipment and the money to conduct a study with thirteen highly resistance train men (age 21.9 ± 2.9; 76.5 ± 8.5 kg, height 172.7 ± 5.4 cm, body fat 12.4 ± 2.7), the Spanish scientists are yet in a much better position to elucidate where exactly these sweet spots would be.

Figure 1: Illustration of the procedure on the testing days (Pallarés. 2013)

To this ends, Pallarés et al. had their volunteers undergo a battery of muscle strength and power tests, namely a  free-weight fullsquat (SQ) and bench press (BP) exercises against  4 incremental loads (25%, 50%, 75% and 90% 1RM), as well as a test in which their cycling peak power output (PPO) was measured using a 4s inertial load test in a randomized in a double-blind, cross over design.

On the four separate testing days, the subjects ingested either a placebo supplement (PLAC) or, caffeine at dosages of ...

• 3mg/kg body weight (CAFF3mg), 
• 6mg/kg body weight (CAFF6mg) and
• 9mg/kg body weight (CAFF9mg)

The day before and during the seven days that the experiment lasted, the subjects lived at the sports performance center where they slept and ate all meals. They all consumed a diet of 2800-3000 kcal·day/day that had a macronutrient make-up where 55% energy intake came from carbohydrates, 25% from fat and 20% from protein. The energy intake was evenly distributed across three meals each day (breakfast at 7:00 a.m., lunch at 13:30 p.m. and dinner at 20:00 p.m.). Subjects refrained from physical activity other than that required by the experimental trials, and withdrew from alcohol, tobacco and any kind of caffeine intake 10 days before testing and while the experiment lasted.

On the actual testing day some baseline measurements, such as height, body fat %, as well as blood and urine samples were taken (PRE). Afterwards the subjects consumed a standardized "breakfast" consisting of a 330 mL of fruit milkshake (168 kcal) and a pastry (456 kcal; total energy for both 624 kcal; 68 g of carbohydrates) along with the their individualized randomized caffeine dose (3, 6 or 9 mg/kg) or placebo in capsule form. After this "delicious" *lol* breakfast, the participants performed

"[...] a standardized warm-up that consisted of 10 min of jogging at 10 km/h and 10 min of static stretches and joint mobilization exercises, the subjects entered the laboratory to start the neuromuscular test battery assessments under a paced schedule (see figure 1).  These tests consisted of the measurement of bar displacement velocity and muscle power output against 4 incremental loads (25%, 50%, 75% and 90% of 1RM) for upper and lower body musculature (BP and SQ).  Those step measures allowed a continuous representation of the load-velocity and load-power curves to study the interaction between load and caffeine dose on neuromuscular performance.  Cycling peak power output (PPO) was assessed next using a nonfatiguing inertial load test of 4 s duration.  Subjects remained blinded to the results during the whole experiment. Instructions prior to lifting were standardized and always delivered by the same experimenter.

The whole procedure took about 60min and upon completion of the test battery a second  urine  and  blood  sample  was  collected  (POST). Moreover, all participants were required to fill out an obligatory questionnaire (QUEST+0h) that was aimed to address whether side-effects of caffeine were present during the trial.

Caffeine a side effect free ergogenic? Not exactly, no...

As some of you may know from their own lingering experience things that work, usually don't do that without side effects and the study at hand confirmed that this is no different for caffeine. Somewhat surprisingly, though the side effects the subjects who had refrained from caffeine intake for at least 10 days before the the first test, reported "very similar side effects" for the medium and high dose caffeine trials:

• a limited increase in the sensations of tachycardia and heart palpitations,
• self-reported urine output and gastrointestinal problems (8% of the subjects)

At the same time, the subject’s perception of performance and vigor increased 5 to 7 times above PLAC during the CAFF 3mg and CAFF6mg trials (38% and 54% of the subjects, respectively), which would appear to be well worth the minor problems.

Figure 2: Overview over the number of participants reporting side effects / perceived ergogenic effects (Pallarés. 2013)

In the course of the 9mg trial (remember: this was a bolus of 693mg caffeine for the average study participant) the men did yet report a "drastic increase" of side-effects (Table 1), of which the researchers consider the reported increase in the estimates of urine output and gastrointestinal problems (62% and 31%, respectively) to be most important. So important, in fact that it is questionable whether that was worth the increased perception of performance and vigor or activeness of 62% and 54%.

On the subsequent day, participants in the CAFF6mg trials were complaining of increased muscle soreness, headaches and an increase in the estimates of urine output in comparison to the PLAC and CAFF3mgtreatments. Sleep problems and persistently increased vigor occurred only in the  CAFF6mg an CAFF9mg trials with a much higher incidence (23-54% vs. 8% in the high vs. medium dose trial).

What Pallarés et al. find particularly noteworthy is that "23% of participants reported tachycardia and anxiety or nervousness, 38% with gastrointestinal problems and 54% with insomnia or sleep disturbances" (Pallarés. 2013). This is also the main reason that the researchers recommend "administering the minimal ergogenic dose". But what exactly is this dosage?

What delivers the most bang with the least side effects?

In order to answer this question we will have to take a closer look at the performance measures and compare the increases in mean propulsive velocity and muscle power, as well as the cycling PPO and the likelihood and severity of side effects for all four dosing regimen (see figure 3)

Figure 3: Propulsive velocity during bench presses (left) and propulsive power during bench presses and squats (right) in the placebo, 3mg, 6mg and 9mg trials (Pallarés. 2013)

As the data in figure 3 goes to show you, caffeine produced ergogenic effects at all dosages. With the heaviest weights, however, the propulsive velocity during bench presses and the squat power required the side-effect laden 9mg dose of caffeine to reach statistical significance. The same goes for the cycling peak power output (not shown).

---

Suggested read: "Coffee - The Good, The Bad & The Interesting: 2-4 Cups of Coffee for Adiponectin. Roasted Filtered Coffee & High LDL!? The Optimal Caffeine / Taurine Ratios & the Buzz ". Could taking taurine ameliorate w/out compromising the benefits of caffeine (read more)?

Bottom line: The study at hand is actually a good example of the myriad of cases, where statistical significance and the real world collide. Let's take another look at the results in figure 3 and the side effects in figure 2. Assuming that you have not whacked your adrenal gland to an extend that you don't respond to caffeine any longer (in that case you better stop taking it all along, anyway), there clearly is no reason to even remotely consider taking caffeine in dosages of more than 6mg/kg body weight before a workout (personally I have found that anything beyond 200-300mg will - in the long run do more harm than good for me, but I guess this really depends on the individual).

Aside from the subjective side-effects the latter has also been shown to have profoundly detrimental effects on the cortisol to testosterone ratio after a workout (cf. "Revisited: Caffeine's Dose-Dependent Effects on the Testosterone to Cortisol Response to Exercise"; read more)...

... and yes, I know that the relevance of this ratio in terms of the "productivity" of your workouts is highly questionable, the latter has been proven for a normal, non-stimulant based increase in cortisol / testosterone, not for the exorbitant increase in cortisol Beavan et al. observed in their 2008 study. If you add the detrimental down-stream effects of messed up sleep, and the obvious dehydration that follows the increased urination observed in the study at hand - overdosing may thus well turn the "proven ergogenic" caffeine into a highly ergolytic agent.

References:

• Beaven CM, Hopkins WG, Hansen KT, Wood MR, Cronin JB, Lowe TE. Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Int J Sport Nutr Exerc Metab. 2008 Apr;18(2):131-41. 
•  Pallarés JG, Fernández-Elías VE, Ortega JF, Muñoz G, Muñoz-Guerra J, Mora-Rodríguez R. Neuromuscular Responses to Incremental Caffeine Doses: Performance and Side Effects. Med Sci Sports Exerc. 2013 May 10.

On Short Notice: Red Onions For Glutathion & Jiagulan For Muscle Glycogen, Low Iron & Obesity, Sodium Caprate, Useless Probiotics & Leaky Gut, Perivascular Fat & Heat Shock Proteins for Your Heart & Magnesium vs. Migraine

Image 1: You may already have read it on the SuppVersity Facebook Wall; "Sacrificing sleep in order to study won't improve your college grades..." it could however easily whack your circadian rhythm and give you headaches. If those turn into a migraine, you may be happy to have read about beneficial effects of magnesium on the incidence of these crippling and painful attacks (see last item in this installment of "On Short Notice" ).

In order to avoid having another weekend of "On Short Notice" posts, I decided to post the first collection today, already. The topics are, as usually, only loosely related and I hope that each and everyone of you will find something he or she considers interesting. We'll start out by having a brief look at the amazing antioxidant effects of red onions, and then delve deeper into the connection between obesity and low ferritin levels and a brief reminder that sometimes good things can become bad, if they are not handled properly, next on the list are the tight gut junction opening effects of sodium caprate which may be a good thing if your goal is to increase the bioavailability of berberine, but a very bad thing, if other molecules take the opportunity and pass through the open doors, as we are then going to see Dr. Shirota's probiotics are probably not going to help you avoid this problem and they are certainly not helping patients with metabolic syndrome: The latter is probably also true for PPAR-gamma antagonists, which may help prevent visceral fat accumulation, but could at the same time precipitate to heart disease by decreasing the surprisingly heart-healthy perivascular fat.

Although more of an ergogenic, Gynostemma penthaphylum (aka Jiagulan) is probably a more promising strategy to get in better shape. If it allows you to train harder, it will also allow you to make better use of potential systemic health effects of exercised induced heat shock protein expression... and just in case all that was so much information that you are having a headache once you have arrived at the end of this blogpost, a 500mg dose of magnesium could help you reduce the incidence of migraine attacks by more than 60% whether additional 500mg of carnitine make this treatment even more effective does yet remain to be elucidated!

• Do your liver and body antioxidant system a favor and add a couple of red onions to your diet! That's the straight forward take home message from a recently conducted study by a group of Korean scientists (Lee. 2012). The researchers had investigated  the effect of red onion on the total activity of antioxidant enzymes in 18-week-old Sprague-Dawley rats. To this ends the rodent had been kept on a diet enriched with red onion peel, flesh or both (all pulverized and mixed into the standard chow for a total content of 5g per 100g) for for weeks.

  

  Figure 1: The red onions outperformed easily outperformed their uncolored white brethren and cousin, white onions and garlic, in the in vitro dish and had profound antioxidant boosting effects in the in vivo study (Lee. 2012).

  The results, (a) a significant increase in plasma SOD activity in the red onion peel and red onion (peel + flesh) groups, (b) a significantly higher GPX (enzyme that recycles glutathione) activity in the in the red onion flesh group and (c) a general tendency towards higher catalase and ORAC activity in the livers and profoundly reduced liver malondialdehyde (=marker of lipid peroxidation) levels in the red onion groups provide an in vivo (allegedly only "in rodent vivo" ;-) confirmation of the in vitro data in figure 1 which is - as usual - to be treated with caution before respective experiments in complex, real organisms confirm that they are more than artifacts of the respective essay.
• Low iron (ferritin) associated with obesity in adolescents, but simple eating more iron probably won't solve either the iron deficiency, nor the (central) obesity. That's at least what the results of a recent investigation in normal and fat Greek kids would suggest, after all the fat kids did already consume more iron in their diets than their lean age-mates (Moschonis. 2012).
  What makes this study worth mentioning is the (as usual hasty) conclusion that iron must be a bad guy, when just its mismanagement (probably as a result of adiposity induced liver problems, or, as a handful of older and recent studies would suggest vitamin A deficiency; e.g. Arruda. 2009; Citelli. 2012; Yohsikawa. 2012) is a problem - so don't get fooled, donating blood every other week won't lean healthy people out, it will just drain them out.

• 

  Figure 2: Sodium caprate won't "open" the tight gut junctions for berberine, only, but also for all sorts of other, mostly unwanted junk - self-induced temporary leaky gut so to say!

  Sodium caprate opens tight junctions of the gut and let's berberine in. The consequence is an amplification of the hypoglycemic effects of berberine (Lv. 2012), but at the same time it is likely to amplify the effects of whatever you else put into your mouth or the critters that live in your stomach are pooping out - I guess it should be obvious that I am referring to the LPS assault from your gut microbiome, here and that the potential increase in lipopolysaccharide could well outweigh (in a negative sense) the benefits you would see from an increased bioavailability (~1.5-2.3 fold; cf. Lv. 2010) of berberine.
  
  Against that background I am really not sure how sensible the use of sodium caprate or other "tight junction openers" of natural or pharamacological origin really is. But hey, that's just me - maybe you are less cautious...  if there are not yet any products like that on the market, it probably won't be long until the first "enhanced" berberine appear in the line-ups of the large "health supplement" vendors on the Internet.

• 

  Image 2: Patented lactobacillus strains are all the rave, and probably big business... that does yet not mean that they work - regardless of whether they carry the name of famous Drs or not ;-)

  Probiotic supplements don't cure everything - although many ads may give just this impression. In a recently published study, Swiss researchers were not able to show any beneficial effects of the patented L. casei Shirota strain on the increased gut permeability of 28 patients with metabolic syndrome (Leber. 2012). In the course of the three months study period, it rather exasperated the already elevated C-reactive protein levels, due to liposaccharide leakage through the leaky gut into the system and I bet the only reason that the conclusion states that the dosage may have been too low instead of "this is initial evidence that the use of L. casei Shirota is not useful if  not counter-indicated in to treat gut permeability in patients with MetS", was the financial support by Yakult Europe the patent holder of L. casei Shirota ;-)
• PPAR-gamma ablation leads to loss of perivascular adipose tissue (PVAT). What may at first sound great could in fact be deadly. The recently published results of Chang et al. show quite clearly that non-tissue-specific blockade of the "fat builder" PPAR-gamma (cf. "Tangeritin, Natural Metformin from the Rind of Mandarin Oranges Hits the OFF-Switch on Diet Induced Obesity") is a dangerous undertaking. While keeping the differentiation and growth of body fat at bay, especially in the abdominal region, would be a good thing, the high rate of atherosclerosis among the mice from the laboratories of the University of Michigan confirms that "not all body fat is created evil" (Chang. 2012).

  

  Figure 3: Fitzgibbons et al. were already able to show that the UCP-1 expression, which is a marker of metabolic activity, in PVAT is equally high as in the meanwhile infamous brown adipose tissue. In short - PVAT just like BAT will not just store superfluous lipids, it will also burn them and prevent them from accumulating in the vasculature (Fitzgibbons. 2011)

  As it turned out, PVAT, rather than being proinflammatory and hazardous, actually has a protective function on the vasculature it is sourrounding. In fact, the results Chang et al. are presenting in the latest issue of Circulation suggest the assumption that PVAT is anti-inflammatory and functionally similar to the metabolically active brown adipose tissue that has gotten quite some attention by experts ad laymen as of lat. When it's suddenly missing, the lipids inside the vascular can no longer be cleared into the perivascular adipose tissue where they would be oxidized and disposed of. In addition, the ensuing pro-atherogenic coupled with the absence of PVAT-derived prostacyclin, a prostanoid that's metabolized from endogenous arachidonic acid through the cyclooxygenase (COX) pathway and acts as a potent vasodilator (cf. Ruan. 2010) could thus easily set you up to die before your time - regardless of how lean you may have become...
  And though it is very unlikely that this is going to happen from the use of one of the freely available herbs with anti-PPAR-gamma effects (e.g. tashinones from Salvia miltiorrhiza, or the previously cited tangeritin), it certainly is a good reminder of how fatal our constant black-and-white thinking can be, when it is injudiciously applied to such complex matters as our own body.

• 

  Image 4 (dracoherbs.com): Gynostemma penthaphylum is also known as Jiaogulan, is often mentioned in the same breath with ginseng in TCM

  Gynostemma penthaphylum boosts endurance by ROS scavenging and multiplying skeletal muscle glycogen stores. Not yet another potent anti-oxidant was what I first thought,when I hit upon the soon-to-be published study from Shaanxi Normal University in Xi'an, China, but after taking a closer look it turned out that the way this century old adaptogen that goes by the name jiaogulanin TCM and is an herbaceous vine of the family Cucurbitaceae (cucumber or gourd family) indigenous to the southern reaches of China, northern Vietnam, southern Korea, and Japan, could actually make quite an exciting supplement (Chi. 2012). After all its high ROS(radical oxygen specimen) scavenging abilities are only part of what allowed the rodents in the study by Chi, Tang, Zhang & Zhang that had been treaded with isolated polysaccharides from this plant to go significantly longer during a standardized exercise performance test.
  The more intruiging part of the performance boost, however came from the direct pro-gluconeogenic and glyocogen storage promoting effects of the alpha variety of the three Gynostemma penhaphylum polyssacharides the scientists had extracted. If similar effects would be seen in humans, GP would certainly make a valuable addition to the regimen of anyone who does not just perform 1-rep maxes day in and day out - and let's face it: In view of the fact that the glycogen can't be synthesized from nothing, it could also help to burn body fat, by it's repartitioning effects.

• 

  Figure 4: It would certainly be an unwarranted overgeneralization to ascribe all beneficial effects of exercise to the systemic expression of heat shock proteins. But still, there is increasing evidence that their controlled expression does at least contribute to the numerous beneficial effects exercise has on our brains, hearts and other organs; interestingly these effects are likewise mediated by the breakdown and the protection and "recycling" of organ tissue.

  Will training your biceps, heal your heart and protect your brain!? You probably know that the scientists at the McMaster University have put the myth of the pro-anabolic effects of systemically circulating hormones that are released response to isolated muscle training (eg. "train your legs to increase your testosterone and see your arms grow") at rest, years ago. Now, a study that's soon going to be published in theh Journal of Experimental Biology suggests that testosterone, growth hormone and co. may not be the only molecules we should be looking for, when we talk about possible non-localized effects of exercise (Jammes. 2012). Another class of proteins that has gotten quite some attention esp. in the context of the profound effects of occlusion training, the so-called heat-shock proteins, which are released in response not just to heat, but to exhaustive contractions / trauma / hypoxia / etc., could in fact play a likewise, probably more important role not so much in skeletal muscle growth, maybe, but in the overall systemic response to exhaustive skeletal muscle contractions. 
  After all, Jammes et al. observed a delayed, but significant elevation of non phosphorylated HSP25 and HSP70 in skeletal and respiratory muscles, kidney, and brain. Now, of HSP70, for example, it has long been known that it exerts cardio-protective effects (Martin. 1997). In addition to its anti-apoptotic effects, it does yet also contribute to the proteolysis (=protein breaking) that's a necessary part of the continuous clean-up processes that remove the "junk" and "clutter" (defect protein structures) from your body in order to keep everything functional (Lüders. 2000). Similarly, HSP25 (aka HSPB1) exerts both cytoprotective effects due to its ability to modulate reactive oxygen species and raise glutathione levels, as well as proteolytic effects and is working hand in hand with HSP70 by inhibiting protein aggregation and stabilizing partially denatured proteins, so that they can be refolded by the former. That the latter could be of particular importants in view of the neuroprotective effects of exercise is also supported by a couple of trials in which HSPB1, to be precise, its exogenous administration or endogenous overexpression, have been evaluated as treatment or preventive strategies in ALS (Lou Gehrig's Disease), Huntington's, Parkinson's, Stroke and acute nerve injury (for an overview see table 3 in Brownell. 2012).

• 

  Figure 5: The benefit of l-carnitine is questionable, despite the fact that the serum l-carnitine in the Mg group dropped to a similar extent as in the control group; over time the carnitine depletion could however become important (Tarighat Esfanjani. 2012)

  Headaches? Magnesium and l-carnitin help! At a dosage of 500mg/day magnesium oxide, alone did already have significant beneficial effects on the occurrence of migraine in  106 females and 27 males volunteers who were diagnosed with headache according to the International Headache Society criteria, were between the age of 18 and 55 years old and "had severe and continual headache lasting from 4 to 72 h, unilateral and pulsating headaches with moderate or severe intensity, migraine with or without aura, at least two attacks per month, headaches which were aggravated by routine physical activity and associated with nausea and/or photophobia, and phonophobia" (Tarighat Esfanjani. 2012).
  So, if that sounds like you (I don't hope it does) magnesium should be the least you should take, the additional 500 mg/day L-carnitine is questionable - just as whether ALCAR may have provided greater benefits. Apropos, you do realize that this is neither transdermal nor any fancy chelated magnesium or at least magnesium citrate that did the trick? Yeah, right: The same "worthless" (put name of random nutrition guru, here) mg-oxide you find in the cheapest fizzy tablet from the supermarket did the trick!

If you are now thirsty for more, I suggest you check out the SuppVersity Facebook Wall (which is by the way updated several times a day), like the career-boosting information that sacrificing sleep in order to study is a bad idea, that Caucasians, compared to Asians, lose weight relatively easily, but have a hard time getting rid of their bellies, or, if all that ain't for you, how the wise producers of "functional foods" are planning to add a little wood aka methylcellulose into your yogurts and smoothies to curb the cravings you probably would not have, if they had not removed all the fat from it, before ;-)

 References:

• Brownell SE, Becker RA, Steinman L. The protective and therapeutic function of small heat shock proteins in neurological diseases. Front Immunol. 2012;3:74. Epub 2012 May 1.
• Chang L, Villacorta L, Li R, Hamblin M, Xu W, Dou C, Zhang J, Wu J, Zeng R, Chen YE. Loss of Perivascular Adipose Tissue upon PPARγ Deletion in Smooth Muscle Cells Impairs Intravascular Thermoregulation and Enhances Atherosclerosis. Circulation. 2012 Aug 1. 
• Chi A, Tang L, Zhang J, Zhang K. Chemical Composition of three Ingredients of Polysaccharides from Gynostemma pentaphyllum and Comparison of their Antioxidant Activity in Skeletal Muscle of Exhaustive Exercise Mice. Int J Sport Nutr Exerc Metab. 2012 Aug 14.
• Citelli M, Bittencourt LL, da Silva SV, Pierucci AP, Pedrosa C. Vitamin A Modulates the Expression of Genes Involved in Iron Bioavailability. Biol Trace Elem Res. 2012 Apr 14. 
• Fitzgibbons TP, Kogan S, Aouadi M, Hendricks GM, Straubhaar J, Czech MP. Similarity of mouse perivascular and brown adipose tissues and their resistance to diet-induced inflammation. Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1425-37.
• Jammes Y, Steinberg JG, By Y, Brerro-Saby C, Condo J, Olivier M, Guieu R, Delliaux S. Fatiguing stimulation of one skeletal muscle triggers heat shock proteins activation in several rat organs: the role of muscle innervation. J Exp Biol. 2012 Aug 16.  
• Leber B, Tripolt NJ, Blattl D, Eder M, Wascher TC, Pieber TR, Stauber R, Sourij H, Oettl K, Stadlbauer V. The influence of probiotic supplementation on gut permeability in patients with metabolic syndrome: an open label, randomized pilot study. Eur J Clin Nutr. 2012 Aug 8.
• Lee B, Jung JH, Kim HS. Assessment of red onion on antioxidant activity in rat. Food and Chemical Toxicology. August 10, 2012.
• Lüders J, Demand J, Höhfeld J. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J Biol Chem. 2000 Feb 18;275(7):4613-7. 
• Lv, X.Y., Li, J., Zhang, M., Wang, C.M., Fan, Z., Wang, C.Y., Chen, L., 2010. Enhancement of sodium caprate on intestine absorption and antidiabetic action of berberine. AAPS.PharmSciTech. 11, 372–382. 
• Martin JL, Mestril R, Hilal-Dandan R, Brunton LL, Dillmann WH. Small heat shock proteins and protection against ischemic injury in cardiac myocytes. Circulation. 1997 Dec 16;96(12):4343-8. 
• Moschonis G, Chrousos GP, Lionis C, Mougios V, Manios Y. Association of total body and visceral fat mass with iron deficiency in preadolescents: the Healthy Growth Study. Br J Nutr. 2011 Nov 16:1-10.
• Ruan CH, Dixon RA, Willerson JT, Ruan KH. Prostacyclin therapy for pulmonary arterial hypertension. Tex Heart Inst J. 2010;37(4):391-9. 
• Tarighat Esfanjani A, Mahdavi R, Ebrahimi Mameghani M, Talebi M, Nikniaz Z, Safaiyan A. The Effects of Magnesium, L-: Carnitine, and Concurrent Magnesium-L-: Carnitine Supplementation in Migraine Prophylaxis. Biol Trace Elem Res. 2012 Aug 17. 
• Yoshikava O, Ebata Y, Tsuchiya H, et al. A retinoic acid receptor agonist tamibarotene suppresses iron accumulation in the liver. Obesity. 2012 Aug.
• Zhanga M, Lvc X, Lia J, Menga Z, Wangd Q, Changa W, Lia W, Chena L. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis. Molecular and Cellular Endocrinology. 16 August 2012