Science Round Up Seconds: 30-60% More Testosterone w/ 2.5g D-Aspartic Acid in Fertility Trial and Nicotine Amplifies Cardiotoxic Effects of ECA. Plus: Data on DHEA & Estrogen & Breast Cancer, Fermented Teas, AMPK, AKT & Co

DAA is probably not going to hurt your heart, but it's more likely to father a child than to build those abs. Ephedrine & Caffeine on the other hand, could help you get there, but esp. if you are also smoking you are increasing the risk that the kids you fathered using DAA will soon be without their begetter.

I guess most of all will have listened to the podcast of yesterday's installment of the SuppVersity Science Round Up already. If you didn't you have been missing Carl and me discuss new on the pro-carcinogenic effects of aspartame, the never-ending story of the fattening artificial sweeteners, the benefits of oat beta-glucans for weightloss, -maintenance and gut health, the way sorghum proanthocyanidins can lower the GI of carbohydrates and make them less susceptible to enzymatic breakdown in the small intestine, and more.

Actually this more, i.e. the news on DHEA, its metabolits and their proliferative effect on breast cancer cells, as well as the information about the beneficial effects of fermented teas on blood glucose management, reminded me of the fact that as how like the SuppVersity Science Round Up is a very good place discuss and explain things, but not exactly the place to present detailed data. Therefore, I decided to prelude the Seconds by adding a couple of graphs which illustrate what has been said on the last show. Thus, you can look at the figures while listening to the podcast.

Supportive material for the DHEA and fermented tea news

For this first installment of the Seconds I did, you guessed it, pick the aformentioned news on DHEA and the different fermented teas (see figure 1) that are  based on studies by Miller (2012) and Yamashita  (2012), respectively.

Effect of 7 days of oolong tea, black tea, pu-erh tea, instead of water on Δglucose AUC (left), AMPK, AKT and PI3K expression in skeletal muscle  of male mice (Yamashita. 2012)

Effect of estradiol (E2), DHEA and its metabolits 7-OXO,  androstenediol, and androstenedione on breast cancer cell proliferation (based on Miller 2012)

So much for the additions to visuals for the podcast, let's get to the new stuff... or actually the seconds. Of course, the seconds ;-)

• How to brew your own sodium d-aspartic acid The best thing about this study actually is that the scientists disclose how you can easily make your own PH stable sodium-d-aspartate from the cheap stuff you buy at your favorite bulk supplier: Take 2.66 g of D-aspartic acid neutralize it with 0.46 g of NaOH in 10 ml distilled water and you get a final pH of 6.5 - 7-0 - that's it, you are good to go.
  New study on d-aspartic acid confirms - 30-60% increase in testosterone and LH in infertile men (D’Aniello. 2012) Despite the fact that this is a non-sponsored study by researchers from the Hospital “S. Luca” in Vallo della Lucania, Italy, I am about as 'unpsyched' about the data the scientists present, as I am about the real world results of d-aspartic acid (DAA) supplementation in young weight training men.
  
  It's already telling that D'Aniello et al. mention the increase in testosterone and luteinizing hormone (LH) only as an aside and consider it as a "save", or I guess you better say "tolerable" side effect of a treatment  that did effectively double the amount of D-aspartic acid in the seminal plasma and did thus (at least the scientists belive in a mechanism here) increase the fertility in both, patients with reduced sperm motility and sperm count, and those who suffered only from reduced motility.
  
  The actual 'success rate' in terms of pregnancy rates after 2-3 months of treatment with 2.66g/day of DAA per day was however not exactly really earth-shattering, either. Of the patients with both low sperm count and sperm motility (oligo-asthenozoospermia) 4% fathered a child; of those who suffered 'only' from a low sperm motility (asthenozoospermia) 33% eventually managed to become daddy.
  
  Without baseline testosterone levels, of which I would not be surprised if they had been rock bottom (both oligo-asthenozoospermia and asthenozoospermia usually go hand in hand with increased oxidation and that in turn is associated with low testosterone and suppressed LH levels), this study is however about as worthless in terms of the purported ergogenic effects of DAA, as all previous human trials. That said, you could obviously mix yourself the above concussion in case you and your significant other are planning to start a new or to expand your existing family in the near future. I guess, it's unlikely that it's going to hurt.
  
  Suggested read: All About the Role of Androgens & Co in Building Muscle
   
• Putting an "N" as in "nicotine" into "EC" amplifies the negative effects of ephedrine and caffeine on your heart and may well be the reason for many of the (few) deadly side effects that occurred in the day before the ban (Brown. 2012) When a group of researchers from the Arkansas State University tried to get to the bottom of the (in some cases) fatal cardiovascular side-effects, which were the main reason for the FDA to pull ephedra-containing supplements from the market, Christopher E. Brown and his colleagues observed ...

  "[...] a synergistic effect on the rat cardiac morphology [...] as a result of intera tions between nicotine, caffeine, and Ephedra. The cardiotoxicity caused by combination dosing of Ephedra and caffeine has already been shown; however, the present study revealed an enhancement of cardiotoxicity when nicotine was administered in combination with Ephedra and caffeine." (Brown. 2012)

  The scientists had exposed male Sprague-Dawley rats to (1) synthetic combinations of nicotine (0.2 mg/kg/day), ephedrine (0–30 mg/kg/day), and/or caffeine (0–24 mg/kg/day) as well as (2) an extract from a caffeine-containing Ephedra supplement (Metabolife 356). The relatively high dose treatments were administered for only 3 days either in the full or half dose and with and without nicotine pre-treatment to model the effects of different dosing regimen on smokers and non-smokers.
  
  

  

  Figure 1: Light micrograph of representative nuclear pro-files (background, red = atypical, green = normal nuclei; my emphasis) and volume (%) of atypical cardiac cells in anterior left ventricle of the rodents (Brown. 2012)

  As far as the results go, a a brief glance on the exemplary data in figure 1 should actually suffice to see, that a baseline "N" + "EC"  stack (as in any smoker who would take ephedrine + caffeine to lose weight or psyche himself up) could eventually pave the way to the emergency room.
  
  While the data from the anterior left ventricle and anterior interventricular septum (not shown) would suggest that the identically dosed synthetic versions of caffeine and ephedrine were slightly more detrimental, than the herbal supplement  in which the Ephedra came from a standardized Ma Huang extract and part of the caffeine from Guarana, this effect was not present in either the posterior left or the anterior right or posterior right ventricle (data not shown).
  
  Apropos interventricular septum (IVS), with increases in atypical cardiac cell volume of up to 1.5% in the anterior IVS even without nicotine pre-treatment, the stout wall that separates the lower chambers was most susceptible to the effects of caffeine and ephedrine:
  

  "In the anterior section of this region, both caffeine + ephedrine combination as well as the multicomponent supplement Metabolife 356 resulted in larger numbers of atypical cells compared to water controls, in both saline- and nicotine-pretreated rats. However, only rats pretreated with nicotine responded negatively to supplements in the posterior region of the IVS. " (Brown. 2012)

  If you consider the high-pressure forces it must sustain for proper ejection volume to the arterial vasculature it should be obvious that "these changes to the ventricular tissue could be particularly detrimental to overall cardiovascular health" (Brown. 2012). Bad news? Why? At least you do now have another good reason to stop smoking... what, oh yeah, I forgot: This is irrelevant because Ephedra has been banned anyway ;-)

While I do have a couple of other Seconds I am a bit pressed on time, today. Don't worry sooner or later they will appear ither on the SuppVersity Facebook Wall, where I am posting at least half a dozen of exclusive links and mini-items, comments and more you won't find on www.suppversity.com. So, I'd suggest you do now first listen to the podcast (if you have not already done so), then check out the latest SuppVersity Facebook News and when you are done with that wait till tomorrow for this weeks installment of On Short Notice.  

References

• Brown CE, Trauth SE, Grippo RS, Gurley BJ, Grippo AA. Combined Effects of Ephedrine-Containing Dietary Supplements, Caffeine, and Nicotine on Morphology and Ultrastructure of Rat Hearts. Journal of Caffeine Research. 2012; 2(3).
• D’Aniello G, Ronsini S, Notari T, et al. D-Aspartate, a Key Element for the Improvement of Sperm Quality. Advances in Sexual Medicine, 2012, 2, 47-53.
• Miller KKM, Al-Rayyan N, Ivanova MM, Mattingly KA, Ripp SL, Klinge CM, Prough RA. DHEA metabolites activate estrogen receptors alpha and beta. Sterespectivelyroids. November 01, 2012. Ahead of print.
• Yamashita Y, Wang L, Tinshun Z, Nakamura T, Ashida H. Fermented Tea Improves Glucose Intolerance in Mice by Enhancing Translocation of Glucose Transporter 4 in Skeletal Muscle. J Agric Food Chem. 2012 Nov 5.

True or False: You Can (Ab-)Use Nicotine Chewing Gums to Get Shredded Without Compromising Your Health

Nicotine gums are made for smokers. Smokers are leaner than no-smokers. Chewing nicotine gums helps you lean out... broscience? Logic? Or bullshit?

It's one of the better-known pieces of broscience: "Nicotine chewing gums will promote weight loss!" Aside from being "better-known", it's yet also highly controversial. In that, people usually don't question the fact that nicotine chewing gums may promote weight loss (we do all know that smokers, are leaner, don't we?), but rather that they do so in the absence of significant ill-health effects.

Since this is the SuppVersity and not the bb.com bulletin board, I am not going to restrict today's analysis on the health issues. Instead, I will start by looking for scientific evidence that would confirm the common sense assumption that chewing nicotine gums does in fact promote weight loss -- in humans, not in rodents (Lupien. 1988).

You can find more True or False articles at the SuppVersity

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High Volume Diet = Success

Let's first take a look at the connection between nicotine and body weight management in general. In 2006 Chen et al. published an intriguing paper the title of which could in fact explain why smokers tend to be lighter than non-smokers (for US citizens that's ~ 3.7% leaner; cf. Albanes. 1987): "Cigarette Smoke Exposure Reprograms the Hypothalamic Neuropeptide Y Axis to Promote Weight Loss" (Chen. 2006)

According to Chen et al., the anorexic effects they observed in a 4 week rodent study are behind the anti-obesity effects of smoking. Similar effects on appetite in general and reductions in sugar cravings (Grunberg. 1982) in human studies as well. Nevertheless, if a reduction in appetite was the only beneficial effect of nicotine would be limited to phases of ad-libitum dieting. A direct effect on fat loss, as it is implied by broscience, on the other hand, would not exist.

Beware of becoming skinny fat! While the average smoker may be lighter, he is not necessarily leaner. The results of a 1989 study by Shimokata et al. show that smokers have higer waist-to-hip ratios and "indicate that there are harmful effects of cigarette smoking on the pattern of distribution of body fat" i.e. away from the harmless body parts, i.e. the extremities and right to the epicenter of unhealthy fat: the waist! Due to the fact that cigarette smoking is also associated with unhealthy eating habits (Dallongeville. 1998), it's yet difficult to tell, whether this effect is (solely) due to the cigarettes.

If it was not for Schechter et al. and other scientists who report "nicotine-induced weight loss in rats without an effect on appetite" (Schechter. 1976), I could stop here and tell you that (a) you obviously don't want to chew nicotine gums for the rest of your life to benefit from its appetite suppressing phases and that (b) it wouldn't make sense to chew them in a phase, where you're counting calories, anyway (if you want the appetite suppressing effects, anyway, add caffeine, this will enhance them; Jessen. 2005).

Figure 1: Body weight and food intake in 13 week rodent study with 0.4mg/kg and 0.8mg/kg (right) of nicotine administered in solution or saline control thrice daily (Schechter. 1976)

Thanks to the impressive reduction in body weight Schlechter et al. observed in the previously cited rodent study in the absence of statistically significant reductions in food intake (graphs at the bottom of Figure 1), it's worth to keep digging further.

Figure 2: (a) Male body weights before, during, and after nicotine or saline administration; (b) Female body weights before, during, and after nicotine or saline administration (Grunberg. 1987)

Ladies, beware! The non-food related weight loss could be a "male only thing"! According to Grunberg et al. "the nicotine-related changes in body weight were accompanied by changes in bland food and water consumption" in female rodents - as the authors point out, a significant difference to previous studies (Grunberg. 1986). Accordingly, a follow-up study showed: "The body weight of females that had received nicotine were indistinguishable from controls up to 4 months after cessation of nicotine. The body weight of males that had received 12 mg nicotine per kg per day remained lower than controls." (Grunberg. 1897). Notably, the dreaded weight regain occured in male & female rodents (Figure 2)!

If you take a close look at the results you will yet realize that there is a big caveat to the impressive weight loss (specifically in the 3x0.8mg/kg group | human equivalent ~ 3x4mg or three high dose nicotine chewing gums). Yes, I am talking about the the nasty weight regain that occurred - likewise in the absence of increased food intakes - when the nicotine administration was seized.

Against that background, it's all the more important to find evidence from human studies. Unfortunately, the majority of studies on nicotine gums is not relevant to the topic, because they are (a) dealing with the success of smoking cessations, or (b) dealing with weight regain after smoking cessation. We will therefore have to resort to ostensibly unrelated results such as...

• 

  Figure 3: Plasma leptin levels in non-smokers, long-term nicotine gum users and smokers after adjustment for age and body composition (Eliasson. 1999)

  the increase in leptin levels researchers from the Sahlgrenska University Hospital in Göteborg (Sweden) observed in a 1999 study in 73 subjects: 23 non-smokers, 31 smokers and 19 long-term nicotine gum chewers (NGCs) with similar ranges of age, body mass index (BMI) and per cent body fat. As the authors of the corresponing paper point out, "[t]he increased leptin levels may be an important reason for the lower body weight in smokers." (Eliasson. 1999). Unfortunately "long-term" is nothing you would associate with the use of nicotine gums as diet adjuvant.
  
  As suggestive as they may be, the increases in leptin are thus probably not relevant for short term decreases in body weight - or even better body fat - as you would expect them, when you're dieting.
• the association with hyperinsulinemia and insulin resistance the same Swedish researchers from the Sahlgrenska University Hospital observed in a previous investigation (Taskinen. 1996) clearly suggest that the chronic consumption of nicotine leads to insulin resistance, metabolic abnormalities associated with the insulin resistance syndrome, and increased cardiovascular morbidity.
  
  On the other hand, we are - I can't repeat that often enough - not talking about the chronic use of nicotine gums, but their (ab-)use for 4-6 weeks to propel your fat loss results. Eventually, the results are thus as irrelevant as the previously mentioned beneficial effects on leptin (see previous bullet-point).

• 

  Figure 4: Thermogenic effect in 150min after the ingestion of nicotine and / or caffeine (Jessen. 2003)

  the "pronounced" thermogenic effect researchers from the The Royal Veterinary and Agricultural University in Denmark observed in their 2003 study. Aside from scientific evidence that the administration of nicotine has thermogenic effects, the second important result of the study at hand is the observation hat the thermogenic effects  of 1 mg nicotine (measured over 150 min after the ingestion) can be (almost) doubled, if the nicotine is administered in conjunction with 100 mg of caffeine (Jessen. 2004).
  
  It's also important to note that "[i]ncreasing the nicotine dose to 2 mg does not increase the thermogenic effect but produces side effects in most subjects." (Jessen. 2003) More is thus, as so often, not better for nicotine (a similar non-linear dose-response effect was observed with cigarettes, as well; cf. Collins. 1996). A previous study by Collinset al. (1994) found a 7.5% increase in resting energy expenditure with 200mg of caffeine and a similarly low amount of nicotine, i.e. 0.8mg of nicotine from cigarette smoke over a 3h period.

If you take a look at the evidence I provided, it supports the previously raised concerns about the long-term use of nicotine gums. On the other hand, the study by Jessen et al., as well as the study Collins et al. who didn't just find a similar synergistic effect of caffeine and nicotine, but were also able to show that the effects occur in both smokers and non-smokers (Collins. 1994; similar results in Perkins. 1989), clearly indicate that the short-term (ab-)use of nicotine gums may in fact promote the loss of body weight and - assuming you're getting your 1.5g/kg protein and lifting heavy objects - body fat, as well.

Figure 5: The increase in thermo- genesis due to 4x20µg intranasal nicotine is impressive in men, non- significant in women (Perkins. 1996)

Do men better sniff their nicotine?! While snuff is obviously not identical to an intranasal nicotine spray, the results Perkins et al. present in their 1996 study which investigated the effects of 4x20µg/kg nicotine that was administered intranasally every 30 minutes for 2h after the consumption of tonic water or alcohol are quite impressive... well, at least in men. In contrast to the male subjects in whom the nicotine only increased the energy expenditure by almost 13%, the 3.8% increase in the female study subjects was not significant! Whether that's a result of the absolutely lower dosage (remember the nicotine was dose per body weight) or a true sex-difference is uncertain.

Unfortunately, it is difficult to say whether these benefits come with significant negative effects on your health. Evidence on short-term effects of nicotine abuse in human beings is scarce. Furthermore studies in non-smokers suggest that healthy people and people with pre-existing problems with glucose management react differently, with the former experiencing no and the latter experiencing severe reductions in insulin resistance in response to the acute infusion of nicotine in a 2001 study by Axelsson et al.

Figure 6: Negative effects of nicotine on insulin sensitivity occur only in diabetics (Axelsson. 2001)

As far as the dreaded increases in insulin resistance are concerned, you could thus argue that the contemporary evidence suggest that healthy athletic individuals have nothing to fear. Since the same appears to be true for the negative effects on platelet count (Mundal. 1995), blood pressure and other markers of cardiovascular health (Benowitz. 2002). For people who belong to one of the classic risk groups, i.e. men and women with metabolic syndrome and / or existing heart condition, the use of nicotine gum may yet easily result in a hospital stay or worse (Rigotti. 1986).

If you want to try it, try this: 200mg caffeine + 1mg nicotine from chewing gums upon rising, another 200mg of caffeine and 1mg nicotine at lunch or pre-workout, additional 2x 100mg caffeine + 1mg nicotine between breakfast and lunch and lunch and dinner.

Bottom line - True! For healthy athletic folks! Just to make that clear. I am not, by any means recommending the use of nicotine gums for weight loss. All I do is to answer the often heard question whether the bro-scientific assumption that they'd help you shed body fat is true.

And, by the way, the study that would confirm that "dieting + nicotine" = greater weight / fat loss than "dieting alone" has not yet been conducted. If you want to do your own N=1 study, do it at your own risk. Next to potential (albeit for healthy people probably controllable health issues), it appears as if there was also a minimal risk of addiction for never-smokers (Etter. 2007) | Comment on Facebook!

References:

• Albanes, Demetrius, et al. "Associations between smoking and body weight in the US population: analysis of NHANES II." American Journal of Public Health 77.4 (1987): 439-444.
• Axelsson, T., et al. "Nicotine infusion acutely impairs insulin sensitivity in type 2 diabetic patients but not in healthy subjects." Journal of internal medicine 249.6 (2001): 539-544.
• Benowitz, Neal L., Anna Hansson, and Peyton Jacob. "Cardiovascular effects of nasal and transdermal nicotine and cigarette smoking." Hypertension 39.6 (2002): 1107-1112.
• Chen, Hui, et al. "Cigarette smoke exposure reprograms the hypothalamic neuropeptide Y axis to promote weight loss." American journal of respiratory and critical care medicine 173.11 (2006): 1248-1254.
• Collins, L. C., et al. "Effect of caffeine and/or cigarette smoking on resting energy expenditure." International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 18.8 (1994): 551-556. 
• Collins, Lynell C., Jerome Walker, and Bryant A. Stamford. "Smoking multiple high-versus low-nicotine cigarettes: impact on resting energy expenditure." Metabolism 45.8 (1996): 923-926.
• Dallongeville, Jean, et al. "Cigarette smoking is associated with unhealthy patterns of nutrient intake: a meta-analysis." The Journal of nutrition 128.9 (1998): 1450-1457.
• Eliasson, Björn, and Ulf Smith. "Leptin levels in smokers and long‐term users of nicotine gum." European journal of clinical investigation 29.2 (1999): 145-152. 
• Etter, Jean-François. "Addiction to the nicotine gum in never smokers." BMC public health 7.1 (2007): 159.
• Grunberg, Neil E., Deborah J. Bowen, and Suzan E. Winders. "Effects of nicotine on body weight and food consumption in female rats." Psychopharmacology 90.1 (1986): 101-105.
• Grunberg, Neil E. "The effects of nicotine and cigarette smoking on food consumption and taste preferences." Addictive behaviors 7.4 (1982): 317-331.
• Grunberg, N. E., S. E. Winders, and K. A. Popp. "Sex differences in nicotine's effects on consummatory behavior and body weight in rats." Psychopharmacology 91.2 (1987): 221-225.
• Jessen, Anna B., Søren Toubro, and Arne Astrup. "Effect of chewing gum containing nicotine and caffeine on energy expenditure and substrate utilization in men." The American journal of clinical nutrition 77.6 (2003): 1442-1447.
• Jessen, A., et al. "The appetite‐suppressant effect of nicotine is enhanced by caffeine*." Diabetes, Obesity and Metabolism 7.4 (2005): 327-333. 
• Mundal, H. H., K. Gjesdal, and P. Hjemdahl. "Acute effects of low dose nicotine gum on platelet function in non-smoking hypertensive and normotensive men." European journal of clinical pharmacology 47.5 (1995): 411-416. 
• Lupien, John R., and George A. Bray. "Nicotine increases thermogenesis in brown adipose tissue in rats." Pharmacology Biochemistry and Behavior 29.1 (1988): 33-37.
• Perkins, Kenneth A., et al. "Metabolic effects of nicotine in smokers and non-smokers." Problems of Drug Dependence 1989 (1989): 469.
• Perkins, Kenneth A., Joan E. Sexton, and Amy DiMarco. "Acute thermogenic effects of nicotine and alcohol in healthy male and female smokers." Physiology & behavior 60.1 (1996): 305-309.
• Rigotti, Nancy A., and Kim A. Eagle. "Atrial fibrillation while chewing nicotine gum." Jama 255.8 (1986): 1018-1018.
• Schechter, Martin D., and Peter G. Cook. "Nicotine-induced weight loss in rats without an effect on appetite." European journal of pharmacology 38.1 (1976): 63-69.
• Taskinen, Marja-Riitta, and Ulf Smith. "Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance." Circulation 94.5 (1996): 878-881.

Sex, Drugs and... Exercise? Caffeine, Alcohol, Marihuana and Nicotine - Do All Our Favorite Addictions Clash With Being Healthy, Lean and Athletic?

The only truly ergogenic addiction is a SuppVersity addiction ;-)

I am not sure if you remember my detailed elaborations on the effects of sexual intercourse on exercise performance from May 30, 2012 [see "Will Sex Before a Competition Hamper Your Performance?" | more], but if you don't I'd suggest you start out with this SuppVersity Classic before you devote yourself to Rock'n'Roll by reading up on that in my article "Acoustic Gear" [read more] and return here for the missing third part of the triumvirate: Drugs!

Drug #1: Caffeine - From your coffee mug to the doping list

I am actually 100% confident that 99% of you have already trained "on drugs". Most of you probably do it regularly. Either with caffeine, about which Tony Chou reported in a 1992 paper that it is consumed on a daily basis by ~90% of the adult population (Chou. 1992). With average amounts of "only" 200 mg or 2.4 mg/kg/day (about 2 cups of coffee).

Why are you laughing? Caffeine was on the WADA's list of banned substances from 1962 to 1972 and again from 1984 to 2003. Whether the average coffee consumer will ever achieve concentrations of 12 μg/ml+ in the urine and thus fail a doping test is obviously a whole different question, but during the second banned period from 1984-2003, a whole host of athletes passed the magic 12 µg/ml line and were tested positive for caffeine. The sanctions ranged from warnings up to

2 year suspensions (maximum penalty, usually only 2–6 months; cf. Pesta. 2013).
In view of the fact that its ergogenic effects are so well established as with hardly any other substance, I will stick to a very brief overview of the surprising benefits the world's "drug" #1 will have on preformance:

• Antagonism of adenosine ➲ analgesic effects (reduced perception of pain; Derry. 2012)
• Increased fatty acid oxidation ➲  higher endurance (Spriet. 1992)
• Decreased respiratory ration ➲ increased use of fat, decreased use of glycogen (Rush. 2001)
• Increases cAMP by inhibiting phospodiesterase ➲ increase lipolysis = more fuel (Umemur. 2006)
• Activation of protein kinase A ➲ s. above + increase in gluconeogenesis = more fuel (Graham. 2001)
• Increases glycogen storage ➲ faster recovery (Pedersen. 2008; learn more)
• Modulation of muscular calciusm flux ➲ increase contractile forces (Tarnopolsky. 2000)

In view of it's various beneficial health effects and the insufficient evidence of significant side-effects, when it is consumed in moderation, exercise performance should thus not be a reason to give up drinking coffee (and as you remember, contrary to the claims of certain "fad brands" the same is true for mycotoxins, as well).

Drug #2: Alcohol - From the track to the bar and into the gutter

While caffeine made it from everyone's coffee mug onto the WADA list of prohibited substances for all sports, alcohol is prohibited in-competition only and only in the following sports: aeronautic, archery, auto mobile, karate, motorcycling and powerboating (until 2010, modern pentathlon was also included in this list; Pesta. 2013).

Alcohol is a killer: According to WHO, morbidity attributable to alcohol in countries with an established market economy (10.3% of disability adjusted life years) comes second only to that of tobacco (11.7%; Murray. 1997). According to a very recent study by published in the scientific journal Addiction by the Pan American Health Organization, a branch of the World Health Organization alcohol was a 'necessary' cause of death (i.e., death would not have occurred in the absence of alcohol consumption) in an average of 79,456 cases per year in 16 North and Latin American countries (Gawryszewski. 2014).

In view of its effects on exercise performance and the generally reckless approach to the #2 on the list of the most diligent killers among all, not just the freely available drugs the decision of the World Anti Doping Association appears not reasonable, but at least consequent.

For many cyclists at the Tour de France, it was common practice to drink one, two or three glasses, sometimes even a bottle of wine before during and after a race, but that was in the (good?) old days and its ergogenic effects are certainly questionable. Nevertheless, it took some time until the wine that was often laced with strychnine to help ease the pain and decrease the feeling of fatigue (Fife. 2000) got replaced by EPO, glucocorticoids & co [note: the cyclists also used cocaine or sympathomimetic drugs in order to attenuate the feeling of fatigue associated with such a prolonged exercise; cf. Lucia. 2003].

Now, aside from certain analgesic (=pain reducing) effects, alcohol has little to offer to the average athlete. It may still be the "the most commonly consumed drug in athletic communities" (Pesta. 2013), but in moderation and certainly not for ergogenic purposes.

Table 1: Summary of the effects of alcohol on performance (adapted from Pesta. 2013)

It has after all been shown to adversely affects psychomotor skills and exercise performance. The beneficial reductions in maximal oxygen consumption (~greater muscular efficiency), on the other hand are pathetic, so that the American College of Sports Medicine (ACSM) rightly recommends that "if an athlete must consume alcohol, that they should refrain from alcohol consumption for at least 48 hours prior to competition." (ACSM)

Remember the irony in the article " Ultimate Post-Workout Testosterone Booze" [more] - Don't use hard liquor to increase your post-workout testosterone levels by almost 100%,  unless figures on a lab report are more important to you than health & performance.

If you stick to this recommendation even on training days, this will probably eliminate alcohol from your diet altogether or restrict its consumption on the weekend; and that's certainly a good thing. Chronic alcohol abuse will after all

• lead to significant impairments in cardiac and skeletal muscle structure and function in 99% of the cases
• slow down post-exercise recovery, and 
• inhibit protein synthesis 

There is obviously no debating: Alcohol is a uniformly ergolytic agent, It has significant detrimental effects on exercise performance and it's use must be minimized not just for performance, but also, and more importantly, for health reasons.

Apropos health! I am sure all of you will be aware that the government of Colorado believes that marijuana should be part of a healthy lifestyle... ah, I mean medical protocol to deal with pain and other issues and decided to legalize the renown preparation of the Cannabis plant that's intended for use as a psychoactive drug and as medicine.

Drug #3: Cannabis, Mariuhana, Pot, Weed

As we have learned from the Tour de France athletes of the past, pain obviously is a major issue for athletes. So, wouldn't it make sense to switch from wine + strichnine to marijuana? Ok, you can't consume it "intra-workout", but maybe before and after the Queen's stage at L’Alpe d’Huez?!

Cannabis is everywhere and has been used for ages: While the legalization of cannabis in Colorado may be innovative, the sue of cannabis and its principal active ingredient, tetrahydrocannabinol (THC  is only one of 483 known compounds in the plant, including at least 84 other cannabinoids, such as cannabidiol, cannabinol, tetrahydrocannabivarin, and cannabigerol) is not. It has been used for generations by people all over the world (see table to the left, cf. Chopra. 1969). Whether it is "paleo" or not is yet something I can't tell you for sure ;-)

To answer that question, it may be useful to take a closer look at the structure of THC, which enables it to dock with the cannaboid receptors in the central nervous system (CNS). As Anand et al. point out (Anand. 2009):

• The centrally expressed CB1 receptors trigger the psychotropic effects of marijuana.
• The CB2 receptors in the periphery (spec. the sensory tissue) mediate the analgesic effects.

For the average Tour de France cyclist a selective CB1 receptor modulator (a "SCBRM", so to say ;o) could thus be the drug of choice. In view of the fact that some of the beneficial effects of exercise are also mediated by endogenous cannabinoid receptor antagonists (Hill. 2010), the analgesic effects could potentially be complemented by additional physiological benefits or side effects that are unrelated to the psychotropic effects of marijuana.

If these effects exist is yet probably almost as uncertain as the general usefulness of marijuana as an ergogenic, of which Pesta et al. write that if there were any, they would yet have to be established (Pesta. 2013).

• You don't have to smoke the weed to mess yourself up: Bird et al. demonstrated in 1980 that the previously mentioned detrimental effects on other aspects of performance occur with orally administered THC (215 µg/kg), as well. So don't even think of it ;-)
  Reduced work capacity of the heart at elevated heart rates -- Steadward and Singh (Steadward. 1971) were probably among the first scientists to test the effects of marijuana on exercise performance. In their study that was published as a dissertation at the University of Alberta in 1971 they found significant elevations in resting heart rate and both systolic and diastolic blood pressure at rest after marijuana consumption compared to both control and placebo. This lead to a highly significant decrease in physical work capacity at a heart rate of 170 (-25%) 
• Decrease in time to exhaustion -- Renaud's and Cormier's finding from a 1986 study appear to confirm the earlier results Steadward and Singh present in their thesis paper. The researchers  tested subjects 10 min after smoking a marijuana cigarette (containing 1.7% of Δ9-THC) of 7 mg/kg of body weight, and noted a slight, but significant decrease in cycle ergometry time to exhaustion. Avakian et al. [156] demonstrated that double.

In 1977, already Tashkin et al. (1977) hypothesized that the decrease in exercise performance may be due to itschronotropic effects, which would lead to achievement of maximum heart rate at reduced workloads.It goes without saying that - as long as you dig long enough - you will always find studies with conflicting results. The beneficial effects Tashkin et al. (1975) report in their paper, for example, occured in patients with asthma benefit from the bronchodilating effects of cannabis. For healthy individuals similar benefits are thus more than unlikely.

If there even is a benefit for pot-heads, it's probably a psychological one that could be brought about by anxiety reducing and euphorigenic effects of cannabis... but let's be honest: Isn't a healthy amount of pre-competition anxiety a necessary prerequisite for world-class performance?

Drug #4: Nicotine - Better smoke tobacco than pot?

If alcohol doesn't help and pot is downright bad for you what else could you add to your beloved caffeine? Of course! Cigarettes. I mean, nicotine and caffeine that does even sound alike! Plus: Some "experts" say that they synergistically promote weight loss (which is a non-verified hypothesis that is often supported by a single short-term human trial by Jessen et al. (2003) and entails the risk of developing diabetes; cf. Attvall. 1993).

A note on different deliver routes: Both snus and nicotine gums enable nicotine to diffuse across the mucous membranes and are taken up by the bloodstream. The effects are yet still not necessarily identical to what we see, when it is inhaled and diffuses across the alveolar membrane - particularly if the source of the nicotine is a carcinogen-packed cigarette.

With its CNS stimulating and dopaminergic effects 3-(1-methyl-2-pyrrolidinyl)pyridine aka nicotine does at first appear to be a very likely candidate for every pre-workout supplement. Unfortunately, it does also enhance the effect of serotonin and opiate activity and will thus override its own stimulatory with a calming and depressing effect (Silvette. 1962). Against that background it sounds funny that nicotine will still increase the heart rate and blood pressure (Narkiewicz. 1998), as well as cardiac stroke volume and output and coronary blood flow (Bargeron. 1957).

The question is thus: Which effects prevail? The stimulatory or the the sedating effects? The WADA apparently doesn't believe that nicotine doping is worth it. 3-(1-methyl-2-pyrrolidinyl)pyridine is currently on the watch list, but it's neither banned or officially tested for. That does yet not mean that  it cannot yield small but significant benefits for endurance athletes (17% improvement in time to exhaustion in Mündel et al. 2006) or sports where dexterity / skills play an important role (improvement in the degree in a real-life motor task, Tucha et al. 2004; positive effect on fine-motor abilities, West et al. 1986; cf. Martin. 2009). None of these effects was observed with cigarettes, though, but with a 7mg nicotine patch, a  2mg nicotine chewing gum and 2mg intranasal nicotine, respectively.

Figure 1: Cigarette smoking and risk of diabetes among 41 810 men during six years follow up (Rimm. 1995)

Whether the 17% endurance increase in the Mundal study qualifies as an incentive to "go on the patch" is yet questionable. Nicotine is not just addictive (Stolerman. 1995), going off of it will also trigger declines in motor performance that won't come handy for any athlete (Burtscher. 1994). This as well as the previously cited potential of developing insulin resistance that has been reported for both cigarettes and nicotine gums (Taskinen. 1996; the downside of the Taskinen study is that the increased diabetes risk may be a result of previous cigarette smoking - we can thus not be totally sure that chewing nicotine gums regularly increases your diabetes risk).

Nicotine + caffeine = heart damage, w/ and without ephedra | more

Bottom line: If you take a look at the results of this mini-summary, caffeine addiction isn't just the only scientifically proven "ergogenic addiction", it's also the only one without certain (alcohol and pot) and almost certain (nicotine) negative side effects.

 If I had to pick my poison I would thus always go for caffeine and ignore alcohol, pot and even nicotine; and that in spite of the fact that the latter may exert (mainly neurological) benefits in certain sports.

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