ONLINE DRIVERS MEDIA

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 dont Id suggest you start out with this SuppVersity Classic before you devote yourself to RocknRoll 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).
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 worlds "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 its 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 everyones 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).
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] - Dont 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 thats 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 its 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 thats 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, wouldnt it make sense to switch from wine + strichnine to marijuana? Ok, you cant consume it "intra-workout", but maybe before and after the Queens stage at L’Alpe d’Huez?!
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 dont 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 dont 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 -- Renauds and Cormiers 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 ?9-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, its probably a psychological one that could be brought about by anxiety reducing and euphorigenic effects of cannabis... but lets be honest: Isnt a healthy amount of pre-competition anxiety a necessary prerequisite for world-class performance?

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

If alcohol doesnt 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).
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 doesnt believe that nicotine doping is worth it. 3-(1-methyl-2-pyrrolidinyl)pyridine is currently on the watch list, but its 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 wont 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).
References:

• Anand, Praveen, et al. "Targeting CB2 receptors and the endocannabinoid system for the treatment of pain." Brain research reviews 60.1 (2009): 255-266.
• Attvall, S., et al. "Smoking induces insulin resistance—a potential link with the insulin resistance syndrome." Journal of internal medicine 233.4 (1993): 327-332. 
• Burtscher, M., et al. "Motor symptoms similar to parkinsonism in heavy smokers." International journal of sports medicine 15.04 (1994): 207-212.
• Margeron, L., et al. "Effect of cigarette smoking on coronary blood flow and myocardial metabolism." Circulation 15.2 (1957): 251-257.
• Bird, K. D., et al. "Intercannabinoid and cannabinoid-ethanol interactions and their effects on human performance." Psychopharmacology 71.2 (1980): 181-188.
•  Chopra, Gurbakhsh Singh. "Man and marijuana." Substance Use & Misuse 4.2 (1969): 215-247.
• Chou, Tony. "Wake up and smell the coffee. Caffeine, coffee, and the medical consequences." Western Journal of Medicine 157.5 (1992): 544.
• Derry, Christopher J., Sheena Derry, and R. Andrew Moore. "Caffeine as an analgesic adjuvant for acute pain in adults." Cochrane Database Syst Rev 3 (2012). 
• Fife W, eds. Tour de France – The History, the Legend, the Riders, Vol. 100. Edinburgh and London: Mainstream Publishing, 2000: 1–255.
• Graham, Terry E. "Caffeine and exercise." Sports medicine 31.11 (2001): 785-807. 
• Gawryszewski V.P., and Monteiro M.G. "Mortality from diseases, conditions, and injuries where alcohol is a necessary cause in the Americas, 2007-2009". Addiction (2014) [ahead of print].
• 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.
• Hill, Matthew N., et al. "Endogenous cannabinoid signaling is required for voluntary exercise?induced enhancement of progenitor cell proliferation in the hippocampus." Hippocampus 20.4 (2010): 513-523.
• Lucia, Alejandro, Conrad Earnest, and Carlos Arribas. "The Tour de France: a physiological review." Scandinavian journal of medicine & science in sports 13.5 (2003): 275-283.
• Martin, Laura F., Deana B. Davalos, and Michael A. Kisley. "Nicotine enhances automatic temporal processing as measured by the mismatch negativity waveform." Nicotine & Tobacco Research 11.6 (2009): 698-706.
• Mündel, Toby, and David A. Jones. "Effect of transdermal nicotine administration on exercise endurance in men." Experimental physiology 91.4 (2006): 705-713.
• Murray, Christopher JL, and Alan D. Lopez. "Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study." The Lancet 349.9063 (1997): 1436-1442.
• Narkiewicz, Krzysztof, et al. "Cigarette smoking increases sympathetic outflow in humans." Circulation 98.6 (1998): 528-534.
• Pesta, Dominik H., et al. "The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance." Nutrition & metabolism 10.1 (2013): 71.
• Pedersen, David J., et al. "High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine." Journal of Applied Physiology 105.1 (2008): 7-13. 
• Renaud, A.M., and Cormier, Y. "Acute effects of marihuana smoking on maximal exercise performance." Medicine and science in sports and exercise 18.6 (1986): 685-689. 
• Rimm, Eric B., et al. "Prospective study of cigarette smoking, alcohol use, and the risk of diabetes in men." Bmj 310.6979 (1995): 555-559.
• Rush, James WE, and Lawrence L. Spriet. "Skeletal muscle glycogen phosphorylase akinetics: effects of adenine nucleotides and caffeine." Journal of Applied Physiology 91.5 (2001): 2071-2078. 
• Silvette, H., et al. "The actions of nicotine on central nervous system functions." Pharmacological reviews 14.1 (1962): 137-173.
• Spriet, L. L., et al. "Caffeine ingestion and muscle metabolism during prolonged exercise in humans." American Journal of Physiology-Endocrinology And Metabolism 262.6 (1992): E891-E898.
• Steadward, R. D-, and Singh M. The effects of smoking marihuana on physical performance. Diss. University of Alberta, 1971. 
• Stolerman, Ian P., and M. J. Jarvis. "The scientific case that nicotine is addictive." Psychopharmacology 117.1 (1995): 2-10.
• 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.
• Tarnopolsky, Mark, and Cynthia Cupido. "Caffeine potentiates low frequency skeletal muscle force in habitual and nonhabitual caffeine consumers." Journal of applied physiology 89.5 (2000): 1719-1724. 
• Tashkin, Donald P., et al. "Effects of smoked marijuana in experimentally induced asthma." Am Rev Respir Dis 112.3 (1975): 377-86.
• Tashkin, D. P., et al. "Cannabis, 1977." Annals of Internal Medicine 89.4 (1978): 539-549. 
• Tucha, Oliver, and Klaus W. Lange. "Effects of nicotine chewing gum on a real-life motor task: a kinematic analysis of handwriting movements in smokers and non-smokers." Psychopharmacology 173.1-2 (2004): 49-56.
• West, R. J., and M. J. Jarvis. "Effects of nicotine on finger tapping rate in non-smokers." Pharmacology Biochemistry and Behavior 25.4 (1986): 727-731.
• Umemura, Takashi, et al. "Effects of acute administration of caffeine on vascular function." The American journal of cardiology 98.11 (2006): 1538-1541.

It doesnt matter if you want to turn fat into fit, fit into fitter or strong into stronger. Todays SuppVersity science potpourri has something to offer for every physical culturist who is looking for ways to improve his health, performance and physique and for trainers and coaches who work with this challenging clientele.

In view of the fact that the last news-potpourri on appetite related scientific studies was a major success, I thought it may be worth writing another of these long-neglected short-news items. This time about exercise and supplementation, though.

You may already have seen the link to Stuart Philipps latest "Review of Higher Dietary Protein Diets in Weight Loss" with a "A Focus on Athletes" on Facebook. For those of you who have been following the SuppVersity News theres probably little new information in the document, though. When I read the paragraph about optimal protein intakes for maximal muscle retention, I still thought that it may be worth to remind you of the results of the Pasiokos study which clearly suggest that eating more protein is not always going to increase the net protein retention when you are dieting.
A fact that brings me back to Philipps review in which he points out that dieters commonly overlook that any increase in protein intake will go at the expense of either fat or carbohydrate. A "side effect" that could be particularly problematic for athletes, for whom Philipps recommends (just like I do) "to balance the increase in protein consumption with what macronutrient is reduced" (Phillips. 2014). In particular, athletes should "focus on reducing intakes of lipids to allow carbohydrate intakes to achieve performance" (Phillips. 2014).

After this brief introductory interlude, I would like to get to the actual topic at hand, a brief overview of a couple of interesting, but not exactly "full-article worthy" papers from the realms of exercise, nutrition and supplementation:

• Low volume, high intensity the exercise key to perfect health? A recent paper in the latest edition of Sports Medicine reviewed the health benefits of two different low volume exercise regimen: The classic sprint interval training (black spikes in Figure 1) and a HIIT protocol (grey bars in Figure 1).
  
  The researchers from the McMaster University in Hamilton, Ontario, highlight that the currently available evidence is largely based on short-term interventions. And while long(er)-term interventions would be needed to " to advance our basic understanding of how manipulating the exercise stimulus translates into physiological remodeling" (Gibala. 2014), it can already be said that...

  Figure 1: Comparison of the power output (% of VO2peak) during sprint interval training (SIT, black peaks), high intensity interval training (HIIT, grey bars) and moderate intenstity continuous training (MICT, striped box)

  "[f]rom an applied perspective, there is value in trying to establish the minimum ‘dose’ of HIIT or SIT needed to stimulate meaningful improvements in clinical markers that are associated with disease risk.
  
  This is particularly germane given that ‘lack of time’ remains the most commonly cited barrier to regular exercise participation, and considering evidence that suggests that low-volume interval training is perceived to be more enjoyable than MICT." (Gibala. 2014)

  As Gibala et al. point out, there is also evidence that nutritional interventions can influence both acute and chronic adaptations to interval training - with one of my personal favorites, i.e. sodium bicarbonate being the #1 candidate to among the "interval-specific" ergogenics that are currently available on the market (learn why).

  Figure 2: Everything works, as long as you pick the right type of exercise for your type.

  Moreover, as suggested by van Loon and Tipton (van Loon. 2013), the significantly greater adaptation efficiency compared to "regular" steady state cardio training has clinical relevance, especially for individuals with severe exercise intolerance.
• Low dose caffeine (200mg) not effective for everyone - A recent study from the University of Guelph found that low doses of caffeine (<3 mg/kg body mass, ~200 mg) can be ergogenic in some exercise and sport situations, but for most athletes they will not alter the peripheral wholebody responses to exercise, or improve vigilance, alertness, and mood and cognitive processes during and after exercise.
  
  

  Figure 3: Effects of ingesting no caffeine (0) or 3, 6 or 9 mg/kg body mass of caffeine (dose) on running time to exhaustion at ~85 % of VO2max (Graham. 1995).

  In view of the fact that low dose caffeine regimen are also "associated with few, if any, side effects" (Spriet. 2014), and generally depend on an athletes individual response to caffeine, Lawrence L. Spriet still suggests that athletes should "determine whether the ingestion of ~200 mg of caffeine before and/or during training and competition is ergogenic on an individual basis" (Spriet. 2014); and, assuming that it is, make use of the lowest effective dose, of which the data in Figure 3 clearly indicates that it is not necessarily the one with the lowest performance benefits.
• Science-Based Recommendations for Training to Maximize Concurrent Training - Right from the desk of Keith Baar comes a set of recommendations to maximize the benefits of concomitant training, i.e. combined / sequential endurance and strength training that consists of a set of four tips:
  
  • Do HIIT in the AM: Any high-intensity endurance training sessions should be performed early in the day. Then, a period of recovery of at least 3 h should be given, so that AMPK and SIRT1 activity can return to baseline levels, before resistance exercise is performed. This suggestion is based on the fact that AMPK activity increases rapidly and then returns to baseline levels within the first 3 h after high-intensity exercise (Wojtaszewski. 2000), whereas mTORC1 activity can be maintained for at least 18 h after resistance exercise (Baar. 1999; MacKenzie. 2009).

  • Build 3.2kg of lean mass overnight w/ 40g of casein pre-bed | learn more.

    Drink your whey protein shake right after your strength workout: Resistance exercise should be supported by readily digestible, leucine-rich protein as soon as possible after training to maximize leucine uptake, mTOR recruitment to the lysosome, and protein synthesis.
    
    In view of the fact that Baar recommends to do your RT sessions later in the day, it is also advisable to consume another protein shake right before bed to maximize the synthetic response overnight (learn more).
  • Fully refuel between the morning high-intensity endurance training session and the afternoon strength session: Its not going to reduce the exercise induced increase in AMPK and SIRT1 activation, but will allow you to perform at maximal intensity during your resistance training session later in the day.
    
    As Baar points, out athletes who have to diet during certain phases of their training cycle should make sure to "reserve a portion of the offseason (and short periods in season) exclusively for increasing muscle size and strength and then use higher dietary protein intakes to maintain that muscle mass as the aerobic load increases through the season" (Baar. 2014).
  • If you do low-intensity cardio, do your resistance training right after cardio: To improve the endurance response to lower-intensity endurance training sessions and provide a strong strength stimulus, Baar recommends performing strength training immediately after low-intensity, non-depleting, endurance sessions.
    
    Performing a strength session immediately after a low-intensity endurance session results in a greater stimulus for endurance adaptation than the low-intensity endurance session alone (Wang. 2011) and the low-intensity session will not affect signaling pathways regulating strength gains (Coffey. 2009; Lundberg. 2012; Apró. 2013).
  At first, these rrecommendations may sound somewhat random. If you take a closer look at the long paper, you will yet have to concede that the simple recommendations are based on our current understanding of the molecular response to exercise. In that, they should allow for the maximal adaptive response to both endurance and strength exercise.
  

References:

• Apró, William, et al. "Resistance exercise induced mTORC1 signaling is not impaired by subsequent endurance exercise in human skeletal muscle." American Journal of Physiology-Endocrinology and Metabolism 305.1 (2013): E22-E32.
• Baar, Keith, and Karyn Esser. "Phosphorylation of p70S6kcorrelates with increased skeletal muscle mass following resistance exercise." American Journal of Physiology-Cell Physiology 276.1 (1999): C120-C127. 
• Coffey, Vernon G., et al. "Consecutive bouts of diverse contractile activity alter acute responses in human skeletal muscle." Journal of applied physiology 106.4 (2009): 1187-1197.
• Graham, T. E., and L. L. Spriet. "Metabolic, catecholamine, and exercise performance responses to various doses of caffeine." Journal of Applied Physiology 78.3 (1995): 867-874. 
• Lundberg, Tommy R., et al. "Aerobic exercise alters skeletal muscle molecular responses to resistance exercise." Medicine and science in sports and exercise 44.9 (2012): 1680-1688.
• Pasiakos, Stefan M., et al. "Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial." The FASEB Journal 27.9 (2013): 3837-3847.
• van Loon, Luc JC, and Kevin D. Tipton. "Concluding Remarks: Nutritional Strategies to Support the Adaptive Response to Prolonged Exercise Training." (2013): 135-141. 
• Wall, et al. "Dietary Protein Considerations to Support Active Aging." Sports Med (2014) 44 (Suppl 2):S185–S194.
• Wang, Li, et al. "Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle." Journal of applied physiology 111.5 (2011): 1335-1344.
• Wojtaszewski, Jørgen FP, et al. "Isoform-specific and exercise intensity-dependent activation of 5?-AMP-activated protein kinase in human skeletal muscle." The Journal of physiology 528.1 (2000): 221-226.

Ever since the Vinson study showed that green coffee bean extracts can help overweight women lose weight, green coffee is sexier than roasted one.

Only weeks after Vinson et al. were able to show that "Green Coffee Bean Extract Helps Pre-Obese Men and Women Shed 16lbs in 22 Weeks" (read more), green coffee bean supplements began to swamp the market - a great financial success for the supplement producers, and that despite the fact that follow-up studies that would confirm the amazing effects Vinson et al. report are still lacking. Two recent studies, one from the Queen Margaret University in the UK (Revuelta-Iniesta. 2014), the other from the  Jiangxi Agricultural University in the Peoples Republic of China (Zheng. 2014) could now shed a little more light on the weight loss effects of green coffee beans and the combination of caffeine and cholorgenic acid (CGA), the allegedly most important active ingredient in unroasted, green coffee beans.
In their 24-week rodent study, Zhang et al. (2014) tried to elucidate the mechanism by which CGA and caffeine regulate lipid metabolism. To this ends, they randomized their forty hairy subjects to diets containing no CGA or caffeine, CGA, caffeine, or CGA + caffeine.

Figure 1: Rel. (vs. control) body weight changes and liver and intraperitoneal adipose tissue weight (Zhang. 2014)

Over the course of the 24-weeks study, the scientists recorded body weight, intraperitoneal adipose tissue (IPAT) weight, and serum biochemical parameters of the rodents, tracked the the activities and mRNA and protein expression of lipid metabolism-related enzymes and analyzed the effects of caffeine, CGA and the combination of the two. What they found was...

1. Figure 2: Effects of chlorogenic acid (CGA) and caffeine on the hepatic protein expression levels of AMP-activated protein kinase (AMPK), adipose TAG lipase (ATGL) and fatty acid synthase (FAS; Zhang. 2014)

   decreases in the body weight and IPAT weight of mice fed the CGA + caffeine diet,
2. significant decreases in the serum and hepatic concentrations of total cholesterol, TAG and leptin of mice fed the CGA + caffeine diet,
3. increases of the activity of carnitine acyltransferase (CAT) and acyl-CoA oxidase (ACO), 
4. decreased levels of fatty acid synthase (FAS) and the respective mRNA levels
5. significantly upregulated mRNA expression levels of AMP-activated protein kinase (AMPK), CAT and ACO
6. pronounced reductions of PPARg2

If we group these findings as follows 3 + 5 and 4+6, we could say that they triggered 1 + 2 by (a) increasing the oxidation of fatty acids (3+5) and (b) decreasing the synthesis and storage of fatty acids (4+6) - an observation that could certainly explain the benefits Vinson et al. observed in their human study which has been retracted in October 2014, though. On the other hand, the amount of CGA and caffeine in the rodent diets (0.2 % CGA + 0.03 % caffeine) was quite significant and previous rodent studies on other allegedly promising fat burners were not replicable in human beings either (example: CLA). Against that background its good to have study #2 by R. Revuelta-Iniesta and E. A. S. Al-Dujaili, who investigated the effects of green coffee (GC), rich in chlorogenic acid, and black coffee (BC) on cardiovascular markers.

New human data with surprising results

The researchers designed a randomised pilot crossover study with healthy subjects who consumed both coffees for 2 weeks.

• The green coffee (GC) used in this project was Ethiopian Harrar 4 (100% Arabica) and the black coffee (BC) was Sainsbury’s Original Blend Cafetitère Coffee.
• The BC was  a blend of Brazilian, Colombian, Mexican, Nicaraguan, Peruvian, and Rwandan beans.

The study participants were asked to have 40 g of GC and BC per day distributed throughout the day into four cups of coffee. Thus, the scientists tried to ensure that high plasma coffee antioxidant concentrations were maintained over a period of time, "allowing effects to take place and the body to develop tolerance to caffeine, which can take 2-3 days." (Revuelta-Iniesta. 2014).

Table 1: Concentration of total polyphenols and antioxidant capacity determined in GC and BC as compared by the three methods of  coffee preparation (Revuelta-Iniesta. 2014).

The GC beans were grounded to powder using an electric coffee grinder. Instructions on how to make the coffee were provided and the Italian cafetière, the French cafetière, or the filter coffee machine was used to prepare the coffee drink.

The researchers measured anthropometry, blood pressure, and arterial elasticity after each intervention and collected urine samples to monitor antioxidant capacity. The free cortisol and cortisone levels you see in Table 2 were obtained from urine and analysed by specific ELISA methods.

Table 2: Comparison of results obtained (mean±SEM) after 14 days of green coffee vs. black coffee intervention (2-week cross over study); F: cortisol; E: cortisone; orange = almost bordeline significant; green = statist. significant inter-group difference (Revuelta-Iniesta. 2014).

In view of the short duration of the study (remember 2 weeks on each coffee), its not really surprising that we didnt see changes in any of the anthropometric measures. On the other hand, the mere fact that the cortisol/cortisone ratio (indicating 11beta-HSD1 activity) was reduced after GC (from 3.5 +/- 1.9 to 1.7 +/- 1.04, P = 0.002) does not suggest that you will see beneficial effects on body composition in the absence of significant reductions in energy intake. A reduction in glucocorticoid activity can in fact hamper not accelerate weight loss (learn more) and the researchers hypothesis that "GC can play a role in reducing cardiovascular risk factors" (Revuelta-Iniesta. 2014) is a possible, but unconfirmed hypothesis.
References:

• Jaquet, Muriel, et al. "Impact of coffee consumption on the gut microbiota: a human volunteer study." International journal of food microbiology 130.2 (2009): 117-121.
• Revuelta-Iniesta, R., and E. A. S. Al-Dujaili. "Consumption of Green Coffee Reduces Blood Pressure and Body Composition by Influencing 11?-HSD1 Enzyme Activity in Healthy Individuals: A Pilot Crossover Study Using Green and Black Coffee." BioMed Research International 2014 (2014).
• Vinson, Joe A., Bryan R. Burnham, and Mysore V. Nagendran. "Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects." Diabetes, metabolic syndrome and obesity: targets and therapy 5 (2012): 21.
• Zheng, et al. "Chlorogenic acid and caffeine in combination inhibit fat accumulation by regulating hepatic lipid metabolism-related enzymes in mice." British Journal of Nutrition (2014). Ahead of Print.