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Stimulants – Pros and Cons for Use

Stimulants – The Pros and Cons

Caffeine

It is well known that caffeine makes us all feel great! Caffeine has been used as a medicinal and recreational drug since before recorded history, by consumption of caffeine bearing plants. However, the discovery of the chemical did not occur until a young physician called Friedlieb Ferdinand Runge isolated and purified the white crystalline substance in 1819.[1] Can you imagine the first ingestion of caffeine and how it made the scientist feel? They may have thought they had discovered the antidote to ‘fatigue’!

How Caffeine Works

Caffeine has been shown to enhance performance during exercise requiring dynamic contractions of a large muscle mass. It has also been shown to have direct effects on neuromuscular output during isometric tasks using isolated muscle groups.

Evidence suggests that caffeine can potentiate twitch and tetanic tensions, increase Maximal Voluntary Contraction torque, and increase spinal excitability. More pertinently, caffeine has been repeatedly demonstrated to increase muscular endurance. Studies conducted on the knee extensors alone have found single-leg isometric time to task failure to increase by in excess of 20%. The enhancement of exercise performance following caffeine administration has been attributed to both peripheral and central mechanisms.

Caffeine On Skeletal Muscle

Although a direct effect of caffeine on skeletal muscle calcium kinetics has been inferred from measurements of dorsiflexor torque in response to low-frequency electrical stimulation, millimolar concentrations of caffeine, toxic to humans, seem to be required to demonstrate this effect in isolated muscle preparations. As a result, it is thought that the primary ergogenic effect of caffeine is to enhance central drive, through an antagonistic effect on adenosine receptors.

Caffeine and Adenosine

Adenosine preferentially inhibits the release of excitatory neurotransmitters, and thus decreases the firing rate of cortical neurons. The resulting central effects of caffeine in exercising humans are diverse, including reduced pain sensation and perceived exertion, and increased spinal and/or supraspinal excitability.[2]

Caffeine-induced adenosine receptor inhibition may influence motor function by reducing the de-facilitation of α-motoneurons or by increasing spinal excitability. These should maintain a central drive to the motoneurone pool during muscle contractions (i.e. reduce the rate of central fatigue development) and thus delay task failure. Under these conditions, if the loss of torque output complexity is driven, in part, by central mechanisms, we would expect caffeine to blunt the development of central fatigue and delay the fatigue-induced loss of torque complexity during intense intermittent contractions. It is therefore hypothesized that caffeine ingestion would reduce the rate at which torque output complexity fell during fatiguing contractions.[3]

Coffee or Caffeine?

Coffee consumption is associated with reduced risk of conditions that share low-grade inflammation as their physiopathological basis. It is therefore summarized the effects of coffee or coffee components on serum levels of inflammatory markers. Clinical trials assessing the effect of coffee, caffeine or other coffee components on inflammatory markers were searched without restriction to publication date.

Researchers have looked at fifteen studies 8 involving coffee and 7 caffeine were included. Increased adiponectin (protein hormone that regulates glucose and fatty acid metabolism) levels were found in four of seven trials comparing filtered coffee/caffeinated coffee with placebo or comparing its levels at baseline and after consumption of medium or dark roasted coffee, but no change was seen in caffeine trials. None of the five studies assessing the effects of coffee found changes in C-reactive protein (CPR), but one out of three trials found decreased CPR levels in response to caffeine. Interleukin (IL)-6 was increased by caffeinated coffee compared with placebo in one of four coffee trials, and by caffeine in three out of five studies.

The Results 

Caffeine increased IL-10 levels in two of three trials. These data suggest a predominant anti-inflammatory action of coffee but not of caffeine consumption. Moreover, the proinflammatory and anti-inflammatory responses to caffeine point to its complex effects on the inflammatory response. This means that coffee has other components that are active in the body and not just caffeine.[4]

Caffeine’s brain benefits

Caffeine is one of the most consumed stimulants of the central nervous system. Similar to those of other stimulants, its effects are to improve brain activity and stimulate cognition learning and memory. Caffeine affects the brain by acting mainly as a non-selective blocker of the adenosine receptors (A1, A2A, A2B, and A3).

Caffeine has been found in some studies to effectively counteract several neurodegenerative disorders such as Alzheimer’s, Parkinson’s, Huntington’s diseases, Multiple sclerosis, and Amyotrophic lateral sclerosis and Epilepsy. What emerges is a significant therapeutic and prophylactic potentiality of caffeine because of its antioxidant activity combined with multiple molecular targets.[5]

Caffeine may reduce Testosterone

Prepubertal chronic caffeine exposure adversely affected the development of the testes in male rats. Researches investigated dose- and time-related effects of caffeine consumption on the testis throughout sexual maturation in prepubertal rats. A total of 80 male SD rats were randomly divided into four groups: controls and rats fed different amount of caffeine, respectively, via gavage for 10, 20, 30, or 40 days.

Caffeine exposure significantly increased the relative weight of the testis in a dose-related manner after 30 days of exposure, whereas the absolute testis weight tended to decrease at the higher dose of caffeine. Put simply, caffeine may act directly on Leydig cells and interfere with testosterone production in a dose-related manner, consequently delaying the onset of sexual maturation.[7]

Caffeine affects hormones in Performance

Caffeine has beneficial effects on various aspects of athletic performance, but its effects on training have been neglected. Researches investigated the acute effect of caffeine on the exercise-associated increases in testosterone and cortisol in a double-blind crossover study.

Twenty-four professional rugby-league players ingested caffeine doses of 0, 200, 400, and 800 mg in random order 1 hr before a resistance-exercise session. Saliva was sampled at the time of caffeine ingestion, at 15-min intervals throughout each session, and 15 and 30 min after the session. Data were log-transformed to estimate percent effects with mixed modeling, and effects were standardized to assess magnitudes.

Testosterone concentration showed a small increase of 15% (90% confidence limits, +/- 19%) during exercise. Caffeine raised this concentration in a dose-dependent manner by a further small 21% (+/- 24%) at the highest dose. While this sounds good, the 800-mg dose also produced a moderate 52% (+/- 44%) increase in cortisol. The effect of caffeine on the testosterone: cortisol ratio was a small decline (14%; +/- 21%).

Pre-workout Stimulant Powders – Don’t Boost Performance

The use of pre-workout beverages is becoming an increasingly common method of improving performance during exercise in athletic and recreationally active populations. Therefore, the purpose of this study was to investigate the effects of a commercially available energy drink on exercise performance. Thirty-one healthy males (n=23) and females (n=8) participated in this study and were separated into two groups: supplement (SU; n=16) or placebo (PL; n=15).

Post-testing revealed no significant difference between groups in total push-ups completed or RPE at any time point, when compared to baseline. In conclusion, the commercially available PWEDS offered no additional ergogenic effects when compared to the placebo.[8]

Pre-workout Stimulant Powders – Doesn’t Improve Body Composition

Pre-workout supplements containing numerous ingredients claim to increase performance and strength. Product-specific research is important for identifying efficacy of combined ingredients. The purpose of this study was to evaluate the effects of a proprietary pre-workout dietary supplement containing creatine monohydrate, beta-alanine, L-Tarurine, L-Leucine, and caffeine, on anaerobic power, muscular strength, body composition, and mood states.

The research

In a double-blind, randomized, matched-pair design, twenty male subjects (mean ± SD; 22.4 ± 9.5 yrs, 76.9 ± 11.2 kg, 22.7 ± 9.5% body fat), consumed either 30 g of a pre-workout supplement (SUP) or maltodextrin placebo (PLC) 30 minutes before a resistance training workout, after completing baseline testing.

There was no significant treatment × time interactions (p > 0.05). There were no significant changes in %body fat (%BF; ∆-0.43 ± 0.58; p = 0.920), fat mass (∆-2.45 ± 5.72; p = 0.988), or lean body mass (LBM; 10.9 ± 12.2; p = 0.848). There was no significant difference in mood states between groups or over time.

The researchers found that the proprietary pre-workout blend combined with eight days of training did not significantly (ANOVA) improve body composition or performance.[9]

The Bottom line?

The bottom line is that caffeine has some potential to benefit training outcomes via the anabolic effects of the increase in testosterone concentration, but this benefit might be counteracted by the opposing catabolic effects of the increase in cortisol and the resultant decline in the testosterone: cortisol ratio.[10]

Here are the mechanisms of action behind cortisol’s testosterone suppressing effects if you’re not yet familiar with them:

  • Your testicles produce this enzyme called 11ßHSD-1 which normally protects your testosterone molecules from cortisol, but in the times of prolonged stress and chronically elevated levels of the stress hormone, there simply is too much cortisol for 11ßHSD-1 to handle.
  • When cortisol levels are high for a long time, the body directs more of its available cholesterol into cortisol synthesis, which leaves less of the good stuff for testosterone synthesis.

DMAA

DMAA was originally developed by Eli-Lilly in 1948 and then later trademarked as Forthane to be used as a nasal decongestant (there are varying accounts but it seems that Eli Lilly patented the molecule in the early 1940s, trademarked and marketed it as Forthane in 1971 for allergic rhinitis, and then voluntarily withdrew it in 1983).

The mechanism of action was vasoconstriction – the blood vessels in the nose would constrict so that less blood flow would lead to less nasal discharge. This is a mechanism used by common OTC nasal sprays like oxymetazoline (Afrin) and is indeed quite effective. However, Forthane was later withdrawn from the market because of significant side effects including headaches, tremors, and increased blood pressure.

These effects likely occur because DMAA is structurally similar to amphetamine and as a result, the compound is not only a vasoconstricting agent but is also a central nervous system (CNS) stimulant.[11]

The Science for DMAA

Analysis of seven participants showed DMAA had an oral clearance of 20.02 ± 5 L∙hr-1, an oral volume of distribution of 236 ± 38 L, and a terminal half-life of 8.45 ± 1.9 hr. Lag time, the delay in the appearance of DMAA in the circulation following extravascular administration, varied among participants but averaged approximately 8 minutes (0.14 ± 0.13 hr). The peak DMAA concentration for all subjects was observed within 3–5 hours following ingestion and was very similar across subjects, with a mean of ~70 ng∙mL-1. Heart rate, blood pressure, and body temperature were largely unaffected by DMAA treatment.[12]

The Systemic Banning of DMAA

DMAA was banned in Canada in 2011 and has since been banned or heavily restricted in other countries including New Zealand (banned in 2012) and the United States (illegal to market as a dietary supplement). Prior to 2012, DMAA was not a scheduled substance in Australia. In June 2012, the Advisory Committee on Medicines Scheduling proposed including DMAA in Schedule 9 (‘Prohibited Substances’) of the Standard for the Uniform Scheduling of Medicines and Poisons (SUSMP). Six premeeting submissions were received; of these, five were against the prohibition (Therapeutic Goods Association, 2012).

TGA Banning of DMAA

The Therapeutic Goods Association (TGA) ultimately included DMAA in Appendix C of the SUSMP, noting that DMAA has no currently accepted therapeutic use; a stimulant effect which can include psychoactive effects; that the substance was actively promoted as a ‘party drug’ as well as a sports supplement; and that a number of significant adverse events had been reported due to the use of DMAA (Therapeutic Goods Association, 2012). Given this decision, sports supplements that contained DMAA were also banned.[13]

The findings from a current review suggest that there may be some harm related to DMAA use, and while the current findings suggest serious adverse effects may be possible, these may very infrequently be reported.[14]

The bottom line for DMAA

This means that for most people, it is likely to be safe, but if you are sensitive to DMAA or consume too much, DMAA may be harmful. Also, if you are reading this, it is likely DMAA is banned in your country so please check this before you purchase it.

So, to Stimulate or not?

Ok, the research shows there are benefits and side effects from taking stimulants. Because chemicals like caffeine are consumed by probably billions of people, it is likely that it is safe in lower doses and may help you get to the gym. If this is the case then good for you. The worst type of exercise is none at all.

However; if you are glugging down a super-charged pre-workout powder with 300+mg of caffeine in it, it is likely to have side effects. The most obvious one is that it may keep you awake if you take it after work in the evening. It also blunts growth hormone release and increases cortisol levels, both lead to catabolism of precious muscle tissue. And while testosterone levels may increase, it is completely offset by the increased cortisol level. Also, consuming a pre-workout powder and working out was no better than taking a placebo powder and working out.

References: 

[1] http://www.chm.bris.ac.uk/webprojects2001/tilling/isolation.htm

[2] Med Sci Sports Exerc. 2017 Oct 3. Caffeine Ingestion Attenuates Fatigue-induced Loss of Muscle Torque Complexity. Pethick J1, Winter SL, Burnley M.

[3] Med Sci Sports Exerc. 2017 Oct 3. Caffeine Ingestion Attenuates Fatigue-induced Loss of Muscle Torque Complexity. Pethick J1, Winter SL, Burnley M.

[4] Crit Rev Food Sci Nutr. 2017 Oct 2:0. Consumption of coffee or caffeine and serum concentration of inflammatory markers: a systematic review. Clrs P1, Bts B1, Ceg R2, Jg D2, Thm C2, Aa A1.

[5] Curr Med Chem. 2017 Oct 9. Protective effects of the caffeine against neurodegenerative diseases. Tellone E1, Galtieri A1, Russo A1, Ficarra S1.

[6] J Sports Sci Med. 2010 Jun 1;9(2):262-9. Caffeine attenuates acute growth hormone response to a single bout of resistance exercise. Wu BH1, Lin JC.

[7] Exp Anim. 2017 Jan 27;66(1):29-39. Dose- and time-related effects of caffeine on the testis in immature male rats. Bae J1, Choi H, Choi Y, Roh J.

[8] Int J Exerc Sci. 2016 Nov 1;9(5):667-676. Effects of a Pre-workout Energy Drink Supplement on Upper Body Muscular Endurance Performance. Magrini MA1, Colquhoun RJ1, Dawes JJ2, Smith DB1.

[9] J Int Soc Sports Nutr. 2014 Aug 15;11:40. Acute effects of a commercially-available pre-workout supplement on markers of training: a double-blind study. Outlaw JJ1, Wilborn CD1, Smith-Ryan AE2, Hayward SE1, Urbina SL1, Taylor LW1, Foster CA1.

[10] Int J Sport Nutr Exerc Metab. 2008 Apr;18(2):131-41. Dose effect of caffeine on testosterone and cortisol responses to resistance exercise. Beaven CM1, Hopkins WG, Hansen KT, Wood MR, Cronin JB, Lowe TE.

[11] M. Dunn, Have prohibition policies made the wrong decision? A critical review of studies investigating the

effects of DMAA, International Journal of Drug Policy (2016),

[12] Physiological and pharmacokinetic effects of oral 1,3-dimethylamylamine administration in men

Brian K SchillingEmail author, Kelley G Hammond, Richard J Bloomer, Chaela S Presley and Charles R Yates

BMC Pharmacology and Toxicology201314:52

[13] M. Dunn, Have prohibition policies made the wrong decision? A critical review of studies investigating the

effects of DMAA, International Journal of Drug Policy (2016),

[14] M. Dunn, Have prohibition policies made the wrong decision? A critical review of studies investigating the

effects of DMAA, International Journal of Drug Policy (2016),