Robbie Durand, M.A. Muscular Development
"All my athletes took it. It is bigger than creatine." —Victor Conte
Victor Conte is of course referring to Viagra. Like Viagra, Cialis also is used to treat erectile dysfunction. What’s the difference between the two? Although Viagra and Cialis both work by inhibiting an enzyme called phosphodiesterases, which increases vasodilatation, there are pharmacologic distinctions between Viagra and Cialis, being that Cialis has a longer half-life (17.50 hours) compared to Viagra (4.0–5.0 hours) and Levitra (4.0–5.0 hours), resulting in longer duration of action14 which is partly responsible for Cialis being dubbed "The Weekend Pill." Cialis’ molecular structure differs significantly from Viagra; one of the benefits of Cialis is there are no visual side effects like Viagra and an absence of effect of food on absorption. Nitric oxide is a hot topic of debate in bodybuilding, as NO-producing supplements are always one of the top-selling products. Being in touch with many bodybuilders and powerlifters, many swear that by taking Cialis, they get better pumps in the gym and can recuperate from exercise faster.
Many suspect its enhanced nutrient delivery or some other mechanism. Cialis demonstrates similar vasodilator (blood pressure-lowering) effects in healthy subjects when compared with Viagra in studies of 10mg or 20mg doses (mean systolic blood pressure reduction, of ~4.3mg).12 Many of the experts in sports will attest that nitric oxide only increases performance in environments with low oxygen availability, such as high-altitude training or areas with high air pollution. Brazilian Eduardo de Rose, president of the medical commission of the Pan-American Sports Organization, stated in a recent interview: "Scientifically, the only proof that Viagra improves sports performance happened at high altitude. That is why it was decided not to include it in the banned substance list. You will hardly get to play a football match on Mount Everest." If there are no performace-enhacing effects, then why were Olympic athltetes using it? There have only been a handful of studies on the performance-enhancing effects of Cialis and sports performance, and none yielded beneficial effects:
• In one study, 14 healthy young males were given a 20mg dose of Cialis or a placebo and performed a maximal exercise test on a treadmill. The study found that a single dose of Cialis had no effect on exercise performance, exercise tolerance or cardiopulmonary responses.5
• The second study involved three “all-out” sprints to determine if Cialis could increase anaerobic threshold. The study found no significant differences in peak power, average power or fatigue index compared to a placebo. One positive finding noted was that Cialis decreased the time to reach peak power. The author concluded, “Cialis did not have an effect on peak power, but time to peak power output was reduced. Only to sports that need to reach maximum power output in a few seconds could Cialis administration be beneficial.”13
Bodybuilders are known for bringing cutting-edge pharmacology to the forefront of science. If NO (nitric oxide) products really don’t work, then why do so many people use them? Given that the second study reported that the author claimed that Cialis may increase peak force, the powerlifters who swear by Cialis increasing performance may be onto something that research has not discovered yet.
Nitric Oxide Supplements Increase Satellite Cells
You may have read in the Nutrition Performance section that aging results in a blunted anabolic gene response to exercise. It has been previously reported that aging results in a blunted satellite cell response to exercise. A decrease in NO production with aging may be a contributing role of the decrease in muscle mass with aging. Previous research has shown that blunting production of NO decreases muscle hypertrophy during muscle overload.9, 10 Others have reported that NO is a primary signal for satellite cell activation.11 NO is an important regulator of hepatocyte growth factor (HGF), which is a cytokine with various cellular functions on muscle.2 Specific to skeletal muscle hypertrophy, HGF activates satellite cells and may be responsible for causing satellite cells to migrate to the injured area.1 A previous research study that stretched muscle-induced hypertrophy via release of HGF found that the release of HGF was dependent on NO concentrations.3 Interestingly, researchers measured HGF levels in serum after an intense bout of eccentric exercise. They found that liver-derived HGF rose 19 percent approximately 4 hours after exercise, which resulted in an activation of satellite cells! It is possible that the observed rise in serum HGF showed that HGF may be carried to the site of injury by immune cells rushing to the site of injury, which are increased in number during the inflammatory response to muscle damage… or that muscle itself produces HGF, so they were not sure which one it really was.
NO Increases Satellite Cells!
Researchers from the Center for Exercise Science in Gainesville, Florida reported that increasing nitric oxide increased satellite cell activity! They took old and young mice and induced muscle damage in both groups. They found that the older mice had an impaired satellite cell response. More importantly, they found that L-arginine and nitric oxide precursors effectively increased satellite cell activation and that nitric oxide precursors “rescued” satellite cell activation in older mice.4 This study suggests that taking a NO precursor supplement may increase satellite cell and lead to greater muscle growth! Another interesting study reported in the Journal of Muscle and Nerve was that NO was able to reverse the damaging effects of cortisol-induced satellite cell depletion. They found that NO had a dose-dependent effect on increasing satellite cell levels.20
Cialis Increases Testosterone!
Based on the research, acute dosages of Cialis do not have performance-enhancing effects, but new research suggests that Cialis increases testosterone! Researchers had participants perform three 30-second “all-out” sprints to exhaustion and measured testosterone and cortisol responses to exercise. They found that only after Cialis and exercise did testosterone increase, however Cialis also increased cortisol levels. Cialis also lowered the DHEA to cortisol response. The study demonstrates that Cialis increases the “stress” response to the body, but also has some testosterone-enhancing effects as well. It’s interesting that a large dosage of caffeine, which is a weak, non-specific PDE inhibitor, also caused an increase in testosterone and also an increase in cortisol.21 So it seems that Cialis has both positive and negative effects on muscle. Cialis does not directly stimulate testosterone secretion per se, meaning it does not stimulate LH release or SHBG release directly. This is not the first study to find that Cialis raises testosterone:
• In a study of 74 patients with erectile dysfunction treated on demand with 50mg of Viagra or 20mg of Cialis for three months, basal levels of total testosterone and free testosterone were at the bottom of the normal range that was reversed after treatment in both groups. Testosterone increase in Viagra-treated cases was significantly lower than in those treated with Cialis, suggested to be due to the higher frequency of full sexual intercourse in the Cialis-treated group.15
• Another study reported that the increase in testosterone from taking Cialis is mediated by a reduction in estrogen demonstration that Cialis may have anti-estrogen actions. It was pointed out that the T/estradiol ratio was associated with long-term Cialis treatment. There was no increase in LH levels from Cialis, demonstrating that Cialis did not directly increase testosterone, but indirectly increased testosterone by lowering estrogen.16
• One of the primary reasons that many older men have problems “rising to the occasion” is that they have excess estrogen levels. Furthermore, in men with hypogonadism, a low dose of clomiphene citrate (Clomid) is effective in improving testosterone:estrogen ratio, thus giving more long-term benefit for the management of erectile dysfunction in hypogonadal patients.18 It seems that based on the current study, Cialis has similar actions to Clomid by improving T:E ratio.
Natural Phosphodiesterase Inhibitors: Horny Goat Weed and Quercetin
In 1960, the first mechanism discovered for caffeine was PDE inhibition, although this drug has effects on other non-PDE proteins that cause some of its symptoms. Thus, caffeine was the first known PDE inhibitor. It was later shown that at least 11 PDE families exist, and that caffeine inhibits most of them. Moreover, caffeine is not a very potent inhibitor of these PDEs.17 Thus, caffeine has often been referred to as the “poor man’s Viagra.” Cialis, on the other hand, is a select PDE inhibitor. There are several natural alternatives to Cialis and Viagra that have demonstrated similar biochemistry.
For example, it was recently demonstrated that Horny Goat Weed was found to have similar effects to Cialis and Viagra on PDE enzymes. Horny Goat Weed was able to inhibit PDE by 80 percent; interestingly, other sexual-enhancement supplements such as cinnamon and Tribulus terrestris had small effects on PDE activity (15-23 percent). The other benefit of Horny Goat Weed is its low toxicity. Horny Goat Weed has been used to treat erectile dysfunction in China for more than 1,000 years.7, 8 Quercetin is the other natural ingredient that is a natural PDE inhibitor. Quercetin is a photochemical that is part of the coloring found in the skins of apples and red onions. It has been isolated and is sold as a dietary supplement. A recent study showed that purified quercetin has similar effects as Viagra and acted as a strong PDE inhibitory activity not likely related to its antioxidant effects.6 Many studies have shown that quercetin has been able to lower blood pressure through increasing vasodilatation.19
NO is clearly necessary for muscle growth in animals and test cultures, but unfortunately no real long-term studies on subjects taking NO-enhancing drugs have been investigated. We do know that Cialis has no effect on maximal performance, but the recent study showing that Cialis increases testosterone makes one wonder…what about long term use? Are the gym rats using Cialis onto something new, not yet validated by long-term studies? Based on the research, NO-enhancing products should contribute to muscle hypertrophy; it just has not yet be validated.
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Tatsumi, R., Hattori, A., Ikeuchi, Y., Anderson, J.E., Allen, R.E., 2002. Release of hepatocyte growth factor from mechanically stretched skeletal muscle satellite cells and role of pH and nitric oxide. Mol Bio Cell, 13(8), 2909-2918.
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Corbin JD, Francis SH. Molecular biology and pharmacology of PDE-5-inhibitor therapy for erectile dysfunction. J Androl, 2003 Nov-Dec;24(6 Suppl):S38-41. Review.
Shabsigh A, Kang Y, Shabsigh R, Gonzalez M, Leberson G, Fisch H, Goluboff E. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med, 2005;2:716–21.
Nicholson SK, Tucker GA, Brameld JM. Effects of dietary polyphenols on gene expression in human vascular endothelial cells. Proc Nutr Soc, 2008 Feb;67(1):42-7. Review.
Betters JL, Long JH, Howe KS, Braith RW, Soltow QA, Lira VA, Criswell DS. Nitric oxide reverses prednisolone-induced inactivation of muscle satellite cells. Muscle Nerve, 2008 Feb;37(2):203-9.
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.