понедельник, 3 ноября 2014 г.

VIAGRA: THE LATEST RESEARCH ON EXERCISE PERFORMANCE

http://musculardevelopment.com/articles/chemical-enhancement/3703-viagra-the-latest-research-on-exercise-performance.html#.VFeTM4ehYW0


Written by Thomas Fahey


Viagra has moved from the bedroom to the locker room. The buzz on the street was that Yankee superstar Roger Clemens had a bottle of Viagra disguised as vitamin pills stashed in his locker. Last May, Italian cyclist Andrea Moletta was removed from the Giro d'Italia after police found a cache of Viagra and syringes in his car. Not surprisingly, the tabloids had a field day following these incidents and charged that legions of athletes in baseball, football, bodybuilding and Olympic sports took Viagra to boost endurance and physical performance. The World Anti-Doping Association (WADA) considered banning Viagra before the Beijing Olympics, but backed off because it had no evidence that the drug provided a competitive advantage.
What do firm erections have to do with sports like bodybuilding? Viagra improves blood flow control. Muscles need plenty of blood to remove wastes and deliver energy, oxygen, and hormones. Increased blood flow could speed the delivery of key amino acids to the muscles, which would promote muscle protein synthesis and growth. It seems reasonable that Viagra could boost performance and that bodybuilders might take it.
A Stanford University study by Ann Friedlander and colleagues published in 2006 triggered the Viagra craze among athletes. The researchers found that Viagra improved cardiovascular capacity during exercise on a stationary bike at a simulated altitude of 12,710 feet but not at sea level. Viagra increased cardiac output (blood pumped by the heart per minute), stroke volume (blood pumped by the heart per heartbeat), and oxygen saturation (percent of red blood cells carrying oxygen). Cycling performance at altitude improved by 15 percent. The drug increased exercise capacity by reducing blood pressure in the lungs, which increases at high altitude. Not all subjects benefited from the drug— there were responders and non-responders. Other researchers confirmed the Stanford results and also showed that Viagra improved exercise capacity in people suffering from lung disease and heart failure.
Bodybuilding is an incredibly difficult sport that requires years of backbreaking work to achieve success. Most athletes will do whatever it takes to increase muscle mass and win contests. It’s understandable that they take Viagra: it’s not on any banned substances list; it’s readily available; it has few side effects; and it might provide a significant edge. The fact that it only worked in some people above 12,000 feet altitude and didn’t work at sea level was somehow lost in the shuffle.
Why Viagra Might Be an Effective Bodybuilding Drug
 Viagra (sildenafil) is one of three FDA-approved, erection-promoting drugs called PDE-5 inhibitors that also include tadalafil (Cialis) and vardenafil (Levitra). They work by inhibiting the PDE-5 enzyme, which then increases the concentration of a chemical called nitric oxide that promotes blood flow to the penis and other tissues throughout the body. Blood vessels, smooth muscle, skeletal muscle, blood platelets, and lung tissue contain this and similar PDE enzymes. In addition to promoting erections, PDE-5 inhibitors decrease systemic blood pressure, lung blood pressure, lung resistance, and promote coronary (heart) blood flow. Long-term use improves endothelial function, which is critical to blood flow control.
 The drugs reduce stress in pressure-overloaded hearts, which is important for bodybuilders because large increases in muscle tension restrict blood flow to working muscles. Increasing muscle blood flow during training could increase muscle strength, size, and fitness, while reducing stress on the heart. They also improve lung blood flow and boost quality of life in patients suffering from lung disease.  These drugs have promising pulmonary and cardiovascular applications that go beyond firm erections.
To date, no study has found that Viagra improves exercise performance in athletes at sea level. The drug is helpful in people with blood pressure limitations that interfere with oxygen transport to the tissues. For example, lung blood pressure increases substantially in some people at altitude, which makes it difficult to move oxygen from the air into the bloodstream. Viagra reduces lung blood pressure, which enhances oxygen consumption and the capacity to exercise.
A small percentage of elite endurance athletes have a performance imbalance between the heart and lungs. Their powerful hearts exceed breathing capacity, which causes a mismatch between the pulmonary and cardiovascular systems. Viagra might increase lung function to match their superior heart capacity, which could give them a significant competitive advantage. However, other athletes might benefit as well.
Physical inactivity, diets high in saturated and trans-fats and simple sugars, and reduced muscle mass impair the ability of insulin receptors to regulate carbohydrates, amino acids (building blocks of proteins) and fats. Insulin sensitivity affects the health of the endothelium, the cells that line the blood vessels. These cells release nitric oxide (NO) that opens blood vessels in tissues throughout the body. Long-term use of Viagra has training-like effects on the endothelium, which increases its capacity to release NO. While the Viagra-induced improvements in blood flow control might be greater in men suffering from poor metabolic health, they might also promote blood flow in the muscles and nervous systems in bodybuilders and physically fit adults. Viagra doesn’t appear to increase endurance performance following short-term use, but it might have long-term benefits in well-trained athletes.
Long-term use of Viagra might also benefit metabolic capacity by enhancing blood sugar control and increasing testosterone levels. Scientists from Vanderbilt University School of Medicine found that the drug helped restore energy balance and boosted insulin metabolism in mice fed high-fat diets (compared to a placebo). The animals showed lower blood sugar and insulin levels and improved blood sugar regulation after a high-carbohydrate meal. They also lost bodyweight and fat mass during the 12-week study. In humans, long-term use of Viagra increased the production of the blood vessel controlling chemical nitric oxide, which has strong links to insulin metabolism.
 Viagra boosts testosterone, which is a critical hormone for increasing muscle mass, strength, and aggressiveness— all critical for athletes. Testosterone is linked to sexual arousal and performance. Middle-aged men who take testosterone supplements improve sex drive, capacity for erections, self-confidence, and aggressiveness. Italian researchers found that total and free testosterone levels increased by 50 percent in men treated for erectile dysfunction with Cialis or Viagra. It’s not clear whether these drugs increased testosterone directly or if they increased it indirectly through increased sexual activity. Frequency of sexual intercourse was greatest in men who took Cialis (a longer-acting PDE-5 inhibitor), which makes it the preferred drug for men in stable relationships. Men who had the most sex also had the highest testosterone levels.
Factors affecting testosterone include psychological health, diet, exercise, and sexual activity. Men who have a lot of sex are happier, more confident, and have better-functioning sex organs than men who don’t. The sex organs— like your muscles— function best when you use them, so Viagra might give them a boost. We don’t know if Viagra increases testosterone levels in healthy, fit bodybuilders.
Long-term use of Viagra might also increase muscle strength, power, and size by triggering biochemical pathways that increase protein synthesis and prevent protein breakdown in muscle cells. As discussed, Viagra increases nitric oxide (NO) release by the blood vessels. NO helps turn on protein synthesis in muscles, particularly when the fibers are under tension or stretch. NO also triggers the formation of satellite cells that add mass to the muscle fibers. To date, no study has shown that Viagra and similar drugs have steroid-like effects in athletes, but we can infer from biochemical studies that they might.
 Viagra is on WADA’s Radar
WADA first took notice of Viagra following the Stanford University study and reports that the drug was given to greyhounds to improve running performance. They were concerned that Viagra might improve performance at lower altitudes and provide a competitive advantage at venues such as Denver, Mexico City, or areas hosting the Winter Olympics. The margin of victory is often a matter of seconds in endurance events in cycling and cross-country skiing, so a drug that provides even a small advantage could be very significant.
WADA is currently funding a series of studies at Marywood University in Scranton, Pennsylvania and at the University of Miami, to determine the effects of Viagra on exercise capacity and performance at sea level, moderate altitudes, and in polluted environments. They also want to know if the drug has different effects in men and women. The results of these studies will determine whether Viagra ends up on the banned substances list.
 Will Viagra Make You a Superstar?
 Viagra can help make you a sexual Olympian, provided that you have game, good hygiene, and a reasonably firm body. It definitely won’t get you a spot on the Yankee’s roster or the Olympic team if you don’t have the talent. To date, no study has found that Viagra improves exercise capacity at sea level. However, long-term use of the drug might promote muscle protein synthesis and improve metabolic fitness enough to have a small effect on endurance or strength. Viagra and similar drugs have side effects; so don’t use them without following the advice of a physician. We need many more studies before we can adequately assess the effects of these drugs on exercise capacity and athletic performance.
References:
            Ayala, J. E., et al. Chronic treatment with sildenafil improves energy balance and insulin action in high fat-fed conscious mice. Diabetes, 56: 1025-1033, 2007.
            Betters, J. L., J. H. Long, K. S. Howe, R. W. Braith, Q. A. Soltow, V. A. Lira, and D. S. Criswell. Nitric oxide reverses prednisolone-induced inactivation of muscle satellite cells. Muscle Nerve, 37: 203-209, 2008.
            Di Luigi, L., et al. The long-acting phosphodiesterase inhibitor tadalafil does not influence athletes' VO2max, aerobic, and anaerobic thresholds in normoxia. Int J Sports Med. 29:110-115, 2008.
Faoro, V., et al. Effects of sildenafil on exercise capacity in hypoxic normal subjects. High Alt Med Biol, 8:155-163, 2007.
            Ghofrani, H. A., et al. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: A randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med, 141:169-177, 2004.
            Hsu, A. R., K. E. Barnholt, N. K. Grundmann, J. H. Lin, S. W. McCallum, and A. L. Friedlander. Sildenafil improves cardiac output and exercise performance during acute hypoxia, but not normoxia. J Appl Physiol, 100:2031-2040, 2006.
            Jackson, G. Hemodynamic and exercise effects of phosphodiesterase 5 inhibitors. Am J Cardiol, 96:32M-36M, 2005.
            Lewis, G. D. et al. Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension. Circulation, 116:1555-1562, 2007.
            Perimenis, P. Sildenafil for the treatment of altitude-induced hypoxaemia. Expert Opin Pharmacother, 6:835-837, 2005.
            Ricart, A., et al. Effects of sildenafil on the human response to acute hypoxia and exercise. High Alt Med Biol,6:43-49, 2005.
            Rubin, L. J. and R. Naeije. Sildenafil for enhanced performance at high altitude? Ann Intern Med, 141:233-235, 2004.
            Siepmann, M., R. Rauh, O. Dill, M. W. Agelink, and M. Mueck-Weymann. The effects of sildenafil on heart rate variability in healthy subjects. J Cardiovasc Pharmacol, 50:598-600, 2007.
            Snyder, E. M., T. P. Olson, B. D. Johnson, and R. P. Frantz. Influence of sildenafil on lung diffusion during exposure to acute hypoxia at rest and during exercise in healthy humans. Eur J Appl Physiol, 2008.
            Spring, R. M., et al. Sildenafil for pulmonary hypertension: Dose-dependent improvement in exercise performance. Pulm Pharmacol Ther, 21: 516-521, 2008.
            Tatsumi, R., et al. Satellite cell activation in stretched skeletal muscle and the role of nitric oxide and hepatocyte growth factor. Am J Physiol Cell Physiol, 290:C1487-1494, 2006.
            Wozniak, A. C. and J. E. Anderson. Nitric oxide-dependence of satellite stem cell activation and quiescence on normal skeletal muscle fibers. Dev Dyn, 236:240-250, 2007.
            Wozniak, A. C. and J. E. Anderson. The dynamics of the nitric oxide release-transient from stretched muscle cells. Int J Biochem Cell Biol, 41:625-631, 2009.

Testosterone and the Heart— A New Era?

http://musculardevelopment.com/articles/chemical-enhancement/3271-testosterone-and-the-heart-a-new-era-.html#.VFeRe4ehYW2

 

If you are a man, at some point in your life you are likely to be a candidate for hormone replacement therapy. As we age, our testosterone levels decline, and with them often a number of physical and psychological characteristics. It has long been understood that low testosterone levels can be linked to reduced libido, sexual dysfunction, diminished energy, and a reduced overall sense of well-being. For these reasons, replacement therapy with testosterone drugs is a strong and steadily growing area of medicine for aging men.
Beyond these basic facts, testosterone remains a controversial drug. Its abuse is linked to changes in the body that may increase the likelihood of cardiovascular disease, and partly because of this, the potential benefits and risks of testosterone replacement therapy have long been the subject of much debate. Is this therapy actually safe?
In recent years, evidence has been surfacing that testosterone replacement may actually reduce cardiovascular disease risk. Usually isolated in scope, these papers concern many favorable changes in cardiovascular health markers, such as the management of triglycerides and cholesterol. I believe I’ve discussed some of these papers in this column before. Hopefully, a paper published in the Journal of Andrology will further this discussion a great deal.
This 37-page report entitled “The Dark Side of Testosterone Deficiency” is the third in a series of papers covering the potential benefits of hormone replacement therapy in men.1 It specifically reviews the mounting evidence in favor of the use of testosterone for reducing heart disease risk, addressing the most detailed and relevant studies on the subject. This is the most extensive paper on testosterone therapy and heart disease to date, and covers several specific potential benefits.

[ANDROGEL PICTURE] Growing evidence suggests that testosterone administration may actually reduce the risk of heart disease in older men.

Serum Lipids
One of the first potential benefits of testosterone replacement therapy (TRT) reviewed in this paper is the management of triglyceride and cholesterol levels. As detailed in a growing number of studies, testosterone replacement therapy consistently improves the lipid profile in men with hormone deficiency. The most consistent endpoints of improvement appear to be a reduction in total cholesterol, a reduction in LDL (‘bad’) cholesterol, and a lowering of serum triglycerides. The improvements in lipid profile appear to be more pronounced in older men, although both young and old populations tend to show improvements in serum lipids when testosterone is given to correct a deficient state.
The effect of TRT on HDL (‘good’) cholesterol levels is less consistent. Studies giving testosterone gels, patches, or the longest-acting ester (testosterone undecanoate) tend to show improvement or no consistent effect on HDL. Studies with the more common esters such as cypionate and enanthate tend to show minor decreases in HDL during therapy, likely owing to the brief supraphysiological peaks for several days after administration. Note that HDL is often improved when TRT is combined with exercise and other lifestyle modifications.

Inflammatory Markers
Androgen deficiency is associated with an increase in certain inflammatory markers that can support the progression of atherosclerosis. Testosterone replacement therapy has been shown to reduce some of the same inflammatory mediators, specifically TNF-alpha (tumor necrosis factor-alpha) and IL-1B (interleukin-1beta).
Inflammation in the vascular system is an especially important concern with heart disease. For one, vascular inflammation is associated with the deposition of arterial plaque, a key component of this disease. Inflammation of the blood vessels may also damage the arteries, making them both thicker and weaker. Scarring may be noticed, and blood flow may be reduced. All of this can restrict blood flow and reduce the heart’s blood pumping capacity.
By helping to reduce the production of TNF-alpha and IL-1B, hormone replacement therapy may reduce inflammation, vascular damage, and the chance for atherosclerosis. Again, instead of seeing a neutral or ‘negative’ effect, we find a specific improvement in the cardiovascular disease risk profile with the administration of this drug.

Abdominal Obesity, Insulin Resistance
A growing number of studies have linked androgen deficiency to insulin resistance, as well as increased abdominal obesity. These two factors are also common with men suffering from cardiovascular disease, and may directly contribute to (among other things) endothelial cell dysfunction and vascular damage. Androgen substitution has been shown in several studies to reduce midsection fat deposits, increase glucose tolerance, and improve the overall metabolic state. It has additionally been postulated that due to the important role of testosterone in managing insulin sensitivity, androgen deficiency may be a contributing factor to adult-onset (type 2) diabetes. Likewise, the substitution of testosterone in aging men with hypogonadism might reduce the likelihood of developing diabetes.

Endothelial Function
The endothelium is a layer of cells that lines the blood vessels throughout the entire circulatory system. These cells are responsible for managing the passage of some materials in and out of the blood vessels, and supporting the flow of blood through the system. Endothelial cells play a role in vasoconstriction and vasodilation, they regulate certain inflammatory processes, and they’re involved in blood clotting and in supporting the formation of new blood vessels. Endothelial dysfunction is linked to androgen deficiency in men, and may result in elevated blood pressure (hypertension), vascular ‘stiffness,’ and significantly increased risk of cardiovascular disease. Likewise, replacement of testosterone in men with a deficiency has been shown to improve endothelial function, blood vessel dilation, arterial vasoreactivity, and blood flow.
One additional important ‘endpoint’ of improvement to this therapy appears to be an increase in endothelial progenitor cell activity, which helps repair damage to the vascular system.

Conclusion
Traditionally, most physicians are extremely cautious with testosterone drugs. Many family doctors are very willing to prescribe estrogens to their female menopausal patients complaining of symptoms such as sexual dysfunction, but when it comes to their male patients with similar complaints, the response is often different. Many of these same physicians are much more willing to prescribe a drug like Viagra than the basic male androgen testosterone. Some mistakenly consider testosterone to be ‘too dangerous’ to give most of their patients, and reserve its use for extreme cases. And when testosterone is considered, it is given only for a very narrow and specific set of psychological or physical symptoms.
Of course in the era of AndroGel, some physicians are much more enlightened. Still, the troubling common fear of this hormone remains. Perhaps this is changing, and perhaps the accepted set of symptoms and therapies for prescribing this hormone is changing.
It seems clear that we can no longer paint testosterone as simply a ‘bad’ hormone for the cardiovascular system. While excessive high-level elevations of this hormone may indeed damage an individual’s cardiovascular health, we have strong evidence that within a certain physiological range, it may also protect the cardiovascular system from some of the same health issues. As such, its replacement may indeed turn out to be very important medical intervention for millions of men across the country, helping us to not only live better— but also live longer.
After all this time, it appears that this very controversial hormone, the same steroid demonized in the media, might actually help reduce the risk of cardiovascular disease in aging male patients. The study we reviewed this month is, likewise, something all men should take to heart— literally.

Reference:
1.The Dark Side of Testosterone Deficiency: III. Cardiovascular Disease. Traish AM, Saad F et al. Journal of Andrology, April 2, 2009. ePub, Ahead of Print.

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