TRENTAL

This month, I am going to discuss a drug. It is not a steroid or anabolic peptide hormone, or anything like that. As far as I know, it is not currently banned by any athletic organization, but just like any drug out there, that does not mean it cannot be added to the list at any time and acted on retroactively. It's just a drug that I find intriguing and although it has been written about in regard to performance enhancement here and there in other forums, it is still relatively unknown, so I thought I would take the topic on and share the wealth with MD readers.

The drug is called pentoxifylline (brand name Trental). Chemically, it falls into a class called methylxanthines, which includes caffeine and its chemical cousins, theophylline and theobromine. Unlike those three natural compounds, though, pentoxifylline is synthetic.

The main use of pentoxifylline is to treat a condition known as intermittent claudication. Intermittent claudication happens when a person's peripheral arteries become obstructed, which can lead to poor blood flow to muscles during physical exercise. The most common manifestation of this is painful cramping and fatigue in the calves when walking. Pentoxifylline can reduce the viscosity of blood, which can improve blood flow to the limbs and ease the symptoms of intermittent claudication. Pentoxifylline also has been studied, and occasionally used, as a treatment to fight the catabolism due to infection or cancer. It has been shown to reduce whole-body protein loss in a variety of catabolic conditions.

So it is mainly these two properties— the ability to improve blood flow to muscles and the ability to suppress protein catabolism— that makes pentoxifylline potentially useful for athletes.

Improving Blood Flow

Efficient blood flow is obviously of paramount importance to athletic performance. It is also vital to proper recovery from training. Oxygen, as well as nutrients necessary for contraction and growth, must get to working muscles. Unfortunately in some athletes, a variety of conditions (some natural and some drug related) can conspire to impede optimal blood flow. Now I assume that most people reading this are relatively healthy people who don't suffer from serious, age-related vascular disorders such as peripheral artery disease. However, some of you might be into bodybuilding pretty seriously and your body may possess a formidable amount of muscle mass and body water. You may find that when you are on your bulking stage, you cannot perform certain exercises without experiencing a substantial amount of cramping and pain. Maybe you find that you cannot walk too far without your calves feeling like they are gonna explode. Or maybe certain exercises provoke that dreaded condition we refer to as the "back pump," where your lower back seizes up in a massive cramp that has you lying on the floor writhing in pain. As you have probably guessed, these are all variations on the condition I described above called intermittent claudication. However, the culprit is not blocked or hardened arteries. The culprit is muscles that are so massive and/or overtoned that the small blood vessels that feed them are being pinched shut.

The use of drugs can also lead to conditions that threaten proper blood flow to the heart and skeletal muscles. The use of anabolic steroids and the use of synthetic EPO can lead to the condition known as polycythemia vera, which is an overproduction of red blood cells (erythrocytes) by the bone marrow. An excess of erythrocyte production can increase the percentage of blood cells in your blood (called the hematocrit) above levels that are safe. This dangerously elevated hematocrit may be present at rest, or in some cases, excessive dehydration due to exhaustive exercise may take a borderline hematocrit and put it over the safe threshold.

Whichever the case, the result is overly viscous blood that cannot easily circulate. Blood that does not easily circulate requires the heart to work harder and the blood pressure to increase— conditions that can precipitate a heart attack or stroke. Furthermore, an increased tendency of blood to clot can occur, potentially leading to dangerous embolisms which can be life threatening.

Now you are obviously waiting for me to tell you if and how pentoxifylline can help these conditions. Yes, it potentially can help and I will explain how by telling you in minor detail the mechanisms behind pentoxifylline's effects on erythrocytes. As you may already know, erythrocytes are concave, disc-shaped cells that circulate throughout the blood and deliver oxygen to tissues. Like many other tissues in the body, erythrocytes contain an enzyme called phosphodiesterase, which regulates the levels of the important biochemical messenger cAMP. The particular form of phosphodiesterase in erythrocytes (erythrocyte phosphodiesterase) is inhibited by pentoxifylline, and by inhibiting the enzyme levels of cAMP in the erythrocytes are increased. Administration of pentoxifylline will increase cAMP in the erythrocytes, thereby increasing their flexibility and ability to deform as they pass through narrow passages such as capillaries. As a result, an increase in what is known as "microcirculation" is achieved and tissues such as skeletal muscle will gain greater access to circulating oxygen, glucose, amino acids and other vital factors. Additionally, pentoxifylline increases the breakdown of fibrin (fibrinolysis), which is an important protein involved in the development of clots.

So, for those athletes who suffer from the aforementioned occlusive conditions, the combination of increased erythrocyte flexibility and increased fibrinolytic activity can reduce blood viscosity, leading to substantially increased blood flow to working muscles. The "back pump" may be alleviated and complications due to elevated hematocrit may be partially minimized.



Effect On Pro-Inflammatory Cytokines And Protein Catabolism

In addition to erythrocytes, there are many other cells circulating in the blood. Cells that are involved in the immune response such as leukocytes, macrophages and mast cells constitute a primary portion of the cells circulating throughout the body. These cells protect us from infection and also serve to assist in the repair of damaged tissue. These immune cells communicate with each other through chemical messengers known as cytokines. Cytokines are released in response to infection or injury.

I don't want to get into too much cellular biology stuff, because it is not my field and I don't want to embarrass myself. You do need to know that there is a class of cytokines that increase the inflammatory response, and chronic elevations of some of these can be very catabolic. The relevance of this pro-inflammatory cytokine catabolism is most apparent in conditions of systemic infection or cancer, however for many athletes, conditions can exist where an excess of these chemicals also present real problems.

Some of the more well known of these pro-inflammatory cytokines are IL-1, IL-6 and TNF-alpha. These cytokines cannot only be directly catabolic, but they can also suppress the production of anabolic factors such as IGF-1, as well as increase the production of catabolic hormones like cortisol. Overtraining in athletes is believed to be strongly associated with an overactive immune system, specifically as it relates to these catabolic cytokines. In addition, chronic degenerative connective tissue conditions such as arthritis and tendonitis have at their root a dysfunction of repair and regeneration stemming from overproduction of these pro-inflammatory cytokines.

The good news is that these circulating immune cells also contain a phosphodiesterase which can be blocked by pentoxifylline, and by doing so the levels of pro-inflammatory cytokines they produce are greatly reduced. In fact, in conditions such as sepsis or cancer, levels of the most notorious pro-inflammatory cytokine TNF-alpha are often reduced by over 90 percent, while levels of IL-1 and other cytokines are also reduced. This property of pentoxifylline has been exploited by many researchers who have discovered that administration of pentoxifylline to patients suffering from these serious illnesses can result in a marked reduction in protein loss, as well as an improvement in insulin sensitivity.

But what does this mean to you, the athlete guy, the guy who wants to lift more weights and feel younger and healthier? Well I don’t know about you, but my body is full of aches and pains…many of which are chronic and really get in the way of my exercising. I have some pretty damn bad tendonitis in my knees and my shoulders are a mess, too. If I start pushing it too much, then the inflammation starts and the connective tissue starts breaking down. I would love to end this cycle, or at least give my body a fighting chance to be healthy enough so I can do my favorite exercises. For guys like me, there is a reasonable chance that pentoxifylline could help. The cytokine-mediated degeneration of the tissue in my joints might be halted, which in addition to the possible increased blood flow to these parts of the body via the effects on erythrocyte flexibility could lead to some noticeable improvements in my condition.

Trental

Some of you reading this may feel as though pentoxifylline might be of benefit to you. You have to remember that I am not a doctor and being perceived as dispensing medical advice could land my ass in a sling. So my suggestion to you is read up more on the subject and find an open-minded doctor to discuss the subject with.

As far as the availability of the drug goes, it is a prescription drug available in the U.S. and overseas and is sold under the name Trental. It comes in 400mg controlled-release pink tablets and daily doses are usually one tablet taken two or three times a day. Tablets must be taken with meals, because the stuff can tear the innards of some sensitive people up sometimes. Because the drug can reduce clotting time, it should not be taken by people who are currently taking other blood thinning-type drugs. Nervousness and sleepiness are short-term side effects sometimes seen when first taking the drug.