Research Update: Cycling Creatine, Steroids and the Heart, Meal Replacement Drinks

by Bryan Haycock MS
bryan@thinkmuscle.com 

As we approach the new millennium we find the science of building muscle progressing faster than ever before. Long gone are the days of simple trial and error when it comes to building muscle. The modern bodybuilder demands more than just "hear say" if they are to adopt a new training routine or nutritional supplement. This column was created to keep today’s bodybuilder on the cutting edge of scientific research that might benefit them in their quest for body perfection.

Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle.

Guerrero-Ontiveros ML, Wallimann T.
Institute for Cell Biology, Swiss Federal Institute of Technology, ETH-Honggerberg, Zurich.

Mol Cell Biochem 1998 Jul;184(1-2):427-37

These researchers studied the in vivo effect of dietary creatine as well as 3-GPA (a creatine analog that is a competitive inhibitor of creatine entry) on the expression of the creatine transporter (creatine T). Long term feeding of rats with 3-GPA has been previously shown to decrease creatine levels in skeletal muscles without effecting creatine T expression. In this study, the expression of the creatine T was examined in rats chronically fed either 4% creatine or 2.5% GPA. Dietary creatine administered for 3-6 months, significantly lowered the expression of creatine T polypeptides. The rats fed the creatine analog GPA showed virtually no change (perhaps even a slight increase) in creatine T polypeptide expression.

The wide spread use of creatine among athletes and bodybuilders has raised concerns about possible negative side effects. Of course most of the nay sayers are looking to control its availability with little real concern for the well being of those who use it. This study has answered a question that has rested on the minds of many, which is, "Is there any reason to cycle creatine?" From the study above we see that the abundance and activity of the creatine transporter is negatively effected by long term creatine ingestion. The creatine transporter is down regulated with continued exposure to extracellular creatine.

Human skeletal muscle has an upper limit of creatine that can, or will, be contained within the cell. This limit is around 150-160 mmol/kg of dry muscle. As the intracellular concentration of creatine approaches this level, the synthesis of creatine transporters declines and even stops depending on the amount of creatine ingested over time. In the study above, it was shown that the creatine transporter is regulated by the content of creatine in the cell rather than by the interaction of creatine, or it’s analog 3-GPA, with the transporter.

All the arguments about creatine absorption being a limiting factor in creatine content within the cell are bogus. Creatine does not need to be "micronized" or "effervesent" to lead to an increase in creatine content within your muscles. The activity of the creatine transporter is the limiting factor. Any trick increase in creatine absorption will only hasten creatine transporter down regulation. It only requires about 5 grams per day for 30 days to increase the content of creatine within muscle tissue to the same extent as 30 grams per day for 6 days. The sooner you reach the upper limit the sooner your muscles become unable to take up creatine. It is better to maintain sufficient levels of creatine transporters in order not to cause a rapid decline in creatine content once creatine supplementation is discontinued. Clearly there appears to be good reason to cycle creatine supplementation.

The authors of this study recommend not using creatine for over 3 months at a time. To truly cycle creatine you will have to take at least 4 weeks off. Creatine levels take at least one month to return to pre-supplement levels. It may be important to take the entire month off because one speculated mechanism of creatine transporter downregulation is that when the intracellular levels (levels inside the muscle cell) are increased the creatine transporters are taken down and not replaced as long as creatine levels remain elevated. Thus it might take as long as a month for creatine transporters to return to normal after chronic creatine supplementation. Keep in mind that no one has actually shown that long-term supplementation with creatine is a bad thing.

Left ventricular wall thickening does occur in elite power athletes with or without anabolic steroid Use.

Dickerman RD, Schaller F, McConathy WJ
Department of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, Tex., USA.

Cardiology 1998 Oct;90(2):145-8

Researchers examined 4 elite resistance-trained athletes by two-dimensional echocardiography. In addition, they retrospectively examined the individual left ventricular dimensions of 13 bodybuilders from our previous echocardiographic studies. All 4 elite resistance-trained athletes had left ventricular wall thicknesses beyond 13 mm. One of the elite bodybuilders has the largest left ventricular wall thickness (16 mm) ever reported in a power athlete. Retrospectively, 43% of the drug-free bodybuilders and 100% of the steroid users had left ventricular wall thickness beyond the normal range of 11 mm. In addition, 1 drug-free subject and 3 steroid users were beyond the critical mark of 13 mm. No subjects demonstrated diastolic dysfunction. In contrast to previous reports, we have demonstrated that left ventricular wall thicknesses >/=13 mm can be found routinely in elite resistance-trained athletes who do not use anabolic steroids.

Left ventricular hypertrophy is characterized by thickening of the left ventricular wall secondary to cardiac fiber enlargement. Left ventricular hypertrophy is normally caused by a chronic increase in systemic blood pressure. It may also be seen with sudden or rapid weight gain. The thickening of the ventricular wall due to increased afterload from elevated vascular resistance can be viewed as adaptive protection up to a point. Beyond minor wall thickening, left ventricular hypertrophy is a strong predictor of serious cardiovascular risk.

During heavy lifting, systemic blood pressure is increase from what is called the valsalva maneuver. It is simply the act of forceful expiration with the mouth and nose closed producing a "bearing down" on the abdomen. Pressure also increases due to blood vessels being occluded by contracting muscles. It should be noted that the LVH seen in bodybuilders and power lifters is called "concentric left ventricular hypertrophy", meaning that it is the result of contracting against acute increased systemic pressure, and was not considered pathological. "Eccentric" LVH is caused by constant increases of blood pressure not as a result of the valsalva maneuver but instead clinical hypertension that forces the ventrical to expand against resistance. It was previously believed that the intermittent increase in blood pressure that is caused by heavy lifting was not sufficient to elicit left concentric ventricular hypertrophy (CLVH). Any evidence of CLVH in strength athletes or bodybuilders was seen as a sign of anabolic steroid use.

In the study above researchers identified LVH at or beyond 13mm in not only bodybuilders using anabolic steroids but also in "drug free" athletes as well. Although it was shown that those using anabolics showed significantly more ventricular thickening, at least one drug free athlete was beyond the 13mm limit.

Hormonal responses to consecutive days of heavy-resistance exercise with or without nutritional supplementation.

Kraemer WJ, Volek JS, Bush JA, Putukian M, Sebastianelli aWJ
The Human Performance Laboratory, Ball State University, Muncie, Indiana 47306, USA.

J Appl Physiol 1998 Oct;85(4):1544-55

Nine resistance-trained men consumed either a protein-carbohydrate supplement (Twin Lab’s MassFuel) or placebo for 1 wk in a crossover design separated by 7 days. The last 3 days of each treatment, subjects performed resistance exercise. The supplement was consumed (half serving) 2 h before and immediately after (half serving) the workout, and blood was obtained before and after exercise (0, 15, 30, 45, and 60 min postexercise). Lactate, growth hormone, and testosterone were significantly (P </= 0.05) elevated immediately postexercise in both placebo and supplemented groups. The lactate response was significantly lower during supplementation on days 2 and 3. Growth hormone and prolactin responses on day 1 were significantly higher during supplementation. After exercise, testosterone declined below resting values during supplementation. Cortisol decreased immediately postexercise on day 1; the response was diminished on days 2 and 3. Glucose and insulin were significantly elevated by 30 min during supplementation and remained stable during placebo. Insulin-like growth factor-I was higher during supplementatiom on days 2 and 3. These data indicate that protein-carbohydrate supplementation before and after training can alter the metabolic and hormonal responses to consecutive days of heavy-resistance exercise.

The reason for performing this study was to see what would happen after consecutive days of training and supplementation with a carb/protein drink. Most all previous studies looking at the effect of macronutrient supplementation are done acutely after a single bout of exercise.

The results of this study are not surprising. There was a significant increase in post-exercise glucose and insulin due to the carbs and BCAAs in the supplement drink. As with previous studies, there was also an increase in post exercise growth hormone however, it was only greater than placebo after the first workout. After the second and third workouts the differences were very small. There was a significant increase in resting IGF-1 levels in the supplemented group with no difference in post exercise levels when compared to placebo. This is not unusual in conditions of "over feeding". The supplement added between 1575 - 2475 kcals per day in this study.

There was a trend for reduced cortisol levels for both placebo and the supplement groups. Surprisingly, cortisol levels were not greatly different after post exercise supplementation. Performance appeared to be unaffected by supplementation. This is not unusual after such a short training protocol (3 days). There was one significant difference that should be noted, namely serum testosterone was significantly lower in the MassFuel group. The authors explained this observation from a macro nutrient ratio perspective. You see, while supplementing with MassFuel the percentage of calories from fat drops to 14% compared to 24% for the placebo period. It is well known that the highest resting testosterone levels are achieved when fat provides ~30% calories. It can be optimistically speculated that free testosterone levels remained the same from data measuring the ratio of total serum test and SHBG.

What is the take home message from all this? First, there was virtually no difference in the way the body responded to three consecutive days of training the same body parts. It is not unreasonable to consider training a body part for two or three days in a row and then giving it a couple days off. And finally, by using a carb/protein supplement in liquid form after training you can ensure that protein synthesis will begin as soon as possible after exercise.