Polyamines – Laying Down the Foundations for Anabolism!

October 2005


1- Featured Article: Polyamines – Laying Down the Foundations for Anabolism!

The objective of any athlete should be to promote muscle anabolism through exercise while curbing the catabolic stress response. This strategy is especially important during periods of intense training when catabolism frequently outweighs anabolism.

This month, I discuss a very important class of growth promoting agent that is (oddly) frequently overlooked in the popular fitness media when discussing muscle anabolism. Such discussions typically focus on the role that our anabolic hormones, such as testosterone, play in muscle anabolism.

Unknown to many, however, new evidence is emerging indicating that the anabolic hormones largely owe their growth promoting effects to a class of molecules known as the polyamines that act at the level of our genes. In truth, the polyamines lay down the foundation on which new tissue is built and are imperative for a strong anabolic response.

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This Month’s Featured Article:

Polyamines: Laying Down the Foundation for Anabolism!

by Alfredo Franco, PhD

Succinctly speaking, the polyamines are a family of broad-range growth promoters. The polyamines are best known for their role in increasing the expression of those genes responsible for stimulating cell proliferation. Accordingly, any physiological response requiring a robust increase in cell number will be associated with polyamine activation. For instance, the ability to mount a strong immune response as well as to repair damaged tissues is reliant on the expression of the polyamines (ref. 1).

The three principal polyamines are putrescine, spermidine and spermine. Polyamine biosynthesis commences with ornithine (the amino acid), which is converted into putrescine via the actions of an enzyme known as Ornithine DeCarboxylase (ODC, see figure below). Virtually any growth stimuli that a muscle encounters must first activate the ornithine pathway of producing putrescine to reach fruition. Putrescine, although possessing inherent growth promoting properties, is further activated with the addition of methyl groups to first produce spermidine and then spermine. As was explained in previous issues of the Creatine Newsletter, the source of these methyl groups is a molecule known as S-AdenosylMethionine, or SAM. Interestingly, the potency of the distinct polyamines at inducing cell proliferation correlates well with their degree of methylation, spermine being the most powerful of the three at stimulating cell division. Obviously, methylation is extremely important for tissue growth.

Polyamine synthesis commencing from the amino acid, ornithine. Putrescine is sequentially methylated to first produce spermidine, then spermine. Some steps have been omitted for clarity. Ornithinedecarboxylase: ODC.

It should come as no surprise that the polyamines are expressed at their highest levels in rapidly dividing tissues. In fact, spermine and spermidine derive their names from sperm, from which they were first isolated. Also not surprising is the fact that spermidine is also expressed at very high levels in newborn animals, clearly reflecting its involvement in rapidly growing organisms. For example, in rats, spermidine levels are 20-fold greater at birth than just 5 months later!

Polyamines and Exercise

Surprisingly, very few scientific studies have actually examined the influence of polyamines on exercise-induced muscle anabolism. One recent study merits mentioning, however, as it examined the effects of exercise on polyamine and testosterone synthesis (ref. 2). This study found that endurance and resistance exercise provoked a three- and fourfold increase in serum testosterone levels, respectively, that was followed a few hours later by an increase in polyamine synthetic rate. Moreover, the fact that testosterone levels rose before the polyamines, strongly suggested that testosterone was responsible for triggering polyamine synthesis. This effect may represent one of the physiological mechanisms whereby testosterone promotes muscle anabolism. In support of this conclusion, it has been shown that the levels of ODC, the enzyme responsible for converting ornithine into putrescine, is ten-times greater in the muscles of males than females, correlating with the higher testosterone levels in male mice. Furthermore, administration of exogenous testosterone has been similarly shown to stimulate polyamine synthesis in rodents. Nevertheless, the message seems clear: testosterone exerts at least part of its anabolic effect through the actions of the polyamines.

Seemingly paradoxical, however, was the fact that the rise in polyamines was greatest in slow twitch muscle, despite the larger increase in testosterone induced by resistance exercise (primarily recruiting fast twitch fibers). In truth, this is not that surprising given that slow twitch muscle fibers possess greater amounts of testosterone-binding receptors. The increased number of receptors would make slow twitch fibers more responsive to circulating testosterone levels. Another important consideration is that exhaustive exercise causes greater oxidative stress in slow muscle fibers due to their greater reliance of oxidative energy production. Recall from last month’s newsletter that large increases in oxygen consumption (as seen during exercise) increase the production of Reactive Oxygen Species (ROS) that can severely damage muscle. Muscle injury, in turn, stimulates the local proliferation of neutrophils and macrophages that literally eat away damaged muscle tissue in preparation for subsequent regeneration. Therefore, polyamine expression is obviously very important in helping slow muscle fibers recover from exhaustive exercise.

The major caveat of this study, however, is that it was conducted on rats, not humans. Studies of this sort clearly need to be repeated in humans undergoing training.

Take Home

This previous study clearly showed that exercise recruits the assistance of polyamines to help promote muscle anabolism. Therefore, to create the strongest anabolic environment, an athlete needs to assure that his/her polyamines levels are sufficiently stocked. Importantly, a key step in facilitating polyamine synthesis is to enhance your methylation status by strategically combining creatine supplementation with targeted B-vitamins intervention. How to do this most effectively is discussed in my creatine guide.

You can also read more about this novel nutritional strategy.

Scientific References

1. Moinard, C. et al., (2005) Polyamines: metabolism and implications in human diseases. Clinical Nutrition, Volume 24, pages 184–197.

2. Turchanowa, L. et al., (2000) Influence of physical exercise on polyamine synthesis in the rat skeletal muscle. European Journal of Clinical Investigation, Volume 30, pages 72–78.

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