Oxidative Stress And Exercise: Role Of Glycine Propionyl-L-Carnitine (GPLC)!

Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds antioxidant defense … Discover how GPLC could play a role in stabilizing its negative effects!

Oxidative stress occurs when the production of reactive oxygen species (ROS), often referred to as "free radicals," exceeds antioxidant defense (Halliwell and Cross, 1994; Sies, 1997).

The antioxidant system is comprised of both endogenous (within the body) and exogenous (outside of the body) defense mechanisms. Oxidative stress may progress to oxidative damage involving cellular proteins (contractile, structural, and enzymatic), lipids, DNA, and other molecules in ways that might lead to abnormal cellular function.

The degree of oxidative damage, as well as the time course for elevation in oxidative stress biomarkers has varied across studies, and appears dependent on the type, intensity, volume and duration of exercise, the exercise training and nutritional status of the research subjects, and the tissues being investigated (Bloomer and Goldfarb, 2004).

It should be noted that despite the potential for excessive ROS production to be problematic, low levels of ROS appears necessary for important physiological functions such as cell signaling, immune response, and apoptosis (Volaard et al., 2005).

While ROS are constantly produced in small quantities within biological systems, their presence increases when exposed to both environmental and physical stressors (Halliwell and Cross, 1994). Exercise is one such stressor; hence, the use of antioxidant agents to combat ROS has been popular in recent years.

Exercise And ROS Production

The topic of exercise-induced oxidative stress has received much attention over the past 30 years since it was first reported that lipid peroxidation was increased following 60 minutes of cycling exercise (Dilliard et al., 1978).

Based on the available evidence, it is clear that exercise of sufficient intensity (typically >60% VO2 max or 50% one repetition maximum) and duration increases the formation of ROS, having the potential to create an imbalance between oxidant and antioxidant levels.

Interestingly, while acute exercise appears to increase ROS transiently, this same exercise stimulus is needed to allow for an up-regulation in endogenous antioxidant defenses (Powers et al., 1999). In this way, the generation of ROS acts as the "signal" to allow for these important adaptations in antioxidant defense, which may have significant implications for protection against future elevations in ROS.

The specific sites of ROS generation with acute exercise have been previously discussed in detail (Bloomer and Goldfarb, 2004; Jackson et al., 2007). These include both primary sources in which ROS are generated in direct response to a given condition, as well as secondary sources in which ROS production may occur in response to damage induced through other mechanisms, such as eccentric muscle actions which are common with strength/bodybuilding type exercise.

A major pathway for ROS generation during exercise involves oxygen, where oxygen is ultimately used for ATP production. Under normal physiological conditions, most of the oxygen consumed by cells is reduced to water in the mitochondria.

However, some of the oxygen (1-5%) passing through the mitochondrial respiratory chain may give rise to superoxide, which may lead to other harmful ROS. This is especially apparent during acute sessions of strenuous exercise when oxygen uptake may increase 10-20 fold.

In addition to generation through mitochondrial electron transport, ROS can be produced through other primary sources including prostanoid metabolism, and enzymatic reactions involving NADPH oxidase and xanthine oxidase, which are radical species generators (Jackson, 2007).

Secondary sources of ROS initiation can arise from exercise which involves muscle injury, such as high force eccentric muscle actions. This involves to a large extent the invasion of phagocytic cells into damaged tissue in an attempt to promote healing. In addition, muscle injury may be accompanied by disruption of iron containing proteins such as erythrocytes and myoglobin, which can lead to an increase in free iron which is known to catalyze radical reactions.

Therefore, exercise that creates significant trauma such as high impact aerobic exercise or high force eccentric actions, may lead to destruction of these proteins, allowing for increased free iron availability to aid in the production of ROS. Finally, any imbalance in calcium handling, such as excessive intracellular calcium accumulation, may lead to ROS production. This appears to occur through the activation of phospholipase and proteolytic enzymes.

In the above ways, intense physical activity has been reported in several investigations to lead to an oxidative stress, as previously reviewed in detail (Bloomer and Goldfarb, 2004; Finaud et al., 2006; Volaard et al., 2005).

One concern that many athletes have is the impact of ROS formation on physical performance. While few direct human investigations have focused on this area of research, the following section provides a brief summary for consideration.

Association Between ROS And Physical Function

While human data are scarce, animal studies have noted impaired contractile function, reductions in muscle force output, and greater fatigue rates in isolated skeletal muscle as a function of increased ROS (Reid et al., 2001).

It is important to keep in mind that oxidative alteration to proteins in particular can lead to impaired physical performance (Goldhaber and Qayyum, 2000), as proteins are involved in enzymatic reactions as well as actual muscle contraction (actin and myosin filaments).

Two human studies have investigated the relationship between oxidative stress and exercise overtraining/overreaching. In this work, four weeks of aerobic overtraining was linked to decreased blood antioxidant status (Palazzetti et al., 2003).

Findings of increased total peroxides have been noted in professional football players over the course of a five month competitive season (Schippinger et al., 2002). Clearly, additional work using human subjects is needed in this area of research.

Because the potential for impaired performance exists due to heightened oxidative stress, methods to reduce the degree of oxidative stress resulting from exercise have been studied. The most common method is the intake of antioxidant nutrients. The following section describes the antioxidant defense system, which is comprised of both endogenous and exogenous components.

Antioxidant Defense

Although ROS are constantly generated and can increase with physical exertion, the extent of oxidative damage is largely dependent on the ability of the body to defend against ROS production. This defense is collectively referred to as the antioxidant defense system, and includes both enzymatic and non-enzymatic antioxidants.

Common antioxidant enzymes include superoxide dismutase (SOD), of which three primary forms are known to exist: a cytosolic copper-zinc enzyme (Cu-ZnSOD), a mitochondrial enzyme requiring manganese (MnSOD), and an extracellular SOD (EC-SOD).

Other antioxidant enzymes include glutathione peroxidase (GPx) and catalase (CAT), both of which function to inactivate hydrogen peroxide prior to reacting with the transition metals.

The major non-enzymatic antioxidant within the body is glutathione, which typically exists primarily in the reduced form (GSH). Dietary intake (via whole food or nutritional supplements) supplies further antioxidants in the form of vitamins (e.g., A, C, E), minerals (e.g., selenium, zinc), flavonoids, carotenoids (e.g., beta-carotene), and phenols.

It should be noted that many of these antioxidants function together to provide cellular protection within the body. For example, vitamin C acts to "recycle" vitamin E when vitamin E forms the vitamin E radical while performing its function as a potent chain-breaking antioxidant, intercepting lipid peroxyl radicals.

As mentioned earlier, regular exercise can increase endogenous antioxidant defense, often coupled with decreased ROS formation (Ji, 2002; Powers et al., 1999). This often leads to a decrease in oxidative stress at rest and following acute exercise. While most studies have focused on adaptations resulting from aerobic exercise, positive findings are also available in reference to anaerobic exercise (e.g., weight training).

Regular Exercise Can Increase Endogenous Antioxidant Defense.
Regular Exercise Can Increase Endogenous Antioxidant Defense.

Glycine Propionyl-L-Carnitine (GPLC) as an Antioxidant Agent

Antioxidant micronutrient intake has been widely used in an attempt to decrease oxidative stress resulting from exercise (Urso and Clarkson, 2003). One antioxidant nutrient that has received considerable attention is L-carnitine, with the amino acid precursor, glycine, also noted as having antioxidant properties.

In fact, previous work involving animals has noted decreased protein and lipid peroxidation following glycine use (Malyshev et al., 1996; Senthilkumar et al., 2004; Zhong et al., 1996).

More specifically, propionyl-L-carnitine (PLC), a propionyl ester of L-carnitine, has potent antioxidant properties (Reznick et al., 1992; Vanella et al., 2000), which protect tissue from oxidative stress-induced injury. This effect has been suggested to be partly related to the role of PLC to enhance blood flow (Loffredo et al., 2007), possibly mediated by an increase in nitric oxide, a finding that has been replicated in two recent studies using a combination of PLC and glycine (Bloomer et al., 2007; Bloomer et al., in press).

This unique combination of PLC and glycine is a molecularly bonded USP grade nutritional ingredient called glycine propionyl-L-carnitine (GPLC). Aside from the effect of oral GPLC to increase blood nitric oxide production, GPLC has been reported to decrease ROS mediated oxidation of lipids in a recent study (Bloomer et al., in press).

In this study, subjects received oral GPLC at a dosage of either 1.5 or 4.5 grams per day over the course of an eight week intervention period. With both dosages, the level of oxidative damage to lipids measured in a rested state was significantly lower at the end of the intervention period as compared to pre intervention. The same was not true for subjects receiving a placebo.

These findings highlight the significant antioxidant properties of GPLC. While these preliminary results are of interest, future work is needed to investigate the impact of GPLC on decreasing oxidative stress resulting from strenuous exercise.

Practical Applications of GPLC

The dietary ingredient GPLC has been shown to possess both antioxidant properties (Bloomer et al., in press) and to increase blood nitric oxide (Bloomer et al., 2007; Bloomer et al., in press). This dual action role makes this ingredient one to consider for both general health enthusiasts and athletes who are interested in improving antioxidant defense while potentially stimulating an increase in blood flow due to the increased levels of nitric oxide.


  1. Bloomer RJ, Smith WA, Fisher-Wellman KH. Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men. J Inter Soc Sports Nutr. 4: 22, Epub Dec 3, 2007.
  2. Bloomer RJ, Tschume LC, Smith WA. Glycine propionyl-L-carnitine modulates lipid peroxidation and nitric oxide in human subjects. Int J Vit Nutr Res. In Press.
  3. Bloomer RJ, Goldfarb AH. Anaerobic exercise and oxidative stress: a review. Can J Appl Physiol. 29(3): 245-263, 2004.
  4. Dhalla NS, Temsha RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens. 18: 655-673, 2000.
  5. Dillard CJ, Litov RE, Savin WM, Dumelin EE, Tappel AL. Effects of exercise, vitamin E, and ozone on pulmonary function and lipid peroxidation. J Appl Physiol. 45(6):927-932, 1978.
  6. Finaud J, Lac G, Filaire E. Oxidative stress: relationship with exercise and training. Sports Med. 36: 327-358, 2006.
  7. Goldhaber JI, Qayyum MS. Oxygen free radicals and excitation-contraction coupling. Antioxid Redox Signal. 2(1): 55-64, 2000.
  8. Halliwell B, Cross CE. Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect. 102, Suppl 10, 5-12, 1994.
  9. Jackson MJ, Pye D, Palomero J. The production of reactive oxygen and nitrogen species by skeletal muscle. J Appl Physiol. 102(4):1664-1670, 2007.
  10. Ji LL. Exercise-induced modulation of antioxidant defense. Ann NY Acad Sci. 959:82-92, 2002.
  11. Loffredo L, Marcoccia A, Pignatelli P, Andreozzi P, Borgia MC, Cangemi R, Chiarotti F, Violi F. Oxidative-stress-mediated arterial dysfunction in patients with peripheral arterial disease. Eur Heart J. 28, 608-612, 2007.
  12. Malyshev VV, Oshchepkova OM, Seminokii IZH, Nefedova TV, Morozona TP. The limitation of lipid hyeroxidation nad the prevention of stressor damages to the heart by glycine derivatives. J Exp Clin Pharmocol. 59, 23-25, 1996.
  13. Palazzetti S, Richard MJ, Favier A, Margaritis I. Overloaded training increases exercise-induced oxidative stress and damage. Can J Appl Physiol. 28(4):588-604, 2003.
  14. Powers SK, Ji LL, Leeuwenburgh C. Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med Sci Sports Exerc. 31, 987-997, 1999.
  15. Reid MB. Nitric oxide, reactive oxygen species, and skeletal muscle contraction. Med Sci Sports Exerc. 33(3):371-376, 2001.
  16. Reznick AZ, Kagan VE, Ramsey R. Antiradical effects in L-propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation. Arch Biochem Biophys. 296, 394-401, 1992.
  17. Senthilkumar R, Sengottuvelan M, Nalini N. Protective effect of glycine supplementation on the levels of lipid peroxidation and antioxidant enzymes in the erythrocytes of rats with alcohol-induced liver injury. Cell Biochem Funct. 22, 123-128, 2004.
  18. Schippinger G, Wonisch W, Abuja PM, Fankhauser F, Winklhofer-Roob BM, Halwachs G. Lipid peroxidation and antioxidant status in professional American football players during competition. Eur J Clin Invest. 32(9):686-692, 2002.
  19. Sies H. Oxidative stress: oxidants and antioxidants. Exp Physiol. 82, 291-295, 1997.
  20. Urso ML, Clarkson PM. Oxidative stress, exercise, and antioxidant supplementation. Toxicol. 189(1-2):41-54, 2003.
  21. Vanella A, Russo A, Acquaviva R, Campisi A, Di Giacomo C, Sorrenti V, Barcellona ML. L-propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage protector. Cell Biol Toxicol. 16, 99-104, 2000.
  22. Vollaard NB, Shearman JP, Cooper CE. Exercise-induced oxidative stress: myths, realities and physiological relevance. Sports Med. 35, 1045-1062, 2005.
  23. Zhong Z, Jones S, Thurman RG. Glycine minimizes reperfusion injury in a low-flow, reflow liver perfusion model in the rat. Am J Physiol Gastrointest Liver Physiol. 270, G332-G338, 1996.

Bookmark and Share