Long-term glycine propionyl-l-carnitine supplemention and paradoxical effects on repeated anaerobic sprint performance

Exercise capacity is generally considered as the greatest amount of physical exertion that can be sustained at a given level of intensity. Success in endurance sports is related to an ability to continue with relatively high efforts for extended periods of time. In contrast, most team sports involve intermittent bouts of high intensity exertion with limited recovery intervals. A number of strategies are commonly utilized to increase exercise capacity as a means of enhancing sport performance. These include various approaches to training and conditioning as well as nutritional strategies to improve peak exercise capacity as well as exercise efficiency.

While numerous factors underlie exercise capacity, a primary consideration is that of energy demand versus energy supply. The intensity of exercise corresponds- to a great degree- to the specific energy demands of the activity. The capacity to perform at a given intensity of effort is limited by the localized energy supplies and the ability to replenish those energy stores as exercise continues. In conjunction with the increased metabolic demand for energy during exercise, there is increased blood flow to the exercising muscles [1]. During exercise, the vasculature system is the sole means to deliver energy replenishment as well as to remove metabolites that may limit ongoing efforts. A close pairing of exercise intensity and local blood flow suggests that potential strategies capable of increasing blood flow to exercising muscles may enhance maximal work capacity and/or increase resistance to localized muscle fatigue during ongoing exercise at submaximal intensities.

The process of increasing blood flow to exercising musculature involves shunting of blood from non-active tissues to working muscle. As physical exercise increases in intensity, there are a number of mechanisms involved in the vasodilation of the arterioles and the pre-capillary sphincters [2]. These vasodilatory mechanisms are diverse but share two distinct characteristics in that the activity of each of the differing mechanisms increases in direct response to increasing intensities of exercise and those mechanisms all initiate the synthesis of nitric oxide (NO). Nitric oxide is the endothelial factor responsible for relaxation of smooth musculature surrounding the arterials and the pre-capillary sphincters thereby producing vasodilation and increased blood flow into the capillary bed of the exercising muscle tissue. Since its identification approximately twenty years ago, various research studies and subsequent sports nutrition products have emerged in an effort to manipulate levels of NO in order to enhance exercise performance. This quest has resulted in a sizable nutritional supplement market, primarily composed of arginine based products. While arginine is the precursor of NO, there is no scientific evidence to support such an approach. In fact, all published studies in this area indicate that oral administration of arginine in dosages tolerated by the gastrointestinal system are not effective in producing endothelium-dependent vasodilation or in elevating NO levels [3–5].

It has been demonstrated that short term administration of an oral carnitine compound, glycine propionyl-L-carnitine (GPLC), produces significantly elevated levels of nitric oxide metabolites at rest in both sedentary and trained persons [6, 7]. Increased nitric oxide activity has also been demonstrated in resistance trained persons with reactive hyperaemia testing, an assessment used in clinical settings that, to some degree, simulates the physical stresses encountered during very intense exercise such as resistance training [7]. These studies are the first to document the effectiveness of an oral nutritional supplement to directly affect NO synthesis.

It has also been recently shown that acute GPLC supplementation (4.5 g) enhances anaerobic work capacity with reduced lactate production in resistance trained males [8]. However, little is known regarding the effects chronic GPLC supplementation has on exercise performance in trained persons. It was the purpose of the present investigation to examine the effects of 28 days of varying GPLC dosing on anaerobic work capacity and lactate accumulation.

Findings of the present investigation suggest that increasing daily intake of GPLC has somewhat paradoxical influences on the performance of repeated high intensity cycle sprints. These authors have previously reported that GPLC may produce acute enhancement of anaerobic power output during repeated cycle sprints [8]. Based on those results, it was speculated that long-term supplementation would, in general, provide further performance enhancements with those improvements related directly to the greater duration of supplementation and to the daily GPLC intake. However, these current findings indicate that long-term GPLC supplementation at the higher dosages examined (3.0 and 4.5 g/d) did not result in greater values of power output but rather lower mean values of PP and MP. In contrast, the lower intake group (1.5 g/d) exhibited mean values of PP and MP greater than baseline across the five sprints. Those increases in power output were similar to those previously reported with acute intake of 4.5 g GPLC.

The results of this study are not sufficient to definitively explain the apparent decline in sprint performance with higher GPLC intake. However, examination of the mechanisms of action may allow useful supposition. Potential mechanisms involved in the observed acute performance improvements include the unique vasodilatory actions of GPLC as well as supply of an energy source in the form of the propionyl group. An increased cellular supply of carnitine may also provide anaerobic buffering thereby reducing lactate production and enabling greater resistance to fatigue with high intensity exercise. It is likely that blood serum and tissue concentration levels of carnitine and propionate increase over time to some point of saturation. It is recommended that future investigations examine the time by dosage dynamics involved in GPLC supplementation.

The mechanisms involved in acute enhancement of power output and reduced lactate accumulation are possibly (in higher intake levels) also responsible for the reduced mean values of power seen with long-term intake. These authors suggest that it is unlikely that greater levels of propionate or carnitine in the blood stream or muscle tissue would reduce the production of power during the repeated sprints. However, it appears quite probable that the vasodilatory effects of GPLC surpassed a beneficial magnitude in the 3.0 and 4.5 g/d groups. A post-hoc examination of participant statements regarding their condition following the final testing session revealed that 13 of the 38 individuals completing the study complained that discomfort associated with leg pump limited their sprinting performance. These 13 included five of the 12 individuals in the 3.0 g/d group, and seven of the 14 participants in the 4.5 g/d group but only one individual in the 1.5 g/d group reported leg pump as a limiting factor. While not statistically significant, the 3.0 and 4.5 g/d groups displayed greater mean increases in thigh girth with sprinting compared with baseline while the 1.5 g/d group exhibited the same relative leg pump. Thus, while the results of this study cannot definitively explain the lack of power output enhancement with long-term intake of GPLC, the limited information available suggests that excessive localized muscle pumping is involved.

With increasing intensity of exercise, there is proportional increase in local blood flow of the exercising musculature. Vasodilation provides up to 25 -50 times resting levels of local blood flow by means of relaxation of the smooth arterial musculature and of the sphincter allowing flow into the capillary bed [9]. The process of vasodilation is closely associated with NO as this short-lived, reactive nitrogen molecule is responsible for regulation of vascular muscle tone [10]. Since it was determined that NO has a vital role in the control of blood flow, scientists have speculated on the effects increased levels would have on cardiovascular functioning in particular and exercise performances in general. However, this question has remained a matter of supposition as no nutritional supplementation has proven capable of influencing NO synthesis, until recently.

The only food supplement shown to directly affect the production of NO is GPLC. It has been shown that 28 d GPLC at 4.5 g/d produces significantly elevated levels of nitrites and nitrates [6, 7]. Acute supplementation at 4.5 g resulted in significant improvements in cycling power output [8], but in the current study long-term supplementation of GPLC at that daily intake was not associated with power enhancement. Rather after 28 d GPLC at 4.5 g/d there was a significantly greater rate of power decline within individual sprints with reduced mean power output. In contrast, 28 d at a lower dosage, 1.5 g/d, provided increased mean values of power similar to those exhibited acutely with 4.5 g. The increases in NO reported after 28 d GPLC at 4.5 g/d are apparently associated with the extreme leg pump that limited cycling power in the present study. Similarly, with 4.5 g/d there was a significant reduction in net lactate accumulation per unit power acutely - with like reductions also observed after 28 d at 1.5 g/d, but not but not after 28 d at 4.5 g/d. Apparently, the long-term effects of GPLC are related to the timed effects of different individual mechanisms. The vasodilatory effects are certainly directly related to NO levels while the increased power output may be related to increased cellular supply of the propionate unit which when converted to succinate provides an anaplerotic energy substrate. Greater carnitine supply may be responsible for the reduced lactate accumulation due to buffering of the Coenzyme A pool thereby reducing the rate of fatigue and enabling a higher rate of power output. It would appear that both the vasodilatory effects and power output enhancement effects increased in magnitude over the 28 d period of the present study.

The present study is limited by several factors including a modest sample size which restricted the statistical analyses. Some variability within groups could be associated with the lack of control of the study supplement. Study participants were provide with 28 days of GPLC in the respective group levels and directed to take six capsules daily. However, there were no means available to ensure daily intake of the respective supplements. This investigation applied three absolute dosage levels (1.5, 3.0, 4.5 g/d) in all research participants. The absolute dosing regardless of body mass likely increased the variability of response within supplementation groups thereby limiting the findings of the present study. It is recommended that future investigations examine GPLC dosing relative to body mass.

Regardless of these potential limitations, the total subject pool in this study did not display the same main effects for enhancement of power output with reduced lactate accumulation as had been observed with acute supplementation. While the lower intake group (1.5 g/d) did display improvements in mean values of power output with significantly lower net lactate accumulation per unit power output, the higher intake groups (3.0 and 4.5 g/d) actually produced lower mean values of power output. From the participant reports and the relatively crude thigh girth measurements, it would appear that the higher intake levels produced greater levels of leg pump which acted as a hindrance during high speed, high intensity cycle sprints. However, this is not to imply that the higher intake levels would be disadvantageous in all sports situations and could possibly prove to be beneficial in some particular settings. Significant increases of blood flow to exercising muscles may provide training benefits for some athletes during certain types of competition or physical conditioning. For example, the high degree of leg pump might provide unique athletic conditioning benefits to those in the competitive bodybuilding field and others during particular phases of training.

Chronic supplementation of GPLC appears to provide benefits that are dose dependent. While acute supplementation of 4.5 grams was previously shown to provide significant enhancement of anaerobic work capacity, the present study suggests that chronic supplementation of GPLC at 3.0 or 4.5 grams daily does not improve anaerobic performance of repeated high speed high intensity bouts and may actually produce detrimental effects with high velocity, high intensity exercise. However, these results also suggest that 1.5 g GPLC does provide enhancement of anaerobic capacity. These findings also suggest that long term supplementation with this dosage (1.5 g/day) results in significantly lower lactate accumulation with high intensity exercise.