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Glycine Propionyl-L-Carnitine (GPLC)

What is Glycine Propionyl-l-carnitine (GPLC/Glycocarn)?

Glycine propionyl-L-carnitine (GPLC/Glycocarn) is a molecularly-bonded combination of propionyl-l-carnitine and the amino acid glycine. Propionyl-l-carnitine is a type of acylcarnitine that has a high affinity for skeletal and cardiac muscles. It has a number of physiological effects, including: 1) a vasodilatory effect, 2) providing a source of propionyl units which can be converted into succinate for use by the mitochondria during the citric acid cycle, and 3) replenishing free carnitine levels during intense exercise or where there is any deficiency. Glycine is believed to be a glucogenic amino acid and therefore may help to regulate blood sugar. It is also required for the formation of creatine and appears to also have a vasodillatory effect. Research has shown that short and long term supplementation with GPLC can significantly enhance anaerobic capacity and reduced lactate production. This is believed to be mainly due to GPLC’s ability to increase Nitric Oxide production, which in turn enhances blood flow to the active muscles. In fact GPLC is considered to be the only supplement proven to directly affect the production of Nitric Oxide. GPLC also has potent antioxidant properties and may protect against lipid peroxidation.

GPLC/Glycocarn Review

Both propionyl-l-carnitine (PLC) and glycine are believed to have a vasodilatory effect (Cipolla et al., 1999; Hafidi et al., 2006). More recently researchers have looked at molecular-bonded combination of PLC and glycine (GPLC) which has been demonstrated to increase plasma nitrate/nitrite concentrations – a measure of nitric oxide production (Bloomer et al., 2007; Bloomer et al., 2009). Nitric oxide is a very short-lived molecule that has a number of physiological functions including: 1) increased vasodilation, through the relaxation of vascular smooth muscles; 2) inhibition of platelet aggregation and platelet adhesion; 3) increased blood flow both at rest and during exercise. Improved blood flow can be beneficial for endurance and strength athletes in two main ways: 1) improved exercise performance due to increased delivery of oxygen to the working muscles and improved removal of lactate and ammonia; 2) increased blood flow may lead to greater delivery of nutrients (carbohydrates, lipids, amino acids, vitamins etc) both during and after exercise and may lead to improved performance, recovery and protein synthesis. As such there has been vast interest within the fitness industry for any supplement purported to increase nitric oxide production.

GPLC and Nitric Oxide Levels
GPLC appears to significantly increase nitric oxide levels (Bloomer et al 2009; Bloomer et al., 2007). A 2007 study looked at the effect of oral consumption of 4.5g daily of Glycine Propionyl-l-carnitine (consisting of 3g of PLC and 1.044g of Glycine) over a four week period (Bloomer et al., 2007). On the 29th day subjects underwent six minutes of upper-arm cuff occlusion at 200 mmHg – basically using a blood pressure cuff to block blood flow - in conjunction with submaximal isometric hand gripping to induce ischemia (restriction of blood and oxygen to a part of the body). After the 6 minutes the pressure was removed to allow rapid reperfusion of blood. This rapid reperfusion of blood is mediated by nitric oxide and provides an opportunity to study nitric oxide activity. Nitric oxide activity was measured by measuring blood nitrite/nitrate levels at 0, 3, and 10 minutes after reperfusion. The researchers found that blood nitrite/nitrate levels were significantly higher in the GPLC group (45.6 ± 2.8 μmol•L-1) compared with the placebo group (34.9 ± 1.2 μmol•L-1). Following the reperfusion of blood nitrite/nitrate levels increased by 16 and 17% in the GPLC group, but only 4 and 6% in the placebo group after 3 and 10 minutes respectively. The researchers concluded that GPLC supplementation can increase nitrite/nitrate levels in resistance trained men and may be of benefit to athletes looking to enhance blood flow as well as those with ishemic conditions (conditions where there is a restriction of blood supply). The authors did however note that there were some individuals who were “non-responders” to GPLC - this is common with most nutritional supplements including other popular supplements like creatine monohydrate.

GPLC Anaerobic Capacity and the Lactate Threshold
In addition to increasing nitric oxide production research has also demonstrated that GPLC supplements can enhance anaerobic work capacity and reduce lactate accumulation (Jacobs et al., 2009). In this study 24 resistance trained males participated in two testing sessions consisting of 5x10second maximal sprints with 60 second active recoveries. The subjects were given either 4.5g of GPLC or 4.5g of cellulose in a randomized order. Heart rate and blood lactate were measured before during and after the maximal sprints. GPLC had a significant effect on peak power, it was greater in each of the five sprints (1.7%, 0.2%, 4.1%, 15.7%, and 4.4% greater) and significantly greater in sprints 3, 4 and 5. Lactate levels were found to be 15.6% and 16.2% lower at 4 and 14 minutes post exercise with GPLC. Interestingly GPLC produced 22.8% less lactate per watt than the placebo (0.947 and 1.227 mmol. watt-1, respectively). Heart rate were similar with both GPLC and placebo both during and after the testing period. The researchers concluded that “GPLC can enhance peak power production in resistance trained males with significantly less LAC accumulation”

Further research looked at the effect of GPLC dosage on anaerobic work capacity and lactate accumulation when taken over 28-days (Jacobs and Goldstein 2010). In this study subjects completed two testing protocols, separated by 7-days – the testing protocol was the same as in the earlier study by Jacobs et al., 2009 described above. In each of the tests subjects were randomly given either 4.5g of cellulose (placebo) or 4.5g of GPLC. The results from the placebo test were used as baseline figures for the second part of the study. The subjects were then randomly assigned to receive either 1.5g, 3.0g or 4.5g of GPLC for 28days. Following the 28 days the subjects completed a third test to compare values with baseline figures. The results indicated that longer term supplementation with GPLC at doses of 3.0g and 4.5g resulted in reduced peak power (2-5% lower), mean power (3-7% lower) and significant greater rates of power decrement (15-20%) compared with baseline. Conversely, the lower 1.5g dosage of GPLC produced higher values for peak power (3-6%), mean power (2-5%), and significantly reduced net lactate accumulation compared with baseline figures. The results suggests that long term supplementation with GPLC of 3.0 or 4.5g daily does not improve anaerobic performance of repeated intervals. However, the results suggest that long term supplementation with 1.5g of GPLC enhances anaerobic capacity whilst significantly lowering lactate accumulation during high intensity exercise. It is not clear exactly why there was reduced performance with prolonged supplementation of GPLC at 3 and 4.5 g although it appears that the higher intake produced significantly greater levels of leg pump which may have acted as a hindrance during high speed, high intensity cycle sprints. The researchers reported that 12 out of the 25 subjects (48%) who took the higher dose complained that discomfort associated with the pump effect limited their sprinting performance. Of the subjects who took the lower (1.5g) dose only 1 of the 13 reported the same discomfort (8%). Although it appears that long term supplementation with GPLC at a dose of 3 or 4.5 g may not be beneficial for endurance athletes it may be that the increased pump effect associated with the higher dose could prove beneficial for bodybuilding.

Further Considerations with GPLC and Lactate levels
It’s always important to consider that there is always a trade-off with the longer term usage of supplements that lower/reduce lactic acid levels. On the one hand lower lactic acid levels should allow you to train at higher intensities for longer, and may also lower the level of cortisol. However, higher lactic acid levels are known to elicit a significantly greater natural increase in human growth hormone levels. Previous research has shown that when lactic acid levels were reduced during a high intensity interval training session by administration of bicarbonate there was a diminished HGH response compared with the placebo group (Wahl et al., 2010). Research has also indicated that increased lactate levels can lead to increases in testosterone (Lu et al., 1997). This further clouds the situation making it more difficult to decide which dosage of GPLC to utilise. However, based on the data from these studies it seems logical that different approaches may be required for different sporting populations – I’ll discuss this more in the section below how to take GPLC.

GPLC and exercise induced lipid peroxidation
Supplementation with GPLC decreased the amount of exercise induced lipid peroxidation as indicated by decreased levels of Malondialdehyde (Bloomer et al 2009; Bloomer et al., 2010) - a naturally occurring product of lipid peroxidation that is both mutagenic and carcinogenic.

Is GPLC effective?

GPLC appears to be effective at increasing nitric oxide synthesis, improving muscle blood flow, increasing anaerobic work capacity, reducing lactate accumulation and appears to act as a potent antioxidant. However, the dosage and duration appears to have a significant influence on lactate accumulation, anaerobic capacity, and the degree of muscle pump and must be considered when choosing the best strategy. It should also be noted that as with most popular sports supplements there will be a small number of people who will not benefit from GPLC.

How to take GPLC?

Recommendations for Athletes looking to enhance athletic performance during competition – if using GPLC to enhance anaerobic capacity and muscle blood flow there are two strategies highlighted by the research to date: firstly; the consumption of a single dose of 4.5g of GPLC approximately 90 minutes prior to competition – the longer term use of 4.5g of GPLC appears to limit performance through an excessive muscle pump; or 2; longer term usage of 1.5g of GPLC over 4 weeks or more. Both strategies appear to be effective at enhancing anaerobic capacity and reducing lactate accumulation. However, the first approach would appear to be a more beneficial strategy for any competitive athlete for the simple reason that exposure to higher Lactic acid levels during training is a very important mechanism through which we adapt to stress, and is considered by many to be one of the key contributors to success in high intensity sport. Therefore, the prolonged use of any supplement that limits lactic acid levels may negatively impact on longer term progression. The only time that I would consider option 2 to have a benefit would be during a key competitive phase and even then you should consider that there’s the possibility that prolonged use may limit progression.

Recommendations for bodybuilders – the best approach for muscle building appears to be 4.5g of GPLC over longer periods (4weeks or more) particularly when considering that lower doses over longer periods did not significantly increase nitric oxide levels (Bloomer et al., 2009) and did not appear to increase muscle pump (Jacobs and Goldstein 2010). The prolonged higher dose (4.5g) approach led to a more significant muscle pump, which may be more beneficial to bodybuilders, there was also no reduction in lactate accumulation which as we have discussed above is actually beneficial for natural increases in both growth hormone levels and testosterone levels.

GPLC benefits and phyiological Effects:

  • GPLC increases Nitric Oxide Production
  • Has a vasodillatroy effect
  • Appears to increase blood flow to the working muscles
  • Has antioxidant properties
  • Reduces lipid peroxidation and significantly reduces amount of Malondialdehyde – a carcinogenic and mutagenic substance
  • Enhance anaerobic work capacity
  • Can Reduce blood lactate accumulation

Who may benefit from GPLC/Glycocarn?

Anyone looking to directly increase nitric oxide production should find Glycine Propionyl-l-carnitine (GPLC) more effective than arginine formulations. GPLC appears to be of benefit for anyone looking to enhance blood flow to the muscles, anaerobic capacity, and reduce lactate levels. Glycine Propionyl-l-carnitine may be of benefit to strength athletes, bodybuilders, boxers, martial arts, cyclists, runners, and for team sports like football, rugby etc. GPLC may also be of benefit to those with conditions where there is a restriction of blood supply such as peripheral vascular disease and ischemic heart disease.

GPLC Side Effects

Recent research has found GPLC appears to be safe and well tolerated. However as with any nutritional supplement there will be a small number of people that may notice some mild side effects, these include nausea, diarrhea, sleeplessness and rash.

GPLC References

Anand I, Chandrashekhan Y, De Guili F, Pasini E, et al. Acute and chronic effects of propionyl-L-carnitine on the hemodynamics, exercise capacity, and hormones in patients with congestive heart failure. Cardiovasc Drugs Ther. 1998;12:291–299.

Bloomer RJ, Smith WA, Fisher-Wellman KH (2007) Glycine propionyl-L-carnitine increases plasma nitrate/nitrite in resistance trained men. J Int Soc Sports Nutr 2007, 4(1):22.

Bloomer RJ, Tschume LC, Smith WA. (2009) Glycine propionyl-L-carnitine modulates lipid peroxidation and nitric oxide in human subjects.Int J Vitam Nutr Res. 2009 May;79(3):131-41.

Bloomer R J, Farney T M, Trepanowski J F, McCarthy C G, Canale R E, and Schilling B K. (2010)Comparison of pre-workout nitric oxide stimulating dietary supplements on skeletal muscle oxygen saturation, blood nitrate/nitrite, lipid peroxidation, and upper body exercise performance in resistance trained men. Journal of the International Society of Sports Nutrition 2010, 7:16

Cipolla MJ, Nicoloff A, Rebello T, Amato A, Porter JM (1999). Propionyl-L-carnitine dilates human subcutaneous arteries through an endothelium-dependent mechanism. J Vasc Surg 1999, 29(6):1097-1103.

Dal Lago A, De Martini D, Flore R, et al. Effects of propionyl-L-carnitine on peripheral arterial obliterative disease of the lower limbs: a double-blind clinical trial. Drugs Exp Clin Res. 1999;25:29–36.

Hafidi ME, Perez I, Banos G (2006). Is glycine effective against elevated blood pressure? Curr Opin Clin Nutr Metab Care 2006, 9:26-31.

Hetenyi G Jr, Anderson PJ, Raman M, Ferrarotto C. (1988) Gluconeogenesis from glycine and serine in fasted normal and diabetic rats.Biochem J. 1988 Jul 1;253(1):27-32.

Jacobs PL, Goldstein ER, Blackburn W, Orem I, Hughes JJ (2009) Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males. J Int Soc Sports Nutr 2009, 6:9.

Jacobs PL, Goldstein ER.(2010) Long-term glycine propionyl-l-carnitine supplemention and paradoxical effects on repeated anaerobic sprint performance.J Int Soc Sports Nutr. 2010 Oct 28;7:35.

Lu SS, Lau CP, Tung YF, Huang SW, Chen YH, Shih HC, Tsai SC, Lu CC, Wang SW, Chen JJ, Chien EJ, Chien CH, Wang PS.(1997) Lactate and the effects of exercise on testosterone secretion: evidence for the involvement of a cAMP-mediated mechanism.Med Sci Sports Exerc. 1997 Aug;29(8):1048-54.

Podoprigora GI, Nartsissov YR, Aleksandrov PN. Effect of glycine on microcirculation in pial vessels of rat brain. Bull Exp Biol Med. 2005;139:675–677. doi: 10.1007/s10517-005-0375-2.

Wahl P, Zinner C, Achtzehn S, Bloch W, Mester J. (2010) Effect of high- and low-intensity exercise and metabolic acidosis on levels of GH, IGF-I, IGFBP-3 and cortisol. Growth Horm IGF Res. 2010 Oct;20(5):380-5.