This section doesn’t currently include any content. Add content to this section using the sidebar.

Image caption appears here



Increased muscle carnitine levels by supplementing L-carnitine with carbohydrates

Previous discussions about the efficacy of L-carnitine regarding increased lipid oxidation basically argued with the difficulty of reaching higher muscle carnitine levels by supplementation of L-carnitine. It was not before two recent studies, which indeed could prove elevated muscle carnitine after oral supplementation (Stephens, J Appl Physiol, 2006; Stephens, J Physiol, 2013). The interest in increased muscle carnitine levels is based on a subsequent enhanced lipid oxidation for energy provision, thereby sparing muscle glycogen and improve endurance performance.
One of these two studies (Stephens, J Appl Physiol, 2006) concluded, that only after 100 (!) days of oral L-carnitine-carbohydrate supplementation (94 g CHO plus 3 g L-carnitine, twice daily!) increased muscle carnitine levels in an efficacy-relevant level similarly to an infusion could be expected. A more recent study (Wall, J Physiol, 2011) reviewed this hypthesis and demonstrated with a daily intake of 2 x 80 g carbohydrates plus 2 g L-carnitine tartrate (CARNIPURE) muscle carnitine levels could be increased by 21%. But it was necessary to follow this intake scheme during 24 weeks, i.e. 168 days! This very study was performed on 14 moderately trained triathletes, training 3-5 times weekly. The increased muscle carnitine levels after 24 weeks of supplementation resulted in a 35% sparing of muscle glycogen after 30 min on a cycle ergometer with 50% VO2max. This corresponds in fact to the halving of total glycogen use during performance, and consequently increased lipid oxidation. Furthermore, following a 30 min time-trial with 80% VO2max directly afterwards 44% lower muscle lactate levels could be measured! Finally, athletes had to perform another 30 min all-out time-trial where performance was improved by 11% compared to prior supplementation and by 35% compared to the control group!
These are very impressive results! But one has to consider that such a long supplementing protocol with a daily intake of 2 x 80 g of carbohydrates provides 1360 kJ (640 kcal), which have to be calculated into the individual daily energy needs in order to prevent a body mass increase. Indeed, body mass increased in the 7 athletes of the control group by 2.4 kg in average, whereas it remained unchanged in the carnitine group. It remained unclear, if carnitine inhibited weight gain in the supplemental group.

Performance enhancement of carnitine confirmed
A recent study (Stephens, J Physiol, 2013) demonstrated with an identical supplementing protocol (80 g CHO plus 2 g L-carnitine tartrate, twice daily) a 20% increase in muscle carnitine levels already after 12 weeks. Also in this study no weight gain occurred – in contrast to the control group taking the same carbohydrates amount without L-carnitine, which gained almost 2 kg of fat mass! It seems indeed, that the previously suspected fat mass gain caused by the (necessary!) high carbohydrates intake does not occur with concomitant carnitine supplementation.
The enhancement of extensive endurance performance thanks to a 20% increase of muscle carnitine levels, respectively its subsequent increase in lipid oxidation, is proven by earlier studies. Out from gene analyses it could also be demonstrated that 73 out of 187 examined genes related to energy metabolism were expressed to a greater extent in the carnitine group or attenuated in the control group, respectively. In summary, such outcome suggests an overall optimized lipid metabolism by L-carnitine.

Acute vascular effect of L-carnitine without loading
There are indeed previous studies, which found a clear effect of L-carnitine also with short-term supplementation. Some studies demonstrated decreased oxidative stress, lactate, cortisol, creatinekinase, and ammonia levels after physical exertion with L-carnitine supplementation (Galloway, FASEB, 2004; O’Connor, Adv Exp Med Biol, 1990; Spiering, J Strenght Cond Res, 2008). The more pronounced such stress factors, the longer recovery time takes. Obviously, such results cannot rely on increased muscle carnitine levels, but must depend on a vascular effect of circulating carnitine. This point of view is also backed up with an expertise undertaken by the Medical Faculty of the University of Geneva, which states that the recovery-enhancing effects of L-carnitine do not depend on increased muscular levels. Instead, circulating carnitine shall have a vascular protective effect against oxidative damage in micro-blood vessels. It was also outlined in this report that a dosage below 1 g is ineffective. Under this viewing angle the supplementation with L-carnitine in higher doses also shortly prior to physical activity seems advantageous.
But with the above mentioned new studies there is now also proof for a glycogen-sparing effect and a direct performance enhancement grace to increased muscular carnitine levels.

Conclusion and recommendations of combinbine L-carnitine and carbohydrates
An increased muscular carnitine level improves not only aerobic performance (glycogen sparing, increased lipid oxidation) but also anaerobic performance in high-intensity sports (decelerated lactate accumulation). Somewhat critical is yet the necessarily long supplementation combined with a high carbohydrate intake. Evidentially, such a supplementation protocol is not suitable for everybody, but has to be considered case-by-case. In some cases acute shortterm L-carnitine intake may be more appropriate and sufficient.
Most studies applied a supplemental protocol of 2-4 g L-carnitine daily. To increase muscular carnitine, a daily intake of 2 x 2 g L-carnitine tartrate, combined with 80 g of high-glycemic carbohydrates each and during at least 12 weeks, seems necessary as discussed above. The lower threshold for the vascular effect of L-carnitine seems to be at 1 g daily, which also constitutes the regulatory upper limit for dietary supplements in Europe.
A convenient intake means are CARNITIN 1000 or the branded, pure L-carnitine tartrate CARNIPURE, which was also used in the study (Wall, J Physiol, 2011). Because maximum blood levels of carnitine are found 2 ½ to 4 h after supplementation it seems likely that insulin peaks should reached within this time period. If the additional 2 x 80 g of high-glycemic carbs are inappropriate for any reason, it is recommended to combine L-carnitine supplementation with a carbohydrate-reach meal, or carbohydrate products used anyway in the context of physical activity (sports drinks, gels, recovery products). Particularly athletes concerned with weight control should consider such advice. In contrast the necessary high-glycemic carbohydrates can be ingested conveniently, in a concentrated drink, by means of a CARBOLOADER.

Increased fat oxidation targeting weight loss
It is deemed important to note that we were discussing increased lipid oxidation hitherto, in order to spare glycogen stores and improve endurance performance. L-carnitine loading combined with carboloading is not a suitable means to reduce body fat stores and body mass, of course! After all a diet is not meant to maximise lipid oxidation in the muscle cell, but to reduce lipid tissues, like visceral and subcutaneous fat stores. Regarding the discussed study results, it has to be stressed that the absence of body mass gain by supplementing L-carnitine plus increased energy intake (160 g of carbohydrates) daily, does not necessarily mean a reduction of body mass when taking L-carnitine but maintaining energy intake. It is not clear yet, if increased muscular carnitine levels cause a higher fat oxidation not just during physical activity, but also under rest.
L-carnitine’s acute, vascular activity regarding lipid oxidation is postulated to be connected with its buffer function inside and outside the cells, not with an enrichment of carnitine in muscle. This is assumed to improve the use of fatty acids as energy source (see box). Some research suggests an inhibition of a drop in muscle carnitine, or maintaining (not increasing!) circulating (vascular) carnitine levels. Nevertheless, fat oxidation has to be activated by physical exercise in a sufficient manner in order to profit from a buffering effect of carnitine supplementation.
In summary, there are plausible reasons for both an acute (vascular) effect and a chronic (muscle carnitine level) intake of L-carnitine – both for endurance athletes as well as for weight reduction! However, for the latter purpose chronic intake is only recommended without additional carboloading. Please find further product recommendations on the SPONSER website under FIGURE & SHAPE.

Mechanism of L-carnitine in lipid and energy metabolism
Fatty acid transport is often considered the main function of L-carnitine. However, according to existing evidence its pH-buffering activity seems more crucial. L-carnitine stabilises extracellular pH by buffering of coenzyme A (CoA) through formation of acetyl-carnitine. This attenuates the accumulation of acetyl-CoA, thereby upholding the activity of an important enzyme (pyruvate dehyrodgenase) for the carnitine-dependent transport of fatty acids into mitochondria (the «burning site» of fatty acids).
On the intracellular level the amount of free CoA is crucial for the oxidation («burning») of fatty acids in the mitochondria. For example, a fatty acid with 18 carbons (C-18) has to be cut into 9 acetyl units (C-2), whereof each needs a free CoA in order to enter the «Krebs-Cycle». Consequently, CoA demand increases dramatically. L-carnitine can temporarily also bind those C-2 units and maintain the energy producing steps, thereby permitting increased lipid oxidation.

O’Connor JE et al. (1990): New roles of Carnitine metabolism in ammonia cytotoxicity. Adv Exp Med Biol 272:183-195.
Galloway SDR et al. (2004): Effect of 2 weeks supplementation with L-Carnitine-L-Tartrate on plasma ammonia response to exercise. Conference proceedings, FASEB.
Stephens FB et al. (2006): Carbohydrate ingestion augments L-carnitine retention in humans. J Appl Physiol, 102(3):1065-70.
Spiering BA et al. (2008): Effects of L-carnitine L-tartrate supplementation on muscle oxygenation responses to resistance exercise. J Strenght Cond Res, 22(4):1130-5
Wall BT et al. (2011): Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol, 589(4):963-73
Stephens FB et al. (2013): Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans. J Physiol, 591(18):4655-66.

Author: Remo Jutzeler
Ing. Applied Food Sciences UAS
MAS Nutrition & Health ETHZ